Datasets:

---

ahmedselhady

/

ms2_dataset_restructured

like 0

[ "The extent of sphincter division by the subcutaneous or the open technique is examined by comparing the change in anal canal pressure after either method of sphincterotomy in twenty‐eight patients with chronic anal fissure r and omly allocated . In all patients the fissures healed at one month with significant reduction ( P of anal canal pressures to 52 ( 17–75 ) cmH2O after subcutaneous and 47.5 ( 35–100 ) cmH2O after open sphincterotomy , a 51 ( 22–77 ) and 50 ( 11–68 ) per cent reduction of their respective pre‐operative measurements . Adequate sphincterotomy can be achieved by both techniques", "BACKGROUND Anal fissure is a frequent proctologic disease . There are many and various treatments adopted to cure this disease . In this study we applied radiofrequencies to the subcutaneous lateral internal sphincterotomy and we compared the techniques in a r and omised trial . METHODS Patients have been r and omized in two groups : in group A 18 patients underwent subcutaneous lateral internal sphincterotomy using radiofrequency bistoury while in group B 17 patients underwent the conventional lateral internal sphincterotomy described by Parks . RESULTS The mean values for operative time were 6.6 min for group A and 9.1 min for group B. According to pain score , patients ' mean values were 1.8 for group A and 1.9 for group B. Healing of the wound was faster in group A than group B , while healing of the anal fissure was approximately the same . CONCLUSION Lateral subcutaneous sphincterotomy is the most advantageous operation for the treatment of the idiopathic anal fissure . The radiofrequency bistoury easies the procedure , lessens operating times and healing process of the surgical wounds", "PURPOSE : Internal sphincterotomy remains the “ gold st and ard ” for treatment of anal fissure but is associated with a risk of imperfect continence . Recent studies have suggested that surgical technique ( open vs. closed ) may influence incontinence rates after sphincterotomy . This study was design ed to assess the short-term and long-term incidence of incontinence after open and closed internal sphincterotomy . METHODS : Seventy-nine patients were r and omly assigned to open or closed internal sphincterotomy , performed in st and ardized fashion by trainee staff . St and ardized question naires assessing continence ( modified Wexner score ) were administered preoperatively and at 1 , 6 , and 52 weeks . Postoperative stay , pain scores , complications , and fissure healing were prospect ively assessed by an independent observer . RESULTS : Three patients were lost to follow-up , leaving 36 closed ( 16 males ; mean age , 45.1 years ) and 40 open ( 21 males ; mean age , 47.9 years ) internal sphincterotomy patients for assessment . All operations were performed as day case procedures with no readmissions . At six weeks postoperative , 96 percent of fissures had healed . There were no significant differences in pain scores between closed and open internal sphincterotomy at Day 1 or Day 3 postoperative . New incontinence of any grade was seen in 6.8 percent of patients at 52-week follow-up . Three patients ( 4.1 percent , 1 closed , 2 open ) suffered major incontinence at 52 weeks . There were no significant differences in continence at 1 , 6 , or 52 weeks , although more open patients experienced minor imperfections at 1 week . CONCLUSIONS : Incontinence after internal sphincterotomy is not insignificant . The technique ( closed vs. open ) does not seem to influence incontinence rates", "Twenty patients with chronic anal fissure were r and omized into two groups . Ten patients were treated with lateral subcutaneous sphincterotomy and 10 with anal dilatation . Anal dilatation was carried out preoperatively , and at 1 and 3 months after the operation in all patients . Preoperatively there was a significantly increased maximal resting pressure in the 20 fissure patients ( 80 mmHg median ) compared with 20 control subjects ( 50 mmHg median ) . Postoperatively a significant decrease in pressure occurred in the dilated group ( 49 mmHg medianp recurrent symptoms of anal fissure in the dilated group compared with one in the sphincterotomy group . Minor continence disturbance was noted in two patients in both groups", "PURPOSE Conventional practice in colorectal surgery involves stoma education being imparted postoperatively . Proficiency in stoma management often delays patients ’ discharge following colorectal surgery . The aim of this r and omized , controlled trial was to compare preoperative intensive , community-based stoma education with conventional postoperative stoma education after elective colorectal surgery . METHODS Forty-two elective colorectal patients requiring a stoma were r and omized into an intensive preoperative teaching ( study ) or postoperative ( control ) group . Intervention for the study group included two preoperative visits in the community during which patients were taught with audiovisual aids to use and change the stoma pouching system . Goal -directed postoperative stoma education was st and ardized for both groups . Outcomes measured included time to stoma proficiency , postoperative hospital stay , unplanned stoma-related interventions in the community within six weeks of discharge , and preoperative and postoperative hospital anxiety and depression scores . Cost-effectiveness of the intervention was also evaluated . RESULTS All outcomes measured were improved in the study group , including time to stoma proficiency(5.5 vs. 9 days ; P = 0.0005 ) , hospital stay ( 8 vs. 10 days ; P = 0.029 ) , and unplanned stoma-related community interventions per patient ( median 0 vs. 0.5 ; P = 0.0309 ) . No adverse effects of the intervention were noted . The average cost saving per patient was £ 1,119 ( $ 2,104 ) for the study group compared with the control group . CONCLUSIONS Stoma education is more effective if undertaken in the preoperative setting . It results in shorter times to stoma proficiency and earlier discharge from the hospital . It also reduces stoma-related interventions in the community and has no adverse effects on patient well-being", "Background Troublesome fecal incontinence following a lateral internal sphincterotomy is often attributed to faulty surgical technique . However , it may be associated with coexisting occult sphincter defects . Whether continence is related to the extent of sphincterotomy remains debatable . The aim of the study is to identify fecal incontinence related to chronic anal fissure before and after lateral internal sphincterotomy and its relationship to the extent of internal anal sphincter division . Methods One hundred eight patients with chronic anal fissure were prospect ively studied before and after lateral internal sphincterotomy . A question naire was completed for each patient before and after surgery with regard to any degree of fecal incontinence . Fecal incontinence severity index was assessed using the Clevel and Clinic Incontinence Score . The patients with preoperative perfect continence were r and omized into two groups ( 46 patients in each group ) : Group 1 underwent traditional lateral internal sphincterotomy ( up to the dentate line ) and Group 2 were underwent a conservative internal anal sphincterotomy ( up to the height of the fissure apex or just below it ) . Results Minor degrees of incontinence were present before surgery in 16 patients ( 14.8 % ) . Results of the r and omized trial revealed that temporary postoperative incontinence was newly developed in 6/92 of patients ( 6.52 % ) who did not have it before surgery . Five of the six ( 10.86 % ) were in Group 1 one ( 2.17 % ) was in Group 2 ( p = 0.039 ) . Persistent incontinence occurred in two in Group 1 ( 4.35 % ) . All of them were females . All have had a history of one or more vaginal deliveries . Conclusion A mild degree of fecal incontinence may be associated with chronic anal fissure at presentation rather than as a result of internal sphincterotomy . Troublesome fecal incontinence after lateral internal sphincterotomy is uncommon . Sphincterotomy up to the dentate line provided faster pain relief and faster anal fissure healing , but it was associated with a significant postoperative alteration in fecal incontinence than was sphincterotomy up to the fissure apex . Care should be exercised in female patients with a history of previous obstetric trauma , as internal anal sphincter division may further compromise sphincter function", "Background Several surgical methods are accepted for the treatment of chronic anal fissure . The most popular are anal dilatation ( AD ) and left lateral sphincterotomy ( LLS ) . The objective of the current study was to prospect ively evaluate the results of these two procedures in terms of recurrence rate , complications and patient satisfaction . Methods The study enrolled all patients who required operation for chronic anal fissure in the Division of General Surgery , Campus Golda , Rabin Medical Center , between the years 1997 and 2001 . Exclusion criteria were acute anal fissure or inflammatory bowel disease . Results A total of 108 patients participated in the study , at an average age of 42.4 years ( SD=12.5 ) . The patients were r and omly assigned to two groups ; one for LLS ( 53 patients , 49.1 % ) and one for AD ( 55 patients , 50.9 % ) . The study protocol included a question naire and a physical examination performed 1 , 2 , 3 , 6 and 12 months after operation . The question naire contained questions about pain , bloody stool , incontinence for gas , fluid or hard feces , during the day or night , and soiling . The patients were also asked about their satisfaction on an analog scale from 1 to 10 . The average follow-up was 11.2 months ( SD=4.1 ) . Minor incontinence occurred in 8 patients of AD group and in 2 patients of LLS group ( p Recurrence occurred in 6 cases of the AD group and in one case of the LLS group ( p . Satisfaction score was insignificantly higher in the LLS group ( 9.1±0.8 in the LLS group and 7.4±2.0 in the AD group ) . Conclusions These results suggest that LLS is the preferred method for the treatment for chronic anal fissure", "A prospect i ve r and omised study compared anal dilatation ( n = 37 ) , posterior internal sphincterotomy ( n = 21 ) and lateral sphincterotomy ( n = 20 ) in the surgical treatment of chronic anal fissures in 78 consecutive patients . All the operations were performed under general anaesthesia using st and ard techniques . Anal dilatation relieved anal pain early ( immediate relief in 57 % of patients ; the mean pain-days + /- SD of 3.2 + /- 5.4 days ) . Anal fissures after this operation healed in a mean time + /- SD of 20.3 + /- 12.5 days , coming in second place to lateral sphincterotomy . Anal dilatation was followed by insignificant wound infection but its main disadvantage was a high rate of post operative anal incontinence ( in 24.3 % of patients ) . Fissurectomy and posterior internal sphincterotomy was followed by the longest period of post operative anal pain ( mean + /- SD of 32.4 + /- 10 days ) as compared to the other two operations . It was the least favourable operation . Lateral sphincterotomy was followed by early relief of pain ( immediate relief in 95 % of patients ) . It was not followed by wound infection . It had the quickest healing time for the fissures ( a mean + /- SD of 14.7 + /- 8.7 days ) . It was followed by anal incontinence in only one patient . In conclusion lateral sphincterotomy was the most favourable operation and it is perhaps the operation of choice to perform in patients with chronic anal fissures needing surgical treatment", "Abstract . Background : Hypertrophied anal papillae and fibrous anal polyps are frequently found in association with chronic fissure in ano . Usually , no specific attention is given to them and they are considered normal findings . The present prospect i ve study was aim ed at determining whether removal of hypertrophied anal papillae and fibrous anal polyps while dealing with chronic fissure in ano confers long-term benefit to patients . Methods : Between July 1999 and December 2000 , 140 patients undergoing anal sphincterotomy were r and omized into two groups to have their fibrous polyps and hypertrophied anal papillae either removed by radiofrequency surgery or left intact . After two years , they underwent a detailed interview by an independent , masked investigator . Results : Overall 84 % of patients who had polyp and papilla removal rated the outcome of their surgery as excellent or good in comparison to 58 % of controls . The mean satisfaction grading was 9.2 on a visual analogue scale in the treatment group compared to 8.1 in controls ( p=0.004 ) . Conclusion : Removal of hypertrophied anal papillae and fibrous anal polyps should be an essential part of treatment of chronic fissure in ano . Persistence of these structures leaves behind a sense of incomplete treatment , reducing the overall satisfaction on the part of the patient . Radiofrequency procedure is useful in eradication of these concomitant pathologies", "A prospect i ve study comparing open and subcutaneous lateral internal sphincterotomy for chronic anal fissure was conducted . One hundred twelve patients were r and omized to open ( n=54 ) or subcutaneous ( n=58 ) sphincterotomy . There was no significant difference in acute complications between the subcutaneous ( 8.6 percent ) and open ( 7.4 percent ) groups . Postoperative length of stay was significantly shorter for the subcutaneous group ( 1.7±0.2 days ) than for the open group ( 2.3±0.1 days;P the response rate to a pain question naire was lower level of postoperative pain in the subcutaneous group . Fissure healing was similar between the subcutaneous ( 96.6 percent ) and open ( 94.4 percent ) groups . We conclude that subcutaneous lateral internal sphincterotomy for chronic fissure-in-ano is effective and may result in significantly less postoperative discomfort , shorter postoperative lengths of stay , and a comparable rate of complications compared with the open technique", "Background Sitz bath is frequently recommended by physicians for a variety of anal disorders including anal fissure . The aim of the present study was to determine whether sitz bath does have any therapeutic properties improving upon a patient ’s postoperative symptoms after a closed lateral sphincterotomy . Material s and Methods Forty-six patients were r and omly assigned to receive analgesics and fiber supplement alone ( control patients ) or a twice-daily sitz bath along with identical fiber and analgesics ( sitz bath group ) . A 24-h pain score — post-defecation anal burning and symptom improvement — was evaluated on a visual analog scale ( VAS ) . Results The groups were equally matched for age , gender distribution , and duration of disease . No significant difference in mean pain score between groups ( p = 0.284 ) was noticed after one week . However , the patients from the control group experienced significant anal burning compared with patients from sitz bath group ( p improvement score was higher in the sitz bath group when compared with the control group ; however , it did not reached a statistically significant level . Conclusions Patients after sphincterotomy for anal fissure receiving sitz bath experienced similar levels of pain when compared with those not receiving sitz bath . However , they reported a significant relief in anal burning and a marginally better satisfaction score and no reported adverse side effects ", "PURPOSE : Lateral internal sphincterotomy is an effective treatment for chronic anal fissures ; however , the risk of “ incontinence ” has generated interest in pharmacologic approaches that are far less effective and may be poorly tolerated . This study was design ed to objective ly define the risk of incontinence with sphincterotomy using the Fecal Incontinence Severity Index and assess the implication s for quality of life using the Fecal Incontinence Quality of Life Scale . METHODS : A prospect i ve study was undertaken on all patients undergoing lateral internal sphincterotomy for a chronic anal fissure by a single surgeon at a university teaching hospital from January 1 , 2000 to September 30 , 2002 . All patients had failed at least six weeks of nonoperative management . Patient demographics and use of nitroglycerin were noted . The Fecal Incontinence Severity Index was measured preoperatively and at a six-week postoperative visit when fissure healing and postoperative complications were assessed . The Fecal Incontinence Quality of Life Scale was administered to patients with an incontinence score > 0 . RESULTS : Thirty-five patients ( 15 males ) underwent sphincterotomy during the study period . Thirty-one of 35 had failed nitrates : 10 because of unacceptable side effects , and 21 because of lack of efficacy . Thirty-two patients returned for their six-week postoperative visits , and two completed their question naires by telephone . One patient was lost to follow-up . Mean age was 41.2 ( range , 21–67 ) years . Thirty of 32 ( 94 percent ) evaluable fissures had healed by six weeks , one healed by three months , and the other required V-Y anoplasty . There were two minor complications . Three patients had postoperative deterioration in their continence score . Quality of life deteriorated in only one patient . CONCLUSIONS : Lateral internal sphincterotomy is a safe and effective treatment for chronic anal fissures that only occasionally impairs continence and rarely diminishes quality of life", "BACKGROUND Much of the lateral internal sphincterotomy ( LIS ) complications is related to LIS incision . In this study , incisions sutured primarily or left to secondary healing after open LIS procedure are compared regarding the wound healing and complications associated with wounds . METHODS Planning a prospect i ve , r and omized clinical study , 39 patients were separated into two groups . Open LIS was performed on both of the groups . While the incisions of the patients in group 1 ( n = 22 ) were closed with two interrupted sutures using 3 - 0 chromic catgut , the incisions of the patients in group 2 ( n = 17 ) were left open . The patients were followed up for 90 days postoperatively . RESULTS Hematoma in 1 ( 4.5 % ) , ecchymosis in 7 ( 31.8 % ) , and wound infection in 1 ( 4.5 % ) developed in patients of group 1 . In this group no significant external bleeding was seen . Wound healing duration was 15.05 + /- 5.60 days . In group 2 no hematoma developed ( P = 0.98 ) , but 2 ( 11.7 % ) ecchymoses ( P = 0.25 ) , 4 ( 23.5 % ) , wound infections ( P = 0.14 ) , and 3 ( 17.6 % ) postoperative significant external bleedings ( P = 0.07 ) were seen . Wound healing duration was 33.94 + /- 6.67 days ( P closure of open LIS incision is useful , but this technique has no significant effect on wound-related complications in comparison with secondary healing", "BACKGROUND The aim of this prospect i ve r and omized trial was to compare the effectiveness and morbidity of open and closed sphincterotomy performed as an outpatient procedure under local anesthesia in the treatment of chronic anal fissure . STUDY DESIGN Eighty patients with chronic anal fissure were treated by open ( group 1 ) or closed lateral internal sphincterotomy ( group 2 ) . Clinical and manometric results were recorded at the time of admission and at 1-week , 2-month , 6-month , 1-year , and 2-year followup visits . RESULTS Overall healing after 2 years was 92.5 % in the open sphincterotomy group and 90 % in the closed sphincterotomy group ( p > 0.05 ) . Fissures were notably less likely to heal in patients in whom the condition had been present for longer than 12 months and who had a sentinel pile before treatment . At the 2-year revision , incontinence was present in two patients ( 5 % ) in the open sphincterotomy group and one patient ( 2.5 % ) in the closed sphincterotomy group ( p > 0.05 ) . In all cases , the incontinence was mild ( mean resting pressure ( 113.9 mmHg ) was found in patients with anal fissure before treatment compared with the healthy control group ( mean resting pressure = 66 mmHg ) ( p mean resting pressure in patients cured after 2 years was 75.65 mmHg , and in those with a recurrent fissure was 112.85 mmHg ( p Morbidity and recurrence were similar in open and closed sphincterotomies when the procedures were performed under local anesthetic , and sphincterotomy under local anesthesia as an outpatient procedure has several socioeconomic advantages ( high degree of satisfaction and comfort to the patient , rapid solution of the problem , and no admission to the hospital or an operating room and no preoperative studies )", "OBJECTIVE To evaluate lateral sphincterotomy under a mixture of local anesthesia versus general anesthesia in the treatment of anal fissures . METHODS A r and omized clinical trial of 62 consecutive patients requiring lateral sphincterotomy was carried out at Princess Haya Al-Hussein Hospital in Jordan . One group underwent lateral sphincterotomy under general anesthesia , while the 2nd group had topical anesthetic cream ( xylocaine 2 % ) applied followed by local anesthesia . RESULTS There were no differences between the 2 groups in terms of operating time , postoperative pain , nausea or vomiting , pain-free interval after operation , analgesia requirements or patients satisfaction with the method of anesthesia . CONCLUSION Topical anesthetics and local anesthesia can be used effectively for lateral sphincterotomy and provides an alternative to general anesthesia", " Fifty eight patients with idiopathic chronic anal fissure were included in a r and omised prospect i ve trial of lateral subcutaneous sphincterotomy versus simple anal dilatation carried out as outpatient procedures . Operations were performed under local anaesthesia and the patients review ed 10 - 30 months later ( median follow up time 18 months ) . Altogether 30 patients were treated by lateral subcutaneous sphincterotomy and 28 by anal dilatation . No serious complications were observed in either group . One recurrence was observed in the group treated by sphincterotomy , whereas eight occurred in the other group ( p less than 0.05 ) . Functional results with respect to impaired control of flatus and soiling of underwear were significantly better after sphincterotomy ( p less than 0.002 ) . It is concluded that lateral subcutaneous sphincterotomy is the treatment of choice for idiopathic chronic anal fissure resistant to conservative measures", "PURPOSE : This study was design ed to assess differences between lateral internal anal sphincterotomy and anal advancement flap for chronic anal fissure . METHODS : Forty patients with chronic anal fissure were prospect ively studied . Patients r and omized to the sphincterotomy group ( n=20 ; median age , 34 ( range , 16–61 ) years ) underwent lateral internal anal sphincterotomy . Patients r and omized to the flap group ( n=20 ; median age , 32 ( range , 20–44 ) years ) had an anal advancement flap . RESULTS : All fissures in the sphincterotomy group healed following surgery compared with three patients that failed to heal in the flap group ( P= 0.12 ) . No patient in either group was incontinent to any degree following surgery . Patient satisfaction with surgery was similar in both groups . CONCLUSION : Anal advancement flap is an alternative to lateral sphincterotomy for chronic anal fissure", "PURPOSE : It is postulated that an anterior anal fissure can result from mucosal trauma occurring during distention of a rectocele and that repair of the rectocele by anterior levatorplasty can lead to healing of these anal fissures . This study was design ed to compare anterior levatorplasty with internal sphincterotomy for the management of anterior anal fissures in females with a rectocele . METHODS : From June 2000 until May 2002 , 54 consecutive females with an anterior anal fissure and a rectocele were r and omized to be managed by internal sphincterotomy or anterior levatorplasty . Preoperatively , manometry was performed , continence was measured using the Clevel and Clinic scoring system , pain scores were obtained using a visual analog scale , and the symptoms of bleeding and straining to defecate were assessed . Postoperatively , pain scores were obtained at Days 2 , 7 , and 21 . Manometry , continence scores , and resolution of symptoms were measured between 8 and 12 weeks . Patient satisfaction and fissure healing also were assessed between 8 and 12 weeks . The average length of follow-up was 20 ( range , 6–30 ) months . RESULTS : Postoperatively , lateral sphincterotomy caused a decrease in the resting pressures and anterior levatorplasty result ed in an increased length of the anal canal . Anterior levatorplasty also caused increased postoperative pain scores . There were no differences in fissure healing and patient satisfaction . CONCLUSIONS : These data suggest that anterior levatorplasty is an option for the management of patients with a rectocele , which may avoid the risk of incontinence with lateral internal sphincterotomy and better address the etiology of anterior anal fissures", "Summary A prospect i ve r and omized trial has compared manual dilatation of the anus ( MDA ) during general anesthesia with lateral subcutaneous sphincterotomy ( LSS ) during local anesthesia for the management of anal fissure in 156 patients . The two groups were similar with respect to age , sex and symptoms . There was no difference in the duration of time off work or early complications of treatment but , four months after operation , 93 per cent cl aim ed to have been improved by MDA compared with 78 per cent after LSS ( P ) . Recurrent fissure was recorded in 13 patients after LSS ( 29 per cent ) compared with four ( 10 per cent ) after MDA ( P reduction in anal pressure at four months ( P MDA , ( 123±31 to 97±33 ) and LSS ( 127±36 to 104±32 ) , but the anal pressure remained unchanged by operation in all patients where pressures were measured with recurrent fissure . These data indicate that MDA gives better results than LSS for treatment of anal fissure and that successful treatment is associated with a reduction in anal pressure", "The results of a prospect i ve r and omized trial in 111 patients were recorded to compare manual dilatation of the anus with lateral subcutaneous sphincterotomy performed under general anesthesia . There was no significant difference in the clinical results nor in the incidence of complications . Persistent or recurrent fissure occurred in three of 59 patients after manual dilatation of the anus and two of 39 patients after lateral subcutaneous sphincterotomy , an incidence of 5.1 percent in each group . Only one patient developed serious impairment of continence , and this occurred following lateral subcutaneous sphincterotomy ( 5.1 percent )", "PURPOSE The aim of this r and omized , prospect i ve study was to compare the results of lateral internal sphincterotomy up to the dentate line or up to the fissure apex in the treatment of chronic anal fissure . METHODS Adult patients with chronic anal fissure were r and omly assigned to undergo lateral internal sphincterotomy to the level of the dentate line or to the level of the fissure apex . The patients were reexamined on postoperative Days 1 , 7 , 14 , 28 , and then at 2 and 12 months . RESULTS The time required for relief of pain postoperatively was 2.08 ± 1.44 days in the dentate line group , which was significantly shorter than that for the fissure apex group ( 4.72 ± 4.86 days ; P = 0.002 ) . Objective healing was achieved in 23.7 percent and 17.6 percent at 14 days , 97.4 percent and 88.2 percent at 28 days , and 100 percent and 97.7 percent at 2 months in the dentate line and fissure apex groups , respectively ( P > 0.05 for all comparisons ) . Only sphincterotomy up to the dentate line caused a significant change in anal incontinence ( P = 0.016 ) . Both groups had significantly lower anal resting pressures at 4 months postoperatively , compared with their corresponding preoperative levels ( P = 0.005 and P = 0.007 ) . The postoperative resting pressures did not differ significantly between the two groups ( P = 0.273 ) . By 12 months postoperatively , no treatment failures or recurrences were noted in the dentate line group ( 100 percent healing rate ) . In the fissure apex group , there was one nonhealing case and four recurrences , result ing in a 13.2 percent rate of treatment failure ( P = 0.058 ) . CONCLUSIONS Sphincterotomy up to the dentate line provided a faster and definitive healing within the time limits of this study , but it was associated with a significant alteration in anal continence . In turn , sphincterotomy up to the fissure apex was free of significant disturbance of continence , but its healing effect was slower and it was prone to an insignificantly higher rate of treatment failure ", "PURPOSE Pneumatic balloon dilation has been shown to be effective in the management of chronic anal fissure , but its effect on the anal sphincter has not been fully investigated . The aim of this study was to evaluate prospect ively the clinical , anatomic , and functional pattern in a group of patients treated by pneumatic balloon dilation . METHODS A series of 33 consecutive patients suffering from chronic anal fissure underwent pneumatic balloon dilation . Anal manometry and ultrasonography were performed prior to and 6 to 12 months after the treatment . Manometry was accomplished by means of an endoanal 40-mm balloon inflated with a pressure of 1.4 atmospheres that was left in situ for six minutes under local anesthesia . All patients were interviewed daily for three days after surgery and then clinical ly evaluated between the third and fifth postoperative weeks . Most patients were interviewed after 25.7 ± 8.4 months ( mean ± st and ard deviation ) . Anal incontinence was evaluated by means of a vali date d score of 1 to 6 . RESULTS The chronic anal fissure healed between the third and fifth weeks in 31 patients ( 94 percent ) , who became asymptomatic 2.5 ± 1.4 days after pneumatic balloon dilation . None of them reported anal pain two years after the treatment ( n = 20 ) . The first post-pneumatic balloon dilation defecation was painless in 27 cases ( 82 percent ) . Two multiparous females ( 6 percent of the patients ) complained of minor transient anal incontinence ( score , 3 ) . Chronic anal fissure recurred in one case ( 3 percent ) after treatment . At manometry , the preoperative anal resting pressure decreased from 91 ± 11.2 to 70.5 ± 5.6 and to 78 ± 5.7 mmHg , 6 and 12 months after pneumatic balloon dilation , respectively ( P 0.0001 ) . Anal ultrasonography did not show any significant sphincter defect . CONCLUSIONS Pneumatic balloon dilation seems to be an effective , safe , easy procedure that decreases anal resting pressure without endosonographically detectable significant sphincter damage", "BACKGROUND AND OBJECTIVE The function of the internal sphincter is disturbed in patients with chronic anal fissure due to persistent hypertonia and it may lead to a certain degree of incontinence . Our aim is to assess the results of lateral internal sphincterotomy and to identify any degree of incontinence related to the disease . METHODS This prospect i ve study included a review of all patients operated upon by the authors who performed division of the internal sphincter at or below the upper limit of the fissure . A question naire was completed by each patient before surgery and then after surgery with regard to any degree of incontinence such as soiling of underclothes , control of flatus and accidental bowel motion . RESULTS 126 patients with chronic anal fissure were studied . The male to female ratio was 0.8:1 . Minor degrees of incontinence were present prior to surgery in 35 patients ( 28 % ) and in 31 ( 25 % ) patients after surgery , the majority of them were incontinent before surgery . CONCLUSION Based on the results of this study , minor degrees of incontinence could be a symptom of chronic anal fissure and not the sequelae of lateral internal sphincterotomy" ]

[ "BACKGROUND The effects of cholesterol-lowering treatment with statins on mortality and risk of cancer beyond the usual 5 - 6-year trial periods are unknown . We extended post-trial follow-up of participants in the Sc and inavian Simvastatin Survival Study ( 4S ) to investigate cause-specific mortality and incidence of cancer 5 years after closure of the trial . METHODS 4S was a r and omised double-blind trial of simvastatin or placebo in patients with coronary heart disease , serum total cholesterol 5.5 - 8.0 mmol/L , and serum triglycerides 2.5 mmol/L or lower . The double-blind period lasted for a median of 5.4 years ( range for survivors 4.9 - 6.3 ) and ended in 1994 . After the trial , most patients in both groups received open-label lipid-lowering treatment . National registers were used to assess mortality and causes of death and cancer incidence in the original treatment groups for a median total follow-up time of 10.4 years ( range for survivors 9.9 - 11.3 ) . Analysis was by intention to treat . FINDINGS 414 patients originally allocated simvastatin and 468 assigned placebo died during the 10.4-year follow-up ( relative risk 0.85 [ 95 % CI 0.74 - 0.97 ] , p=0.02 ) , a difference largely attributable to lower coronary mortality in the simvastatin group ( 238 vs 300 deaths ; 0.76 [ 0.64 - 0.90 ] , p=0.0018 ) . 85 cancer deaths arose in the simvastatin group versus 100 in the placebo group ( 0.81 [ 0.60 - 1.08 ] , p=0.14 ) , and 227 incident cancers were reported in the simvastin group versus 248 in the placebo group ( 0.88 [ 0.73 - 1.05 ] , p=0.15 ) . Incidence of any specific type of cancer did not rise in the simvastatin group . INTERPRETATION Simvastatin treatment for 5 years in a placebo-controlled trial , followed by open-label statin therapy , was associated with survival benefit over 10 years of follow-up compared with open-label statin therapy for the past 5 years only . No difference was noted in mortality from and incidence of cancer between the original simvastatin group and placebo group", "BACKGROUND The PREVEND IT investigated whether treatment targeted at lowering urinary albumin excretion ( UAE ) would reduce adverse cardiovascular events . We obtained extended follow-up data to approximately 10 years to investigate the long-term effects of fosinopril 20 mg and pravastatin 40 mg on cardiovascular outcomes in subjects with UAE > 15 mg per 24 hours . METHODS The original PREVEND IT consisted of 864 participants and 839 survivors after 4 years . For every survivor , the primary end point determined by the combined incidence of cardiovascular mortality and hospitalization for cardiovascular morbidity was registered in several national data bases and electronic hospital systems . RESULTS Mean total follow-up of the extended PREVEND IT was 9.5 years ( range 9.4 - 10.7 years ) . Four years of treatment with fosinopril was not associated with a reduction in the primary end point compared with placebo ( hazard ratio 0.87 , 95 % CI 0.61 - 1.24 [ P = .42 ] ) during long-term follow-up . After 9.5 years , subjects with a baseline UAE in the upper quintile ( > 50 mg/24 hours ) had a total event rate of 29.5 % and were at a higher risk for developing cardiovascular disease compared with less UAE ( hazard ratio 2.03 , 95 % CI 1.38 - 2.97 [ P ≤ .01 ] ) . In addition , 4 years of fosinopril treatment result ed in a risk reduction of 45 % ( 95 % CI 6%-75 % [ P = .04 ] ) in this group compared with placebo . Subjects originally assigned to pravastatin had no overall risk reduction in the primary end point ( P = .99 ) . CONCLUSIONS Elevated UAE is associated with increased cardiovascular mortality and morbidity after 9.5 years of follow-up , with a doubling of the risk if the UAE is > 50 mg per 24 hours . In this group , the benefits of 4-year treatment with fosinopril were sustained during posttrial follow-up for cardiovascular mortality and morbidity . We propose that UAE be used to estimate risk in the general population and that large clinical trials be design ed to confirm the hypothesis that angiotensin-converting enzyme-inhibitor treatment may be beneficial in patients with mildly elevated UAE despite the absence of other comorbidities", "Background The PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) , a placebo-controlled trial of pravastatin , demonstrated a 19 % reduction in coronary outcomes ( p = 0.006 ) after a mean of 3.2 years , with no impact on stroke outcomes or all-cause mortality . However , there was a suggestion of increased cancer risk . Our aim is to determine the long-term benefits and safety of pravastatin treatment in older people using post-trial follow-up of the PROSPER participants . Methods 5,804 ( 2,520 Scottish ) men and women aged 70–82 years with either pre-existing vascular disease or increased risk of such disease because of smoking , hypertension or diabetes , were r and omised to 40 mg pravastatin or matching placebo . Using record linkage to routinely collected health records , all participants ( full cohort ) were linked to death and cancer registries , and the Scottish cohort additionally to hospital admissions , to provide composite fatal/non-fatal cardiovascular outcomes ( total mean follow-up 8.6 years ) . Results Pravastatin treatment for 3.2 years reduced CHD death in the full cohort , hazard ratio ( HR ) 0.80 , 95 % confidence interval ( CI ) 0.68–0.95 , p = 0.0091 and fatal coronary events or coronary hospitalisations in the Scottish cohort ( HR 0.81 , 95 % CI 0.69–0.95 , p = 0.0081 ) over 8.6 years . There was no reduction in stroke or all-cause mortality . Cancer risk was not increased in the full cohort ( HR 1.08 , 95 % CI 0.96–1.21 , p = 0.22 ) . Conclusions Pravastatin treatment of elderly high-risk subjects for 3.2 years provided long-term protection against CHD events and CHD mortality . However , this was not associated with any increase in life expectancy , possibly due to competing mortality with deaths from other causes . There was no evidence of long-term increased risk of cancer . Trial registration IS RCT N40976937", "BACKGROUND Post-trial monitoring of patients in the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) examined whether risk reductions for microvascular and macrovascular disease , achieved with the use of improved blood-pressure control during the trial , would be sustained . METHODS Among 5102 UKPDS patients with newly diagnosed type 2 diabetes mellitus , we r and omly assigned , over a 4-year period beginning in 1987 , 1148 patients with hypertension to tight or less-tight blood-pressure control regimens . The 884 patients who underwent post-trial monitoring were asked to attend annual UKPDS clinics for the first 5 years , but no attempt was made to maintain their previously assigned therapies . Annual question naires completed by patients and general practitioners were used to follow patients who were unable to attend the clinic in years 1 through 5 , and question naires were used for all patients in years 6 to 10 . Seven prespecified aggregate clinical end points were examined on an intention-to-treat basis , according to the previous r and omization categories . RESULTS Differences in blood pressure between the two groups during the trial disappeared within 2 years after termination of the trial . Significant relative risk reductions found during the trial for any diabetes-related end point , diabetes-related death , microvascular disease , and stroke in the group receiving tight , as compared with less tight , blood-pressure control were not sustained during the post-trial follow-up . No risk reductions were seen during or after the trial for myocardial infa rct ion or death from any cause , but a risk reduction for peripheral vascular disease associated with tight blood-pressure control became significant ( P=0.02 ) . CONCLUSIONS The benefits of previously improved blood-pressure control were not sustained when between-group differences in blood pressure were lost . Early improvement in blood-pressure control in patients with both type 2 diabetes and hypertension was associated with a reduced risk of complications , but it appears that good blood-pressure control must be continued if the benefits are to be maintained . ( UKPDS 81 ; Current Controlled Trials number , IS RCT N75451837 .", "BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces mortality among survivors of acute myocardial infa rct ion , but whether to use ACE inhibitors in all patients or only in selected patients is uncertain . METHODS We screened 6676 consecutive patients with 7001 myocardial infa rct ions confirmed by enzyme studies . A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction ( ejection fraction , On days 3 to 7 after infa rct ion , 1749 patients were r and omly assigned to receive oral tr and olapril ( 876 patients ) or placebo ( 873 patients ) . The duration of follow-up was 24 to 50 months . RESULTS During the study period , 304 patients ( 34.7 percent ) in the tr and olapril group died , as compared with 369 ( 42.3 percent ) in the placebo group ( P = 0.001 ) . The relative risk of death in the tr and olapril group , as compared with the placebo group , was 0.78 ( 95 percent confidence interval , 0.67 to 0.91 ) . Tr and olapril also reduced the risk of death from cardiovascular causes ( relative risk , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ; P = 0.001 ) and sudden death ( relative risk , 0.76 ; 95 percent confidence interval , 0.59 to 0.98 ; P = 0.03 ) . Progression to severe heart failure was less frequent in the tr and olapril group ( relative risk , 0.71 ; 95 percent confidence interval , 0.56 to 0.89 ; P = 0.003 ) . In contrast , the risk of recurrent myocardial infa rct ion ( fatal or nonfatal ) was not significantly reduced ( relative risk , 0.86 ; 95 percent confidence interval , 0.66 to 1.13 ; P = 0.29 ) . CONCLUSIONS Long-term treatment with tr and olapril in patients with reduced left ventricular function soon after myocardial infa rct ion significantly reduced the risk of overall mortality , mortality from cardiovascular causes , sudden death , and the development of severe heart failure . That mortality was reduced in a r and omized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infa rct ion", "BACKGROUND Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals , their efficacy and safety in elderly people is not fully established . Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with , or at high risk of developing , cardiovascular disease and stroke . METHODS We did a r and omised controlled trial in which we assigned 5804 men ( n=2804 ) and women ( n=3000 ) aged 70 - 82 years with a history of , or risk factors for , vascular disease to pravastatin ( 40 mg per day ; n=2891 ) or placebo ( n=2913 ) . Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death , non-fatal myocardial infa rct ion , and fatal or non-fatal stroke . Analysis was by intention-to-treat . FINDINGS Pravastatin lowered LDL cholesterol concentrations by 34 % and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo ( hazard ratio 0.85 , 95 % CI 0.74 - 0.97 , p=0.014 ) . Coronary heart disease death and non-fatal myocardial infa rct ion risk was also reduced ( 0.81 , 0.69 - 0.94 , p=0.006 ) . Stroke risk was unaffected ( 1.03 , 0.81 - 1.31 , p=0.8 ) , but the hazard ratio for transient ischaemic attack was 0.75 ( 0.55 - 1.00 , p=0.051 ) . New cancer diagnoses were more frequent on pravastatin than on placebo ( 1.25 , 1.04 - 1.51 , p=0.020 ) . However , incorporation of this finding in a meta- analysis of all pravastatin and all statin trials showed no overall increase in risk . Mortality from coronary disease fell by 24 % ( p=0.043 ) in the pravastatin group . Pravastatin had no significant effect on cognitive function or disability . INTERPRETATION Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals . PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people", "Objective To assess if very elderly people with hypertension obtain early benefit from antihypertensive treatment . Design One year open label active treatment extension of r and omised controlled trial ( Hypertension in the Very Elderly Trial ( HYVET ) ) . Setting Hospital and general practice based centres mainly in eastern and western Europe , China , and Tunisia . Participants People on double blind treatment at the end of HYVET were eligible to enter the extension . Interventions Participants on active blood pressure lowering treatment continued taking active drug ; those on placebo were given active blood pressure lowering treatment . The treatment regimen was as used in the main trial — indapamide SR 1.5 mg ( plus perindopril 2 - 4 mg if required)—with the same target blood pressure of less than 150/80 mm Hg . Main outcome measures The primary outcome was all stroke ; other outcomes included total mortality , cardiovascular mortality , and cardiovascular events . Results Of 1882 people eligible for entry to the extension , 1712 ( 91 % ) agreed to participate . During the extension period , 1682 patient years were accrued . By six months , the difference in blood pressure between the two groups was 1.2/0.7 mm Hg . Comparing people previously treated with active drug and those previously on placebo , no significant differences were seen for stroke ( n=13 ; hazard ratio 1.92 , 95 % confidence interval 0.59 to 6.22 ) or cardiovascular events ( n=25 ; 0.78 , 0.36 to 1.72 ) . Differences were seen for total mortality ( 47 deaths ; hazard ratio 0.48 , 0.26 to 0.87 ; P=0.02 ) and cardiovascular mortality ( 11 deaths ; 0.19 , 0.04 to 0.87 ; P=0.03 ) . Conclusion Very elderly patients with hypertension may gain immediate benefit from treatment . Sustained differences in reductions of total mortality and cardiovascular mortality reinforce the benefits and support the need for early and long term treatment . Trial registration Clinical trials NCT00122811", "BACKGROUND In the Action in Diabetes and Vascular Disease : Preterax and Diamicron Modified Release Controlled Evaluation ( ADVANCE ) factorial trial , the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes , but intensive glucose control , targeting a glycated hemoglobin level of less than 6.5 % , did not . We now report results of the 6-year post-trial follow-up . METHODS We invited surviving participants , who had previously been assigned to perindopril-indapamide or placebo and to intensive or st and ard glucose control ( with the glucose-control comparison extending for an additional 6 months ) , to participate in a post-trial follow-up evaluation . The primary end points were death from any cause and major macrovascular events . RESULTS The baseline characteristics were similar among the 11,140 patients who originally underwent r and omization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years ( blood-pressure-lowering comparison ) or 5.4 years ( glucose-control comparison ) . Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit . The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure-lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up ; the hazard ratios were 0.91 ( 95 % confidence interval [ CI ] , 0.84 to 0.99 ; P=0.03 ) and 0.88 ( 95 % CI , 0.77 to 0.99 ; P=0.04 ) , respectively . No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the st and ard-glucose-control group ; the hazard ratios were 1.00 ( 95 % CI , 0.92 to 1.08 ) and 1.00 ( 95 % CI , 0.92 to 1.08 ) , respectively . CONCLUSIONS The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure-lowering therapy were attenuated but still evident at the end of follow-up . There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events . ( Funded by the National Health and Medical Research Council of Australia and others ; ADVANCE-ON Clinical Trials.gov number , NCT00949286 . )", "Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival . The present trial was design ed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease ( CHD ) . 4444 patients with angina pectoris or previous myocardial infa rct ion and serum cholesterol 5.5 - 8.0 mmol/L on a lipid-lowering diet were r and omised to double-blind treatment with simvastatin or placebo . Over the 5.4 years median follow-up period , simvastatin produced mean changes in total cholesterol , low-density-lipoprotein cholesterol , and high-density-lipoprotein cholesterol of -25 % , -35 % , and + 8 % , respectively , with few adverse effects . 256 patients ( 12 % ) in the placebo group died , compared with 182 ( 8 % ) in the simvastatin group . The relative risk of death in the simvastatin group was 0.70 ( 95 % CI 0.58 - 0.85 , p = 0.0003 ) . The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6 % and 91.3 % , respectively . There were 189 coronary deaths in the placebo group and 111 in the simvastatin group ( relative risk 0.58 , 95 % CI 0.46 - 0.73 ) , while noncardiovascular causes accounted for 49 and 46 deaths , respectively . 622 patients ( 28 % ) in the placebo group and 431 ( 19 % ) in the simvastatin group had one or more major coronary events . The relative risk was 0.66 ( 95 % CI 0.59 - 0.75 , p escaping such events were 70.5 % and 79.6 % . This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more . Other benefits of treatment included a 37 % reduction ( p risk of undergoing myocardial revascularisation procedures . This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients", "Background —Microalbuminuria is associated with increased risk of cardiovascular events . We assessed whether therapeutic intervention aim ed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects ( 15 to 300 mg/24 hours ) . Methods and Results —From the Prevention of Renal and Vascular Endstage Disease ( PREVEND ) cohort ( n=8592 ) , 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial ( PREVEND IT ) . Of these subjects , 864 were r and omized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo . The mean follow-up was 46 months , and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity . Mean age was 51±12 years ; 65 % of subjects were male , and 3.4 % had a previous cardiovascular event . Mean cholesterol level was 5.8±1.0 mmol/L , mean systolic/diastolic blood pressure was 130±18/76±10 mm Hg , and median urinary albumin excretion was 22.8 ( 15.8 to 41.3 ) mg/24 hours . The primary end point occurred in 45 subjects ( 5.2 % ) . Fosinopril reduced urinary albumin excretion by 26 % ( P with fosinopril showed a 40 % lower incidence of the primary end point ( hazard ratio 0.60 [ 95 % CI 0.33 to 1.10 ] , P=0.098 , log-rank ) . Pravastatin did not reduce urinary albumin excretion , and subjects treated with pravastatin showed a 13 % lower incidence of the primary end point than subjects in the placebo group ( 0.87 [ 0.49 to 1.57 ] , P=0.649 , log-rank ) . Conclusions —In microalbuminuric subjects , treatment with fosinopril had a significant effect on urinary albumin excretion . In addition , fosinopril treatment was associated with a trend in reducing cardiovascular events . Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events ", "BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 years ) , who after 3 months ' diet treatment had a mean of two fasting plasma glucose ( FPG ) concentrations of 6.1 - 15.0 mmol/L were r and omly assigned intensive policy with a sulphonylurea ( chlorpropamide , glibenclamide , or glipizide ) or with insulin , or conventional policy with diet . The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group , the aim was the best achievable FPG with diet alone ; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment : any diabetes-related endpoint ( sudden death , death from hyperglycaemia or hypoglycaemia , fatal or non-fatal myocardial infa rct ion , angina , heart failure , stroke , renal failure , amputation [ of at least one digit ] , vitreous haemorrhage , retinopathy requiring photocoagulation , blindness in one eye , or cataract extraction ) ; diabetes-related death ( death from myocardial infa rct ion , stroke , peripheral vascular disease , renal disease , hyperglycaemia or hypoglycaemia , and sudden death ) ; all-cause mortality . Single clinical endpoints and surrogate sub clinical endpoints were also assessed . All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy . FINDINGS Over 10 years , haemoglobin A1c ( HbA1c ) was 7.0 % ( 6.2 - 8.2 ) in the intensive group compared with 7.9 % ( 6.9 - 8.8 ) in the conventional group -- an 11 % reduction . There was no difference in HbA1c among agents in the intensive group . Compared with the conventional group , the risk in the intensive group was 12 % lower ( 95 % CI 1 - 21 , p=0.029 ) for any diabetes-related endpoint ; 10 % lower ( -11 to 27 , p=0.34 ) for any diabetes-related death ; and 6 % lower ( -10 to 20 , p=0.44 ) for all-cause mortality . Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25 % risk reduction ( 7 - 40 , p=0.0099 ) in microvascular endpoints , including the need for retinal photocoagulation . There was no difference for any of the three aggregate endpoints between the three intensive agents ( chlorpropamide , glibenclamide , or insulin ) . Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis ( both p rates of major hypoglycaemic episodes per year were 0.7 % with conventional treatment , 1.0 % with chlorpropamide , 1.4 % with glibenclamide , and 1.8 % with insulin . Weight gain was significantly higher in the intensive group ( mean 2.9 kg ) than in the conventional group ( p insulin had a greater gain in weight ( 4.0 kg ) than those assigned chlorpropamide ( 2.6 kg ) or glibenclamide ( 1.7 kg ) . INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications , but not macrovascular disease , in patients with type 2 diabetes . ( ABSTRACT TRUNCATED", "Background —We have previously demonstrated that ramipril reduces vascular events and new diagnoses of diabetes when given for a 4.5-year period . However , it is not known whether the benefits are observed in subgroups of patients at varying risk or on other proven therapies and whether the benefits are sustained beyond the current trial . The 2 aims of this investigation were to assess whether the benefits observed during the HOPE trial were ( 1 ) maintained after trial cessation during an additional 2.6 years of follow-up and ( 2 ) observed in subgroups based on risk and ancillary treatments . Methods and Results —Of the initial 267 study centers and 9297 patients , 174 centers and 4528 patients agreed to further follow-up . The rates of use of angiotensin-converting-enzyme inhibitors ( ACEIs ) in the 2 groups ( 72 % ramipril versus 68 % placebo ) were similar after the end of the trial . During the posttrial follow-up , patients allocated to ramipril had a 19 % further lower relative risk ( RR ) of myocardial infa rct ion ( 95 % confidence interval [ CI ] , 0.65 to 1.01 ) , a 16 % lower RR ( 95 % CI , 0.70 to 0.99 ) of revascularization , and a 34 % lower RR of a new diagnosis of diabetes ( 95 % CI , 0.46 to 0.95 ) . Similar RR reductions in vascular events were observed during and after the active phase of the trial , regardless of baseline risk ( RR of 0.76 , 0.89 , and 0.83 for low- , medium- , and high-risk patients , respectively ) or ancillary treatments ( RR of 0.90 for aspirin , 0.76 for & bgr;-blockers , and 0.84 for lipid-lowering medication ) . Conclusions —The benefits of ramipril observed during the active period of the HOPE trial were maintained during posttrial follow-up for cardiovascular death , stroke , and hospitalization for heart failure . Additional reductions in myocardial infa rct ion , revascularization , and the development of diabetes were observed during the follow-up phase despite similar rates of ACEI use in the 2 r and omized groups . These benefits were consistent regardless of patient risk or ancillary treatments", "BACKGROUND The West of Scotl and Coronary Prevention Study was a r and omized clinical trial comparing pravastatin with placebo in men with hypercholesterolemia who did not have a history of myocardial infa rct ion , with an average follow-up of approximately 5 years . The combined outcome of death from definite coronary heart disease or definite nonfatal myocardial infa rct ion was reduced from 7.9 to 5.5 % ( P deaths , hospitalizations and deaths due to coronary events and stroke , and incident cancers and deaths from cancer were tracked with the use of a national computerized record-linkage system . The results were analyzed with time-to-event analyses and use of Cox proportional-hazards models . RESULTS Five years after the trial ended , 38.7 % of the original statin group and 35.2 % of the original placebo group were being treated with a statin . In the period approximately 10 years after completion of the trial , the risk of death from coronary heart disease or nonfatal myocardial infa rct ion was 10.3 % in the placebo group and 8.6 % in the pravastatin group ( P=0.02 ) ; over the entire follow-up period , the rate was 15.5 % in the placebo group and 11.8 % in the pravastatin group ( P combined rate of death from coronary heart disease and hospitalization for coronary events for both periods . The rate of death from cardiovascular causes was reduced ( P=0.01 ) , as was the rate of death from any cause ( P=0.03 ) , over the entire follow-up period . There were no excess deaths from noncardiovascular causes or excess fatal or incident cancers . CONCLUSIONS In this analysis , 5 years of treatment with pravastatin was associated with a significant reduction in coronary events for a subsequent 10 years in men with hypercholesterolemia who did not have a history of myocardial infa rct ion", "BACKGROUND Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear . It has been suggested that antihypertensive therapy may reduce the risk of stroke , despite possibly increasing the risk of death . METHODS We r and omly assigned 3845 patients from Europe , China , Australasia , and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide ( sustained release , 1.5 mg ) or matching placebo . The angiotensin-converting-enzyme inhibitor perindopril ( 2 or 4 mg ) , or matching placebo , was added if necessary to achieve the target blood pressure of 150/80 mm Hg . The primary end point was fatal or nonfatal stroke . RESULTS The active-treatment group ( 1933 patients ) and the placebo group ( 1912 patients ) were well matched ( mean age , 83.6 years ; mean blood pressure while sitting , 173.0/90.8 mm Hg ) ; 11.8 % had a history of cardiovascular disease . Median follow-up was 1.8 years . At 2 years , the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group . In an intention-to-treat analysis , active treatment was associated with a 30 % reduction in the rate of fatal or nonfatal stroke ( 95 % confidence interval [ CI ] , -1 to 51 ; P=0.06 ) , a 39 % reduction in the rate of death from stroke ( 95 % CI , 1 to 62 ; P=0.05 ) , a 21 % reduction in the rate of death from any cause ( 95 % CI , 4 to 35 ; P=0.02 ) , a 23 % reduction in the rate of death from cardiovascular causes ( 95 % CI , -1 to 40 ; P=0.06 ) , and a 64 % reduction in the rate of heart failure ( 95 % CI , 42 to 78 ; P serious adverse events were reported in the active-treatment group ( 358 , vs. 448 in the placebo group ; P=0.001 ) . CONCLUSIONS The results provide evidence that antihypertensive treatment with indapamide ( sustained release ) , with or without perindopril , in persons 80 years of age or older is beneficial . ( Clinical Trials.gov number , NCT00122811 [ Clinical Trials.gov ] . )", "AIMS The aim of this study was to determine the outcome benefits in those originally assigned atorvastatin in the Anglo-Sc and inavian Cardiac Outcomes Trial-8 years after closure of the lipid-lowering arm ( LLA ) of the trial ( ASCOT-LLA ) among the U.K. population . METHODS AND RESULTS ASCOT-LLA was a factorially design ed double-blind placebo-controlled trial of atorvastatin in 10 305 hypertensive patients enrolled into the ASCOT-Blood Pressure Lowering Arm ( BPLA ) of the trial and with total cholesterol concentrations , at baseline , of ASCOT-LLA was stopped prematurely after a median 3.3-year follow-up because of a 36 % relative risk reduction ( RRR ) in non-fatal myocardial infa rct ion and fatal coronary heart disease ( CHD ) ( the primary outcome ) in favour of atorvastatin and a non-significant reduction in CV deaths ( 16 % ) and all-cause mortality ( 13 % ) . After a further 2.2 years at the end of ASCOT-BPLA , despite extensive crossovers from and to statin usage , the RRR in all endpoints remained essentially unchanged . A median 11 years after initial r and omization and ∼8 years after closure of LLA , all-cause mortality ( n=520 and 460 in placebo and atorvastatin , respectively ) remained significantly lower in those originally assigned atorvastatin ( HR 0.86 , CI 0.76 - 0.98 , P=0.02 ) . CV deaths were fewer , but not significant ( HR 0.89 , CI 0.72 - 1.11 , P=0.32 ) and non-CV deaths were significantly lower ( HR 0.85 , CI 0.73 - 0.99 , P=0.03 ) in those formerly assigned atorvastatin attributed to a reduction in deaths due to infection and respiratory illness . CONCLUSION Legacy effects of those originally assigned atorvastatin may contribute to long-term benefits on all-cause mortality . An explanation for long-term benefits on non-CV deaths has not been established", "CONTEXT Hypertension is a leading cause of end-stage renal disease ( ESRD ) in the United States , with no known treatment to prevent progressive declines leading to ESRD . OBJECTIVE To compare the effects of 2 levels of blood pressure ( BP ) control and 3 antihypertensive drug classes on glomerular filtration rate ( GFR ) decline in hypertension . DESIGN R and omized 3 x 2 factorial trial with enrollment from February 1995 to September 1998 . SETTING AND PARTICIPANTS A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease ( GFR , 20 - 65 mL/min per 1.73 m(2 ) ) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years . INTERVENTIONS Participants were r and omly assigned to 1 of 2 mean arterial pressure goals , 102 to 107 mm Hg ( usual ; n = 554 ) or 92 mm Hg or less ( lower ; n = 540 ) , and to initial treatment with either a beta-blocker ( metoprolol 50 - 200 mg/d ; n = 441 ) , an angiotensin-converting enzyme inhibitor ( ramipril 2.5 - 10 mg/d ; n = 436 ) or a dihydropyridine calcium channel blocker , ( amlodipine 5 - 10 mg/d ; n = 217 ) . Open-label agents were added to achieve the assigned BP goals . MAIN OUTCOME MEASURES Rate of change in GFR ( GFR slope ) ; clinical composite outcome of reduction in GFR by 50 % or more ( or > or = 25 mL/min per 1.73 m2 ) from baseline , ESRD , or death . Three primary treatment comparisons were specified : lower vs usual BP goal ; ramipril vs metoprolol ; and amlodipine vs metoprolol . RESULTS Achieved BP averaged ( SD ) 128/78 ( 12/8 ) mm Hg in the lower BP group and 141/85 ( 12/7 ) mm Hg in the usual BP group . The mean ( SE ) GFR slope from baseline through 4 years did not differ significantly between the lower BP group ( -2.21 [ 0.17 ] mL/min per 1.73 m2 per year ) and the usual BP group ( -1.95 [ 0.17 ] mL/min per 1.73 m2 per year ; P = .24 ) , and the lower BP goal did not significantly reduce the rate of the clinical composite outcome ( risk reduction for lower BP group = 2 % ; 95 % confidence interval [ CI ] , -22 % to 21 % ; P = .85 ) . None of the drug group comparisons showed consistent significant differences in the GFR slope . However , compared with the metoprolol and amlodipine groups , the ramipril group manifested risk reductions in the clinical composite outcome of 22 % ( 95 % CI , 1%-38 % ; P = .04 ) and 38 % ( 95 % CI , 14%-56 % ; P = .004 ) , respectively . There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups . CONCLUSIONS No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal . Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline", "Background To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension , we extended the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) trial by an open-label follow-up study lasting 4 years . Methods The Syst-Eur trial included 4695 r and omized patients with minimum age of 60 years and an untreated blood pressure of 160–219 mmHg systolic and below 95 mmHg diastolic . The double-blind trial ended after a median follow-up of 2.0 years ( range 1–97 months ) . Of 4409 patients still alive , 3517 received open-label treatment consisting of nitrendipine ( 10–40 mg daily ) with the possible addition of enalapril ( 5–20 mg daily ) , hydrochlorothiazide ( 12.5–25 mg daily ) , or both add-on drugs . Non- participants ( n = 892 ) were also followed up . Results Median follow-up increased to 6.1 years . Systolic pressure decreased to below 150 mmHg ( target level ) in 2628 participants ( 75.0 % ) . During the 4-year open-label follow-up , stroke and cardiovascular complications occurred at similar frequencies in patients formerly r and omized to placebo and those continuing active treatment . These rates were similar to those previously observed in the active-treatment group during the double-blind trial . Considering the total follow-up of 4695 r and omized patients , immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28 % ( P = 0.01 ) and 15 % ( P = 0.03 ) , respectively , with a similar tendency for total mortality ( 13 % , P = 0.09 ) . In 492 diabetic patients , the corresponding estimates of long-term benefit ( P blood pressure control in most older patients with isolated systolic hypertension . Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years . These findings underscore the necessity of early treatment of isolated systolic hypertension", "A multicenter double-blind r and omized study was carried out to compare the effect of timolol ( 10 mg twice daily ) with that of placebo in patients surviving acute myocardial infa rct ion . Treatment was started seven to 28 days after infa rct ion in 1884 patients ( 945 taking timolol , and 939 placebo ) , who represented 52 per cent of those evaluated for entry ; the patients were followed for 12 to 33 months ( mean , 17 ) . There were 152 deaths in the placebo group and 98 in the timolol group . When deaths that occurred during treatment or within 28 days of withdrawal were considered , the cumulated sudden-death rate over 33 months was 13.9 per cent in the placebo group and 7.7 per cent in the timolol group -- a reduction of 44.6 per cent ( P = 0.0001 ) . The cumulated reinfa rct ion rate was 20.1 per cent in the placebo group and 14.4 per cent in the timolol group ( P = 0.0006 ) . We conclude that long-term treatment with timolol in patients surviving acute myocardial infa rct ion reduces mortality and the rate of reinfa rct ion", "The Hypertension Detection and Follow-up Program ( HDFP ) previously described a significant reduction in five-year , all-cause mortality in its intensively treated stepped care ( SC ) group relative to its referred care ( RC ) control group . At the time this finding was described , a proportion of the SC cohort had been treated for periods as long as 6.7 years , but comparable RC and SC mortality data beyond five years were not available . These data , which are described herein , indicate that the 6.7-year life-table mortality rates were 95.1/1000 participants for SC vs 116.3/1000 participants for RC , a larger mortality difference than was observed at five years . This favorable finding for SC extended to all major subgroups , including white women and those aged 30 to 49 years at trial entry . Six months after the close of the treatment trial , a two-year posttrial surveillance study , which extended mortality follow-up to 8.3 years , was conducted . The posttrial use of antihypertensive medication declined in SC and increased in RC participants so that by the end of the posttrial period , there was little difference in the percentages of SC and RC participants taking medication . Control of blood pressure , indicated by mean diastolic blood pressure and by percent of participants with a pressure of 90 mm Hg or less , was slightly better for SC than for RC participants ( SC group , 86.5 mm Hg and 68 % controlled ; RC group , 87.8 mm Hg and 62 % controlled ) . The absolute mortality advantage found at 6.7 years persisted and increased throughout the posttrial period of follow-up despite discontinuation of the formal SC therapy program . It is postulated that regression of hypertensive end-organ changes brought about by the more effective SC treatment caused this favorable outcome", "BACKGROUND Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes , and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension . We assessed the effects of the routine administration of an angiotensin converting enzyme ( ACE ) inhibitor-diuretic combination on serious vascular events in patients with diabetes , irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs . METHODS The trial was done by 215 collaborating centres in 20 countries . After a 6-week active run-in period , 11 140 patients with type 2 diabetes were r and omised to treatment with a fixed combination of perindopril and indapamide or matching placebo , in addition to current therapy . The primary endpoints were composites of major macrovascular and microvascular events , defined as death from cardiovascular disease , non-fatal stroke or non-fatal myocardial infa rct ion , and new or worsening renal or diabetic eye disease , and analysis was by intention-to-treat . The macrovascular and microvascular composites were analysed jointly and separately . This trial is registered with Clinical Trials.gov , number NCT00145925 . FINDINGS After a mean of 4.3 years of follow-up , 73 % of those assigned active treatment and 74 % of those assigned control remained on r and omised treatment . Compared with patients assigned placebo , those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg . The relative risk of a major macrovascular or microvascular event was reduced by 9 % ( 861 [ 15.5 % ] active vs 938 [ 16.8 % ] placebo ; hazard ratio 0.91 , 95 % CI 0.83 - 1.00 , p=0.04 ) . The separate reductions in macrovascular and microvascular events were similar but were not independently significant ( macrovascular 0.92 ; 0.81 - 1.04 , p=0.16 ; microvascular 0.91 ; 0.80 - 1.04 , p=0.16 ) . The relative risk of death from cardiovascular disease was reduced by 18 % ( 211 [ 3.8 % ] active vs 257 [ 4.6 % ] placebo ; 0.82 , 0.68 - 0.98 , p=0.03 ) and death from any cause was reduced by 14 % ( 408 [ 7.3 % ] active vs 471 [ 8.5 % ] placebo ; 0.86 , 0.75 - 0.98 , p=0.03 ) . There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline . INTERPRETATION Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events , including death . Although the confidence limits were wide , the results suggest that over 5 years , one death due to any cause would be averted among every 79 patients assigned active therapy", "BACKGROUND Renal transplant recipients are at increased risk of premature cardiovascular disease . Although statins reduce cardiovascular risk in the general population , their efficacy and safety in renal transplant recipients have not been established . We investigated the effects of fluvastatin on cardiac and renal endpoints in this population . METHODS We did a multicentre , r and omised , double-blind , placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0 - 9.0 mmol/L. We r and omly assigned patients fluvastatin ( n=1050 ) or placebo ( n=1052 ) and follow up was for 5 - 6 years . The primary endpoint was the occurrence of a major adverse cardiac event , defined as cardiac death , non-fatal myocardial infa rct ion ( MI ) , or coronary intervention procedure . Secondary endpoints were individual cardiac events , combined cardiac death or non-fatal MI , cerebrovascular events , non-cardiovascular death , all-cause mortality , and graft loss or doubling of serum creatinine . Analysis was by intention to treat . FINDINGS After a mean follow-up of 5.1 years , fluvastatin lowered LDL cholesterol concentrations by 32 % . Risk reduction with fluvastatin for the primary endpoint ( risk ratio 0.83 [ 95 % CI 0.64 - 1.06 ] , p=0.139 ) was not significant , although there were fewer cardiac deaths or non-fatal MI ( 70 vs 104 , 0.65 [ 0.48 - 0.88 ] p=0.005 ) in the fluvastatin group than in the placebo group . Coronary intervention procedures and other secondary endpoints did not differ significantly between groups . INTERPRETATION Although cardiac deaths and non-fatal MI seemed to be reduced , fluvastatin did not generally reduce rates of coronary intervention procedures or mortality . Overall effects of fluvastatin were similar to those of statins in other population", "BACKGROUND Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction , whether or not they have heart failure . We assessed the role of an angiotensin-converting-enzyme inhibitor , ramipril , in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure . METHODS A total of 9297 high-risk patients ( 55 years of age or older ) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were r and omly assigned to receive ramipril ( 10 mg once per day orally ) or matching placebo for a mean of five years . The primary outcome was a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes . The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper . RESULTS A total of 651 patients who were assigned to receive ramipril ( 14.0 percent ) reached the primary end point , as compared with 826 patients who were assigned to receive placebo ( 17.8 percent ) ( relative risk , 0.78 ; 95 percent confidence interval , 0.70 to 0.86 ; P rates of death from cardiovascular causes ( 6.1 percent , as compared with 8.1 percent in the placebo group ; relative risk , 0.74 ; P myocardial infa rct ion ( 9.9 percent vs. 12.3 percent ; relative risk , 0.80 ; P stroke ( 3.4 percent vs. 4.9 percent ; relative risk , 0.68 ; P death from any cause ( 10.4 percent vs. 12.2 percent ; relative risk , 0.84 ; P=0.005 ) , revascularization procedures ( 16.3 percent vs. 18.8 percent ; relative risk , 0.85 ; P cardiac arrest ( 0.8 percent vs. 1.3 percent ; relative risk , 0.62 ; P=0.02 ) , [ corrected ] heart failure ( 9.1 percent vs. 11.6 percent ; relative risk , 0.77 ; P complications related to diabetes ( 6.4 percent vs. 7.6 percent ; relative risk , 0.84 ; P=0.03 ) . CONCLUSIONS Ramipril significantly reduces the rates of death , myocardial infa rct ion , and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure", " The original Norwegian Multicenter Study on Timolol after Myocardial Infa rct ion was a double-blind , r and omized study comparing the effect of timolol with that of placebo for up to 33 months after acute myocardial infa rct ion . The initial results showed that the cumulated mortality rate was 39.4 per cent lower among 945 patients r and omly assigned to timolol treatment than among 939 patients r and omly assigned to placebo ( P = 0.0003 ) . After the end of the double-blind period the majority of participating patients in the timolol group continued to receive beta-adrenergic blockade , whereas the majority of placebo-treated patients continued without such blockade . During an extended follow-up of participating patients up to 72 months after r and omization , the mortality curves of the two groups continued to rise in parallel . Cumulated mortality rates were 32.3 per cent in the placebo group and 26.4 per cent in the timolol group ( P = 0.0028 ) . We conclude that the previously observed early beneficial effect of beta-adrenergic blocking therapy is maintained for at least six years after infa rct ion", "BACKGROUND It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity . We studied the effect of an angiotensin-converting -- enzyme inhibitor , enalapril , on total mortality and mortality from cardiovascular causes , the development of heart failure , and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure . METHODS Patients were r and omly assigned to receive either placebo ( n = 2117 ) or enalapril ( n = 2111 ) at doses of 2.5 to 20 mg per day in a double-blind trial . Follow-up averaged 37.4 months . RESULTS There were 334 deaths in the placebo group , as compared with 313 in the enalapril group ( reduction in risk , 8 percent by the log-rank test ; 95 percent confidence interval , -8 percent [ an increase of 8 percent ] to 21 percent ; P = 0.30 ) . The reduction in mortality from cardiovascular causes was larger but was not statistically significant ( 298 deaths in the placebo group vs. 265 in the enalapril group ; risk reduction , 12 percent ; 95 percent confidence interval , -3 to 26 percent ; P = 0.12 ) . When we combined patients in whom heart failure developed and those who died , the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group ( 630 vs. 818 ; risk reduction , 29 percent ; 95 percent confidence interval , 21 to 36 percent ; P less than 0.001 ) . In addition , fewer patients given enalapril died or were hospitalized for heart failure ( 434 in the enalapril group ; vs. 518 in the placebo group ; risk reduction , 20 percent ; 95 percent confidence interval , 9 to 30 percent ; P less than 0.001 ) . CONCLUSIONS The angiotensin-converting -- enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations , as compared with the rates in the group given placebo , among patients with asymptomatic left ventricular dysfunction . There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril", "Renal transplant recipients ( RTR ) have an increased risk of premature cardiovascular disease . The ALERT study is the first trial to evaluate the effect of statin therapy on cardiac outcomes following renal transplantation . Patients initially r and omized to fluvastatin or placebo in the 5–6 year ALERT study were offered open‐label fluvastatin XL 80 mg/day in a 2‐year extension to the original study . The primary endpoint was time to first major adverse cardiac event ( MACE ) . Of 1787 patients who completed ALERT , 1652 ( 92 % ) were followed in the extension . Mean total follow‐up was 6.7 years . Mean LDL‐cholesterol was 98 mg/dL ( 2.5 mmol/L ) at last follow‐up compared to a pre‐ study level of 159 mg/dL ( 4.1 mmol/L ) . Patients r and omized to fluvastatin had a reduced risk of MACE ( hazards ratio [ HR ] 0.79 , 95 % CI 0.63–0.99 , p = 0.036 ) , and a 29 % reduction in cardiac death or definite non‐fatal MI ( HR 0.71 , 95 % CI 0.55–0.93 , p = 0.014 ) . Total mortality and graft loss did not differ significantly between groups . Fluvastatin produces a safe and effective reduction in LDL‐cholesterol associated with reduced risk of MACE in RTR . The lipid‐lowering and cardiovascular benefits of fluvastatin are comparable to those of statins in other patient groups , and support use of fluvastatin in RTR", "BACKGROUND The Post Coronary Artery Bypass Graft Trial , design ed to compare the effects of 2 lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery , demonstrated that aggressive lowering of LDL cholesterol ( LDL-C ) levels to Low-dose anticoagulation did not significantly affect progression . METHODS AND RESULTS Approximately 3 years after the last trial visit , Clinical Center Coordinators contacted each patient by telephone to ascertain the occurrence of cardiovascular events and procedures . The National Death Index was used to ascertain vital status for patients who could not be contacted . Vital status was established for all but 3 of 1351 patients . Information on nonfatal events was available for 95 % of surviving patients . A 30 % reduction in revascularization procedures and 24 % reduction in a composite clinical end point were observed in patients assigned to aggressive strategy compared with patients assigned to moderate strategy during 7.5 years of follow-up , P=0 . 0006 and 0.001 , respectively . Reductions of 35 % in deaths and 31 % in deaths or myocardial infa rct ions with low-dose anticoagulation compared with placebo were also observed , P=0.008 and 0.003 , respectively . CONCLUSIONS -The long-term clinical benefit observed during extended follow-up in patients assigned to the aggressive strategy is consistent with the angiographic findings of delayed atherosclerosis progression in grafts observed during the trial . The apparent long-term benefit of low-dose warfarin remains unexplained", "OBJECTIVE To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal ( total ) stroke in isolated systolic hypertension . DESIGN Multicenter , r and omized , double-blind , placebo-controlled . SETTING Community-based ambulatory population in tertiary care centers . PARTICIPANTS 4736 persons ( 1.06 % ) from 447,921 screenees aged 60 years and above were r and omized ( 2365 to active treatment , 2371 to placebo ) . Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg . Of the participants , 3161 were not receiving antihypertensive medication at initial contact , and 1575 were . The average systolic blood pressure was 170 mm Hg ; average diastolic blood pressure , 77 mm Hg . The mean age was 72 years , 57 % were women , and 14 % were black . INTERVENTIONS -- Participants were stratified by clinical center and by antihypertensive medication status at initial contact . For step 1 of the trial , dose 1 was chlorthalidone , 12.5 mg/d , or matching placebo ; dose 2 was 25 mg/d . For step 2 , dose 1 was atenolol , 25 mg/d , or matching placebo ; dose 2 was 50 mg/d . MAIN OUTCOME MEASURES Primary . Nonfatal and fatal ( total ) stroke . Secondary . Cardiovascular and coronary morbidity and mortality , all-cause mortality , and quality of life measures . RESULTS Average follow-up was 4.5 years . The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group , and the 5-year average diastolic blood pressure was 72 and 68 mm Hg , respectively . The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo . The relative risk by proportional hazards regression analysis was 0.64 ( P = .0003 ) . For the secondary end point of clinical nonfatal myocardial infa rct ion plus coronary death , the relative risk was 0.73 . Major cardiovascular events were reduced ( relative risk , 0.68 ) . For deaths from all causes , the relative risk was 0.87 . CONCLUSION In persons aged 60 years and over with isolated systolic hypertension , antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36 % , with 5-year absolute benefit of 30 events per 1000 participants . Major cardiovascular events were reduced , with 5-year absolute benefit of 55 events per 1000", "BACKGROUND The Long-term Intervention with Pravastatin in Ischaemic Disease ( LIPID ) study showed that pravastatin therapy over 6 years reduced mortality and cardiovascular events in patients with previous acute coronary syndromes and average cholesterol concentrations . We assessed the longer-term effects of initial treatment with pravastatin on further cardiovascular events and mortality over a total follow-up period of 8 years . METHODS In the main trial , 9014 patients with previous myocardial infa rct ion or unstable angina and a baseline plasma cholesterol concentration of 4.0 - 7.0 mmol/L were r and omly assigned pravastatin 40 mg daily or placebo and followed up for 6 years . Subsequently , all patients were offered open-label pravastatin for 2 more years . Major cardiovascular events and adverse events were compared according to initial treatment assignment . FINDINGS 7680 ( 97 % of those still alive ) had 2 years of extended follow-up . 3766 ( 86 % ) of those assigned placebo and 3914 ( 88 % ) assigned pravastatin agreed to take open-label pravastatin . During this period , patients originally assigned pravastatin had almost identical cholesterol concentrations to those assigned placebo , but a lower risk of death from all causes ( 219 [ 5.6 % ] vs 255 [ 6.8 % ] , p=0.029 ) , coronary heart disease ( CHD ) death ( 108 [ 2.8 % ] vs 137 [ 3.6 % ] , p=0.026 ) , and CHD death or non-fatal myocardial infa rct ion ( 176 [ 4.5 % ] vs 196 [ 5.2 % ] , p=0.08 ) . Over the total 8-year period , all-cause mortality was 888 ( 19.7 % ) in the group originally assigned placebo and 717 ( 15.9 % ) in the group originally assigned pravastatin , CHD mortality was 510 ( 11.3 % ) versus 395 ( 8.8 % ) , myocardial infa rct ion was 570 ( 12.7 % ) versus 435 ( 9.6 % ; each p stroke was 272 ( 6.0 % ) versus 224 ( 5.0 % ; p=0.015 ) . Stronger evidence of separate treatment benefits than in the main trial was seen in important prespecified subgroups ( women , patients aged > or = 70 years , and those with total cholesterol . Pravastatin had no significant adverse effects . INTERPRETATION The evidence of sustained treatment benefits and safety of long-term pravastatin treatment reinforces the importance of long-term cholesterol-lowering treatment for almost all patients with previous CHD events", "The authors conducted a r and omized , controlled , multicenter trial , in which they assigned well-controlled hypertensive participants aged 55 years and older with moderate hypercholesterolemia to receive pravastatin ( n=5170 ) or usual care ( n=5185 ) for 4 to 8 years , when trial therapy was discontinued . Passive surveillance using national data bases to ascertain deaths and hospitalizations continued for a total follow-up of 8 to 13 years to assess whether mortality and morbidity differences persisted or new differences developed . During the post-trial period , fatal and nonfatal outcomes were available for 98 % and 64 % of participants , respectively . The primary outcome was all-cause mortality and the secondary outcomes included cardiovascular mortality , coronary heart disease ( CHD ) , stroke , heart failure , cardiovascular disease , and end-stage renal disease . No significant differences appeared in mortality for pravastatin vs usual care ( hazard ratio [ HR ] , 0.96 ; 95 % confidence interval [ CI ] , 0.89 - 1.03 ) or other secondary outcomes . Similar to the previously reported in-trial result , there was a significant treatment effect for CHD in black patients ( HR , 0.79 ; 95 % CI , 0.64 - 0.98 ) . However , the in-trial result showing a significant treatment by race effect did not remain significant during the entire follow-up ( P=.08 ) . These findings are consistent with evidence from other large trials that show statins prevent CHD and add evidence that they are effective for CHD prevention in black patients", "BACKGROUND In the studies of left ventricular dysfunction ( SOLVD ) , enalapril reduced mortality in patients with symptomatic but not asymptomatic left ventricular systolic dysfunction during the trial . We did a 12-year follow-up of SOLVD to establish if the mortality reduction with enalapril among patients with heart failure was sustained , and whether a subsequent reduction in mortality would emerge among those with asymptomatic ventricular dysfunction . METHODS Of the 6797 patients previously enrolled in the SOLVD prevention and treatment trials , we ascertained the subsequent vital status of 5165 individuals who were alive when the trials had been completed . Follow-up was done through direct contacts in Belgium and linkages with national death registries and federal beneficiary or historic tax summary files in the USA and Canada . FINDINGS Follow-up was 99.8 % ( 6784/6797 ) complete . In the prevention trial , 50.9 % ( 1074/2111 ) of the enalapril group had died compared with 56.4 % ( 1195/2117 ) of the placebo group ( generalised Wilcoxon p=0.001 ) . In the treatment trial , 79.8 % ( 1025/1285 ) of the enalapril group had died compared with 80.8 % ( 1038/1284 ) of the placebo group ( generalised Wilcoxon p=0.01 ) . The reductions in cardiac deaths were significant and similar in both trials . When data for the prevention and treatment trials were combined , the hazard ratio for death was 0.90 for the enalapril group compared with the placebo group ( 95 % CI 0.84 - 0.95 , generalised Wilcoxon p=0.0003 ) . Enalapril extended median survival by 9.4 months in the combined trials ( 95 % CI 2.8 - 16.5 , p=0.004 ) . INTERPRETATION Treatment with enalapril for 3 - 4 years led to a sustained improvement in survival beyond the original trial period in patients with left ventricular systolic dysfunction , with an important increase in life expectancy", "The LIPID study is a placebo-controlled , double-bind , r and omized trial , performed in 9014 patients with coronary heart disease and total cholesterol levels of 155 to 271 mg/dl . After a mean follow-up of 6.1 years , patients receiving pravastatin ( 40 mg/day ) had significantly ( p death rate from coronary heart disease ( 24 % ) , lower overall mortality ( 22 % ) and lower incidence of all cardiovascular outcomes ( 20 to 29 % depending on the event ) . Interestingly enough , the reduction in death from coronary heart disease or nonfatal myocardial infa rct ion was observed whatever the initial cholesterol concentration , and already significant if total cholesterol was LDL cholesterol was statin on the coronary heart disease outcomes is observed even in case of initial cholesterol levels yet considered as \" normal \"", "BACKGROUND Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently . We studied the effect of an angiotensin-converting-enzyme inhibitor , enalapril , on mortality and hospitalization in patients with chronic heart failure and ejection fractions less than or equal to 0.35 . METHODS Patients receiving conventional treatment for heart failure were r and omly assigned to receive either placebo ( n = 1284 ) or enalapril ( n = 1285 ) at doses of 2.5 to 20 mg per day in a double-bind trial . Approximately 90 percent of the patients were in New York Heart Association functional classes II and III . The follow-up averaged 41.4 months . RESULTS There were 510 deaths in the placebo group ( 39.7 percent ) , as compared with 452 in the enalapril group ( 35.2 percent ) ( reduction in risk , 16 percent ; 95 percent confidence interval , 5 to 26 percent ; P = 0.0036 ) . Although reductions in mortality were observed in several categories of cardiac deaths , the largest reduction occurred among the deaths attributed to progressive heart failure ( 251 in the placebo group vs. 209 in the enalapril group ; reduction in risk , 22 percent ; 95 percent confidence interval , 6 to 35 percent ) . There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure . Fewer patients died or were hospitalized for worsening heart failure ( 736 in the placebo group and 613 in the enalapril group ; risk reduction , 26 percent ; 95 percent confidence interval , 18 to 34 percent ; P less than 0.0001 ) . CONCLUSIONS The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions", "BACKGROUND Obstructive changes often occur in aortocoronary saphenous-vein bypass grafts because of atherosclerosis and thrombosis . We studied whether aggressive lowering of low-density lipoprotein ( LDL ) cholesterol levels or low-dose anticoagulation would delay the progression of atherosclerosis in grafts . METHODS We studied 1351 patients who had undergone bypass surgery 1 to 11 years before base line and who had an LDL cholesterol level between 130 and 175 mg per deciliter and at least one patent vein graft as seen on angiography . We used a two-by-two factorial design to assign patients to aggressive or moderate treatment to lower LDL cholesterol levels ( with lovastatin and , if needed , cholestyramine ) and to treatment with warfarin or placebo . Angiography was repeated an average of 4.3 years after base line . The primary angiographic outcome was the mean percentage per patient of grafts with a decrease of 0.6 mm or more in lumen diameter . RESULTS As measured annually during the study period , the mean LDL cholesterol level of patients aggressive treatment ranged from 93 to 97 mg per deciliter ; with moderate treatment , the range was from 132 to 136 mg per deciliter ( P mean international normalized ratio was 1.4 in the warfarin group and 1.1 in the placebo group ( P mean percentage of grafts with progression of atherosclerosis was 27 percent for patients whose LDL cholesterol level was lowered with aggressive treatment , and 39 percent for those who received moderate treatment ( P angiographic outcome between the warfarin and placebo groups . The rate of revascularization over four years was 29 percent lower in the group whose LDL cholesterol level was lowered aggressively than in the group receiving moderate treatment ( 6.5 percent vs. 9.2 percent , P= 0.03 ) . CONCLUSIONS Aggressive lowering of LDL cholesterol levels to below 100 mg per deciliter reduced the progression of atherosclerosis in grafts . Low-dose warfarin did not reduce the progression of atherosclerosis", "CONTEXT Studies have demonstrated that statins administered to individuals with risk factors for coronary heart disease ( CHD ) reduce CHD events . However , many of these studies were too small to assess all-cause mortality or outcomes in important subgroups . OBJECTIVE To determine whether pravastatin compared with usual care reduces all-cause mortality in older , moderately hypercholesterolemic , hypertensive participants with at least 1 additional CHD risk factor . DESIGN AND SETTING Multicenter ( 513 primarily community-based North American clinical centers ) , r and omized , nonblinded trial conducted from 1994 through March 2002 in a subset of participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) . PARTICIPANTS Ambulatory persons ( n = 10 355 ) , aged 55 years or older , with low-density lipoprotein cholesterol ( LDL-C ) of 120 to 189 mg/dL ( 100 to 129 mg/dL if known CHD ) and triglycerides lower than 350 mg/dL , were r and omized to pravastatin ( n = 5170 ) or to usual care ( n = 5185 ) . Baseline mean total cholesterol was 224 mg/dL ; LDL-C , 146 mg/dL ; high-density lipoprotein cholesterol , 48 mg/dL ; and triglycerides , 152 mg/dL. Mean age was 66 years , 49 % were women , 38 % black and 23 % Hispanic , 14 % had a history of CHD , and 35 % had type 2 diabetes . INTERVENTION Pravastatin , 40 mg/d , vs usual care . MAIN OUTCOME MEASURES The primary outcome was all-cause mortality , with follow-up for up to 8 years . Secondary outcomes included nonfatal myocardial infa rct ion or fatal CHD ( CHD events ) combined , cause-specific mortality , and cancer . RESULTS Mean follow-up was 4.8 years . During the trial , 32 % of usual care participants with and 29 % without CHD started taking lipid-lowering drugs . At year 4 , total cholesterol levels were reduced by 17 % with pravastatin vs 8 % with usual care ; among the r and om sample who had LDL-C levels assessed , levels were reduced by 28 % with pravastatin vs 11 % with usual care . All-cause mortality was similar for the 2 groups ( relative risk [ RR ] , 0.99 ; 95 % confidence interval [ CI ] , 0.89 - 1.11 ; P = .88 ) , with 6-year mortality rates of 14.9 % for pravastatin vs 15.3 % with usual care . CHD event rates were not significantly different between the groups ( RR , 0.91 ; 95 % CI , 0.79 - 1.04 ; P = .16 ) , with 6-year CHD event rates of 9.3 % for pravastatin and 10.4 % for usual care . CONCLUSIONS Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C. The results may be due to the modest differential in total cholesterol ( 9.6 % ) and LDL-C ( 16.7 % ) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention", "BACKGROUND Lowering the blood cholesterol level may reduce the risk of coronary heart disease . This double-blind study was design ed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infa rct ion reduced the combined incidence of nonfatal myocardial infa rct ion and death from coronary heart disease . METHODS We r and omly assigned 6595 men , 45 to 64 years of age , with a mean ( + /- SD ) plasma cholesterol level of 272 + /- 23 mg per deciliter ( 7.0 + /- 0.6 mmol per liter ) to receive pravastatin ( 40 mg each evening ) or placebo . The average follow-up period was 4.9 years . Medical records , electrocardiographic recordings , and the national death registry were used to determine the clinical end points . RESULTS Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent , whereas there was no change with placebo . There were 248 definite coronary events ( specified as nonfatal myocardial infa rct ion or death from coronary heart disease ) in the placebo group , and 174 in the pravastatin group ( relative reduction in risk with pravastatin , 31 percent ; 95 percent confidence interval , 17 to 43 percent ; P definite nonfatal myocardial infa rct ions ( 31 percent reduction , P death from coronary heart disease ( definite cases alone : 28 percent reduction , P = 0.13 ; definite plus suspected cases : 33 percent reduction , P = 0.042 ) , and death from all cardiovascular causes ( 32 percent reduction , P = 0.033 ) . There was no excess of deaths from noncardiovascular causes in the pravastatin group . We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group ( 95 percent confidence interval , 0 to 40 percent ; P = 0.051 ) . CONCLUSIONS Treatment with pravastatin significantly reduced the incidence of myocardial infa rct ion and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infa rct ion" ]

[ "BACKGROUND Little is known about how the intensity of exercise influences cardiovascular fitness and body composition , especially in obese adolescents . OBJECTIVE Our goal was to determine the effects of physical training intensity on the cardiovascular fitness , percentage of body fat ( % BF ) , and visceral adipose tissue ( VAT ) of obese adolescents . DESIGN Obese 13 - 16-y-olds ( n = 80 ) were assigned to 1 ) biweekly lifestyle education ( LSE ) , 2 ) LSE + moderate-intensity physical training , or 3 ) LSE + high-intensity physical training . The intervention lasted 8 mo . Physical training was offered 5 d/wk , and the target energy expenditure for all subjects in physical training groups was 1047 kJ ( 250 kcal)/session . Cardiovascular fitness was measured with a multistage treadmill test , % BF with dual-energy X-ray absorptiometry , and VAT with magnetic resonance imaging . RESULTS The increase in cardiovascular fitness in the high-intensity physical training group , but not in the moderate-intensity group , was significantly greater than that in the LSE alone group ( P = 0.009 ) ; no other comparisons of the 3 groups were significant . Compared with the LSE alone group , a group composed of subjects in both physical training groups combined who attended training sessions > or=2 d/wk showed favorable changes in cardiovascular fitness ( P % BF ( P = 0.001 ) , and VAT ( P = 0.029 ) . We found no evidence that the high-intensity physical training was more effective than the moderate-intensity physical training in enhancing body composition . CONCLUSIONS The cardiovascular fitness of obese adolescents was significantly improved by physical training , especially high-intensity physical training . The physical training also reduced both visceral and total-body adiposity , but there was no clear effect of the intensity of physical training", "Exercise during growth has a positive influence on bone mineral accrual , yet little is known about how bone geometry and strength adapt to loading during growth . Our primary objective was to compare changes in proximal femur bone geometry and strength between 31 prepubertal ( Tanner Stage 1 ) boys who participated in a school-based , high-impact circuit intervention ( 12 min , three times a week ) for 20 months and 33 maturity-matched controls . Our secondary objective was to compare changes in total body ( TB ) , proximal femur ( PF ) , and lumbar spine ( LS ) bone mineral content ( BMC ) and bone area ( BA ) in these groups . We assessed geometric variables and bone strength at the narrow neck ( NN ) , intertrochanteric ( TR ) region , and femoral shaft regions by applying the Hip Structure Analysis program to proximal femur dual energy X-ray absorptiometry scans ( DXA , Hologic QDR 4500 ) . Further , we assessed total body , lumbar spine , and proximal femur BMC and BA by DXA and derived total body lean mass and fat mass from total body scans . Intervention ( 10.2 + /- 0.5 years ) and control boys ( 10.1 + /- 0.5 years ) had similar baseline height ( 140.8 vs. 141.3 cm ) and weight ( 36.9 vs. 35.4 kg ) , and average 20-month physical activity scores ( Physical Activity Question naire for Children , PAQ-C ) and calcium intakes ( 861 vs. 852 mg/day , food frequency question naire ) . Twenty-month height and weight changes were not significantly different between groups ; lean mass changed more ( P intervention boys ( 22.8 % ) than control boys ( 18.6 % ) . At the NN region , intervention boys had greater bone expansion on both the periosteal ( + 2.6 % , P = 0.1 ) and endosteal ( + 2.7 % , P = 0.2 ) surfaces , result ing in significantly greater changes in section modulus ( bone bending strength ) ( + 7.5 % , P = 0.02 , ANCOVA , adjusting for height change , final Tanner Stage , and baseline bone values ) . Changes at the intertrochanteric and femoral shaft regions were not significantly different between groups . Femoral neck ( FN ) BMC changes were significantly greater in intervention boys ( + 4.3 % , P in BA and BMC for other regions were not significantly different between groups . In summary , a school-based , high-impact exercise intervention implemented three times a week for 12 min is an effective strategy for site-specific gains in bone strength at the narrow neck region of the proximal femur", "Background and design Few studies have investigated the association between maximal cardiorespiratory capacity ( fitness ) and the clustered cardiovascular disease ( CVD ) risk in children and youth from culturally diverse countries . This cross-sectional study examined the association between fitness and clustered CVD risk in children and adolescents from three European countries . Methods Participants were 2845 r and omly selected school children aged 9 or 15 years from Portugal ( n = 944 ) , Denmark ( n = 849 ) and Estonia ( n = 1052 ) . Cardiorespiratory fitness was determined during a maximal test on a cycle ergometer . CVD risk factors selected to assess the degree of clustering were the total cholesterol/high-density lipoprotein cholesterol ratio , plasma triglycerides , insulin resistance ( homeostasis model assessment ) , sum of four skinfolds , and systolic blood pressure . Results There was a strong association between cardiorespiratory fitness and the clustering of CVD risk factors . The odds ratios for clustering in each quartile of fitness , using the quartile with the highest fitness as reference , were 13.0 [ 95 % confidence interval ( CI ) 8.8 - 19.1 ] ; 4.8 ( 95 % CI 3.2 - 7.1 ) and 2.5 ( 95 % CI 1.6 - 3.8 ) , respectively , after adjusting for country , age , sex , socio-economic status , pubertal stage , family history of CVD and diabetes . In stratified analyses by age group , sex and country , similar strong patterns were observed . Conclusion Low cardiorespiratory fitness is strongly associated with the clustering of CVD risk factors in children independent of country , age and sex", "OBJECTIVES To evaluate the relationship between changes in physical activity ( PA ) , sedentary behavior , and physical self-perceptions and global self-worth in 30 , 8 - 12 years old , overweight/obese children ( 13 boys , 17 girls ) . METHODS Secondary analyses from a r and omized controlled trial design ed to increase PA and reduce sedentary behavior . PA was measured by accelerometers worn by participants every day for 8 weeks . Sedentary behavior , defined as minutes per day spent in television viewing , was assessed by self-report . RESULTS Increases in PA were associated with increases in perceived physical conditioning ( r = .54 , p body satisfaction ( r = .55 , p overall physical self-worth ( r = .44 , p TV viewing were also related to increased physical and global self-worth . CONCLUSIONS Increases in PA are associated with improvements in physical self-perceptions but not global self-worth , while reductions in TV viewing are associated with increased physical and global self-worth , and these psychosocial benefits appear to be independent of changes in adiposity", "The aim of the present study was to examine the effect of exercise training on adipokines , inflammatory markers , and oxidative stress in overweight children . Nineteen overweight children were r and omly assigned to an aerobic exercise training or sedentary control group for 8 weeks . Measurements included peak oxygen uptake ( V o(2)max ) , body weight and composition , adipokines ( C-reactive protein , interleukin 6 , tumor necrosis factor alpha , adiponectin , leptin , and resistin ) , and oxidative stress ( 8-isoprostane ) . There were no differences between groups for change in body weight or composition over the 8 weeks . Exercise training improved V o(2)max ( exercise group , 1.64 + /- 0.13 to 1.85 + /- 0.17L/min vs control group , 1.83 + /- 0.12 to 1.60 + /- 0.13 L/min , P measured adipokines or the marker of systemic oxidative stress , 8-isoprostane . These data suggest that in the absence of weight loss , exercise training alone does not improve the adipokine profile or levels of oxidative stress in overweight children", "Background The purpose was to conduct systematic review s of the relationship between physical activity of healthy community-dwelling older ( > 65 years ) adults and outcomes of functional limitations , disability , or loss of independence . Methods Prospect i ve cohort studies with an outcome related to functional independence or to cognitive function were search ed , as well as exercise training interventions that reported a functional outcome . Electronic data base search strategies were used to identify citations which were screened ( title and abstract ) for inclusion . Included articles were review ed to complete st and ardized data extraction tables , and assess study quality . An established system of assessing the level and grade of evidence for recommendations was employed . Results Sixty-six studies met inclusion criteria for the relationship between physical activity and functional independence , and 34 were included with a cognitive function outcome . Greater physical activity of an aerobic nature ( categorized by a variety of methods ) was associated with higher functional status ( expressed by a host of outcome measures ) in older age . For functional independence , moderate ( and high ) levels of physical activity appeared effective in conferring a reduced risk ( odds ratio ~0.5 ) of functional limitations or disability . Limitation in higher level performance outcomes was reduced ( odds ratio ~0.5 ) with vigorous ( or high ) activity with an apparent dose-response of moderate through to high activity . Exercise training interventions ( including aerobic and resistance ) of older adults showed improvement in physiological and functional measures , and suggestion of longer-term reduction in incidence of mobility disability . A relatively high level of physical activity was related to better cognitive function and reduced risk of developing dementia ; however , there were mixed results of the effects of exercise interventions on cognitive function indices . Conclusions There is a consistency of findings across studies and a range of outcome measures related to functional independence ; regular aerobic activity and short-term exercise programmes confer a reduced risk of functional limitations and disability in older age . Although a precise characterization of a minimal or effective physical activity dose to maintain functional independence is difficult , it appears moderate to higher levels of activity are effective and there may be a threshold of at least moderate activity for significant outcomes", "OBJECTIVE Childhood weight-bearing physical activity is recognized as an important determinant of peak bone mass , and physical activity intervention may represent a feasible strategy for primary prevention of osteoporosis . Previous school-based exercise interventions have all been of high-impact , circuit-based , jumping intervention ( 10 minutes , 3 times a week ) over 2 school years and compared changes in bone mineral content ( BMC ) over 20 months ( 2 school years ) in 9.9 + /- 0.6-year-old intervention girls ( N = 32 ) and controls ( 10.3 + /- 0.4 years , N = 43 ) . METHODS We measured BMC for the total body , lumbar spine , proximal femur ( and femoral neck and trochanteric subregions ) , and lean and fat mass by dual-energy radiograph absorptiometry ( Hologic QDR 4500 ) , and height , sitting height , leg length , and weight at baseline and 20 months . We assessed Tanner stage , general physical activity , and calcium intake by question naire . RESULTS Girls were Tanner breast stage 1 to 3 at baseline . There were no significant differences in baseline or 20-month change in body size or composition , average physical activity , or calcium intake between groups . There were substantially greater gains in lumbar spine ( 41.7 % vs 38.0 % ) and femoral neck ( 24.8 % vs 20.2 % ) BMC in intervention than in control girls ( P high-impact exercise per week implemented over 2 consecutive years within the elementary school curriculum elicited a substantial bone mineral accrual advantage in pubertal girls", "OBJECTIVE Hyperinsulinemia , hyperlipidemia , hypertension , and coronary artery disease comprise a quartet known as Syndrome X. This syndrome was first described in adults , but has recently been described in children and adolescents . The purpose of our study was to determine if diet or exercise is able to change the clinical profile of Syndrome X in children . STUDY DESIGN We recruited 36 obese ( % ideal body weight = 170.3 + /- 31.1 ) , children ( 9 to 12 yrs old ) known to have high fasting cholesterol levels ( 177.5 + /- 33.5 mg/dL ) . Each participated in a 6-week protocol in one of three groups : control ( C ) , diet ( D ) , or exercise ( E ) . Twenty-five of the patients completed the study with full compliance . At the beginning and end of the study , we measured weight , height , blood pressure , serum insulin , and a lipid profile including : cholesterol , low density lipoprotein , high density lipoprotein ( HDL ) , triglycerides , and apolipoprotein A ( ApoA ) . All subject groups were similar before the study . The D group had the greatest attrition ( 40 % ) and all of the E group completed the study . RESULTS After the 6-week study period , there was no significant weight loss or change in body mass index for any group . There was no significant change in blood pressure and there was no significant decline of fasting cholesterol or low density lipoprotein levels in any of the groups . HDL levels were low in all groups and did not significantly change with treatment . There was a significant decline in the triglyceride levels in both the diet and exercise groups after the study ( preD = 150 + /- 60 ; postD = 122 + /- 50 ; preE = 165 + /- 50 ; postE = 116 + /- 39 ) . Both the D and E groups also demonstrated a significant decrease in ApoA levels ( preD = 174 + /- 33 ; postD = 142 + /- 24 ; preE = 200 + /- 50 ; postE = 161 + /- 23 ) . Most impressively , fasting insulin levels significantly decreased with both diet and exercise , but did not change in controls during the 6 weeks ( preC = 52 + /- 19 ; postC = 53 + /- 21 ; preD = 54 + /- 23 ; postD = 15 + /- 8 ; preE = 48 + /- 21 ; postE = 9 ) . CONCLUSIONS The findings of this study are consistent with previous studies describing the presence of Syndrome X in childhood . Both diet and exercise were effective in lowering triglyceride , ApoA levels , and insulin levels . However , due to the large rate of noncompliance in the diet group , exercise seems to be the best treatment for improvement in Syndrome X in children", "According to the Centers for Disease Control and Prevention , 1 in 3 children born in 2000 in the United States will become diabetic . The odds are higher for African American and Hispanic children as nearly 50 % of them will develop diabetes . R and om screening is not effective in identifying children at risk for type 2 diabetes mellitus ( T2DM ) ; therefore , there is a need to apply screening strategies that guide the development of appropriate primary prevention efforts . To assess the prevalence of risk factors for T2DM , 1066 fifth- grade children were screened using American Diabetes Association guidelines . Overall , 22.6 % were found at risk ; African American and Hispanic children were almost 8 times more likely to be at risk when compared to Caucasians ( odds ratio = 7.41 and 7.87 ) . Children who reported watching TV/playing video games 2 or more hours/day were 73 % more likely to be at risk . Children identified to be at risk were referred to their primary care provider and were invited to participate in a counseling session . The environmental risk factors for T2DM identified in this study are modifiable and should be targeted in preventive interventions at the school and community level to reduce overweight and consequently prevent T2DM in children , especially among minority children", "BACKGROUND Atherosclerosis develops from early childhood ; physical activity could positively affect this process . This study 's aim was to assess the associations of objective ly measured physical activity with clustering of cardiovascular disease risk factors in children and derive guidelines on the basis of this analysis . METHODS We did a cross-sectional study of 1732 r and omly selected 9-year-old and 15-year-old school children from Denmark , Estonia , and Portugal . Risk factors included in the composite risk factor score ( mean of Z scores ) were systolic blood pressure , triglyceride , total cholesterol/HDL ratio , insulin resistance , sum of four skinfolds , and aerobic fitness . Individuals with a risk score above 1 SD of the composite variable were defined as being at risk . Physical activity was assessed by accelerometry . FINDINGS Odds ratios for having clustered risk for ascending quintiles of physical activity ( counts per min ; cpm ) were 3.29 ( 95 % CI 1.96 - 5.52 ) , 3.13 ( 1.87 - 5.25 ) , 2.51 ( 1.47 - 4.26 ) , and 2.03 ( 1.18 - 3.50 ) , respectively , compared with the most active quintile . The first to the third quintile of physical activity had a raised risk in all analyses . The mean time spent above 2000 cpm in the fourth quintile was 116 min per day in 9-year-old and 88 min per day in 15-year-old children . INTERPRETATION Physical activity levels should be higher than the current international guidelines of at least 1 h per day of physical activity of at least moderate intensity to prevent clustering of cardiovascular disease risk factors", "OBJECTIVE To prospect ively examine potential benefits of active commuting to school on measures of weight status and physical activity in a sample of youth . RESEARCH METHODS AND PROCEDURES A cohort of students from seven elementary schools was measured four times -- in the fall and spring of fourth grade ( N = 1083 ) and fifth grade ( N = 924 ) . Participants were classified as active ( walking , biking , or skateboarding to school almost every day for baseline analyses or at least 2 d/wk for analyses of consistent active commuting ) or non-active commuters to school . Accelerometers were used to measure physical activity . Height , weight , and skinfolds were objective ly assessed . RESULTS Boys who actively commuted to school had lower BMI ( p skinfolds ( p BMI change or overweight status . DISCUSSION Walking and cycling to school may contribute to preventing excessive weight gain , or leaner children may walk or cycle to school", "OBJECTIVE To evaluate the effects of an elementary school-based physical education exercise intervention program on bone mineral accrual in prepubertal and early pubertal girls . STUDY DESIGN A total of 14 schools were r and omly assigned to control ( C ) and intervention ( I ) groups . Girls in the I group completed a 10-minute , 3 times per week circuit of varied jumping activities over 7 months . We measured total body , lumbar spine , proximal femur , femoral neck , and trochanteric bone mineral content and areal bone mineral density and estimated femoral neck volumetric bone mineral density at baseline and final measurement in 87 girls in the I group and 90 girls in the C group . Girls were between 8.7 and 11.7 years at baseline . Tanner stage 1 girls were considered prepubertal ; Tanner stages 2 and 3 girls were considered early pubertal . We used analysis of covariance ( adjusting for baseline bone values , change in size , age , and maturity ) to compare 7-month change in bone mineral content , areal bone mineral density , and volumetric bone mineral density between C and I groups within prepubertal and early pubertal girls . RESULTS There was no difference in 7-month change in bone parameters between prepubertal I and C groups . Early pubertal girls in the I group gained 1.5 % to 3.1 % more bone at the femoral neck and lumbar spine than early pubertal girls in the C group ( P exercise interventions to have a positive effect on bone health", "OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity", "OBJECTIVE : To determine the effect of exercise training ( ET ) on components of the insulin resistance syndrome ( IRS ) in obese children . DESIGN : R and omized , modified cross-over study , with subjects assigned to one of two conditions : ( 1 ) 4 months of ET followed by 4 months of no-ET ; or ( 2 ) 4 months of no-ET followed by 4 months of ET . Measurements were made at three time points : 0 , 4 and 8 months . SUBJECTS : 79 obese , but otherwise healthy children ( age : 7–11 y , percent fat ( % fat ) 27–61 % ) . MEASUREMENTS : Plasma lipid and lipoprotein concentrations , plasma insulin and glucose concentrations ; % fat ; submaximal heart rate ( HR ) as an index of fitness . EXERCISE TRAINING : ET was offered 5 d/week 40 min/d . For the 73 children who completed 4 months of ET , the mean attendance was 80 % ( that is , 4 d/week ) and the average HR during ET was 157 bpm . RESULTS : Significant ( P for plasma triglyceride ( TG ) and insulin concentrations and % fat . The average change for both groups , from just before ET to just after the 4 month ET was −0.24 mmolċl−1 for TG , −25.4 pmolċl−1 for insulin and −1.6 units for % fat . When Group 1 ceased ET , over the following 4 month period the average change for insulin was + 26.6 pmolċl−1 and for % fat + 1.3 units . CONCLUSION : Some components ( plasma TG , insulin , % fat ) of the IRS are improved as a result of 4 months of ET in obese children . However , the benefits of ET are lost when obese children become less active", "PURPOSE Children with high levels of total body fat mass ( TFM ) and visceral adipose tissue ( VAT ) have elevated levels of certain risk factors for coronary artery disease and non-insulin-dependent diabetes mellitus . We tested the hypothesis that controlled physical training , without dietary intervention , would have a favorable impact on VAT and percent body fat ( % BF ) in obese children . METHODS A volunteer sample of 74 obese children , 7 - 11 yr of age , accepted r and om assignment to physical training or control groups . Before and after 4 months of intervention , measurements were obtained for VAT , TFM , % BF , daily physical activity , and cardiovascular fitness . The intervention involved 4 months of controlled physical training 5 d x wk(-1 ) , 40 min per session , at a mean heart rate ( HR ) of 157 beats x min(-1 ) . The estimated energy expenditure ( EE ) per training session was 925+/-201 kJ. RESULTS Compared with the control group , the physical training group declined significantly in % BF ( delta = -2.2 % ) ( P TFM ( delta = -3.1 % ) ( P subcutaneous abdominal adipose tissue ( delta = - 16.1 % ) ( P fat-free mass ( delta = + 6.1 % ) ( P moderate-to-very hard physical activity ( delta = + 14.1 % ) ( P VAT was significantly less in the physical training group ( delta = + 0.5 % ) as compared with that in the control group ( delta = + 8.1 % ) ( P physical training obese children : 1 ) were capable of participating in a substantial amount of high intensity physical training over a 4-month period : 2 ) accumulated significantly less VAT as compared with nonexercising controls ; and 3 ) experienced other beneficial changes in total and regional body composition", "To determine whether participating in physical activity affects psychological well-being in an adolescent population , 147 adolescents completed self-reports of exercise and psychological stress and well-being . Analysis revealed that those who reported greater physical activity also reported less stress and lower levels of depression . Adolescents who experienced a higher incidence of life events also demonstrated a strong association between stress and anxiety/depression/hostility . To investigate the effects of exercise training on psychological well-being , adolescents were assigned to either high or moderate intensity aerobic training , flexibility training or a control group . The training groups met twice per week for 25 - 30 min . Aerobic fitness levels , heart rate , blood pressure and self-report of stress and well-being were measured prior to and following 10 weeks of training . Post-training fitness measures confirmed the effectiveness of the high intensity aerobic exercise and between groups differences for physiological and some psychological measures were found . Subjects undergoing high intensity exercise reported significantly less stress than subjects in the remaining three groups . The relationship between stress and anxiety/depression/hostility for the high intensity group was considerably weakened at the end of the training period . For the remaining subjects , however , this relationship was , if anything , strengthened . This experiment provides evidence to suggest that in an adolescent population , high intensity aerobic exercise has positive effects on well-being", "OBJECTIVE To examine the effects of 15 months of resistance training on bone mineral density ( BMD ) in female adolescents ( aged 14 to 17 years ) . STUDY DESIGN Participants were r and omly assigned to either a training ( n = 46 ) or control group ( n = 21 ) . BMD and body composition were measured by using dual-energy x-ray absorptiometry . Strength was assessed by means of one-repetition maximums for the leg press and bench press . The exercise group trained 30 to 45 minutes a day , 3 days per week , using 15 different resistance exercises . Control participants remained sedentary ( Leg strength increased significantly ( 40 % ) in the exercise group , but there were no changes in the control group . Femoral neck BMD increased significantly in the training group ( 1.035 to 1.073 g/cm(2 ) , P lumbar spine BMD ( 1.113 to 1.142 g/cm(2 ) and 1.158 to 1.190 g/cm(2 ) , respectively ) or total body BMD ( 1.103 to 1.134 g/cm(2 ) and 1.111 to 1.129 g/cm(2 ) , respectively ) . CONCLUSION Resistance training is a potential method for increasing bone density in adolescents , although such a program would be best done as part of the school curriculum", " Sixteen postmenarcheal Type 1 diabetic adolescent girls were r and omized into training ( involving aerobic and strength exercises ) and nontraining groups . Body composition ( skinfold thickness ) , aerobic fitness ( PWC170 ) , plasma lipids , serum apolipoproteins , lipoprotein(a ) , leptin , and adiponectin were assessed before and after the 6-month period . After the 6-month period , fat mass and leptin increased significantly in the nontraining group but not in the training group . Conversely , in the latter group , fat-free mass increased ( P PWC170 improved and apolipoproteinB : apolipoproteinA-1 ratio decreased with physical training ( P physical training reduces cardiovascular risks and the increase of insulin resistance risk factors in diabetic adolescent girls", "BACKGROUND Obesity and poor physical fitness constitute a health problem affecting an increasing number of children . Causes include a pervasive \" toxic \" environment that facilitates increased caloric intake and reduced physical activity . An effective strategy for prevention and treatment of childhood obesity likely includes a collaborative effort in the school setting . OBJECTIVE To determine whether a school-based fitness program can improve body composition , cardiovascular fitness level , and insulin sensitivity in overweight children . DESIGN Fifty overweight middle school children with a body mass index ( BMI ) above the 95th percentile for age were r and omized to lifestyle-focused , fitness-oriented gym classes ( treatment group ) or st and ard gym classes ( control group ) for 9 months . Children underwent evaluation of fasting insulin and glucose levels , body composition by means of dual energy absorptiometry , and maximum oxygen consumption ( V0(2)max ) treadmill testing at baseline ( before the school year ) and at end of the school year . SETTING S Rural middle school and an academic children 's hospital . MAIN OUTCOME MEASURES Baseline test results for cardiovascular fitness , body composition , and fasting insulin and glucose levels . RESULTS At baseline , there were no differences between groups before intervention ( values for age , 12 + /- 0.5 years [ all results , mean + /- SD ] ; BMI [ calculated as weight in kilograms divided by the square of height in meters ] , 31.0 + /- 3.7 ; percentage of body fat , 36.5 % + /- 4.6 % ; lean body mass , 41.4 + /- 8.6 kg ; and V0(2)max , 31.5 + /- 5.1 mL/kg per minute ) . Compared with the control group , the treatment group demonstrated a significantly greater loss of body fat ( loss , -4.1 % + /- 3.4 % vs -1.9 % + /- 2.3 % ; P = .04 ) , greater increase in cardiovascular fitness ( V0(2)max , 2.7 + /- 2.6 vs 0.4 + /- 3.3 mL/kg per minute ; P fasting insulin level ( insulin level , -5.1 + /- 5.2 vs 3.0 + /- 14.3 microIU/mL [ -35.4 + /- 36.1 vs 20.8 + /- 99.3 pmol/L ] ; P = .02 ) . CONCLUSIONS Children enrolled in fitness-oriented gym classes showed greater loss of body fat , increase in cardiovascular fitness , and improvement in fasting insulin levels than control subjects . The modification to the school physical education curriculum demonstrates that small but consistent changes in the amount of physical activity has beneficial effects on body composition , fitness , and insulin levels in children . Partnering with school districts should be a part of a public health approach to improving the health of overweight children", "Objectives : To examine the effects of a simple and inexpensive physical activity intervention on change in bone mass and structure in school aged children . Methods : Fifty one children ( n = 23 boys and 28 girls ; mean age 10.1 years ) participated in “ Bounce at the Bell ” which consisted of 10 counter-movement jumps 3 × per day ( total ∼3 min/day ) . Controls were 71 matched children who followed usual school practice . We assessed dietary calcium , physical activity , physical performance , and anthropometry in September and after 8 months of intervention ( June ) . We measured bone mineral content ( BMC ) and bone area at the lumbar spine , total body , and proximal femur . Proximal femur scans were also analysed for bone geometry and structural strength using the hip structural analysis program . Lean and fat mass ( g ) were also calculated . Results : Groups were similar at baseline and did not differ in weight , height , total body , lumbar spine , proximal femur , or femoral neck BMC . Control children had a greater increase in adjusted total body BMC ( 1.4 % ) . Intervention children gained significantly more BMC at the total proximal femur ( 2 % ) and the intertrochanteric region ( 27 % ) . Change in bone structural parameters did not differ between groups . Conclusions : This novel , easily implemented exercise program , took only a few minutes each day and enhanced bone mass at the weight bearing proximal femur in early pubertal children . A large , r and omised study of boys and girls should be undertaken powered to test the effectiveness of Bounce at the Bell in children at different stages of maturity , and in boys and girls independently", "OBJECTIVES We examined the relationship between comprehensive fitness tests and overweight using a school surveillance system in a racially diverse city in the United States . RESEARCH METHODS AND PROCEDURES Trained physical education teachers measured weight , height , and fitness annually from 2001 to 2003 . We compiled data for a cross-sectional analysis ( 11,845 measurements on 6297 students , 5 to 14 years of age ) and a 1-year prospect i ve analysis ( 4215 measurements on 2927 students not overweight at baseline , 5 to 13 years of age ) . Overweight was defined as a BMI > or = 95th percentile ( Centers for Disease Control and Prevention 2000 growth charts ) , and underfit was defined as failing at least one of five fitness tests : endurance run , abdominal strength , flexibility , upper body strength , and agility ( Amateur Athletic Union and Fitnessgram ) . Associations between fitness and overweight were examined using multivariate logistic regression models , adjusting for sociodemographic status and repeated measurements over time . RESULTS The mean number of fitness tests passed was lower among students with a BMI above the 80th percentile . Overweight incidence over 1 year was 7 % and 2 % for underfit and fit girls , respectively ( odds ratio , 3.3 ; 95 % confidence interval , 2.0 to 5.6 ) . Not passing either the endurance run or upper body strength test was associated with overweight incidence in both boys and girls . After adjusting for baseline BMI , the endurance run remained a significant predictor of incident overweight among girls ( odds ratio , 2.0 ; 95 % confidence interval , 1.1 to 3.5 ) . DISCUSSION Findings support a cross-sectional inverse relationship between physical fitness and overweight among school-aged children . The direction of causation between fitness and overweight is not clearly established and merits further study", "BACKGROUND The authors investigated correlates of depression in a general population sample of adolescents ( 15 - 19 years ) and young adults ( 20 - 24 years ) . METHODS As part of the Finnish Health Care Survey a r and om sample of 509 adolescents ( 281 females , 228 males ) and 433 young adults ( 224 females , 209 males ) was interviewed in 1996 . DSM-IIR major depressive episode ( MDE ) was assessed by the University of Michigan Composite International Diagnostic Interview Short Form ( UM-CIDI SF ) . RESULTS In multivariable regression analysis , current smoking ( odds ratio ( OR ) 5.54 ; 95 % confidence interval ( CI ) 1.44 , 21.3 ) and chronic illness ( OR 3.77 ; 95 % CI : 1.04 , 13.7 ) associated with MDE among adolescents . Among young adults , drunkenness at least twice a month ( OR 4.48 ; 95 % CI : 1.44 , 14.0 ) or once a month ( OR 2.79 ; 95 % CI : 1.14 , 6.83 ) , not being married nor cohabiting ( OR 3.50 ; 95 % CI : 1.35 , 9.08 ) and infrequent physical exercise ( OR 4.01 ; 95 % CI : 1.18 , 14.0 ) were related to MDE . Female MDE associated with not being married nor cohabiting ( OR 3.56 ; 95 % CI : 1.23 , 10.1 ) and living in southern Finl and ( OR 2.30 ; 95 % CI : 1.06 , 5.02 ) . Drunkenness at least twice a month was related to MDE among males ( OR 4.54 ; 95 % CI : 1.27 , 16.3 ) . CONCLUSIONS Attention should be paid to compromised health and health-related behaviour associating with MDE in youth . Specifically , the association between smoking and major depression in early adolescence should be borne in mind , and drinking habits or frequency of drunkenness should be carefully noted", "OBJECTIVES The present study aim ed to assess the effect of a 6-month exercise program in obese children on flow-mediated vasodilation ( FMD ) carotid intima-media thickness ( IMT ) and cardiovascular risk factors ( RF ) . BACKGROUND Childhood obesity contributes to adult obesity and subsequent cardiovascular disease . Physical inactivity is a major RF for obesity , endothelial dysfunction , and elevated carotid IMT , culminating in early atherosclerotic disease . METHODS Sixty-seven obese subjects ( age 14.7 + /- 2.2 years ) were r and omly assigned to 6 months ' exercise or non-exercise protocol . We examined the influence of exercises ( 1 h , 3 times/week ) on FMD , IMT , and cardiovascular risk profile . RESULTS Compared with lean control subjects , obese children demonstrated at baseline significantly impaired FMD ( 4.09 + /- 1.76 % vs. 10.65 + /- 1.95 % , p increased IMT ( 0.48 + /- 0.08 mm vs. 0.37 + /- 0.05 mm , p obesity-related cardiovascular RF . Significant improvements were observed in the exercise group for IMT ( 0.44 + /- 0.08 mm , p = 0.012 , -6.3 % ) and FMD ( 7.71 + /- 2.53 % , p body mass index st and ard deviation scores , body fat mass , waist/hip ratio , ambulatory systolic blood pressure , fasting insulin , triglycerides , low-density lipoprotein/high-density lipoprotein ratio , and low-degree inflammation ( C-reactive protein , fibrinogen ) . CONCLUSIONS The present study documented increased IMT , impaired endothelial function , and various elevated cardiovascular RF in young obese subjects . Regular exercise over 6 months restores endothelial function and improves carotid IMT associated with an improved cardiovascular risk profile in obese children", "UNLABELLED This 2-year prospect i ve controlled exercise intervention trial in 99 girls at Tanner stage 1 , evaluating a school curriculum-based training program on a population -based level , showed that the annual gain in BMC , aBMD , and bone size was greater in the intervention group than in the controls . INTRODUCTION Most exercise intervention studies in children , evaluating the accrual of BMD , include volunteers and use specifically design ed osteogenic exercise programs . The aim of this study was to evaluate a 2-year general school-based exercise intervention program in a population -based cohort of girls at Tanner stage 1 . MATERIAL S AND METHODS Forty-nine girls 7 - 9 years of age in grade s 1 and 2 in one school were included in a school curriculum-based exercise intervention program of general physical activity for 40 minutes per school day ( 200 minutes/week ) . Fifty healthy age-matched girls in three neighboring schools , assigned to the general Swedish school curriculum of physical activity ( 60 minutes/week ) , served as controls . All girls were premenarchal , remaining in Tanner stage 1 during the study . BMC ( g ) and areal BMD ( aBMD ; g/cm2 ) were measured with DXA of the total body ( TB ) , the lumbar spine ( L2-L4 vertebrae ) , the third lumbar vertebra ( L3 ) , the femoral neck ( FN ) , and the leg . Volumetric BMD ( vBMD ; g/cm3 ) and bone size were calculated at L3 and FN . Total lean body mass and total fat mass were estimated from the total body scan . Height and weight were also registered . Baseline measurements were performed before the intervention was initiated . Follow-up was done after 2 years . RESULTS No differences between the groups were found at baseline in age , anthropometrics , or bone parameters . The annual gain in BMC was greater in the intervention group than in the controls : L2-L4 , mean 3.8 percentage points ( p = 0.007 ) ; L3 vertebra , mean 7.2 percentage points ( p annual gain in aBMD : total body , mean 0.6 percentage points ( p = 0.006 ) , L2-L4 , mean 1.2 percentage points ( p = 0.02 ) , L3 vertebra , mean 1.6 percentage points ( p = 0.006 ) ; legs , mean 1.2 percentage points ( p = 0.007 ) . There was also a greater mean annual gain in bone size in the L3 vertebra ( mean 1.8 percentage points ; p general school-based exercise program for 2 years for 7- to 9-year-old girls ( baseline ) enhances the accrual of BMC and BMD and increases bone size", "BACKGROUND There is a need to find ways to increase the physical activity levels and improve the body composition and blood pressure of girls . METHODS Thirty 11-year-old girls were recruited from two after school programs in Houston Texas in Spring 2005 . Participants from one program ( 16 ) were r and omly assigned to intervention , the other ( 14 ) served as controls . BMI , BMI percentile , waist circumference and blood pressure were assessed before and after the intervention . Pilates classes were provided free of charge for an hour per day at the intervention site , 5 days a week , for 4 weeks . Four participants wore heart rate monitors during every session and completed enjoyment and perceived exertion question naires . Repeated measures analysis of variance with time ( within ) and group ( between ) as factors was performed . RESULTS Mean attendance was 75 % , mean heart rate 104 bpm , mean perceived exertion 5.9 ( 1 - 10 scale ) and enjoyment 4.4 ( 1 - 5 scale ) . There was a significant ( P = 0.039 ) time by group interaction for BMI percentile . Graphs indicated that this difference was influenced by large reductions in the BMI percentile of healthy girls . CONCLUSIONS Girls enjoyed Pilates , and participation for 4 weeks lowered BMI percentile . Pilates holds promise as a means of reducing obesity", "PURPOSE Insulin resistance is thought to be a core defect in the pathophysiology of obesity-related comorbidities in children , such as type 2 diabetes . Exercise training is known to improve insulin resistance and reduce the risk of type 2 diabetes in adults . However , very little is known regarding the effects of exercise on insulin resistance in youth . Therefore , we examined the effects of a 16-wk resistance training exercise intervention on insulin sensitivity in youth at high risk for developing type 2 diabetes . METHODS Twenty-two overweight Latino adolescent males were r and omly assigned to either a twice-per-week resistance training group ( RT=11 ) or a nonexercising control group ( C=11 ) for 16 wk . Strength was assessed by one-repetition maximum , body composition was quantified by dual-energy x-ray absorptiometry , and insulin sensitivity was determined by the frequently sample d intravenous glucose tolerance test with minimal modeling . RESULTS Significant increases in upper- and lower-body strength were observed in the RT compared with the C group . The RT group significantly increased insulin sensitivity compared with the C group ( P baseline values , insulin sensitivity increased 45.1+/-7.3 % in the RT group versus -0.9+/-12.9 % in controls ( P resistance training program can significantly increase insulin sensitivity in overweight Latino adolescent males independent of changes in body composition", "The effects of regular aerobic exercise on blood concentrations on high‐density lipoprotein cholesterol and prostacyclin were studied in 18 healthy sedentary boys who exercised on a bicycle ergometer for 1 h , four times per week , for 2 months at 75 % of their physical working capacity . The results were compared with those of 10 control boys who did not participate in any specific program . The exercise group revealed a significantly higher mean high‐density lipoprotein cholesterol and 6‐keto‐PGF1a concentration at the end of the training program ( p that regular aerobic exercise has beneficial effects upon the high‐density lipoprotein cholesterol and 6‐keto‐PGF1a in healthy young boys and may be beneficial in the long term , by preventing atherosclerosis of coronary artery disease in adulthood", "The skeletal response to exercise and training on bone is exceptionally good during the growing years . However , it is not known whether the benefit of training on bone is maintained after the training . This 20-month follow-up study assessed the effect of a 9-month jumping intervention on bone gain and physical performance in 99 girls ( mean age 12.5 + /- 1.5 years at the beginning of the study ) one year after the end of the intervention . Both bone mineral content ( BMC ) , by dual energy X-ray absorptiometry ( DXA ) at the lumbar spine and proximal femur , and physical performance parameters ( st and ing long jump , leg extension strength , and shuttle run tests ) were measured at baseline and at 20 months . A multivariate regression analysis was first used to determine the best predictors of the BMC accrual by time . Analysis showed that age at baseline and square of age , changes in height and weight , and pubertal development into Tanner stages 4 and 5 during the follow-up explained the majority of the BMC gain . Then , the effect of participation in the 9-month exercise intervention on BMC accrual and physical performance was analysed adding this variable ( participation : yes/no ) into the model . The regression analysis showed that the trainees ( N = 50 ) had 4.9 % ( 95 % CI , 0.9 % to 8.8 % , p = 0.017 ) greater BMC increase in the lumbar spine than the controls ( N = 49 ) . The mean 20-month BMC increase in the lumbar spine was 28 % ( SD 19 ) in the trainees compared to 22 % ( 12 ) increase in the controls . In the proximal femur , the trend was similar but the obtained 2 to 3 % higher BMC accrual in the trainees ( compared to that in controls ) were statistically insignificant . Among the performance variables , using the same model that best predicted the BMC accrual , the only statistically significant between-groups difference , in favour of the trainees , was the improvement in the st and ing long jump test ( 6.4 % , 95 % CI , 2.3 % to 10.4 % , p = 0.002 ) . Improvements in the leg extension strength and shuttle run tests showed no between-groups difference . In conclusion , although the greatest proportion of bone mineral accrual in growing girls is attributable to growth , an additional bone gain achieved by jumping training is maintained at the lumbar spine at least a year after the end of the training", "BACKGROUND Of the few exercise intervention studies focusing on pediatric population s , none have confined the intervention to the scheduled physical education curriculum . OBJECTIVE To examine the effect of an 8-month school-based jumping program on the change in areal bone mineral density ( aBMD ) , in grams per square centimeter , of healthy third- and fourth- grade children . STUDY DESIGN Ten elementary schools were r and omized to exercise ( n = 63 ) and control groups ( n = 81 ) . Exercise groups did 10 tuck jumps 3 times weekly and incorporated jumping , hopping , and skipping into twice weekly physical education classes . Control groups did regular physical education classes . At baseline and after 8 months of intervention , we measured aBMD and lean and fat mass by dual-energy x-ray absorptiometry ( Hologic QDR-4500 ) . Calcium intake , physical activity , and maturity were estimated by question naire . RESULTS The exercise group showed significantly greater change in femoral trochanteric aBMD ( 4.4 % vs 3.2 % ; P ( baseline aBMD change in height , change in lean , calcium , physical activity , sex , and ethnicity ) in hierarchical regression . CONCLUSIONS An easily implemented school-based jumping intervention augments aBMD at the trochanteric region in the prepubertal and early pubertal skeleton", "At the end of a long week in the office , you sink back into your chair , reflecting on some of the more memorable patients you cared for and counseled . Through gentle history taking , you discovered that urinary incontinence is the underlying cause of an elderly patient 's increasing social isolation . During a careful physical examination , you detected bruising on the torso of a woman with chronic headaches and began to explore the longst and ing abusive relationship between the woman and her alcoholic partner . You discontinued procainamide therapy in a 72-year-old man who had asymptomatic premature ventricular contractions after myocardial infa rct ion . To prevent bleeding from esophageal varices , you started -blocker therapy in a woman with long-st and ing cryptogenic cirrhosis and portal hypertension . In couples ' therapy , discussing the future quality of life of a middle-aged gay man with human immunodeficiency virus infection , you journeyed through emotionally intense dialogue about advance directives . You presented the risk factors for major and minor bleeding to a 39-year-old woman who was considering warfarin therapy because of recently diagnosed atrial fibrillation and valvular heart disease . You listened to , made diagnoses for , treated , advised , and comforted many patients . Yet there were some hiccoughs in your practice along the way . You stumbled while debating the pros and cons of breast cancer screening with a healthy 48-year-old woman who has been staying current with information on the Internet . You question ed the merits of a personalized walking program suggested to you by a motivated 66-year-old man with severe claudication . Explaining that you wanted to review the best current evidence on these issues , you resolved to address your uncertainties before these patients made their next office visits , in a week 's time . Sighing deeply , you acknowledge that you have little time to read . You subscribe to three journals , which you browse months after they arrive-either when your journal stack becomes precariously high or when your guilt is sufficiently motivational . You sometimes find the conclusions of individual articles conflicting or confusing . You know that some of the decisions and suggestions you made this week , specifically your decisions about stopping procainamide therapy and starting -blocker therapy and your advice about bleeding risks from anticoagulant therapy , were based on the best current research evidence [ 1 - 3 ] . On the other h and , your patients ' inquiries about breast cancer screening and exercise treatment for claudication highlight your need for a concise , current , rigorous synthesis of the best available evidence on each of these topics : in brief , a systematic review [ 4 , 5 ] . Incorporating Research Evidence into Clinical Decision Making The foregoing scenario is familiar to practitioners . In a typical week , we encounter patients with diverse problems ; exercise numerous clinical , interpersonal , and technical skills ; and make many decisions . The factors that affect these decisions and their outcomes are complex . For instance , each patient has unique sociodemographic characteristics , cultural circumstances , and personal preferences . Each physician has unique knowledge , experiences , and values . Moreover , practitioners and their patients make decisions within the context of a rapidly changing health care system that influences the availability , accessibility , and cost of diagnostic tests and therapies [ 6 ] . Timely , useful evidence from the biomedical literature should be an integral component of clinical decision making . If one treatment has been shown to be better than another , we need to know , so that we can recommend the treatment to the appropriate patients . The worldwide effort to develop new tests and treatments , and to determine their usefulness , has never been stronger , and our patients and their families expect us to be fonts of the knowledge that results from this effort [ 7 ] . Unfortunately , it is easy for current best research evidence to pass us by [ 8 ] . We may lack the time , motivation , and basic skills needed to find , critically appraise , and synthesize information , all of which we must do if we are to integrate the results of original studies into our practice . Fortunately , several potent methods are emerging that can greatly enhance our ability to interpret and apply research evidence ; foremost among them is the systematic review . This article begins a series in Annals that will examine systematic review s in detail and explore their many applications . Systematic review s represent the best chance that most practitioners will have to underst and and accurately apply the key signals arising from the robust and increasingly productive search for solutions to medical problems . A properly conducted systematic review faithfully summarizes the evidence from all relevant studies on the topic of interest , and it does so concisely and transparently . What Is a Systematic Review ? Systematic review s are scientific investigations in themselves , with pre-planned methods and an assembly of original studies as their subjects . They synthesize the results of multiple primary investigations by using strategies that limit bias and r and om error [ 9 , 10 ] . These strategies include a comprehensive search of all potentially relevant articles and the use of explicit , reproducible criteria in the selection of articles for review . Primary research design s and study characteristics are appraised , data are synthesized , and results are interpreted . When the results of primary studies are summarized but not statistically combined , the review may be called a qualitative systematic review . A quantitative systematic review , or meta- analysis , is a systematic review that uses statistical methods to combine the results of two or more studies . The term overview is sometimes used to denote a systematic review , whether quantitative or qualitative . Summaries of research that lack explicit descriptions of systematic methods are often called narrative review s. Review articles are one type of integrative publication ; practice guidelines , economic evaluations , and clinical decision analyses are others . These other types of integrative articles often incorporate the results of systematic review s. For example , practice guidelines are systematic ally developed statements intended to assist practitioners and patients with decisions about appropriate health care for specific clinical circumstances [ 11 ] . Evidence -based practice guidelines are based on systematic review s of the literature , appropriately adapted to local circumstances and values . Economic evaluations compare both the costs and the consequences of different courses of action ; the knowledge of consequences that are considered in these evaluations is often generated by systematic review s of primary studies . Decision analyses quantify both the likelihood and the valuation of the expected outcomes associated with competing alternatives . Differences between Systematic and Narrative Review s All review s , narrative and systematic alike , are retrospective , observational research studies and are therefore subject to systematic and r and om error . Accordingly , the quality of a review - and thus its worth-depends on the extent to which scientific review methods have been used to minimize error and bias . This is the key feature that distinguishes traditional narrative review s from systematic review s ( Table 1 ) . If a review is prepared according to the steps outlined in the right column of Table 1 , it is more likely to be systematic and to provide unbiased conclusions . If review methods approximate those found in the middle column of Table 1 , the article is more likely to be a narrative review , and the conclusions are less likely to be based on an unbiased summary of all relevant evidence . Table 1 . Differences between Narrative Review s and Systematic Review s Systematic review s are generated to answer specific , often narrow , clinical questions in depth . These questions can be formulated explicitly according to four variables : a specific population and setting ( such as elderly out patients ) , the condition of interest ( for example , hypertension ) , an exposure to a test or treatment ( such as pharmacologic management ) , and one or more specific outcomes ( such as cardiovascular and cerebrovascular events and mortality ) [ 12 ] . Thus , an example of a well-formulated , clinical ly relevant question is , Does pharmacologic treatment of hypertension in the elderly prevent strokes and myocardial infa rct ions or delay death ? If the question that is driving the review is not clear from the title , abstract , or introduction , or if no methods section is included , the paper is more likely to be a narrative review than a systematic review [ 13 ] . Most narrative review articles deal with a broad range of issues related to a given topic rather than addressing a particular issue in depth [ 9 ] . For example , a narrative review on diabetes ( such as that which might be found in a textbook chapter ) might include sections on the physiology and pathophysiology of carbohydrate , lipid , and protein metabolism ; the epidemiology of and prognosis associated with diabetes ; diagnostic and screening approaches ; and preventive , therapeutic , rehabilitative , and palliative interventions . Thus , narrative review s may be most useful for obtaining a broad perspective on a topic ; they are less often useful in furnishing quantitative answers to specific clinical questions . Narrative review s are appropriate for describing the history or development of a problem and its management . Narrative review s may better describe cutting-edge developments if research is scant or preliminary or if studies are very limited by flawed design or execution [ 13 ] . They may be particularly useful for discussing data in light of underlying theory and context . Narrative review s can draw analogies and can conceptually integrate two independent fields of research , such as", "We compared 7-month changes in bone structural properties in pre- and early-pubertal girls r and omized to exercise intervention ( 10-minute , 3 times per week , jumping program ) or control groups . Girls were classified as prepubertal ( PRE ; Tanner breast stage 1 ; n = 43 for intervention [ I ] and n = 25 for control [ C ] ) or early-pubertal ( EARLY ; Tanner stages 2 and 3 ; n = 43 for I and n = 63 for C ) . Mean + /- SD age was 10.0 + /- 0.6 and 10.5 + /- 0.6 for the PRE and EARLY groups , respectively . Proximal femur scans were analyzed using a hip structural analysis ( HSA ) program to assess bone mineral density ( BMD ) , subperiosteal width , and cross-sectional area and to estimate cortical thickness , endosteal diameter , and section modulus at the femoral neck ( FN ) , intertrochanter ( IT ) , and femoral shaft ( FS ) regions . There were no differences between intervention and control groups for baseline height , weight , calcium intake , or physical activity or for change over 7 months ( p > 0.05 ) . We used analysis of covariance ( ANCOVA ) to examine group differences in changes of bone structure , adjusting for baseline weight , height change , Tanner breast stage , and physical activity . There were no differences in change for bone structure in the PRE girls . The more mature girls ( EARLY ) in the intervention group showed significantly greater gains in FN ( + 2.6 % , p = 0.03 ) and IT ( + 1.7 % , p = 0.02 ) BMD . Underpinning these changes were increased bone cross-sectional area and reduced endosteal expansion . Changes in subperiosteal dimensions did not differ . Structural changes improved section modulus ( bending strength ) at the FN ( + 4.0 % , p = 0.04 ) , but not at the IT region . There were no differences at the primarily cortical FS . These data provide insight into geometric changes that underpin exercise-associated gain in bone strength in early-pubertal girls", "OBJECTIVES This study evaluated the effects of aerobic exercise physical education on blood pressure in high-risk , predominantly African-American , adolescent girls . METHODS Ninth- grade girls ( n = 99 ) with blood pressure above the 67th percentile were r and omized to 1 semester of aerobic exercise classes or st and ard physical education classes . RESULT The study was completed by 88 girls . At posttest , only members of the aerobic exercise group increased their estimated cardiorespiratory fitness . The aerobic exercise group had a greater decrease in systolic blood pressure than the st and ard physical education group ( P Aerobic exercise physical education is a feasible and effective health promotion strategy for high-risk adolescent girls" ]

[ "It has long been proposed that the renin-angiotensin system exerts a stimulatory influence on the sympathetic nervous system , including augmentation of central sympathetic outflow and presynaptic facilitation of norepinephrine release from sympathetic nerves . We tested this proposition in 19 patients with essential hypertension , evaluating whether the angiotensin receptor blockers ( ARBs ) eprosartan and losartan had identifiable antiadrenergic properties . This was done in a prospect i ve , r and omized , three-way placebo-controlled study of crossover design . Patients were r and omized to 600 mg of eprosartan daily , 50 mg of losartan daily , or placebo . The treatment period was 4 wk , with 2-wk washout periods . Multiunit firing rates in efferent sympathetic nerves distributed to skeletal muscle vasculature ( muscle sympathetic nerve activity , MSNA ) were measured with microneurography , testing whether ARBs inhibit central sympathetic outflow . In parallel , isotope dilution methodology was used to measure whole body norepinephrine spillover to plasma . Mean blood pressure on placebo was 151/98 mmHg , with both ARBs causing reductions of approximately 11 mmHg systolic and 6 mmHg diastolic pressure , placebo corrected . Both MSNA [ 35 + /- 12 bursts/min ( mean + /- SD ) on placebo ] and whole body norepinephrine spillover [ 366 + /- 247 ng/min ] were unchanged by ARB administration , indicating that the ARBs did not material ly inhibit central sympathetic outflow or act presynaptically to reduce norepinephrine release at existing rates of nerve firing . These findings contrast with the easily demonstrable reduction in sympathetic nervous activity produced by antihypertensive drugs of the imidazoline-binding class , which are known to act within the brain to inhibit sympathetic nervous outflow . We conclude that sympathetic nervous inhibition is not a major component of the blood pressure-lowering action of ARBs in essential hypertension", "Impaired nitric oxide ( NO ) vasodilation ( endothelial dysfunction ) is associated with obesity and thought to be a factor in the development of hypertension . We previously found that NO synthesis inhibition had similar pressor effects in obese hypertensives compared with healthy control during autonomic blockade , suggesting that impaired NO vasodilation is secondary to sympathetic activation . We tested this hypothesis by determining the effect of autonomic blockade ( trimethaphan 4 mg/min IV ) on NO-mediated vasodilation ( increase in forearm blood flow to intrabrachial acetylcholine ) compared with endothelial-independent vasodilation ( intrabrachial sodium nitroprusside ) in obese hypertensive subjects ( 30 Acetylcholine and sodium nitroprusside were given at equipotent doses ( 10 , 30 , and 50 & mgr;g/min and 1 , 2 , and 3 & mgr;g/min , respectively ) to 14 obese subjects ( 49±3.6 years , 34±1 kg/m2 , 165/94±7/6 mm Hg ) , on separate occasions 1 month apart , r and omly assigned . Autonomic blockade increased basal forearm blood flow ( from 3.9±0.7 to 5.2±1.2 mL/100 mL per minute , P=0.078 ) . As expected , NO-mediated vasodilation was blunted on the intact day compared with NO-independent vasodilation ; forearm blood flow increased from 3.6±0.6 to 10.1±1.1 with the highest dose of nitroprusside , but only from 3.7±0.4 to 7.2±0.8 mL/100 mL per minute with the highest dose of acetylcholine , P contrast , forearm blood flow responses to acetylcholine were restored by autonomic blockade and were no longer different to nitroprusside ( from 6.2±1.1 to 11.4±1.6 mL/100 mL per minute and from 5.2±0.9 to 12.5±0.9 , respectively , P=0.58 ) . Our results support the concept that sympathetic activation contributes to the impairment in NO-mediated vasodilation seen in obesity-associated hypertension and provides further rationale to explore it as a therapeutic target", "Renal sympathetic denervation ( RDN ) is under investigation as a treatment option in patients with resistant hypertension ( RH ) . Determinants of arterial compliance may , however , help to predict the BP response to therapy . Aortic distensibility ( AD ) is a well-established parameter of aortic stiffness and can reliably be obtained by CMR . This analysis sought to investigate the effects of RDN on AD and to assess the predictive value of pre-treatment AD for BP changes . We analyzed data of 65 patients with RH included in a multicenter trial . RDN was performed in all participants . A st and ardized CMR protocol was utilized at baseline and at 6-month follow-up . AD was determined as the change in cross-sectional aortic area per unit change in BP . Office BP decreased significantly from 173/92 ± 24/16 mmHg at baseline to 151/85 ± 24/17 mmHg ( p . Maximum aortic areas increased from 604.7 ± 157.7 to 621.1 ± 157.3 mm2 ( p = 0.011 ) . AD improved significantly by 33 % from 1.52 ± 0.82 to 2.02 ± 0.93 × 10−3 mmHg−1 ( p AD at follow-up was significantly more pronounced in younger patients ( p = 0.005 ) and responders to RDN ( p = 0.002 ) . Patients with high-baseline AD were significantly younger ( 61.4 ± 10.1 vs. 67.1 ± 8.4 years , p = 0.022 ) . However , there was no significant correlation of baseline AD to response to RDN . AD is improved after RDN across all age groups . Importantly , these improvements appear to be unrelated to observed BP changes , suggesting that RDN may have direct effects on the central vasculature", "Background Whether the sympathetic nervous system can directly alter central aortic stiffness remains controversial , mainly because of the difficulty in experimentally augmenting peripheral vasoconstrictor activity without changing blood pressure . Methods and Results To address this limitation , we utilized low‐level cardiopulmonary baroreflex loading and unloading shown previously to alter sympathetic outflow without evoking parallel hemodynamic modulation . Blood pressure and carotid‐femoral aortic pulse wave velocity ( cf‐PWV ) were measured in 32 healthy participants ( 24±2 years ; women : n=15 ) before and during 12‐minute applications of low‐level lower body negative pressure ; −7 mm Hg ) and lower body positive pressure ; + 7 mm Hg ) , applied in a r and om order . Fibular nerve microneurography was used to collect muscle sympathetic nerve activity ( MSNA ) in a subset ( n=8 ) to confirm peripheral sympathetic responses . During lower body negative pressure , heart rate , blood pressure , stroke volume , cardiac output , and total peripheral resistance were not statistically different ( all P>0.05 ) ; MSNA burst frequency ( + 15 % ; P=0.007 ) , total MSNA ( + 44 % ; P=0.006 ) , and cf‐PWV ( ∆+0.3±0.2 m/s ; P increase in cf‐PWV greater than the baseline typical error of measurement . During lower body positive pressure , heart rate , stroke volume , cardiac output , and total peripheral resistance were not statistically different ( all P>0.05 ) , though blood pressure increased ( P and pulse pressure decreased ( P=0.01 ) ; MSNA burst frequency ( −4 % ; P=0.37 ) , total MSNA ( −7 % ; P=0.89 ) , and cf‐PWV ( ∆0.0±0.2 m/s ; P=0.68 ) were not statistically different . Conclusions These findings provide evidence that acute elevations in peripheral sympathetic activity can increase central aortic PWV in young participants independent of a change in distending or pulsatile blood pressure or heart rate", "Background : Recent research efforts on bariatric surgery have focused on metabolic and diabetes mellitus resolution . R and omized trials design ed to assess the impact of bariatric surgery in patients with obesity and hypertension are needed . Methods : In this r and omized , single-center , nonblinded trial , we included patients with hypertension ( using ≥2 medications at maximum doses or > 2 at moderate doses ) and a body mass index between 30.0 and 39.9 kg/m2 . Patients were r and omized to Roux-en-Y gastric bypass plus medical therapy or medical therapy alone . The primary end point was reduction of ≥30 % of the total number of antihypertensive medications while maintaining systolic and diastolic blood pressure included 100 patients ( 70 % female , mean age 43.8±9.2 years , mean body mass index 36.9±2.7 kg/m2 ) , and 96 % completed follow-up . Reduction of ≥30 % of the total number of antihypertensive medications while maintaining controlled blood pressure occurred in 41 of 49 patients from the gastric bypass group ( 83.7 % ) compared with 6 of 47 patients ( 12.8 % ) from the control group with a rate ratio of 6.6 ( 95 % confidence interval , 3.1–14.0 ; P was present in 25 of 49 ( 51 % ) and 22 of 48 ( 45.8 % ) patients r and omized to gastric bypass , considering office and 24-hour ambulatory blood pressure monitoring , respectively , whereas no patient su bmi tted to medical therapy was free of antihypertensive drugs at 12 months . A post hoc analysis for the primary end point considering the SPRINT ( Systolic Blood Pressure Intervention Trial ) target reached consistent results , with a rate ratio of 3.8 ( 95 % confidence interval , 1.4–10.6 ; P=0.005 ) . Eleven patients ( 22.4 % ) from the gastric bypass group and none in the control group were able to achieve SPRINT levels without antihypertensives . Waist circumference , body mass index , fasting plasma glucose , glycohemoglobin , low-density lipoprotein cholesterol , triglycerides , high-sensitivity C-reactive protein , and 10-year Framingham risk score were lower in the gastric bypass than in the control group . Conclusions : Bariatric surgery represents an effective strategy for blood pressure control in a broad population of patients with obesity and hypertension . Clinical Trial Registration : URL : https:// clinical trials.gov . Unique identifier : NCT01784848", "Objective The increase in blood pressure that accompanies the obese state is almost invariably associated with alterations in metabolism ( insulin resistance and dyslipidaemia ) and the neurohumoral profile ( activation of the renin – angiotensin system , sympathetic overactivity ) , which potentiate the cardiovascular risk associated with hypertension . However , debate remains as to the antihypertensive drug on which treatment of obesity-related hypertension should be based . The CROSS ( C and esartan Role on Obesity and on Sympathetic System ) study was undertaken to examine the antihypertensive , neuroadrenergic , and metabolic effects of an angiotensin II receptor blocker in comparison with a diuretic in obese hypertensive individuals . Methods In 127 obese hypertensive individuals aged 50.7 ± 5.1 years ( mean ± SD ) , we measured clinic blood pressure , heart rate , plasma glucose , and insulin at rest and during an oral glucose load before and 12 weeks after treatment with either c and esartan cilexetil ( 8–16 mg once daily ) or hydrochlorothiazide ( HCTZ , 25–50 mg once daily ) , administered orally in accordance with a double-blind , r and omized , placebo-controlled , two-parallel-groups study design . Insulin sensitivity was expressed as insulin resistance index ( IRI ) , calculated as the ratio of the area under the curve ( AUC ) for glucose to that for insulin . In a subgroup of patients , measurements also included direct microneurographic recording of muscle sympathetic nerve activity ( MSNA ) in the peroneal nerve . Results C and esartan cilexetil caused a significant ( P reduction in both mean blood pressure ( from 114.2 ± 5.1 to 99.6 ± 6.0 mmHg ) and MSNA ( from 51.0 ± 12.3 to 40.4 ± 12.5 bursts per 100 heart beats ) , and a significant ( P increase in insulin sensitivity ( AUC IRI : from −23.2 ± 22.1 to −17.6 ± 12.2 ) . In contrast , HCTZ did not significantly affect MSNA and worsened insulin sensitivity , while achieving blood pressure reductions similar to those produced by c and esartan cilexetil . Conclusions These data provide evidence that , in obese hypertensive individuals , treatment with c and esartan cilexetil has an antihypertensive effect similar to that of HCTZ . Unlike diuretic treatment , however , treatment with c and esartan cilexetil improves insulin sensitivity and exerts sympathoinhibitory effects", "BACKGROUND In the 2.8 years of the Diabetes Prevention Program ( DPP ) r and omised clinical trial , diabetes incidence in high-risk adults was reduced by 58 % with intensive lifestyle intervention and by 31 % with metformin , compared with placebo . We investigated the persistence of these effects in the long term . METHODS All active DPP participants were eligible for continued follow-up . 2766 of 3150 ( 88 % ) enrolled for a median additional follow-up of 5.7 years ( IQR 5.5 - 5.8 ) . 910 participants were from the lifestyle , 924 from the metformin , and 932 were from the original placebo groups . On the basis of the benefits from the intensive lifestyle intervention in the DPP , all three groups were offered group-implemented lifestyle intervention . Metformin treatment was continued in the original metformin group ( 850 mg twice daily as tolerated ) , with participants unmasked to assignment , and the original lifestyle intervention group was offered additional lifestyle support . The primary outcome was development of diabetes according to American Diabetes Association criteria . Analysis was by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT00038727 . FINDINGS During the 10.0-year ( IQR 9.0 - 10.5 ) follow-up since r and omisation to DPP , the original lifestyle group lost , then partly regained weight . The modest weight loss with metformin was maintained . Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years ( 95 % CI 4.1 - 5.7 ) in the intensive lifestyle intervention group , 7.8 ( 6.8 - 8.8 ) in the metformin group , and 11.0 ( 9.8 - 12.3 ) in the placebo group . Diabetes incidence rates in this follow-up study were similar between treatment groups : 5.9 per 100 person-years ( 5.1 - 6.8 ) for lifestyle , 4.9 ( 4.2 - 5.7 ) for metformin , and 5.6 ( 4.8 - 6.5 ) for placebo . Diabetes incidence in the 10 years since DPP r and omisation was reduced by 34 % ( 24 - 42 ) in the lifestyle group and 18 % ( 7 - 28 ) in the metformin group compared with placebo . INTERPRETATION During follow-up after DPP , incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group , but the cumulative incidence of diabetes remained lowest in the lifestyle group . Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years . FUNDING National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK )", "BACKGROUND Lifestyle interventions produce short-term improvements in glycemia and cardiovascular disease ( CVD ) risk factors in individuals with type 2 diabetes mellitus , but no long-term data are available . We examined the effects of lifestyle intervention on changes in weight , fitness , and CVD risk factors during a 4-year study . METHODS The Look AHEAD ( Action for Health in Diabetes ) trial is a multicenter r and omized clinical trial comparing the effects of an intensive lifestyle intervention ( ILI ) and diabetes support and education ( DSE ; the control group ) on the incidence of major CVD events in 5145 overweight or obese individuals ( 59.5 % female ; mean age , 58.7 years ) with type 2 diabetes mellitus . More than 93 % of participants provided outcomes data at each annual assessment . RESULTS Averaged across 4 years , ILI participants had a greater percentage of weight loss than DSE participants ( -6.15 % vs -0.88 % ; P improvements in treadmill fitness ( 12.74 % vs 1.96 % ; P ( -0.36 % vs -0.09 % ; P ( -5.33 vs -2.97 mm Hg ; P .001 ) and diastolic ( -2.92 vs -2.48 mm Hg ; P = .01 ) blood pressure , and levels of high-density lipoprotein cholesterol ( 3.67 vs 1.97 mg/dL ; P ) and triglycerides ( -25.56 vs -19.75 mg/dL ; P .001 ) . Reductions in low-density lipoprotein cholesterol levels were greater in DSE than ILI participants ( -11.27 vs -12.84 mg/dL ; P = .009 ) owing to greater use of medications to lower lipid levels in the DSE group . At 4 years , ILI participants maintained greater improvements than DSE participants in weight , fitness , hemoglobin A(1c ) levels , systolic blood pressure , and high-density lipoprotein cholesterol levels . CONCLUSIONS Intensive lifestyle intervention can produce sustained weight loss and improvements in fitness , glycemic control , and CVD risk factors in individuals with type 2 diabetes . Whether these differences in risk factors translate to reduction in CVD events will ultimately be addressed by the Look AHEAD trial . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00017953", "BACKGROUND Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infa rct ion and stroke . There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma ( PPAR gamma ) could reduce macrovascular complications . Our aim , therefore , was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes . METHODS We did a prospect i ve , r and omised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease . We recruited patients from primary -care practice s and hospitals . We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg ( n=2605 ) or matching placebo ( n=2633 ) , to be taken in addition to their glucose-lowering drugs and other medications . Our primary endpoint was the composite of all-cause mortality , non fatal myocardial infa rct ion ( including silent myocardial infa rct ion ) , stroke , acute coronary syndrome , endovascular or surgical intervention in the coronary or leg arteries , and amputation above the ankle . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N NCT00174993 . FINDINGS Two patients were lost to follow-up , but were included in analyses . The average time of observation was 34.5 months . 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint ( HR 0.90 , 95 % CI 0.80 - 1.02 , p=0.095 ) . The main secondary endpoint was the composite of all-cause mortality , non-fatal myocardial infa rct ion , and stroke . 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint ( 0.84 , 0.72 - 0.98 , p=0.027 ) . Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified . 6 % ( 149 of 2065 ) and 4 % ( 108 of 2633 ) of those in the pioglitazone and placebo groups , respectively , were admitted to hospital with heart failure ; mortality rates from heart failure did not differ between groups . INTERPRETATION Pioglitazone reduces the composite of all-cause mortality , non-fatal myocardial infa rct ion , and stroke in patients with type 2 diabetes who have a high risk of macrovascular events", "Objective : To examine whether experimentally induced weight gain raises ambulatory blood pressure ( BP ) in healthy subjects and identify any relationship between changes in BP and changes in regional fat distribution . Patients and Methods : Twenty‐six normal weight subjects were r and omized to 8 weeks of weight gain through overfeeding ( n=16 ; age , 30.4±6.6 years ) or to weight maintenance ( controls ; n=10 ; age , 27.1±7.7 years ) between July 2004 and August 2010 . Measures of body composition via dual energy X‐ray absorptiometry and computed tomography , circulating biomarkers , and 24‐hour ambulatory BP were obtained at baseline and after the 8‐week experimental phase . Results : Overfeeding result ed in 3.7 kg ( 95 % CI , 2.9‐4.5 ) increase in body weight in weight gainers , with increments in total ( 46.2 cm2 ; 95 % CI , 27.6‐64.9 ) , visceral ( 13.8 cm2 ; 95 % CI , 5.8‐21.9 ) , and subcutaneous fat ( 32.4 cm2 ; 95 % CI , 13.5‐51.3 ) . No changes occurred in the maintenance group . Increases in 24‐hour systolic BP ( 4 mm Hg ; 95 % CI , 1.6‐6.3 ) , mean BP ( 1.7 mm Hg ; 95 % CI , 0.3‐3.3 ) , and pulse pressure ( 2.8 mm Hg ; 95 % CI , 1.1‐4.4 ) were evident after weight gain in the experimental group , whereas BP remained unchanged in controls . Changes in mean BP correlated only with changes in visceral fat ( & rgr;=0.45 ; P=.02 ) , but not with changes in other body composition measures . Conclusion : Modest weight gain causes elevation in 24‐hour BP in healthy subjects . The association between increased BP and abdominal visceral fat accumulation suggests that visceral deposition of adipose tissue may contribute specifically to the enhanced risk of hypertension associated with weight gain", "Hyperinsulinemia and increased sympathetic nervous system ( SNS ) activity are thought to be pathophysiological links between obesity and hypertension . In the present study , we examined the relation among heart rate ( HR ) , blood pressure ( BP ) , and percent body fat ( hydrodensitometry or DEXA ) , fasting plasma insulin concentration , and muscle sympathetic nerve activity ( MSNA , microneurography ) in male , normotensive whites ( n=42 ) and Pima Indians ( n=77 ) . Pima Indians have a high prevalence of obesity and hyperinsulinemia but a relatively low prevalence of hypertension . Compared with whites , Pima Indian men had a higher percent body fat ( 28 % versus 21 % ) and higher fasting insulin concentrations ( 210 versus 132 pmol/L ) but lower MSNA ( 27 versus 33 bursts/min ) ( all P HR and BP were positively related to percent body fat and MSNA , and both were significant independent determinants of HR and BP in multiple regression analyses . However , MSNA was positively related to percent body fat and the fasting insulin concentration in whites ( r = 0.60 and r = 0.47 , both P normal BP regulation but indicate that the roles of hyperinsulinemia and increased SNS activity as mediators for the relation between obesity and hypertension can differ between different ethnic groups . The lack of an increase in SNS activity with increasing adiposity and insulinemia in Pima Indians may contribute to the low prevalence of hypertension in this population", "Glucagon-like peptide-1 ( GLP-1 ) , an incretin , which is used to treat diabetes mellitus in humans , inhibited vagal activity and activated nitrergic pathways . In rats , GLP-1 also increased sympathetic activity , heart rate , and blood pressure ( BP ) . However , the effects of GLP-1 on sympathetic activity in humans are unknown . Our aims were to assess the effects of a GLP-1 agonist with or without alpha(2)-adrenergic or -nitrergic blockade on autonomic nervous functions in humans . In this double-blind study , 48 healthy volunteers were r and omized to GLP-1-(7 - 36 ) amide , the nitric oxide synthase ( NOS ) inhibitor N(G)-monomethyl-l-arginine acetate ( l-NMMA ) , the alpha(2)-adrenergic antagonist yohimbine , or placebo ( i.e. , saline ) , alone or in combination . Hemodynamic parameters , plasma catecholamines , and cardiac sympathetic and parasympathetic modulation were measured by spectral analysis of heart rate . Thereafter , the effects of GLP-1-(7 - 36 ) amide on muscle sympathetic nerve activity ( MSNA ) were assessed by microneurography in seven subjects . GLP-1 increased ( P = 0.02 ) MSNA but did not affect cardiac sympathetic or parasympathetic indices , as assessed by spectral analysis . Yohimbine increased plasma catecholamines and the low-frequency ( LF ) component of heart rate power spectrum , suggesting increased cardiac sympathetic activity . l-NMMA increased the BP and reduced the heart rate but did not affect the balance between sympathetic and parasympathetic activity . GLP-1 increases skeletal muscle sympathetic nerve activity but does not appear to affect cardiac sympathetic or parasympathetic activity in humans", "The purpose of this study was to determine the contribution of the adrenergic system in mediating hypertension in obese and lean patients . Thirteen obese , hypertensive patients with a body mass index ( BMI ) > or = 28 kg/m2 ( obese ) and nine lean patients with a BMI After a 1-week washout period , participants underwent daytime ambulatory blood pressure monitoring ( ABPM ) . Participants were then treated with the alpha-adrenergic antagonist doxazosin , titrating to 4 mg QHS in 1 week . In the next week , the beta-adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and titrated to 50 mg/day within 1 week . One month after the addition of atenolol , all patients underwent a second ABPM session . There were no differences between the obese and lean subjects in baseline systolic ( SBP ) , diastolic ( DBP ) , or mean arterial pressures ( MAP ) measured by office recording or ABPM . However , obese subjects had higher heart rates than lean subjects ( 87.5+/-2.4 v 76.8+/-4.9 beats/min ) . After 1 month of treatment with the adrenergic blockers , obese patients had a significantly lower SBP ( 130.0+/-2.5 v 138.9+/-2.1 mm Hg , P = .02 ) and MAP ( 99.6+/-2.3 v 107.0+/-1.5 mm Hg , P = .02 ) than lean patients . Obese patients also tended to have a lower DBP than lean patients ( 84.3+/-2.5 v 90.9+/-1.6 mm Hg , P = .057 ) , but there was no significant difference in heart rate after 1 month of adrenergic blockade . These results indicate that blood pressure is more sensitive to adrenergic blockade in obese than in lean hypertensive patients and suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity", "To evaluate the effect of metformin on insulin sensitivity and to further examine the relationship between insulin resistance , sympathetic nerve activity and blood pressure , 6 obese insulin resistant , normoglycemic hypertensive men were investigated ( age 49 + /- 2 years , BMI 27.6 + /- 1.2 , mean + /- SEM ) . The study had a placebo controlled , double blind , cross over design with 6 weeks ' metformin treatment ( 850 mg b.i.d ) vs placebo . Blood pressure was measured weekly . At the end of each treatment period , glucose infusion rate ( GIR ) , muscle sympathetic nerve activity ( MSA ) and renal and total body norepinephrine ( NE ) kinetics ( radioisotope dilution ) were examined during euglycemic hyperinsulinemic clamp . Fasting insulin was 13 + /- 3 and 10 + /- 2 mU/l and fasting glucose 5.3 + /- 0.2 and 5.1 + /- 0.1 mmol/l after placebo and metformin treatment , respectively ( ns ) . GIR during the last hour of the insulin clamp was 3.7 + /- 0.6 vs 3.6 + /- 0.6 mg/kg x min ( ns ) . Resting MSA , total body and right renal NE spillover did not differ significantly after placebo and metformin treatment . Systolic and diastolic blood pressures were 151 + /- 10/95 + /- 5 mmHg after placebo and 146 + /- 5/94 + /- 5 mmHg after metformin treatment ( ns ) . Thus metformin treatment did not have any significant effect on insulin sensitivity , blood pressure or sympathetic activity in this small group of patients . Renal plasma flow and MSA increased significantly during the insulin clamp , whereas renal NE and total body NE spillover remained unchanged , suggesting nonuniform regional sympathetic nerve responses to acute hyperinsulinemia", "OBJECTIVES In view of previous experimental evidence relating sympathetic nervous overactivity in the heart to myocardial necrosis and ventricular arrhythmias , we prospect ively examined the hypothesis that heightened cardiac sympathetic nervous activity is associated with an adverse outcome in patients with moderate to severe heart failure . BACKGROUND Despite recent therapeutic advances , patients with heart failure continue to have high mortality from progressive hemodynamic decompensation and lethal ventricular arrhythmias . It is believed that initially compensatory increases in sympathetic nervous system activity may ultimately be maladaptive , potentially contributing to subsequent adverse events . METHODS Sixty patients with moderate to severe heart failure ( left ventricular ejection fraction 18.9 + /- 0.9 % [ mean + /- SE ] ) were studied prospect ively . In addition to the compilation of a hemodynamic , biochemical and electrocardiographic profile for each patient , whole-body and cardiac sympathetic activity were determined by isotope dilution . The relation of these variables to outcome was determined by Cox proportional hazards analysis . RESULTS The mean follow-up period of the study group was 7 + /- 1 months ( range 1 to 24 ) with a 12-month actuarial survival of 75 % . Deaths ( 14 in all ) were accounted for either by sudden death or progressive heart failure in equal numbers . The rate of release of norepinephrine from the heart was significantly higher in patients with heart failure than in healthy subjects ( 402 + /- 37 vs. 105 + /- 19 pmol/min , p pulmonary capillary wedge pressure ( p mean pulmonary artery pressure ( p serum sodium levels ( p cardiac norepinephrine spill-over rate ( p cardiac norepinephrine spillover rate was identified as the most powerful prognostic marker ( p = 0.0006 ) of those evaluated in this study . CONCLUSIONS These results suggest that activation of the sympathetic nervous system in patients with heart failure , specifically the cardiac sympathetic nerves , may contribute to the poor prognosis associated with severe heart failure . The data therefore provide a rationale for the use of drugs such as beta-adrenergic blocking agents in the management of patients with heart failure", "Endothelial dysfunction is considered an important prognostic factor in atherosclerosis . To determine the long-term association of brachial artery flow-mediated dilation ( FMD ) and adverse cardiovascular ( CV ) events in healthy subjects , we prospect ively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease , 387 men ( 63 % ) , and mean age 54 ± 11 years . After overnight fasting and discontinuation of all medications for ≥12 hours , FMD was assessed using high-resolution linear array ultrasound . Subjects were divided into 2 groups : FMD ≤11.3 % ( n = 309 ) and > 11.3 % ( n = 309 ) , where 11.3 % is the median FMD , and were comparable regarding CV risk factors , lipoproteins , fasting glucose , C-reactive protein , concomitant medications , and Framingham 10-year risk score . In a mean clinical follow-up of 4.6 ± 1.8 years , the composite CV events ( all-cause mortality , nonfatal myocardial infa rct ion , hospitalization for heart failure or angina pectoris , stroke , coronary artery bypass grafting , and percutaneous coronary interventions ) were significantly more common in subjects with FMD ≤11.3 % rather than > 11.3 % ( 15.2 % vs 1.2 % , p = 0.0001 , respectively ) . Univariate analysis demonstrated that the median FMD significantly predicted CV events ( odds ratio 2.78 , 95 % CI 1.35 to 5.71 , p that median FMD was the best independent predictor of long-term CV adverse events ( odds ratio 2.93 , 95 % CI 1.28 to 6.68 , p , brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment", "Augmented sympathetic nerve activity is associated with heart failure with preserved left ventricular ejection fraction ( HFpEF ) . Lipophilic statins reduce sympathetic nerve activity in patients with heart failure with reduced left ventricular ejection fraction . However , little is known about whether all types of statins , regardless of solubility , reduce sympathetic nerve activity in HFpEF . We evaluated the effect of atorvastatin , a lipophilic statin , and rosuvastatin , a hydrophilic statin , on muscle sympathetic nerve activity ( MSNA ) in HFpEF patients . This study was conducted as a prospect i ve , r and omized , open-label , crossover trial . Ten HFpEF patients with untreated hyperlipidemia participated in this study . Subjects were assigned to either the atorvastatin ( lipophilic ) or the rosuvastatin ( hydrophilic ) group with each drug administered for 8 weeks . Atorvastatin and rosuvastatin treatment result ed in a similar reduction in low-density lipoprotein cholesterol ( LDL-C ) levels . There was no difference in the effect of either treatment on blood pressure , heart rate , or left ventricular function . Atorvastatin significantly decreased MSNA frequency compared with baseline ( 31.5 ± 6.3 vs. 47.5 ± 10.7 bursts/min , p rosuvastatin had no effect on MSNA ( 40.9 ± 7.3 bursts/min ) . MSNA was significantly lower in the atorvastatin group than rosuvastatin group ( p reduction in MSNA seen in either group did not correlate with the reduction in LDL-C. No significant differences were observed in either the baroreflex control of heart rate or MSNA between the two groups . These results suggest that lipophilic statins have a favorable effect on sympathetic nerve activity beyond lowering LDL-C in HFpEF , but hydrophilic statins do not", "Background Lorcaserin , a selective serotonin 2C receptor agonist that modulates appetite , has proven efficacy for weight management in overweight or obese patients . The cardiovascular safety and efficacy of lorcaserin are undefined . Methods We r and omly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin ( 10 mg twice daily ) or placebo . The primary safety outcome of major cardiovascular events ( a composite of cardiovascular death , myocardial infa rct ion , or stroke ) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4 . If noninferiority was met , the primary cardiovascular efficacy outcome ( a composite of major cardiovascular events , heart failure , hospitalization for unstable angina , or coronary revascularization [ extended major cardiovascular events ] ) was assessed for superiority at the end of the trial . Results At 1 year , weight loss of at least 5 % had occurred in 1986 of 5135 patients ( 38.7 % ) in the lorcaserin group and in 883 of 5083 ( 17.4 % ) in the placebo group ( odds ratio , 3.01 ; 95 % confidence interval [ CI ] , 2.74 to 3.30 ; P the lorcaserin group had slightly better values with respect to cardiac risk factors ( including blood pressure , heart rate , glycemic control , and lipids ) than those in the placebo group . During a median follow‐up of 3.3 years , the rate of the primary safety outcome was 2.0 % per year in the lorcaserin group and 2.1 % per year in the placebo group ( hazard ratio , 0.99 ; 95 % CI , 0.85 to 1.14 ; P the rate of extended major cardiovascular events was 4.1 % per year and 4.2 % per year , respectively ( hazard ratio , 0.97 ; 95 % CI , 0.87 to 1.07 ; P=0.55 ) . Adverse events of special interest were uncommon , and the rates were generally similar in the two groups , except for a higher number of patients with serious hypoglycemia in the lorcaserin group ( 13 vs. 4 , P=0.04 ) . Conclusions In a high‐risk population of overweight or obese patients , lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo . ( Funded by Eisai ; CAMELLIA – TIMI 61 Clinical Trials.gov number , NCT02019264 .", "Objectives : The objective of this study is to determine the effects of renin -- angiotensin -- aldosterone system inhibition , sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension . Methods : A r and omized , four-way , double-blind , crossover study in 31 adults with previously untreated obesity-related hypertension , in which the effects of 8 weeks ’ inhibition of the renin -- angiotensin -- aldosterone system ( using aliskiren 300 mg ) , sympathoinhibition ( using moxonidine 0.4 mg ) , diuretic therapy ( using hydrochlorothiazide 25 mg ) or placebo on flow-mediated dilation and 24-h blood pressure were compared . Results : The median flow-mediated dilation during placebo was 4.0 % [ interquartile range ( IQR ) 2.9–5.5 % ] and was increased by aliskiren [ 0.81 % , 95 % confidence interval ( CI ) 0.02–1.79 ] , but not by moxonidine ( 0.20 % , 95 % CI −0.46 to 1.03 ) or hydrochlorothiazide ( 0.39 % , 95%CI −0.31%–1.26 % ) . Similarly , compared with placebo , mean 24-h blood pressure was most reduced by aliskiren ( −9.8/−6.3 mmHg ) and to a lesser degree by hydrochlorothiazide ( −5.9/−2.6 mmHg ) . Moxonidine did not significantly affect blood pressure despite reduction of muscle sympathetic nerve activity . Insulin sensitivity deteriorated during hydrochlorothiazide treatment and was unaffected by aliskiren or moxonidine . Unlike aliskiren and moxonidine , hydrochlorothiazide reduced urinary 8-iso-prostagl and in F2&agr;-VI , a marker of oxidative stress . Vascular stiffness , systemic inflammation , leptin , adiponectin and other oxidative stress markers ( plasma malondialdehyde , myeloperoxidase activity and urinary 8-hydroxydeoxyguanosine ) were unaffected by treatment . Conclusion : Renin inhibition , but not sympathoinhibition or diuretic therapy , improves endothelial function and results in larger reductions of 24-h , office , and central blood pressure in obesity-related hypertension . This adds weight to the hypothesis that inhibition of the renin -- angiotensin -- aldosterone system is an effective first step in the treatment of obesity-related hypertension", "The association between glomerular hyperfiltration and cardiovascular events is not well known . To investigate whether glomerular hyperfiltration is independently associated with risk of adverse outcome we analyzed 8794 participants , average age 52 years enrolled in 8 prospect i ve studies . Of these , 89 % had hypertension . Using the 5th and 95th percentiles of the age- and sex-specific quintiles of CKD-EPI-calculated estimated glomerular filtration rate ( eGFR ) , we identified three participant groups with low , high and normal eGFR . The ambulatory pulse pressure interval was wider and nighttime blood pressure fall was smaller in both the low and high than in the normal eGFR participants . During a mean follow-up of 6.2 years , there were 722 cardiovascular events . Crude event rates were significantly higher for both high ( 1.8 per 100-person-year ) and low eGFR groups ( 2.1 per 100 person-year ) as compared with group with normal eGFR ( 1.2 per 100 person-year ) . In multivariable Cox models including age , sex , average 24-hour blood pressure , smoking , diabetes , and cholesterol , both high eGFR ( hazard ratio 1.5 ( 95 % confidence interval 1.2 - 2.1 ) and low eGFR ( 2.0 [ 1.5 - 2.6 ] ) participants had a significantly higher risk of cardiovascular events as compared to those with normal eGFR . Addition of body mass index to the multivariable survival model did not change the magnitude of hazard estimates . Thus , glomerular hyperfiltration is a strong and independent predictor of cardiovascular events in a large multiethnic population of predominantly hypertensive individuals . Our findings support a U-shaped relationship between eGFR and adverse outcome" ]

[ "Background Patients suffering from Multiple Sclerosis ( MS ) experience a wide array of symptoms , including balance problems , mobility impairment , fatigue and depression . Physical exercise has recently been acknowledged as a treatment option complementary to medication . However , information regarding putative effects of structured exercise programs on neurological symptoms is sparse . Tai Chi , a Chinese martial art incorporating physical exercise and mindfulness training , has been shown to yield health benefits in various neurological groups . It seems particularly suitable for patients with motoric deficits as it challenges coordination and balance . The purpose of the current study was to explore the therapeutic value of structured Tai Chi training for coordination , balance , fatigue and depression in mildly disabled MS patients . Methods A sample of 32 MS patients ( Exp and ed Disability Status Scale , EDSS A structured Tai Chi course was devised and a Tai Chi group participated in two weekly sessions of 90 minutes duration for six months , while a comparison group received treatment as usual ( TAU ) . Both groups were examined prior to and following the six-months interval with regards to balance and coordination performance as well as measures of fatigue , depression and life satisfaction . Results Following the intervention , the Tai Chi group showed significant , consistent improvements in balance , coordination , and depression , relative to the TAU group ( range of effect-sizes : partial η2 = 0.16 – 0.20 ) . Additionally , life satisfaction improved ( partial η2 = 0.31 ) . Fatigue deteriorated in the comparison group , whereas it remained relatively stable in the Tai Chi group ( partial η2 = 0.24 ) . Conclusions The consistent pattern of results confirms that Tai Chi holds therapeutic potential for MS patients . Further research is needed to determine underlying working mechanisms , and to verify the results in a larger sample and different MS subgroups", "Background Many breast cancer survivors experience fatigue , mood , and sleep disturbances . Purpose This study aims to compare a meditative movement practice , Qigong/Tai Chi Easy ( QG/TCE ) with sham Qigong ( SQG ) , testing effects of meditation/breath aspects of QG/TCE on breast cancer survivors ’ persistent fatigue and other symptoms . Methods This double-blind , r and omized controlled trial tested 12 weeks of QG/TCE versus SQG on fatigue , depression , and sleep among 87 postmenopausal , fatigued breast cancer survivors , stages 0–III , age 40–75 . Results Fatigue decreased significantly in the QG/TCE group compared to control at post-intervention ( p = 0.005 ) and 3 months follow-up ( p = 0.024 ) , but not depression and sleep quality . Improvement occurred over time for both interventions in depression and sleep quality ( all p QG/TCE showed significant improvement over time compared to SQG for fatigue , but not depression or sleep . Both QG/TCE and SQG showed improvement for two prevalent symptoms among breast cancer survivors , depression and sleep dysfunction", "OBJECTIVE Evaluate effectiveness of the Arthritis Foundation Tai Chi Program for community participants with arthritis . METHODS 343 individuals were r and omized to either the intervention or wait-list control group . Performance and self-reported outcome ( SRO ) measures were assessed at baseline and eight weeks . At one year , SROs only were assessed . Adjusted means were determined using regression models adjusting for covariates , and effect sizes ( ES ) were calculated . RESULTS Average participant age was 66 years , 87 % were female , and 87 % were Caucasian . Among 284 ( 83 % ) participants who returned at eight weeks , balance by reach ( ES = 0.30 ) and helplessness , sleep , and role participation satisfaction ( ES = 0.24 - 0.54 ) improved significantly ; pain , fatigue , and stiffness improvement ( ES = 0.15 - 0.23 ) approached significance . No change was noted in mobility , lower extremity strength , or single-leg stance balance . At one year , improvements in pain , fatigue , stiffness , helplessness , and role participation satisfaction at eight weeks were maintained ; 30 % continued tai chi practice . CONCLUSION Moderate effectiveness of the Arthritis Foundation Tai Chi Program was confirmed", "Background Cancer-related fatigue ( CRF ) is a common and often long-lasting symptom for many breast cancer survivors . Evidence for its management is scarce . However , the Traditional Chinese Medicine ( TCM ) Shu Gan Jian Pi ( SGJP ) granules is an effective and practical therapy for CRF . Methods / Design We will conduct a multicenter , r and omized , double-blind , placebo-controlled clinical trial to determine whether the SGJP granules can effectively manage CRF . Breast cancer survivors experiencing fatigue within 5 years of primary treatment completion will be enrolled and r and omly assigned to Group S ( SGJP ) or Group P ( placebo ) . The primary outcome measures will include Revised Piper Fatigue Scale score . Outcome measures will be collected at baseline and at weeks 2 , 4 , and 8 . Discussion This study ’s findings may contribute to the development of an effective intervention for CRF.Trial registration Current controlled trials IS RCT N12702489 , 14 August , 2013", "Background . Multiple sclerosis ( MS ) is a chronic demyelinating neurological disease . Several studies have reported that complementary and alternative therapies can have positive effects against pain in these patients . Objective . The objective was to investigate the effectiveness of an Ai-Chi aquatic exercise program against pain and other symptoms in MS patients . Methods . In this r and omized controlled trial , 73 MS patients were r and omly assigned to an experimental or control group for a 20-week treatment program . The experimental group underwent 40 sessions of Ai-Chi exercise in swimming pool and the control group 40 sessions of abdominal breathing and contraction-relaxation exercises in therapy room . Outcome variables were pain , disability , spasm , depression , fatigue , and autonomy , which were assessed before the intervention and immediately and at 4 and 10 weeks after the last treatment session . Results . The experimental group showed a significant ( P pain intensity versus baseline , with an immediate posttreatment reduction in median visual analogue scale scores of 50 % that was maintained for up to 10 weeks . Significant improvements were also observed in spasm , fatigue , disability , and autonomy . Conclusion . According to these findings , an Ai-Chi aquatic exercise program improves pain , spasms , disability , fatigue , depression , and autonomy in MS patients", "This study examined the effects of Tai Chi , a low-impact mind-body movement therapy , on severity of depression , anxiety , and stress symptoms in central ly obese people with elevated depression symptoms . In total , 213 participants were r and omized to a 24-week Tai Chi intervention program or a wait-list control group . Assessment s were conducted at baseline and 12 and 24 weeks . Outcomes were severity of depression , anxiety , and stress symptoms , leg strength , central obesity , and other measures of metabolic symptom . There were statistically significant between-group differences in favor of the Tai Chi group in depression ( mean difference = −5.6 units , P ( −2.3 units , P ( −3.6 units , P ( 1.1 units , P Tai Chi group relative to the control group during the second 12 weeks of follow-up . Tai Chi appears to be beneficial for reducing severity of depression , anxiety , and stress and leg strength in central ly obese people with depression symptoms . More studies with longer follow-up are needed to confirm the findings . This trial is registered with ACTRN12613000010796", "BACKGROUND Patients with chronic heart failure ( HF ) and with elevated depression symptoms are at greater risk of morbidity and mortality . Somatic symptoms of depression are particularly prevalent in HF and are related to worse disease prognosis . T'ai chi practice is related to increased emotional well-being in various clinical population s ; however , relatively little is known about t'ai chi 's effects on somatic versus cognitive symptom dimensions of depression in HF . PURPOSE The objective of the study was to measure whether a t'ai chi intervention effectively reduces somatic and /or cognitive symptoms of depression in patients with HF . METHODS Patients with HF were assigned to either t'ai chi training ( n=16 ) or a usual-care group ( n=12 ) . At baseline and after the 12-week intervention period , participants were evaluated for changes in depressive symptoms using Beck Depression Inventory ( BDI ) total scores ( BDI-t ) and subcategorized scores of BDI-somatic ( BDI-s ) and BDI-cognitive ( BDI-c ) , and for symptoms of fatigue using the Multidimensional Fatigue Symptom Inventory-Short Form . RESULTS Patients with HF in the t'ai chi group compared to the usual-care group had reduced BDI-s ( p≤0.017 ) , but not BDI-c ( p=0.50 ) scores from pre- to postintervention . Although t'ai chi did not significantly reduce fatigue , changes in physical fatigue ( p≤0.05 ) were independently associated with changes in BDI-t scores . CONCLUSIONS T'ai chi practice reduced somatic symptoms of depression , which have been linked to worse prognosis in HF . Reductions in fatigue appear to explain some but not all of the reductions in somatic symptoms of depression ", "BACKGROUND Epidemiologic data is available on chronic fatigue for Western , but not for Chinese population s. The aims of the present study were to determine the prevalence of chronic fatigue in the general population of Hong Kong , compare health and lifestyle characteristics of non-chronic fatigue and chronic fatigue cases , and identify risk factors for chronic fatigue . METHODS We performed telephone interviews on 5001 r and omly selected Chinese adults aged ≥18 years administering the Chinese version of Chronic Fatigue Scale ( ChCFS ) , the Hospital Anxiety and Depression Scale ( HADS ) , and quality of life ( QoL ) indexed by Medical Outcomes Study 12-item Short-Form Health Survey ( SF12 ) . Lifestyle , and sociodemographic data were also collected . Chronic fatigue was defined according to Fukuda et al. 's ( 1994 ) criteria and case criterion was a ChCFS total scores ≥4 . RESULTS The weighted prevalence of chronic fatigue was 10.7 % , which was equivalent to 0.6 million adults in Hong Kong . Higher prevalence rates were found in females , older age groups , and low socioeconomic status . Fully adjusted stepwise regression analyses identified older age , retirees , housewife , existing long-term health problems , higher HADS scores , poor QoL , and low self-perceived health to be significantly associated with increased risk of chronic fatigue , whereas regular exercise was associated with decreased risk of chronic fatigue ( all p chronic fatigue is common in the general population of Hong Kong , and the prevalence increased with age and was higher in the women and lower socioeconomic population", "OBJECTIVES To evaluate the sustaining effects of Tai chi Qigong in improving the physiological health for COPD patients at sixth month . DESIGN A r and omized controlled trial . Subjects were in three r and omly assigned groups : Tai chi Qigong group , exercise group , and control group . SETTING The 206 subjects were recruited from five general outpatient clinics . INTERVENTIONS Tai chi Qigong group completed a 3-month Tai chi Qigong program . Exercise group practice d breathing and walking as an exercise . Control group received usual care . MAIN OUTCOME MEASURES Primary outcomes included six-minute walking distance and lung functions . Secondary outcomes were dyspnea and fatigue levels , number of exacerbations and hospital admissions . RESULTS Tai chi Qigong group showed a steady improvement in exercise capacity ( P mean walking distance increased from 298 to 349 meters ( + 17 % ) . No significant changes were noted in the other two groups . Tai chi Qigong group also showed improvement in lung functions ( P Mean forced expiratory volume in 1s increased from .89 to .99l ( + 11 % ) . No significant change was noted in the exercise group . Deterioration was found in the control group , with mean volume decreased from .89 to .84l ( -5.67 % ) . Significant decreased in the number of exacerbations was observed in the Tai chi Qigong group . No changes in dyspnea and fatigue levels were noted among the three groups . CONCLUSIONS Tai chi Qigong has sustaining effects in improving the physiological health and is a useful and appropriate exercise for COPD patients", "CONTEXT Tai Chi is a traditional Chinese health-promoting exercise . It has been shown to enhance mental health and improve psychological condition . OBJECTIVES We aim ed to assess the effectiveness of Tai Chi exercise for cancer-related fatigue in patients with lung cancer undergoing chemotherapy . METHODS We conducted a r and omized trial of Tai Chi exercise as compared with low-impact exercise as a control intervention . Exercises were practice d every other day , a one-hour session for 12 weeks for each of the study groups . The primary end point was a change in total score of the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) . Secondary end points were changes in five subscale scores of the MFSI-SF . All assessment s were repeated at three time points , T0 : before first course of chemotherapy ; T1 : before third course of chemotherapy ; and T2 : at the end of the fourth course of chemotherapy . RESULTS Between January 2012 and December 2014 , 96 patients were enrolled in this trial . At six and 12 weeks , the Tai Chi group had a lower MFSI-SF total score compared with the control group ( 59.5 ± 11.3 vs. 66.8 ± 11.9 , P Tai Chi group had lower MFSI-SF general subscale scores ( 18.1 ± 4.6 vs. 20.4 ± 4.5 , P 0.05 ) and physical subscale scores ( 17.5 ± 4.4 vs. 19.1 ± 4.5 , P 0.05 ) , and higher MFSI-SF vigor subscale scores ( 14.5 ± 3.3 vs. 11.6 ± 3.4 , P found in emotional subscale ( 20.2 ± 3.6 vs. 20.0 ± 3.5 , P > 0.05 ) and mental subscale ( 18.2 ± 4.0 vs. 18.9 ± 3.9 , P > 0.05 ) scores between the Tai Chi group and the control group . At 12 weeks , the MFSI-SF subscale scores showed the same trends as at six weeks . CONCLUSION Tai Chi is an effective intervention for managing cancer-related fatigue in patients with lung cancer undergoing chemotherapy , especially for decreasing general fatigue and physical fatigue , and increasing vigor", "STUDY OBJECTIVES To investigate the comparative efficacy of cognitive behavioral therapy ( CBT ) , Tai Chi Chih ( TCC ) , and sleep seminar education control ( SS ) on the primary outcome of insomnia diagnosis , and secondary outcomes of sleep quality , fatigue , depressive symptoms , and inflammation in older adults with insomnia . DESIGN R and omized controlled , comparative efficacy trial . SETTING Los Angeles community . PATIENTS 123 older adults with chronic and primary insomnia . INTERVENTIONS R and om assignment to CBT , TCC , or SS for 2-hour group sessions weekly over 4 months with follow-up at 7 and 16 months . MEASUREMENTS Insomnia diagnosis , patient-reported outcomes , polysomnography ( PSG ) , and high-sensitivity C-reactive protein ( CRP ) levels . RESULTS CBT performed better than TCC and SS in remission of clinical insomnia as ascertained by a clinician ( P improvement in sleep quality , sleep parameters , fatigue , and depressive symptoms than TCC and SS ( all P values CBT was associated with a reduced risk of high CRP levels ( > 3.0 mg/L ) at 16 months ( odds ratio [ OR ] , 0.26 [ 95 % CI , 0.07 - 0.97 ] P Remission of insomnia was associated with lower levels of CRP ( P TCC was associated with improvements in sleep quality , fatigue , and depressive symptoms as compared to SS ( all P 's insomnia remission . PSG measures did not change . CONCLUSIONS Treatment of late-life insomnia is better achieved and sustained by cognitive behavioral therapies . Insomnia treatment and remission reduces a marker of inflammatory risk , which has implication s for cardiovascular morbidity and diabetes observed with sleep disturbance in epidemiologic surveys", "OBJECTIVE To examine the effects of a 10-week Tai Chi ( TC ) program on neuropsychological , psychological , and physical health of female cancer survivors . DESIGN Twenty-three women with a history of cancer participated in 60-min TC classes two times/week for 10-weeks . MAIN OUTCOME MEASURES Before and after the intervention , participants completed neuropsychological tests ( memory , executive functioning , language , and attention ) ; 5 tests of balance ; and self-report question naires of neuropsychological complaints , stress and mood , and fatigue . RESULTS After the 10-week session , participants evidence d fewer neuropsychological complaints and enhanced neuropsychological functioning . They also demonstrated improved balance and reported better psychological functioning . CONCLUSIONS Results suggest that TC may promote gains in neuropsychological functioning , in addition to previously demonstrated improvements in physical and psychological health . These findings support the need for controlled trials examining the potential benefits of TC on neuropsychological functioning after cancer", "BACKGROUND / AIMS Rheumatoid arthritis ( RA ) is a serious health problem result ing in significant morbidity and disability . Tai Chi may be beneficial to patients with RA as a result of effects on muscle strength and ' mind-body ' interactions . To obtain preliminary data on the effects of Tai Chi on RA , we conducted a pilot r and omized controlled trial . Twenty patients with functional class I or II RA were r and omly assigned to Tai Chi or attention control in twice-weekly sessions for 12 weeks . The American College of Rheumatology ( ACR ) 20 response criterion , functional capacity , health-related quality of life and the depression index were assessed . RESULTS At 12 weeks , 5/10 patients ( 50 % ) r and omized to Tai Chi achieved an ACR 20 % response compared with 0/10 ( 0 % ) in the control ( p = 0.03 ) . Tai Chi had greater improvement in the disability index ( p = 0.01 ) , vitality subscale of the Medical Outcome Study Short Form 36 ( p = 0.01 ) and the depression index ( p = 0.003 ) . Similar trends to improvement were also observed for disease activity , functional capacity and health-related quality of life . No adverse events were observed and no patients withdrew from the study . CONCLUSION Tai Chi appears safe and may be beneficial for functional class I or II RA . These promising results warrant further investigation into the potential complementary role of Tai Chi for treatment of RA" ]

[ "CONTEXT Physical activity can reduce the risk of hip fractures in older women , although the required type and duration of activity have not been determined . Walking is the most common activity among older adults , and evidence suggests that it can increase femoral bone density and reduce fracture risk . OBJECTIVE To assess the relationship of walking , leisure-time activity , and risk of hip fracture among postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve analysis begun in 1986 with 12 years of follow-up in the Nurses ' Health Study cohort of registered nurses within 11 US states . A total of 61,200 postmenopausal women ( aged 40 - 77 years and 98 % white ) without diagnosis of cancer , heart disease , stroke , or osteoporosis at baseline . MAIN OUTCOME MEASURES Incident hip fracture result ing from low or moderate trauma , analyzed by intensity and duration of leisure-time activity and by time spent walking , sitting , and st and ing , measured at baseline and up date d throughout follow-up . RESULTS From 1986 to 1998 , 415 incident hip fracture cases were identified . After controlling for age , body mass index , use of postmenopausal hormones , smoking , and dietary intakes in proportional hazards models , risk of hip fracture was lowered by 6 % ( 95 % confidence interval [ CI ] , 4%-9 % ; P of hip fracture ( relative risk [ RR ] , 0.45 ; 95 % CI , 0.32 - 0.63 ) compared with sedentary women with less than 3 MET-h/wk . Even women with a lower risk of hip fracture due to higher body weight experienced a further reduction in risk with higher levels of activity . Risk of hip fracture decreased linearly with increasing level of activity among women not taking postmenopausal hormones ( P risk of hip fracture ( RR , 0.59 ; 95 % CI , 0.37 - 0.94 ) compared with less than 1 h/wk . More time spent st and ing was also independently associated with lower risks . CONCLUSION Moderate levels of activity , including walking , are associated with substantially lower risk of hip fracture in postmenopausal women", "Background : Existing data suggest that physical activity reduces colon cancer risk , but the association is not consistently observed in women . One potential explanation for this inconsistency is that hormone therapy , which is associated with lower colon cancer risk , acts as a modifier of the physical activity/colon cancer relationship . Methods : Participants in the California Teachers Study ( N = 120,147 ) , a prospect i ve cohort of female teachers and administrators residing in California , ages 22 to 84 years at baseline and with no prior history of colon cancer were eligible for study . Between 1996 and 2002 , 395 patients were diagnosed with invasive colon cancer . The relative risks ( RR ) associated with lifetime ( high school through age 54 years or current age ) and recent ( past 3 years ) strenuous and moderate recreational physical activity were estimated using Cox proportional hazards regression models . Results : Combined lifetime moderate and strenuous recreational physical activity was only modestly associated with colon cancer risk in the cohort [ ≥4 versus ≤0.5 h/wk/y : RR , 0.75 ; 95 % confidence interval , 0.57 - 1.00 ; Ptrend = 0.23 ] . Lifetime physical activity reduced colon cancer risk among postmenopausal women who had never taken hormone therapy ( ≥4 versus ≤0.5 h/wk/y : RR , 0.51 ; 95 % confidence interval , 0.31 - 0.85 ; Ptrend = 0.02 ) . Postmenopausal women with histories of hormone therapy use had lower colon cancer risk , but their risk was not associated with physical activity . The likelihood ratio test for interaction between hormone use and lifetime moderate plus strenuous physical activity was of borderline statistical significance ( P = 0.05 ) . We observed no effect modification by age , body mass index , smoking status , menopausal status , or folate intake . Conclusions : Lifetime recreational physical activity may protect against colon cancer among postmenopausal women who have never used hormone therapy . Among hormone therapy users , who have lower risk of colon cancer , recreational physical activity does not seem to provide any additional benefit . With declining rates of hormone therapy use , physical activity offers one possible means for reducing women 's colon cancer risk . ( Cancer Epidemiol Biomarkers Prev 2007;16(3):517–25", "Background Lifestyle is a well-established risk factor for colorectal cancer ( CRC ) and is also found to be associated with occurrence of adenomas . In the present study we evaluated risk factors for both low-risk adenomas and advanced neoplasia in asymptomatic individuals using a single-paged question naire . Aim ing to see if the question naire was a useful tool in picking up high-risk individuals . Methods A cross-sectional study was carried out within a r and omised controlled colorectal cancer screening trial ( n = 6961 ) . The population comprised men and women born between 1946 and 1950 . Before screening in year 2001 they were asked to fill in a question naire about their present lifestyle . Cases were categorised according to the most severe findings at screening . Analyses were then conducted to find risk factors associated with the presence of either low-risk adenomas or advanced neoplasia . Results The response rate among attendees was 97 % ( 3998/4111 ) . Among these , 3447 ( 86 % ) had no neoplasia , 443 ( 11 % ) had low-risk adenomas , and 108 ( 3 % ) had advanced neoplasia . Low-risk adenomas were significantly associated with current smoking , and obesity . Participants with advanced neoplasia had a two-fold increased risk of not adhering to any of the selected lifestyle recommendations compared to controls . However , current smoking was the only variable that reached statistical significance in the multivariate analysis for these lesions . A dose-response relationship to the consumption of cigarettes per day was shown , where OR was 2.04 ( CI 1.07–3.89 ) for the lowest consumption category . Conclusion The present findings indicate that a short question naire may be adequate in picking up the most consistent associations between lifestyle risk factors and colorectal neoplasia . Smoking and BMI were found to be the most significant risk factors for neoplasia , but adhering to recommendations on diet , and physical activity seems also to be of importance", "BACKGROUND In older people , it is unclear whether obesity relates to mortality , which calls into question its etiologic role in disease and its public health relevance . This apparent lack of relationship in older people could be an artifactual result of their diverse health states . METHODS We used Cox regression analysis to determine whether the effect of body mass index ( BMI ) ( calculated as weight in kilograms divided by the square of height in meters ) or physical activity on mortality varied with health status in a prospect i ve cohort study of Chinese people 65 years or older enrolled from 1998 to 2000 at all of the 18 Elderly Health Centers of the Hong Kong Government Department of Health . Health status was categorized into 5 morbidity groups using a 12-item index covering illnesses , medications , frailty , and smoking . RESULTS After a mean follow-up of 4.1 years , there were 3819 deaths in 54 088 subjects ( 96.5 % successful follow-up ) . The effect of BMI on mortality varied with baseline health status ( P /=25 ) had higher mortality ( adjusted hazard ratio [ HR ] , 1.54 ; 95 % confidence interval [ CI ] , 1.02 - 2.33 ) , but in the unhealthiest group they had lower mortality ( HR , 0.55 ; 95 % CI , 0.49 - 0.63 ) compared with subjects of normal weight . Daily physical activity was associated with lower mortality compared with inactivity in the unhealthiest group ( HR , 0.70 ; 95 % CI , 0.61- 0.81 ) but not in the healthiest group . CONCLUSIONS In the elderly , the relationship between obesity and mortality varies according to the underlying health status . In those with poor health status , obesity is associated with better outcome , whereas in those with initially good health status , obesity is associated with worse outcome", "Background and Purpose — The role of physical activity , especially that of occupational and commuting physical activity , in the prediction of stroke risk is not properly established . We assessed the relationship of different types of physical activity with total and type-specific stroke risk . Methods — We prospect ively followed 47 721 Finnish subjects 25 to 64 years of age without a history of coronary heart disease , stroke , or cancer at baseline . Hazard ratios ( HRs ) for incident stroke were estimated for different levels of leisure time , occupational , and commuting physical activity . Results — During a mean follow-up of 19.0 years , 2863 incident stroke events were ascertained . The multivariate-adjusted ( age , sex , area , study year , body mass index , systolic blood pressure , cholesterol , education , smoking , alcohol consumption , diabetes , and other 2 types of physical activity ) HRs associated with low , moderate , and high leisure time physical activity were 1.00 , 0.86 , and 0.74 ( Ptrend respectively . Occupational activity had a modest association with ischemic stroke in the multivariate analysis ( Ptrend=0.046 ) . Conclusion — A high level of leisure time physical activity reduces the risk of all subtypes of stroke . Daily active commuting also reduces the risk of ischemic stroke", "OBJECTIVES The association between the risk of breast cancer and the physical load of work was studied because physical activity may reduce breast cancer risk via hormonal mechanisms . METHODS Occupational physical activity was estimated from a self-determined rating [ scale 1 (low)-5 ( high ) ] of occupational physical load for 1800 r and omly selected women born in 1930 - 1969 . The medians of the ratings were used as occupation-specific indices of occupational physical activity . All 65 occupations with at least 5 ratings , covering 75 % of the economically active female population in Finl and , were included in further analyses . The occupation-specific numbers of observed and expected cases of breast cancer during 1971 - 1995 among women born in 1906 - 1945 ( 17,986 cases ) were grouped according to the index for occupational physical activity . Expected rates were calculated with the social-class-specific population and the entire Finnish female population as reference population s. The relative risks ( RR ) of breast cancer for categories 3 - 5 , in comparison with categories 1 - 2 were calculated using Poisson regression models . The occupation-specific mean number of children and mean age at first childbirth were adjusted for . RESULTS The RR was lower for occupations in category 5 than for those in categories 1 - 4 , especially in the youngest ( 25 - 39 years ) age group ( RR 0.51 , 95 % confidence interval 0.44 - 0.58 ) . Adjustment for social class and reproductive factors raised the RR ( 95 % confidence interval 0.56 - 0.74 ) for category 5 in different age strata , all the RR values still being statistically significant . CONCLUSIONS The results support the hypothesis that occupational physical activity , if high enough , markedly reduces breast cancer risk", "BACKGROUND AND PURPOSE Physical activity reduces the risk of premature death and cardiovascular disease , but the relationship to stroke is less well studied . The objective of this study was to investigate the association between leisure-time physical activity and ischemic stroke in an urban , elderly , multiethnic population . METHODS The Northern Manhattan Stroke Study is a population -based incidence and case-control study . Case subjects had first ischemic stroke , and control subjects were derived through r and om-digit dialing with 1:2 matching for age , sex , and race/ethnicity . Physical activity was recorded through a st and ardized in-person interview regarding the frequency and duration of 14 activities over the 2 prior weeks . Conditional logistic regression was used to calculate odds ratios ( OR ) and 95 % confidence intervals after adjustment for medical and socioeconomic confounders . RESULTS Over 30 months , 369 case subjects and 678 control subjects were enrolled . Mean age was 69.9 + /- 12 years ; 57 % were women , 18 % whites , 30 % blacks , and 52 % Hispanics . Leisure-time physical activity was significantly protective for stroke after adjustment for cardiac disease , peripheral vascular disease , hypertension , diabetes , smoking , alcohol use , obesity , medical reasons for limited activity , education , and season of enrollment ( OR = 0.37 ; 95 % confidence interval=0.25 to 0.55 ) . The protective effect of physical activity was detected in both younger and older groups , in men and women , and in whites , blacks , and Hispanics . A dose-response relationship was shown for both intensity ( light-moderate activity OR = 0.39 ; heavy OR = 0.23 ) and duration ( or = 5 h/wk OR = 0.31 ) of physical activity . CONCLUSIONS Leisure-time physical activity was related to a decreased occurrence of ischemic stroke in our elderly , multiethnic , urban subjects . More emphasis on physical activity in stroke prevention campaigns is needed among the elderly", "CONTEXT Multiple factors contribute to mortality in older adults , but the extent to which sub clinical disease and other factors contribute independently to mortality risk is not known . OBJECTIVE To determine the disease , functional , and personal characteristics that jointly predict mortality in community-dwelling men and women aged 65 years or older . DESIGN Prospect i ve population -based cohort study with 5 years of follow-up and a validation cohort of African Americans with 4.25-year follow-up . SETTING Four US communities . PARTICIPANTS A total of 5201 and 685 men and women aged 65 years or older in the original and African American cohorts , respectively . MAIN OUTCOME MEASURES Five-year mortality . RESULTS In the main cohort , 646 deaths ( 12 % ) occurred within 5 years . Using Cox proportional hazards models , 20 characteristics ( of 78 assessed ) were each significantly ( P mortality : increasing age , male sex , income less than $ 50000 per year , low weight , lack of moderate or vigorous exercise , smoking for more than 50 pack-years , high brachial ( > 169 mm Hg ) and low tibial ( diuretic use by those without hypertension or congestive heart failure , elevated fasting glucose level ( > 7.2 mmol/L [ 130 mg/dL ] ) , low albumin level ( creatinine level ( > or = 106 micromol/L [ 1.2 mg/dL ] ) , low forced vital capacity ( aortic stenosis ( moderate or severe ) and abnormal left ventricular ejection fraction ( by echocardiography ) , major electrocardiographic abnormality , stenosis of internal carotid artery ( by ultrasound ) , congestive heart failure , difficulty in any instrumental activity of daily living , and low cognitive function by Digit Symbol Substitution test score . Neither high-density lipoprotein cholesterol nor low-density lipoprotein cholesterol was associated with mortality . After adjustment for other factors , the association between age and mortality diminished , but the reduction in mortality with female sex persisted . Finally , the risk of mortality was vali date d in the second cohort ; quintiles of risk ranged from 2 % to 39 % and 0 % to 26 % for the 2 cohorts . CONCLUSIONS Objective measures of sub clinical disease and disease severity were independent and joint predictors of 5-year mortality in older adults , along with male sex , relative poverty , physical activity , smoking , indicators of frailty , and disability . Except for history of congestive heart failure , objective , quantitative measures of disease were better predictors of mortality than was clinical history of disease", "Colon cancer incidence rates have been rapidly increasing in Shanghai , China , for reasons still unclear . Low physical activity is a known risk factor for colon cancer . The authors examined the effects of physical activity , particularly commuting physical activity , and its joint effects with body mass index on colon cancer risk in a population -based , case-control study . The study included 931 incident colon cancer patients and 1,552 r and omly selected controls in Shanghai between 1990 and 1993 . Colon cancer risk was significantly reduced among subjects with high commuting physical activity ( odds ratio ( OR ) = 0.52 , 95 % confidence interval ( CI ) : 0.27 , 0.87 for men ; OR = 0.56 , 95 % CI : 0.21 , 0.91 for women ) , particularly among those who had high commuting physical activity for at least 35 years ( OR = 0.34 , 95 % CI : 0.09 , 0.76 for men ; OR = 0.31 , 95 % CI : 0.07 , 0.72 for women ) . Commuting physical activity significantly modified the risk conferred by high body mass index , with the highest risk observed among those at the highest quintile of body mass index and the lowest activity level ( OR = 6.43 , 95 % CI : 1.82 , 8.54 for men ; OR = 7.42 , 95 % CI : 2.84 , 10.01 for women ) . Our results suggest that regular and frequent physical activity over a long period of time protects from colon cancer and significantly modifies the body mass index-associated risk", "BACKGROUND AND PURPOSE From a physiological perspective , physical activity might be expected to decrease the risk of developing stroke . However , epidemiological studies of physical activity and stroke risk have yielded divergent findings . We therefore sought to examine the association between exercise and stroke risk . METHODS This was a prospect i ve cohort study of 21 823 men , followed up for an average of 11.1 years . Participants were from the Physicians ' Health Study , a r and omized trial of low-dose aspirin and beta carotene . Men , aged 40 to 84 years at baseline , were free of self-reported myocardial infa rct ion , stroke , transient ischemic attack , and cancer . At baseline , they reported on the frequency of exercise vigorous enough to work up a sweat . Stroke occurrence was reported by participants and confirmed after medical record review ( n=533 ) . We used Cox proportional hazards regression to analyze the data . RESULTS With adjustment for age , treatment assignment , smoking , alcohol intake , history of angina , and parental history of myocardial infa rct ion , the relative risks of total stroke associated with vigorous exercise /=5 times per week at baseline were 1.00 ( referent ) , 0.79 ( 95 % confidence interval [ CI ] , 0.61 to 1 . 03 ) , 0.80 ( 95 % CI , 0.65 to 0.99 ) , and 0.79 ( 95 % CI , 0.61 to 1.03 ) , respectively ; P for trend=0.04 . In subgroup analyses , the inverse association appeared stronger with hemorrhagic than ischemic stroke . When we additionally adjusted for body mass index , history of hypertension , high cholesterol , and diabetes mellitus , corresponding relative risks for total stroke were 1.00 ( referent ) , 0.81 ( 95 % CI , 0.61 to 1.07 ) , 0.88 ( 95 % CI , 0.70 to 1.10 ) , and 0.86 ( 95 % CI , 0.65 to 1.13 ) , respectively ; P for trend=0.25 . CONCLUSIONS Exercise vigorous enough to work up a sweat is associated with decreased stroke risk in men . In the present study , the inverse association with physical activity appeared to be mediated through beneficial effects on body weight , blood pressure , serum cholesterol , and glucose tolerance . Apart from its favorable influences on these variables , physical activity had no significant residual association with stroke incidence", "A population -based case-control study was conducted to assess the relation between physical activity and colon cancer among men and women aged 30 - 62 years . Cases were 251 men and 193 women diagnosed with colon cancer in 1985 - 1989 in three countries in the Seattle metropolitan area who were identified from the Seattle-Puget Sound Surveillance , Epidemiology , and End Results registry . Controls were 233 men 194 women identified by r and om digit telephone dialing who were selected by stratified r and om sampling to approximate the age , sex , and county distribution of cases . Physical activity was assessed by questions on frequency and duration of types of recreational and occupational activities during the 10-year period ending 2 years before diagnosis . Each activity was classified as low intensity ( or = 4.5 METs ) . For men and women combined , moderate or high intensity recreational activity was associated with a decreased risk of colon cancer ( relative risk ( RR ) for two or more times per week vs. none = 0.70 , 95 % confidence interval ( CI ) 0.49 - 1.00 ) . This relation was stronger for men than women . Occupational activity was not associated with colon cancer , except among men younger than 55 ( RR for > or = 14.5 hours per week of moderate activity vs. none = 0.29 , 95 % CI 0.12 - 0.69 ) . Among men and women combined , total moderate or high intensity activity ( occupational plus recreational ) was marginally related to colon cancer ( RR for > or = 5 hours per week vs. none = 0.78 , 95 % CI 0.55 - 1.10 ) . These results were adjusted for age ( and sex in the combined sex analyses ) and were not confounded by body mass index , dietary factors , or other measured health behaviors . The results of this study provide modest support to the growing number of studies showing that recreational and /or occupational physical activity is associated with a reduced risk of colon cancer", "Physical activity may reduce colon cancer risk , but the underlying mechanisms remain unclear . Relating physical activity to cancer risk in anatomic segments of the colon may advance our underst and ing of possible mechanisms . We conducted a prospect i ve study of 59,369 Norwegian men and women who were followed up for cancer incidence and mortality . Cox proportional hazards models were used to estimate multivariably adjusted hazard ratios ( HR ) and 95 % confidence intervals ( 95 % CI ) . All statistical tests were two sided . During 17 years of follow-up , 736 colon cancers and 294 rectal cancers were diagnosed . Overall , we found an inverse association between recreational physical activity and colon cancer risk , but subsite analyses showed that the association was confined to cancer in the transverse and sigmoid colon . The adjusted HR , comparing people who reported high versus no physical activity , was 0.44 ( 95 % CI , 0.25 - 0.78 ) for cancer in the transverse colon and 0.48 ( 95 % CI , 0.31 - 0.75 ) for cancer in the sigmoid colon . The corresponding HR for cancer mortality was 0.33 ( 95 % CI , 0.14 - 0.76 ) for the transverse colon and 0.29 ( 95 % CI , 0.15 - 0.56 ) for the sigmoid colon . For rectal cancer , there was no association with physical activity in these data . In conclusion , the inverse association of recreational physical activity with cancer risk and mortality in the transverse and sigmoid segments of the colon may point at increased colon motility and reduced fecal transit time as possible underlying mechanisms . ( Cancer Epidemiol Biomarkers Prev 2008;17(1):183–8", "CONTEXT Women who are physically active have a decreased risk for breast cancer , but the types , amounts , and timing of activity needed are unknown . OBJECTIVE To prospect ively examine the association between current and past recreational physical activity and incidence of breast cancer in postmenopausal women . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study in 74 171 women aged 50 to 79 years who were recruited by 40 US clinical centers from 1993 through 1998 . MAIN OUTCOME MEASURE Incident invasive and in situ breast cancer . RESULTS We documented 1780 newly diagnosed cases of breast cancer over a mean follow-up of 4.7 years . Compared with less active women , women who engaged in regular strenuous physical activity at age 35 years had a 14 % decreased risk of breast cancer ( relative risk [ RR ] , 0.86 ; 95 % confidence interval [ CI ] , 0.78 - 0.95 ) . Similar but attenuated findings were observed for strenuous physical activity at ages 18 years and 50 years . An increasing total current physical activity score was associated with a reduced risk for breast cancer ( P = .03 for trend ) . Women who engaged in the equivalent of 1.25 to 2.5 hours per week of brisk walking had an 18 % decreased risk of breast cancer ( RR , 0.82 ; 95 % CI , 0.68 - 0.97 ) compared with inactive women . Slightly greater reduction in risk was observed for women who engaged in the equivalent of 10 hours or more per week of brisk walking . The effect of exercise was most pronounced in women in the lowest tertile of body mass index ( BMI ) ( physical activity is associated with reduced risk for breast cancer in postmenopausal women , longer duration provides most benefit , and that such activity need not be strenuous", "BACKGROUND Because the risks of sudden cardiac death and myocardial infa rct ion are transiently increased during acute bouts of high-intensity activity , it is an important question from the public health perspective whether regular participation in moderate-intensity activity confers overall protection from sudden cardiac death . PARTICIPANTS AND METHODS We used data from a population -based case-control study to assess the associations of regular high-intensity and moderate-intensity leisure-time physical activity with primary cardiac arrest . Cases were patients with primary cardiac arrest , aged 25 to 74 years , attended by paramedics between 1988 and 1994 in King County , Washington ( n = 333 ) . Controls were r and omly identified from the same community ( n = 503 ) , matched for age and sex . All case patients and controls were free of prior clinical heart disease , major comorbidity , and self-reported poor health . Spouses of case patients and controls were interviewed to assess participation in 15 high-intensity and 6 moderate-intensity physical activities during the prior year . RESULTS Compared with subjects who performed none of the activities , the odds ratio for primary cardiac arrest from matched analyses was 0.34 ( 95 % confidence interval , 0.13 - 0.89 ) among subjects who performed only gardening activities for more than 60 minutes per week ; 0.27 ( 95 % confidence interval , 0.11 - 0.67 ) among subjects who walked for exercise for more than 60 minutes per week ; and 0.34 ( 95 % confidence interval , 0.16 - 0.75 ) among subjects who engaged in any high-intensity activities , after adjustment for age , smoking , education , diabetes , hypertension , and health status . CONCLUSIONS The results suggest that regular participation in moderate-intensity activities , such as walking and gardening , are associated with a reduced risk of PCA and support current exercise recommendations", "CONTEXT Although many studies suggest that physical activity may reduce risk of type 2 diabetes , the role of moderate-intensity activity such as walking is not well understood . OBJECTIVES To examine the relationship of total physical activity and incidence of type 2 diabetes in women and to compare the benefits of walking vs vigorous activity as predictors of subsequent risk of type 2 diabetes . DESIGN AND SETTING The Nurses ' Health Study , a prospect i ve cohort study that included detailed data for physical activity from women surveyed in 11 US states in 1986 , with up date s in 1988 and 1992 . PARTICIPANTS A total of 70,102 female nurses aged 40 to 65 years who did not have diabetes , cardiovascular disease , or cancer at baseline ( 1986 ) . MAIN OUTCOME MEASURE Risk of type 2 diabetes by quintile of metabolic equivalent task ( MET ) score , based on time spent per week on each of 8 common physical activities , including walking . RESULTS During 8 years of follow-up ( 534 , 928 person-years ) , we documented 1419 incident cases of type 2 diabetes . After adjusting for age , smoking , alcohol use , history of hypertension , history of high cholesterol level , and other covariates , the relative risks ( RRs ) of developing type 2 diabetes across quintiles of physical activity ( least to most ) were 1.0 , 0.77 , 0.75 , 0.62 , and 0.54 ( P for trend multivariate RRs of type 2 diabetes across quintiles of MET score for walking were 1.0 , 0.91,0.73 , 0.69 , and 0.58 ( P for trend walking pace was independently associated with decreased risk . Equivalent energy expenditures from walking and vigorous activity result ed in comparable magnitudes of risk reduction . CONCLUSIONS Our data suggest that greater physical activity level is associated with substantial reduction in risk of type 2 diabetes , including physical activity of moderate intensity and duration", "Considerable epidemiological data have accumulated in support of a lower risk of breast cancer among physically active women . Few studies , however , have examined the relation with lifetime physical activity from all sources , and moderate activity in particular . We conducted a population -based case-control study of breast cancer in Latinas , African Americans , and whites aged 35 - 79 years to assess the association with lifetime histories of moderate and vigorous physical activity , including recreational activity , walking , bicycling , household and outdoor chores , and occupation . Patients diagnosed with invasive breast cancer between 1995 and 1998 were identified through the cancer registry in the San Francisco Bay area , and a r and om sample of women without breast cancer was identified through r and om-digit dialing . A structured question naire administered in-person was completed by 403 premenopausal cases and 483 controls and 847 postmenopausal cases and 1065 controls . Summing activities from all sources over an individual 's lifetime , we found reduced breast cancer risk in both pre- and postmenopausal women with the highest versus lowest tertile of average lifetime activity ( premenopausal : multivariate adjusted odds ratio = 0.74 , 95 % confidence interval = 0.52 - 1.05 ; postmenopausal : odds ratio = 0.81 , 95 % confidence interval = 0.64 - 1.02 ) , with similar reductions in the three racial/ethnic groups . In premenopausal women , risk reductions were similar for different types of activities , whereas in postmenopausal women , they were limited to occupational activity . Considering the intensity of activities , risk reductions were similar for moderate and vigorous activities . Because few of the currently known risk factors for breast cancer are modifiable , these results underline the public health importance of promoting physically active lifestyles", "OBJECTIVE To evaluate the effects of two exercise approaches , Tai Chi ( TC ) and computerized balance training ( BT ) , on specified primary outcomes ( biomedical , functional , and psychosocial indicators of frailty ) and secondary outcomes ( occurrence of falls ) . DESIGN The Atlanta FICSIT ( Frailty and Injuries : Cooperative Studies of Intervention Techniques ) , a prospect i ve , r and omized , controlled clinical trial with three arms ( TC , BT , and education [ ED ] . Intervention length was 15 weeks , with primary outcomes measured before and after intervention and at 4-month follow-up . Falls were monitored continuously throughout the study . SETTING Persons aged 70 and older living in the community . PARTICIPANTS A total of 200 participants , 162 women and 38 men ; mean age was 76.2 . MEASUREMENTS Biomedical ( strength , flexibility , cardiovascular endurance , body composition ) , functional ( IADL ) , and psychosocial well-being ( CES-D scale , fear of falling question naire , self-perception of present and future health , mastery index , perceived quality of sleep , and intrusiveness ) variables . RESULTS Grip strength declined in all groups , and lower extremity range of motion showed limited but statistically significant changes . Lowered blood pressure before and after a 12-minute walk was seen following TC participation . Fear of falling responses and intrusiveness responses were reduced after the TC intervention compared with the ED group ( P = .046 and P = .058 , respectively ) . After adjusting for fall risk factors , TC was found to reduce the risk of multiple falls by 47.5 % . CONCLUSIONS A moderate TC intervention can impact favorably on defined biomedical and psychosocial indices of frailty . This intervention can also have favorable effects upon the occurrence of falls . Tai Chi warrants further study as an exercise treatment to improve the health of older people", "CONTEXT Physical activity has been related to reduced mortality , but it is not clear whether changes in physical activity affect mortality among older women . OBJECTIVE To examine the relationship of changes in physical activity and mortality among older women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study conducted at 4 US research centers ( Baltimore , Md ; Portl and , Ore ; Minneapolis , Minn ; and Monongahela Valley , Pa ) among 9518 community-dwelling white women aged 65 years or older who were assessed at baseline ( 1986 - 1988 ) , 7553 of whom were reassessed at a follow-up visit ( 1992 - 1994 ; median , 5.7 years later ) . MAIN OUTCOME MEASURES Walking and other physical activities at baseline and follow-up ; vital status , with cause of death confirmed by death certificates/discharge summaries , tracked for up to 12.5 years after baseline ( up to 6.7 years after the follow-up visit ) . RESULTS Compared with continually sedentary women , those who increased physical activity levels between baseline and follow-up had lower mortality from all causes ( hazard rate ratio [ HRR ] , 0.52 ; 95 % confidence interval [ CI ] , 0.40 - 0.69 ) , cardiovascular disease ( HRR , 0.64 ; 95 % CI , 0.42 - 0.97 ) , and cancer ( HRR , 0.49 ; 95 % CI , 0.29 - 0.84 ) , independent of age , smoking , body mass index , comorbid conditions , and baseline physical activity level . Associations between changes in physical activity and reduced mortality were similar in women with and without chronic diseases but tended to be weaker among women aged at least 75 years and among those with poor health status . Women who were physically active at both visits also had lower all-cause mortality ( HRR , 0.68 ; 95 % CI , 0.56 - 0.82 ) and cardiovascular mortality ( HRR , 0.62 ; 95 % CI , 0.44 - 0.88 ) than sedentary women . CONCLUSION Increasing and maintaining physical activity levels could lengthen life for older women but appears to provide less benefit for women aged at least 75 years and those with poor health status", "Abstract Objective : It is biologically plausible for physical activity to decrease breast cancer risk ; however , epidemiologic studies have yielded inconsistent findings . We therefore examined physical activity and breast cancer risk in the Women 's Health Study . Methods : We assessed physical activity among 39,322 apparently healthy women , aged ≥45 years , and prospect ively followed them for an average of 48 months . Four hundred eleven women developed breast cancer , with 222 positive for both estrogen and progesterone receptors . Results : Among all women the multivariate relative risks of all breast cancer associated with on recreational activities and stair climbing were 1.00 ( referent ) , 1.04 ( 95 % confidence interval , 0.77–1.40 ) , 0.86 ( 0.64–1.17 ) , and 0.80 ( 0.58–1.12 ) , respectively ; p-trend = 0.11 . However , among postmenopausal women there was a significant inverse trend for all breast cancer ; the corresponding relative risks were 1.0 ( referent ) , 0.97 ( 0.68–1.4 ) , 0.78 ( 0.54–1.1 ) , and 0.67 ( 0.44–1.0 ) , respectively ; p-trend = 0.03 . Physical activity was unrelated to breast cancers positive for both estrogen and progesterone receptors either among all or postmenopausal women ( p-trend = 0.50 and 0.26 , respectively ) . When we assessed only vigorous recreational activity , requiring ≥6 METs or multiples of resting metabolic rate , we observed no significant associations with all or steroid hormone receptor positive breast cancer , either among all or postmenospausal women . Conclusions : These data suggest that physical activity during middle age and older is not uniformly associated with decreased breast cancer risk . Among postmenopausal women only , higher levels of physical activity may decrease the risk of breast cancer . This study , however , had limited statistical power to detect small effects", "OBJECTIVE To evaluate the association between physical activity and all case mortality in postmenopausal women . DESIGN Prospect i ve cohort study with 7 years of follow-up through December 31 , 1992 . SETTING AND PARTICIPANTS Subjects were 40417 postmenopausal Iowa women , aged 55 to 69 years at baseline in 1986 . Physical activity was assessed by mailed question naire . MAIN OUTCOME MEASURE All-cause mortality ( n=2260 ) . RESULTS After adjustment for potential confounders and excluding women who reported having cancer or heart disease and those who died in the first 3 years of follow-up , women who reported regular physical activity were at significantly reduced risk of death during follow-up compared with women who did not ( relative risk [ RR ] , 0.77 ; 95 % confidence interval [ CI ] , 0.66 - 0.90 ) . Increasing frequency of moderate physical activity was associated with reduced risk of death during follow-up ( from rarely or never engaging in activity to activity at least 4 times per week , RRs , 1.0 [ referent ] , 0.76 , 0.70 , and 0.62 ; P value for trend risks of death with increased physical activity were evident for cardiovascular diseases ( n=729 ) and respiratory illnesses ( n=147 ) . Women who engaged only in moderate but not vigorous physical activity also benefited , with moderate activity as infrequently as once per week demonstrating a reduced mortality risk of 0.78 ( 95 % CI , 0.64 - 0.96 ) . CONCLUSIONS These results demonstrate a grade d , inverse association between physical activity and all-cause mortality in postmenopausal women . These findings strengthen the confidence that population recommendations to engage in regular physical activity are applicable to postmenopausal women", "BACKGROUND Physical activity has been related to reduced risk of osteoporotic hip fractures , but the evidence among men is weak . OBJECTIVE To determine the association between baseline leisure physical activity and future risk of osteoporotic hip fracture in men . METHODS At baseline in 1975 our prospect i ve study cohort included 3,262 men who were 44 years or older and did not have chronic disease restricting their ability to exercise . At baseline , physical activity was assessed by a question naire . Hip fractures were followed for 21 years , or from the age of 50 years for subjects who were initially younger than 50 years . RESULTS The hazard ratio of osteoporotic hip fracture , adjusted for other possible predictors ( height , body mass index , baseline diseases , smoking , use of alcohol , work-related physical activity , and occupational group ) , in men participating in vigorous physical activity compared with men not participating was 0.38 ( 95 % confidence interval , 0.16 - 0.91 ) ( P = .03 ) . CONCLUSION These results provide further evidence that there is an inverse association between baseline physical activity and future hip fracture risk among men", "Background — Higher levels of physical activity are associated with fewer cardiovascular disease ( CVD ) events . Although the precise mechanisms underlying this inverse association are unclear , differences in several cardiovascular risk factors may mediate this effect . Methods and Results — In a prospect i ve study of 27 055 apparently healthy women , we measured baseline levels of hemoglobin A1c , traditional lipids ( total , low-density lipoprotein , and high-density lipoprotein cholesterol ) , novel lipids [ lipoprotein(a ) and apolipoprotein A1 and B-100 ] , creatinine , homocysteine , and inflammatory/hemostatic biomarkers ( high-sensitivity C-reactive protein , fibrinogen , soluble intracellular adhesion molecule-1 ) and used women 's self-reported physical activity , weight , height , hypertension , and diabetes . Mean follow-up was 10.9±1.6 years , and 979 incident CVD events occurred . The risk of CVD decreased linearly with higher levels of activity ( P for linear trend relative risk reductions associated with 200 to 599 , 600 to 1499 , and ≥1500 kcal/wk of 27 % , 32 % , and 41 % , respectively . Differences in known risk factors explained a large proportion ( 59.0 % ) of the observed inverse association . When sets of risk factors were examined , inflammatory/hemostatic biomarkers made the largest contribution to lower risk ( 32.6 % ) , followed by blood pressure ( 27.1 % ) . Novel lipids contributed less to CVD risk reduction compared with traditional lipids ( 15.5 % and 19.1 % , respectively ) . Smaller contributions were attributed to body mass index ( 10.1 % ) and hemoglobin A1c/diabetes ( 8.9 % ) , whereas homocysteine and creatinine had negligible effects ( physical activity and CVD risk is mediated in substantial part by known risk factors , particularly inflammatory/hemostatic factors and blood pressure ", "OBJECTIVE : To assess the value of broadly based customary physical activity scores , derived from a question naire inventory , in predicting 10 year mortality among elderly people . DESIGN : A 10 year survival analysis of participants in the first wave of the Nottingham longitudinal study of activity and ageing who , in face to face interviews in 1985 , provided detailed information on customary physical activity , health , and lifestyle . SETTING : Urban and suburban Nottingham PARTICIPANTS : A total of 1042 people aged 65 years and over r and omly sample d from general practitioner records . MAIN RESULTS : On the basis of factor scores derived from the interview question naire , activity levels were grade d as \" high \" , \" intermediate \" , or \" low \" . In Cox regression models controlling for age , health status , and cigarette smoking at the time of the activity assessment , these gradings were significantly related to 10 year survival . Relative to the \" high \" activity groups , the risk of dying was significantly increased in both the \" intermediate \" ( hazard ratio ( HR ) 1.53 ; 95 % CI 1.12 , 2.09 ) and \" low \" ( HR 2.07 ; 95 % CI 1.53 , 2.79 ) groups for women , and in the \" low \" group ( HR 1.59 ; 95 % CI 1.12 , 2.25 ) for men ( p elderly population , recall based survey assessment s covering a wide range of customary or habitual physical activities , can provide indices showing both cross sectional utility and predictive validity", "Abstract — Prospect i ve studies on physical activity in relation to the risk for hypertension are scant , particularly in women . This study aim ed at finding out whether regular physical activity can reduce the risk of hypertension in both men and women , and in subjects with and without overweight . We prospect ively followed 8302 Finnish men and 9139 women aged 25 to 64 years without a history of antihypertensive drug use , coronary heart disease , stroke , and heart failure at baseline . Both single and joint associations of physical activity and body mass index with the risk of hypertension were examined using Cox proportional hazard models . During a mean followup of 11 years , there were 1600 incident cases of drug-treated hypertension . Multivariate-adjusted hazards ratios of hypertension associated with light , moderate , and high physical activity were 1.00 , 0.63 , and 0.59 in men ( Ptrend Multivariate-adjusted hazards ratios of hypertension based at different levels of body mass index ( for baseline systolic blood pressure did not affect the protective effect associated with physical activity , but it weakened markedly the association between body mass index and hypertension . The present study indicates that regular physical activity and weight control can reduce the risk of hypertension . The protective effect of physical activity was observed in both sexes regardless of the level of obesity", "OBJECTIVE To examine the independent associations of vigorous ( > or = 6 resting metabolic rate [ MET ] score ) and nonvigorous ( MET score ) physical activity with longevity . DESIGN Prospect i ve cohort study , following up men from 1962 or 1966 through 1988 . SETTING / PARTICIPANTS Subjects were Harvard University alumni , without self-reported , physician-diagnosed cardiovascular disease , cancer , or chronic obstructive pulmonary disease ( n = 17,321 ) . Men with a mean age of 46 years reported their physical activities on question naires at baseline . MAIN OUTCOME MEASURE All-cause mortality ( 3728 deaths ) . RESULTS Total energy expenditure and energy expenditure from vigorous activities , but not energy expenditure from nonvigorous activities , related inversely to mortality . After adjustment for potential confounders , the relative risks of dying associated with increasing quintiles of total energy expenditure were 1.00 ( referent ) , 0.94 , 0.95 , 0.91 and 0.91 , respectively ( P [ trend ] relative risks of dying associated with less than 630 , 630 to less than 1680 , 1680 to less than 3150 , 3150 to less than 6300 , and 6300 or more kJ/wk expended on vigorous activities were 1.00 ( referent ) , 0.88 , 0.92 , 0.87 , and 0.87 , respectively ( P [ trend ] = .007 ) . Corresponding relative risks for energy expended on nonvigorous activities were 1.00 ( referent ) , 0.89 , 1.00 , 0.98 , and 0.92 , respectively ( P [ trend ] = .36 ) . Analyses of vigorous and nonvigorous activities were mutually adjusted . Among men who reported only vigorous activities ( 259 deaths ) , we observed decreasing age-st and ardized mortality rates with increasing activity ( P = .05 ) ; among men who reported only nonvigorous activities ( 380 deaths ) , no trend was apparent ( P = .99 ) . CONCLUSIONS These data demonstrate a grade d inverse relationship between total physical activity and mortality . Furthermore , vigorous activities but not nonvigorous activities were associated with longevity . These findings pertain only to all-cause mortality ; nonvigorous exercise has been shown to benefit other aspects of health", "BACKGROUND The positive health effects of physical activity are well known . However , there are few studies of the association between different levels of physical activity and all-cause mortality among elderly people . METHODS A national r and om sample of 3206 women and men aged > /=65 were interviewed in 1988 and 1989 and followed until December 31 , 2000 , for all-cause mortality . Cox regression was used to analyze the association between five different levels of physical activity and all-cause mortality , after adjustment for gender , age , education , smoking habits , body mass index , diabetes , hypertension , and self-rated health . All analyses were conducted in 2003 . RESULTS For elderly people who were physically active occasionally , the risk of all-cause mortality was 28 % lower than for those who were physically inactive ( hazard ratio [HR]=0.72 ; confidence interval [CI]=0.64 - 0.81 ) , after adjustment for all explanatory variables . For those who were physically active once a week , the risk of all-cause mortality was 40 % lower than for those who were physically inactive ( HR=0.60 ; CI=0.50 - 0.71 ) . For those who were physically active more frequently , the reduction in all-cause mortality risk was about the same as for those who were physically active once a week . Diabetes , hypertension , and daily smoking were , as expected , significant risk factors for all-cause mortality . CONCLUSIONS Physical activity , even occasionally , decreases the risk of all-cause mortality among elderly people . Preventive re sources among the elderly should include moderate exercise such as walking", "There is good evidence that physical activity reduces the risk for cardiovascular disease ( 1 - 6 ) , possibly in part by lowering blood pressure ( 7 ) . Although mild or moderate physical activity , such as brisk walking , is a recommended part of the treatment protocol for persons with hypertension ( 8 , 9 ) , it is not known whether mild physical activity , especially walking , reduces the risk for hypertension . With few exceptions , epidemiologic studies of physical activity and hypertension have been cross-sectional rather than prospect i ve . Physical activity was inversely related to blood pressure in cross-sectional and controlled studies ( 7 ) , and in two prospect i ve studies ( 10 , 11 ) , vigorous exercise was inversely related to the subsequent risk for hypertension . Physicians in Japan usually advise their patients to walk to work as often as they can , and indeed , for middle-aged working Japanese men , the journey to and from work seems to be the main source of exercise . We prospect ively examined the relation of mild physical activity , especially walking to work , and leisure-time physical activity to the risk for hypertension during 6 to 16 years of observation . Methods The Osaka Health Survey The Osaka Health Survey is an ongoing cohort study of risk factors for chronic diseases , including hypertension and diabetes . Study participants are male employees of a gas company in Osaka , Japan . Japanese law requires all employers to conduct annual health screenings for all employees . For the purpose s of the Osaka Health Survey , in addition to these annual screenings , all employees 35 years of age or older undergo more detailed biennial clinical examinations and complete question naires on health-related behaviors , including exercise . Study Sample Between 1981 and 1990 , 7979 Japanese men 35 to 63 years of age at entry who had sedentary occupations were enrolled in the study . We excluded 1875 men because they had physician-diagnosed hypertension , borderline hypertension ( systolic blood pressure 140 and glucose tolerance ( fasting plasma glucose level 6.1 mmol/L [ 110 mg/dL ] and Data Collection and Measurements The biennial clinical examination consisted of a medical history ; a physical examination ; blood pressure measurement ; anthropometric measurements ; measurement of the fasting plasma glucose level ; and surveys of health-related behaviors , such as physical activity , smoking , and daily alcohol consumption . Trained nurses took all measurements . Participants were asked to fast for 12 hours and to avoid smoking and heavy physical activity for more than 2 hours before the examination . After a 5-minute rest in a quiet room , a st and ard mercury sphygmomanometer was used to measure systolic and diastolic blood pressures in the right arm while the participant was seated . Pressure was measured twice , at an interval of a few minutes . Anthropometric measurements included height and body weight , which were measured while the participant was wearing light clothing without shoes . Body mass index was calculated as the weight in kilograms divided by the height in meters squared . The question naire completed by each participant elicited information on leisure-time physical activity , the duration of the walk to work , the nature of the participant 's occupation , and the level of activity involved . Leisure-time physical activity was defined as physical activity unrelated to the participant 's work . Questions about leisure-time physical activity were as follows : Do you engage in any regular physical exercise , such as jogging , bicycling , swimming , and tennis , long enough to work up a sweat ( lasting 30 minutes or more ) ? If yes , how many times per week ? What exercise is this ? The questions about regular physical exercise have been vali date d as a measure of physical exercise ( 12 - 15 ) . In the analysis , participants were classified as engaging in regular physical exercise at least once per week or less than once per week . They were also classified into one of three categories of exercise frequency : 0 ( less than once per week ) , once per week , or two or more times per week . The question about the duration of the walk to work was How long does it take you to walk to this office ? Occupational activity was scored as 1 if the participant 's work was mostly sedentary and 2 if he worked outside or if the job required a lot of lifting and walking . In the present study , we excluded all participants who reported a score of 2 for their occupational activities . Questions about alcohol intake included items about the type of alcoholic beverage , the weekly frequency of alcohol consumption , and the usual amount consumed daily . Alcohol intake was converted to total alcohol consumption ( in milliliters of ethanol per day ) by using st and ard Japanese tables . Current and past smoking habits were classified according to the type and quantity of cigarettes smoked daily . Participants were classified as current smokers , past smokers , or nonsmokers . Hypertension was also diagnosed during the biennial study clinical examinations . All participants underwent medical screening by a physician at least once annually , and hypertension was also diagnosed by the physicians . Hypertension was defined by using World Health Organization criteria as physician-diagnosed hypertension ( systolic blood pressure 160 mm Hg , diastolic blood pressure 95 mm Hg , or both ) or use of antihypertensive medication ( 16 ) . Statistical Analysis Age-adjusted mean values and relevant population characteristics were computed for the duration of the walk to work by using analysis of covariance for continuous variables and the direct method for categorical variables . For each participant , person-years of follow-up were counted from the date at study entry to the date of diagnosis of hypertension or 1 April 1997 , whichever came first . The rate of follow-up was 94 % of the total potential person-years of follow-up . Multivariate Cox proportional-hazards regression models were used to evaluate the simultaneous effects of the duration of the walk to work , the frequency of leisure-time physical activity , age , body mass index , daily alcohol consumption , smoking status , and fasting plasma glucose level . Baseline systolic and diastolic blood pressure were not included in our primary analyses because they could presumably be in the causal pathway between the exposures ( such as physical activity , age , body mass index , and alcohol consumption ) and risk for hypertension . However , we included systolic and diastolic blood pressure in further models to assess the effect of physical activity on the risk for hypertension independent of their effects on systolic and diastolic blood pressure . The linear trends in risks were evaluated by entering indicators for each categorical level of exposure or by using the median value for each category . As a reference category , we used men with the lowest level of physical activity . To address the potential misclassification of leisure-time physical activity over time , additional analyses were performed on the basis of the data at both study entry ( 1981 to 1990 ) and the examination done 4 years after ( 1985 to 1994 ) each participant was enrolled . We also performed analyses that excluded participants who developed hypertension between study entry ( 1981 to 1990 ) and the third examination done 4 years later ( 1985 to 1994 ) . We calculated the 95 % CI for each relative risk ( 17 ) , and all P values are two-tailed . Statistical analyses were performed by using the SPSS 7.5J software package ( SPSS , Inc. , Chicago , Illinois ) . We estimated the number needed to walk , a value analogous to the number needed to treat . The number needed to treat for a given therapy is the reciprocal of the absolute risk reduction for that treatment ( 18 ) . A 95 % CI for the number needed to treat is obtained simply by taking reciprocals of the values defining the 95 % CI of the absolute risk reduction ( 19 ) . In our study , the number needed to walk was defined as the number of men who would have to adopt walking to avoid a single case of hypertension . The number needed to treat must always be based on an outcome for a specific period of time ( 20 ) ; thus , in estimating the number needed to walk , we chose an observation period of 10 years between study entry ( 1981 to 1986 ) and the examination done 10 years after ( 1991 to 1996 ) each participant was enrolled . Role of the Funding Source The funding agencies did not participate in the collection , analysis , or interpretation of data presented in this report or in the decision to su bmi t the manuscript for publication . Results Of the 6104 men eligible for this study between 1981 and 1990 , we excluded 87 men who did not undergo medical check-ups during the follow-up period . The study sample for analysis consisted of 6017 men . During the 59 784 person-years of follow-up between 1981 and 1997 , 626 men developed hypertension . As the duration of the walk to work increased , body weight and the body mass index decreased ( P for trend=0.037 and 0.035 , respectively ) ( Table 1 ) . We identified no significant relation between the duration of the walk to work and the levels of leisure-time physical activity ( P for trend=0.062 ) . Table 1 . Baseline Characteristics according to Duration of the Walk to Work Duration of the Walk to Work The duration of the walk to work was associated with a decreased risk for incident hypertension ( Table 2 ) . After adjustment for age , body mass index , daily alcohol consumption , smoking status , frequency of leisure-time physical activity , systolic blood pressure , diastolic blood pressure , and fasting plasma glucose level , the relative risk for hypertension was 0.71 ( 95 % CI , 0.52 to 0.97 ) in men whose walk to work lasted 21 minutes or more compared with those", "The aim of this study was to describe changes in grip strength over a follow-up period of approximately 27 yr and to study the associations of rate of strength decline with weight change and chronic conditions . The data are from the Honolulu Heart Program , a prospect i ve population -based study established in 1965 . Participants at exam 1 were 8,006 men ( ages 45 - 68 yr ) who were of Japanese ancestry and living in Hawaii . At follow-up , 3,741 men ( age range , 71 - 96 yr ) participated . Those who died before the follow-up showed significantly lower grip-strength values at baseline than did the survivors . The average annualized strength change among the survivors was -1.0 % . Steeper decline ( > 1.5%/yr ) was associated with older age at baseline , greater weight decrease , and chronic conditions such as stroke , diabetes , arthritis , coronary heart disease , and chronic obstructive pulmonary disease . The risk factors for having very low h and -grip strength at follow-up , here termed grip-strength disability ( strength was strong ( r = 0.557 , P grip strength at baseline were also likely to do so 27 yr later . Consequently , those in the lowest grip-strength tertile at baseline had about eight times greater risk of grip-strength disability than those in the highest tertile because of their lower reserve of strength . In old age , maintenance of optimal body mass may help prevent steep strength decrease and poor absolute strength", "Physical activity improves health , and current recommendations encourage daily exercise . However , little is known about any health benefits associated with infrequent bouts of exercise ( e.g. , 1 - 2 episodes/week ) that generate the recommended energy expenditure . The authors conducted a prospect i ve cohort study among 8,421 men ( mean age , 66 years ) in the Harvard Alumni Health Study , without major chronic diseases , who provided details about physical activity on mailed question naires in 1988 and 1993 . Men were classified as \" sedentary \" ( expending /=1,000 kcal/week from sports/recreation 1 - 2 times/week ) , or \" regularly active \" ( all others expending > /=1,000 kcal/week ) . Between 1988 and 1997 , 1,234 men died . The multivariate relative risks for mortality among the sedentary , insufficiently active , weekend warriors , and regularly active men were 1.00 ( referent ) , 0.75 ( 95 % confidence interval ( CI ) : 0.62 , 0.91 ) , 0.85 ( 95 % CI : 0.65 , 1.11 ) , and 0.64 ( 95 % CI : 0.55 , 0.73 ) , respectively . In stratified analysis , among men without major risk factors , weekend warriors had a lower risk of dying , compared with sedentary men ( relative risk = 0.41 , 95 % CI : 0.21 , 0.81 ) . This was not seen among men with at least one major risk factor ( corresponding relative risk = 1.02 , 95 % CI : 0.75 , 1.38 ) . These results suggest that regular physical activity generating 1,000 kcal/week or more should be recommended for lowering mortality rates . However , among those with no major risk factors , even 1 - 2 episodes/week generating 1,000 kcal/week or more can postpone mortality", "BACKGROUND In several epidemiological studies , breast cancer risk has been reduced among women who reported high levels of occupational or leisure-time physical activity . We used data from a population -based case control study to evaluate the effect of occupational physical activity on breast cancer risk . METHODS Two hundred-thirty three incident cases of breast cancer and 670 controls or their next of kin were interviewed for information on breast cancer risk factors and a complete job history . Physical activity level of jobs were classified using a Department of Labor rating scheme . We calculated adjusted odds ratios for light and medium/heavy activity jobs compared to sedentary jobs . RESULTS Odds ratios for women who held medium/heavy jobs for less than 10 years and more than ten years were , respectively , 0.7 ( 95 % CI = 0.4,1.3 ) and 1.7 ( 95 % CI = 0.9,3.3 ) . CONCLUSIONS In these data there was no evidence that holding a job of medium/heavy activity reduced breast cancer risk . The study was limited by misclassification inherent in the occupational exposure scheme and by the lack of information on leisure time physical activity . The modest risk increase for subjects holding a medium/heavy job for at least 10 years probably represents either confounding or r and om variation", "BACKGROUND Physical activity is associated with low mortality in men , but little is known about the association in women , different age groups , and everyday activity . OBJECTIVE To evaluate the relationship between levels of physical activity during work , leisure time , cycling to work , and sports participation and all-cause mortality . DESIGN Prospect i ve study to assess different types of physical activity associated with risk of mortality during follow-up after the subsequent examination . Mean follow-up from examination was 14.5 years . SETTING Copenhagen University Hospital , Copenhagen , Denmark . PARTICIPANTS Participants were 13,375 women and 17,265 men , 20 to 93 years of age , who were r and omly selected . Physical activity was assessed by self-report , and health status , including blood pressure , total cholesterol level , triglyceride levels , body mass index , smoking , and educational level , was evaluated . MAIN OUTCOME MEASURE All-cause mortality . RESULTS A total of 2,881 women and 5,668 men died . Compared with the sedentary , age- and sex-adjusted mortality rates in leisure time physical activity groups 2 to 4 were 0.68 ( 95 % confidence interval , 0.64 - 0.71 ) , 0.61 ( 95 % confidence interval , 0.57 - 0.66 ) , and 0.53 ( 95 % confidence interval , 0.41 - 0.68 ) , respectively , with no difference between sexes and age groups . Within the moderately and highly active persons , sports participants experienced only half the mortality of non participants . Bicycling to work decreased risk of mortality in approximately 40 % after multivariate adjustment , including leisure time physical activity . CONCLUSIONS Leisure time physical activity was inversely associated with all-cause mortality in both men and women in all age groups . Benefit was found from moderate leisure time physical activity , with further benefit from sports activity and bicycling as transportation", "Background The purpose was to conduct systematic review s of the relationship between physical activity of healthy community-dwelling older ( > 65 years ) adults and outcomes of functional limitations , disability , or loss of independence . Methods Prospect i ve cohort studies with an outcome related to functional independence or to cognitive function were search ed , as well as exercise training interventions that reported a functional outcome . Electronic data base search strategies were used to identify citations which were screened ( title and abstract ) for inclusion . Included articles were review ed to complete st and ardized data extraction tables , and assess study quality . An established system of assessing the level and grade of evidence for recommendations was employed . Results Sixty-six studies met inclusion criteria for the relationship between physical activity and functional independence , and 34 were included with a cognitive function outcome . Greater physical activity of an aerobic nature ( categorized by a variety of methods ) was associated with higher functional status ( expressed by a host of outcome measures ) in older age . For functional independence , moderate ( and high ) levels of physical activity appeared effective in conferring a reduced risk ( odds ratio ~0.5 ) of functional limitations or disability . Limitation in higher level performance outcomes was reduced ( odds ratio ~0.5 ) with vigorous ( or high ) activity with an apparent dose-response of moderate through to high activity . Exercise training interventions ( including aerobic and resistance ) of older adults showed improvement in physiological and functional measures , and suggestion of longer-term reduction in incidence of mobility disability . A relatively high level of physical activity was related to better cognitive function and reduced risk of developing dementia ; however , there were mixed results of the effects of exercise interventions on cognitive function indices . Conclusions There is a consistency of findings across studies and a range of outcome measures related to functional independence ; regular aerobic activity and short-term exercise programmes confer a reduced risk of functional limitations and disability in older age . Although a precise characterization of a minimal or effective physical activity dose to maintain functional independence is difficult , it appears moderate to higher levels of activity are effective and there may be a threshold of at least moderate activity for significant outcomes", "Objective To prospect ively examine the association between physical activity and the risk of developing colorectal cancer in a large population -based cohort study of Japanese men and women , and to investigate whether the effects of physical activity on colorectal cancer risk differ by sex and subsite . Methods We analyzed data from a population -based cohort of 65,022 subjects . A total of 486 incident colorectal cancers ( 154 proximal colon , 166 distal colon and 149 rectal cancers ) was identified during 6 years of follow-up . Results We observed a significant inverse association between physical activity and the risk of developing colorectal cancer , particularly colon cancer , among men . Relative to men in the lowest level of metabolic equivalent ( MET ) hours per day , those in the highest level had a RR of 0.69 ( 95 % CI = 0.49–0.97 ) . A significant decrease in risk of colorectal cancer was associated with increasing MET hours per day among men . This inverse association was essentially limited to colon cancer . A significant decrease in risk with increasing MET-hour score was observed predominantly for proximal colon cancer among men . In contrast , no significant decrease was seen among women . Conclusion These findings suggest that physical activity may prevent colon cancer among Japanese men", "BACKGROUND Physical activity has been found to be associated with decreased risk of breast cancer in postmenopausal women in the majority of epidemiologic studies , but the association is inconsistent in premenopausal women . METHODS We studied the effect of physical activity at various ages on the incidence of breast cancer in 99,504 women from 30 to 49 years of age at enrollment in the Women 's Lifestyle and Health Study , a prospect i ve population -based cohort study in Norway and Sweden . Physical activity level on an ordinal scale at age 14 , age 30 , and age at enrollment , participation in competitive sports , as well as information on other covariates was obtained using a self-administered question naire . Complete follow-up with data on incident invasive breast cancer and mortality was collected by linkage to national registries . The relation between physical activity and time to breast cancer development was assessed using Cox proportional hazard models , controlling for potential confounders . RESULTS During an average 9.1 years of follow-up , there were 1,166 incident breast cancer cases . The mean age of the women was 41 years at enrollment , and the mean age at breast cancer diagnosis was 48 years . Compared to inactive women , women with higher levels of physical activity at enrollment had a similar risk of incident breast cancer ( adjusted relative risk , 1.24 for vigorous activity compared with no activity ; 95 % CI , 0.85 - 1.82 ) . Physical activity at age 30 or at age 14 also did not afford any significant protection from breast cancer , nor did a consistently high level of activity from younger ages to enrollment . CONCLUSIONS We did not find evidence of a protective effect of physical activity on breast cancer risk in this group of primarily premenopausal women", "We set out to examine the long-term effect of work-related and leisure time physical activity on risk of death from coronary heart disease ( CHD ) and other causes . Data were obtained from a large prospect i ve population study of 7142 participant men aged 47 to 55 years at baseline in 1970 - 1973 and without symptomatic CHD . Data on physical activity at work and at leisure were assessed by way of a question naire . After 20 years follow-up men with physically dem and ing work had a slightly higher mortality from all causes , but not from CHD . The association with all-cause mortality disappeared after controlling for smoking , occupational class , and alcohol abuse . Men who were physically active during leisure time had a lower risk of death from CHD , cancer , and all causes . After controlling for smoking , diastolic blood pressure , serum cholesterol , body mass index , diabetes alcohol abuse , and low occupational class , the most active men had a relative risk ( RR ) of dying from CHD of 0.72 ( 0.56 - 0.92 95 % CI ) and of all causes of 0.70 ( 0.61 - 0.80 95 % CI ) . The adjusted relative risk for cancer death was of borderline significance . Noncardiovascular deaths other than cancer showed a strong relationship with low physical activity in the present study that remained after controlling for smoking , alcohol abuse , and other factors ( adjusted RR 0.55 ( 0.42 - 0.73 95 % CI ) ) . The protective effect of CHD and on mortality was present after excluding the first 8 years of follow-up , and at all levels of other risk factors , such as smoking , diastolic blood pressure , serum cholesterol , and body mass index . In conclusion , this long-term study demonstrates the protective effect of leisure time physical activity on CHD death , cancer death , and on death from all causes . The effect on coronary death and on death from all causes was independent of other risk factors", "BACKGROUND Increased physical activity has been hypothesized to prevent breast cancer , largely by reducing cumulative lifetime exposure to circulating ovarian hormones . However , epidemiologic findings are inconsistent , and there is no consensus on the best way to quantify physical activity . We thus examined this issue in a large cohort of women , using several different measures of adult physical activity . METHODS We analyzed data from the Nurses ' Health Study , a prospect i ve study of women aged 30 to 55 years in 1976 . In 1980 and on subsequent surveys , women were asked about the average number of hours per week spent in various moderate and vigorous recreational physical activity during the past year . We computed a \" baseline-only \" ( 1980 ) measure of hours per week of physical activity , as well as a cumulative average measure that used up date d reports on physical activity . During 16 years of follow-up , we identified 3137 cases of invasive breast cancer ( 1036 premenopausal and 2101 postmenopausal women ) . Data were analyzed by use of multivariate pooled logistic regression to produce relative risks of breast cancer , and the associated confidence intervals . RESULTS Women who were more physically active in adulthood had a lower risk of breast cancer than those who were less physically active . Comparing those who reported engaging in moderate or vigorous physical activity for 7 or more hours per week with those who engaged in such physical activity for less than 1 hour per week , the relative risk was 0.82 ( 95 % confidence interval , 0.70 - 0.97 ) , using the cumulative average updating . The dose-response trend was statistically significant ( P = .004 ) . Using the baseline-only measure of physical activity produced slightly weaker relative risks . CONCLUSION These results contribute to the body of evidence suggesting that higher levels of adult physical activity afford modest protection against breast cancer", "BACKGROUND To evaluate the hypothesis that physical activity independently predicts type 2 diabetes risk in postmenopausal African-American , Hispanic , Asian , and Caucasian women . METHODS We prospect ively evaluated the relationship between incident type 2 diabetes , walking , and total physical activity at baseline in the Women 's Health Initiative Observational Study . Baseline data were collected between September 1994 and December 1998 ; incident diabetes was identified through August 2002 . Hazard ratios for self-reported diabetes adjusted for body mass index ( BMI ) and other variables were evaluated across categories of physical activity in Caucasian , African-American , Hispanic , and Asian/Pacific Isl and er women . RESULTS Incident diabetes was reported by 2.2 % of Caucasian , 6.2 % of African-American , 4.5 % of Hispanic , 3 % of Asian , and 5.7 % of American Indian women ( p Caucasian women , walking ( multivariate-adjusted hazard ratios 1.00 , 0.85 , 0.87 , 0.75 , 0.74 ; p total physical activity score ( hazard ratios 1.00 , 0.88 , 0.74 , 0.80 , 0.67 ; p = 0.002 ) demonstrated a strong inverse relationship with diabetes risk . In BMI -adjusted models , African-American women in higher physical activity categories were less likely to develop diabetes than women in the lowest physical activity category . After adjusting for age and multiple risk factors , however , no significant association between physical activity and diabetes risk was apparent for African-American , Hispanic , or Asian women . CONCLUSIONS These findings suggest a stronger and more independent association of physical inactivity with development of diabetes in Caucasian women than in minority women , but could also be explained by less precise risk estimates in minority women or the role of chance", "BACKGROUND About two-thirds of Canadians are physically inactive . As a risk factor for several chronic diseases , physical inactivity can potentially be a substantial public health burden . We estimated the direct health care costs attributable to physical inactivity in Canada , the number of lives lost prematurely each year that are attributable to a sedentary lifestyle and the effect that a reduction of 10 % in inactivity levels ( a Canadian objective for 2003 ) could have on reducing direct health care costs . METHODS We calculated summary relative risk ( RR ) estimates from prospect i ve longitudinal studies of the effects of physical inactivity on coronary artery disease , stroke , colon cancer , breast cancer , type 2 diabetes mellitus and osteoporosis . We then computed the population -attributable fraction ( PAF ) for each illness from the summary RR and the prevalence of physical inactivity ( i.e. , 62 % ) and applied the PAF to the total direct health care expenditures for 1999 and to the number of deaths in 1995 associated with each disease to determine the health care costs and lives lost prematurely that were directly attributable to physical inactivity . RESULTS About $ 2.1 billion , or 2.5 % of the total direct health care costs in Canada , were attributable to physical inactivity in 1999 . A sensitivity analysis ( simultaneously varying each of the health care costs and PAF by + /- 20 % ) indicated that the costs could be as low as $ 1.4 billion and as high as $ 3.1 billion . About 21,000 lives were lost prematurely in 1995 because of inactivity . A 10 % reduction in the prevalence of physical inactivity has the potential to reduce direct health care expenditures by $ 150 million a year . INTERPRETATION Physical inactivity represents an important public health burden in Canada . Even modest reductions in inactivity levels could result in substantial cost savings", "Abstract Objectives : To examine any association between social , productive , and physical activity and 13 year survival in older people . Design : Prospect i ve cohort study with annual mortality follow up . Activity and other measures were assessed by structured interviews at baseline in the participants ' homes Proportional hazards models were used to model survival from time of initial interview . Setting : City of New Haven , Connecticut , United States . Participants : 2761 men and women from a r and om population sample of 2812 people aged 65 and older . Main outcome measure : Mortality from all causes during 13 years of follow up . Results : All three types of activity were independently associated with survival after age , sex , race/ethnicity , marital status , income , body mass index , smoking , functional disability , and history of cancer , diabetes , stroke , and myocardial infa rct ion were controlled for . Conclusions : Social and productive activities that involve little or no enhancement of fitness lower the risk of all cause mortality as much as fitness activities do . This suggests that in addition to increased cardiopulmonary fitness , activity may confer survival benefits through psychosocial pathways . Social and productive activities that require less physical exertion may complement exercise programmes and may constitute alternative interventions for frail elderly people . Key messages Little is known about predictors of survival among elderly people Physical activity is clearly good for health , but the potential benefits of social activities have not been studied Social and productive activities are as effective as fitness activities in lowering the risk of death Enhanced social activities may help to increase the quality and length of", "Background and Purpose The objective of this study was to determine the risk factors of stroke incidence and mortality . Methods Our data are based on a prospect i ve cohort study of men aged 40 to 49 years after 12 years of follow-up . Results In age-adjusted Cox proportional-hazards regression analysis of 14 403 healthy men , diastolic blood pressure was a stronger predictor for stroke incidence and mortality than systolic blood pressure . Smoking was a stronger predictor of mortality than of incidence . However , there was no dose-response relation among smokers by increased cigarette consumption . Total serum cholesterol was a significant ( P physical activity at leisure was associated with reduced stroke incidence but not mortality . The myocardial infa rct ion risk score comprising systolic blood pressure , total serum cholesterol , and daily cigarette smoking was a strong predictor of mortality and incidence . Body mass index , triglycerides , blood glucose , and physical activity at work were not found to be risk factors for stroke . Conclusions Reduction of blood pressure , cessation of smoking , lowered cholesterol , and increased physical activity at leisure are individual measures to reduce the risk of stroke", "The Canadian Heart Health Surveys are cross-sectional , population -based cardiovascular disease risk factor surveys that took place in each of the 10 Canadian provinces between 1986 and 1992 . Hypertension awareness , treatment , and control status are examined . Of 23,129 r and omly selected , noninstitutionalized respondents aged 18 to 74 years , 85 % had four blood pressure ( BP ) measurements taken under st and ardized conditions , two at home during a home interview and two at a following clinic visit . The mean of all available measurements was used to determine hypertension status . Estimates are weighted and represent population values . Only 2 % of respondents had never had their BP checked , and 73 % had had their BP checked in the last 12 months . A systolic or diastolic BP > or = 140/90 mm Hg was found in 22 % of participants ( 26 % of men , 18 % of women ) , representing 4.1 million Canadians . Overall , 16 % of participants were treated and controlled ; 23 % were treated and not controlled ; 19 % were not treated and not controlled ; and 42 % were unaware of their hypertension ( 47 % of men and 35 % of women ) . Among hypertensives 18 to 34 years old , 64 % of men and 19 % of women were unaware of their hypertension . Among treated and not controlled hypertensives 63 % had a mean systolic BP > or = 150 mm Hg , and 29 % a diastolic BP > or = 95 mm Hg , suggesting that an important number of Canadians treated for hypertension are still at increased risk . Despite frequent interactions with the health care system , too many Canadians are still not well controlled or are unaware of their hypertension", "Background Physical activity is associated with a decreased risk of coronary heart disease ( CHD ) . However , it is unclear whether the duration of exercise episodes is important : Are accumulated shorter sessions as predictive of decreased risk as longer sessions if the same amount of energy is expended ? Methods and Results In the Harvard Alumni Health Study , we prospect ively followed 7307 Harvard University alumni ( mean age 66.1 years ) from 1988 through 1993 . At baseline , men reported their walking , stair climbing , and participation in sports or recreational activities . For each of the latter activities , they also reported the frequency and average duration per episode . During follow-up , 482 men developed CHD . In age-adjusted analysis , a longer duration of exercise episodes predicted lower CHD risk ( P trend=0.04 ) . However , after total energy expended on physical activity and potential confounders was accounted for , duration no longer had an independent effect on CHD risk ( P trend=0.25 ) ; that is , longer sessions of exercise did not have a different effect on risk compared with shorter sessions , as long as the total energy expended was similar . In contrast , higher levels of total energy expenditure significantly predicted decreased CHD risk in both age-adjusted ( P trend=0.009 ) and multivariate ( P trend=0.046 ) analyses . Conclusions These data clearly indicate that physical activity is associated with decreased CHD risk . Furthermore , they lend some support to recent recommendations that allow for the accumulation of shorter sessions of physical activity , as opposed to requiring 1 longer , continuous session of exercise . This may provide some impetus for those sedentary to become more active", "BACKGROUND AND PURPOSE Physiologically , it appears plausible for physical activity to decrease stroke risk ; however , epidemiological studies have produced mixed findings . Furthermore , few studies have examined specific kinds and intensities of activities . The purpose of this study was to examine the association between physical activity , including its various components ( walking , climbing stairs , participation in sports and recreational activities ) , and stroke risk . METHODS This was a prospect i ve cohort study of 11 130 Harvard University alumni ( mean age , 58 years ) without cardiovascular disease and cancer at baseline . Men reported their walking , stair climbing , and participation in sports or recreation on baseline question naires in 1977 . Stroke occurrence was assessed with another question naire in 1988 . Death certificates were obtained for decedents through 1990 to determine strokes not previously reported ( total strokes=378 ) . We used Cox proportional hazards regression to estimate the relative risks and 95 % CIs for stroke occurrence associated with physical activity . RESULTS After adjustment for age , smoking , alcohol intake , and early parental death , the relative risks of stroke associated with /=4000 kcal/wk of energy expenditure at baseline were 1.00 ( referent ) , 0.76 ( 95 % CI , 0.59 to 0.98 ) , 0.54 ( 0.38 to 0 . 76 ) , 0.78 ( 0.53 to 1.15 ) , and 0.82 ( 0.58 to 1.14 ) , respectively ; P=0 . 05 for linear trend . Walking > /=20 km/wk was associated with significantly lower risk , independent of other physical activity components . Climbing stairs and activities of at least moderate intensity ( > /=4.5 METs , or multiples of resting metabolic rate ) each showed U-shaped relations to stroke risk , with the risk being significantly lower at the nadir of the curve . Light intensity activities ( stroke risk . CONCLUSIONS Physical activity is associated with decreased stroke risk in men . A decreased risk was observed at energy expenditures of 1000 to 1999 kcal/wk , with further risk decrement seen at 2000 to 2999 kcal/wk but not beyond . Confirmation of the U-shaped relation observed in these data requires similar observations in other population", "CONTEXT Individual contributions of obesity and physical fitness ( physical activity and functional capacity ) to risk of coronary heart disease in women remain unclear . OBJECTIVE To investigate the relationships of measures of obesity ( body mass index [ BMI ] , waist circumference , waist-hip ratio , and waist-height ratio ) and physical fitness ( self-reported Duke Activity Status Index [ DASI ] and Postmenopausal Estrogen-Progestin Intervention question naire [ PEPI-Q ] scores ) with coronary artery disease ( CAD ) risk factors , angiographic CAD , and adverse cardiovascular ( CV ) events in women evaluated for suspected myocardial ischemia . DESIGN , SETTING , AND PARTICIPANTS The National Heart , Lung , and Blood Institute-sponsored Women 's Ischemia Syndrome Evaluation ( WISE ) is a multicenter prospect i ve cohort study . From 1996 - 2000 , 936 women were enrolled at 4 US academic medical centers at the time of clinical ly indicated coronary angiography and then assessed ( mean follow-up , 3.9 [ SD , 1.8 ] years ) for adverse outcomes . MAIN OUTCOME MEASURES Prevalence of obstructive CAD ( any angiographic stenosis > or=50 % ) and incidence of adverse CV events ( all-cause death or hospitalization for nonfatal myocardial infa rct ion , stroke , congestive heart failure , unstable angina , or other vascular events ) during follow-up . RESULTS Of 906 women ( mean age , 58 [ SD , 12 ] years ) with complete data , 19 % were of nonwhite race , 76 % were overweight ( BMI > or=25 ) , 70 % had low functional capacity ( DASI scores first adverse event , 118 ( 13 % ) had a major adverse event , and 68 ( 8 % ) died . Overweight women were more likely than normal weight women to have CAD risk factors , but neither BMI nor abdominal obesity measures were significantly associated with obstructive CAD or adverse CV events after adjusting for other risk factors ( P = .05 to.88 ) . Conversely , women with lower DASI scores were significantly more likely to have CAD risk factors and obstructive CAD ( 44 % vs 26 % , P DASI score was independently associated with an 8 % ( hazard ratio , 0.92 ; 95 % confidence interval , 0.85 - 0.99 ; P = .02 ) decrease in risk of major adverse CV events during follow-up . CONCLUSIONS Among women undergoing coronary angiography for suspected ischemia , higher self-reported physical fitness scores were independently associated with fewer CAD risk factors , less angiographic CAD , and lower risk for adverse CV events . Measures of obesity were not independently associated with these outcomes", "BACKGROUND Long-term physical activity may affect breast cancer risk . Few prospect i ve studies have evaluated in situ or invasive breast cancer risk , or breast cancer receptor subtypes , in relation to long-term activity . METHODS We examined the association between recreational physical activity and risk of invasive and in situ breast cancer in the California Teachers Study , a cohort of women established in 1995 - 1996 . Of 110 599 women aged 20 to 79 years with no history of breast cancer followed up through December 31 , 2002 , 2649 were diagnosed as having incident invasive breast cancer and 593 were diagnosed as having in situ breast cancer . Information was collected at cohort entry on participation in strenuous and moderate recreational activities during successive periods from high school through the current age or age 54 years ( if older at enrollment ) and in the past 3 years . A summary measure of long-term activity up to the current age , or age 54 years if older , was constructed for each woman . RESULTS Invasive breast cancer risk was inversely associated with long-term strenuous activity ( > 5 vs situ breast cancer risk ( > 5 vs Strenuous and moderate long-term activities were associated with reduced risk of ER-negative ( strenuous : P trend = .003 ; moderate : P trend = .003 ) but not ER-positive ( strenuous : P trend = .23 ; moderate : P trend = .53 ) invasive breast cancer . CONCLUSION These results support a protective role of strenuous long-term exercise activity against invasive and in situ breast cancer and suggest differing effects by hormone receptor status", "BACKGROUND The purpose of this study was to analyse both cross-sectional associations and how longitudinal changes in lifestyle factors from one state in 1980 - 1981 to another in 1988 - 1989 influence self-reported health status . Another aim was to estimate the hazard ratios for all-cause mortality for the changes in lifestyle factors and self-reported hypertension during the same period of time . METHOD The cross-sectional and the longitudinal analyses are based on the same simple r and om sample of 3,843 adults , aged 25 - 74 , interviewed in 1980 - 1981 and 1988 - 1989 and is part of the Swedish Annual Level-of-Living Survey . About 85 % of the respondents in the first interview participated in a second interview in 1988 - 1989 . Cross-sectional odds ratios , based on a marginal model , were estimated using the generalized estimating equations . The transitional models were analysed using unconditional logistic regression . A proportional hazard model was applied to investigate the influence of lifestyle transitions on mortality . RESULTS Physical inactivity , being a current or former smoker and obesity ( women only ) were strong risk factors for poor health either as main effects and /or combined ( interactions ) . There was a strong interaction between physical activity and smoking , and for women , also between body mass index ( BMI ) and physical activity . Smoking , physically inactive and obese women had about a ten times higher risk of poor health status than non-smoking , physically active , and normal-weight women . The corresponding risk for men was about five times higher . Physically active , but smoking and obese individuals showed only moderately increased risks for poor health status . The transitional model showed that those who were physically inactive in 1980 - 1981 , but did exercise in 1988 - 1989 , improved their health after adjustments for sociodemographic and other lifestyle factors . Continuing to smoke or being physically inactive or having hypertension at both points in time were all associated with higher hazard ratios for all-cause mortality ( 1.6 , 1.9 and 1.8 , respectively ) than those who reported that they were in good status at both points in time . CONCLUSIONS We found that physical activity protects against poor health irrespective of an increased BMI and smoking . The major clinical implication s are the long-st and ing benefits of physical activity and not smoking", "BACKGROUND Whether national physical activity recommendations are related to mortality benefit is incompletely understood . METHODS We prospect ively examined physical activity guidelines in relation to mortality among 252,925 women and men aged 50 to 71 years in the National Institutes of Health-American Association of Retired Persons ( NIH-AARP ) Diet and Health Study . Physical activity was assessed using 2 self-administered baseline question naires . RESULTS During 1,265,347 person-years of follow-up , 7,900 participants died . Compared with being inactive , achievement of activity levels that approximate the recommendations for moderate activity ( at least 30 minutes on most days of the week ) or vigorous exercise ( at least 20 minutes 3 times per week ) was associated with a 27 % ( relative risk [ RR ] , 0.73 ; 95 % confidence interval [ CI ] , 0.68 - 0.78 ) and 32 % ( RR , 0.68 ; 95 % CI , 0.64 - 0.73 ) decreased mortality risk , respectively . Physical activity reflective of meeting both recommendations was related to substantially decreased mortality risk overall ( RR , 0.50 ; 95 % CI , 0.46 - 0.54 ) and in subgroups , including smokers ( RR , 0.48 ; 95 % CI , 0.44 - 0.53 ) and nonsmokers ( RR , 0.54 ; 95 % CI , 0.45 - 0.64 ) , normal weight ( RR , 0.45 ; 95 % CI , 0.39 - 0.52 ) and overweight or obese individuals ( RR , 0.48 ; 95 % CI , 0.44 - 0.54 ) , and those with 2 h/d ( RR , 0.53 ; 95 % CI , 0.44 - 0.63 ) and more than 2 h/d of television or video watching ( RR , 0.50 ; 95 % CI , 0.45 - 0.55 ) . Engaging in physical activity at less than recommended levels was also related to reduced mortality risk ( RR , 0.81 ; 95 % CI , 0.76 - 0.86 ) . CONCLUSIONS Following physical activity guidelines is associated with lower risk of death . Mortality benefit may also be achieved by engaging in less than recommended activity levels", "OBJECTIVE To investigate the association between cardiorespiratory fitness and the incidence of type 2 diabetes among Japanese men . RESEARCH DESIGN AND METHODS This prospect i ve cohort study was conducted in 4747 nondiabetic Japanese men , aged 20 - 40 years at baseline , enrolled in 1985 with follow-up to June 1999 . Cardiorespiratory fitness was measured using a cycle ergometer test , and Vo(2max ) was estimated . During a 14-year follow-up , 280 men developed type 2 diabetes . RESULTS The age-adjusted relative risks of developing type 2 diabetes across quartiles of cardiorespiratory fitness ( lowest to highest ) were 1.0 ( referent ) , 0.56 ( 95 % CI 0.42 - 0.75 ) , 0.35 ( 0.25 - 0.50 ) , and 0.25 ( 0.17 - 0.37 ) ( for trend , P BMI , systolic blood pressure , family history of diabetes , smoking status , and alcohol intake , the association between type 2 diabetes risk and cardiorespiratory fitness was attenuated but remained significant ( 1.0 , 0.78 , 0.63 , and 0.56 , respectively ; for trend , P = 0.001 ) . CONCLUSIONS These results indicate that a low cardiorespiratory fitness level is an important risk factor for incidence of type 2 diabetes among Japanese men", "BACKGROUND Scientific evidence shows that physically active people are protected from developing acute myocardial infa rct ion ( MI ) . However , the effect of the intensity , duration and type of activity remains unclear . OBJECTIVE To evaluate the relation between physical activity and MI , according to different intensity levels and types , we conducted a community-based case-control study , based on the Risk of Coronary Heart Disease ( EPIcardis ) study . METHODS We evaluated 381 consecutive cases of first MI ( 297 males ; 84 females ) and 726 community controls ( 310 males ; 416 females ) , older than 39 years , selected by r and om digit dialing ( 70 % participation rate among the controls ) . Data were collected using a structured question naire . For evaluation of physical activity , the question naire assessed all professional and leisure-time activities , specifying the type of exercise and the time spent in each activity . Activities were grouped according to intensity using energy expenditure at rest as the baseline ( 1.0 MET ) : very light ( 1.5 MET ) , light ( 2.5 MET ) , moderate ( 5.0 MET ) and strenuous ( 7.0 MET ) . Odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) were calculated using unconditional logistic regression and separate models for each sex . RESULTS Among men , after adjusting for age , education , family history of MI , energy intake and smoking , the OR ( 95 % CI ) were 0.51 ( 0.29 - 0.91 ) , 0.36 ( 0.19 - 0.68 ) , 0.53 ( 0.30 - 0.93 ) , and 0.68 ( 0.39 - 1.20 ) , for increasing quintiles of activity ( p for trend = 0.199 ) . Among women , after adjusting for the same variables plus parity and menopausal status , the OR ( 95 % CI ) were 0.51 ( 0.25 - 1.03 ) , 0.37 ( 0.17 - 0.83 ) , and 0.34 ( 0.14 - 0.83 ) , for increasing quartiles of activity ( p for trend = 0.006 ) . We found a protective effect of leisure-time physical activity in men ( p for trend leisure-time physical activity , but not of occupational activities , for risk of myocardial infa rct ion", "OBJECTIVE To determine whether self-reported physical activity predicts a decreased rate of coronary heart disease ( CHD ) and all-cause mortalities in middle-aged men when rates are adjusted for known confounders . DESIGN Cohort Analytic Study of Israeli government employees in 1963 . SUBJECTS Eight thous and four hundred sixty-three Israeli male government employees , aged 40 years or older , representing six areas of birth , excluding those with known cardiovascular disease in either 1963 or 1965 , from an original cohort of 10,059 . MAIN OUTCOME MEASURE Comparison of rates of death due to CHD and all causes , determined from death certificates in 21 years of follow-up , for subjects with different baseline levels of self-reported leisure-time and work-related physical activities measured in 1965 . RESULTS Self-reported leisure-time but not work-related physical activity was inversely related to both CHD ( adjusted relative risk , 0.79 ; 95 % confidence interval , 0.66 to 0.95 ) and all-cause mortalities ( adjusted relative risk , 0.91 ; 95 % confidence interval , 0.83 to 0.99 ) . Most of the apparent benefit accrued was from light physical activity on less than a daily basis . These inverse relationships persisted after adjustment for age , systolic blood pressure , cigarette smoking , total and high-density lipoprotein cholesterol levels , body mass index , psychosocial factors , and other potential confounders . CONCLUSION Baseline levels of self-reported leisure-time physical activity predicted a decreased rate of CHD and all-cause mortalities in employed middle-aged Israeli men followed up prospect ively for 21 years", "BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects", "BACKGROUND The epidemiologic observation that physical activity reduces the risk for hypertension has only been made for white men who self-reported hypertension . This study examined physical activity and clinical ly determined incident hypertension in black and white men and women of the Atherosclerosis Risk in Communities ( ARIC ) Study . METHODS ARIC is a population -based prospect i ve study with four U.S. clinic centers . The present analyses included 7,459 black and white adults 45 - 65 years of age . Hypertension ( systolic/diastolic blood pressure > /= 140/90 mm Hg ) was defined by blood pressure measured by a r and om-zero device or medication use . Physical activity was assessed with the Baecke question naire . RESULTS After adjustment for age , baseline blood pressure , ARIC center , education , body mass index , waist-hip ratio , parental history of hypertension , cigarette smoking , alcohol consumption , and diet , white men in the highest quartile of leisure activity ( primarily cycling and walking ) had a 34 % lower odds of developing hypertension over 6 years compared to the least active ( OR = 0.66 , 95 % CI = 0.47 - 0.94 ; P for quartile trend = 0.01 ) . Baseline activity was not associated with incident hypertension in white women or blacks . CONCLUSIONS Leisure-time physical activity reduces the odds of hypertension in middle-aged white men . Additional studies in women and blacks are needed", "We investigated several aspects of the role of physical activity in colon and rectal cancer etiology that remain unclear in the European Prospect i ve Investigation into Nutrition and Cancer . This cohort of 413,044 men and women had 1,094 cases of colon and 599 cases of rectal cancer diagnosed during an average of 6.4 years of follow-up . We analyzed baseline data on occupational , household , and recreational activity to examine associations by type of activity , tumor subsite , body mass index ( BMI ) , and energy intake . The multivariate hazard ratio for colon cancer was 0.78 [ 95 % confidence interval ( 95 % CI ) , 0.59 - 1.03 ] among the most active participants when compared with the inactive , with evidence of a dose-response effect ( Ptrend = 0.04 ) . For right-sided colon tumors , the risk was 0.65 ( 95 % CI , 0.43 - 1.00 ) in the highest quartile of activity with evidence of a linear trend ( Ptrend = 0.004 ) . Active participants with a BMI under 25 had a risk of 0.63 ( 95 % CI , 0.39 - 1.01 ) for colon cancer compared with the inactive . Finally , an interaction between BMI and activity ( Pinteraction = 0.03 ) was observed for right-sided colon cancers ; among moderately active and active participants with a BMI under 25 , a risk of 0.38 ( 95 % CI , 0.21 - 0.68 ) was found as compared with inactive participants with BMI > 30 . No comparable decreased risks were observed for rectal cancer for any type of physical activity for any subgroup analyses or interactions considered . We found that physical activity reduced colon cancer risk , specifically for right-sided tumors and for lean participants , but not rectal cancer . ( Cancer Epidemiol Biomarkers Prev 2006;15(12):2398–407", "BACKGROUND Physical inactivity and high body mass index ( weight in kilograms divided by height in square meters ) have been linked to increased risk of colon cancer . However , none of the few prospect i ve studies in women has shown a statistically significant reduction in colon cancer incidence or mortality associated with increased leisure-time physical activity . PURPOSE In this prospect i ve study , we asked whether leisure-time physical activity , body mass index , or body fat distribution could significantly influence the risk of colon cancer in women . METHODS The participants in this study were enrolled in the Nurses ' Health Study , which began in 1976 . Every 2 years , the women provided additional personal information and information on medical risk factors and major medical events . The time spent per week at a variety of leisure-time physical activities was determined , and the time spent at each activity was multiplied by its typical energy expenditure , expressed in terms of metabolic equivalents or METs . The result ing values for each woman were added to yield an MET-hours-per-week score . Reported diagnoses of colon cancer were confirmed by review of hospital records and pathology reports . Relative risks and associated 95 % confidence intervals were calculated . RESULTS In multivariate analyses that included body mass index , women who expended more than 21 MET-hours per week on leisure-time physical activity had a relative risk of colon cancer of 0.54 ( 95 % confidence interval [ CI ] = 0.33 - 0.90 ) in comparison with women who expended less than 2 MET-hours per week . Women who had a body mass index greater than 29 kg/m2 had a relative risk of colon cancer of 1.45 ( 95 % CI = 1.02 - 2.07 ) in comparison with women who had a body mass index less than 21 kg/m2 . A tendency toward higher colon cancer risk was observed for increasing waist-to-hip ratio ( relative risk = 1.48 [ 95 % CI = 0.88 - 2.49 ] for comparison of the highest quintile ratio [ > 0.833 ] to the lowest [ leisure-time physical activity and incidence of colon cancer in women in this study is consistent with what has been found in men . Recommendations to increase physical activity and maintain lean body weight should receive greater emphasis as part of a feasible approach to the prevention of colon cancer", "Westernization or industrialization leads to an increase in rates of colon cancer , which is the second leading cause of malignant death in the United States [ 1 ] . Although the precise causes of colon cancer remain unclear , a diet high in red meat or animal fat and low in fruits and vegetables appears to increase the risk for this malignancy [ 2 , 3 ] . It is perhaps less well recognized that an inverse association between physical activity and risk for colon cancer has been seen in studies of occupational activity only [ 4 - 12 ] and of both job-related and recreational activity [ 13 - 23 ] . In addition , many studies have found an association between body mass and elevated risk for colon cancer in men ; this association is weaker in women [ 24 - 33 ] . The fact that the association is stronger in men suggests that the abdominal distribution of adiposity typical in men may be an important component of enhanced risk . More limited evidence suggests that height , which may be a proxy for a person 's net energy intake during childhood and adolescence , is related to a higher risk for colon cancer [ 33 - 35 ] . We examine the association between physical activity , obesity , and attained height in relation to risk for colon cancers and their precursory adenomas in a large cohort of male health professionals in the United States . Waist and hip circumferences were available for a subcohort of the study population . We address the hypotheses that physical inactivity , obesity , and height increase the risk for colon cancer and adenoma independently of each other and of diet , and that the abdominal pattern of obesity is an additional independent risk factor . Methods Study Population The Health Professionals Follow-up Study [ 36 ] was started in 1986 ; in that year , 51 529 male dentists , optometrists , osteopaths , podiatrists , pharmacists , and veterinarians in the United States between 40 and 75 years of age responded to a mailed question naire . They reported on their leisure-time physical activity ( described below ) ; current body weight ; weight at age 21 years ; height ; history of cancer and other medical conditions ; parental history of various diseases , including colorectal cancer ; and use of aspirin and other nonsteroidal anti-inflammatory medications . They also reported dietary and alcohol intake using a vali date d [ 37 , 38 ] , semi-quantitative food-frequency question naire . We mailed an optional question naire in 1987 to assess waist and hip circumferences . In 1988 , 1990 , and 1992 , we up date d exposure information and ascertained newly diagnosed medical conditions and history of colonoscopy or sigmoidoscopy , including the indications for endoscopy : bleeding in stool , positive results from tests for occult fecal blood , abdominal pain , diarrhea or constipation , family history of colorectal cancer , routine screening without symptoms , or follow-up [ 39 ] . Most of the deaths in the cohort were reported by family members or by the postal system in response to the follow-up question naires . We also used the National Death Index to identify deaths among nonrespondents [ 40 ] . Assessment of Physical Activity The 1986 question naire included a section about mainly recreational or leisure-time physical activity . The reliability and validity of question naires design ed to assess physical activity have been investigated [ 41 - 43 ] . A question naire such as the one used in our cohort was evaluated in a cohort of U.S. nurses and was found to provide useful information [ 44 ] , and similar results were found during a similar validation study done within the Health Professionals cohort ( Chasan-Taber S. Personal communication ) . Participants reported the average time per week spent doing each of eight moderate and vigorous activities , choosing from among 10 possible responses that ranged from 0 minutes to 11 or more hours per week . The specific activities listed were walking or hiking outdoors ( including walking during golf ) ; jogging ( slower than 10 minutes/mile ) ; running ( 10 minutes/mile or faster ) ; bicycling ( including that done on a stationary machine ) ; lap swimming ; tennis , squash , or racquetball ; and calisthenics or rowing . In addition , each respondent reported the number of flights of stairs he climbed daily and his usual walking pace . The reported time spent at each activity per week was multiplied by its typical energy expenditure requirements expressed in metabolic equivalents ( METs ) [ 45 ] to yield a MET-hour score . One MET , which is the energy expended by sitting quietly , is equivalent to 3.5 mL of oxygen uptake per kilogram of body weight per minute for a 70-kg adult . For example , 1 hour per week of running contributed 10.2 MET-hours , 1 hour of tennis contributed 6 MET-hours , and 1 hour of walking at a moderate pace contributed 3.2 MET-hours . Body weight was excluded from the derivation of energy expenditure from physical activity to avoid confounding the expenditure variable by body weight . If more than one published intensity level was available for a given activity , the moderate or general MET value was chosen . An average MET value was assigned to the categories that listed more than one activity , such as rowing or calisthenics , and squash or racquetball . Assessment of Anthropometric Variables Each man reported his current weight and height and his weight at age 21 years on the 1986 question naire . In 1987 , we mailed an optional question naire once to obtain additional exposure information , including body circumference measurements . We instructed each participant to measure ( to the nearest quarter inch ) his waist at the umbilicus and his hips at the largest circumference between the waist and thighs while st and ing and without measuring over bulky clothing [ 46 ] . We provided a tape measure and an illustration to help st and ardize the measurements . Sixty-five percent of the cohort responded . We used the Quetelet index ( kilograms/height in meters2 ) as a measure of total adiposity , waist-to-hip ratio to measure relative distribution of fat , and waist circumference to estimate total abdominal fat . Although the waist-to-hip ratio has been used more widely , waist circumference provides an estimate of absolute abdominal adiposity , the component most closely related to important metabolic abnormalities , including hyperinsulinemia , hypertension , and high triglyceride levels . To remove extraneous variation in the waist circumference because of height ( taller men tend to have larger waist circumferences due to their larger body size rather than to obesity ) , we adjusted waist for height using residual analysis [ 47 ] . We first regressed waist on height using multiple linear regression and then added the residual to the average waist size ( 37.4 inches ) for a man of average height ( 70 inches ) to convert this measure back to the initial scale . This conversion created for each man a st and ardized waist circumference unconfounded by height . We evaluated the precision of self-reported anthropometric measures among 123 cohort members who were part of a dietary validation study [ 46 ] . Trained technicians paid the sub study participants two visits , approximately 6 months apart , to measure current weight and waist and hip circumferences . The Pearson correlation between self-report and the average of the technicians ' two measurements was 0.97 for weight , 0.95 for waist circumference , 0.88 for hip circumference , and 0.69 for waist-to-hip ratio . The men 's self- measurements of their waist circumferences were 0.36 inches greater , their self- measurements of hip circumferences were 0.78 inches smaller , and their self- measurements of weight were 2.3 pounds less than the technician 's measurements . Identification of Patients with Colorectal Cancers In 1988 , 1990 , and 1992 , we asked each participant whether cancer had been diagnosed during the previous 2 years . The response rate to the follow-up question naires was 94 % through 31 January 1992 . When a participant ( or a decedent 's next-of-kin ) reported a diagnosis of cancer of the colon or rectum , we sought permission to obtain hospital records and pathology reports . A study physician , blinded to exposure information , review ed all medical records received and extracted data about histologic type , anatomic location , and stage of the cancer . Proximal colon cancers were defined as those from the cecum to and including the splenic flexure , and distal colon cancers were defined as those in the descending and sigmoid colon . We confirmed 249 new cases of colorectal adenocarcinoma ( excluding carcinoma in situ ) , 90 % by medical records and the remainder with corroborating information about diagnosis and treatment from the cohort member . Two hundred three cancers were in the colon and 46 were in the rectum . Identification of Patients with Colorectal Adenomas and Controls Because more than 90 % of the adenomas were diagnosed during endoscopic procedures for screening or for unrelated gastrointestinal conditions , we restricted the adenoma analysis to men who had had a colonoscopy or sigmoidoscopy . This was done to reduce the potential for detection bias . Most procedures were sigmoidoscopies ; thus , we analyzed only adenomas of the distal colorectum . Although we did not examine proximal colon adenomas , this should not have biased inferences for the distal colorectum . However , different causes for proximal adenomas may exist . A total of 12 879 men who did not meet any of the exclusion criteria ( see Data Analysis ) reported having had an endoscopy between 1986 and 1992 . In 1993 , we sent a mailing to a r and om sample of 200 controls ( men who reported negative results from an endoscopy ) to confirm that they did not have adenomas . After one mailing , 140 ( 70 % ) controls granted us permission to review the medical records of their endoscopic procedure ; none had an unreported , histologically confirmed adenoma . We were able to recontact 96 % of the men who reported a diagnosis of polyp , and we received medical records in response to more than 96 % of the requests sent to medical record departments ,", "PURPOSE Middle-aged and older women who are physically active have decreased risk of coronary heart disease ( CHD ) ; however , little is known about how physical activity during young adulthood influences activity during middle age and older , and CHD risk . We examined the relationship between 1 ) physical activity during young adulthood and middle age , and 2 ) physical activity during each time period and CHD occurring in middle age or older . METHODS Cohort study of 39,876 healthy U.S. female health professionals , age > or = 45 yr , in the Women 's Health Study . Physical activity was reported at baseline . Additionally , physical activity in high school and age 18 - 22 yr was reported on the 24-month follow-up survey . Women were followed for an average of 9 yr , after the 24-month survey , for CHD occurrence ( N = 477 ) . RESULTS Among 37,169 eligible participants at baseline , the most active women ( vigorous physical activity 10 - 12 months x yr ) during high school and age 18 - 22 yr were more than twice as likely to meet physical activity recommendations at baseline than the least active women ( no vigorous activity ) during high school and age 18 - 22 yr ( multivariate-adjusted odds ratio = 2.43 ; 95 % C.I. 2.24 , 2.63 ) . At baseline , the most active women ( > or = 1500 kcal x wk(-1 ) ) had a 39 % lower risk of CHD during follow-up than the least active ( physical activity during young adulthood was not associated with risk of CHD occurring during middle age and older . CONCLUSION Women who are physically active during young adulthood are more likely to be active when middle-aged and older , when rates of CHD increase , and physical activity during middle-age predicts lower risk of CHD", "OBJECTIVES To examine the association between physical activity and the risk of incident disability , including impairment in activities of daily living ( ADLs ) and instrumental activities of daily living ( IADLs ) , in community-based older persons free of dementia . DESIGN Prospect i ve , observational cohort study . SETTING Approximately 40 retirement communities across the Chicago metropolitan area . PARTICIPANTS More than 1,000 older persons from the Rush Memory and Aging Project , an ongoing longitudinal clinical -pathological study of common chronic conditions of old age . MEASUREMENTS All participants underwent detailed annual clinical evaluations that included assessment s of physical activity , ADLs , IADLs , and gait performance . The associations between physical activity , mortality , and incident disability were examined using a series of Cox proportional hazards models controlled for age , sex , education , and baseline gait . RESULTS At baseline , participants spent a mean+/-st and ard deviation of 3.0+/-3.5 hours per week engaging in physical activity ( range 0 - 35 ) . In a proportional hazards model , the risk of death decreased 11 % ( hazard ratio (HR)=0.89 , 95 % confidence interval (CI)=0.83 - 0.95 ) for each additional hour of physical activity per week . For those who were not disabled at baseline , the risk of developing disability in ADLs decreased 7 % ( HR=0.93 , 95 % CI=0.88 - 0.98 ) for each additional hour of physical activity per week . Similarly , the risk of disability in IADLs decreased 7 % ( HR=0.93 , 95 % CI=0.89 - 0.99 ) for each additional hour of physical activity . CONCLUSION For community-based older persons without dementia , physical activity is associated with maintenance of functional status , including a reduced risk of developing impairment in ADLs and IADLs", "BACKGROUND Increased physical activity has been hypothesized to be a means of breast cancer prevention . We examined the associations between physical activity at two different times in life and breast cancer risk . METHODS We analyzed data from the Nurses ' Health Study II , a prospect i ve study of women aged 25 - 42 years in 1989 . On the baseline survey , women were asked , \" While in high school and between the ages 18 and 22 years , how often did you participate in strenuous physical activity at least twice a week ? \" We averaged answers to these two questions to develop a measure of late adolescent activity . Women were also asked at baseline to report the number of hours per week they currently spent in different nonoccupational activities . During 6 years of follow-up , we identified 372 cases of invasive breast cancer . Data were analyzed by use of multivariate pooled logistic regression to produce relative risk ( RR ) and confidence intervals ( CIs ) of being diagnosed with the disease . RESULTS Women who were more active in late adolescence were not at reduced risk of breast cancer compared with less active women . For those women who reported engaging in strenuous activity at least twice per week for 10 - 12 months per year in late adolescence , the RR of cancer , compared with those who never engaged in such activity , was 1.1 ( 95 % CI = 0.8 - 1.6 ) . Similarly , higher levels of recent nonoccupational physical activity were not associated with reduced risk of breast cancer ( RR for > or = 7 hours of activity/week relative to physical activity , in late adolescence or in the recent past , and breast cancer risk among young adult women", "BACKGROUND As epidemiological studies have become more complex , dem and s for short , easily administered measures of risk factors have increased . This study investigates whether such a measure of physical activity is associated with the risk of death from all causes and death from specific causes . METHODS A prospect i ve follow-up study of 11,090 men and women , aged 35 - 64 years , recruited from five UK general practice s who responded to a postal question naire in 1989 . Self-reported frequency of vigorous-intensity physical activity and data on confounding factors were collected at baseline survey . Death notifications up to 31 December 2001 were provided by the Office for National Statistics . The relative risk ( and 95 % confidence interval ) of dying associated with each level of exposure to physical activity was estimated by the hazard ratio in a series of Cox regression models . RESULTS After > 10 years ' follow-up there were 825 deaths among the 10 522 subjects with no previous history of angina or myocardial infa rct ion . Participation in vigorous exercise was associated with a significantly lower risk of all-cause mortality . Similar associations were found for ischaemic heart disease and cancer mortality , although the relationships were not significant at the 5 % level . CONCLUSIONS Simple measures of self-reported vigorous physical activity are associated with the risk of future mortality , at least all-cause mortality in a somewhat selected group . Interpretation of the finding should be treated with caution due to the reliance on self-report and the possibility that residual confounding may underlie the associations . Because moderate-intensity physical activity is also beneficial to health , short physical activity question naires should include measures of such physical activity in the future", "OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity", "BACKGROUND This study analyzed the long-term effect of leisure-time physical activity on incident cases of coronary heart disease ( CHD ) among women and men . METHODS A national , r and om sample of 2,551 women and 2,645 men , aged 35 - 74 , was interviewed in 1988 and 1989 and followed until December 31 , 2000 , with respect to CHD incident cases . Women and men hospitalized for CHD 2 years before the start of the study and those who rated their general health as poor were not included in the sample . Leisure-time physical activity was divided into four levels according to the frequency of physical activity . The relationship between leisure-time physical activity and CHD was studied in a Cox regression model , adjusted for sex , age , income , smoking , and BMI . RESULTS When leisure-time physical activity increased , the risk of CHD decreased . Women and men who were physically active at least twice a week had a 41 % lower risk of developing CHD than those who performed no physical activity ( hazard ratio = 0.59 , CI = 0.37 - 0.95 ) , after adjustment for all the explanatory variables . CONCLUSIONS The positive long-term effect of leisure-time physical activity on CHD risk among women and men remains even after accounting for income and other important CHD risk factors", "Aim /hypothesisLeisure-time physical activity can reduce the risk of Type 2 diabetes , but the potential effect of different types of physical activity is still uncertain . This study is to examine the relationship of occupational , commuting and leisure-time physical activity with the incidence of Type 2 diabetes . Methods We prospect ively followed 6898 Finnish men and 7392 women of 35 to 64 years of age without a history of stroke , coronary heart disease , or diabetes at baseline . Hazards ratios of incidence of Type 2 diabetes were estimated by levels of occupational , commuting , and leisure-time physical activity . Results During a mean follow-up of 12 years , there were 373 incident cases of Type 2 diabetes . In both men and women combined , the hazards ratios of diabetes associated with light , moderate and active work were 1.00 , 0.70 and 0.74 ( p=0.020 for trend ) after adjustment for confounding factors ( age , study year , sex , systolic blood pressure , smoking , education , the two other types of physical activity and BMI ) . The multivariate-adjusted hazards ratios of diabetes with none , 1 to 29 , and more than 30 min of walking or cycling to and from work were 1.00 , 0.96 , and 0.64 ( p=0.048 for trend ) . The multivariate-adjusted hazards ratios of diabetes for low , moderate , high levels of leisure-time physical activity were 1.00 , 0.67 , and 0.61 ( p=0.001 for trend ) ; after additional adjustment for BMI , the hazards ratio was no longer significant . Conclusions /interpretationModerate and high occupational , commuting or leisure-time physical activity independently and significantly reduces risk of Type 2 diabetes among the middle-aged general population", "BACKGROUND The role of walking , as compared with vigorous exercise , in the prevention of cardiovascular disease remains controversial . Data for women who are members of minority racial or ethnic groups are particularly sparse . METHODS We prospect ively examined the total physical-activity score , walking , vigorous exercise , and hours spent sitting as predictors of the incidence of coronary events and total cardiovascular events among 73,743 postmenopausal women 50 to 79 years of age in the Women 's Health Initiative Observational Study . At base line , participants were free of diagnosed cardiovascular disease and cancer , and all participants completed detailed question naires about physical activity . We documented 345 newly diagnosed cases of coronary heart disease and 1551 total cardiovascular events . RESULTS An increasing physical-activity score had a strong , grade d , inverse association with the risk of both coronary events and total cardiovascular events . There were similar findings among white women and black women . Women in increasing quintiles of energy expenditure measured in metabolic equivalents ( the MET score ) had age-adjusted relative risks of coronary events of 1.00 , 0.73 , 0.69 , 0.68 , and 0.47 , respectively ( P for trend , total MET score and the risk of cardiovascular events remained strong ( adjusted relative risks for increasing quintiles , 1.00 , 0.89 , 0.81 , 0.78 , and 0.72 , respectively ; P for trend Walking and vigorous exercise were associated with similar risk reductions , and the results did not vary substantially according to race , age , or body-mass index . A brisker walking pace and fewer hours spent sitting daily also predicted lower risk . CONCLUSIONS These prospect i ve data indicate that both walking and vigorous exercise are associated with substantial reductions in the incidence of cardiovascular events among postmenopausal women , irrespective of race or ethnic group , age , and body-mass index . Prolonged sitting predicts increased cardiovascular risk", "Background The purpose of this study was to describe the associations between different levels of long-term physical activity in leisure time and subsequent causes of deaths . Design The Copenhagen City Heart Study is a prospect i ve cardiovascular population study of 19 329 men and women aged 20–93 in 1976 . Physical activity in leisure time was estimated at the examinations in 1976–78 and 1981–83 . This analysis consists of 2136 healthy men and 2758 women aged 20–79 years , with unchanged physical activity at the two examinations , and with all covariates included in the multivariate analyses : smoking , total-cholesterol , high-density lipoprotein-cholesterol , systolic blood pressure , diabetes mellitus , alcohol consumption , body mass index , education , income , and forced expiratory volume in 10.78 ( % predicted ) . Results Adjusted relative risks ( 95 % confidence interval ) for coronary heart disease were , for moderate physical activity 0.71 ( 0.51 , 0.99 ) and for high 0.56 ( 0.38 , 0.82 ) . For cancer , moderate activity 0.77 ( 0.61 , 0.97 ) and high activity 0.73 ( 0.56 , 0.95 ) and for all-cause mortality , moderate 0.78 ( 0.68 , 0.89 ) and high 0.75 ( 0.64 , 0.87 ) for both sexes combined . Using Kaplan — Meier plots we calculated gained years of expected lifetime from age 50 . Men with high physical activity survived 6.8 years longer , and men with moderate physical activity 4.9 years longer than sedentary men . For women the figures were 6.4 and 5.5 years , respectively . Conclusion Long-term moderate or high physical activity was in both sexes associated with significantly lower mortality from coronary heart disease , cancer and all-causes . The same tendency was found for stroke and respiratory diseases , but the associations did not reach statistical significance . Eur J Cardiovasc Prev Rehabil 13:173–179 © 2006 The European Society of", "Objective : To examine the optimal intensity of leisure time physical activity ( LTPA ) to decrease the risk of all cause , cardiovascular disease ( CVD ) , and coronary heart disease ( CHD ) mortality in a population sample of middle aged British men . Design : Prospect i ve study of middle aged men with an 11 year follow up . Setting : A whole population sample of men from Caerphilly , South Wales , UK . Subjects : 1975 men aged 49–64 years without historical or clinical evidence of CHD at baseline examination . Main outcome measures : All cause , CVD , and CHD mortality . Results : Total ( cumulative ) LTPA had a grade d , significant relation with all cause , CVD , and CHD mortality but no trend with cancer deaths . When different intensities of activity were considered , light and moderate intensity LTPA had inconsistent and non-significant relations with all cause , CVD , or CHD mortality whether adjusted only for age or for other cardiovascular risk factors . In contrast a significant dose – response relation was found for heavy intensity LTPA for all cause , CVD , and CHD mortality fully adjusted for other risk factors . Conclusions : These data suggest that , in a population of men without evidence of CHD at baseline , only leisure exercise classified as heavy or vigorous was independently associated with reduced risk of premature death from CVD", "CONTEXT Current public health campaigns to reduce obesity and type 2 diabetes have largely focused on increasing exercise , but have paid little attention to the reduction of sedentary behaviors . OBJECTIVE To examine the relationship between various sedentary behaviors , especially prolonged television ( TV ) watching , and risk of obesity and type 2 diabetes in women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study conducted from 1992 to 1998 among women from 11 states in the Nurses ' Health Study . The obesity analysis included 50 277 women who had a body mass index ( BMI ) of less than 30 and were free from diagnosed cardiovascular disease , diabetes , or cancer and completed questions on physical activity and sedentary behaviors at baseline . The diabetes analysis included 68 497 women who at baseline were free from diagnosed diabetes mellitus , cardiovascular disease , or cancer . MAIN OUTCOME MEASURES Onset of obesity and type 2 diabetes mellitus . RESULTS During 6 years of follow-up , 3757 ( 7.5 % ) of 50 277 women who had a BMI of less than 30 in 1992 became obese ( BMI > or = 30 ) . Overall , we documented 1515 new cases of type 2 diabetes . Time spent watching TV was positively associated with risk of obesity and type 2 diabetes . In the multivariate analyses adjusting for age , smoking , exercise levels , dietary factors , and other covariates , each 2-h/d increment in TV watching was associated with a 23 % ( 95 % confidence interval [ CI ] , 17%-30 % ) increase in obesity and a 14 % ( 95 % CI , 5%-23 % ) increase in risk of diabetes ; each 2-h/d increment in sitting at work was associated with a 5 % ( 95 % CI , 0%-10 % ) increase in obesity and a 7 % ( 95 % CI , 0%-16 % ) increase in diabetes . In contrast , st and ing or walking around at home ( 2 h/d ) was associated with a 9 % ( 95 % CI , 6%-12 % ) reduction in obesity and a 12 % ( 95 % CI , 7%-16 % ) reduction in diabetes . Each 1 hour per day of brisk walking was associated with a 24 % ( 95 % CI , 19%-29 % ) reduction in obesity and a 34 % ( 95 % CI , 27%-41 % ) reduction in diabetes . We estimated that in our cohort , 30 % ( 95 % CI , 24%-36 % ) of new cases of obesity and 43 % ( 95 % CI , 32%-52 % ) of new cases of diabetes could be prevented by adopting a relatively active lifestyle ( or = 30 min/d of brisk walking ) . CONCLUSIONS Independent of exercise levels , sedentary behaviors , especially TV watching , were associated with significantly elevated risk of obesity and type 2 diabetes , whereas even light to moderate activity was associated with substantially lower risk . This study emphasizes the importance of reducing prolonged TV watching and other sedentary behaviors for preventing obesity and diabetes", "OBJECTIVES To compare the effectiveness of group resistance and agility-training programs in reducing fall risk in community-dwelling older women with low bone mass . DESIGN A r and omized , controlled , single-blind 25-week prospect i ve study with assessment s at baseline , midpoint , and trial completion . SETTING Community center . PARTICIPANTS Community-dwelling women aged 75 to 85 with low bone mass . INTERVENTION Participants were r and omly assigned to one of three groups : resistance training ( n=32 ) , agility training ( n=34 ) , and stretching ( sham ) exercises ( n=32 ) . The exercise classes for each study arm were held twice weekly . MEASUREMENTS The primary outcome measure was fall risk ( derived from weighted scores from tests of postural sway , reaction time , strength , proprioception , and vision ) , as measured using a Physiological Profile Assessment ( PPA ) . Secondary outcome measures were ankle dorsiflexion strength , foot reaction time , and Community Balance and Mobility Scale score . RESULTS Attendance at the exercise sessions for all three groups was excellent : resistance training ( 85.4 % ) , agility training ( 87.3 % ) , and stretching program ( 78.8 % ) . At the end of the trial , PPA fall-risk scores were reduced by 57.3 % and 47.5 % in the resistance and agility-training groups , respectively , but by only 20.2 % in the stretching group . In the resistance and agility groups , the reduction in fall risk was mediated primarily by improved postural stability , where sway was reduced by 30.6 % and 29.2 % , respectively . There were no significant differences between the groups for the secondary outcomes measures . Within the resistance-training group , reductions in sway were significantly associated with improved strength , as assessed using increased squat load used in the exercise sessions . CONCLUSION These findings support the implementation of community-based resistance and agility-training programs to reduce fall risk in older women with low bone mass . Such programs may have particular public health benefits because it has been shown that this group is at increased risk of falling and sustaining fall-related fractures", "CONTEXT Physical inactivity and body mass index ( BMI ) are established independent risk factors in the development of type 2 diabetes ; however , their comparative importance and joint relationship with diabetes are unclear . OBJECTIVE To examine the relative contributions and joint association of physical activity and BMI with diabetes . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 37 878 women free of cardiovascular disease , cancer , and diabetes with 6.9 years of mean follow-up . Weight , height , and recreational activities were reported at study entry . Normal weight was defined as a BMI of less than 25 ; overweight , 25 to less than 30 ; and obese , 30 or higher . Active was defined as expending more than 1000 kcal on recreational activities per week . MAIN OUTCOME MEASURE Incident type 2 diabetes , defined as a new self-reported diagnosis of diabetes . RESULTS During the follow-up , 1361 cases of incident diabetes occurred . Individually , BMI and physical activity were significant predictors of incident diabetes . Compared with normal-weight individuals , the multivariate-adjusted hazard ratio ( HR ) was 3.22 ( 95 % confidence interval [ CI ] , 2.69 - 3.87 ) for overweight individuals and 9.09 ( 95 % CI , 7.62 - 10.8 ) for obese individuals . For overall activity ( kilocalories expended per week ) , compared with the least active first quartile , the multivariate-adjusted HRs were 0.91 ( 95 % CI , 0.79 - 1.06 ) for the second quartile , 0.86 ( 95 % CI , 0.74 - 1.01 ) for the third , and 0.82 ( 95 % CI , 0.70 - 0.97 ) for the fourth ( P for trend = .01 ) . In the combined analyses , overweight and obese participants , whether active or inactive , had significantly elevated risks , compared with normal-weight active individuals . The multivariate-adjusted HRs were 1.15 ( 95 % CI , 0.83 - 1.59 ) for normal-weight inactive , 3.68 ( 95 % CI , 2.63 - 5.15 ) for overweight active , 4.16 ( 95 % CI , 3.05 - 5.66 ) for overweight inactive , 11.5 ( 95 % CI , 8.34 - 15.9 ) for obese active , and 11.8 ( 95 % CI , 8.75 - 16.0 ) for obese inactive participants . CONCLUSIONS Although BMI and physical inactivity are independent predictors of incident diabetes , the magnitude of the association with BMI was greater than with physical activity in combined analyses . These findings underscore the critical importance of adiposity as a determinant of diabetes", "Type 2 diabetes is a common disease in industrialized countries . It is a major cause of cardiovascular disease and all-cause mortality ( 1 - 6 ) , and its prevalence has increased continuously over the past few decades ( 1 ) . The American Diabetes Association currently defines impaired fasting glucose as a fasting plasma glucose level from 6.1 to 6.9 mmol/L ( 110 to 125 mg/dL ) and type 2 diabetes as a fasting plasma glucose level of 7.0 mmol/L ( 126 mg/dL ) or more ( 1 ) . Data from several prospect i ve studies show an inverse association between physical activity and diabetes ( 7 - 13 ) . However , these studies are limited by the use of self-reporting of physical activity and presence of type 2 diabetes ( 7 - 12 ) . Self-reporting of physical activity tends to be imprecise , and type 2 diabetes is undiagnosed in about 50 % of the prevalent cases ( 14 ) . This leads to misclassification on both exposure and outcome measures ( 15 ) . These limitations may result in underestimation of the true association between sedentary habits and risk for type 2 diabetes . Impaired fasting glucose is a strong predictor of type 2 diabetes , cardiovascular disease , and other diabetic complications ( 6 , 16 - 18 ) . The underlying cause of impaired fasting glucose is unknown , and no prospect i ve study of the association between physical activity and impaired fasting glucose has been published . We examined the relation of cardiorespiratory fitness , objective ly determined by a maximal exercise test on a treadmill , to the incidence of impaired fasting glucose and type 2 diabetes . Cases of impaired fasting glucose and diabetes at baseline and follow-up were determined by using the American Diabetes Association 's current guidelines ( 1 ) . Methods Patients In our population -based prospect i ve study , we included 8633 men 30 to 79 years of age at baseline ( mean , 43.5 years ) who completed at least two medical evaluations at the Cooper Clinic in Dallas , Texas , from 1970 to 1995 . Patients come to the Cooper Clinic for preventive medical examinations and health promotion counseling . Many are sent by their employers for these services , some are referred by their personal physicians , and others are self-referred . More than 97 % of the patients are white , and most are employed in executive or professional occupations . More than 75 % are college graduates . Although study participants came from middle and upper socioeconomic strata , they were similar to other well-characterized population -based cohorts in terms of blood pressure , cholesterol level , body weight , and cardiorespiratory fitness ( 19 ) . The study was review ed and approved annually by the institutional review board at the Cooper Institute for Aerobics Research . Additional details of the study methods and population characteristics of the cohort have been published elsewhere ( 20 , 21 ) . Because clinical or sub clinical heart disease and other conditions associated with type 2 diabetes may alter the level of physical activity and thus cardiorespiratory fitness , we excluded men with an abnormal resting or exercise electrocardiogram or a history of heart attack , stroke , or cancer at the baseline clinical examination ( n=2350 ) . The baseline evaluation was performed after participants gave written informed consent for the initial medical examination and registration in the follow-up study . Examinations were done after patients had fasted for at least 12 hours and included personal and family health histories , a question naire on demographic characteristics and health habits , a physical examination , an exercise test , anthropometric measurement , electrocardiography , blood chemistry analyses , and blood pressure measurement . Technicians who followed a st and ard manual of operations administered all procedures . Impaired fasting glucose and type 2 diabetes were diagnosed according to American Diabetes Association criteria that define impaired fasting glucose as a fasting plasma glucose level of 6.1 to 6.9 mmol/L ( 110 mg/dL to 125 mg/dL ) and diabetes as a fasting plasma glucose level of 7.0 mmol/L ( 126 mg/dL ) or more ( 1 ) . Patients who did not meet these criteria but who reported a history of diabetes or current therapy with oral antidiabetic agents or insulin were also considered to have diabetes . We excluded patients who had diabetes at baseline according to any of these criteria ( n=377 ) . Cardiorespiratory fitness was assessed with a maximal exercise test that followed a modified Balke protocol ( 22 ) . Details of treadmill speed and elevation have been described elsewhere ( 20 , 21 ) . Briefly , the test began with the patient walking on a horizontal treadmill at 88 m/min . After the first minute , the elevation increased to 2 % ; the elevation then increased 1 % each minute up to 25 minutes . For the few patients who were still able to continue , the elevation was held constant after 25 minutes and the speed was increased by 5.4 m/min until the patient reached volitional fatigue . Use of this protocol for the exercise test correlates highly ( r=0.92 ) with measured maximal oxygen uptake ( 23 ) . All patients in our study achieved at least 85 % of their age-predicted maximal heart rate ; average maximal heart rates ( SD ) in each age group were 186 11 beats/min for patients 30 to 39 years of age , 179 12 beats/min for those 40 to 49 years of age , 172 13 beats/min for those 50 to 59 years of age , and 162 17 beats/min for those 60 years of age or older . Average maximal heart rates in each age group exceeded the age-predicted rate ( 220 beats/min age in years ) , which indicates that the exercise test can be considered maximal performance . We defined level of fitness by total time on the treadmill at the baseline examination , as in our previous studies ( 20 , 21 ) . Treadmill times were placed in frequency distributions for specific age groups ( 30 to 39 , 40 to 49 , 50 to 59 , or 60 or more years of age ) . The least fit 20 % of the participants in each age group were classified as low fitness , the next 40 % as moderate fitness , and the remaining 40 % as high fitness . The respective cut-points for total treadmill time in the low- , moderate- , and high-fitness groups were 945 seconds or less , 946 to 1259 seconds , and 1260 seconds or more for patients 30 to 39 years of age ; 849 seconds or less , 850 to 1020 seconds , and 1021 seconds or more for patients 40 to 49 years of age ; 750 seconds or less , 751 to 1035 seconds , and 1036 seconds or more for patients 50 to 59 years of age ; and 644 seconds or less , 645 to 953 seconds , and 954 seconds or more for patients 60 years of age or older . These cut-points at the 20th and 60th percentiles to define fitness levels were used in previous studies ( 20 , 21 ) and were selected before analysis for our investigation . However , we calculated these cut-points with patients in the current study , from which unhealthy persons were excluded . Therefore , they differ somewhat from the cut-points derived from the entire cohort of the Aerobics Center Longitudinal Study ( 21 ) . For some analyses , such as the models that included change in fitness from baseline to follow-up , cardiorespiratory fitness was expressed as maximal metabolic units ( metabolic equivalents [ METs ] , calculated as the working metabolic rate/resting metabolic rate ; 1 MET is equivalent to an oxygen uptake of 3.5 mL1 kg1 ) achieved on the exercise test . In other analyses , time on the treadmill was used as a continuous variable . Serum sample s were analyzed by using automated techniques in a laboratory that participates in the Centers for Disease Control and Prevention Lipid St and ardization Program . Blood pressure was measured by using auscultatory methods with a mercury sphygmomanometer . We defined high blood pressure as systolic blood pressure of at least 140 mm Hg , diastolic blood pressure of at least 90 mm Hg , or a history of hypertension . Height and weight were measured with a st and ard physician 's scale and stadiometer , and body mass index was calculated as weight in kg/height in m2 . Waist circumference was measured with a st and ard anthropometric tape . Statistical Analysis We used SAS statistical software for data analyses ( 24 ) . The incidence of impaired fasting glucose was calculated for men with normal fasting glucose at baseline , and the incidence of diabetes was based on data from all 8633 patients . For analyses with impaired fasting glucose as the outcome , we excluded 1122 men who had impaired fasting glucose at baseline and an additional 69 men who had normal fasting plasma glucose at baseline but developed diabetes during follow-up . Rates of impaired fasting glucose or diabetes were calculated by dividing the number of incident cases during the study period by the number of person-years over the same period . We defined the study period as the interval between the baseline examination and the last follow-up visit . We used logistic regression to estimate the association between dependent variables and independent variables after adjustment for possible confounding factors . We used general linear models to study the cross-sectional association of fitness level and parental history of diabetes ( 24 , 25 ) . To account for the possible cohort effect of baseline year , we examined the relation between incident cases and baseline year and found no association . We used tests for ordinal linear trend to evaluate the possible relation of higher treadmill time with risk for impaired fasting glucose or diabetes after dividing the sample into the three fitness groups . All P values are two-sided , and those less than 0.05 were considered statistically significant . Role of the Funding Source The funding agencies did not participate in the collection , analysis , or interpretation of data presented in this report or in the decision to su bmi t the manuscript for publication . Results During an average follow-up of 6.1 4.8 years ( range , 1 to 24.8 years ) that included 52 588 person-years , 593 men developed impaired fasting glucose and 149 developed diabetes . Of the men with incident diabetes , 139 ( 93 % ) were not aware of", "To investigate breast cancer risk in Hispanic and non-Hispanic White women , the authors conducted a population -based case-control study of New Mexican women during 1992 - 1994 using incident breast cancer cases aged 35 - 74 years and frequency-matched controls selected using r and om digit dialing . Activity type and weekly duration of usual nonoccupational physical activity were used to calculate weekly metabolic equivalent (MET)-hours of total and vigorous physical activity ( > or = 5 METs ) . Conditional logistic regression models were fitted to estimate the relative risk of breast cancer for levels of physical activity and to assess the difference in effects by ethnicity , body mass index , energy intake , and menopausal status . Vigorous physical activity was associated with reduced breast cancer risk in both Hispanic and non-Hispanic White women . Women in the highest category of vigorous activity had lower risk of breast cancer ( adjusted odds ratio = 0.34 , 95 % confidence interval : 0.22 , 0.51 for Hispanic ; adjusted odds ratio = 0.60 , 95 % confidence interval : 0.41 , 0.89 for non-Hispanic White women ) compared with women reporting no vigorous physical activity . Both pre- and postmenopausal Hispanic women showed decreasing risk with increasing level of activity . Physical activity was protective only among postmenopausal non-Hispanic White women . The effects of physical activity were independent from reproductive factors , usual body mass index , body mass index at age 18 , adult weight gain , and total energy intake", "BACKGROUND The observation that exercise training reduces cardiovascular mortality is robust and consistent , but the amount and intensity of exercise that is required for risk reduction is not yet resolved . METHODS We studied the association between the amount and intensity of exercise and cardiovascular mortality in 27 143 men and 28 929 women who were free from known cardiovascular disease at the beginning of follow-up between 1984 and 1986 . The relative risk of death was calculated as the rate of death among participants within a given physical activity category compared with the rate of death in the reference category ( no physical activity ) . We used Cox regression analysis to adjust for age and other potentially confounding factors . RESULTS After 16 years ( SD 4 years ) of follow-up , 2946 men ( 10.8 % ) and 2486 women ( 8.6 % ) had died from ischaemic heart disease or stroke . A single weekly bout of exercise of high intensity reduced the risk of cardiovascular death , both in men [ relative risk ( RR ) 0.61 , 95 % confidence interval ( CI ) 0.49 - 0.75 ] , and women ( RR 0.49 , 95 % CI 0.27 - 0.89 ) , compared with those who reported no activity . There was no additional benefit from increasing the duration or the number of exercise sessions per week . The risk reduction related to exercise increased with increasing age in men , but not in women . CONCLUSION These results challenge the current recommendation that expenditure of at least 1000 kcal per week is required to achieve exercise-induced protection against premature cardiovascular mortality", "Physical activity has frequently been reported to decrease the risk of colon cancer in men , but data on the relation of physical activity to colon cancer risk in women have generally been less consistent . To further investigate the relationship of physical activity with colon cancer risk in women , we studied a cohort of 31,783 US women participating in the Breast Cancer Detection Demonstration Project Follow-up Study . Information on daily physical activity over the past year was ascertained using a self-administered question naire at study baseline . The Cox proportional hazards model was used to estimate relative risks ( RRs ) relating physical activity to the risk of incident colon cancer . During 270,325 person-years of follow-up , 243 colon cancer cases were identified . No association was observed between physical activity and the subsequent risk of colon cancer . The multivariable RRs of colon cancer across increasing quintiles of total physical activity were 1.0 , 1.45 , 1.16 , 1.27 and 1.15 ( 95 % CI : 0.76 , 1.75 ; p(trend ) = 0.77 ) . The multivariable RRs comparing women at the extremes of moderate and vigorous physical activity , respectively , were 1.07 ( 95 % CI : 0.70 , 1.62 ) and 1.10 ( 95 % CI : 0.78 , 1.55 ) . The relationship between physical activity and colon cancer risk did not vary by anatomic subsite or across subgroups defined by age , body mass , dietary fiber intake , menopausal status , menopausal hormone use or aspirin use . The results of this large prospect i ve cohort study among women do not support the hypothesis that physical activity is related to a lower incidence of colon cancer", "BACKGROUND Physical activity has been advocated as an important factor in the primary prevention of non-insulin-dependent diabetes mellitus ( NIDDM ) , but information concerning the specific intensities and duration s that are protective has been unavailable . OBJECTIVE To examine prospect ively the association between self-reported levels of the intensity and duration of physical activities , and cardiorespiratory fitness ( assessed by respiratory gas exchange ) and incident cases of NIDDM ( assessed by the oral glucose tolerance test ) in a population -based sample of 897 middle-aged Finnish men . RESULTS After adjustment for age , baseline glucose values , body mass index , serum triglyceride levels , parental history of diabetes , and alcohol consumption , moderately intense physical activities ( > or = 5.5 metabolic units ) that were undertaken for at least a 40-minute duration per week were associated with a reduced risk of NIDDM ( odds ration [ OR ] , 0.44 ; 95 % confidence interval [ CI ] , 0.22 - 0.88 ) . Activities with less than an intensity of 5.5 metabolic units , regardless of their duration , were not protective . Cardiorespiratory fitness levels greater than 31.0 mL of oxygen per kilogram per minute were protective against NIDDM ( OR , 0.26 ; 95 % CI , 0.08 - 0.82 ) . A subgroup of men at high risk of NIDDM , because they were overweight and were hypertensive and had a positive parental history of NIDDM , who engaged in moderately intense physical activities above the 40-min/wk duration reduced their risk of NIDDM by 64 % compared with men who did not participate in such activities . CONCLUSIONS After adjustment for age , baseline glucose levels , and known risk factors , physical activities with an intensity of 5.5 metabolic units or greater and a duration of 40 minutes or greater per week protected against the development of NIDDM . These protective effects were even more pronounced in a subgroup of men who were at high risk for the development of the disease", "OBJECTIVE To evaluate the relationship between changes in physical fitness and risk of mortality in men . DESIGN Prospect i ve study , with two clinical examinations ( mean interval between examinations , 4.9 years ) to assess change or lack of change in physical fitness as associated with risk of mortality during follow-up after the subsequent examination ( mean follow-up from subsequent examination , 5.1 years ) . SETTING Preventive medicine clinic . STUDY PARTICIPANTS Participants were 9777 men given two preventive medical examinations , each of which included assessment of physical fitness by maximal exercise tests and evaluation of health status . MAIN OUTCOME MEASURES All cause ( n = 223 ) and cardiovascular disease ( n = 87 ) mortality . RESULTS The highest age-adjusted all-cause death rate was observed in men who were unfit at both examinations ( 122.0/10,000 man-years ) ; the lowest death rate was in men who were physically fit at both examinations ( 39.6/10,000 man-years ) . Men who improved from unfit to fit between the first and subsequent examinations had an age-adjusted death rate of 67.7/10,000 man-years . This is a reduction in mortality risk of 44 % ( 95 % confidence interval , 25 % to 59 % ) relative to men who remained unfit at both examinations . Improvement in fitness was associated with lower death rates after adjusting for age , health status , and other risk factors of premature mortality . For each minute increase in maximal treadmill time between examinations , there was a corresponding 7.9 % ( P = .001 ) decrease in risk of mortality . Similar results were seen when the group was stratified by health status , and for cardiovascular disease mortality . CONCLUSIONS Men who maintained or improved adequate physical fitness were less likely to die from all causes and from cardiovascular disease during follow-up than persistently unfit men . Physicians should encourage unfit men to improve their fitness by starting a physical activity program", "A prospect i ve cohort study of London civil servants was used to examine the relation of physical activity to various causes of death . 6,702 men aged 40 - 64 y who participated in a baseline examination between 1969 and 1970 were followed up for 25 y during which time there were 2859 deaths . The association of two measures of physical activity ( leisure time activity and usual walking pace ) with cause-specific mortality was examined . Walking pace demonstrated inverse relations with mortality from all-causes , coronary heart disease ( CHD ) , other cardiovascular disease ( CVD ) , all cancers , respiratory disease , colorectal cancer and haematopoietic cancer following adjustment for risk factors which included age , employment grade , smoking , body mass index , and forced expiratory volume ( P [trend] all-cause , CHD , other cardiovascular disease , and haematopoietic cancer mortality ( P [trend] Leisure time activity was also inversely associated with mortality from all-causes , CHD , other CVD , and all-cancers following adjustment for risk factors ( P [trend] deaths in the first 5 and 10 y of follow-up did not greatly alter these associations . It is concluded that physical activity may confer protection against death due to some cancers , in addition to reducing cardiovascular disease risk", "BACKGROUND Few studies have examined the association of physical activity with coronary heart disease among women . OBJECTIVE To examine whether participation in physical activity during leisure time decreases the risk of myocardial infa rct ion in postmenopausal women . METHOD A population -based , case-control study among enrollees of the Group Health Cooperative of Puget Sound , a health maintenance organization based in Seattle , Wash. Cases were postmenopausal women who sustained an incident nonfatal myocardial infa rct ion during the period 1986 through 1991 . Controls were a r and om sample of Group Health Cooperative enrollees who were frequency matched to the cases by age and calendar year . Participation in physical activity during leisure time was assessed from a telephone interview . A total of 268 cases and 925 controls were interviewed . RESULTS After adjustment for potential confounding factors , the odds ratios for nonfatal myocardial infa rct ion for women in the second , third , and fourth quartile of total energy expenditure , relative to women in the first quartile , were 0.52 ( 95 % confidence interval , 0.34 to 0.80 ) , 0.40 ( 95 % confidence interval , 0.26 to 0.63 ) , and 0.40 ( 95 % confidence interval , 0.25 to 0.63 ) , respectively . Similar odds ratios were associated with the energy expended in nonstrenuous leisure-time physical activity , and with walking for exercise . CONCLUSION This case-control study suggests that the risk of myocardial infa rct ion among postmenopausal women is decreased by 50 % with modest leisure-time energy expenditures , equivalent to 30 to 45 minutes of walking for exercise three times a week", "OBJECTIVE To examine prospect ively the association between regular exercise and the subsequent development of non-insulin-dependent diabetes mellitus ( NIDDM ) . DESIGN Prospect i ve cohort study including 5 years of follow-up . PARTICIPANTS 21,271 US male physicians participating in the Physicians ' Health Study , aged 40 to 84 years and free of diagnosed diabetes mellitus , myocardial infa rct ion , cerebrovascular disease , and cancer at baseline . Morbidity follow-up was 99.7 % complete . MAIN OUTCOME MEASURE Incidence of NIDDM . RESULTS At baseline , information was obtained about frequency of vigorous exercise and other risk indicators . During 105,141 person-years of follow-up , 285 new cases of NIDDM were reported . The age-adjusted incidence of NIDDM ranged from 369 cases per 100,000 person-years in men who engaged in vigorous exercise less than once weekly to 214 cases per 100,000 person-years in those exercising at least five times per week ( P , trend , less than .001 ) . Men who exercised at least once per week had an age-adjusted relative risk ( RR ) of NIDDM of 0.64 ( 95 % Cl , 0.51 to 0.82 ; P = .0003 ) compared with those who exercised less frequently . The age-adjusted RR of NIDDM decreased with increasing frequency of exercise : 0.77 for once weekly , 0.62 for two to four times per week , and 0.58 for five or more times per week ( P , trend , .0002 ) . A significant reduction in risk of NIDDM persisted after adjustment for both age and body-mass index : RR , 0.71 ( 95 % Cl , 0.56 to 0.91 ; P = .006 ) for at least once per week compared with less than once weekly , and P , trend , .009 , for increasing frequency of exercise . Further control for smoking , hypertension , and other coronary risk factors did not material ly alter these associations . The inverse relation of exercise to risk of NIDDM was particularly pronounced among overweight men . CONCLUSIONS Exercise appears to reduce the development of NIDDM even after adjusting for body-mass index . Increased physical activity may be a promising approach to the primary prevention of NIDDM", "PURPOSE The purpose of this study was to examine the long-term relationships between total physical activity and mortality from all causes and coronary heart disease ( CHD ) in the general population . METHODS A prospect i ve design was used , following participants for 29 years , beginning in 1960 . The study population consisted of a r and omly selected sample of white male ( n = 698 ) and female ( n = 763 ) residents of Buffalo , New York with a 79.0 % participation rate and follow-up rates of 96.0 % and 90.2 % in males and females , respectively . At baseline , comprehensive information was obtained regarding participants ' usual physical activity at work and during leisure time . RESULTS As of December 31 , 1989 , three hundred and two ( 43.3 % ) men and 276 ( 41.0 % ) women died , 109 ( 15.6 % ) and 81 ( 10.6 % ) from CHD , respectively . In men , a significant interaction was found between activity and body mass index ( BMI ) for both outcomes . In women , a significant activity by age interaction was observed . In non-obese men ( BMI 27.02 ) , activity was inversely associated with all-cause [ relative risk ( RR ) = 0.59 ; 95 % confidence interval ( CI ) , 0.39 - 0.89 ] and CHD mortality ( RR = 0.39 ; 95 % CI , 0.18 - 0.83 ) , independent from the effects of age and education . No such associations were found in obese men and increased risks could not be ruled out . Among women , younger participants ( age had a significantly reduced risk of CHD death with increased activity ( RR = 0.26 ; 95 % CI , 0.07 - 0.99 ) . No other significant associations were observed . CONCLUSIONS Physical activity favorably influences mortality risks in non-obese men and younger women . Gender-specific factors should be considered for potential effect modification", "We have used data from a large population -based case-control study inthe United States to evaluate the effect of occupational physical activity onbreast cancer risk . Women diagnosed with breast cancer identified from fourstate cancer registries , and controls r and omly selected from lists oflicensed drivers or Medicare beneficiaries , were interviewed by telephone forinformation on usual occupation and other factors . We classified usualoccupation into one of four categories of physical activity . After excludingsubjects for whom a strength rating could not be assigned , we had a final sample size of 4,863 cases and 6,783 controls . Using conditional logisticregression models , we calculated adjusted odds ratios ( OR ) and 95 percentconfidence intervals ( CI ) for occupations having light , medium , and heavyactivity compared with sedentary ones . Women with heavy-activity occupationshad a lower risk of breast cancer than women with sedentary jobs ( OR = 0.82,CI = 0.63 - 1.08 ) , as di d women with jobs with medium activity ( OR = 0.86 , CI= 0.77 - 0.97 ) or light activity ( OR = 0.92 , CI = 0.84 - 1.01 ) . There was asignificant decreasing trend in the ORs from sedentary to heavy work ( P = 0.007 ) . Although limited by exposure misclassification , these data areconsistent with the hypothesis that physical activity reduces the risk ofbreast cancer", "AIMS To investigate separately for men and women whether moderate or high leisure time physical activity , occupational physical activity , and commuting activity are associated with a reduced cardiovascular disease ( CVD ) and all-cause mortality , independent of CVD risk factors and other forms of physical activity . METHODS AND RESULTS Prospect i ve follow-up of 15,853 men and 16,824 women aged 30 - 59 years living in eastern and south-western Finl and ( median follow-up time 20 years ) . CVD and all-cause mortality were lower ( 9 - 21 % ) in men and women ( 2 - 17 % ) who were moderately or highly physically active during leisure time . Moderate and high levels of occupational physical activity decreased CVD and all-cause mortality by 21 - 27 % in both sexes . Women spending daily 15 min or more in walking or cycling to and from work had a reduced CVD and all-cause mortality before adjustment for occupational and leisure time physical activity . Commuting activity was not associated with CVD or all-cause mortality in men . CONCLUSION Moderate and high levels of leisure time and occupational physical activity are associated with a reduced CVD and all-cause mortality among both sexes . Promoting already moderate levels of leisure time and occupational physical activity are essential to prevent premature CVD and all-cause mortality", "BACKGROUND The role of walking , as compared with vigorous exercise , in the prevention of coronary heart disease remains controversial , and data for women on this topic are sparse . METHODS We prospect ively examined the associations between the score for total physical activity , walking , and vigorous exercise and the incidence of coronary events among 72,488 female nurses who were 40 to 65 years old in 1986 . Participants were free of diagnosed cardiovascular disease or cancer at the time of entry and completed serial detailed question naires about physical activity . During eight years of follow-up , we documented 645 incident coronary events ( nonfatal myocardial infa rct ion or death from coronary disease ) . RESULTS There was a strong , grade d inverse association between physical activity and the risk of coronary events . As compared with women in the lowest quintile group for energy expenditure ( expressed as the metabolic-equivalent [ MET ] score ) , women in increasing quintile groups had age-adjusted relative risks of 0.77 , 0.65 , 0.54 , and 0.46 for coronary events ( P for trend risk of coronary events ; women in the highest quintile group for walking , who walked the equivalent of three or more hours per week at a brisk pace , had a multivariate relative risk of 0.65 ( 95 percent confidence interval , 0.47 to 0.91 ) as compared with women who walked infrequently . Regular vigorous exercise ( > or = 6 MET ) was associated with similar risk reductions ( 30 to 40 percent ) . Sedentary women who became active in middle adulthood or later had a lower risk of coronary events than their counterparts who remained sedentary . CONCLUSIONS These prospect i ve data indicate that brisk walking and vigorous exercise are associated with substantial and similar reductions in the incidence of coronary events among women", "BACKGROUND AND PURPOSE Few studies have reported a protective effect of physical activity on stroke in women , particularly among elderly women . This study was conducted to examine the association between different levels of leisure-time physical activity and stroke mortality in a large prospect i ve study of middle-aged and elderly women . METHODS We conducted a 10-year mortality follow-up of women aged > /=50 years , free from stroke at baseline ( n=14 101 ) , who participated in the Nord-Trondelag Health Survey in Norway during 1984 - 1986 . Main outcome measures were relative risk of stroke mortality according to increasing levels of physical activity , with the least active group used as reference . RESULTS In groups aged 50 to 69 , 70 to 79 , and 80 to 101 years , the relative risk of dying decreased with increasing physical activity , after adjustment for potentially confounding factors . In groups aged 50 to 69 and 70 to 79 years , the most active women had an adjusted relative risk of 0 . 42 ( 95 % CI , 0.24 to 0.75 ) and 0.56 ( 95 % CI , 0.36 to 0.88 ) , respectively . In the group aged 80 to 101 years , there was a consistent negative association with physical activity ; the adjusted relative risk for the most active was 0.57 ( 95 % CI , 0.30 to 1.09 ) . CONCLUSIONS Physical activity was associated with reduced risk of death from stroke in middle-aged and elderly women . This association persisted after we excluded individuals with prevalent cardiovascular and cerebrovascular disease at baseline and women who died during the first 2 years of follow-up . These observations strengthen the evidence that physical activity should be part of a primary prevention strategy against stroke in women", "The purpose of this analytical review was to estimate the direct and indirect economic costs of physical inactivity and obesity in Canada in 2001 . The relative risks of diseases associated with physical inactivity and obesity were determined from a meta- analysis of existing prospect i ve studies and applied to the health care costs of these diseases in Canada . Estimates were derived for both the direct health care expenditures and the indirect costs , which included the value of economic output lost because of illness , injury-related work disability , or premature death . The economic burden of physical inactivity was $ 5.3 billion ( $ 1.6 billion in direct costs and $ 3.7 billion in indirect costs ) while the cost associated with obesity was $ 4.3 billion ( $ 1.6 billion of direct costs and $ 2.7 billion of indirect costs ) . The total economic costs of physical inactivity and obesity represented 2.6 % and 2.2 % , respectively , of the total health care costs in Canada . The results underscore the importance of public health efforts aim ed at combating the current epidemics of physical inactivity and obesity in Canada", "Background : Leisure time physical activity has previously been shown to be protective against cardiovascular disease . We estimated the influence of exercise , occupational physical activity , and household work with regard to risk of acute myocardial infa rct ion ( MI ) . Special interest was focused on potential interaction among these aspects of physical activity . Method : We analyzed data from a large population -based case-control study conducted in Stockholm , Sweden , 1992–1994 . Cases comprised 1204 men and 550 women , age 45–70 years , who experienced their first MI during the study period . The controls , 1538 men and 777 women , were r and omly selected from the study base , matched on sex , age , and hospital catchment area . The results were adjusted for several potential confounding factors . Results : Exercise , walking or st and ing at work , and doing dem and ing household work were all associated with decreased risk of acute MI ; the estimated relative risks ( RRs ) ranged from 0.31 to 0.90 when all cases ( fatal and nonfatal ) were considered . In contrast , lifting or carrying at work , and an occupational workload perceived to be strenuous , were related to an increased risk of MI ( RRs ranging from 1.10–1.57 ) . We observed a synergistic benefit from exercise and walking or st and ing at work , and from household work and walking or st and ing at work . Conclusion : Aerobic physical activities such as exercise or walking at work seemed to reduce the risk of MI , whereas anaerobic activities such as heavy lifting at work were related to increased risk of MI", "Background —The influence of physical activity on the incidence of angina pectoris and hard coronary events ( myocardial infa rct ion and coronary deaths ) was examined in Northern Irel and and France at contrasting risk for coronary heart disease ( CHD ) and with different physical activity patterns . Methods and Results — Participants of the Prospect i ve Epidemiological Study of Myocardial Infa rct ion ( PRIME ) ( n=9758 ; age , 50 to 59 years ) , free of CHD at baseline , were followed up for 5 years : 167 hard CHD and 154 angina events were recorded . Net energy expenditure ( EE ) as the result of physical activity was assessed by means of the MONICA Optional Study of Physical Activity Question naire ( MOSPA-Q ) . Leisure-time physical activity EE was calculated ; subjects were also categorized as to whether they performed high-intensity leisure-time activities or walked or cycled to work . After multivariate adjustment , leisure-time physical activity EE was associated with a lower risk of hard CHD events ( P walking or cycling to work was not independently related to hard CHD events . No interaction by country was found . The beneficial effect of leisure-time physical activity was also present among subjects who did not report high-intensity activities ( P leisure-time physical activity was associated with a higher risk of angina in both countries . Conclusions —These data indicate a beneficial effect of leisure-time physical activity EE on hard CHD incidence in middle-aged men , which could partly explain the unfavorable rate of CHD in Northern Irel and . The higher level of leisure-time activities in France could , in part , explain its lower rate of CHD", "BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin", "Previous epidemiological studies have shown that vigorous physical activity reduces the development of type 2 diabetes ( 1–3 ) . A recommendation from the Centers for Disease Control and Prevention reported that individuals should engage in ≥30 min of moderate-intensity physical activity , such as brisk walking , on most days of the week for health promotion and disease prevention ( 4 ) ; however , it is unclear whether mild physical activity ( i.e. , walking to walk ) reduces the risk for type 2 diabetes . In the present study , we examined the relationship between walking to work and the development of type 2 diabetes during a 4-year observational period . The Kansai Healthcare Study is an ongoing cohort investigation design ed to clarify the risk factors for cardiometabolic diseases . Between April 2000 and March 2001 , 12,647 male employees of a company in the area of Kansai , Japan , who were aged 40–55 years at entry and considered to be involved in sedentary jobs were enrolled in this study . All employees aged ≥40 years underwent annual detailed medical check-ups . The protocol for this research was review ed by the Human Subjects Review Committee at Osaka City University . For current analysis , study participants consisted of 11,073 Japanese men aged 40–55 years at entry with a fasting plasma glucose ( FPG ) A 4-year follow-up examination after baseline was conducted between April 2004 and March 2005 . We excluded 53 men because of death and 2,016 men because of", "Few prospect i ve studies have assessed the relation between physical activity and diabetes . The authors examined this relation prospect ively among 6,815 Japanese-American men in the Honolulu Heart Program who were aged 45 - 68 years and initially free of diagnosed diabetes in 1965 - 1968 . A physical activity index was calculated based on time spent per day in different activity levels and a weighting factor correlated with estimated oxygen consumption . Incidence of clinical ly recognized diabetes was based on self-reported use of diabetic medication at one of two subsequent examinations . The age-adjusted 6-year cumulative incidence of diabetes decreased progressively with increasing quintile of physical activity from 73.8 to 34.3 per 1,000 ( p men and from 53.9 to 21.7 per 1,000 ( p men with a non-fasting glucose level one hour after a 50-gm load , the latter group being less likely to have unrecognized diabetes at baseline . When stratified by tertile of baseline glucose , trends in incidence across physical activity quintiles were statistically significant in the low and middle tertiles but not in the high tertile . Similar inverse trends were observed for men in the lower four quintiles of body mass index , however , these trends were weaker and not significant for men in the upper quintile of body mass index . Age-adjusted odds ratios for diabetes comparing the upper with the lower four quintiles of physical activity were 0.55 ( 95 % confidence interval ( CI ) 0.41 - 0.75 ) for all men and 0.50 ( 95 % CI 0.33 - 0.74 ) for men with glucose age , body mass index , subscapular/triceps skinfold ratio , systolic blood pressure , triglycerides , glucose , hematocrit , and parental history of diabetes , odds ratios were still statistically significant and similar in magnitude . Restriction of analyses to men who remained free of cardiovascular disease during the study period produced similar results , which suggests that inactivity due to sub clinical cardiovascular disease is unlikely to be responsible for these findings . Risk factor-adjusted odds ratios for older men ( 55 - 68 years ) demonstrated that physical activity confers at least the same degree of protection as in younger men ( 45 - 54 years ) . These results indicate that physical activity is associated inversely with incident diabetes and that the beneficial effect does not appear to be mediated through improvements in other risk factors assessed in this study", "OBJECTIVE : To examine the association of physical activity and body mass index ( BMI ) , and their combined effect , with the risk of total , cardiovascular disease ( CVD ) and cancer mortality . DESIGN : Prospect i ve follow-up study .SUBJECTS : In all , 22 528 men and 24 684 women aged 25–64 y at baseline having 7394 deaths during a mean follow-up of 17.7 y . MEASUREMENT : A self-administered question naire data on smoking , socioeconomic factors , physical activity and medical history , together with measured height , weight , blood pressure and serum cholesterol using st and ardized protocol . RESULT : Physically active subjects had significantly lower age-adjusted mortality from cardiovascular , cancer and all causes compared with sedentary ones . Further adjustment for smoking , systolic blood pressure , cholesterol , BMI , diabetes and education affected the results only slightly . Obese subjects ( BMI ≥30 kg/m2 ) had significantly higher cardiovascular and total mortality than the normal weight ( 18.5≤ BMI increased mortality among obese subjects was mediated through obesity-related cardiovascular risk factors . BMI had an inverse association with cancer mortality among men and almost significant direct association among women . Total mortality was also increased among the lean ( BMI Regular physical activity and normal weight are both important indicators for a decreased risk of mortality from all causes , CVD and cancer . Physical activity had a strong independent effect on mortality , whereas the effect of BMI was partly mediated through other obesity-related risk factors", "Energy restriction remains one of the most effective ways known to prevent breast cancer in animal models . However , energy intake has not been consistently associated with risk of breast cancer in humans . In a prospect i ve study , we assessed whether energy intake , body size , and physical activity each independently influence breast cancer risk in postmenopausal women and estimated the joint effect of combinations of these individual factors . As part of the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial , 38,660 women , ages 55 to 74 years and recruited from 10 centers in the United States during 1993 to 2001 , were r and omized to the screening arm of the trial . At baseline , the women completed a self-administered question naire , including a food frequency question naire . During follow-up from 1993 to 2003 , 764 incident breast cancer cases were ascertained . Women in the highest quartile of energy intake ( ≥2,084 kcal/d ) compared with those in the lowest quartile ( increased risk for breast cancer [ multivariate relative risk ( RR ) , 1.25 ; 95 % confidence interval ( 95 % CI ) , 1.02 - 1.53 ; Ptrend continuous = 0.03 ] . Current body mass index ( BMI ) was also positively and significantly associated with risk ( multivariate RR comparing > 30 kg/m2 with reduced risk of breast cancer compared with those who reported no recreational physical activity ( multivariate RR , 0.78 ; 95 % CI , 0.60 - 0.99 ; Ptrend = 0.15 ) . None of these associations with individual energy balance measures was substantially confounded by the other two measures . When we estimated the joint effect of all three variables , women with the most unfavorable energy balance ( the highest energy intake , highest BMI , and least physical activity ) had twice the risk ( RR , 2.10 ; 95 % CI , 1.27 - 3.45 ) of women with the most favorable energy balance ( the lowest energy intake , lowest BMI , and most physical activity ) . Although our estimates of absolute energy intake , based on a food frequency question naire , are imperfect , these results suggest that energy intake , in addition to BMI and physical activity may be independently associated with breast cancer risk . In addition , these three aspects of energy balance may act jointly in determining breast cancer risk . ( Cancer Epidemiol Prev 2006;15(2):334–41", "Most studies to date support a protective role of physical activity in reducing stroke risk . However , they were not able to take into account combined work and leisure activity . We prospect ively followed up 22,602 men and women aged 40–79 years , who had no history of stroke and myocardial infa rct ion at baseline , participating in the European Prospect i ve Investigation into Cancer-Norfolk . Participants were categorized into four levels of physical activity based on a vali date d self-reported question naire , which assesses combined work and leisure activities , at baseline during the period from 1993 to 1997 . Stroke incidence was ascertained by death certificate and hospital record linkage data up to 2004 , average 8.6 years of follow-up . We used the Cox proportional hazards model . There were 361 incident strokes during follow-up ( total person years = 195,092 ) . After adjusting for age , sex , systolic blood pressure , body mass index , cholesterol , history of diabetes and smoking , men and women who were physically active were less likely to have a stroke ( relative risk = 0.70 , 95 % CI : 0.49–0.99 , p = 0.024 ) compared to those who were inactive . This highlights the fact that efforts to increase physical activity in both the work place and in leisure time should be encouraged", "Due to its potential effects on ovarian hormone production , physical activity has been proposed as a modifiable risk factor for breast cancer . The authors analyzed data from the American Cancer Society Cancer Prevention Study II ( CPS-II ) Nutrition Cohort to examine the association between various measures of physical activity and postmenopausal breast cancer risk . Information on physical activity was obtained in 1992 via a self-administered question naire for 72,608 postmenopausal female participants who were cancer-free . During the five year prospect i ve follow-up , 1520 incident breast cancer cases were identified among these women . Cox proportional hazards modeling was used to compute hazard rate ratios ( RR ) and to adjust for potential confounding factors including mammography . Women who were most physically active ( > 42.0 MET-h/week ) at baseline had 29 % lower incidence rates than active women with the least activity ( > 0–7.0 MET-h/week ) ( 95 % CI , 0.49–1.02 ) . The difference in risk was largest for localized breast cancer , and for women who did not use hormone replacement therapy ( HRT ) at enrollment . Our findings are consistent with other studies that show lower risk of postmenopausal breast cancer associated with regular physical activity", "There is convincing evidence for a decreased risk of breast cancer with increased physical activity . Uncertainties remain , however , about the role of different types of physical activity on breast cancer risk and the potential effect modification for these associations . We used data from 218,169 premenopausal and postmenopausal women from nine European countries , ages 20 to 80 years at study entry into the European Prospect i ve Investigation into Cancer and Nutrition . Hazard ratios ( HR ) from multivariate Cox regression models were calculated using metabolic equivalent value – based physical activity variables categorized in quartiles , adjusted for age , study center , education , body mass index , smoking , alcohol use , age at menarche , age at first pregnancy , parity , current oral contraceptive use , and hormone replacement therapy use . The physical activity assessment included recreational , household , and occupational activities . A total physical activity index was estimated based on cross-tabulation of these separate types of activity . During 6.4 years of follow-up , 3,423 incident invasive breast cancers were identified . Overall , increasing total physical activity was associated with a reduction in breast cancer risk among postmenopausal women ( Ptrend = 0.06 ) . Specifically , household activity was associated with a significantly reduced risk in postmenopausal ( HR , 0.81 ; 95 % confidence interval , 0.70 - 0.93 , highest versus the lowest quartile ; Ptrend = 0.001 ) and premenopausal ( HR , 0.71 ; 95 % confidence interval , 0.55 - 0.90 , highest versus lowest quartile ; Ptrend = 0.003 ) women . Occupational activity and recreational activity were not significantly related to breast cancer risk in both premenopausal and postmenopausal women . This study provides additional evidence for a protective effect of physical activity on breast cancer risk . ( Cancer Epidemiol Biomarkers Prev 2007;16(1):36–42", "CONTEXT Physical activity and fitness are believed to reduce premature mortality , but whether genetic factors modify this effect is not known . OBJECTIVE To investigate leisure physical activity and mortality with respect to familial aggregation of health habits during childhood and factors that may enable some individuals to achieve higher levels of fitness . DESIGN Prospect i ve twin cohort study . SETTING Finl and . SUBJECTS In 1975 , at baseline , 7925 healthy men and 7977 healthy women of the Finnish Twin Cohort aged 25 to 64 years who responded to a question naire on physical activity habits and known predictors of mortality . Those who reported exercising at least 6 times per month with an intensity corresponding to at least vigorous walking for a mean duration of 30 minutes were classified as conditioning exercisers , those who reported no leisure physical activity were classified as sedentary , and other subjects were classified as occasional exercisers . MAIN OUTCOME MEASURES All-cause mortality and discordant deaths among same-sex twin pairs from 1977 through 1994 . RESULTS Among the entire cohort , 1253 subjects died . The hazard ratio for death adjusted for age and sex was 0.71 ( 95 % confidence interval [ CI ] , 0.62 - 0.81 ) in occasional exercisers and 0.57 ( 95 % CI , 0.45 - 0.74 ) in conditioning exercisers , compared with those who were sedentary ( Pfor trend death ( n=434 ) , the odds ratio for death was 0.66 ( 95 % CI , 0.46 - 0.94 ) in occasional exercisers and 0.44 ( 95 % CI , 0.23 - 0.83 ) in conditioning exercisers compared with those who were sedentary ( P for trend , .005 ) . The beneficial effect of physical activity remained after controlling for other predictors of mortality . CONCLUSION Leisure-time physical activity is associated with reduced mortality , even after genetic and other familial factors are taken into account", "The potential role of physical activity in the primary prevention of non-insulin-dependent diabetes mellitus ( NIDDM ) is largely unknown . We examined the association between regular vigorous exercise and the subsequent incidence of NIDDM in a prospect i ve cohort of 87,253 US women aged 34 - 59 years and free of diagnosed diabetes , cardiovascular disease , and cancer in 1980 . During 8 years of follow-up , we confirmed 1303 cases of NIDDM . Women who engaged in vigorous exercise at least once per week had an age-adjusted relative risk ( RR ) of NIDDM of 0.67 ( p less than 0.0001 ) compared with women who did not exercise weekly . After adjustment for body-mass index , the reduction in risk was attenuated but remained statistically significant ( RR = 0.84 , p = 0.005 ) . When analysis was restricted to the first 2 years after ascertainment of physical activity level and to symptomatic NIDDM as the outcome , age-adjusted RR of those who exercised was 0.5 , and age and body-mass index adjusted RR was 0.69 . Among women who exercised at least once per week , there was no clear dose-response gradient according to frequency of exercise . Family history of diabetes did not modify the effect of exercise , and risk reduction with exercise was evident among both obese and nonobese women . Multivariate adjustments for age , body-mass index , family history of diabetes , and other variables did not alter the reduced risk found with exercise . Our results indicate that physical activity may be a promising approach to the primary prevention of NIDDM", "BACKGROUND Since falling is associated with serious morbidity among elderly people , we investigated whether the risk of falling could be reduced by modifying known risk factors . METHODS We studied 301 men and women living in the community who were at least 70 years of age and who had at least one of the following risk factors for falling : postural hypotension ; use of sedatives ; use of at least four prescription medications ; and impairment in arm or leg strength or range of motion , balance , ability to move safely from bed to chair or to the bathtub or toilet ( transfer skills ) , or gait . These subjects were given either a combination of adjustment in their medications , behavioral instructions , and exercise programs aim ed at modifying their risk factors ( intervention group , 153 subjects ) or usual health care plus social visits ( control group , 148 subjects ) . RESULTS During one year of follow-up , 35 percent of the intervention group fell , as compared with 47 percent of the control group ( P = 0.04 ) . The adjusted incidence-rate ratio for falling in the intervention group as compared with the control group was 0.69 ( 95 percent confidence interval , 0.52 to 0.90 ) . Among the subjects who had a particular risk factor at base line , a smaller percentage of those in the intervention group than of those in the control group still had the risk factor at the time of re assessment , as follows : at least four prescription medications , 63 percent versus 86 percent , P = 0.009 ; balance impairment , 21 percent versus 46 percent , P = 0.001 ; impairment in toilet-transfer skills , 49 percent versus 65 percent , P = 0.05 ; and gait impairment , 45 percent versus 62 percent , P = 0.07 . CONCLUSIONS The multiple-risk-factor intervention strategy result ed in a significant reduction in the risk of falling among elderly persons in the community . In addition , the proportion of persons who had the targeted risk factors for falling was reduced in the intervention group , as compared with the control group . Thus , risk-factor modification may partially explain the reduction in the risk of falling", "OBJECTIVE : To investigate the independent associations and the possible interaction of body mass index ( BMI ) , leisure time physical activity ( LTPA ) and perceived physical fitness and functional capability with the risk of mortality . DESIGN : Prospect i ve 16 y follow-up study .SUBJECTS : A regionally representative cohort of 35–63 -y-old Finnish men ( n=1090 ) and women ( n=1122 ) . MEASUREMENTS : All-cause , cardiovascular disease ( CVD ) and coronary heart disease ( CHD ) mortality were derived from the national census data until the end of September 1996 while the initial levels of BMI , LTPA , physical fitness and function were determined from self-administered question naires . RESULTS : After adjustment for age , marital and employment status , perceived health status , smoking and alcohol consumption , the Cox proportional hazards model showed that BMI was not associated with the risk of death among the men or the women . Compared with the most active subjects the men and women with no weekly vigorous activity had relative risks of 1.61 ( 95 % confidence interval , CI , 0.98–2.64 ) and 4.68 ( 95 % CI , 1.41–15.57 ) , respectively , for CVD mortality , and for the men there was a relative risk of 1.66 ( 95 % CI , 0.92–2.99 ) for CHD mortality . When compared with the men who perceived their fitness as better than their age-mates , the men with the ‘ worse ’ assessment had a relative risk of 3.29 ( 95 % CI , 1.80–6.02 ) for all-cause mortality and 4.37 ( 95 % CI , 1.80–10.6 ) for CVD mortality . Men with at least some difficulty in walking a distance of 2 km had a relative risk of 1.62 ( 95 % CI , 1.05–2.50 ) for all-cause mortality when compared with those who had no functional difficulties . In addition , in the comparison with subjects with no functional difficulties , the men and women who had some difficulty climbing several flights of stairs had relative risks of 1.47 ( 95 % CI , 0.97–2.23 ) and 2.39 ( 95 % CI , 1.25–4.60 ) for all-cause mortality , respectively . For CVD mortality the relative risks were 1.85 ( 95 % CI , 1.04–3.30 ) and 3.38 ( 1.22–9.41 ) , respectively . CONCLUSIONS : Although BMI did not prove to be an independent risk factor for mortality from CVD , CHD or from all causes combined , perceived physical fitness and functional capability did . An increase in LTPA seems to have a similar beneficial effect on the mortality risk of obese and nonobese men and women , and the effect also seems to be similar for fit and unfit subjects", "The authors prospect ively examined the influence of increased levels of physical activity on risk of stroke in members of the Framingham Study cohort . Two separate analyses were performed , one during midlife in 1,897 men ( mean age = 49.7 years ) and 2,299 women ( mean age = 49.9 years ) and another when the cohort was older ( 1,361 men ( mean age = 63.0 ) and 1,862 women ( mean age = 63.7 ) ) . A structured question naire administered at two separate examinations was used to estimate the amount of metabolic work done during a typical 24-hour period . Physical activity was categorized into tertiles , and medium and high levels of physical activity were compared with a low level of physical activity , which was used as the referent group . Cox proportional hazards , life table , and time-dependent covariate analyses were used to examine the relation between level of physical activity and stroke risk over a follow-up period of up to 32 years . In men , adjusted analyses revealed that increased levels of physical activity were protective . The strongest effect was obtained from an analysis involving older cohort members in the medium tertile ( risk ratio = 0.41 , 95 % confidence interval 0.24 - 0.69 ) . High levels of physical activity did not confer an additional benefit over medium levels . Adjusted analyses showed no significant protective effect in women . These results indicate that medium and high levels of physical activity among men are protective against stroke relative to low levels", "OBJECTIVE To identify risk factors and preventive measures for stroke in elderly men and women . DESIGN Observational prospect i ve cohort study . SUBJECTS Women ( N = 8532 ) and men ( N = 4722 ) between the ages of 44 and 101 ( median age , 74 ) residing in a retirement community in southern California who had no previous history of stroke . METHODS Upon entering the study in 1981 , 1983 , or 1985 , study participants filled out a detailed health survey question naire about their medical history , exercise habits , intake of caffeinated beverages , alcohol , vitamins , and foods containing vitamins A or C , and history of smoking . Women also reported their use of estrogen replacement therapy . Cohort members were followed by periodic resurvey and by examination of death records through 1998 . Age-adjusted stroke incidence rates , relative risks , and 2-sided P values were calculated . RESULTS Between 1981 and 1998 , 1211 women and 773 men were hospitalized for cerebrovascular disease . In women , risk of cerebral occlusion decreased significantly with increasing duration and recency of estrogen use . Hypertension , diabetes , heart attack , and smoking were significant stroke risk factors in both women and men . Exercise reduced stroke risk in general , and antioxidant vitamin supplements decreased the risk of cerebral occlusion . CONCLUSION These results emphasize the role of lifestyle modification in the primary prevention of stroke and suggest that estrogen replacement therapy may be a potential preventive measure for women", "It is considered that skeletal mass in humans may respond to loading or the number of loading cycles . The aim of this study was to examine the effect of a 1 year progressive resistance training program on the bone mass of 56 postmenopausal women . Assignment was by block r and omization to one of two resistance training groups : a strength trained group ( 3 x 8 repetition maximum ) or an endurance group ( 3 x 20 repetition maximum ) . The resistance exercises were selected to stress the ipsilateral forearm and hip region . The exercising side was r and omly assigned with one side exercised while the alternate side acted as the nonexercise control . Bone mineral density ( BMD ) was measured every 3 months at the radial forearm and four hip sites using the Hologic QDR 2000 bone densitometer . A linear regression function was fitted for each individual 's bone density results , and the slope was compared for the exercise and control side using paired t-tests . The bone mass increase with the strength regimen was significantly greater at the trochanteric hip site ( control -0.6 + /- 2.2 % , exercise 1.7 + /- 4.1 % , p increase in BMD with the endurance regimen except at the radius midsite ( control -1.0 + /- 2.3 % , exercise 0.1 + /- 1.4 % , p muscle strength , tested by a one-repetition maximum ( 1RM ) test , increased significantly for all 10 exercises ( p change in BMD and the percentage increase in strength as follows : trochanter with leg press ; intertrochanter with leg press ( p resistance exercise in that although the trochanter and intertrochanter bone density was elevated by the resistance exercises undertaken , there was no effect on the femoral neck value . Postmenopausal bone mass can be significantly increased by a strength regimen that uses high-load low repetitions but not by an endurance regimen that uses low-load high repetitions . We conclude that the peak load is more important than the number of loading cycles in increasing bone mass in early postmenopausal women", "Objective —To test the efficacy of a community based 10 week exercise intervention to reduce fall risk factors in women with osteoporosis . Methods —Static balance was measured by computerised dynamic posturography ( Equitest ) , dynamic balance by timed figure of eight run , and knee extension strength by dynamometry . Subjects were r and omised to exercise intervention ( twice weekly Osteofit classes for 10 weeks ) or control groups . Results —The outcome in 79 participants ( 39 exercise , 40 control ) who were available for measurement 10 weeks after baseline measurement is reported . After confounding factors had been controlled for , the exercise group did not make significant gains compared with their control counterparts , although there were consistent trends toward greater improvement in all three primary outcome measures . Relative to the change in control subjects , the exercise group improved by 2.3 % in static balance , 1.9 % in dynamic balance , and 13.9 % in knee extension strength . Conclusions —A 10 week community based physical activity intervention did not significantly reduce fall risk factors in women with osteoporosis . However , trends toward improvement in key independent risk factors for falling suggest that a study with greater power may show that these variables can be improved to a level that reaches statistical significance", "BACKGROUND We studied the relations between physical activity and changes in physical activity , all-cause mortality , and incidence of major coronary-heart-disease events in older men . METHODS In 1978 - 80 ( Q1 ) , 7735 men aged 40 - 59 were selected from general practice s in 24 British towns , and enrolled in a prospect i ve study of cardiovascular disease , which included physical activity data . In 1992 ( Q92 ) , 12 - 14 years later , 5934 of the men ( 91 % of available survivors , mean age 63 years ) gave further information on physical activity and were then followed up for a further 4 years . The main endpoints were all-cause mortality during 4 years of follow-up from Q92 , and major fatal and non-fatal coronary-heart-disease events during 3 years of follow-up from Q92 . FINDINGS Among 4311 men with no history of coronary heart disease , stroke , or \" other heart trouble \" by Q92 and who did not report \" poor health \" , there were 219 deaths . In the inactive/occasionally active , light , moderate , and moderately vigorous/vigorous activity groups there were 101 ( 18.5/1000 person-years ) 48 ( 11.4 ) , 23 ( 7.3 ) , and 47 ( 9.1 ) deaths , respectively ( adjusted risk ratios 1.00 , 0.61 [ 95 % CI 0.48 - 0.86 ] , 0.50 [ 0.31 - 0.79 ] , 0.65 [ 0.45 - 0.94 ] ) . Men who were sedentary at Q1 and who began at least light activity by Q92 had significantly lower all-cause mortality than those who remained sedentary , even after adjustment for potential confounders ( risk ratio=0.55 [ 0.36 - 0.84 ] ) . Physical activity improved both cardiovascular mortality ( 0.66 [ 0.35 - 1.23 ] ) and non-cardiovascular mortality ( 0.48 [ 0.27 - 0.85 ] ) . The relation between physical activity at Q92 , changes in physical activity , and mortality were similar for men with pre-existing cardiovascular disease . INTERPRETATION Maintaining or taking up light or moderate physical activity reduces mortality and heart attacks in older men with and without diagnosed cardiovascular disease . Our results support public-health recommendations for older sedentary people to increase physical activity , and for active middle-aged people to continue their activity into old age", "This case-control study examines the association of vigorous and mild physical activity with fall-related fractures in a community-dwelling population age 65 and older in South Florida . Vigorous physical activity was defined as exercising , doing heavy housecleaning , or other hard labor three or more times per week in the month prior to the index date ; mild physical activity was defined as the number of hours per day subjects reported spending on their feet . A case was any subject who sustained a fall-related fracture ( ICD-9CM-800 through ICD-9CM-829 ) over a 21-month period ( n = 471 ) . Controls were at 10 % r and om sample selected from the Health Care Financing Administration Medicare files ( n = 712 ) . The presence of any limitation in activities of daily living ( ADL ) significantly modified the effect of vigorous physical activity . Physically active subjects with no limitations ( ADL = 0 ) were less likely to sustain a fall-related fracture than were inactive subjects with an adjusted odds ratio ( aOR ) of 0.6 , ( 0.5 - 0.8 95 % CI ) , and active subjects with any limitation ( ADL > or = 1 ) had an aOR of 3.2 ( 1.1 - 9.8 95 % CI ) . Limiting this analysis to 159 hip fracture cases produced similar results . Mild physical activity was not associated with fracture . These results suggest that vigorous physical activity is associated with a lower fracture risk among elderly persons who have no limitation in ADL and with a higher risk among those with any limitations", "& NA ; To investigate the relation between recreational physical activity and breast cancer , we conducted an analysis of a population ‐based case‐control study of women age 50‐64 years in western Washington State . The study included 537 patients with breast cancer diagnosed during 1988‐1990 and 492 r and omly selected population control women . Detailed information on recreational exercise habits and other risk factors for breast cancer was ascertained by structured in‐person interviews . A similar proportion of cases and controls reported exercise in the 2 years before the referent date ( about 50 % ) , or during ages 12‐21 years ( about 40 % ) . Compared with women who reported no exercise , there was a slightly decreased risk of breast cancer in women who exercised more than 1.5 hours per week in the 2 years before diagnosis ( cases ) or referent date ( controls ) [ odds ratio ( OR ) = 0.7 ; 95 % confidence interval ( CI ) = 0.4‐1.1 ] , or who engaged in at least some high‐intensity exercise ( OR = 0.7 ; 95 % CI = 0.4‐1.1 ) , but there was no clear decline in risk at the highest categories of duration or intensity . There was no association between any intensity exercise at ages 12‐21 years and risk of breast cancer . These results indicate a weak negative association between physical activity and risk of breast cancer in middle‐aged women", "OBJECTIVES The purpose of this study was to determine whether walking is associated with a reduced risk of cardiovascular disease hospitalization and death in community-dwelling older men and women . DESIGN A prospect i ve study , with follow-up time of 4 to 5 years ( average 4.2 years ) . SETTING A western Washington health maintenance organization . PARTICIPANTS Men and women aged 65 years and older from a r and om sample of HMO enrollees invited by mail to participate in a health promotion intervention trial ( 36 % accepted the invitation and completed question naires ) . This report is based on 1645 older adults without severe disability and without history of heart disease . Vital status ascertainment was complete ( 100 % ) , and only 2.6 % did not complete the follow-up . MEASUREMENTS Reported frequency and duration of walking for exercise , work , err and s , pleasure , and hiking in the 2 weeks before baseline were used to classify hours of walking per week . The two main outcomes were : ( 1 ) cardiovascular disease hospitalizations with a discharge diagnosis of coronary ( ICD-9-CM 410 - 414 ) or other cardiovascular diseases ( ICD-9-CM 390 - 409 , 415 - 448 ) documented by computerized hospitalization records and ( 2 ) death . Numerous potential confounding factors were considered , including age , sex , treated high blood pressure , current estrogen use and chronic disease score ( ascertained by computerized medical and pharmacy records ) , and ethnicity , education , income , physical function , self-rated health status , smoking , alcohol intake , and body mass index ( ascertained by self-report on the mailed question naire ) . RESULTS Walking more than 4 hours/week was associated significantly with a reduced risk of cardiovascular disease hospitalization in both sexes combined compared with walking less than 1 hour/week ( age and sex-adjusted relative risk = 0.69 ; 95 % confidence interval , 0.52 - 0.90 ) . This association was not altered by adjustment for baseline cardiovascular risk factors and indicators of general health status . The association was present in all age groups , among those with and without physical limitations , and also among those who did and did not also participate in more vigorous physical activities . Walking more than 4 hours/week was also associated with a reduced risk of death ( age and sex-adjusted relative risk = 0.73 ; 95 % confidence interval , 0.48 - 1.10 ) , however , this association was substantially diminished by adjustment for cardiovascular risk factors and measures of general health status . CONCLUSIONS Walking more than 4 hours/week may reduce the risk of hospitalization for cardiovascular disease events . The association of walking more than 4 hours/week with reduced risk of death may be mediated by effects of walking on other risk factors . These findings provide much stronger evidence than previously available for advising older men and women to embark on or maintain a sustained program of walking to prevent cardiovascular disease events", "PURPOSE To examine the long-term association of leisure time physical activity ( LTPA ) and risk of death from coronary heart disease ( CHD ) and all-causes . METHODS Data are from a prospect i ve study of 12,138 middle-aged men at high risk for CHD participating in the MRFIT . Men were classified into deciles based on average min/d of LTPA reported at baseline , which were compared with cumulative CHD and all-cause mortality endpoints at the 16-year follow-up . RESULTS Men in the least-active decile of LTPA who averaged 4.9 min/d of LTPA ( range 0 to .9 min/d ) had excess age-adjusted mortality rates of 29 % and 22 % for CHD and all-causes , respectively , as compared to those in combined deciles 2 to 4 , who averaged 22.7 min/d of predominantly light and moderate LTPA ( range 10 - 36 min/d ) . No further decrement in mortality rates was noted in those in the higher declines of LTPA . These associations remained significant ( P premature mortality , particularly from CHD , in middle-aged and older men at high risk for CHD", "BACKGROUND Whether the major components of leisure physical activity ( number of types , intensity , frequency , and duration ) have independent contribution to mortality reduction and there is a minimum amount of activity beneficial for the elderly remain unclear . METHODS The prospect i ve follow-up study aim ed at examining the relationship between exercise components and total mortality in general elderly population . A total of 2113 persons aged 65 and older participating in 2001 Taiwan National Health Interview Survey were studied . Information regarding leisure physical activity , its energy parameters , other factors at baseline , and vital status at the end of 2003 was analyzed with Cox model . RESULTS A total of 197 deaths occurred during a 2-year follow-up . Regular exercisers reduced 35 % risk of death compared with sedentary individuals after adjustment for covariates . Moreover , exercisers with a weekly amount of energy exceeding 1000 kcal had significant benefit of risk reduction when energy expenditure is considered . There was a significant dose-response relationship between number of activity and the reduction in total mortality . The benefit on mortality reduction among the three components of total energy amount was only observed in intensity . CONCLUSIONS For the amount of energy dedicated to leisure physical activity , older persons are recommended to expend at least 1000 kcal per week through regular exercise for mortality reduction . In addition to energy amount , protection of exercise against death also increases with the number of activities . Among the three components of total amount of energy , only intensity is significantly associated with mortality reduction", "PURPOSE We examined the association between cardiorespiratory fitness and stroke mortality in men . METHODS This is a prospect i ve cohort study . We followed 16,878 men , ages 40 - 87 yr , who had a complete medical evaluation including a maximal treadmill exercise test and self-reported health habits . There were 32 stroke deaths during an average of 10 yr of follow-up ( 167,961 man-yr ) . RESULTS After adjustment for age and examination year , there was an inverse association between cardiorespiratory fitness and stroke mortality ( P = 0.005 for trend ) . This association remained after further adjustment for cigarette smoking , alcohol intake , body mass index , hypertension , diabetes mellitus , and parental history of coronary heart disease ( P = 0.02 for trend ) . High-fit men ( most fit 40 % ) had 68 % ( 95 % CI : 0.12 , 0.82 ) and moderate-fit men had 63 % ( 95 % CI : 0.17 , 0.83 ) lower risk of stroke mortality when compared with low-fit men ( least fit 20 % ) , respectively . CONCLUSIONS Moderate and high levels of cardiorespiratory fitness were associated with lower risk of stroke mortality in men in the Aerobics Center Longitudinal study population" ]

[ "INTRODUCTION Up-to- date studies comparing endodontic treatment versus implant-supported prosthesis have shown similar clinical outcome and survival rates . However , no data are available comparing both treatment modalities based on the patient 's perception of quality of life . This study was design ed to qualitatively describe and compare the quality of life of patients with restored , single endodontically treated teeth versus patients with single implant-supported fixed prostheses . METHODS Forty-eight patients agreed to participate in the study ( n = 24 from each treatment modality ) . Of those , 37 actually participated in the study : 17 were endodontically treated and 20 had an implant-supported prosthesis . Patients in each of the two groups were r and omly selected from the Graduate Endodontics and Graduate Periodontics Departments , respectively . Six focus group discussion s ( n = 3 per treatment group ) were held and audio-recorded for subsequent thematic analysis . Data were analyzed to identify common themes within each category and compared to assess any differences in quality of life between the two treatments . Additionally , a quality of life survey , the shortened version of the Oral Health Impact Profile ( OHIP-14 ) , was given before the discussion group and the responses analyzed . RESULTS The results obtained from this study show similar overall OHIP scores and show a high rate of satisfaction with both treatment modalities . Content analysis of the discussion groups revealed several themes and subthemes . The major themes were importance of overall health , financial implication s of the treatments , perception of the treatments and its outcomes , time since treatment , and follow-up dental visits . CONCLUSIONS The results help identify patients ' perception and concerns with each treatment modality and assist the clinician and patient in the selection of an optimal treatment for their given situation . In addition to the prognosis and outcomes , clinicians should consider patients ' perceptions and preferences as well as the influence each therapy may have on their quality of life , both short- and long-term . Overall , all the participants in this study were pleased with the treatment received and expressed a clear message to save their natural dentition whenever possible", "INTRODUCTION : Pulpectomy of primary teeth is commonly carried out with h and files and broaches ; a tricky and time consuming procedure . The purpose of this in vitro study was to compare the cleaning efficacy and time taken for instrumentation of deciduous molars using h and K-files and Flex Master rotary system . MATERIAL S AND METHODS : In this study , 68 canals of 23 extracted primary molars with at least two third intact roots and 7 - 12 mm length were selected . After preparing an access cavity , K-file size # 15 was introduced into the root canal and India ink was injected with an insulin syringe . Sixty sample s were r and omly divided in to experimental groups in group I ( n=30 ) , root canals were prepared with h and K-files ; in group II ( n=30 ) , rotary Flex Master files were used for instrumentation , and in group III 8 remained sample s were considered as negative controls . After clearing and root sectioning , the removal of India ink from cervical , middle , and apical thirds was scored . Data was analyzed using student 's T-test and Mann-Whitney U test . RESULTS : There was no significant difference between experimental groups cleaning efficacy at the cervical , middle and apical root canal thirds . Only the coronal third scored higher in the h and instrumented group ( P Flex Master rotary files was significantly less time consuming ( P cleanliness efficacy at the apical and middle thirds , the coronal third was more effectively cleaned with h and files . Predictably , time efficiency was a significant advantage with rotary technique", "AIM To compare in vitro intracanal bacterial reduction using nickel-titanium rotary instruments with and without apical enlargement . METHODOLOGY Thirty-eight palatal roots of maxillary molar teeth , with mature apices were subdivided according to lengths and then r and omly assigned to two experimental and one control groups . The roots were sterilized and then reinfected with Enterococcus faecalis , which served as a bacteriological marker . All roots in the experimental groups were prepared in a step-down sequence with engine-driven GT rotary files at 350 rpm . In experimental group A ( n = 16 ) additional apical enlargement to ISO size 35 was performed . In group B ( n = 16 ) a serial step-back technique was followed with no apical enlargement . This was combined in groups A and B with irrigation with NaOCl and EDTA . In the control group ( group C , n = 6 ) irrigation only was carried out , with no mechanical preparation . Sample s were then taken from the root canals to determine the numbers of remaining bacteria . RESULTS In groups A and B , 15 ( 94 % ) and 13 ( 81 % ) specimens were rendered bacteria-free , respectively . In the control group C none of the specimens were bacteria-free . There was a significant difference ( P antibacterial effects of experimental and control regimens . There was , however , no significant difference ( P = 0.276 ) between the preparation methods used in the experimental groups . CONCLUSIONS There was no significant difference in intracanal bacterial reduction when Ni-Ti GT rotary preparation with NaOCl and EDTA irrigation was used with or without apical enlargement preparation technique . It may therefore not be necessary to remove dentine in the apical part of the root canal when a suitable coronal taper is achieved to allow satisfactory irrigation of the root canal system with antimicrobial agents", "OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review", "INTRODUCTION The aim of any root canal treatment is to achieve a canal free of micro organisms , residual pulp remnants , debris and smear layer for the long term success of the procedure . Manual and automated instrumentation techniques along with proper irrigation regime is used to arrive at the aforementioned goal . Many authors focused on the preparation capabilities of various manual and rotary instruments but very few investigators stressed on the actual cleaning abilities of these instruments . AIMS AND OBJECTIVES This study was undertaken to evaluate the cleaning efficiency of manual K flex files and rotary Pro File systems in the root canals using a scanning electron microscope . MATERIAL AND METHODS Thirty single rooted m and ibular first premolars were divided into two groups and r and omized ( the manual group-M and the ProFile group-P ) with respect to the preparation technique . The Manual group was h and instrumented with stainless steel K- Flexofiles by means of a conventional filing technique . The Pro File group was instrumented according to the manufacturer 's instructions using a rotary h and piece . All canals were shaped and cleaned under frequent irrigation with EDTA . Final irrigation was carried out with 3 mL of normal saline solution to neutralize the action of the irrigant . The roots were split , one half of each tooth was selected for further SEM technique analysis and examined under the scanning electron microscope . The canal walls were quantitatively evaluated for the amount of debris and smear layer . The apical , middle and coronal regions of the canal surface , were grade d ( 1 - 5 ) for debris and smear layer . A statistical analysis was performed using a Mann-Whitney Rank Sum test . ProFile performed least effective cleaning . Manual K-Flexofiles led to a grooved pattern . RESULTS AND CONCLUSION A statistically significant difference was observed ( p amount of debris and smear layer at the apical level . The manually filed canals had less debris and smear layer than those using a rotary technique . It was concluded from this study that none of the instrumentation techniques employed , produced the canal walls which were free of surface debris and smear layer . The manual instrumentation technique was better in cleaning the canals compared to the ProFile rotary Ni-Ti instruments despite the step-back technique used for manual instrumentation . How to cite this article : Manjunatha M , Kini A , Sudhakar V , Sunil K V C , Hiremath V K , Shah A. Smear Layer Evaluation on Root Canal Preparation with Manual and Rotary Techniques using EDTA as an Irrigant : A Scanning Electron Microscopy Study . J Int Oral Health 2013 ; 5(1):66 - 78", "BACKGROUND The purpose of this in-vitro study was to compare canal transportation and centering ability of Twisted and Hyflex Rotary Files with stainless steel h and k-flexofiles by using Spiral Computed Tomography . MATERIAL S & METHODS A total of 90 freshly extracted human m and ibular single rooted Premolar teeth were selected . The crowns were flattened with steel disks and a final dimension of 18-mm WL was achieved for each tooth . Canals were divided r and omly into 3 groups of 30 teeth each . Group I : Hyflex files , Group II : Twisted files , Group III : stainless steel h and k-flexofiles . Three sections from apical , mid-root , and coronal levels of the canal were recorded . All the teeth were scanned before and after instrumentation by using Spiral Computed Tomography . RESULTS K-files showed highest transportation and less centered when compared to the Twisted and Hyflex rotary files . No significant difference was found between TF and Hyflex CM instruments . CONCLUSION TF and Hyflex files shaped curved root canals without significant shaping errors when compared to the H and stainless steel k-flexofiles . How to cite this article : Kumar BS , Pattanshetty S , Prasad M , Soni S , Pattanshetty KS , Prasad S. An in-vitro Evaluation of canal transportation and centering ability of two rotary Nickel Titanium systems ( Twisted Files and Hyflex files ) with conventional stainless Steel h and K-flexofiles by using Spiral Computed Tomography . J Int Oral Health 2013;5(5):108 - 15", "AIM To investigate the probability of and factors influencing periapical status of teeth following primary ( 1 ° RCT x ) or secondary ( 2 ° RCT x ) root canal treatment . METHODOLOGY This prospect i ve study involved annual clinical and radiographic follow-up of 1 ° RCT x ( 1170 roots , 702 teeth and 534 patients ) or 2 ° RCT x ( 1314 roots , 750 teeth and 559 patients ) carried out by Endodontic postgraduate students for 2 - 4 ( 50 % ) years . Pre- , intra- and postoperative data were collected prospect ively on customized forms . The proportion of roots with complete periapical healing was estimated , and prognostic factors were investigated using multiple logistic regression models . Clustering effects within patients were adjusted in all models using robust st and ard error . RESULTS proportion of roots with complete periapical healing after 1 ° RCT x ( 83 % ; 95 % CI : 81 % , 85 % ) or 2 ° RCT x ( 80 % ; 95 % CI : 78 % , 82 % ) were similar . Eleven prognostic factors were identified . The conditions that were found to improve periapical healing significantly were : the preoperative absence of a periapical lesion ( P = 0.003 ) ; in presence of a periapical lesion , the smaller its size ( P ≤ 0.001 ) , the better the treatment prognosis ; the absence of a preoperative sinus tract ( P = 0.001 ) ; achievement of patency at the canal terminus ( P = 0.001 ) ; extension of canal cleaning as close as possible to its apical terminus ( P = 0.001 ) ; the use of ethylene-diamine-tetra-acetic acid ( EDTA ) solution as a penultimate wash followed by final rinse with NaOCl solution in 2 ° RCT x cases ( P = 0.002 ) ; abstaining from using 2 % chlorexidine as an adjunct irrigant to NaOCl solution ( P = 0.01 ) ; absence of tooth/root perforation ( P = 0.06 ) ; absence of interappointment flare-up ( pain or swelling ) ( P = 0.002 ) ; absence of root-filling extrusion ( P ≤ 0.001 ) ; and presence of a satisfactory coronal restoration ( P ≤ 0.001 ) . CONCLUSIONS Success based on periapical health associated with roots following 1 ° RCT x ( 83 % ) or 2 ° RCT x ( 80 % ) was similar , with 10 factors having a common effect on both , whilst the 11th factor ' EDTA as an additional irrigant ' had different effects on the two treatments", "OBJECTIVE The objective of this study was to evaluate the utility of digital image processing and analysis procedures for the study and comparison of the efficiency of 2 root canal instrumentation techniques . STUDY DESIGN Forty m and ibular incisors with a single canal were r and omly divided into 2 groups of 20 teeth . A step-back technique was followed for the instrumentation of the root canals of Group 1 teeth using h and stainless steel Hedström files ( Dentsply Maillefer , Switzerl and ) , while a crown-down technique using ProFile engine-driven nickel-titanium instruments ( Dentsply Maillefer ) was followed for the instrumentation of the Group 2 root canals . Radiographs of each tooth were taken in bucco-lingual and mesio-distal projections , both before and after instrumentation , under constant conditions and by using a direct digital intraoral radiography system . The postoperative radiographs were digitally subtracted from their respective preoperative radiographs . A contrast enhancement process was applied to the result ant digital subtractive images . The enlargement of the root canals created by each instrumentation technique regarding the apical 6 mm was assessed through the application of region segmentation and area measurement processes . RESULTS Using this methodology no significant difference between the 2 preparation techniques was found in terms of configuration and enlargement of the root canals . CONCLUSIONS The application of this methodology provided the ability to ( 1 ) visualize dentin lost during root canal instrumentation , ( 2 ) simultaneously compare root canal morphology before and after instrumentation , and ( 3 ) quantitatively evaluate the enlargement of the root canal area induced by each of the instrumentation techniques", "The purpose of this study was to compare intracanal bacterial reduction on teeth instrumented with 0.04 tapered nickel-titanium ( NiTi ) rotary instrumentation to bacterial reduction when using a stainless-steel K-file step-back technique using sterile saline irrigation . Forty-eight patients with apical periodontitis were r and omly assigned treatment type . The canals were sample d before , during , and after instrumentation . The sample s were incubated anaerobically for 7 days at 37 degrees C , colony-forming unit numbers calculated , and a log transformation performed to normalize the counts . Teeth exhibiting apical periodontitis were uniformly infected , whereas vital control teeth were not . A similar and uniform reduction occurred with progressive filing , regardless of technique ( p colony-forming unit count after NiTi rotary or stainless-steel h and instrumentation ( p = 0.42 ) . Neither technique could predictably render canals free of bacteria . The results of this study indicate NiTi rotary and stainless-steel h and K-file step-back instrumentation techniques were not significantly different in their ability to reduce intracanal bacteria", "Objectives The purpose of this study was to compare in-vitro the amount of debris extruded apically from extracted teeth , using K3 , Protaper rotary instruments and manual step-back technique . Methods Forty five human single-rooted m and ibular premolar teeth were r and omly divided into 3 groups . The teeth in 3 groups were instrumented until reaching the working length with K3 , Protaper rotary instruments and K-type stainless steel instruments with manual step-back technique , respectively . Debris extruded from the apical foramen was collected into centrifuge tubes and the amount was determined . The data obtained were analyzed using Kruskal-Wallis one-way analysis of variance and Mann-Whitney U tests , with P=.05 as the level for statistical significance . Results Statistically significant difference was observed between K3 , Protaper and step-back groups in terms of debris extrusion ( P mean debris weight , which was significantly different from the K3 and Protaper groups ( P mean debris weight was related to K3 group , which was significantly different from the Protaper group ( P debris extrusion . The engine-driven Ni-Ti systems extruded significantly less apical debris than step-back technique . However , Protaper rotary instruments extruded significantly more debris than K3 rotary instruments", "INTRODUCTION This study sought to present a st and ardized biofilm model in extracted teeth with an artificial apical groove to quantify the efficacy of h and , rotary nickel-titanium , and self-adjusting file ( SAF ) instrumentation in biofilm bacteria removal . METHODS Thirty-six extracted single-rooted teeth with oblong canals were selected . Each tooth was split longitudinally , and a 0.2-mm-wide groove was placed in the apical 2 to 5 mm of the canal . After growing mixed bacteria biofilm inside the canal under an anaerobic condition , the split halves were reassembled in a custom block , creating an apical vapor lock . Teeth were r and omly divided into 3 treatment groups ( n = 10 per group ) using the K-file , ProFile ( Dentsply Tulsa Dental Products , Tulsa , OK ) , and the SAF ( ReDent-Nova , Ra'anana , Israel ) . Irrigation consisted of 10 mL 3 % NaOCl and 4 mL 17 % EDTA . Six teeth received no treatment . Areas inside and outside the groove were examined using a scanning electron microscope . RESULTS The scanning electron microscope showed a consistently thick layer of biofilm grown in the canals of the control group after 4 weeks . Within the groove , a smaller area remained occupied by bacteria after the use of the SAF compared with the ProFile and the K-file ( 3.25 % , 19.25 % , and 26.98 % , respectively ; P bacteria were removed outside the groove than inside ( P .05 ) . CONCLUSIONS Although all techniques equally removed bacteria outside the groove , the SAF reduced significantly more bacteria within the apical groove . No technique was able to remove all bacteria . This biofilm model represents a potentially useful tool for the future study of root canal disinfection", "AIM The purpose of this study was to compare the periapical healing of molar root canal treatment using two instrumentation techniques . METHODS A total of 225 maxillary and m and ibular first and second permanent molars endodontically treated by undergraduate or postgraduate students were r and omly selected from a computerized hospital data base of which 110 molars had been prepared using a hybrid rotary technique with nickel-titanium instruments ( group NR ) and 115 with h and stainless steel files ( group HF ) . Patients were recalled and the teeth were examined both clinical ly and radiographically for signs of periapical inflammation . RESULTS Some 19 % and 39 % of teeth in the NR and HF group , respectively , were judged to have some form of procedural errors . A higher rate of periapical healing was noted for NR ( 77 % ) than the HF group ( 60 % ) ( p preoperative radiolucent lesion . CONCLUSION There was a higher incidence of procedural errors and a lower success rate for primary root canal treatment of teeth prepared with stainless steel files compared with the use of NiTi instruments in a continuous reaming action", "AIM To prospect ively determine the incidence of nickel-titanium rotary instrument fracture in an endodontic clinical practice setting . METHODOLOGY Eleven second year endodontic residents , using four nickel-titanium rotary instrument systems ( ProFile , ProTaper , GTRotary and K3Endo ) according to the recommendations of the manufacturers , instrumented 3181 canals in 1403 teeth of 1235 patients , in a dental school post-graduate endodontic clinic , in 1 year . The incidence of instrument fracture was determined based on the number of instruments used . When fracture occurred , data were collected concerning the type , size , taper and prior use of the fractured instruments , the length and location of the fragment within the root canal and the curvature of the canal . RESULTS The overall incidence of instrument fracture was 0.39 % . The incidence of fracture for ProFile , ProTaper , GTRotary and K3Endo files was 0.28 % , 0.41 % , 0.39 % and 0.52 % , respectively . There was no statistically significant difference between instrument systems . The percentage of teeth in which instruments fractured was 1.9 % ( 0.28 % for anterior teeth , 1.56 % for pre-molars and 2.74 % for molars ) . A total of 26 instruments fractured , of which 23 had tapers of 0.06 or greater . Most of the fragments were located in the apical third of the root canal , and both the median and mode amongst the fragment lengths were 2 mm . CONCLUSIONS The low incidence of nickel-titanium rotary instrument fracture supports the continued use of these instruments in root canal treatment", "AIM To assess the microflora of root canals in primary molars following use of rotary NiTi files and conventional h and NiTi and stainless steel files . STUDY DESIGN This r and omized clinical trial consisted of a total of 60 first and second primary molars requiring root canal treatment , who were selected from children aged 5 - 9 years . Based on type of root canal instrumentation , the teeth were r and omly assigned to three groups of twenty teeth each ; Group A : Rotary NiTi files , Group B : H and NiTi files and Group C : H and stainless steel files . Following administration of local anesthesia , isolation with rubber dam was carried out . For the purpose of instrumentation and sampling , the palatal canal of maxillary molars and the distal canal of m and ibular molars were selected . Prior to sampling , the orifices of other canals in these teeth were sealed , so as to prevent any contamination . Instrumentation was carried out in each group using respective instruments along with intermittent saline irrigation . Root canal sample s were obtained both before and after instrumentation , using sterile absorbent paper points and transferred to a sterile vial with transport fluid . Serial dilutions were prepared and cultured on suitable agar media . Both aerobic and anaerobic microbial counts were made . Data obtained was subjected to statistical analysis using Wilcoxon signed rank test and one-way Analysis of variance . RESULTS In all three groups , there was a significant reduction in both aerobic and anaerobic mean microbial count following root canal instrumentation . ( p Rotary NiTi files were as efficient as conventional h and instruments in significantly reducing the root canal microflora", "OBJECTIVE This study compared the bacterial reduction of in vitro infected root canals after instrumentation by 3 nickel-titanium ( NiTi ) rotary files with different taper and diameter versus manual stainless steel files . STUDY DESIGN Sixty-four single-rooted human teeth were infected with a suspension of Streptococcus sanguis measured by optical density . Teeth were divided r and omly into 4 groups of 16 and prepared with Flexofiles , GT rotary files , HERO 642 , and ProFile . Bacterial samplings were performed before ( S1 ) , during ( S2-S3 ) , and after ( S4 ) instrumentation . RESULTS All techniques significantly reduced the number of bacterial cells in the root canals ( P bacterial reduction , the results suggest that a manual stainless steel file preparation is as efficient as a NiTi rotary instrumentation . CONCLUSION Regardless of the root canal preparation technique , its taper , and diameter , the root dentin remained infected and was not bacteria-free at the end of the experiment", "OBJECTIVE The purpose of this study was to compare in vitro the amount of debris and irrigant extruded apically from extracted teeth , using manual technique and crowndown pressureless technique by K3 , RaCe , and FlexMaster instruments . STUDY DESIGN Sixty human single-rooted m and ibular premolar teeth were r and omly assigned to 4 groups , 15 teeth each . The teeth in 4 groups were instrumented until the working length with RaCe , K3 , FlexMaster , and K-type stainless steel instruments respectively . Debris and irrigant extruded from the apical foramen were collected into vials and the amounts were determined . The data obtained were analyzed using Kruskal-Wallis 1-way analysis of variance and Mann-Whitney U tests , with alpha = 0.05 as the level for statistical significance . RESULTS No statistically significant difference was observed among the groups in terms of debris extrusion ( P > .05 ) . On the other h and , a statistically significant difference was observed between K3 and manual technique groups in terms of irrigant extrusion ( P .05 ) . CONCLUSION Based on the results , all instrumentation techniques produced extruded debris and irrigant ; however , the engine-driven nickel-titanium systems were associated with less apical extrusion and irrigant", "AIM To investigate instrumentation time , working safety and the shaping ability of two rotary nickel-titanium ( NiTi ) systems ( Alpha System and ProTaper Universal ) in comparison to stainless steel h and instruments . METHODOLOGY A total of 45 mesial root canals of extracted human m and ibular molars were selected . On the basis of the degree of curvature the matched teeth were allocated r and omly into three groups of 15 teeth each . In group 1 root canals were prepared to size 30 using a st and ardized manual preparation technique ; in group 2 and 3 rotary NiTi instruments were used following the manufacturers ' instructions . Instrumentation time and procedural errors were recorded . With the aid of pre- and postoperative radiographs , apical straightening of the canal curvature was determined . Photographs of the coronal , middle and apical cross-sections of the pre- and postoperative canals were taken , and superimposed using a st and ard software . Based on these composite images the portion of uninstrumented canal walls was evaluated . RESULTS Active instrumentation time of the Alpha System was significantly reduced compared with ProTaper Universal and h and instrumentation ( P instrument fractures occurred in any of the groups . The Alpha System revealed significantly less apical straightening compared with the other instruments ( P Alpha System result ed in significantly less uninstrumented canal walls compared with stainless steel files ( P apical straightening effect could not be prevented ; areas of uninstrumented root canal wall were left in all regions using the various systems", "AIM The aim of this in vitro study was to compare the efficacy of root canal wall debridement following h and versus LightSpeed instrumentation . METHODOLOGY Twenty recently extracted single-rooted teeth were paired and r and omly placed into two treatment groups of 10 teeth each . In group 1 , a step-back instrumentation without initial coronal flaring with stainless steel Hedstroem files was used ; group 2 was instrumented with Ni-Ti LightSpeed instruments . Both groups had the same irrigation regimen : 2.5 % NaOCl and a 15 % EDTA solution . The teeth were then decoronated and each root split longitudinally into two halves to be examined using the scanning electron microscope ( SEM ) . The presence of superficial debris and smear layer was evaluated by a st and ardized grading system , and the result ing scores su bmi tted to nonparametric statistics . RESULTS Under the conditions of this study , the removal of superficial debris was generally excellent with both canal preparation techniques . Both techniques result ed in variable presence of residual smear layer , with a canal wall covered by smear layer as the predominant characteristic . Generally , the amount of smear layer was greater in the apical than in the middle third of the root , however , this difference was statistically significant ( P LightSpeed instruments was associated with significantly more ( P smear layer presence in the middle region of the root when compared with h and instrumentation . In addition , less smear layer was present in the apical region following LightSpeed instrumentation than stainless steel h and files , but this difference was not statistically significant . Differences in debridement between the two halves of the same root were more evident with LightSpeed than manual instrumentation , however , there was no statistical significance . CONCLUSIONS It may be inferred that the choice between h and and LightSpeed instrumentation should be based on factors other than the amount of root canal debridement , which does not vary significantly according to the instruments used", "INTRODUCTION The purpose of this study was to compare canal transportation and centering ability of 2 rotary nickel-titanium ( NiTi ) systems ( Twisted Files [ TF ] and Pathfile-ProTaper [ PP ] ) with conventional stainless steel K-files . METHODS Ninety root canals with severe curvature and short radius were selected . Canals were divided r and omly into 3 groups of 30 each . After preparation with TF , PP , and stainless steel files , the amount of transportation that occurred was assessed by using computed tomography . Three sections from apical , mid-root , and coronal levels of the canal were recorded . Amount of transportation and centering ability were assessed . The 3 groups were statistically compared with analysis of variance and Tukey honestly significant difference test . RESULTS Less transportation and better centering ability occurred with TF rotary instruments ( P highest transportation followed by PP system . PP system showed significant transportation when compared with TF ( P TF system was found to be the best for all variables measured in this study", "AIM To compare the cleaning ability and preparation time of rotary instruments ( Mtwo ) and conventional manual instruments ( K-file ) in preparing primary and permanent molar root canals . MATERIAL S AND METHODS Access cavities were prepared in 70 primary and 70 permanent teeth and India ink was injected into 120 canals of selected molars . The teeth were r and omly divided into two main subgroups ( n=20 ) and three control groups ( n=10 ) . In each of these main subgroups , either the manual instrument ( K-file ) or the rotary system ( Mtwo ) was used to prepare root canals . After cleaning the canals and clearing the teeth , dye removal was evaluated with the help of a stereomicroscope . In addition , the time needed for root canal preparation was recorded by a chronometer . STATISTICAL ANALYSIS Statistical analyses were done using the Kruskal-Wallis , Mann-Whitney and t tests . RESULTS With regard to the cleaning ability of root canals , there were no significant differences between the K-file and Mtwo rotary system in primary and permanent teeth in the apical , middle or coronal third of the canals . Moreover , there were no significant differences between primary and permanent teeth prepared with K-files and rotary instruments . In all the groups , shorter times were recorded with the rotary technique . The working time was shorter in primary than in permanent teeth . CONCLUSION The Mtwo rotary system showed acceptable cleaning ability in both primary and permanent teeth , and achieved results similar to those of K-files in less time", "INTRODUCTION Nickel-titanium rotary instruments reduce procedural errors and the time required to finish root canal preparation . The goal of this study was to evaluate the occurrences of apical transportation and canal aberrations produced with different instruments used to create a glide path in the preparation of curved root canals , namely manual K-files ( Dentsply Maillefer , Ballaigues , Switzerl and ) and PathFile ( Dentsply Maillefer ) and Mtwo ( Sweden and Martina , Padua , Italy ) nickel-titanium rotary files . METHODS The mesial canals of 45 m and ibular first and second molars ( with curvature angles between 25 ° and 35 ° ) were selected for this study . The specimens were divided r and omly into 3 groups with 15 canals each , and canal preparation was performed by an endodontist using # 10 - 15 - 20 K-type stainless steel manual files ( group M ) , # 13 - 16 - 19 PathFile rotary instruments ( group PF ) , and # 10 - 15 - 20 Mtwo rotary instruments ( group MT ) . The double digital radiograph technique was used , pre- and postinstrumentation , to assess whether apical transportation and /or aberration in root canal morphology occurred . The initial and final images of the central axis of the canals were compared by superimposition through computerized analysis and with the aid of magnification . The specimens were analyzed by 3 evaluators , whose calibration was checked using the Kendall agreement test . RESULTS No apical transportation or aberration in root canal morphology occurred in any of the teeth ; therefore , no statistical analysis was conducted . CONCLUSIONS Neither the manual instruments nor the PathFile or Mtwo rotary instruments used to create a glide path had any influence on the occurrence of apical transportation or produced any canal aberration" ]

[ "OBJECTIVES Although most infants born prematurely do not have major developmental problems , those with perinatal medical problems and lengthy stays in the neonatal intensive care unit are at risk for sensory modulation problems and developmental sequelae . This study compared sensory responsiveness in preterm and full-term infants and examined the relationship of sensory responsiveness to temperament and developmental function . METHOD Caregivers of infants with ( n = 45 ) and without ( n = 22 ) prematurity were asked to complete the Sensory Rating Scale . The preterm infants were also evaluated with the Bayley Scales of Infant Development , Second Edition ( BSID-II ) . RESULTS The preterm infants exhibited more frequent behaviors indicating tactile defensiveness and difficult temperament than did the full-term infants . When specific items were examined , the preterm infants displayed sensory-seeking behaviors and high activity levels . As measured by caregivers ' report , sensory responsiveness was significantly related to temperament . It was not related to BSID-II Mental and Psychomotor scale scores . CONCLUSION This study supports the findings of others that preterm infants have mild problems in sensory responsiveness and temperament . Correlational results do not support a definitive relationship between parents ' reports of their infants ' sensory responsiveness and developmental function", "OBJECTIVE To evaluate the effects of the Infant Behavioral Assessment and Intervention Program ( © ) ( IBAIP ) in very low birth weight infants on sensory processing and daily activities at preschool age . STUDY DESIGN Follow-up of children included in a r and omized controlled trial . Eighty-six infants were enrolled in post-discharge IBAIP until 6 months corrected age , and 90 infants received st and ard care . At 3.5 years of age , the Sensory Profile-Dutch version ( SP-NL ) and Pediatric Evaluation of Disability Inventory-Dutch version ( PEDI-NL ) were administered . For comparison , parents of 41 term-born children also completed the SP-NL . RESULTS Seventy-six children ( 88 % ) in the IBAIP group and 75 children ( 83 % ) children in the control group were examined at 44 months corrected age . After adjustment for pre-r and omization differences in perinatal characteristics , the IBAIP group outperformed the control group significantly on SP-NL domains of oral sensory processing and sensory processing related to endurance/tone and PEDI-NL domains of mobility . The control group only scored significantly lower than the term group on the SP-NL domain endurance/tone . The very low birth weight groups performed significantly below the PEDI-NL 's norm . CONCLUSION In line with the positive developmental effects of the IBAIP until 24 months corrected age , independency in mobility in daily activities was improved at 3.5 years", "Abstract Alterations in neural activity due to pain and injury in early development may produce long‐term effects on sensory processing and future responses to pain . To investigate persistent alterations in sensory perception , we performed quantitative sensory testing ( QST ) in extremely preterm ( EP ) children ( n = 43 ) recruited from the UK EPICure cohort ( born less than 26 weeks gestation in 1995 ) and in age and sex matched term‐born controls ( TC ; n = 44 ) . EP children had a generalized decreased sensitivity to all thermal modalities , but no difference in mechanical sensitivity at the thenar eminence . EP children who also required neonatal surgery had more marked thermal hypoalgesia , but did not differ from non‐surgical EP children in the measures of neonatal brain injury or current cognitive ability . Adjacent to neonatal thoracotomy scars there was a localized decrease in both thermal and mechanical sensitivity that differed from EP children with scars relating to less invasive procedural interventions or from those without scars . No relationship was found between sensory perception thresholds and current pain experience or pain coping styles in EP or TC children . Neonatal care and surgery in EP children are associated with persistent modality‐specific changes in sensory processing . Decreases in mechanical and thermal sensitivity adjacent to scars may be related to localized tissue injury , whereas generalized decreases in thermal sensitivity but not in mechanical sensitivity suggest central ly mediated alterations in the modulation of C‐fibre nociceptor pathways , which may impact on responses to future pain or surgery", "Although many perinatal factors have been linked to adverse neurodevelopmental outcomes in very premature infants , much of the variation in outcome remains unexplained . The impact on brain development of 1 potential factor , exposure to stressors in the neonatal intensive care unit , has not yet been studied in a systematic , prospect i ve manner", "OBJECTIVE To investigate the effects of early experience on brain function and structure . METHODS A r and omized clinical trial tested the neurodevelopmental effectiveness of the Newborn Individualized Developmental Care and Assessment Program ( NIDCAP ) . Thirty preterm infants , 28 to 33 weeks ' gestational age ( GA ) at birth and free of known developmental risk factors , participated in the trial . NIDCAP was initiated within 72 hours of intensive care unit admission and continued to the age of 2 weeks , corrected for prematurity . Control ( 14 ) and experimental ( 16 ) infants were assessed at 2 weeks ' and 9 months ' corrected age on health status , growth , and neurobehavior , and at 2 weeks ' corrected age additionally on electroencephalogram spectral coherence , magnetic resonance diffusion tensor imaging , and measurements of transverse relaxation time . RESULTS The groups were medically and demographically comparable before as well as after the treatment . However , the experimental group showed significantly better neurobehavioral functioning , increased coherence between frontal and a broad spectrum of mainly occipital brain regions , and higher relative anisotropy in left internal capsule , with a trend for right internal capsule and frontal white matter . Transverse relaxation time showed no difference . Behavioral function was improved also at 9 months ' corrected age . The relationship among the 3 neurodevelopmental domains was significant . The results indicated consistently better function and more mature fiber structure for experimental infants compared with their controls . CONCLUSIONS This is the first in vivo evidence of enhanced brain function and structure due to the NIDCAP . The study demonstrates that quality of experience before term may influence brain development significantly", "After birth , preterm infants face a stressful environment , which may negatively impact early brain development and subsequent neurobehavioral outcomes . This r and omized controlled trial involving 45 women with infants , assessed the effectiveness of training parents in reducing stressful experiences . Intervention consisted of 10 sessions in the Neonatal Intensive Care Unit ( NICU ) . Postintervention , at term-equivalent ( 40-wk postmenstrual age ) , magnetic resonance imaging ( MRI ) was performed to evaluate brain structure and development . Quantitative volumetric techniques were used to estimate overall and regional brain volumes for different tissue types including CSF , CGM , DNGM , UWM , and MWM . DTI was used to evaluate the integrity and maturation of white matter by ADC and FA . Maturation and connectivity of white matter , characterized by diffusion MR measures of ADC and FA , were significantly enhanced in the intervention group , who displayed greater restriction in ADC and increase in FA . There were no significant effects on either brain volumes or on short-term medical outcomes . Thus , sensitivity training for parents in the NICU is associated with improved cerebral white matter micro-structural development in preterm infants", "OBJECTIVE To investigate the effectiveness of individualized developmental care in reducing medical and neurodevelopmental sequelae for very low-birth-weight infants . DESIGN R and omized controlled trial . SETTING Newborn intensive care unit . PATIENTS Thirty-eight singleton preterm infants , free of known congenital abnormalities , weighing less than 1250 g , born before 30 weeks ' gestation , mechanically ventilated within 3 hours of delivery and for more than 24 hours in the first 48 hours , r and omly assigned to a control or an experimental group . INTERVENTION Caregiving by nurses specifically trained in individualized developmental care ; observation and documentation of the infants ' behavior within 12 hours of admission , and subsequently every 10th day ; developmental care recommendations and ongoing clinical support for the nurses and parents based on regular observation of the infant by developmental specialists ; and the availability of special caregiving accessories . MAIN OUTCOME MEASURES Medical outcome , including average daily weight gain ; number of days the infant required mechanical ventilation , oxygen , gavage tube feeding , and hospitalization ; severity of retinopathy of prematurity , bronchopulmonary dysplasia , pneumothorax , and intraventricular hemorrhage ; pediatric complications ; age at discharge ; and hospital charges . Neurodevelopmental outcome , including Assessment of Preterm Infants ' Behavior scale and quantified electroencephalography ( 2 weeks after due date ) ; and Bayley Scales of Infant Development and Kangaroo Box Paradigm ( 9 months after due date ) . RESULTS The infants in the experimental group had a significantly shorter duration of mechanical ventilation and supplemental oxygen support ; earlier oral feeding ; reduced incidence of intraventricular hemorrhage , pneumothorax , and severe bronchopulmonary dysplasia ; improved daily weight gain ; shorter hospital stays ; younger ages at hospital discharge ; and reduced hospital charges compared with the infants in the control group . At 2 weeks after their due date s , these infants also showed improved autonomic regulation , motor system functioning , self-regulatory abilities , and visual evoked potential measures ; and at 9 months , they had improved Bayley Mental and Psychomotor Developmental Index scores , as well as Kangaroo Box Paradigm scores . CONCLUSION Very low-birth-weight preterm infants may benefit from individualized developmental care in the neonatal intensive care unit in terms of medical and neurodevelopmental outcome", "The aim of the study was to prospect ively assess the differences in participation and sensory modulation between late preterm infants ( LPI ) and term babies , and to predict it by LPI characteristics . The study population includes 124 late preterm infants at gestational age between 34 and 35 6/7 weeks who were born at the same medical center . The control group comprised of 33 term babies ( 18 boys , 15 girls ) , born during the same period and location ( mean age 12.47 , SD = 0.73 ) . Sensory modulation was assessed by the test of sensory functions in infants and the infant/toddler sensory profile and for assessment of participation and parents ' satisfaction we used question naires . Term infants had better sensory modulation than LPI . Approximately 10 % of the sensory modulation of participants in the study was explained by gestational age and head circumference . LPI participation and parental satisfaction decreased in the LPI group . Among all the explanatory variables only multiple gestations and head circumference contributed to the explained variance of participation ( 16 % ) , and parents ' satisfaction ( 13 % ) . At age of 1 year , children born as late preterm are at increased risk of developing sensory modulation disorder , showing less participation , and result ing in less parental satisfaction", "Background Sensory experience is the basis for learning in infancy . In older children , abnormal sensory reactivity is associated with behavioural and developmental disorders . We hypothesised that in preterm infants , abnormal sensory reactivity during infancy would be associated with perinatal characteristics and correlate with 2-year neurodevelopmental outcomes . Methods We conducted a prospect i ve observational study of infants with birth weight ≤1500 g using the Test of Sensory Function in Infants ( TSFI ) in the first year . Infants with gestational age ≤30 weeks were tested with the Bayley Scales of Infant and Toddler Development III ( BSID III ) at 24 months . Results Of the 72 participants evaluated at 4–12 months corrected age ( median 8 months ) , 59 ( 82 % ) had a least one TSFI score concerning for abnormal sensory reactivity . Lower gestational age was associated with abnormal reactivity to deep pressure and vestibular stimulation ( p . Poor ocular-motor control predicted worse cognitive and motor scores in early childhood ( OR 16.7 ; p=0.004 ) , but was tightly correlated to the presence of severe white matter injury . Poor adaptive motor function in response to tactile stimuli predicted worse BSID III motor ( p=0.01 ) and language scores ( p=0.04 ) at 2 years , even after adjusting for confounders . Conclusions Abnormal sensory reactivity is common in preterm infants ; is associated with immaturity at birth , severe white matter injury and lower primary caregiver education ; and predicts neurodevelopmental delays . Early identification of abnormal sensory reactivity of very preterm infants may promote parental support and education and may facilitate improved neurodevelopment", "OBJECTIVES To determine the mortality and morbidity for infants weighing 401 to 1500 g ( very low birth weight [ VLBW ] ) at birth by gestational age , birth weight , and gender . STUDY DESIGN Perinatal data were collected prospect ively on an inborn cohort from January 1995 through December 1996 by 14 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports . Sociodemographic factors , perinatal events , and the neonatal course to 120 days of life , discharge , or death were evaluated . RESULTS Eighty four percent of 4438 infants weighing 501 to 1500 g at birth survived until discharge to home or to a long-term care facility ( compared with 80 % in 1991 and 74 % in 1988 ) . Survival to discharge was 54 % for infants 501 to 750 g at birth , 86 % for those 751 to 1000 g , 94 % for those 1001 to 1250 g , and 97 % for those 1251 to 1500 g . The incidence of chronic lung disease ( CLD ; defined as receiving supplemental oxygen at 36 weeks ' postmenstrual age ; 23 % ) , proven necrotizing enterocolitis ( NEC ; 7 % ) , and severe intracranial hemorrhage ( ICH ; grade III or IV ; 11 % ) remained unchanged between 1991 and 1996 . Furthermore , 97 % of all VLBW infants and 99 % of infants weighing weights less than the 10th percentile at 36 weeks ' postmenstrual age . Mortality for 195 infants weighing 401 to 500 g was 89 % , with nearly all survivors developing CLD . Mortality in infants weighing 501 to 600 g was 71 % ; among survivors , 62 % had CLD , 35 % had severe ICH , and 15 % had proven NEC . CONCLUSIONS Survival for infants between 501 and 1500 g at birth continued to improve , particularly for infants weighing survival was not associated with an increase in major morbidities , because the incidence of CLD , proven NEC , and severe ICH did not change . However , poor postnatal growth remains a major concern , occurring in 99 % of infants weighing Mortality and major morbidity ( CLD , severe ICH , and NEC ) remain high for the smallest infants , particularly those weighing < 600 g at birth", "Objective : To study whether new pharmacological and nonpharmacological guidelines lowered numbers of painful procedures in neonates and changed the amount and frequency of analgesic therapy as compared to the results of our previous study in 2001 . Design : A prospect i ve observational study . Setting : Level III NICU of the Erasmus MC-Sophia Children 's Hospital , Rotterdam . Participants : Neonates admitted at postnatal ages less than 3 days with length of stay at least 72 h. Main Outcome Measures : Number of all potentially painful procedures and analgesic therapy recorded at the bedside during the first 14 days of NICU stay . Results : A total number of 21,076 procedures were performed in the 175 neonates studied during 1,730 patient-days ( mean 12.2 ) . The mean number of painful procedures per neonate per day was 11.4 ( SD 5.7 ) , significantly lower than the number of 14.3 ( SD 4.0 ) in 2001 ( p use of analgesics was 36.6 % compared to 60.3 % in 2001 . Sixty-three percent of all peripheral arterial line insertions failed versus 37.5 % in 2001 and 9.1 % venipunctures failed versus 21 % in 2001 . Conclusions : The mean number of painful procedures per NICU patient per day declined . Nonpharmacological pain- or stress-reducing strategies like NIDCAP and sucrose were fully embedded in our pain management . As further reduction of the number of painful procedures is unlikely , we should apply more nonpharmacological interventions and explore newer pharmacological agents" ]

[ "Recent studies have suggested a differential influence of mean pressure and pulse pressure on myocardial infa rct ion and stroke , and differences among the major drugs in their efficacy at preventing these individual endpoints . We hypothesized that antihypertensive drugs have differing influences upon the pulse wave even when their effects on blood pressure are the same . We studied 30 untreated hypertensive patients , aged 28 - 55 years , who were rotated through six 6-week periods of daily treatment with amlodipine 5 mg , doxazosin 4 mg , lisinopril 10 mg , bisoprolol 5 mg , bendrofluazide 2.5 mg or placebo . The best drug was repeated at the end of the rotation . Blood pressure readings and radial pulse tonometry ( by Sphygmocor ) were performed at each visit , and blood was taken for measurement of levels of atrial natriuretic peptide and brain natriuretic peptide ( BNP ) . The Sphygmocor derivation of the central aortic pulse wave was used to measure time for transmission of the reflected wave ( T(R ) ) and the augmentation index ( AI ) , which is the proportional increase in systolic pressure due to the reflected wave . There was a dissociation between the effects of the drugs on blood pressure and pulse wave analysis . Bisoprolol caused the greatest falls in blood pressure and T(R ) , but was the only drug to increase AI . This paradoxical response to bisoprolol was associated with a 3-fold increase in plasma BNP levels . There was a smaller elevation of BNP in women compared with men , as described previously , and this elevation also was associated with significantly higher values of AI . Other drugs reduced AI , and this was associated with a significant decrease in BNP by amlodipine . In conclusion , antihypertensive drugs differ in their short-term effects on augmentation of the systolic pulse wave and secretion of BNP from the heart , regarded as a sensitive measure of strain on cardiomyocytes . These differences may help to explain cause-specific differences in outcome in recent trials", "The 24‐h blood pressure control of bisoprolol , a new beta1‐selective , beta‐blocking agent , was studied in 240 mild to moderate hypertensive patients in this 4‐week , r and omized , double‐blind , placebo‐controlled trial . A once‐daily dosing schedule was evaluated by comparing bisoprolol 's antihypertensive effectiveness and safety at 24 h postdose and 3 h postdose , the latter time intended to correspond to peak effectiveness . Results from this trial demonstrated the antihypertensive effectiveness of once‐daily bisoprolol at doses ranging from 5‐20 mg . Mean reductions from baseline diastolic blood pressure , measured 24 h postdose , were 6.3,8.8 , and 10.1 mmHg for patients receiving bisoprolol 5 , 10 , and 20 mg , respectively , compared with 1.6 mmHg for placebo‐treated patients ( p ; mean reductions from baseline systolic blood pressure for the bisoprolol groups were 8.6 , 8.6 , and 10.9 mmHg , respectively , versus 3.3 mmHg for placebo ( p≤0.01 ) ; and mean reductions from baseline heart rate for the bisoprolol groups were 5.1,7.1 , and 10.2 beats/min , respectively , compared with a 0.9 beats/min increase in heart rate for the placebo group ( p The response rates for bisoprolol‐treated patients ranged from 47 to 70 % compared with 18 % for patients on placebo ( p were dose‐related and sustained over the 24‐h dosing interval . Near maximal antihypertensive effects were achieved within 1 week of initiation of therapy with bisoprolol and were sustained over the course of the trial", "Summary Carvedilol 12.5 , 25 and 50 mg was administered once daily for 4 weeks to patients with mild to moderate hypertension . The purpose of the study was to investigate the antihypertensive action of carvedilol when administered once daily and to investigate the pharmacokinetics of carvedilol in patients with mild to moderate hypertension . Measurable decreases in blood pressure ( BP ) occurred within 1 hour after the first dose . Peak decreases in supine diastolic blood pressure ( DBP ) were 9.0 ± 6.8 , 15.5 ± 6.7 , 14.7 ± 10.6 and 22.5 ± 7.6 mm Hg ( ± SD ) for the placebo , 12.5 , 25 and 50 mg carvedilol groups , respectively , and occurred between 3 and 7 hours after the dose . Administration of carvedilol once daily for 4 weeks kept supine DBP below baseline levels for 24 hours . Trough supine DBP after 4 weeks of treatment were 0.6 ± 6.5 , 7.3 ± 7.9 , 8.8 ± 7.4 and 12.1 ± 3.8 mm Hg ( ± SD ) below baseline . Serum levels of carvedilol were proportional to the dose . Peak serum levels were 39 ± 27 , 75 ± 38 and 161 ± 131 μ/L for carvedilol 12.5 , 25 and 50 mg . The kinetics of carvedilol did not change with repeated administration . Carvedilol was well tolerated ; 2 patients experienced dizziness associated with postural hypotension after administration of the 50 mg dose . Carvedilol 12.5 , 25 and 50 mg effectively reduced BP for 24 hours when administered once daily", "OBJECTIVES To investigate prospect ively the effects of the selective beta 1 adrenoceptor blocker bisoprolol on sexuality of men with hypertension . DESIGN In newly diagnosed patients ( group I ) : double-blind , crossover , placebo controlled . In men with hypertension on antihypertensive treatment ( group II ) : crossover design . SETTING Large area in and around Rotterdam , The Netherl and s. PATIENTS Twenty-six men ( criteria : between 25 and 70 ; no disease etc . known to affect sexual functioning ) were recruited through their general practitioners . Group I ( n = 13 ) fulfilled the selection criteria , sitting blood pressure systolic > or = 160 mm Hg and /or diastolic > or = 95 mm Hg , measured on 3 different days . Group II ( n = 13 ) patients already on antihypertensive treatment . MAIN OUTCOME MEASURES Data on blood pressure . Qualitative and quantitative data on sexuality through question naires , including personal and sexual history , sexual functioning , sexual satisfaction and erectile difficulties . RESULTS Bisoprolol is an effective antihypertensive drug with no detrimental effects on sexuality in newly diagnosed men with hypertension . In men already on antihypertensive medication bisoprolol improved sexuality in some parameters , i.e. firmness of erection during coitus , contentedness with sexual functioning and satisfaction with own sexuality . CONCLUSION Bisoprolol is an effective antihypertensive agent with no sexual side effects", "Objective Hypertension guidelines recommend initial treatment with a β-blocker or diuretic and adding the other drug where blood pressure is not controlled . We hypothesized that systematic rotation through the major classes of antihypertensive drugs would demonstrate substantial differences in the pattern of an individual patient 's response , and suggest a more rational approach to choosing best treatment . Design Thirty-four young hypertensives ( age 28–55 , median 47 ) rotated in a double-blind , Latin-square , crossover fashion through 6 weeks of treatment each with amlodipine , doxazosin , lisinopril , bisoprolol , bendrofluazide and placebo . Blood pressure was measured at each visit . ‘ Best ’ drug , defined by efficacy and tolerability , was repeated at the end . Results Rotation doubled the number of patients reaching target blood pressure ( systolic the blood pressure on ‘ best ’ drug was at least 10 mmHg lower than on any other . Response to the ‘ best ’ drug was highly correlated ( r = 0.79 ) with its previous administration . By contrast , there were only weak correlations between responses to pairs of drugs , except for angiotensin-converting enzyme ( ACE ) inhibitor ( A ) with β-blocker ( B ) , and calcium blocker ( C ) with diuretic ( D ) – each r = 0.71 , P the renin system ( A and B ) . Conclusions Patients vary reproducibly in their response to initial treatment , and switching among drugs can increase the efficacy of monotherapy . The results support an AB/CD scheme for choosing therapy , in which the first drug is taken from one of these pairs , and uncontrolled patients switch to one of the other pair", "Beta-blockers with pharmacologic effects that differ from conventional agents might add to antihypertensive treatment options . This study evaluated a new once-daily formulation of the beta-/alpha1-blocker , carvedilol controlled-release ( CR ) , in hypertensive patients off treatment or while still taking up to 2 ( non-beta-blocker ) agents . After a 4-week run-in phase , patients were r and omized either to placebo ( n=76 ) or carvedilol CR 20 mg ( n=82 ) , 40 mg ( n=76 ) , or 80 mg ( n=86 ) once daily . After 6 weeks of treatment , ambulatory blood pressure monitoring was repeated to measure the primary end point of changes in mean 24-hour diastolic blood pressure . During treatment , 24-hour diastolic blood pressure fell in the placebo and carvedilol CR 20-mg , 40-mg , and 80-mg groups by ( mean + /- SE ) 0.4+/-0.9 , 4.4+/-0.9 , 7.9+/-0.9 , and 9.6+/-0.9 mm Hg , respectively ( P 24-hour systolic blood pressure changes were 0.6+/-1.4 , 6.8+/-1.3 , 10.1+/-1.4 , and 12.5+/-1.3 mm Hg , respectively ( P Diastolic blood pressure trough-to-peak ratios ( placebo-corrected ) based on ambulatory blood pressure monitoring ( trough = mean of 20- to 24-hour post-dose readings ; peak = mean of 3- to 7-hour post-dose readings ) for 20-mg , 40-mg , and 80-mg doses were 0.73 , 0.64 , and 0.65 , respectively . Adverse events , including clinical chemistry values , were similar in the drug-treated and placebo groups . Carvedilol CR has a clinical ly meaningful defined dose-dependent antihypertensive effect that persists throughout a 24-hour period", "This 30-center , r and omized , double-blind , placebo-controlled , parallel-group study was design ed to ( 1 ) establish that 6.25 mg of hydrochlorothiazide ( HCTZ ) given once daily with 5 mg of bisoprolol fumarate can contribute to antihypertensive effectiveness in patients with stage I and stage II ( mild to moderate ) systemic hypertension ; and ( 2 ) assess whether this formulation was more effective or possessed a safety advantage over st and ard monotherapy with bisoprolol or 25 mg of HCTZ . Results showed that HCTZ 6.25 mg contributed significantly to the antihypertensive effectiveness of bisoprolol 5 mg . Bisoprolol 5 mg/HCTZ 6.25 mg ( B5/H6.25 ) produced significantly greater mean reductions from baseline in sitting systolic and diastolic blood pressure ( -15.8 mm Hg/-12.6 mm Hg ) than bisoprolol 5 mg alone ( -10.0 mm Hg/-10.5 mm Hg ) and HCTZ 25 mg alone ( -10.2 mm Hg/-8.5 mm Hg ) . A 73 % response rate was achieved with the low-dose formulation compared with 61 % for the bisoprolol 5 mg ( B5 ) group and 47 % for the HCTZ 25 mg ( H25 ) group . B5/H6.25 was found to be significantly more effective than B5 or H25 in all subgroups of patients , regardless of gender , race , age , or smoking history . Antihypertensive effects were maintained during the 24-hour dosing interval . The incremental effectiveness of B5/H6.25 was not accompanied by an increase in the frequency or severity of adverse experiences ; the incidence of adverse experiences in the B5/H6.25 group was comparable to that in the placebo group . B5/H6.25 was shown to provide safety advantages over H25 , as shown by less hypokalemia ( < 1 % with B5/H6.25 versus 6.5 % with H25 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "Blood pressure , heart rate , common carotid and brachial arterial hemodynamics using pulsed Doppler flowmetry and pulse wave velocity determinations were evaluated using a double-blind crossover design versus placebo in 14 patients with sustained essential hypertension treated by the selective beta 1 blocking agent bisoprolol . Blood pressure and heart rate significantly decreased after bisoprolol , whereas no significant change occurred in the diameter , the blood flow and in the vascular resistance of the carotid and brachial circulations . Pulse wave velocity significantly decreased in the brachioradial and the carotid femoral areas . The decrease in the latter was -1.6 + /- 0.8 m/s with bisoprolol and -0.06 + /- 0.80 m/s with placebo ( p = 0.001 ) . Brachial artery compliance significantly increased from 117 + /- 49 to 205 + /- 84 cm4 x dynes-1 x 10(9 ) ( p = 0.001 ) , indicating that the antihypertensive effect of beta 1 blockade is associated with an improvement in the viscoelastic properties of the brachial artery wall" ]

[ "Nondirective ( ND ) , applied relaxation ( AR ) , and cognitive behavioral ( CBT ) therapies for generalized anxiety disorder ( GAD ) were compared . The latter 2 conditions were generally equivalent in outcome but superior to ND at post assessment . The 3 conditions did not differ on several process measures , and ND created the greatest depth of emotional processing . Follow-up results indicated losses in gains in ND , maintained gains in the other 2 conditions , especially CBT , and highest endstate functioning for CBT . AR and CBT thus contain active ingredients in the treatment of GAD ; support exists for further development of imagery exposure methods or cognitive therapy because of their likely role in promoting maintenance of change with this disorder . Expectancy for improvement was also associated with outcome , suggesting the need for further research on this construct for underst and ing the nature of GAD and its amelioration", "OBJECTIVE This report examines the impact of panic disorder and /or generalized anxiety disorder on quality of life and the implication s of these findings on nosological categories . METHOD A total of 357 subjects with a current episode of panic disorder and /or generalized anxiety disorder were diagnosed according to DSM-III-R criteria , using structured clinical interviews , as part of a prospect i ve , naturalistic , longitudinal , multicenter study of a clinical population with anxiety disorders . RESULTS There was a high degree of coexistence of anxiety disorders and major depressive disorder . Subjects with generalized anxiety disorder almost universally had other disorders , were the most likely to have at least one other anxiety disorder or major depressive disorder at intake , had the earliest age at onset , and had the worst emotional health rating . Subjects with panic disorder without agoraphobia had the most likelihood of a history of alcohol abuse . Nine percent of the subjects had a history of suicide attempts or gestures . CONCLUSIONS The subjects showed significant impairment in quality of life . The highly frequent coexistence of other anxiety disorders with generalized anxiety disorder and the overall lack of differences on many quality of life measures raise questions of nosology , particularly for generalized anxiety disorder", "A previous paper , Butler and Anastasiades ( Behaviour Research and Therapy 26 , 531 - 534 , 1988 ) presented evidence for three reliable predictors of response to Anxiety Management in patients with generalised anxiety disorder . It was argued there that these reflected severity of anxiety , demoralisation and depression . A second study ( Butler , Fennell , Robson & Gelder , Journal of Consulting and Clinical Psychology , 59 , 167 - 175 , 1991 ) has compared two treatments for GAD : Behaviour Therapy and Cognitive Behaviour Therapy . Data from this study is used here to answer two questions : ( i ) do the same three variables predict outcome in the second study ? The answer to this question is ' no ' ; and ( ii ) which variables contribute to prediction of outcome when these two treatments are compared ? Information presented here suggests that this depends partly on the nature of the treatment given . Outcome after behaviour therapy is predicted by initial levels of anxiety only , but the gains made are also relatively modest . Outcome after cognitive behaviour therapy is predicted by the degree to which ambiguous ( external ) information is interpreted as threatening . Thus a cognitive variable contributes reliably to the prediction of outcome after a cognitive treatment , but does not predict in the same way to outcome after a behavioural treatment", "Among a sample of 767 high utilizers of health care , 51 % were identified as distressed by an elevated score on the SCL anxiety and depression scales , the SCL somatization scale , or by their primary -care physician . These distressed high utilizers were found to have a high prevalence of chronic medical problems and significant limitation of activities caused by illness . In the prior year , they made an average of 15 medical visits and 15 telephone calls to the clinic . The Diagnostic Interview Schedule was completed on 119 distressed high utilizers r and omly assigned to an intervention group in a controlled trial of psychiatric consultation . The following DSM-III-R disorders were most common : major depression 23.5 % , dysthymic disorder 16.8 % , generalized anxiety disorder 21.8 % , and somatization disorder 20.2 % . Two thirds had a lifetime history of major depression . The examination result ed in an improved diagnostic assessment for 40 % of intervention patients and a revised treatment plan for 67 %", "OBJECTIVE The authors present data from a pilot research program initiated to develop , refine , and test the outcomes of CBT-GAD/PC , a version of cognitive-behavior therapy ( CBT ) that targets the needs of older adults with generalized anxiety disorder ( GAD ) in primary care ( PC ) . METHODS The study involved a small , r and omized clinical trial comparing the impact of CBT-GAD/PC to usual care ( UC ) in a sample of 12 older medical patients with GAD . RESULTS Outcome data suggested significant improvements in worry and depression after CBT-GAD/PC , relative to UC . CONCLUSION Authors discuss results in terms of the \" real-world \" applicability of this treatment for late-life GAD , and present implication s for future research", "Cognitive therapy ( CT ) and applied relaxation ( AR ) as treatments of generalized anxiety disorder ( GAD ) were compared in a sample of 45 patients of a community mental health center , r and omly allocated to condition . Patients were assessed before and after a 12-session treatment , and at one and six months follow-ups . There was a 20 % drop out from CT and 15 % from AR ( NS ) , with some drop outs being considerably improved . Both completers and intention-to-treat analyses revealed that both treatments were effective ( ESs of composite and specific measures ranging from 0.53 to 1.14 ) . At one-month follow-up AR tended to do better than CT , with CT catching up with AR at six months . Recovery rates and proportions of patients showing reliable change were comparable to other studies on AR and CT , with 55 % of CT and 53.3 % of AR patients recovered on the STAI-trait at six-month follow-up . These results confirm that both CT and AR are effective treatments for GAD , and also that there is still room for improvement", "BACKGROUND There have been six r and omized controlled trials of psychological therapy with generalized anxiety disorder ( GAD ) using DSM-III-R and DSM-IV . All have used the Trait version of the Spielberger State-Trait Anxiety Inventory ( STAI-T ) as one of several outcome measures . Each study , however , employed different methods of calculating the clinical significance of outcomes making it difficult to reach a balanced appraisal of the efficacy of psychological treatment . METHODS Raw data on STAI-T scores at pre- , post- and follow-up were obtained for each of the six studies ( total N = 404 ) . Jacobson methodology for defining clinical ly significant change ( criterion c , reliable change index = 8 , cut-off point = 46 ) was used to allocate each patient to one of four outcomes : worse , unchanged , improved and recovered . The proportion of patients in each category was calculated for treatment conditions in each study and also for aggregate data across types of treatment . RESULTS A recovery rate of 40 % was found for the sample as a whole with 12 of the 20 treatment conditions obtaining very modest recovery rates of 30 % or less . Two treatment approaches -- individual cognitive behavioural therapy and applied relaxation -- do relatively well with overall recovery rates at 6-month follow-up of 50 - 60 % . CONCLUSIONS Jacobson methodology , in distinguishing between improvement and recovery on a st and ardized measure of general vulnerability to anxiety , provides a stringent but clinical ly more meaningful evaluation of the efficacy of psychological therapies with GAD than has been available hitherto . Systematic focus on either excessive worry or physiological arousal gives worthwhile results", "In a controlled clinical trial , 57 Ss meeting DSM-III-R criteria for generalized anxiety disorder , and fulfilling an additional severity criterion , were r and omly allocated to cognitive behavior therapy ( CBT ) , behavior therapy ( BT ) , or a waiting-list control group . Individual treatment lasted 4 - 12 sessions ; independent assessment s were made before treatment , after treatment , and 6 months later , and additional follow-up data were collected after an interval of approximately 18 months . Results show a clear advantage for CBT over BT . A consistent pattern of change favoring CBT was evident in measures of anxiety , depression , and cognition . Ss were lost from the BT group , but there was no attrition from the CBT group . Treatment integrity was double-checked in Engl and and in Holl and , and special efforts were made to reduce error variance . Possible explanations for the superiority of CBT are discussed", "Abstract The effects of anxiety management training were evaluated by allocating 66 generally anxious clients to either a wait list condition , non-directive counselling , or a combination of relaxation and brief cognitive therapy . Anxiety management was significantly more effective than the wait list condition on a number of relevant measures at post-treatment , but there were relatively few differencs between anxiety management and non-directive counselling , either at post-treatment or at 6 months follow-up . Those differences which were found could plausibly be explained in terms of the dem and characteristics of training in relaxation or cognitive therapy . It was concluded that anxiety management is clearly better than a non-treatment control condition , but that its superiority to plausible alternatives which lack the specific components thought to be responsible for improvement has yet to be demonstrated", "BACKGROUND Generalized anxiety disorder is a common condition of excessive worry and tension which tends to run a chronic course associated with significant psychiatric and medical problems . Cognitive behaviour therapy ( CBT ) has been shown to be of clinical value in about 50 % of cases with treatment gains maintained over follow-up periods ranging from 6 to 12 months . The potential value of CBT over the longer term has not been subject to rigorous investigation . METHOD Results are reported of 8 - 14 year follow-up of two r and omized controlled trials of cognitive-behaviour therapy for generalized anxiety disorder employing structured interview with an assessor blind to initial treatment condition . Comparison groups included medication and placebo in one study based in primary care , and analytical psychotherapy in the other based in secondary care . Follow-up sample s ( 30 % and 55 % of trial entrants ) were broadly representative of the original cohorts . RESULTS Overall , 50 % of participants were markedly improved of whom 30 - 40 % were recovered ( i.e. free of symptoms ) . Outcome was significantly worse for the study based in secondary care in which the clinical presentation of participants was more complex and severe . For a minority ( 30 - 40 % ) , mainly from the secondary care study , outcome was poor . Treatment with CBT was associated with significantly lower overall severity of symptomatology and less interim treatment , in comparison with non-CBT conditions , but there was no evidence that CBT influenced diagnostic status , probability of recovery or patient perceptions of overall improvement . CONCLUSIONS Both CBT and the complexity and severity of presenting problems appear to influence the long-term outcome of GAD", "BACKGROUND The diagnostic category of generalised anxiety disorder ( GAD ) was originally intended to describe residual anxiety states . Over the years clinical criteria have been refined in an attempt to describe a unique diagnostic entity . Given these changes , little is known about the clinical course of this newly defined disorder . This study investigates the longitudinal course , including remission and relapse rates , for patients with DSM-III-R defined GAD . METHOD Analysis of the 164 patients with GAD participating in the Harvard Anxiety Research Program . Patients were assessed with a structured clinical interview at intake and re-examined at six month intervals for two years and then annually for one to two years . Psychiatric Status Ratings were assigned at each interview point . Kaplan-Meier curves were constructed to assess likelihood of remission . RESULTS Comorbidity was high , with panic disorder and social phobia as the most frequently found comorbid disorders . The likelihood of remission was 0.15 after one year and 0.25 after two years . The probability of becoming asymptomatic from all psychiatric symptoms was only 0.08 . CONCLUSIONS This prospect i ve study confirms the chronicity associated with GAD and extends this finding to define the one and two year remission rates for the disorder . Likelihood of remission for GAD and any other comorbid condition after one year was half the annual remission rate for GAD alone", "BACKGROUND Psychotherapy 's equivalence paradox is that treatments have equivalently positive outcomes despite non-equivalent theories and techniques . We compared the outcomes of contrasting approaches practised in routine care . METHOD Patients ( n = 1309 ) who received cognitive-behavioural therapy ( CBT ) , person-centred therapy ( PCT ) and psychodynamic therapy ( PDT ) at one of 58 National Health Service ( NHS ) primary and secondary care sites in the UK during a 3-year period completed the Clinical Outcomes in Routine Evaluation- Outcome Measure ( CORE-OM ) at the beginning and end of their treatment . Therapists indicated which treatment approaches were used on an End of Therapy form . We compared outcomes of six groups : three treated with CBT , PCT or PDT only , and three treated with one of these plus one additional approach ( e.g. integrative , supportive , art ) , design ated CBT+1 , PCT+1 or PDT+1 respectively . RESULTS All six groups averaged marked improvement ( pre-post effect size = 1.36 ) . Treatment approach and degree of purity ( ' only ' vs. ' + 1 ' ) each accounted for statistically significant but comparatively tiny proportions of the variance in CORE-OM scores ( respectively 1 % and 0.5 % as much as pre-post change ) . Distributions of change scores were largely overlapping . CONCLUSIONS Results for these three treatment approaches as practised routinely across a range of NHS setting s were generally consistent with previous findings that theoretically different approaches tend to have equivalent outcomes . Caution is warranted because of limited treatment specification , non-r and om assignment , lack of a control group , missing data and other issues", "OBJECTIVE Although cognitive-behavior therapy ( CBT ) is an efficacious treatment for generalized anxiety disorder ( GAD ) in younger adults , little is known about its efficacy in older patients . Investigations to date have tested group-format or otherwise nonst and ard versions of CBT . The studies described here are , to our knowledge , the first to test the efficacy of individual-format CBT administered in a mental health clinic for treatment of late-life GAD . METHODS Study 1 tested a st and ard version , and Study 2 tested an enhanced version ( ECBT ) that included learning and memory aids design ed to make the therapy more effective with elderly patients ( e.g. , homework reminder and troubleshooting calls , weekly review of all concepts and techniques ) . RESULTS Study 1 CBT participants showed significant improvement on GAD severity ratings . Study 2 ECBT participants showed significant improvement on two self-report measures , rates of posttreatment GAD , and GAD severity ratings . ECBT result ed in improvement on more measures and yielded larger effect sizes than st and ard CBT , when each was compared against a wait-list control group . CONCLUSION Results of these pilot studies suggest that st and ard individual-format CBT may not be optimally effective for treating late-life GAD ; thus , ECBT should be tested further in r and omized trials", "BACKGROUND We test the hypotheses that ( a ) cognitive therapy is of comparable efficacy to psychodynamic psychotherapy , ( b ) 8 - 10 sessions of therapy is as effective as 16 - 20 sessions , and ( c ) brief therapist training is as effective as intensive training . METHOD Of 178 out- patients referred to a clinical trial of psychological treatment for generalised anxiety , 110 patients met DSM-III-R criteria for generalised anxiety disorder and were r and omly assigned to three different forms of psychotherapy . The main comparison was between cognitive therapy and analytic psychotherapy , delivered by experienced therapists at weekly or fortnightly intervals over six months . A third treatment , anxiety management training , was delivered at fortnightly intervals by registrars in psychiatry after a brief period of training . Eighty patients completed treatment and were assessed before treatment , after treatment , and at six-month follow-up . RESULTS Cognitive therapy was significantly more effective than analytic psychotherapy , with about 50 % of patients considerably better at follow-up . Analytic psychotherapy gave significant improvement but to a lesser degree than cognitive therapy . There was no significant effect for level of contact . Patients receiving anxiety management training showed similar improvements to cognitive therapy after treatment , with rather lower proportions showing clinical ly significant change . CONCLUSIONS Cognitive therapy is likely to be more effective than psychodynamic psychotherapy with chronically anxious patients . Significant improvements in symptoms can be achieved by trainee psychiatrists after only brief instruction in behaviourally based anxiety management . However , the superiority of cognitive therapy at follow-up suggests that the greater investment of re sources required for this approach is likely to pay off in terms of more sustained improvement . There is no evidence that 16 - 20 sessions of treatment is more effective , on average , than 8 - 10 sessions", "The authors used a r and omized trial to compare cognitive-behavioral therapy ( CBT ) and supportive counseling ( SC ) in the treatment of anxiety symptoms in older adults who met Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . : American Psychiatric Association , 1994 ) criteria for anxiety disorders . Both conditions had a 6-week baseline no-treatment phase . Treatment was delivered primarily in patients ' own homes and in an individual format . Outcomes were assessed at posttreatment and at 3- , 6- , and 12-month follow-ups . There was no spontaneous improvement during the baseline phase . Both groups showed improvement on anxiety measures following treatment , with a better outcome for the CBT group on self-rating of anxiety and depression . Over the follow-up period , the CBT group maintained improvement and had significantly greater improvement than the SC group on anxiety and 1 depression measure . Treatment response for anxiety was also superior for the CBT group , although there was no difference between groups in endstate functioning", "BACKGROUND Very few studies have examined the combination of drug and psychological treatment in generalised anxiety disorder ( GAD ) . Theoretically , buspirone should be a useful drug to combine with a learning-based therapy . METHODS Sixty patients with GAD were r and omly assigned to treatment with buspirone or placebo , combined with anxiety management training or non-directive therapy for a period of 8 weeks . RESULTS Forty-four patients with a mean Hamilton Anxiety Scale score of 28 completed treatment . There were no significant differences between treatment groups . All groups showed significant improvement after 8 weeks compared to baseline . There were no baseline differences between those who completed the trial and those who did not but patients given buspirone were more likely to drop out . CONCLUSIONS A short course of psychological therapy , whether or not accompanied by active medication , was an effective treatment for patients diagnosed as having quite severe symptoms of GAD . CLINICAL IMPLICATION S AND LIMITATIONS : Dropouts led to a sample size which may have been too small to detect group differences . Cognitive therapy may have been more effective", "A recently developed cognitive-behavioral treatment for generalized anxiety disorder ( GAD ) targets intolerance of uncertainty by the reevaluation of positive beliefs about worry , problem-solving training , and cognitive exposure . As previous studies have established the treatment 's efficacy when delivered individually , the present study tests the treatment in a group format as a way to enhance its cost-benefit ratio . A total of 52 GAD patients received 14 sessions of cognitive-behavioral therapy in small groups of 4 to 6 participants . A wait-list control design was used , and st and ardized clinician ratings and self-report question naires assessed GAD symptoms , intolerance of uncertainty , anxiety , depression , and social adjustment . Results show that the treatment group , relative to the wait-list group , had greater posttest improvement on all dependent variables and that treated participants made further gains over the 2-year follow-up phase of the study", "BACKGROUND Anxiety disorders are prevalent in primary care . Psychological treatment is effective but time-consuming , and there are waiting lists for secondary care . Interest has therefore grown in developing guidelines for treatment that would be feasible in primary care . AIM To compare the effectiveness and feasibility of guided self-help , the Anxiety Disorder Guidelines of the Netherl and s College of General Practitioners and cognitive behavioural therapy ( CBT ) . DESIGN OF STUDY R and omised controlled study lasting 12 weeks with follow-up at 3 and 9 months for primary care patients with panic disorder and /or generalised anxiety disorder . SETTING The first two forms of treatment were carried out by 46 GPs who were r and omly assigned to one or the other form . CBT was carried out by cognitive behaviour therapists in a psychiatric outpatient clinic . METHOD Participants ( n = 154 ) were r and omly assigned to one of the three forms of treatment . The main outcome measure used was the state subscale of the Spielberger Anxiety Inventory . RESULTS All three forms of treatment gave significant improvement between pre-test and post-test , and this improvement remained stable between post-test and the follow-ups . The results obtained with the three treatment forms did not differ significantly over time . The feasibility of the Anxiety Disorder Guidelines was low compared with that of guided self-help . CONCLUSION Our results indicate that primary care patients with prevalent anxiety disorders for whom the GP does not find referral necessary can be adequately treated by the GP . Psychiatric outpatient clinic referral does not give superior results . Guided self-help is easier for the GP to carry out than a less highly-structured treatment like that laid down in the Anxiety Disorder Guidelines", "Recent advances in the underst and ing of worry have led to the development of treatments for generalized anxiety disorder ( GAD ) . The present study tested a GAD treatment that targeted intolerance of uncertainty , erroneous beliefs about worry , poor problem orientation , and cognitive avoidance . Twenty-six primary GAD patients were r and omly allocated to a treatment condition ( n = 14 ) or a delayed treatment control condition ( n = 12 ) . Self-report , clinician , and significant other ratings assessed GAD and associated symptoms . The results show that the treatment led to statistically and clinical ly significant change at posttest and that gains were maintained at 6- and 12-month follow-ups . Furthermore , 20 of 26 participants ( 77 % ) no longer met GAD diagnostic criteria following treatment . With regard to the treatment 's underlying model , the results show that intolerance of uncertainty significantly decreased over treatment and that gains were maintained at both follow-ups . Although nonspecific factors were not significant predictors of treatment outcome , their role in the treatment of GAD requires further investigation", " Abstract Psychiatric out patients with a diagnosis of chronic anxiety of at least one year 's duration were r and omly assigned to either behaviour therapy or Beck 's cognitive therapy , and to one of two experienced therapists . Both treatment conditions followed the therapeutic processes described in Beck 's treatment manual for anxiety states , but the behaviour therapy condition excluded any attempt to modify automatic thoughts , thinking errors , or underlying assumptions . However , it did include the use of positive self-statements . Treatment consisted of a maximum of 16 1-hour sessions . Several outcome measures were administered before treatment , during treatment , at discharge , and at 6 month follow-up . At the end of treatment there was no difference between the cognitive and behavioural treatments in the amount of improvement observed . By the 6 month follow-up , however , there was a trend , which was significant on a number of outcome measures , for the cognitive therapy patients to maintain or improve upon their progress and for the behaviour therapy patients to revert toward their pre-treatment scores", "The present study investigated the efficacy of a coping-technique , applied relaxation ( AR ) and cognitive therapy ( CT ) , in the treatment of generalized anxiety disorder . Thirty-six out patients fulfilling the DSM-III-R criteria for generalized anxiety were assessed with independent assessor ratings and self-report scales before and after treatment and at a 1 yr follow-up . The patients were r and omized and treated individually for 12 weekly sessions . The results showed that both treatments yielded large improvements , which were maintained , or furthered at follow-up . There was no difference between AR and CT on any measure . The drop-out rate was 12 % for AR and 5 % for CT . The proportions of clinical ly significantly improved patients were 53 and 62 % at post-treatment and 67 and 56 % at follow-up for AR and CT , respectively . Besides affecting generalized anxiety the treatments also yielded marked and lasting changes on ratings of worry , cognitive and somatic anxiety and depression . The conclusion that can be drawn is that both AR and CT have potential as treatments for generalized anxiety disorder but they have to be developed further in order to increase the efficacy to the level usually seen in panic disorder , 80 - 85 % clinical ly improved", "Abstract Sixty-three generally anxious subjects were assigned to anxiety management training , applied relaxation training , relaxation-only , placebo and untreated control conditions . After 6 weeks of treatment , anxiety management training led to reductions on a variety of self-report measures of state and trait anxiety and decreases in maladaptive cognitions during a laboratory stress procedure . On several measures , subjects in anxiety management training differed from relaxation-only and placebo subjects as well as untreated controls . However , treatment effects did not extend to performance and physiological measures of anxiety . Applied relaxation training , which in contrast to anxiety management training lacks structured rehearsal involving the recognition and reduction of tension cues during the treatment sessions , result ed in less consistent decreases in measures of general anxiety", "This study attempted to identify the necessary and sufficient change factors in short-term anxiety-provoking psychotherapy ( STAPP ) . Twenty patients were r and omly assigned to either STAPP or a form of nondirective therapy almost devoid of psychodynamic elements but with common factors of psychotherapy intact . Both treatments were 20 sessions long , were manualized , and therapists in both conditions were experienced clinicians receiving manual-guided supervision . Most patients had a diagnosis of anxiety . Results showed that patients in both treatments improved greatly symptomatically and that no further gains were made after termination . Treatments were equally effective . The therapeutic alliance was a strong predictor of symptom improvement . The findings underscore the importance of common factors pertaining to the therapeutic relationship , and they may open to question , to some degree , the therapeutic effectiveness of psychodynamic technique factors in STAPP . The way in which specific and common factors can be brought together under the umbrella of the concept of affect attunement is discussed", "Abstract Cognitive restructuring , modified systematic desensitization and a combined treatment ( cognitive behaviour modification ) were compared with a no-treatment control group , using a simple r and omized design . Twenty seven general anxiety out- patients selected from the hospital waiting list were used as subjects . Assessment s were made at the beginning and end of treatment , and at follow-up 1 month later . The assessment s included two subjective anxiety measures , the Zung self-rating anxiety scale and fear thermometer scores , a behavioural anxiety measure , a measure of cognitive anxiety as estimated by a diary recording of thinking time , fear survey schedule scores and I/E scores . Cognitive behaviour modification was found to be a superior form of treatment , relative to the no-treatment control and the other active treatment groups as assessed by FSS intensity score . The cognitive behaviour modification group showed greater improvement than the cognitive restructuring group on the diary anxiety scores . The results also demonstrated a relationship between outcome and initial severity of condition . The higher the subjects ' initial scores on neurotic symptoms and subjective anxiety level , the greater the degree of positive change after treatment . Moreover , subjects with high levels of internal control prior to treatment responded most to therapy", "This paper concerns an investigation of outcome predictors in a clinical trial of psychological therapies for generalized anxiety disorder . A variety of information of potential predictive value was obtained at three stages of patient contact : the initial referral , a screening interview and early sessions of therapy . Three measures of the clinical significance of change over a 12-month follow-up period were used to construct a composite measure which categorized outcome in terms of sustained improvement , relapse and no consistent change . Logistic regression was used to examine the validity of predictors identified in previous research and the relative importance of data obtained from the three different stages . Seventy-one per cent of patients were correctly classified as improved or not from initial data with a significant increase in accuracy with information from the screening interview ( 77 per cent ) and early sessions ( 82 per cent ) . Patients who relapsed or not were predicted with considerable accuracy from initial data ( 90 per cent ) and there was no significant increase in predictive power with additional information . The most powerful and robust predictors were : type of treatment received , marital status , marital tension and complexity of clinical presentation in terms of axis 1 co-morbidity . A conceptual framework for prediction is outlined", "Abstract This paper describes the analysis of predictive factors in a group of generally anxious patients treated with anxiety management . Evidence for three reliable predictors is presented . It is argued these reflect anxiety , demoralisation and depression . The same three variables contributed to prediction of outcome after treatment and 6 months later , and their pre-treatment values classified 80 % of the patients correctly into good or poor responders . Lower initial levels of anxiety and demoralisation together with higher depression rated by the assessor predicted a better outcome . Predictions were more accurate for patients with a mild degree of depression than for those who were not depressed " ]

[ "Muscle mass decreases with age , leading to \" sarcopenia , \" or low relative muscle mass , in elderly people . Sarcopenia is believed to be associated with metabolic , physiologic , and functional impairments and disability . Methods of estimating the prevalence of sarcopenia and its associated risks in elderly population s are lacking . Data from a population -based survey of 883 elderly Hispanic and non-Hispanic white men and women living in New Mexico ( the New Mexico Elder Health Survey , 1993 - 1995 ) were analyzed to develop a method for estimating the prevalence of sarcopenia . An anthropometric equation for predicting appendicular skeletal muscle mass was developed from a r and om sub sample ( n = 199 ) of participants and was extended to the total sample . Sarcopenia was defined as appendicular skeletal muscle mass (kg)/height2 ( m2 ) being less than two st and ard deviations below the mean of a young reference group . Prevalences increased from 13 - 24 % in persons under 70 years of age to > 50 % in persons over 80 years of age , and were slightly greater in Hispanics than in non-Hispanic whites . Sarcopenia was significantly associated with self-reported physical disability in both men and women , independent of ethnicity , age , morbidity , obesity , income , and health behaviors . This study provides some of the first estimates of the extent of the public health problem posed by sarcopenia", "Previous studies have shown that low-intensity resistance training with restricted muscular venous blood flow ( Kaatsu ) causes muscle hypertrophy and strength gain . To investigate the effects of daily physical activity combined with Kaatsu , we examined the acute and chronic effects of walk training with and without Kaatsu on MRI-measured muscle size and maximum dynamic ( one repetition maximum ) and isometric strength , along with blood hormonal parameters . Nine men performed Kaatsu-walk training , and nine men performed walk training alone ( control-walk ) . Training was conducted two times a day , 6 days/wk , for 3 wk using five sets of 2-min bouts ( treadmill speed at 50 m/min ) , with a 1-min rest between bouts . Mean oxygen uptake during Kaatsu-walk and control-walk exercise was 19.5 ( SD 3.6 ) and 17.2 % ( SD 3.1 ) of treadmill-determined maximum oxygen uptake , respectively . Serum growth hormone was elevated ( P Kaatsu-walk exercise but not in control-walk exercise . MRI-measured thigh muscle cross-sectional area and muscle volume increased by 4 - 7 % , and one repetition maximum and maximum isometric strength increased by 8 - 10 % in the Kaatsu-walk group . There was no change in muscle size and dynamic and isometric strength in the control-walk group . Indicators of muscle damage ( creatine kinase and myoglobin ) and resting anabolic hormones did not change in both groups . The results suggest that the combination of leg muscle blood flow restriction with slow-walk training induces muscle hypertrophy and strength gain , despite the minimal level of exercise intensity . Kaatsu-walk training may be a potentially useful method for promoting muscle hypertrophy , covering a wide range of the population , including the frail and elderly", "Background We aim ed to determine the effect of resistance exercise intensity ( % 1 repetition maximum—1RM ) and volume on muscle protein synthesis , anabolic signaling , and myogenic gene expression . Methodology /Principal Findings Fifteen men ( 21±1 years ; BMI = 24.1±0.8 kg/m2 ) performed 4 sets of unilateral leg extension exercise at different exercise loads and /or volumes : 90 % of repetition maximum ( 1RM ) until volitional failure ( 90FAIL ) , 30 % 1RM work-matched to 90%FAIL ( 30WM ) , or 30 % 1RM performed until volitional failure ( 30FAIL ) . Infusion of [ ring-13C6 ] phenylalanine with biopsies was used to measure rates of mixed ( MIX ) , myofibrillar ( MYO ) , and sarcoplasmic ( SARC ) protein synthesis at rest , and 4 h and 24 h after exercise . Exercise at 30WM induced a significant increase above rest in MIX ( 121 % ) and MYO ( 87 % ) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only . The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM , with no difference between these conditions ; however , MYO remained elevated ( 199 % ) above rest at 24 h only in 30FAIL . There was a significant increase in AktSer473 at 24h in all conditions ( P = 0.023 ) and mTORSer2448 phosphorylation at 4 h post-exercise ( P = 0.025 ) . Phosporylation of Erk1/2Tyr202/204 , p70S6KThr389 , and 4E-BP1Thr37/46 increased significantly ( P whereas , 4E-BP1Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL ( 237 % ) and 30FAIL ( 312 % ) conditions . Pax7 mRNA expression increased at 24 h post-exercise ( P = 0.02 ) regardless of condition . The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition . Conclusions / Significance These results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes", "This study identified factors associated with exercise participation and adherence in a sample of 102 sedentary , functionally limited , community-dwelling adults aged 60 to 94 years who participated in a home-based resistance training program . Stepwise regression analyses revealed that baseline physical factors ( i.e. , higher levels of mobility , weaker muscle strength , and fewer numbers of new medical conditions ) were associated with higher rates of participation in the home program . Positive attitudes and a sense of control toward exercise , lower levels of confusion and depressive moods , and the development of fewer new medical problems during the program were related to higher levels of adherence to the program . Findings revealed that although physical health variables were the primary indicators of an older person 's overall participation in the program , it was the psychological factors that were most important to adherence to this home-based program", "OBJECTIVES To assess the extent to which physical activity and leg strength are associated with change in mobility in older persons . DESIGN Prospect i ve , observational cohort study . SETTING Retirement communities across the Chicago metropolitan area participating in the Rush Memory and Aging Project . PARTICIPANTS Eight hundred eighty-six ambulatory older persons without dementia . MEASUREMENT Rate of change in mobility . RESULTS In a linear mixed-effects model that controlled for age , sex , education , and a term for baseline physical activity , a higher level of physical activity was associated with a slower rate of mobility decline ( estimate=0.006 , st and ard error (SE)=0.003 , P=.03 ) ; each additional hour of physical activity at baseline was associated with an approximately 3 % decrease in the rate of mobility decline . In a similar model , a higher level of baseline leg strength was associated with a slower rate of mobility decline ( estimate=0.031 , SE=0.132 , P=.02 ) ; each additional unit of leg strength at baseline was associated with an approximately 20 % decrease in the rate of mobility decline . In a final model , which included terms for physical activity and leg strength together , both were associated with decline in mobility . Furthermore , both remained associated with mobility even after controlling for body composition , balance , pulmonary function , cognition , history of joint pain , cardiovascular diseases and risk factors , and medications . CONCLUSION Physical activity and leg strength are relatively independent predictors of mobility decline in older persons . Although physical activity may improve strength , the beneficial effect of physical activity on mobility is likely to involve other pathways", "We have reported that the acute postexercise increases in muscle protein synthesis rates , with differing nutritional support , are predictive of longer-term training-induced muscle hypertrophy . Here , we aim ed to test whether the same was true with acute exercise-mediated changes in muscle protein synthesis . Eighteen men ( 21 ± 1 yr , 22.6 ± 2.1 kg/m(2 ) ; means ± SE ) had their legs r and omly assigned to two of three training conditions that differed in contraction intensity [ % of maximal strength ( 1 repetition maximum ) ] or contraction volume ( 1 or 3 sets of repetitions ) : 30%-3 , 80%-1 , and 80%-3 . Subjects trained each leg with their assigned regime for a period of 10 wk , 3 times/wk . We made pre- and posttraining measures of strength , muscle volume by magnetic resonance ( MR ) scans , as well as pre- and posttraining biopsies of the vastus lateralis , and a single postexercise ( 1 h ) biopsy following the first bout of exercise , to measure signaling proteins . Training-induced increases in MR-measured muscle volume were significant ( P 7.2 ± 1.9 % , P = 0.18 . Isotonic maximal strength gains were not different between 80%-1 and 80%-3 , but were greater than 30%-3 ( P = 0.04 ) , whereas training-induced isometric strength gains were significant but not different between conditions ( P = 0.92 ) . Biopsies taken 1 h following the initial resistance exercise bout showed increased phosphorylation ( P of p70S6 K only in the 80%-1 and 80%-3 conditions . There was no correlation between phosphorylation of any signaling protein and hypertrophy . In accordance with our previous acute measurements of muscle protein synthetic rates a lower load lifted to failure result ed in similar hypertrophy as a heavy load lifted to failure", "BACKGROUND This study tested the hypothesis that a home-based exercise program would improve functional performance in elderly people . METHODS We conducted a 6-month , single-blinded , r and omized controlled trial . 72 community dwelling men and women ( aged > /=70 years ) with self-reported and laboratory-based functional impairment were recruited for the study . Participants were r and omly assigned to either a home-based progressive strength , balance , and general physical activity intervention or an attention-control group that received home-based nutrition education . Functional performance was measured in the laboratory using the Physical Performance Test ( PPT ) and the Established Population s for Epidemiologic Studies of the Elderly ( EPESE ) short physical performance battery . Physiologic capacity was measured by strength ( one repetition maximum ) , dynamic balance ( t and em walk ) , gait speed ( 2-meter walk ) , and cardiovascular endurance ( 6-minute walk ) . RESULTS 70 participants ( 97 % ) completed the 6-month trial . Compliance with study interventions within each group ranged from 75 % in controls to 82 % in exercisers . PPT increased by 6.1 + /- 13.4 % in exercisers and decreased by 2.8 + /- 13.6 % in controls ( p = .02 ) . EPESE improved by 26.2 + /- 37.5 % in exercisers and decreased by 1.2 + /- 22.1 % in controls ( p = .001 ) . Dynamic balance improved by 33.8 + /- 14.4 % in exercisers versus 11.5 + /- 23.7 % in controls ( p = .0002 ) . There were no differences between groups in the change in strength , gait speed , or cardiovascular endurance . CONCLUSIONS Minimally supervised exercise is safe and can improve functional performance in elderly individuals . The improvements in functional performance occurred along with improvements in balance but without a significant change in muscle strength or endurance", "BACKGROUND Identification of the physiologic factors most relevant to functional independence in the elderly population is critical for the design of effective interventions . It has been suggested that muscle power may be more directly related to impaired physical performance than muscle strength in elderly persons . We tested the hypothesis that peak muscle power is closely associated with self-reported functional status in sedentary elderly community-dwelling women . METHODS We used baseline data that were collected as part of a 1-year r and omized controlled clinical trial of a combined program of strength , power , and endurance training in 80 elderly women ( mean age 74.8 + /- 5.0 years ) with 3.2 + /- 1.9 chronic diseases , selected for baseline functional impairment and /or falls . RESULTS Functional status at baseline was related in univariate analyses to physiologic capacity , habitual physical activity level , neuropsychological status , and medical diagnoses . Leg power had the strongest univariate correlation to self-reported functional status ( r = -.47 , p leg press power and habitual physical activity level were the only two factors that contributed independently to functional status ( r = .64 , p Leg power is a strong predictor of self-reported functional status in elderly women", "The aim of the present study was to investigate the effects of home-based exercise without home visits on physical function , falls , and bone mineral density in community-dwelling elderly women . Sixty community-dwelling , elderly ( > or = 65 years of age ) women were recruited from a Japanese community . Subjects were r and omly assigned to a home-based exercise group or a control group . The subjects assigned to the home-based exercise group performed home-based exercise without home visits 3 times per week for 6 months in their homes . Assessment s of physical function and bone mineral density were carried out before and after intervention in both groups . Muscle strength , gait velocity , the timed up and go test ( TUGT ) , single leg stance time , the bend reach performance test , and reaction time were measured to assess physical function . The patients ' history of falls was also assessed before and after the 12-month follow-up . To determine bone mineral density , the speed of sound ( SOS ) at the right calcaneus was measured using a quantitative ultrasound device . There were no significant differences between the two groups in baseline characteristics . 82.6 % of subjects completed the prescribed exercise program in the home-based exercise group . Compared to the control group , TUGT improved significantly ( p Home-based exercise without home visits can be adopted for community-dwelling elderly women , particularly since no specific place or instructor is needed", "Elastic b and ( EB ) training is a common form of resistance training used by the elderly , individuals with joint problems or those recovering from injury . EB training performed at low intensities by these population s may have little effect on muscle hypertrophy . However , when combined with blood flow restriction ( BFR ) , low‐intensity EB resistance training may result in muscle hypertrophy", "Purpose Slow-walk training combined with restricted leg muscular blood flow ( KAATSU ) produces muscle hypertrophy and strength gains in young men , which may lead to increased aerobic capacity and functional fitness . The purpose of this study was to investigate the effects of walk training combined with KAATSU on muscle size , strength , and functional ability , as well as aerobic capacity , in older participants . Methods A total of 19 active men and women , aged 60 to 78 years , were r and omized into either a KAATSU-walk training group ( n = 11 , K-walk ) or a nonexercising control group ( n = 8 , control ) . The K-walk group performed 20-minute treadmill walking ( 67 m/min ) , 5 days/wk for 6 weeks . Results Isometric ( 11 % ) and isokinetic ( 7%-16 % ) knee extension and flexion torques , muscle-bone cross-sectional area ( 5.8 % and 5.1 % for thigh and lower leg , respectively ) , as well as ultrasound-estimated skeletal muscle mass ( 6.0 % and 10.7 % for total and thigh , respectively ) increased ( P Functional ability also increased significantly only in the K-walk group ( P estimated peak oxygen uptake(absolute and relative to body mass ) for either group . Conclusion The results of the current study indicate that 6 weeks of KAATSU-walk training did not simultaneously improve cardiovascular and muscular fitness of older participants . However , it significantly increased muscular size and strength as well as functional ability of active older men and women", "UNLABELLED We conducted a 30-month population -based , r and omized , controlled trial in 160 elderly women at risk for fractures on the basis of a low baseline BMD . Mainly home-based weight-bearing exercise was effective in improving strength , balance , and gait . INTRODUCTION Evidence on the effect of exercise on extraskeletal risk factors for hip fractures comes mainly from studies in voluntary low-risk women , and no population -based , long-term interventions have been performed in elderly women with low bone mass . The aim of this study was to determine the effect of long-term weight-bearing exercise on balance , muscle strength , and gait in elderly women at risk for fractures on the basis of a low baseline BMD . MATERIAL S AND METHODS A birth cohort of 1690 women 70 - 73 years of age were invited to the radius and hip BMD measurements ; 96 women were excluded because of medical reasons ; 160 women with radius and hip BMD values of > 2 SD below the reference value were included in the trial . The participants were r and omly assigned to 30 months of impact , balancing , and strengthening exercises or to no intervention . Main outcome measures were body sway length and leg strength at month 30 . Secondary endpoints included gait speed , endurance , and grip strength . Outcomes were assessed at 0 , 12 , 24 , and 30 months using blinded operators . Repeated- measures ANOVA was used to determine statistical significance . The analyses were performed on an intention-to-treat basis . RESULTS Body sway increased more in the control group than in the exercise group over time ( time-group interaction , p Leg strength improved in the exercise group and decreased in the control group ( interaction , p timed up and go test score , walking speed , and distance walked in 2 minutes . CONCLUSIONS Weight-bearing exercise is an effective way of modifying extraskeletal risk factors for fractures in elderly women", "Elderly participants experiencing difficulty in chair rising and with a maximum knee-extensor torque below 87.5 N . m were r and omized to different versions of a strength-training program for the knee-extensors : to a high-guidance group ( HG ; two group sessions supervised by a physical therapist and one unsupervised home session per week , n = 17 ) , a medium-guidance group ( MG ; one supervised group session and two unsupervised home sessions per week , n = 16 ) , or a control group ( C ; no exercise , n = 16 ) . Maximal isometric knee strength increased more in HG than in C ( p = .03 ) and with increasing guidance ( p = .03 ) . The effect was mainly the result of participants with low initial strength . Walking speed increased more for HG than for C ( p = .02 ) and than for MG ( p = .06 ) . No statistically significant improvements were seen on other functional tests . In summary , the study shows a trend toward better results with more supervision , but more and larger studies are needed to confirm this", "OBJECTIVES This investigation determined whether an in-home resistance training program achieved health benefits in older adults with disabilities . METHODS A r and omized controlled trial compared the effects of assigning 215 older persons to either a home-based resistance exercise training group or a waiting list control group . Assessment s were conducted at baseline and at 3 and 6 months following r and omization . The program consisted of videotaped exercise routines performed with elastic b and s of varying thickness . RESULTS High rates of exercise adherence were achieved , with 89 % of the recommended exercise sessions performed over 6 months . Relative to controls , subjects who participated in the program achieved statistically significant lower extremity strength improvements of 6 % to 12 % , a 20 % improvement in t and em gait , and a 15 % to 18 % reduction in physical and overall disability at the 6-month follow-up . No adverse health effects were encountered . CONCLUSIONS These findings provide important evidence that home-based resistance exercise programs design ed for older persons with disabilities hold promise as an effective public health strategy", "OBJECTIVES This paper describes a videotaped , home-based , strength training program , titled Strong-for-Life and reports on its effectiveness in improving muscle strength , psychological well-being , and health status in a sample of older persons . DESIGN AND SETTING We enrolled 102 nondisabled , community-dwelling older people aged 66 to 87 , identified from the Medicare beneficiary list , into a r and omized , controlled trial . MEASUREMENTS Effectiveness was based on change in isokinetic upper and lower extremity muscle strength , psychologic well-being , and health status . RESULTS Results revealed several statistically significant short-term benefits after 12 to 15 weeks of exercise , especially for men . Younger older adults demonstrated a 10 % improvement in knee extensor strength relative to control subjects . Older male exercisers achieved significant differences relative to controls in perceived anger , tension , and overall social functioning . Male exercisers , in general , achieved significant improvement in perceived vigor . Women did not report psychological benefits following participation in the program . CONCLUSION Study results reveal that the Strong for Life program , design ed to be widely disseminated to the nondisabled older population , has many short-term positive benefits", "Falls are common in elderly people . Possible consequences include serious injuries and the post-fall syndrome , with functional decline and limitation of physical activity . The present r and omized controlled study sought to clarify the benefits of a combined long-term and home-based fall prevention program for elderly Japanese women . The subjects were individuals aged over 73 years , living at home in a western suburb of Tokyo , who had attended a comprehensive geriatric health check . Persons with a marked decline in the basic activities of daily living ( ADL ) , hemiplegia , or those missing baseline data were excluded . Fifty-two subjects who expressed a wish to participate in the trial were r and omized , 28 to an exercise-intervention group and 24 to a control group . Baseline data for age , h and grip force , walking speed , total serum cholesterol , serum albumin , basic ADL , visual and auditory impairments , self-rated health , and experience of falls did not differ significantly between the two groups . Beginning from June 2000 , the intervention group attended a 6-month program of fall-prevention exercise classes aim ed at improving leg strength , balance , and walking ability ; this was supplemented by a home-based exercise program that focused on leg strength . The control group received only a pamphlet and advice on fall prevention . The average rate of attendance at exercise class was 75.3 % ( range , 64 % to 86 % ) . Participants showed significant improvements in t and em walk and functional reach after the intervention program , with enhanced self confidence . At the 8-month follow-up , the proportion of women with falls was 13.6 % ( 3/22 ) in the intervention group and 40.9 % ( 9/22 ) in the control group . At 20 months , the proportion remained unchanged , at 13.6 % in the intervention group , but had increased to 54.5 % ( 12/22 ) in the control group , which showed a statistically significant difference between the two groups ( Fisher ’s exact test ; P = 0.0097 ) . The total number of falls during the 20-month follow-up period was 6 in the intervention group and 17 in the control group . We conclude that a moderate exercise intervention program plus a home-based program significantly decreases the incidence of falls in both the short and the long term , contributing to improved health and quality of life in the elderly" ]

[ "AIM Reduction of elevated blood pressure ( BP ) has been an important treatment goal in elderly hypertensive patients . However , it has been reported that an excessive reduction of systolic BP to less than 120mmHg might be harmful in such patients . We investigated whether this was the case in a study which assessed long-term antihypertensive efficacy , tolerability and impact on cardiovascular/cerebrovascular ( CV ) morbidity/mortality in a large cohort of Japanese patients . METHODS This study was performed at general practitioners ' offices nationwide with a target sample size of 1500 patients . Hypertensive patients aged 60years or more who achieved successful BP control with c and esartan monotherapy , and who tolerated the treatment for at least 8weeks , were enrolled into the study and followed for 3years . RESULTS BP was maintained below the target level of 140/90mmHg over the 3-year period . The incidence of CV events during the study period was 20.4/1000person-years . Investigation of the relationship between BP and the incidence of CV events revealed that patients with higher BP generally had a higher incidence of events . However , very elderly patients ( ≥75years ) with a systolic BP ( SBP ) of less than 120mmHg also had a higher incidence of CV events compared with those with an SBP of 120 - 139mmHg . CONCLUSION This study demonstrated that treatment with c and esartan maintained long-term control of BP in elderly hypertensive patients without serious adverse events . CV events demonstrated a J-curve relationship with SBP in patients aged 75years or older , which suggests that excessive BP reductions might be harmful for very elderly patients", "Whether the strict control of blood pressure ( BP ) of patients with hypertension who are aged 85 years or older is beneficial is unclear . The Japan ’s Benidipine Research on Antihypertensive Effects in the Elderly study is a prospect i ve , observational 3-year study to evaluate the safety and effectiveness of treatment with a calcium channel blocker benidipine in 8897 hypertensive patients aged 65 years or older as a post-marketing surveillance . We examined the relationship between the achieved BP and cardiovascular events ( i.e. , stroke , myocardial infa rct ion , and heart failure ) in a subgroup of 415 patients aged 85 years or older ( mean age 88 years ) . BP decreased significantly from 165 ± 14/84 ± 10 mmHg to 130 ± 11/71 ± 10 mmHg during treatment in patients with a treated systolic BP ( SBP ) ) and BP decreased significantly from 169 ± 16/86 ± 12 mmHg to 143 ± 13/75 ± 10 mmHg in those with a treated SBP ≥ 140 mmHg ( n = 185 ) . There was a nonsignificant trend toward a lower rate of cardiovascular events and higher rate of total death in patients with a treated SBP higher incidence of cardiovascular events . There was no significant difference in the incidence of adverse reactions between the controlled BP group ( 3.04 % ) and the less well controlled BP group ( 3.24 % ) . In conclusion , although this study was not powered for definitive conclusion , there was a nonsignificant trend toward a lower rate of cardiovascular events and higher total death in patients aged 85 years or older with a treated SBP < 140 mmHg", "This study evaluated the impact of renal function on cardiovascular outcomes in elderly hypertensive patients enrolled in the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive patients . The patients were r and omly assigned to either a strict-treatment group ( target systolic blood pressure ( BP ) a mild-treatment group ( target systolic BP , 140 to , each with efonidipine ( a T/L-type Ca channel blocker)-based regimens . Cardiovascular events ( stroke , cardiovascular disease and renal disease ) were evaluated during the 2-year follow-up period following the prospect i ve r and omized open-blinded end-point method . Estimated glomerular filtration rate ( eGFR ) was elevated throughout the trial period in both the strict-treatment ( 59.4–62 ml min−1 per 1.73 m2 ) and the mild-treatment group ( 58.8–61.4 ml min−1 per 1.73 m2 ) . This tendency was also observed in diabetic patients and patients aged ⩾75 years , with baseline eGFR Baseline eGFR ( incidence of cardiovascular events , nor did the level of BP control . Proteinuria at the time of entry into the study , however , was significantly correlated with cardiovascular event rates ( 7.1 % ) , an association that was more apparent in patients with eGFR the event rate was more elevated in patients with greater declines in eGFR and was amplified when the baseline eGFR was of renal function and proteinuria constitute critical risk factors for cardiovascular events in elderly hypertensive patients , trends that are enhanced when baseline eGFR is diminished . Furthermore , the fact that efonidipine-based regimens ameliorate renal function in elderly hypertensive patients with chronic kidney disease may offer novel information on the mechanisms of cardiovascular protection", "In this prospect i ve , r and omized , open-label , blinded end point study , we aim ed to establish whether strict blood pressure control ( moderate blood pressure control ( ≥140 mm Hg to cardiovascular mortality and morbidity in elderly patients with isolated systolic hypertension . We divided 3260 patients aged 70 to 84 years with isolated systolic hypertension ( sitting blood pressure 160 to 199 mm Hg ) into 2 groups , according to strict or moderate blood pressure treatment . A composite of cardiovascular events was evaluated for ≥2 years . The strict control ( 1545 patients ) and moderate control ( 1534 patients ) groups were well matched ( mean age : 76.1 years ; mean blood pressure : 169.5/81.5 mm Hg ) . Median follow-up was 3.07 years . At 3 years , blood pressure reached 136.6/74.8 mm Hg and 142.0/76.5 mm Hg , respectively . The blood pressure difference between the 2 groups was 5.4/1.7 mm Hg . The overall rate of the primary composite end point was 10.6 per 1000 patient-years in the strict control group and 12.0 per 1000 patient-years in the moderate control group ( hazard ratio : 0.89 ; [ 95 % CI : 0.60 to 1.34 ] ; P=0.38 ) . In summary , blood pressure targets of 140 mm Hg are safely achievable in relatively healthy patients ≥70 years of age with isolated systolic hypertension , although our trial was underpowered to definitively determine whether strict control was superior to less stringent blood pressure targets", "BACKGROUND The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain . METHODS We r and omly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk , but without diabetes , to a systolic blood-pressure target of less than 120 mm Hg ( intensive treatment ) or a target of less than 140 mm Hg ( st and ard treatment ) . The primary composite outcome was myocardial infa rct ion , other acute coronary syndromes , stroke , heart failure , or death from cardiovascular causes . RESULTS At 1 year , the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the st and ard-treatment group . The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the st and ard-treatment group ( 1.65 % per year vs. 2.19 % per year ; hazard ratio with intensive treatment , 0.75 ; 95 % confidence interval [ CI ] , 0.64 to 0.89 ; P All-cause mortality was also significantly lower in the intensive-treatment group ( hazard ratio , 0.73 ; 95 % CI , 0.60 to 0.90 ; P=0.003 ) . Rates of serious adverse events of hypotension , syncope , electrolyte abnormalities , and acute kidney injury or failure , but not of injurious falls , were higher in the intensive-treatment group than in the st and ard-treatment group . CONCLUSIONS Among patients at high risk for cardiovascular events but without diabetes , targeting a systolic blood pressure of less than 120 mm Hg , as compared with less than 140 mm Hg , result ed in lower rates of fatal and nonfatal major cardiovascular events and death from any cause , although significantly higher rates of some adverse events were observed in the intensive-treatment group . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT01206062 . )", "In this paper , we present the results of a re analysis of the data of two large r and omized , double-blind , parallel group studies with a similar design , comparing the efficacy of an angiotensin-receptor blocker ( olmesartan medoxomil ) with that of an angiotensin-converting enzyme inhibitor ( ramipril ) , by applying two different blood pressure targets recently recommended by hypertension guidelines for all patients , irrespective of the presence of diabetes ( The efficacy of olmesartan was not negatively affected by age , sex , hypertension type , diabetes status or other concomitant clinical conditions , or cardiovascular risk factors . In most cases , olmesartan provided better blood pressure control than ramipril . Olmesartan was significantly more effective than ramipril in male patients , in younger patients ( aged 65–69 years ) , in those with metabolic syndrome , obesity , dyslipidemia , preserved renal function , diastolic ± systolic hypertension , and , in general , in patients with a high or very high cardiovascular risk . Interestingly , patients previously untreated or treated with two or more antihypertensive drugs showed a significantly larger response with olmesartan than with ramipril . Thus , our results confirm the good efficacy of olmesartan in elderly hypertensives even when new blood pressure targets for antihypertensive treatment are considered . Such results may be relevant for the clinical practice , providing some hint on the possible different response of elderly hypertensive patients to two different drugs acting on the renin – angiotensin system , when patients are targeted according to the blood pressure levels recommended by recent hypertension guidelines", "BACKGROUND Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear . It has been suggested that antihypertensive therapy may reduce the risk of stroke , despite possibly increasing the risk of death . METHODS We r and omly assigned 3845 patients from Europe , China , Australasia , and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide ( sustained release , 1.5 mg ) or matching placebo . The angiotensin-converting-enzyme inhibitor perindopril ( 2 or 4 mg ) , or matching placebo , was added if necessary to achieve the target blood pressure of 150/80 mm Hg . The primary end point was fatal or nonfatal stroke . RESULTS The active-treatment group ( 1933 patients ) and the placebo group ( 1912 patients ) were well matched ( mean age , 83.6 years ; mean blood pressure while sitting , 173.0/90.8 mm Hg ) ; 11.8 % had a history of cardiovascular disease . Median follow-up was 1.8 years . At 2 years , the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group . In an intention-to-treat analysis , active treatment was associated with a 30 % reduction in the rate of fatal or nonfatal stroke ( 95 % confidence interval [ CI ] , -1 to 51 ; P=0.06 ) , a 39 % reduction in the rate of death from stroke ( 95 % CI , 1 to 62 ; P=0.05 ) , a 21 % reduction in the rate of death from any cause ( 95 % CI , 4 to 35 ; P=0.02 ) , a 23 % reduction in the rate of death from cardiovascular causes ( 95 % CI , -1 to 40 ; P=0.06 ) , and a 64 % reduction in the rate of heart failure ( 95 % CI , 42 to 78 ; P serious adverse events were reported in the active-treatment group ( 358 , vs. 448 in the placebo group ; P=0.001 ) . CONCLUSIONS The results provide evidence that antihypertensive treatment with indapamide ( sustained release ) , with or without perindopril , in persons 80 years of age or older is beneficial . ( Clinical Trials.gov number , NCT00122811 [ Clinical Trials.gov ] . )", "AIMS Major guidelines recommend lowering systolic blood pressure ( SBP ) to hypertensives , but evidence is missing whether this is beneficial in ( i ) uncomplicated hypertensives , ( ii ) grade 1 hypertensives , and ( iii ) elderly hypertensives . Providing this missing evidence is important to justify efforts and costs of aggressive therapy in all hypertensives . METHODS AND RESULTS Felodipine Event Reduction ( FEVER ) was a double-blind , r and omized trial on 9711 Chinese hypertensives , in whom cardiovascular outcomes were significantly reduced by more intense therapy ( low-dose hydrochlorothiazide and low-dose felodipine ) achieving a mean of 138 mmHg SBP compared with less-intense therapy ( low-dose hydrochlorothiazide and placebo ) achieving a mean of 142 mmHg . FEVER included older and younger patients , and patients with and without diabetes or cardiovascular disease . In the analyses here reported , Cox regression models assessed outcome differences between more and less-intense treatments in groups of patients with different baseline characteristics . Significant reductions in stroke were found in uncomplicated hypertensives ( -39 % , P = 0.002 ) , in hypertensives with r and omization SBP SBP was lowered by more intense treatment . Significant reductions ( between -29 and -47 % , P = 0.02 to all cardiovascular events and all deaths . Achieving mean SBP values cardiovascular events every 100 patients treated for 3.3 years . CONCLUSIONS These analyses provide strong support , missing so far , to guidelines recommending goal SBP < 140 mmHg in uncomplicated hypertensives , individuals with moderately elevated BP and elderly hypertensives", "The benefits of a systolic blood pressure ( BP ) below 150–160 mmHg are well established ; whether a systolic BP of less than 140 mmHg provides additional benefits remains controversial . This study was design ed to compare the 2-year effect of a strict treatment to maintain systolic BP below 140 mmHg ( group A ) and that of a mild treatment to maintain systolic BP at between 140 and below 160 mmHg ( group B ) . The study design followed the Prospect i ve R and omized Open Blinded End-point ( PROBE ) study . The subjects were elderly patients ( 65–85 years old ) who consistently had a systolic BP of 160 mmHg or higher . The baseline drug was efonidipine hydrochloride ( efonidipine ) , a long-acting dihydropiridine calcium antagonist . The primary endpoints were stroke , cardiac disease , vascular disease , and renal failure . After a run-in period of 2 to 4 weeks , 2,165 patients were assigned to group A and 2,155 patients to group B. There were no significant differences between the groups in sex , age , baseline BP , or other cardiovascular risk factors . The systolic BP was 7.2 mmHg lower ( p occlusive arterial disease in 1 patient , and renal failure in 1 patient ) . Five patients have died of stroke and 2 patients of myocardial infa rct ion . The primary -endpoint-related morbidity rate was 20.9/1,000 patient-years , and the mortality rate was 1.7/1,000 patient-years . Currently available results indicate that this study , one of the largest r and omized trials of antihypertensive therapy in elderly patients in Japan , was conducted safely . The final results are expected to provide important and practical information for the management of hypertension in elderly patients", "BACKGROUND Our underst and ing of the growing population of very old patients ( aged > or=80 years ) with coronary artery disease and hypertension is limited , particularly the relationship between blood pressure and adverse outcomes . METHODS This was a secondary analysis of the INternational VErapamil SR-Tr and olapril STudy ( INVEST ) , which involved 22,576 clinical ly stable hypertensive coronary artery disease patients aged > or=50 years . The patients were grouped by age in 10-year increments ( aged > or=80 , n=2180 ; 70- , n=6126 ; 60- , n=7602 ; , n=6668 ) . Patients were r and omized to either verapamil SR- or atenolol-based treatment strategies , and primary outcome was first occurrence of all-cause death , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS At baseline , increasing age was associated with higher systolic blood pressure , lower diastolic blood pressure , and wider pulse pressure ( P systolic , diastolic , and pulse pressure for each age group . However , the very old retained the widest pulse pressure and the highest proportion ( 23.6 % ) with primary outcome . The adjusted hazard ratio for primary outcomes showed a J-shaped relationship among each age group with on-treatment systolic and diastolic pressures . The systolic pressure at the hazard ratio nadir increased with increasing age , highest for the very old ( 140 mm Hg ) . However , diastolic pressure at the hazard ratio nadir was only somewhat lower for the very old ( 70 mm Hg ) . Results were independent of treatment strategy . CONCLUSION Optimal management of hypertension in very old coronary artery disease patients may involve targeting specific systolic and diastolic blood pressures that are higher and somewhat lower , respectively , compared with other age groups", "Background : Hypertension is associated with impaired cognitive function but the effect of antihypertensive treatment on cognitive function is unclear . Methods : We investigated the effect of treatment of hypertension on cognition with the angiotensin-receptor-blocker , c and esartan , in a placebo-controlled , double-blind , r and omized controlled trial at one center participating in the Study on Cognition and Prognosis in the Elderly . A total of 257 older adults with hypertension ( mean age 76 years , blood pressure 165 ± 8/88 ± 7 mm Hg ) were recruited from general practice and treated with 8–16 mg c and esartan or placebo once daily , for a mean follow-up period of 44 months . Additional antihypertensive therapy was permitted in both groups to achieve treatment targets . Cognitive function was measured using the Cognitive Drug Research computerized assessment battery , trail-making tests , and verbal fluency . Data from annual assessment s were used to calculate individual coefficients of decline by regressing composite test scores over time for five cognitive domains . Results : The blood pressure difference between groups at study close was 8/3 mm Hg . The c and esartan group showed less decline in attention ( 0.004 vs −0.036 , p = 0.04 ) and episodic memory ( 0.14 vs −0.22 , p = 0.04 ) compared to placebo , a similar trend for speed of cognition ( −2.3 vs −17.4 , p = 0.15 ) , but no differences in working memory ( 0.0014 vs 0.0010 , p = 0.90 ) or executive function ( −0.0031 vs −0.0023 , p = 0.95 ) . Effect sizes were in the small-to-moderate range . Conclusions : The potential for blood pressure – lowering with angiotensin-receptor-blockers to reduce the rate of decline of specific areas of cognitive function in older patients with hypertension warrants further investigation to determine clinical efficacy", "This study was performed to investigate whether intensive antihypertensive treatment with achieved blood pressure ( BP ) ≤140/90 mm Hg , as compared with st and ard treatment with achieved BP ≤150/90 mm Hg , could further improve cardiovascular outcomes in Chinese hypertensive patients older than 70 years . A total of 724 participants were r and omly assigned to intensive or st and ard antihypertensive treatment . After a mean follow-up of 4 years , the mean achieved BP was 135.7/76.2 mm Hg in the intensive treatment group and 149.7/82.1 mm Hg in the st and ard treatment group . The visit-to-visit variability in systolic BP and diastolic BP was lower in the intensive group than that in the st and ard group . Intensive antihypertensive treatment , compared with the st and ard treatment , decreased total and cardiovascular mortality by 41.7 % and 50.3 % , respectively , and reduced fatal/nonfatal stroke by 42.0 % and heart failure death by 62.7 % . Cox regression analysis indicated that the mean systolic BP ( P=.020 ; 95 % confidence interval , 1.006 - 1.069 ) and the st and ard deviation of systolic BP ( P=.033 ; 95 % confidence interval , 1.006 - 1.151 ) were risk factors for cardiovascular endpoint events . Intensive antihypertensive treatment with achieved 136/76 mm Hg was beneficial for Chinese hypertensive patients older than 70 years . Long-term visit-to-visit variability in systolic BP was positively associated with the incidence of cardiovascular events", "Reductions in mobility and cognitive function linked to accrual of brain microvascular disease related white matter hyperintensities ( WMHs ) on magnetic resonance imaging can occur in older hypertensive patients in as little as 2 years . We have design ed a trial evaluating 2 levels of ambulatory blood pressure ( ABP ) control in individuals with normal or mildly impaired mobility and cognition who have detectable cerebrovascular disease ( > 0.5 % WMH fraction of intracranial volume ) on functional outcomes . The study is a prospect i ve r and omized , open-label trial with blinded end points , in patients ages ≥75 years with elevated 24-hour systolic blood pressure ( BP ) ( 145 mm Hg in the untreated state ) who do not have unstable cardiovascular disease , heart failure , or stroke . The primary and key secondary outcomes in the trial are change from baseline in mobility and cognitive function and damage to brain white matter as demonstrated by accrual of WMH volume and changes in diffusion tensor imaging . Approximately 300 patients will be enrolled , and 200 r and omized to 1 of 2 levels of ABP control ( intensive to achieve a goal 24-hour systolic BP of ≤130 mm Hg or st and ard to achieve a goal 24-hour systolic BP of ≤145 mm Hg ) for a total of 36 months using similar antihypertensive regimens . The analytical approach provides 85 % power to show a clinical ly meaningful effect in differences in mobility accompanied by quantitative differences in WMH between treatment groups . The INFINITY trial is the first to guide antihypertensive therapy using ABP monitoring rather than clinic BP to reduce cerebrovascular disease", "BACKGROUND The optimal combination drug therapy for hypertension is not established , although current U.S. guidelines recommend inclusion of a diuretic . We hypothesized that treatment with the combination of an angiotensin-converting-enzyme ( ACE ) inhibitor and a dihydropyridine calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic . METHODS In a r and omized , double-blind trial , we assigned 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide . The primary end point was the composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , hospitalization for angina , resuscitation after sudden cardiac arrest , and coronary revascularization . RESULTS The baseline characteristics of the two groups were similar . The trial was terminated early after a mean follow-up of 36 months , when the boundary of the prespecified stopping rule was exceeded . Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril-amlodipine group and 132.5/74.4 mm Hg in the benazepril-hydrochlorothiazide group . There were 552 primary - outcome events in the benazepril-amlodipine group ( 9.6 % ) and 679 in the benazepril-hydrochlorothiazide group ( 11.8 % ) , representing an absolute risk reduction with benazepril-amlodipine therapy of 2.2 % and a relative risk reduction of 19.6 % ( hazard ratio , 0.80 , 95 % confidence interval [ CI ] , 0.72 to 0.90 ; P death from cardiovascular causes , nonfatal myocardial infa rct ion , and nonfatal stroke , the hazard ratio was 0.79 ( 95 % CI , 0.67 to 0.92 ; P=0.002 ) . Rates of adverse events were consistent with those observed from clinical experience with the study drugs . CONCLUSIONS The benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events . ( Clinical Trials.gov number , NCT00170950 .", "BACKGROUND Although it is widely accepted that clinical trials in heart failure may not apply to older population s , the magnitude of the discrepancy between trial population s and patients seen in community-based practice are not known . Our objective was to determine the proportion of older persons meeting enrollment criteria of r and omized controlled trials of agents that prolong life in heart failure . METHODS We conducted a cross-sectional study of Medicare beneficiaries > 64 years old with the principal diagnosis of heart failure who were discharged from acute care hospitals in the United States between April 1998 and March 1999 . Enrollment criteria of the Studies of Left Ventricular Dysfunction ( SOLVD ) , Metroprolol CR/LX R and omized Intervention Trial in Congestive Heart Failure ( MERIT-HF ) , and R and omized Aldactone Evaluation Study ( RALES ) trials were applied to the population , and the proportions meeting the criteria were determined by subgroups of age and sex . RESULTS Of the 20,388 patients studied , 18 % , 13 % , and 25 % met the enrollment criteria of the SOLVD , MERIT-HF , and RALES trials , respectively . Although trial eligibility was less than a third for any sex or age group , significantly fewer women than men met trial criteria ( 13 % vs 23 % for SOLVD , 11 % vs 17 % for MERIT-HF , and 21 % vs 32 % for RALES , P preserved left ventricular systolic function was twice as large as the proportion meeting the inclusion criteria for any trial . CONCLUSIONS A minority of hospitalized older persons with heart failure fit the profile of population s of clinical trials . There is an urgent need for research in heart failure for typical heart failure patients , including the very old , women , and patients with preserved left ventricular systolic function ", "Objective To explore the likely optimum blood pressure ( BP ) level for patients with a history of cerebrovascular disease . Methods The Perindopril Protection Against Recurrent Stroke Study ( PROGRESS ) was a r and omized , placebo-controlled trial that established the beneficial effects of BP lowering in 6105 patients with cerebrovascular disease . The present study comprises two series of post hoc analyses . The first was design ed to investigate the effects of r and omized treatment on recurrent stroke by baseline BP levels , and the second was a corresponding observational analysis investigating the association between achieved follow-up BP levels and recurrent stroke risk . Results Analyses of the r and omized treatment comparisons showed that BP lowering with combination therapy produced similar risk reductions in each of four subgroups defined by baseline BP of less than 120 , 120–139 , 140–159 , and 160 mmHg or greater ( P homogeneity = 0.5 ) . The effects of single-drug therapy were also comparable across these subgroups ( P homogeneity = 0.2 ) , but consistently greater benefits were observed with combination compared to single-drug therapy . The analyses of achieved follow-up BP showed that the lowest risk of recurrence was among the one-quarter of participants with the lowest follow-up BP levels ( median 112/72 mmHg ) , and that risks rose progressively with higher follow-up BP levels . Minor side-effects were progressively more common at lower BP levels ( P homogeneity = 0.04 ) , but there was no excess of serious complications ( all P homogeneity > 0.2 ) . Conclusion These analyses provide no evidence of a J-curve relationship between BP level and stroke risk among patients with cerebrovascular disease , and identify no patient group among whom more intensive BP lowering would not be expected to produce greater risk reductions" ]

[ "The immunological composition of breast milk differs between mothers . The reasons for these differences and the consequences for the breast-fed infants are poorly understood . The aim of this study was to evaluate the effect of probiotic Lactobacillus reuteri supplementation on the immunological composition of breast milk in relation to sensitization and eczema in the babies . Total IgA , secretory IgA ( SIgA ) , TGF-beta1 , TGF-beta2 , IL-10 , TNF , soluble CD14 ( sCD14 ) , and Na/K ratios were analyzed in colostrum and mature milk obtained from women treated with L. reuteri ( n = 54 ) or placebo ( n = 55 ) from gestational week 36 until delivery . Bacteriological analyses of L. reuteri were performed in faecal sample s of the mothers . The infants were followed prospect ively for 2 yr regarding development of eczema and sensitization as defined by a positive skin prick test and /or circulating allergen-specific IgE antibodies at 6 , 12 , and 24 months of age . Supplementation of L. reuteri during pregnancy was associated with low levels of TGF-beta2 and slightly increased levels of IL-10 in colostrum . For TGF-beta2 , this association was most pronounced in mothers with detectable L. reuteri in faeces . Infants receiving breast milk with low levels of TGF-beta2 were less likely to become sensitized during their first 2 yr of life . A similar trend was observed for development of IgE-associated eczema . The levels of total IgA , SIgA , TGF-beta1 , TNF , sCD14 , and Na/K ratios in breast milk were not affected by the intake of L. reuteri . None of these parameters correlated with sensitization or development of eczema in the infant , except for high Na/K ratios that associated with increased risk of sensitization . Supplementation with L. reuteri during late pregnancy reduces breast milk levels of TGF-beta2 , and low levels of this cytokine are associated with less sensitization and possibly less IgE-associated eczema in breast-fed infants", "BACKGROUND Reversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in western societies . In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life . Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora . We assessed the effect on atopic disease of Lactobacillus GG ( which is safe at an early age and effective in treatment of allergic inflammation and food allergy ) . METHODS In a double-blind , r and omised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative ( or partner ) with atopic eczema , allergic rhinitis , or asthma , and postnatally for 6 months to their infants . Chronic recurring atopic eczema , which is the main sign of atopic disease in the first years of life , was the primary endpoint . FINDINGS Atopic eczema was diagnosed in 46 of 132 ( 35 % ) children aged 2 years . Asthma was diagnosed in six of these children and allergic rhinitis in one . The frequency of atopic eczema in the probiotic group was half that of the placebo group ( 15/64 [ 23 % ] vs 31/68 [ 46 % ] ; relative risk 0.51 [ 95 % CI 0.32 - 0.84 ] ) . The number needed to treat was 4.5 ( 95 % CI 2.6 - 15.6 ) . INTERPRETATIONS Lactobacillus GG was effective in prevention of early atopic disease in children at high risk . Thus , gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics , for prevention of atopic disease", "A reduced microbial load early in life has been suggested to be linked to the increasing prevalence of allergic diseases in the industrialized world . Some studies have indicated that probiotics may be effective in the prevention of eczema . In vitro studies indicate that probiotics have immunomodulatory effects . In the present study , we evaluated the effects of feeding Lactobacillus F19 during weaning on the incidence of eczema and Th1/Th2 balance . In a double-blind , placebo-controlled r and omized intervention trial , infants were fed cereals with ( n = 89 ) or without Lactobacillus F19 ( n = 90 ) from 4 to 13 months of age . We assessed the cumulative incidence of eczema at 13 months of age . The ratio of interferon-gamma ( IFN-gamma ) to interleukin 4 ( IL4 ) mRNA expression levels in polyclonally stimulated peripheral blood T cells was used as a proxy for immune balance . Total and specific IgE serum levels were also assessed . The cumulative incidence of eczema at 13 months was 11 % ( 4 - 17 % , 95 % CI ) and 22 % ( 13 - 31 % , 95 % CI ) in the probiotic and placebo groups , respectively ( p IFN-gamma/IL4 mRNA ratio was higher in the probiotic compared with the placebo group ( p serum concentrations of IgE. In summary , feeding Lactobacillus F19 during weaning could be an effective tool in the prevention of early manifestation of allergy , e.g. , eczema . The higher Th1/Th2 ratio in the probiotic compared with the placebo group suggests enhancing effects of Lactobacillus F19 on the T cell-mediated immune response", "Background A modest number of prospect i ve studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results . Objective To examine the relationship between the bacterial diversity of the gut and the development of eczema in early life by methods other than stool culture . Methods Fecal sample s were collected from 21 infants at 1 and 4 months of life . Nine infants were diagnosed with eczema by the age of 6 months ( cases ) and 12 infants were not ( controls ) . After conducting denaturating gradient gel electrophoresis ( DGGE ) of stool sample s , we compared the microbial diversity of cases and controls using the number of electrophoretic b and s and the Shannon index of diversity ( H ' ) as indicators . Results Control subjects had significantly greater fecal microbial diversity than children with eczema at ages 1 ( mean H ' for controls = 0.75 vs. 0.53 for cases , P = 0.01 ) and 4 months ( mean H ' for controls = 0.92 vs. 0.59 for cases , P = 0.02 ) . The increase in diversity from 1 to 4 months of age was significant in controls ( P = 0.04 ) but not in children who developed eczema by 6 months of age ( P = 0.32 ) . Conclusion Our findings suggest that reduced microbial diversity is associated with the development of eczema in early life", "Controversy exists regarding the preventive effect of probiotics on the development of eczema or atopic dermatitis . We investigated whether supplementation of probiotics prevents the development of eczema in infants at high risk . In a r and omized , double-blind , placebo-controlled trial , 112 pregnant women with a family history of allergic diseases received a once-daily supplement , either a mixture of Bifidobacterium bifidum BGN4 , B. lactis AD011 , and Lactobacillus acidophilus AD031 , or placebo , starting at 4 - 8 wks before delivery and continuing until 6 months after delivery . Infants were exclusively breast-fed during the first 3 months , and were subsequently fed with breastmilk or cow 's milk formula from 4 to 6 months of age . Clinical symptoms of the infants were monitored until 1 yr of age , when the total and specific IgE against common food allergens were measured . A total of 68 infants completed the study . The prevalence of eczema at 1 yr in the probiotic group was significantly lower than in the placebo group ( 18.2 % vs. 40.0 % , p=0.048 ) . The cumulative incidence of eczema during the first 12 months was reduced significantly in probiotic group ( 36.4 % vs. 62.9 % , p=0.029 ) ; however , there was no difference in serum total IgE level or the sensitization against food allergens between the two groups . Prenatal and postnatal supplementation with a mixture of B. bifidum BGN4 , B. lactis AD011 , and L. acidophilus AD031 is an effective approach in preventing the development of eczema in infants at high risk of allergy during the first year of life", "Using a double blind r and omized placebo‐controlled trial ( Australian New Zeal and Clinical Trials Registry : ACTRN12607000518460 ) , we have shown that in a high risk birth cohort , maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation until 2 years with Lactobacillus rhamnosus HN001 ( HN001 ) ( 6 × 109 cfu/day ) halved the cumulative prevalence of eczema by age 2 years . Bifidobacterium animalis subsp lactis HN019 ( HN019 ) ( 9 × 109 cfu/day ) had no effect", "BACKGROUND An altered microbial exposure may underlie the increase of allergic diseases in affluent societies . Probiotics may alleviate and even prevent eczema in infants . OBJECTIVE To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri . METHODS Double-blind , r and omized , placebo-controlled trial , which comprised 232 families with allergic disease , of whom 188 completed the study . The mothers received L reuteri ATCC 55730 ( 1 x 10(8 ) colony forming units ) daily from gestational week 36 until delivery . Their babies then continued with the same product from birth until 12 months of age and were followed up for another year . Primary outcome was allergic disease , with or without positive skin prick test or circulating IgE to food allergens . RESULTS The cumulative incidence of eczema was similar , 36 % in the treated versus 34 % in the placebo group . The L reuteri group had less IgE-associated eczema during the second year , 8 % versus 20 % ( P = .02 ) , however . Skin prick test reactivity was also less common in the treated than in the placebo group , significantly so for infants with mothers with allergies , 14 % versus 31 % ( P = .02 ) . Wheeze and other potentially allergic diseases were not affected . CONCLUSION Although a preventive effect of probiotics on infant eczema was not confirmed , the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease . CLINICAL IMPLICATION Probiotics may reduce the incidence of IgE-associated eczema in infancy", "BACKGROUND Probiotics have shown promising potential in reducing the risk of eczema in infants . Optimal probiotic intervention regimen remains to be determined . OBJECTIVE We investigated whether maternal probiotic supplementation during pregnancy and breast-feeding reduces the risk of developing eczema in high-risk infants . METHODS This was a parallel , double-blind placebo-controlled trial of 241 mother-infant pairs . Mothers with allergic disease and atopic sensitization were r and omly assigned to receive ( 1 ) Lactobacillus rhamnosus LPR and Bifidobacterium longum BL999 ( LPR+BL999 ) , ( 2 ) L paracasei ST11 and B longum BL999 ( ST11+BL999 ) , or ( 3 ) placebo , beginning 2 months before delivery and during the first 2 months of breast-feeding . The infants were followed until the age of 24 months . Skin prick tests were performed at the ages of 6 , 12 , and 24 months . RESULTS Altogether 205 infants completed the follow-up and were included in the analyses . The risk of developing eczema during the first 24 months of life was significantly reduced in infants of mothers receiving LPR+BL999 ( odds ratio [ OR ] , 0.17 ; 95 % CI , 0.08 - 0.35 ; P chronically persistent eczema were 0.30 ( 95 % CI , 0.12 - 0.80 ; P = .016 ) and 0.17 ( 95 % CI , 0.05 - 0.56 ; P = .003 ) . Probiotics had no effect on the risk of atopic sensitization in the infants . No adverse effects were related to the use of probiotics . CONCLUSION Prevention regimen with specific probiotics administered to the pregnant and breast-feeding mother , that is , prenatally and postnatally , is safe and effective in reducing the risk of eczema in infants with allergic mothers positive for skin prick test", "To cite this article : Boyle RJ , Ismail IH , Kivivuori S , Licciardi PV , Robins‐Browne RM , Mah L‐J , Axelrad C , Moore S , Donath S , Carlin JB , Lahtinen SJ , Tang MLK . Lactobacillus GG treatment during pregnancy for the prevention of eczema : a r and omized controlled trial . Allergy 2011 ; 66 : 509–516", "BACKGROUND The role of probiotics in prevention of allergic disease is still not clearly established , although early reports suggested Lactobacillus GG halved the risk of eczema at 2 years . OBJECTIVE To determine whether probiotic supplementation in early life could prevent development of eczema and atopy at 2 years . METHODS Double-blind , r and omized placebo-controlled trial of infants at risk of allergic disease . Pregnant women were r and omized to take Lactobacillus rhamnosus HN001 ( L rhamnosus ) , Bifidobacterium animalis subsp lactis strain HN019 or placebo daily from 35 weeks gestation until 6 months if breast-feeding , and their infants were r and omized to receive the same treatment from birth to 2 years ( n = 474 ) . The infant 's cumulative prevalence of eczema and point prevalence of atopy , using skin prick tests to common allergens , was assessed at 2 years . RESULTS Infants receiving L rhamnosus had a significantly ( P = .01 ) reduced risk of eczema ( hazard ratio [ HR ] , 0.51 ; 95 % CI , 0.30 - 0.85 ) compared with placebo , but this was not the case for B animalis subsp lactis ( HR , 0.90 ; 95 % CI , 0.58 - 1.41 ) . There was no significant effect of L rhamnosus ( HR , 0.74 ; 95 % CI , 0.46 - 1.18 ) or B animalis subsp lactis ( HR , 0.82 ; 95 % CI , 0.52 - 1.28 ) on atopy . L rhamnosus ( 71.5 % ) was more likely than B animalis subsp lactis ( 22.6 % ) to be present in the feces at 3 months , although detection rates were similar by 24 months . CONCLUSION We found that supplementation with L rhamnosus , but not B animalis subsp lactis , substantially reduced the cumulative prevalence of eczema , but not atopy , by 2 years . Underst and ing how Lactobacilli act to prevent eczema requires further investigation", "BACKGROUND Supplementation with the probiotic Lactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy . This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age . OBJECTIVE To evaluate whether perinatal and infant supplementation with L. reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects . METHODS A r and omized , placebo-controlled trial with oral supplementation with L. reuteri ATCC 55730 ( 1 × 10(8 ) CFU ) during the last month of gestation and through the first year of life comprising 232 families with allergic disease , of whom 184 completed a 7-yr follow-up . The primary outcomes at 7 yr of age were allergic disease and skin prick test reactivity ( Clinical Trials.gov ID NCT01285830 ) . RESULTS The prevalence of asthma ( 15 % in the probiotic vs. 16 % in placebo group ) , allergic rhinoconjunctivitis ( 27 % vs. 20 % ) , eczema ( 21 % vs. 19 % ) and skin prick test reactivity ( 29 % vs. 26 % ) was similar in the probiotic and placebo group . Growth indices and gastrointestinal symptoms were similar in the two groups . No severe adverse events were reported . CONCLUSION The effect of L. reuteri on sensitization and IgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age . Thus , the effect of L. reuteri on the immune system seems to be transient . Administration of L. reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects", "BACKGROUND . The value of probiotics for primary prevention is controversial . Published trials vary considerably in study design and the applied probiotics , thereby limiting comparability of the results . OBJECTIVE . The purpose of this trial was to study the preventive effect of the probiotic Lactobacillus GG on the development of atopic dermatitis . METHODS . In a double-blind , placebo-controlled prospect i ve trial , 105 pregnant women from families with ≥1 member ( mother , father , or child ) with an atopic disease were r and omly assigned to receive either the probiotic Lactobacillus GG ( American Type Culture Collection 53103 ; 5 × 109 colony-forming units of Lactobacillus GG twice daily ) or placebo . Ninety-four families ( 89.5 % ) completed the trial . The supplementation period started 4 to 6 weeks before expected delivery , followed by a postnatal period of 6 months . The primary end point was the occurrence of atopic dermatitis at the age of 2 years . Secondary outcomes were severity of atopic dermatitis , recurrent episodes of wheezing bronchitis , and allergic sensitization at the age of 2 years . RESULTS . Atopic dermatitis was diagnosed in 14 ( 28 % ) of 50 in the Lactobacillus GG group and in 12 ( 27.3 % ) of 44 in the placebo group . The risk of atopic dermatitis in children on probiotics relative to placebo was 0.96 ( confidence interval 0.38–2.33 ) . Severity of atopic dermatitis was comparable between the 2 groups . Notably , children with recurrent ( ≥5 ) episodes of wheezing bronchitis were more frequent in the Lactobacillus GG group ( 26 % ; n = 13 ) , as compared with the placebo group ( 9.1 % ; n = 4 ) . No difference was observed between both groups in total immunoglobulin E concentrations or numbers of specific sensitization to inhalant allergens . CONCLUSIONS . Supplementation with Lactobacillus GG during pregnancy and early infancy neither reduced the incidence of atopic dermatitis nor altered the severity of atopic dermatitis in affected children but was associated with an increased rate of recurrent episodes of wheezing bronchitis . Therefore , Lactobacillus GG can not be generally recommended for primary prevention", "The prevalence of atopic diseases is increasing throughout the Western world , and means of primary prevention are needed to reverse this trend . The role of breast-feeding , the best source of infant nutrition , in protection against atopic disease remains elusive . In this double-blinded , placebo-controlled study of 62 mother-infant pairs , it is shown that administering probiotics to the pregnant and lactating mother increased the immunoprotective potential of breast milk , as assessed by the amount of anti-inflammatory transforming growth factor beta2 ( TGF-beta2 ) in the milk ( 2885 pg/mL [ 95 % CI , 1624 - 4146 ] in mothers receiving probiotics vs 1340 pg/mL [ 95 % CI , 978 - 1702 ] in mothers receiving placebo ; P = .018 ) . The risk of developing atopic eczema during the first 2 years of life in infants whose mothers received probiotics was significantly reduced in comparison with that in infants whose mothers received placebo ( 15 % and 47 % , respectively ; relative risk , 0.32 [ 95 % CI , 0.12 - 0.85 ] ; P = .0098 ) . Maternal atopy was a clear risk factor for atopic eczema in the infant . The infants most likely to benefit from maternal probiotic supplementation were those with an elevated cord blood IgE concentration . Administering probiotics during pregnancy and breast-feeding thus offers a safe and effective mode of promoting the immunoprotective potential of breast-feeding and provides protection against atopic eczema during the first 2 years of life", "The role of probiotics in prevention of allergic disease is still not clear ; efficacy may depend on the timing , dose , duration , and specific probiotic used . Using a double‐blind r and omized placebo‐controlled trial ( Australian New Zeal and Clinical Trials Registry : ACTRN12607000518460 ) , we have shown that in a high‐risk birth cohort , maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation from birth until 2 years with Lactobacillus rhamnosus HN001 ( HN001 ) ( 6 × 109 cfu/day ) halved the cumulative prevalence of eczema at 2 and 4 years . Bifidobacterium animalis subsp lactis HN019 ( HN019 ) ( 9 × 109 cfu/day ) had no significant effect " ]

[ "OBJECTIVE The aim of this study was to analyze the correlation between thromboembolic complications and antiplatelet drugs before and after neurointervention . METHODS Blood sample s and radiographic data of patients who received a neurointervention ( coil embolization , stent placement or both ) were collected prospect ively . Rapid platelet function assay-aspirin ( RPFA-ASA ) was used to calculate aspirin resistance in aspirin reaction units ( ARU ) . For clopidogrel resistance , a P2Y12 assay was used to analyze the percentage of platelet inhibition . ARU > 550 and platelet inhibition aspirin and clopidogrel resistance , respectively . RESULTS Both aspirin and clopidogrel oral pills were administered in fifty-three patients before and after neurointerventional procedures . The mean resistance values of all patients were 484 ARU and resistance to aspirin with an average of 597 ARU , and 33 ( 62.3 % ) of 53 patients showed resistance to clopidogrel with an average of resistance to both drugs , 5 of which suffered a thromboembolic complication after neurointervention ( mean values : 640 ARU and platelet inhibition Diabetic patients and patients with hypercholesterolemia displayed mean aspirin resistances of 513.7 and 501.8 ARU , and mean clopidogrel resistances of platelet inhibition using st and ard regimens is of great clinical importance and may help prevent cerebral ischemic events in the future . Neurointerventional research should focus on ideal doses , timing , choices , safety , and reliable measurements of antiplatelet drug therapy , as well as confirming the clinical relevance of aggregometry in cerebrovascular patients", "Essential thrombocythemia ( ET ) is characterized by enhanced platelet generation and thrombotic complications . Once-daily low-dose aspirin incompletely inhibits platelet thromboxane A(2 ) ( TXA(2 ) ) in the majority of ET patients . In the present study , we investigated the determinants of aspirin-insensitive platelet TXA(2 ) bio synthesis and whether it could be further suppressed by changing the aspirin dose , formulation , or dosing interval . In 41 aspirin-treated ET patients , the immature platelet count predicted serum TXB(2 ) independently of platelet count , age , JAK-2 V617F mutation , or cytoreduction ( β = 3.53 , P = .001 ) . Twenty-one aspirin-treated patients with serum TXB(2 ) ≥ 4 ng/mL at 24 hours after dosing were r and omized to the following 7-day regimens in a crossover design : enteric-coated aspirin 100 mg twice daily , enteric-coated aspirin 200 mg once daily , or plain aspirin 100 mg once daily . A twice-daily regimen caused a further 88 % median ( IQR , 78%-92 % , P and normalized the functional platelet response to aspirin , as assessed by urinary 11-dehydro-TXB(2 ) excretion and the VerifyNow Aspirin assay . Doubling the aspirin dose reduced serum TXB(2 ) only partially by 39 % median ( IQR , 29%-54 % , P of low-dose aspirin through faster renewal of platelet cyclooxygenase-1 , and impaired platelet inhibition can be rescued by modulating the aspirin dosing interval rather than the dose", "Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items", "Abstract Background : Aspirin resistance may increase up to more then threefold the risk of major cardiovascular events ( MACE ) in patients with stable coronary artery disease . Aim : The aim of our study was to determine ; the prevalence of aspirin resistance in patients with acute coronary syndromes , the role of aspirin resistance on outcome in the follow-up and the effect of clopidogrel therapy in the prevention of MACE in aspirin resistant subjects . Material and methods : We detected the prevelance of aspirin resistance in 105 patients with acute coronary syndrome . Platelet functions were analyzed in Platelet Function Analyzer (PFA)-100 ( Dade Behring , Germany ) with collagen and /or epinephrine ( Col/Epi ) and collagen and /or ADP ( Col/ADP ) cartridges . Primary end points of the study were myocardial infa rct ion , unstable angina , cardiac death . Results : 19 % ( n = 20 ) of patients were aspirin resistant by PFA-100 . In the follow-up , MACE occured in 9 patients ( 45 % ) with aspirin resistance and in 10 patients ( 11.7 % ) with aspirin sensitive platelet aggregation ( p = 0.001 ) . Multivariate analysis showed that aspirin resistance was an independant predictor of MACE . The prevalence of MACE in patients who were on clopidogrel treatment for 12 months were lower compared to those who were on a clopidogrel treatment for the first six months ( p = 0.040 ) . Conclusions : We determined that the MACE risk in patients with acute coronary syndromes having detected aspirin resistance , was higher at statistically significant levels compared to patients having aspirin sensitive platelet aggregation . Our results showed that aspirin resistance , was an independant predictor of MACE in patients with acute coronary syndrome", "Background — Poor clinical outcome in aspirin-treated patients has been termed aspirin resistance and may result from inadequate inhibition of platelet cyclooxygenase-1 ( COX-1 ) by aspirin . The objectives of this study were to determine prospect ively whether COX-1–dependent and other platelet function assays correlate with clinical outcomes in aspirin-treated patients . Methods and Results — Blood was collected before percutaneous coronary intervention from 700 consecutive aspirin-treated ( 81 or 325 mg for ≥3 days ) patients . Platelet function was tested by ( 1 ) serum thromboxane B2 ; ( 2 ) arachidonic acid – stimulated platelet surface P-selectin and activated glycoprotein IIb/IIIa and leukocyte – platelet aggregates ; and ( 3 ) platelet function analyzer (PFA)-100 collagen-epinephrine and collagen-ADP closure time ( CT ) . Adverse clinical outcomes of all-cause death , cardiovascular death , and major adverse cardiovascular events ( cardiovascular death , myocardial infa rct ion , hospitalization for revascularization , or acute coronary syndrome ) were assessed by telephone interview and /or medical record review . Clinical outcomes information was obtained at 24.8±0.3 months after platelet function testing . By univariate analysis , COX-1–dependent assays , including serum thromboxane B2 level , were not associated with adverse clinical outcomes , whereas the COX-1–independent assay , PFA-100 collagen-ADP CT 3.1 ng/mL and PFA-100 collagen-ADP CT 700 aspirin-treated patients presenting for angiographic evaluation of coronary artery disease , residual platelet COX-1 function measured by serum thromboxane B2 and COX-1–independent platelet function measured by PFA-100 collagen-ADP CT , but not indirect COX-1–dependent assays ( arachidonic acid – stimulated platelet markers , shortened PFA-100 collagen-epinephrine CT ) , correlate with subsequent major adverse cardiovascular events . This study suggests that multiple mechanisms , including but not confined to inadequate inhibition of COX-1 , are responsible for poor clinical outcomes in aspirin-treated patients , and therefore the term aspirin resistance is inappropriate", "Background — Patients with type 2 diabetes mellitus ( T2DM ) have reduced aspirin-induced pharmacodynamic effects . This may be attributed to increased platelet turnover rates result ing in an increased proportion of non – aspirin-inhibited platelets during the daily dosing interval . The hypothesis of this study was that an increase in the frequency of drug administration [ twice daily ( bid ) versus once daily ( od ) ] may provide more effective platelet inhibition in T2DM patients . Methods and Results — T2DM patients with stable coronary artery disease were prospect ively recruited . Patients modified their aspirin regimen on a weekly basis according to the following scheme : 81 mg/od , 81 mg/bid , 162 mg/od , 162 mg/bid , and 325 mg/od . Pharmacodynamic assessment s included light-transmittance aggregometry after arachidonic acid , collagen and adenosine diphosphate stimuli ; VerifyNow-Aspirin assay ; and serum thromboxane B2 ( TXB2 ) levels . Twenty patients were analyzed . All patients were sensitive and compliant to aspirin irrespective of dose , as assessed by arachidonic acid – induced aggregation . When aspirin was administered once daily , there was no significant effect on platelet reactivity by increasing the once-daily dosing using aspirin-sensitive assays ( collagen-induced aggregation and VerifyNow-Aspirin ) . An increase in aspirin dose by means of a second daily administration was associated with a significant reduction in platelet reactivity assessed by collagen-induced aggregation and VerifyNow-Aspirin between 81 mg/od and 81 mg/bid ( P aspirin dosing regimens on adenosine diphosphate – induced aggregation . A dose-dependent effect of aspirin was observed on serum TXB2 levels ( P=0.003 ) . Conclusions — Aspirin dosing regimens are associated with different pharmacodynamic effects in platelets from T2DM patients and stable coronary artery disease , with a twice-daily , low-dose aspirin administration result ing in greater platelet inhibition than once-daily administration as assessed by aspirin-sensitive assays and a dose-dependent effect on serum TXB2 levels . The clinical implication s of a modified aspirin regimen tailored to T2DM patients warrant further investigation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01201785", "Background Clopidogrel is administered to prevent stent thrombosis ; however , the uniformity of platelet inhibition after treatment and the influence of pretreatment reactivity on drug response have not been described . Methods and Results Platelet aggregation ( 5 and 20 μmol/L ADP ) , the activation of glycoprotein IIb/IIIa ( PAC‐1 antibody ) , and the expression of P‐selectin were measured in patients undergoing elective coronary stenting ( n=96 ) at baseline and at 2 hours , 24 hours , 5 days , and 30 days after stenting . All patients received aspirin ( 325 mg ) . Clopidogrel ( 300 mg ) was administered in the catheterization laboratory and followed by 75 mg daily . There was marked interindividual variability in drug response as measured by all markers that showed a normal distribution . Resistance , defined as baseline aggregation ( % ) minus posttreatment aggregation ( % ) ≤10 % by 5 μmol/L ADP , was present in 31 % and 15 % of patients at 5 and 30 days , respectively . Patients with the highest pretreatment platelet reactivity remained the most reactive at 24 hours after treatment ( P Interindividual variability in the platelet inhibitory response from clopidogrel occurs in patients undergoing elective coronary stenting . Patients with high pretreatment reactivity are least protected . Alternative pharmacological strategies and the association of adverse ischemic events should be investigated in these patients . ( Circulation . 2003 ; 107:2908‐2913 .", "BACKGROUND Late venous graft thrombosis , leading to recurrent ischemia , is frequently encountered in old , degenerated vein grafts with advanced atherosclerotic plaque formation . Aspirin has been indicated to maintain venous graft patency in the post-operative period . However , there is considerable evidence that aspirin resistance is of concern in patients with venous grafts . MATERIAL AND METHOD Prospect ively enrolled 14 patients ( 11 male , 3 female , Group 1 ) , who were shown to have at least one occluded saphenous vein graft on their late control coronary angiogram after bypass operation , were compared for the presence of aspirin resistance by PFA-100 with age- and sex-matched 14 patients ( 10 male , 4 female , Group 2 ) , who were found patent and well-functioning vein grafts without wall irregularities on late post-operative coronary angiograms ( mean 6.5+/-2.5 years ) , enrolled as a control group . RESULTS Mean CT of collagen/epinephrine cartridge in Group 1 was 197+/-85 s and significantly less than in Group 2 ( 279+/-44 s ; p=0.011 ) . It was found that 50 % of patients in Group 1 were so-called aspirin resistant , whereas in Group 2 , this ratio was 7.1 % ( p=0.033 ) . BMI ( p=0.038 , Beta=-0.322 ) , uric acid level ( p=0.023 , Beta=-0.355 ) , and CT by collagen/epinephrine cartridge ( p=0.008 , Beta=0.431 ) were independently predicting late occlusion of saphenous vein graft . CONCLUSION Aspirin resistance is highly prevalent in patients with occluded venous grafts at a relatively late period", "Background — Incomplete inhibition of platelet thromboxane generation , as measured by elevated urinary 11-dehydro thromboxane B2 concentrations , has been associated with an increased risk of cardiovascular events . We aim ed to determine the external validity of this association in aspirin-treated patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management and Avoidance ( CHARISMA ) trial and to determine whether there are any modifiable factors or interventions that lower urinary 11-dehydro thromboxane B2 concentrations that could thereby reduce cardiovascular risk . Methods and Results — Urinary 11-dehydro thromboxane B2 concentrations were measured in 3261 aspirin-treated patients at least 1 month after they had been r and omly assigned to placebo or clopidogrel . Baseline urinary 11-dehydro thromboxane B2 concentrations in the highest quartile were associated with an increased risk of stroke , myocardial infa rct ion , or cardiovascular death compared with the lowest quartile ( adjusted hazard ratio 1.66 , 95 % CI 1.06 to 2.61 , P=0.03 ) . Increasing age , female sex , history of peripheral artery disease , current smoking , and oral hypoglycemic or angiotensin-converting enzyme inhibitor therapy were independently associated with higher urinary concentrations of 11-dehydro thromboxane B2 , whereas aspirin dose ≥150 mg/d , history of treatment with nonsteroidal antiinflammatory drugs , history of hypercholesterolemia , and statin treatment were associated with lower concentrations . R and omization to clopidogrel ( versus placebo ) did not reduce the hazard of cardiovascular events in patients in the highest quartile of urinary 11-dehydro thromboxane B2 levels . Conclusions — In aspirin-treated patients , urinary concentrations of 11-dehydro thromboxane B2 are an externally valid and potentially modifiable determinant of stroke , myocardial infa rct ion , or cardiovascular death in patients at risk for atherothrombotic events", "A higher rate of clinical events in poor clopidogrel and /or aspirin responders was documented by using different methods to measure platelet function , but no conclusive data about the appropriate methodology to explore platelet reactivity are available . A total of 746 patients included in the cohort of the RECLOSE trial who had successful drug-eluting stent implantation were assessed for post-treatment residual platelet reactivity ( RPR ) in platelet-rich plasma by 10 microM adenosine 5'-diphosphate ( ADP ) , 1 mM arachidonic acid ( AA ) and 2 microg/ml collagen-induced platelet aggregation and in whole blood by the PFA-100 system . At six-month follow-up , RPR by two stimuli ( ADP and AA or ADP and collagen ) and by three stimuli ( ADP , AA and collagen ) is significantly associated with higher percentage of primary ( definite or probable stent thrombosis ) and secondary ( cardiac mortality and stent thrombosis ) end-points than RPR by ADP , AA , collagen and PFA-100 system . According to the primary and secondary end points , the specificity values for RPR identified by two ( ADP and AA:94 % ; ADP and collagen:97 % ) and three stimuli were higher with respect to RPR by ADP ( 88 % ) , or RPR by AA ( 83 % ) or RPR by collagen ( 90 % ) . The positive likelihood ratio values of RPR by three stimuli ( 9.55 ) or of RPR by ADP and collagen ( 8.08 ) were higher than those of RPR by ADP ( 2.59 ) , by AA ( 2.05 ) , by collagen ( 4.73 ) , or by PFA-100 ( 2.63 ) . This prospect i ve study documents that the evaluation of platelet reactivity addressed to identify patients at risk of thrombotic events on dual antiplatelet treatment has to be carried out by methods able to explore different pathways", "The failure of aspirin to inhibit platelet function has been documented in patients undergoing coronary artery bypass graft ( CABG ) surgery , but the causes of \" aspirin-resistance \" remain uncertain . The aim of this study was to investigate the efficacy of aspirin in patients undergoing CABG surgery receiving either 100 mg or 325 mg of oral aspirin for 5-days . Platelet function was tested the day before surgery and on day + 1 and day + 5 , and evaluated by changes in collagen-induced thromboxane-A2 ( TxA2 ) release and platelet aggregation following stimulation with collagen , ADP and epinephrine . In all patients , baseline platelet aggregation was significantly inhibited by pre-incubation with in vitro aspirin ( 150 micromol/l ) , with a mean reduction in TxA2-release of > or=95.5 % ( 82.3,99.1 ) . After 5-days of oral aspirin , platelet aggregation was significantly inhibited , and was not further inhibited by in vitro aspirin . Oral aspirin was also associated with a > or=99.5 % ( 97.8 , 99.7 ) reduction in TxA2-release , and with the reversal of the second-phase of ADP-induced aggregation which is TxA2-dependent . In addition a single-dose of 325 mg aspirin on the first post-operative morning may have a greater inhibitory effect on collagen-induced aggregation than 100 mg aspirin . Western blot analysis provided no evidence for the presence of COX-2 in platelets , while the up-regulation of p38-MAPK following platelet-stimulation and surgery was seen . The inhibition of COX-2 ( NS398 ) or p38-MAPK ( SB203580 ) activity did not affect platelet aggregation and TxA2-release on day + 5 . In summary , there was no evidence for inherent or acquired aspirin-resistance in this surgical population , or for the involvement of either COX-2 or p38-MAPK", "Purpose : Platelets play a critical role in the pathogenesis of acute brain ischaemia . We studied the association between the degree of inhibition of platelet function by aspirin ( ASA ) and the severity and outcome of acute brain ischaemia . Methods : Platelet responsiveness to ASA was assessed in patients with acute brain ischaemia , treated with ASA since hospital admission . The degree of ASA responsiveness was assessed by optical aggregometry and categorized into patients with good response , partial response and complete unresponsiveness to ASA ( good responders , partial responders and non-responders , respectively ) . An additional evaluation of responsiveness to ASA was performed by Impact-R ( cone and platelet analyzer ) . Patients underwent serial clinical assessment during hospitalization , at discharge and during follow-up . Results : Among 105 patients ( mean age 63 ± 12 years ; 66 % men ) , impaired ASA responsiveness at baseline as assessed by aggregometry was associated with increased stroke severity at baseline , unfavourable clinical course , and poor functional outcome during follow-up ( p for severe stroke on admission ( 95 % CI 2.8–34.9 ) , 3.1 for lack of early clinical improvement ( 95 % CI 1.1–8.8 ) and 8.6 for poor functional outcome during follow-up ( 95 % CI 2.4–30.4 ) . Less robust trends were observed with the Impact-R. Conclusions : Impaired responsiveness to ASA in acute brain ischaemia is common and is associated with worse neurological deficits at stroke onset , early clinical deterioration and poorer functional outcome . The clinical significance of these findings requires further evaluation in larger longitudinal studies", "BACKGROUND Various platelet function tests are currently used to measure responsiveness to antiplatelet therapy . We sought to compare 2 point-of-care platelet function tests , VerifyNow Assay ( Accumetrics , San Diego , CA ) and Multiple Electrode Platelet Aggregometry ( MEA ) ( Dynabyte , Munich , Germany ) , for predicting early clinical outcomes after percutaneous coronary intervention . METHODS Platelet reactivity in the arachidonic acid-induced and adenosine diphosphate (ADP)-induced platelet aggregation was measured simultaneously with the VerifyNow Assay and MEA in 222 patients undergoing percutaneous coronary intervention between August and October 2009 . We investigated the correlations between the 2 tests and performed receiver operating characteristic curve analysis for major adverse cardiovascular events ( MACE ) , a composite of death , myocardial infa rct ion ( MI ) , stroke , and target vessel revascularization , at 30 days . RESULTS Major adverse cardiovascular events occurred in 19 patients ( 8.6 % ) , including 14 patients with periprocedural MI and 5 patients with stroke . Correlations were weak between the 2 tests in the arachidonic acid-induced ( Spearman r = 0.189 , P = .006 ) and ADP-induced platelet reactivity ( Spearman r = 0.390 , P VerifyNow P2Y12 Assay ( Accumetrics ) was able to predict periprocedural MI ( area under the aggregation curve 0.680 , P = .024 ) and 30-day MACE ( area under the aggregation curve 0.649 , P = .032 ) , VerifyNow Aspirin Assay ( Accumetrics ) , MEA ASPI test , and MEA ADP test failed to predict such clinical events . Hyporesponsiveness to clopidogrel based on the VerifyNow Assay was associated with about a 6-fold increased risk of MACE at 30 days . CONCLUSIONS Hyporesponsiveness to clopidogrel measured by VerifyNow Assay was able to identify patients with dual antiplatelet therapy who were at higher risk for periprocedural MI and MACE at 30 days . Further r and omized studies are required to vali date the effectiveness of different platelet function tests for predicting long-term clinical outcomes", "OBJECTIVE Evidence is growing that some patients are not responsive to the antithrombotic action of aspirin . We prospect ively evaluated the ability of aspirin resistance status , determined by PFA-100 , to predict new thrombotic events in patients with stable ischemic cerebrovascular disease . METHODS We studied 129 consecutive patients with stroke , transient ischemic attack ( TIA ) or vascular cognitive impairment . We assessed relationships between aspirin resistance , risk factors for ischemic cerebrovascular disease , and occurrence of new thrombotic events ( composite of stroke , TIA , myocardial infa rct ion , and cardiovascular death ) . RESULTS Aspirin resistance , found in 26 ( 20.1 % ) cases , was unrelated to any of the examined vascular risk factors . During mean follow-up of 56 months , new thrombotic events occurred in 19 patients ( 14.7 % ) , four with aspirin resistance ( 15.4 % ) and 15 ( 14.6 % ) without aspirin resistance ( p=1.00 ) . CONCLUSION Aspirin resistance determined by PFA-100 does not predict new thrombotic events in patients with stable ischemic cerebrovascular disease", "OBJECTIVES This study was design ed to determine if aspirin resistance is associated with clinical events . BACKGROUND Aspirin resistance , defined by platelet function testing and presumed clinical unresponsiveness to aspirin , has been previously reported by our group and others . However , little information exists linking the laboratory documentation of aspirin resistance and long-term clinical events . METHODS We prospect ively enrolled 326 stable cardiovascular patients from 1997 to 1999 on aspirin ( 325 mg/day for > or = 7 days ) and no other antiplatelet agents . We tested for aspirin sensitivity by optical platelet aggregation using adenosine diphosphate ( ADP ) and arachidonic acid ( AA ) . The primary outcome was the composite of death , myocardial infa rct ion ( MI ) , or cerebrovascular accident ( CVA ) . Mean follow-up was 679 + /- 185 days . Aspirin resistance was defined as a mean aggregation of > or = 70 % with 10 microM ADP and > or = 20 % with 0.5 mg/ml AA . RESULTS Of the patients studied , 17 ( 5.2 % ) were aspirin resistant and 309 ( 94.8 % ) were not aspirin resistant . During follow-up , aspirin resistance was associated with an increased risk of death , MI , or CVA compared with patients who were aspirin sensitive ( 24 % vs. 10 % , hazard ratio [ HR ] 3.12 , 95 % confidence interval [ CI ] 1.10 to 8.90 , p = 0.03 ) . Stratified multivariate analyses identified platelet count , age , heart failure , and aspirin resistance to be independently associated with major adverse long-term outcomes ( HR for aspirin resistance 4.14 , 95 % CI 1.42 to 12.06 , p = 0.009 ) . CONCLUSIONS This study demonstrates the natural history of aspirin resistance in a stable population , documenting a greater than threefold increase in the risk of major adverse events associated with aspirin resistance", "Recently , great interest has focused on the phenomenon of aspirin resistance , which may be defined as clinical or laboratory resistance . Monitoring the antiplatelet effect appears to be relevant in the presence of clinical implication s , but no data are available on the possible clinical implication s of the failure of aspirin to inhibit tests of platelet function in the setting of acute coronary syndromes . This study evaluated the role of aspirin resistance in the occurrence of 1-year major adverse coronary events ( MACEs ) in patients with acute myocardial infa rct ion ( AMI ) who have undergone percutaneous coronary intervention ( PCI ) . We prospect ively evaluated 146 patients ( 115 men and 31 women ; median age 65 years , range 30 to 84 ) with AMI who underwent primary PCI . Exclusion criteria were the use of glycoprotein IIb/IIIa inhibitors , hematocrit Platelet function analyzer-100 closure times by collagen-epinephrine were used for measuring platelet function in venous blood sample s obtained 12 to 15 hours after revascularization . Patients were considered aspirin resistant in the presence of a collagen-epinephrine closure time of MACEs were recorded in 44 of 146 patients ( 30.1 % ) . A significantly higher percentage of patients with MACEs had aspirin resistance ( 39.1 % vs 23.2 % , p overall risk of MACEs was significantly higher among patients with aspirin resistance ( p = 0.02 ) . A Cox regression analysis that adjusted for age , gender , traditional cardiovascular risk factors , systolic left ventricular function , number of stenosed coronary arteries , and previous AMI , PCI , or coronary artery bypass graft showed aspirin resistance to be a significant and independent risk factor for the future MACEs ( hazard ratio 2.9 , 95 % confidence interval 1.1 to 9.2 , p aspirin resistance after PCI is a significant and independent predictor of MACEs in patients with AMI undergoing primary PCI", "Background Antiplatelet therapy has been proven to be effective for both primary and secondary prevention of myocardial infa rct ion , stroke , and cardiovascular death . However , a significant proportion of patients treated with aspirin experience ischemic events . A number of prospect i ve studies have demonstrated that decreased responsiveness to antiplatelet therapy as measured by various methods , is strongly associated with an increase in clinical events . Our objective was to characterize platelet function in patients presenting with chest pain using a point-of-care assay , PFA-100 ® and correlating results to traditional platelet aggregometry to determine if patients with aspirin non-responsiveness have increased clinical sequelae . Methods Platelet function was assessed using PFA-100 ® , flow cytometry , and optical aggregometry in 94 patients presenting to the emergency department with chest pain . All patients were on aspirin 81–325 mg daily . Clinical events occurring during the index hospitalization were documented . Results Forty-seven patients ( 50 % ) were defined as aspirin non-responders by PFA-100 ® ( collagen-epinephrine closure time ≤ 193 ) . Compared to aspirin responders , aspirin non-responders had higher levels of mean platelet aggregation to adenosine diphosphate ( ADP ) ( P = 0.004 ) and high dose epinephrine ( P = 0.03 ) . Furthermore , expression of PAC-1 was significantly increased in patients with aspirin nonresponse as compared to aspirin responders ( P = 0.003 and P = 0.0006 respectively ) . No significant difference in clinical events during the index hospitalization was noted between aspirin non-responders and aspirin responders . Conclusion Patients presenting with chest pain who have abnormal PFA-100 closure times have increased platelet aggregation and activation however this aspirin non-responsiveness does not correlate with increased clinical events in the index hospitalization", "Background and Purpose — Incomplete platelet inhibition by aspirin ( aspirin resistance ) may be a reason for stroke recurrence in some patients . 11-Dehydrothromboxane B2 ( 11-DTB2 ) is a stable thromboxane A2 metabolite that reflects in vivo platelet activation . This pilot study was intended to evaluate the reproducibility of urinary 11-DTB2 over time and to look for evidence of aspirin resistance . Methods — All subjects were screened for the African American Antiplatelet Stroke Prevention Study ( AAASPS ) 7 to 90 days after noncardioembolic cerebral infa rct ion . Of 83 subjects with at least 1 urine sample , 52 were enrolled in AAASPS ( r and omized to blinded treatment with aspirin 650 mg/d or ticlopidine 500 mg/d ) , and 31 were enrolled in an open-label antiplatelet therapy cohort . Subjects were followed up for 2 years , with 11-DTB2 measurements scheduled at baseline and 6 , 12 , and 24 months . Vascular events were cerebral infa rct ion , myocardial infa rct ion , or vascular death . Results — Despite considerable individual up or down fluctuations , the median 11-DTB2 change did not significantly differ from zero in any of the subgroups . However , in 6 subjects with a 4-fold decrease in aspirin dose from 1300 to 325 or 81 mg/d , the 11-DTB2 level increased from 611 to 1881 pg/mg creatinine ( P = 0.06 ) . Vascular events occurred in 7 of 61 aspirin-treated subjects , and 11-DTB2 levels did not correlate with the events . Conclusions — Fluctuations in urinary 11-DTB2 after cerebral infa rct ion in blacks do not correlate with changes in aspirin doses , except perhaps when the dose changes by a factor of 4 or more . A larger study is needed to look further for aspirin resistance", "OBJECTIVE A population -based point-prevalence study was conducted to determine the prevalence of peripheral arterial disease ( PAD ) in Sweden , with special attention to critical limb ischemia and sex differences . METHODS An age-st and ardized r and omly selected population sample of 8000 women and men , aged 60 to 90 years , from four different regions in Sweden was invited to participate . The sample had the same age and gender distribution as the Swedish population in this age group . Participating subjects completed question naires on medical history , present medication , and symptoms , and their ankle-brachial index ( ABI ) was measured . Subjects were analyzed for presence of PAD according to reported symptoms and an ABI A total of 5080 subjects were included , giving a participation rate of 64 % . The prevalence of any PAD , asymptomatic PAD , intermittent claudication , and severe limb ischemia was , respectively , 18 % ( 95 % confidence interval [ CI ] , 16 % to 20 % ) 11 % ( 9 % to 13 % ) , 7 % ( 6.5 to 7 % ) and 1.2 % ( 1 % to 1.5 % ) . Women had a higher prevalence than men when PAD was diagnosed with ABI only ; that is , asymptomatic PAD ( 12.6 % vs 9.4 % , P=.03 ) and severe limb ischemia ( 1.5 % vs 0.8 % , P prevalence of any PAD was 7.9 % in the age group 60 to 65 years and increased to 47.2 % among the age group 85 to 90 years . Severe limb ischemia occurred in 0.3 % in the youngest age group , was highest in the age group 80 to 84 years at 3.3 % , and declined to 2.5 % among the oldest . The prevalence of PAD differed between regions ( P Sweden , and almost a fifth of all elderly individuals have some stage of this disease . Women are more often afflicted than men . The prevalence of severe ischemia , as a measure of critical limb ischemia , is about 1 % the population", "We tested whether cyclooxygenase 2 ( COX-2 ) expression and unacetylated COX-1 in newly formed platelets might contribute to persistent thromboxane ( TX ) bio synthesis in aspirin-treated essential thrombocythemia ( ET ) . Forty-one patients on chronic aspirin ( 100 mg/day ) and 24 healthy subjects were studied . Platelet COX-2 expression was significantly increased in patients and correlated with thiazole orange-positive platelets ( r = 0.71 , P rate of TXA(2 ) bio synthesis in vivo , as reflected by urinary 11-dehydro-TXB(2 ) ( TXM ) excretion , and the maximal biosynthetic capacity of platelets , as reflected by serum TXB(2 ) , were higher in patients compared with aspirin-treated healthy volunteers . Serum TXB(2 ) was significantly reduced by the selective COX-2 inhibitor NS-398 added in vitro . Patients were r and omized to adding the selective COX-2 inhibitor , etoricoxib , or continuing aspirin for 7 days . Etoricoxib significantly reduced by approximately 25 % TXM excretion and serum TXB(2 ) . Fourteen of the 41 patients were studied again 21 ( + /- 7 ) months after the first visit . Serum TXB(2 ) was consistently reduced by approximately 30 % by adding NS398 in vitro , while it was completely suppressed with 50 microM aspirin . Accelerated platelet regeneration in most aspirin-treated ET patients may explain aspirin-persistent TXA(2 ) bio synthesis through enhanced COX-2 activity and faster renewal of unacetylated COX-1 . These findings may help in reassessing the optimal antiplatelet strategy in ET", "OBJECTIVES This study sought to determine the incidence of aspirin nonresponsiveness in addition to clopidogrel nonresponsiveness and whether this association identifies patients at an increased risk of drug-eluting stent ( DES ) thrombosis . BACKGROUND Nonresponsiveness to clopidogrel is a predictor of DES thrombosis . No prospect i ve data exist about the possible association of dual nonresponsiveness to clopidogrel and aspirin with DES thrombosis . METHODS Platelet function was assessed after a loading dose of 600 mg clopidogrel in 746 patients who had successful DES implantation followed by 6-month dual-antiplatelet therapy . Platelet reactivity was assessed by light transmittance aggregometry using adenosine 5'-diphosphate , arachidonic acid , and collagen . The primary end point was definite/probable DES thrombosis at 6 months . The secondary end point was the composite of cardiac mortality and DES thrombosis . RESULTS The incidence of dual nonresponsiveness to aspirin and clopidogrel was 6 % . Definite/probable DES thrombosis was significantly higher in dual aspirin and clopidogrel nonresponders ( 11.1 % ) than in clopidogrel and aspirin responders ( 2.1 % , p clopidogrel nonresponders ( 2.2 % , p aspirin nonresponders ( 2.3 % , p the secondary end point was 4.4 % in isolated clopidogrel nonresponders , 2.3 % in isolated aspirin nonresponders , and 13.3 % in dual aspirin and clopidogrel nonresponders . Dual clopidogrel and aspirin nonresponsiveness was an independent predictor of DES thrombosis ( hazard ratio : 3.18 , 95 % confidence interval : 1.14 to 8.83 , p = 0.027 ) and the composite of cardiac mortality and DES thrombosis ( hazard ratio : 2.94 , 95 % confidence interval : 1.16 to 7.41 , p = 0.022 ) . CONCLUSIONS Dual nonresponsiveness to aspirin and clopidogrel is a relatively infrequent condition that identifies patients at a very high risk of DES thrombosis or death", "Prognostic markers help to stratify patients for treatment by identifying patients with different risks of outcome ( e.g. recurrence of disease ) , and are important tools in the management of cancer and many other diseases . Systematic review and meta-analytical approaches to identifying the most valuable prognostic markers are needed because ( sometimes conflicting ) evidence relating to markers is often published across a number of studies . To investigate the practicality of this approach , an empirical investigation of a systematic review of tumour markers for neuroblastoma was performed ; 260 studies of prognostic markers were identified , which considered 130 different markers . The reporting of these studies was often inadequate , in terms of both statistical analysis and presentation , and there was considerable heterogeneity for many important clinical /statistical factors . These problems restricted both the extraction of data and the meta- analysis of results from the primary studies , limiting feasibility of the evidence -based approach . Guidelines for reporting the results of primary prognostic marker studies in cancer , and other diseases , are given in order to facilitate both the interpretation of individual studies and the undertaking of systematic review s , meta- analysis and , ultimately , evidence -based practice . General availability of full individual patient data is a necessary step forward and would overcome the majority of problems encountered , including poorly reported summary statistics and variability in cutoff level , outcome assessed and adjustment factors used . It would also limit the problem of reporting bias , although publication bias will remain a concern until studies are prospect ively registered . Such changes in practice would help important evidence -based review s to be conducted in order to establish the most appropriate prognostic markers for clinical use , which should ultimately improve patient care", "Reduced effectiveness of the most common antiplatelet drug , acetylsalicylic acid ( ASA , aspirin ) , in diabetes mellitus has been associated with a lowered platelet sensitivity to ASA and related to glycemic control in diabetic patients . Our objectives were ( a ) to monitor the chemical background of how chronic hyperglycemia affects platelet response to ASA in diabetes and ( b ) to study a chemical competition between the amount of bound acetyl residues and the extent of protein glycation in blood platelets . Using whole-blood impedance aggregometry and platelet function analyzer ( PFA-100 ) we observed a reduced platelet response to ASA in diabetic patients ( 14 % vs. 79 % for PFA-100 collagen-epinephrine occlusion time ) and an association between the index of glycemic control and platelet refractoriness to ASA ( rS=−0.378 ) . Impaired platelet response to ASA was related to enhanced platelet protein glycation ( 3.6±0.4 in diabetes vs. 2.3±0.4 µmol fructosamine/µg protein in control ) and reduced incorporation of acetyl residue into proteins of platelets from diabetic patients ( 47.4±2.0 in control vs. 33.1±0.7 µmol acetyl/µg protein in diabetic subjects ) . Incubation of blood platelets with increasing concentrations of glucose and ASA under in vitro conditions led to excessive modification in protein amino groups : glucose and ASA competed with each other in the course of nonenzymatic modifications , glycosylation , or acetylation , and their contributions to the occupancy of protein amino groups ( R2=0.22 for glucose , R2=0.43 for ASA ) were dependent upon the concentrations of glucose and ASA . Overall the effects of high glucose and high ASA on the overall occupancy of protein free amino groups are not additive . While at higher concentrations ASA overcomes the effects of hyperglycemia and retards glycation , high glucose makes acetylation less efficient , and therefore the result ant chemical modification becomes greatly reduced . In conclusion , diminished susceptibility of various platelet proteins and receptors on blood platelet membranes to acetylation and high ambient glucose might underlie the apparently differentiated sensitivity of blood platelets to ASA and determine platelet “ insensitivity to aspirin ” in diabetic", "Background and Purpose — Recent studies suggest that patients who do not respond to aspirin ( ASA ) therapy may be at increased risk of ischemic vascular events . The availability of simple to use point-of-care ( POC ) platelet function tests now potentially allows aspirin nonresponsiveness to be identified in routine clinical practice . However , there are very few data on whether the different tests produce consistent results . We therefore compared 2 POC tests ( PFA-100 device and the Ultegra-RPFA [ RPFA ] ) with conventional light transmission aggregometry ( LTA ) . Methods — Platelet function was assessed by all 3 tests in 100 patients receiving low-dose ASA therapy after transient ischemic attack ( TIA ) or ischemic stroke . Results — The incidence of ASA nonresponsiveness was 17 % by the RPFA and 22 % by the PFA-100 , compared with only 5 % by LTA ( ie , as defined with both arachidonic acid and ADP ) . Agreement between the RPFA and the PFA-100 and arachidonic acid induced LTA was poor ( & kgr;=0.16 , 95 % CI , −0.08 to 0.39 , P=0.11 ; and & kgr;=0.09 −0.12 to 0.30 , P=0.32 , respectively ) . Agreement between the 2 POC tests was also poor ( & kgr;=0.14 , −0.08 to 0.36 , P=0.15 ) . Only 2 % of patients were aspirin nonresponders by all 3 tests . Conclusions — The prevalence of apparent ASA nonresponsiveness was higher with both the POC tests than with LTA . However , agreement between the tests was poor and very few patients were ASA nonresponsive by all 3 tests . Aspirin nonresponsiveness is therefore highly test-specific and large prospect i ve studies will be required to determine the prognostic value of each of the separate tests", "BACKGROUND Patients ' responses to oral antiplatelet therapy are subject to variation . Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy . METHODS We r and omly assigned 2440 patients scheduled for coronary stenting at 38 centers to a strategy of platelet-function monitoring , with drug adjustment in patients who had a poor response to antiplatelet therapy , or to a conventional strategy without monitoring and drug adjustment . The primary end point was the composite of death , myocardial infa rct ion , stent thrombosis , stroke , or urgent revascularization 1 year after stent implantation . For patients in the monitoring group , the VerifyNow P2Y12 and aspirin point-of-care assays were used in the catheterization laboratory before stent implantation and in the outpatient clinic 2 to 4 weeks later . RESULTS In the monitoring group , high platelet reactivity in patients taking clopidogrel ( 34.5 % of patients ) or aspirin ( 7.6 % ) led to the administration of an additional bolus of clopidogrel , prasugrel , or aspirin along with glycoprotein IIb/IIIa inhibitors during the procedure . The primary end point occurred in 34.6 % of the patients in the monitoring group , as compared with 31.1 % of those in the conventional-treatment group ( hazard ratio , 1.13 ; 95 % confidence interval [ CI ] , 0.98 to 1.29 ; P=0.10 ) . The main secondary end point , stent thrombosis or any urgent revascularization , occurred in 4.9 % of the patients in the monitoring group and 4.6 % of those in the conventional-treatment group ( hazard ratio , 1.06 ; 95 % CI , 0.74 to 1.52 ; P=0.77 ) . The rate of major bleeding events did not differ significantly between groups . CONCLUSIONS This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting , as compared with st and ard antiplatelet therapy without monitoring . ( Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others ; A RCT IC Clinical Trials.gov number , NCT00827411 . )", "INTRODUCTION An increasing amount of evidence indicates that platelet reactivity , despite a st and ard anti-thrombotic therapy , is a potential risk factor for recurrent myocardial ischemia in patients with coronary artery disease . We now hypothesize that this condition , measured by collagen-epinephrine ( CEPI ) or collagen-ADP ( CADP ) closure times ( CT ) by Platelet Function Analyzer ( PFA-100 ) , may predict the recurrence of coronary events after percutaneous coronary intervention ( PCI ) . MATERIAL S AND METHODS CEPI and CADP-CT were measured 30+/-8 h after PCI in 175 consecutive patients admitted with a diagnosis of stable angina ( n=94 ) or acute coronary syndromes ( n=81 ) and prospect ively followed up for a mean period of 6 months . We stratified the patients in accordance to both the CEPI-CT ( 190 s ) , reflecting the intensity of cycloxygenase inhibition by aspirin and the distribution into quartiles for CADP-CT . RESULTS CEPI-CT rate of clinical recurrence ( hazard ratio 8.5 , p Multivariate analysis after adjustment for other risk factors confirmed that the lowest CADP-CT quartile significantly correlates with the risk of recurrent coronary events ( hazard ratio 36.5 , p platelet function after PCI when measured under high shear rates by PFA-100 is an independent predictor of a worst clinical outcome , even during a short term follow-up and may help in patients risk stratification", "Non-responsiveness to aspirin as detected by laboratory tests may identify patients at high risk for future vascular events . The aim of this prospect i ve study was to evaluate whether non-responsiveness to aspirin is stable over time . Ninety-eight patients with stable peripheral arterial occlusive disease ( PAOD ) treated with 100 mg/d aspirin were followed over a median timeframe of 17 months . Platelet function tests were performed initially and at follow-up using arachidonic acid-induced light transmittance aggregometry ( LTA ) in native platelet-rich plasma with the Behring Coagulation Timer ® and by measuring the collagen−epinephrine closure time ( CT ) on a Platelet Function Analyzer ( PFA-100 ® ) . When determining platelet function using LTA , four patients ( 4.1 % ) had residual platelet function ( i.e. , MaxAggr ≥78 % ) despite aspirin treatment , whereas , according to the PFA-100 ® results , 12 patients ( 12.2 % ) were identified as non-responders ( i.e. , CT Fifty-seven patients who were still under treatment with 100 mg/d aspirin at the time of follow-up provided a second blood sample . Further platelet function tests with the PFA-100 ® system identified a persistent non-responsiveness to aspirin over time in three patients ( 5.3 % ) whereas four ( 7.0 % ) and 15 ( 26.3 % ) patients had changes in response status when platelet function was assessed by LTA and on the PFA-100 ® , respectively . We conclude that true non-responsiveness to aspirin is a rare phenomenon in stable PAOD patients . Furthermore , we conclude that in a number of patients , aspirin non-responsiveness is not stable over time", "The efficacy of low-dose aspirin in type 2 diabetes mellitus ( T2DM ) has been question ed . We tested if twice daily dosing of aspirin would be more effective in T2DM , possibly due to increased platelet turnover . A r and omised cross-over study compared 75 mg aspirin OD , 75 mg BID and 320 mg OD ( ≥ 2 week treatment periods ) in 25 patients with T2DM and micro- or macrovascular complications . Platelet responses were examined by impedance aggregometry ( WBA ) and the IMPACT-R aspirin test in whole blood , light transmittance aggregometry in platelet-rich plasma ( LTA ) , and urinary 11-dehydro-thromboxane B2 ( TxM ) . Aspirin 75 mg BID decreased arachidonic acid (AA)-induced WBA compared to 75 mg OD ( 9.7 ± 4.5 vs. 12.6 ± 3.5 ohm ; p = 0.003 ) or to 320 mg OD ( 11.5 ± 4.2 Ohms ; p = 0.049 ) . WBA responses to collagen were similarly attenuated by BID or high dosing ( by 12 - 14 % ; p = 0.02 for both ) . The IMPACT-R showed a better response to 75 mg BID compared to 75 mg OD ( p = 0.049 ) , but not to 320 mg OD . AA-induced aggregation by LTA was between aspirin dosages . TxM was reduced after 320 mg OD ( p = 0.002 ) , but not 75 mg BID ( p = 0.07 ) . Reticulated platelets were highly correlated with mean platelet volume ( MPV ; r2 = 0.74 , p markers for platelet turnover were correlated with AA-induced WBA , but neither identified patients who benefited from BID dosing dependably . In conclusion , twice daily dosing improved laboratory responses to aspirin in high risk T2DM patients . Studies of whether BID dosing of aspirin can improve clinical outcomes in such patients are of interest", "Background Creatinine kinase-MB ( CK-MB ) and cardiac troponin I ( cTnI ) elevations are highly specific for myonecrosis after percutaneous coronary intervention ( PCI ) . Aspirin is used to prevent thrombotic complications . Several studies have shown that some individuals exhibit a reduced or completely missing antiplatelet response to aspirin . The aim of this study is to investigate the effects of platelet reactivity despite aspirin therapy on CK-MB and cTnI levels after elective percutaneous coronary interventions despite 600 mg loading dose of clopidogrel . Methods One hundred fourteen ( mean age 61.2 ± 9.3 years , 78.1 % male ) patients receiving 300 mg daily enteric coated aspirin for at least 7 days with documented coronary artery disease were included in the study . Platelet reactivity despite aspirin was measured by platelet function analyzer (PFA)-100 collagen/epinephrine cartridge . Blood sample s for CK-MB and cTnI were obtained before and at 6 , 24 , and 36 h after the PCI . Persistent platelet reactivity was defined when collagen/epinephrine closure time platelet reactivity ( Group A ) , and 27 ( 23.6 % ) had persistent platelet reactivity ( Group B ) . The elevations of CK-MB and cTnI levels were statistically significant within the groups ( both P the CK-MB and cTnI levels of the groups at baseline and after PCI for all studied hours . Conclusion Persistent platelet reactivity was not associated with increased risk of CK-MB , cTnI elevations in low-to-intermediate risk PCI patients", "BACKGROUND Aspirin is one of the main therapeutics in prevention of cardiovascular events due to its antiplatelet activity . However , a sufficient inhibition of platelet function by aspirin is not always achieved . This means that the extent of protection from cardiovascular event is limited . Recently , several studies have introduced the concept of residual platelet reactivity during aspirin therapy and suggested that about 40 % of aspirin users may not respond adequately . We sought to determine whether the profile and prevalence of residual platelet reactivity , measured with the platelet function analyzer ( PFA-100 ; Dade/Behring , Marburg , Germany ) device could predict a recurrent cardiovascular event in patients undergoing coronary artery bypass surgery . METHODS A cohort of 202 consecutive patients receiving primary coronary artery bypass surgery during 2004 was prospect ively recruited . All patients postoperatively received regular st and ard daily 100 mg aspirin . Platelet function was analyzed by the PFA-100 at 30 + /- 6 days after surgery . A PFA100 closure time less than 190 seconds was defined as residual platelet reactivity . Eighty-six patients ( 43 % ) showed residual platelet reactivity . The mean follow-up time was 32 + /- 10 months and was 100 % complete . RESULTS A total of 75 cardiovascular events have been registered . The majority of these events were among patients with residual platelet activity ( p = 0.001 ) . Out of this number , graft failure was documented in 25 patients . The 42-month freedom from major cardiovascular events was significantly better for patients with adequate platelet inhibition ( p = 0.001 ) . At multivariable analysis residual platelet reactivity ( p = 0.012 ) , incomplete revascularization ( p = 0.029 ) , and diabetes ( p = 0.0009 ) were independently associated with occurrence of negative events . CONCLUSIONS Our results demonstrate that high residual platelet reactivity independently correlates with a worst clinical outcome in patients treated by coronary artery bypass surgery . The PFA-100 point care test could cheaply and simply discover this condition and contribute to improve the outcome of this subset of patients", "This study determined if meloxicam , a selective cyclooxygenase (COX)-2 inhibitor , interferes with the antiplatelet effect of aspirin using platelet aggregation and thromboxane ( Tx ) B(2 ) endpoints in healthy volunteers . Eight male and 8 female volunteers participated in this open-label , r and omized , two-treatment , two-way crossover trial . Treatment 1 was meloxicam ( 15 mg qd ) over 4 days , and then aspirin ( 100 mg qd ) was ingested 2 hours after meloxicam for an additional 7 days . Blood sample s were taken 2 , 6 , and 24 hours after the last dose . Treatment 2 consisted of only aspirin ( 100 mg ) over 2 days . Sample s were taken at the same time points . Each subject received both treatments with a 2-week washout between the treatment periods . Treatments were safe and well tolerated . The initial 4-day treatment with meloxicam had no effect on platelet aggregation but reduced serum TxB(2 ) by 64 % + /- 19 % . Addition of aspirin ( 100 mg qd ) for 7 days result ed in complete inhibition of aggregation and TxB(2 ) for 24 hours . Two-day treatment with only 100 mg aspirin also result ed in complete inhibition of platelet aggregation and TxB(2 ) . These results indicate that meloxicam does not affect the ability of aspirin to inhibit COX-1 in platelets , thereby allowing aspirin to effectively prevent platelet aggregation and reduce TxB(2 ) levels , and that meloxicam is selective for COX-2", "BACKGROUND Interindividual variability in response to aspirin has been popularized as ' resistance ' . We hypothesized that faster recovery of platelet cyclooxygenase-1 activity may explain incomplete thromboxane ( TX ) inhibition during the 24-h dosing interval . OBJECTIVE To characterize the kinetics and determinants of platelet cyclooxygenase-1 recovery in aspirin-treated diabetic and non-diabetic patients . PATIENTS / METHODS One hundred type 2 diabetic and 73 non-diabetic patients on chronic aspirin 100 mg daily were studied . Serum TXB(2 ) was measured every 3 h , between 12 and 24 h after a witnessed aspirin intake , to characterize the kinetics of platelet cyclooxygenase-1 recovery . Patients with the fastest TXB(2 ) recovery were r and omized to aspirin 100 mg once daily , 200 mg once daily or 100 mg twice daily , for 28 days and TXB(2 ) recovery was reassessed . RESULTS AND CONCLUSIONS Platelet TXB(2 ) production was profoundly suppressed at 12 h in both groups . Serum TXB(2 ) recovered linearly , with a large interindividual variability in slope . Diabetic patients in the third tertile of recovery slopes ( ≥ 0.10 ng mL(-1 ) h(-1 ) ) showed significantly higher mean platelet volume and body mass index , and younger age . Higher body weight was the only independent predictor of a faster recovery in non-diabetics . Aspirin 100 mg twice daily completely reversed the abnormal TXB(2 ) recovery in both groups . Interindividual variability in the recovery of platelet cyclooxygenase activity during the dosing interval may limit the duration of the antiplatelet effect of low-dose aspirin in patients with and without diabetes . Inadequate thromboxane inhibition can be easily measured and corrected by a twice daily regimen", "OBJECTIVES The purpose of this study was to evaluate the effects of aspirin and clopidogrel response on myonecrosis after percutaneous coronary intervention ( PCI ) with glycoprotein ( GP ) IIb/IIIa blockade . BACKGROUND Aspirin and clopidogrel resistance is increasingly recognized , but its effects on PCI outcomes with GP IIb/IIIa blockade are unknown . METHODS This was a prospect i ve , pre-specified sub study of the BRIEF-PCI ( Brief Infusion of Intravenous Eptifibatide Following Successful Percutaneous Coronary Intervention ) trial , which r and omized 624 patients to 18-h or To be eligible , patients must have been pre-treated with aspirin ( > or=5 days ) and clopidogrel ( 75 mg/day > or=5 days , 300 mg loading > or=6 h , or 600 mg loading > or=2 h ) and must not have received GP IIb/IIIa inhibitors within 48 h. Verify-Now Aspirin and Clopidogrel ( P2Y(12 ) ) assays were performed at baseline before PCI . Patients with aspirin reaction unit ( ARU ) > or=550 were labeled as aspirin resistant . Clopidogrel low-responders were defined as those in the lowest quartile of platelet inhibition . The primary end point was the prevalence of myonecrosis within 24 h after PCI . RESULTS We enrolled 209 patients into our sub study , of which 185 had aspirin response assessed , 198 had clopidogrel response assessed , and 174 had both assessed . There were 4.9 % who were aspirin resistant . Clopidogrel low-responders were defined as those in the lowest quartile with platelet inhibition myonecrosis prevalence among aspirin-resistant compared with aspirin-sensitive patients ( 11.1 % vs. 27.8 % , p = 0.259 ) or among clopidogrel low-responders compared with clopidogrel responders ( 23.5 % vs. 29.3 % , p = 0.433 ) . CONCLUSIONS Aspirin and clopidogrel response did not affect myonecrosis prevalence amongst patients who received eptifibatide for PCI", "BACKGROUND Aspirin resistance appears to be an important prognostic factor in patients with coronary artery disease , yet there is no st and ardized method to measure it and limited data on its correlation to clinical outcomes . METHODS In a prospect i ve study we followed 103 patients ( mean age 64 years ) with acute coronary syndrome ( ACS ) without ST segment elevation who were treated with 100 mg of aspirin ( ASA ) daily . Optical platelet aggregometry using cationic propyl gallate ( CPG ) as an inductor was measured at ACS onset and after 3 , 12 , 24 , 36 , and 48 months . ASA responsiveness was defined both by the slope of the aggregation curve ( recurrence of ACS or stroke . RESULTS Patients with ACS exhibited a greater prevalence of ASA resistance ( 55 % ) than healthy volunteers ( 4 % ; p ASA resistance occurred more often in patients with type 2 diabetes , hypertriacylglycerolemia , and decreased HDL levels , and in smokers ( p aggregometry was sufficient to identify ASA-resistant patients . During the 4-year follow-up , the patients with ASA resistance had an 88 % incidence of recurrent cardiovascular events versus 46 % for the patients without ASA resistance ( p recurrent cardiovascular ( CV ) events , significantly more patients were ASA-resistant than in the subgroup without recurrent CV events ( 72 % vs. 8 % , p patients with ACS and some metabolic risk factors , and ASA-resistant patients have a significantly higher recurrence of cardiovascular events", "We performed a prospect i ve cohort trial on 220 patients undergoing elective off-pump coronary artery bypass surgery and taking aspirin to evaluate the effect of aspirin resistance on myocardial injury . The patients were divided into aspirin responders and aspirin non-responders by the value of the aspirin reaction units obtained preoperatively using the VerifyNow ™ Aspirin Assay . The serum levels of troponin I were measured before surgery and 1 , 6 , 24 , 48 and 72 hr after surgery . In-hospital major adverse cardiac and cerebrovascular events , graft occlusion , the postoperative blood loss and reexploration for bleeding were recorded . Of the 220 patients , 181 aspirin responders ( 82.3 % ) and 39 aspirin non-responders ( 17.7 % ) were defined . There were no significant differences in troponin I levels ( ng/mL ) between aspirin responders and aspirin non-responders : preoperative ( 0.04 ± 0.08 vs 0.03 ± 0.06 ; P = 0.56 ) , postoperative 1 hr ( 0.72 ± 0.87 vs 0.86 ± 1.10 ; P = 0.54 ) , 6 hr ( 2.92 ± 8.76 vs 1.50 ± 2.40 ; P = 0.94 ) , 24 hr ( 4.16 ± 13.44 vs 1.25 ± 1.95 ; P = 0.52 ) , 48 hr ( 2.15 ± 7.06 vs 0.65 ± 0.95 ; P = 0.64 ) and 72 hr ( 1.20 ± 4.63 vs 0.38 ± 0.56 ; P = 0.47 ) . Moreover , no significant differences were observed with regard to in-hospital outcomes . In conclusion , preoperative aspirin resistance does not increase myocardial injury in patients undergoing off-pump coronary artery bypass surgery . Postoperative dual antiplatelet therapy might have protected aspirin resistant patients", "Background —Postoperative thromboembolic stroke affects 2 % to 3 % of patients undergoing carotid endarterectomy ( CEA ) and is preceded by 1 to 2 hours of increasing cerebral embolization . Previous work has demonstrated that high rates of postoperative embolization are associated with increased platelet reactivity to adenosine 5′-diphosphate ( ADP ) . Our hypothesis was that preoperative administration of the platelet ADP antagonist clopidogrel could reduce postoperative embolization . Methods and Results —One hundred CEA patients on routine aspirin therapy ( 150 mg ) were r and omized to 75 mg clopidogrel ( n=46 ) or placebo ( n=54 ) the night before surgery . Platelet response to ADP was assessed by whole-blood flow cytometry . The number of emboli detected by transcranial Doppler within 3 hours of CEA was independently quantified . Time taken from flow restoration to skin closure was used as an indirect measure of the time to secure hemostasis . In comparison with placebo , clopidogrel produced a small ( 8.8 % ) but significant reduction in the platelet response to ADP ( P 20 emboli in the postoperative period ( odds ratio , 10.23 ; 95 % CI , 1.3 to 83.3 ; P = 0.01 , Fisher ’s exact test ) . However , in the clopidogrel-treated patients , the time from flow restoration to skin closure ( an indirect marker of hemostasis ) was significantly increased ( P = 0.04 , Fisher ’s exact test ) , although there was no increase in bleeding complications or blood transfusions . Conclusions —This is the first study to show that a CEA patient ’s postoperative thromboembolic potential can be significantly reduced by targeted preoperative antiplatelet therapy without increasing the risk of bleeding complications ", "Background The benefits of aspirin as an anti-platelet agent are well established ; however , there has been much debate about the lack of uniformity in the efficacy of aspirin to inhibit platelet function . In some patients , aspirin fails to inhibit platelets even where compliance has been verified , a phenomenon which has been termed “ aspirin resistance ” . These patients may in turn be at a higher risk of future vascular events . The proportion of “ resistant ” patients identified depends on the type of platelet function test . Therefore , the aim of this systematic review is to determine which , if any , platelet function test has utility in terms of identifying patients with a high risk of vascular events . The review has been registered with PROSPERO ( CRD42012002151 ) . Methods Relevant studies will be sought from bibliographic data bases . Trials registers will be search ed for ongoing studies . Reference lists will be checked and subject experts contacted . There will be no date or language restrictions . St and ard review ing methodology to minimise bias will be employed . Any prospect i ve studies in patients on aspirin therapy and assessing platelet function in relation to relevant clinical outcomes will be included , as will studies reporting prognostic models . Risk of bias assessment will be based on the Quality Assessment of Diagnostic Accuracy Studies guidelines , and suitable criteria for assessing quality of prognostic studies . Data on test accuracy measures , relative risks , odds or hazard ratios will be extracted and meta-analysed , where possible , using a r and om-effects model to account for between- study heterogeneity . Where appropriate , the causes of heterogeneity will be explored through meta-regression and sub-group or sensitivity analyses . If platelet function testing is demonstrated to have diagnostic/predictive utility in a specific population , the potential for a cost-effectiveness analysis will be considered and , if possible , an economic model constructed . This will be supported by a systematic review of existing economic evaluation studies . Discussion The results of the review could indicate if platelet function test(s ) could lead to a reliable prediction of the risk of clinical ly important events in a defined population , and thus support investigations into adjustments to therapy in order to compensate for a predicted poor response to st and ard aspirin", "Aim High on-clopidogrel platelet reactivity ( HCPR ) and high on-aspirin platelet reactivity ( HAPR ) are associated with atherothrombotic events following coronary stenting . There are , however , few data concerning high on-treatment platelet reactivity to both aspirin and clopidogrel simultaneously . The aim of the present study was to determine the incidence of dual high on-treatment platelet reactivity ( DAPR ) and its impact on clinical outcome . Methods On-treatment platelet reactivity was measured in parallel by ADP- and arachidonic acid-induced light transmittance aggregometry ( LTA ) ( n=921 ) and the point-of-care VerifyNow system ( P2Y12 and aspirin ) ( n=422 ) in patients on dual antiplatelet therapy undergoing elective stent implantation . HCPR and HAPR were established by receiver-operator characteristic curve analysis . The primary endpoint was a composite of all-cause death , non-fatal acute myocardial infa rct ion , stent thrombosis and ischaemic stroke at 1-year follow-up . Results The incidence of DAPR varied between 14.7 % and 26.9 % depending on the platelet function test used . DAPR , assessed by LTA and the VerifyNow system , was highly associated with an adverse clinical outcome . At 1-year follow-up the primary endpoint occurred more frequently in patients with isolated HCPR ( 11.7 % ) , isolated HAPR ( 9.6 % ) or DAPR ( 10.7 % ) compared with patients without high on-treatment platelet reactivity ( 4.2 % , all p patients undergoing elective percutaneous coronary intervention , DAPR to aspirin and clopidogrel is present in one in five patients and is associated with a high risk for atherothrombotic events . DAPR measured by the point-of-care VerifyNow system has a higher predictability for atherothrombotic events than LTA . Clinical Trial Registration Information www . clinical trials.gov : NCT00352014", "BACKGROUND Platelet hyperfunction contributes to acute coronary syndromes ( ACS ) . Thus , we hypothesized that platelet function under high shear stress predicts recurrent ACS during long-term follow-up of ACS patients . PATIENTS AND METHODS Consecutive ACS patients ( n = 208 ) were prospect ively followed-up for an average of 28 months . Platelet function was measured with the platelet function analyzer ( PFA-100 ; Dade Behring , Marburg , Germany ) at baseline for collagen/adenosine diphosphate closure times ( CADP-CT ) and for collagen/epinephrine closure times ( CEPI-CT ) after infusion of a uniform dose of 250 mg aspirin . RESULTS Of the conventional risk factors , only the prevalence of diabetes was higher in ACS patients with re-events . However , use of clopidogrel and use of beta blockers were also slightly lower in patients with re-events ( P unadjusted risk hazard ratio ( HR ) for re-events was 3.3 [ 95 % confidence interval ( 95 % CI ) : 1.4 - 7.4 ; P = 0.005 ] in those patients with the shortest CADP-CT values ( lowest quartile ) . Similarly , the risk was 2.0-fold higher ( 95 % CI : 1.1 - 3.6 ; P = 0.02 ) in ACS patients with CEPI-CT or = 300 s. Inclusion of diabetes , clopidogrel and beta blockers in a multivariate Cox regression model enhanced the predictive value of CEPI-CT ( HR : 2.7 ) . Inclusion of von Willebr and factor levels did not alter the HR for recurrent ACS ( HR : 2.1 ; 95 % CI : 1.1 - 5.2 ; P = 0.03 ) for CEPI-CT HR for CADP-CT ( HR : 2.8 , 95 % CI : 0.8 - 9.8 ; P = 0.11 ) . CONCLUSION Shortened CT values reflect biologically relevant platelet hyperfunction in patients with ACS because they predict recurrent ACS", "There is some data available on the role of high on-treatment platelet reactivity by ADP whereas , as regards arachidonic acid or other agonists , there is no proof of the best cut-off for identifying population s with a different cardiovascular outcome by the construction of appropriate receiver-operator characteristics ( ROC ) curves . We enrolled 1,108 acute coronary syndrome patients undergoing percutaneous coronary intervention ( PCI ) with stent implantation and followed them up for 12 months . Platelet reactivity was assessed by light transmission aggregometry ( LTA ) using 10 microM ADP , 1 mM arachidonic acid ( AA ) and 2 microg/ml collagen . At a 12-month follow-up , we found 37 cardiovascular deaths ( 3.3 % ) , 54 non-fatal myocardial infa rct ions ( MI ) ( 4.8 % ) and 154 target vessel revascularisations ( TVR ) ( 13.8 % ) . ROC analysis demonstrated that 10 microM ADP LTA , 1 mM AA and 2 microg/ml collagen LTA were able to distinguish between patients with and without subsequent cardiovascular death and non-fatal MI ( area under the curve for 10 microM ADP 0.63 ( 0.55 - 0.71 ) , p TVR . Ten microM ADP LTA > or=55 % , 1 mM AA LTA > or=15 % and 2 microg/ml collagen LTA > or=31 % were identified as the optimal cut-off to predict cardiovascular death and non-fatal MI at 12-month follow-up . The contemporary platelet hyperreactivity to more than one agonist was associated with a higher risk of 12-month cardiovascular death and MI , whereas isolated platelet hyperreactivity to only one agonist had not a predictive value [ 10 microM ADP LTA > or=55 % + 1 mM AA LTA > or=15 % : odds ratio [OR]=3.6(2.4 - 6.1 ) , p or=55 % + 1 mM AA LTA > or=15 % + 2 microg/ml collagen LTA > or=31 % : OR=4.7(2.9 - 7.7 ) , p acute coronary syndrome patients undergoing stent implantation , we have found that high on-treatment platelet reactivity measured by LTA induced by more than one agonist -- AA , ADP , collagen -- is an independent risk factor for 12-month cardiovascular death and non-fatal MI . Isolated platelet hyperreactivity to only one agonist has not a predictive value for clinical recurrences", "BACKGROUND Several studies suggest that acetylsalicylic acid ( ASA ) is less effective in preventing thrombotic events in ASA nonresponder patients . If so , the thrombotic event rate in ASA nonresponders should be higher than in ASA responders . OBJECTIVE To conduct a prospect i ve , multicentre observational pilot study to determine the thrombotic event rates in ASA responders and nonresponders . PATIENTS AND METHODS Patients undergoing nonurgent coronary artery bypass grafting ( CABG ) who were prescribed 325 mg ASA/day were recruited . Patients were classified as an ASA responder or nonresponder based on the ASA effect ( or lack thereof ) on their bleeding times . All thrombotic events that occurred in the two years following CABG were recorded . These data were stored in a blinded fashion until the last patient follow-up , and then adjudicated by a validation committee . RESULTS A total of 289 patients recruited at three sites completed the two-year follow-up . Of these patients , 45.3 % were classified as ASA responders and 54.7 % were classified as ASA nonresponders . Of ASA responders , 6.9 % had thrombotic events compared with 9.5 % of the ASA nonresponders , but this difference was not significant ( P=0.526 ) . CONCLUSIONS While ASA responder or nonresponder status did not appear to affect the thrombotic event rate in patients undergoing nonurgent CABG , the possibility that ASA responder or nonresponder status affects the thrombotic event rate in more acutely ill CABG patients can not be excluded", "Background – We investigated the platelet function in stroke patients treated with aspirin [ acetylsalicylic acid ( ASA ) ] for secondary stroke prevention during a follow‐up period of 1 year", "INTRODUCTION The purpose of the present study was to study the concept of aspirin resistance or non-responsiveness by investigating the response to long-term aspirin therapy in patients with a former acute myocardial infa rct ion ( AMI ) . MATERIAL S AND METHODS Patients with an AMI ( n=202 ) r and omly assigned to aspirin 160 mg/day ( n=71 ) , aspirin 75 mg/day and warfarin ( INR 2.0 - 2.5 ) ( n=58 ) or warfarin ( INR 2.8 - 4.2 ) ( n=73 ) were evaluated by the PFA-100(R ) , biochemical variables and clinical events after a mean treatment period of 4 years . RESULTS The limit for being an aspirin non-responder was defined as the 95th percentile value in the warfarin alone group ( 196 s ) with the epinephrine cartridge . In patients on aspirin alone 25/71 ( 35 % ) were non-responders and on the combination 23/58 ( 40 % ) . With the adenosine diphosphate ( ADP ) cartridge only minor differences were found . The levels of thromboxane B(2 ) in both aspirin groups , in responders as well as in non-responders , were extremely low compared to the warfarin alone group . Evaluating both aspirin groups together ( n=129 ) , the levels of soluble P-selectin were significantly higher in non-responders as compared to responders ( p=0.012 ) . During the observation period of 4 years with limited number of events , there was a tendency for higher event rates in non-responders as compared to responders ( 36 % vs. 24 % , p=0.28 ) . CONCLUSIONS In our evaluation of the PFA-100(R ) a considerable number of post-AMI patients seemed to be non-responders to long-term aspirin therapy in doses of 75 and 160 mg/day . Circulating levels of P-selectin were higher in the non-responders . A tendency to higher incidence of clinical events among non-responders was observed", "In medical research , continuous variables are often converted into categorical variables by grouping values into two or more categories . We consider in detail issues pertaining to creating just two groups , a common approach in clinical research . We argue that the simplicity achieved is gained at a cost ; dichotomization may create rather than avoid problems , notably a considerable loss of power and residual confounding . In addition , the use of a data -derived ' optimal ' cutpoint leads to serious bias . We illustrate the impact of dichotomization of continuous predictor variables using as a detailed case study a r and omized trial in primary biliary cirrhosis . Dichotomization of continuous data is unnecessary for statistical analysis and in particular should not be applied to explanatory variables in regression models", "Aspirin resistance may increase the risk of major adverse cardiac events ( MACE ) more than threefold in patients with stable coronary artery disease ( CAD ) . This study aim ed to determine the prevalence of aspirin resistance in patients with stable CAD , the role of aspirin resistance on outcome in the follow-up , and the effect of clopidogrel therapy in MACE prevention in aspirin-resistant individuals . We detected the prevalence of aspirin resistance in 234 patients with stable CAD . Platelet function was determined by PFA-100 with collagen and /or epinephrine and collagen and /or ADP cartridges . The mean follow-up time was 20.6 ± 6.9 months . The primary endpoints of the study were occurrence of myocardial infa rct ion , unstable angina , stroke and cardiac death . Of patients , 22.2 % ( n = 52 ) were aspirin resistant by PFA-100 . During follow-up , MACE occurred in eight patients ( 15.4 % ) with aspirin resistance and in 20 patients ( 11.0 % ) with aspirin-sensitive platelet aggregation ( P = 0.269 ) . MACE increased in aspirin-resistant patients after termination of clopidogrel therapy . Eleven patients experienced MACE after cessation of clopidogrel therapy ( P 0.001 ) . The MACE risk in patients with stable CAD having detected aspirin resistance was similar compared with patients having aspirin-sensitive platelet aggregation by PFA-100 . The MACE prevalence increased during follow-up , however , just after cessation of clopidogrel therapy", "AIMS We assessed prospect ively the association between occurrence of post-discharge non-CABG-related TIMI major and minor bleeding and post-treatment platelet reactivity in patients with non-ST elevation acute coronary syndrome ( NSTE ACS ) . METHODS AND RESULTS Five hundred and ninety-seven consecutive patients admitted with NSTE ACS were prospect ively included . Between hospital discharge and one month follow-up , we observed 16 ( 2.7 % ) non-CABG-related TIMI haemorrhagic complications including five ( 0.84 % ) major and 11 ( 1.8 % ) minor bleeds . Patients with bleeding had significantly lower post-treatment values of ADP-induced aggregation ( 43+/-14 % versus . 56+/-19 % , p=0.002 ) and platelet reactivity index VASP ( 43+/-14 % versus 54+/-23 % ; p=0.04 ) and a trend for lower values of arachidonic acid-induced aggregation ( 2.4+/-5.4 versus 13+/-21 ; p=0.27 ) . After stratification by quartiles based on post-treatment ADP-induced platelet aggregation , we identified patients in the first quartile as hyper-responders with very low post-treatment platelet reactivity , below risk of TIMI major and minor bleeding was significantly higher in the first quartile of hyper-responders than in the others quartiles : 10 ( 6.6 % ) versus six ( 1.4 % ) , p=0.001 . CONCLUSIONS Our results suggest that assessment of post-treatment platelet reactivity might be used to detect hyper-responders to antiplatelet therapy with higher risk of non-CABG related bleeding and tailor antiplatelet therapy according to both ischaemic and bleeding risk", "OBJECTIVE To study the prevalence and importance of aspirin resistance in patients with an evolving acute myocardial infa rct ion ( AMI ) by use of the Platelet Function Analyzer-100 . INTRODUCTION Previous studies have demonstrated the existence of aspirin resistance , but the clinical relevance of the phenomenon remains to be clarified . If aspirin resistant patients comprise a high-risk subgroup , it might be expected that the prevalence of aspirin resistance in patients with AMI would be higher than in patients without AMI . We hypothesized that the prevalence of aspirin resistance in patients with AMI was twice the prevalence in patients without AMI . METHODS We included 298 consecutive patients with known cardiovascular disease who were admitted to hospital with symptoms suggestive of an AMI . All had been taking aspirin 150 mg/day for at least 7 days prior to hospital admission . Platelet function was measured immediately at admission , and aspirin resistance was defined as a collagen/epinephrine Closure Time ( CT(CEPI)) s. RESULTS We found that 70 ( 23.5 % ) patients were aspirin resistant , and 70 ( 23.5 % ) patients ended up with the diagnosis of an AMI . The prevalence of aspirin resistance was significantly higher in patients with AMI as compared to patients without ( 36 % versus 20 % , OR 2.26 , CI 95 % 1.19 - 4.22 , p=0.0058 ) . The CT(CEPI ) measured at admission was an independent factor associated with an AMI . CONCLUSIONS Aspirin resistance is present in almost one fourth of patients admitted to hospital with symptoms suggestive of an AMI , and aspirin resistance is significantly associated with the diagnosis of a definite AMI", "OBJECTIVES We have prospect ively investigated the association between aspirin and clopidogrel responses and the clinical predictors of non response . METHODS 635 Non ST Elevation Acute Coronary Syndrome ( NSTE ACS ) patients were included and received loading doses of 250 mg aspirin and 600 mg clopidogrel . We analyzed post-treatment maximal intensity of arachidonic acid and ADP-induced platelet aggregation ( AA-Ag and ADP-Ag ) and Platelet Reactivity Index of VAsodilator-Stimulated Phosphoprotein ( PRI VASP ) . Aspirin and clopidogrel non responses were defined respectively by AA-Ag>30 % and ADP-Ag>70 % . RESULTS Aspirin non responders patients had significantly higher ADP-Ag and PRI VASP than aspirin responders : 63.7+/-15.9 % vs 55+/-19 % ( p=0.0001 ) and 73.6+/-13.3 % vs 53+/-23 % ( p=0.0001 ) respectively and the rate of clopidogrel non responders was higher among aspirin non responders than aspirin responders : 36.7 % vs 22.7 % ( p=0.003 ) . In addition , clopidogrel non responders had significantly higher AA-Ag and rate of aspirin non responders than clopidogrel responders : 21.6+/-24 % vs 10.3+/-19 % ( p=0.0001 ) and 22.8 % vs 12.9 % ( p=0.003 ) respectively . Age and Body Mass Index ( BMI ) were significantly associated with non response to Clopidogrel ( p=0.035 and 0.02 respectively ) and diabetes mellitus by trend ( p=0.07 ) . CONCLUSION We observed a relationship between aspirin and clopidogrel non responses and an association between age , BMI and diabetes mellitus and clopidogrel response", "BACKGROUND Hemostatic drugs are widely thought to be unnecessary and potentially detrimental in off-pump coronary artery bypass graft surgery ( OPCABG ) , despite well-established use in on-pump surgery . In a r and omized , prospect i ve OPCABG trial , we assessed efficacy and safety of aprotinin through a comprehensive assessment of graft patency and hematologic function . METHODS Sixty patients were r and omly assigned to full-dose aprotinin or placebo . Heparin was titrated to a kaolin-based activated clotting time of greater than 300 seconds . Exclusionary criteria included creatinine greater than 2 mg/dL , conversion to on-pump CABG , and preoperative GPIIb/IIIa inhibition . Hematologic assessment s were obtained preoperatively , at the end of surgery , and on days 1 and 3 : mean platelet volume , thrombin generation ( prothrombin fragment 1.2 assay ) , and aspirin resistance using a modified thrombelastography , whole blood aggregometry , 11-dehydro-thromboxane B2 levels , and flow cytometry . Thrombotic events were defined as postoperative myocardial infa rct ion by electrocardiography or elevated troponin I , clinical stroke by examination and head computed tomography , and bypass graft failure by multichannel computed tomography angiography on day 5 . RESULTS Aprotinin was associated with a significant reduction in intraoperative and postoperative blood loss compared with placebo but had no effect on transfusion rates . Patients treated with aprotinin had significantly fewer thrombotic events ( 3 % versus 23 % , p postoperative aspirin resistance ( 20 % versus 46 % , respectively , p Postoperative prothrombin fragment 1.2 level was reduced by aprotinin use . CONCLUSIONS Aprotinin reduced perioperative bleeding after OPCABG . Preserved aspirin sensitivity in the aprotinin group may explain the observed reduction in thrombotic events and might be related to the suppression of perioperative and transmyocardial thrombin formation", "BACKGROUND Aspirin and clopidogrel resistance plays a significant role in the development of cardiovascular ischemic events for ninety patients undergoing percutaneous coronary intervention . Recent studies have indicated that increasing the dose of antiplatelet drugs maybe a potent method to improve the inhibition of platelet aggregation . METHODS Thrombelastograph ( TEG ) determinations were used to evaluate the effect of antiplatelet therapy . According to the results , 90 patients were divided into three groups and given different doses of aspirin and clopidogrel . Thirty patients with both an inhibition rate of aspirin > 50 % and an inhibition rate of clopidogrel > 50 % were defined as the control group . Sixty patients with an inhibition rate for aspirin clopidogrel were defined as the resistance group . Patients in resistance group were r and omly assigned to be given a routine dose ( 100 mg aspirin plus 75 mg clopidogrel per day , which we called a resistance plus routine dose group , R + R ) and a loading dose ( 200 mg aspirin and 150 mg clopidogrel per day , which we called resistance plus loading dose group , R + L ) of antiplatelet therapy . A 12-month follow-up was observed to examine the change of inhibition rate of antiplatelet therapy and to estimate the relationship between inhibition rate and the occurrence of cardiovascular ischemic events . RESULTS After 6 months of antiplatelet therapy , the inhibition rate of aspirin in the R + L group increased from ( 31.4 ± 3.7)% to ( 68.6 ± 7.1)% , which was significantly higher than that in R + R group , ( 51.9 ± 8.2)% ( P The inhibition rate of clopidogrel in the R + L group increased from ( 22.1 ± 3.8)% to ( 60.2 ± 7.4)% , which was significantly higher than in the R + R group , ( 45.9 ± 4.3)% ( P ion in the R + R group were 20 % , 36 % and 17 % , respectively . Occurrence was significantly increased compared with that in the control group , 3 % , 10 % and 1 % , respectively ( P the occurrence rates in the R + L group ( 10 % , 23 % and 6 % , respectively ) were attenuated compared with those in the R + R group ( P cardiovascular ischemic events occurred in the first six months after percutaneous coronary intervention . According to the result of TEG determinations , earlier application of a loading dose of aspirin and clopidogrel can decrease the rate of recurrent cardiovascular ischemic events", "Objective : To evaluate residual platelet activity in a consecutive cohort of patients treated with dual antiplatelet therapy after coronary stent implantation Design : Prospect i ve single-centre cohort study . Setting : University hospital in Germany . Patients : 480 patients with symptomatic coronary artery disease ( n = 221 ( 46 % ) or acute coronary syndrome ( ACS ; n = 259 ( 54 % ) stable angina ) were studied . Platelet activity was measured by collagen- ( 5 µg/ml ) and adenosine diphosphate- ( ADP ; 20 µmol/l ) induced platelet aggregation to assess post-treatment activity in patients treated with acetylsalicylic acid ( 500 mg bolus intravenously followed by 100 mg once a day ) and clopidogrel ( 600 mg loading dose followed by 75 mg once a day ) Main outcome measures : Increased residual platelet activity ( IRPA ) was defined if platelet aggregation was in the upper tertile of values in the patient collective . Association of epidemiological factors with IRPA was evaluated in a multivariate logistic regression analysis . Results : IRPA-ADP was found in 53 patients ( 11.0 % ) and IRPA-collagen in 42 patients ( 8.8 % ) . ACS was associated with IRPA independently from other factors ( for IRPA-collagen : odds ratio ( OR ) = 2.3 , 95 % confidence interval ( CI ) 1.2 to 4.5 , p with IRPA despite conventional antiplatelet therapy . Further studies are warranted to demonstrate the effects of intensified antiplatelet therapy for patients with acute coronary events", "OBJECTIVE — Diabetic patients may have a higher prevalence of platelet aspirin resistance than nondiabetic patients . Our goal was to analyze platelet aspirin responsiveness to various aspirin doses in diabetic and nondiabetic patients . RESEARCH DESIGN AND METHODS — We examined the effect of aspirin ( 81 , 162 , and 325 mg/day for 4 weeks each ) on platelet aspirin responsiveness in 120 stable out patients ( 30 diabetic patients and 90 nondiabetic patients ) with coronary artery disease ( CAD ) using light transmittance aggregometry ( LTA ) , VerifyNow , platelet function analyzer (PFA)-100 , and levels of urinary 11-dehydro-thromboxane B2 ( 11-dh-TxB2 ) . RESULTS — In the total group , a low prevalence ( 0–2 % ) of aspirin resistance was observed with all aspirin doses as determined by arachidonic acid – induced LTA . Aspirin resistance was higher at the 81-mg dose in diabetic versus nondiabetic patients using collagen-induced LTA ( 27 vs. 4 % , P = 0.001 ) , VerifyNow ( 13 vs. 3 % , P = 0.05 ) , and urinary 11-dh-TxB2 ( 37 vs. 17 % , P = 0.03 ) . Diabetic patients treated with 81 mg exhibited higher platelet function measured by VerifyNow , collagen- and ADP-induced LTA , and 11-dh-TxB2 levels ( P ≤ 0.02 for all comparisons ) . Higher aspirin doses significantly inhibited platelet function and decreased aspirin resistance in diabetic patients ( P Diabetic patients with CAD treated with 81 mg aspirin exhibit a higher prevalence of aspirin resistance and have significantly higher ADP- and collagen-induced platelet aggregation , 11-dh-TxB2 levels , and aspirin reaction units measured by VerifyNow than nondiabetic patients . Increased aspirin dosing result ed in similar rates of resistance and platelet function levels between groups . These findings indicate that diabetic patients exhibit a global high platelet reactivity phenotype that may be partially overcome by higher aspirin doses", "Aspirin and clopidogrel are proven to prevent thromboembolic events during percutaneous coronary intervention ( PCI ) . Enzyme release of creatine kinase-MB ( CK-MB ) enzyme during PCI has been associated with an increased risk of future adverse cardiac events . This study examined the correlation between measurements of aspirin resistance and the level of inhibition of the thienopyridine-specific P2Y12 platelet receptor and CK-MB release after PCI . We prospect ively studied 330 patients with elective PCI treated with drug-eluting stents . Patients were pretreated with aspirin and clopidogrel . Patients with positive CK-MB or acute coronary syndrome and those on glycoprotein IIb/IIIa inhibitors were excluded . Serum assays of aspirin resistance ( Ultegra Rapid Platelet Function Assay-ASA , Accumetrics ) and clopidogrel resistance ( Rapid Platelet Function Assay P2Y12 , Accumetrics ) were performed before PCI . Serum troponinI and CK-MB levels were measured at 8 , 16 , and 24 hours after PCI . Aspirin resistance unit ( ARU ) measurement > or = 550 was detected in 12 patients ( 3.7 % ) . Mean platelet reactivity unit ( PRU ; measurement of inhibition of P2Y12 activity ) was 192.2 + /- 95.4 ( lower PRU , more inhibition of P2Y12 receptor ) . There was no correlation between level of ARU or PRU and troponin I or CK-MB release after PCI at any time point . Only multivessel coronary disease was found to be a predictor of any increase in CK-MB in a multivariate analysis ( odds ratio 2.2 , 95 % confidence interval 1.4 to 3.3 , p = 0.0003 ) . A positive correlation was found between levels of ARU and PRU . Target vessel revascularization/major adverse cardiac event rate at 6 months was 8.2 % with no correlation between ARU or PRU and release of cardiac enzymes or occurrence of adverse cardiac events . In conclusion , this study does not support routine measurements of aspirin and clopidogrel resistance in stable patients undergoing PCI", "We determined the prevalence and clinical predictors of aspirin resistance by prospect ively study ing 325 patients with stable cardiovascular disease who were receiving aspirin ( 325 mg/day for > or = 7 days ) but no other antiplatelet agents . We also compared the detection of aspirin resistance with optical platelet aggregation , a widely accepted method , with a newer , more rapid method , the platelet function analyzer (PFA)-100 , a whole blood test that measures platelet adhesion and aggregation ex vivo . Blood sample s were analyzed in a blinded fashion for aspirin resistance by optical aggregation using adenosine diphosphate ( ADP ) and arachidonic acid , and by PFA-100 using collagen and /or epinephrine and collagen and /or ADP cartridges to measure aperture closure time . Aspirin resistance was defined as a mean aggregation of > or = 70 % with 10 microM ADP and a mean aggregation of > or = 20 % with 0.5 mg/ml arachidonic acid . Aspirin semiresponders were defined as meeting one , but not both of the above criteria . Aspirin resistance by PFA-100 was defined as having a normal collagen and /or epinephrine closure time ( aspirin resistant and 23.8 % were aspirin semiresponders . By PFA-100 , 9.5 % of patients were aspirin resistant . Of the 18 patients who were aspirin resistant by aggregation , 4 were also aspirin resistant by PFA-100 . Patients who were either aspirin resistant or aspirin semiresponders were more likely to be women ( 34.4 % vs 17.3 % , p = 0.001 ) and less likely to be smokers ( 0 % vs 8.3 % , p = 0.004 ) compared with aspirin-sensitive patients . There was a trend toward increased age in patients with aspirin resistance or aspirin semiresponders ( 65.7 vs 61.3 years , p = 0.06 ) . There were no differences in aspirin sensitivity by race , diabetes , platelet count , renal disease , or liver disease", "OBJECTIVES Although the concept of aspirin resistance is extensively reported in medical literature , its precise mechanisms and clinical outcomes are largely unknown . In this study , we examined individual thromboxane bio synthesis and platelet aggregation in aspirin-treated patients , and whether the results of a platelet aggregation test influenced clinical outcomes . RESULTS Subjects taking 81 mg of aspirin ( n = 50 ) and controls ( n = 38 ) were evaluated for platelet aggregation and platelet cyclooxygenase-1 ( COX-1 ) activity by measuring collagen-induced thromboxane B2 production . For aggregometry , both light transmission ( LT ) and laser-light scattering methods were employed to quantitatively evaluate aggregate sizes and numbers . Aspirin treatment result ed in the inhibition of collagen-induced platelet aggregation , particularly the transition from small to large platelet aggregates . Although platelet COX-1 activity seemed to be uniformly inhibited in all patients , platelet aggregation studies showed great inter-individual differences ; variation in platelet COX-1 activity only accounted for 6 - 20 % of the individual aggregations . Factor analysis revealed the existence of a common factor ( other than platelet COX-1 ) that explained 48.4 % of the variations in platelet aggregation induced by collagen , adenosine diphosphate ( ADP ) , and collagen-related peptide . We then prospect ively enrolled 136 aspirin-treated patients in our study , and we found that being in the upper quartile level of LT , or with large aggregate formation induced by collagen , was an independent risk factor for developing cardiovascular events within 12 months [ hazard ratio ( HR ) = 7.98 , P = 0.008 for LT ; HR = 7.76 , P = 0.007 for large aggregates ] . On the other h and , the existence of diabetes mellitus was an independent risk factor for overall outcomes ( HR 1.30 - 11.9 , P = 0.015 - 0.033 ) . CONCLUSIONS Aspirin resistance expressed as unsuppressed platelet COX-1 activity is a rare condition in an out-patient population . Other factor(s ) affecting collagen-induced platelet aggregation may influence early outcomes in aspirin-treated patients", "Although the platelet aggregation test is the most common method for evaluating response to antiplatelet therapy , little is known about the association of recurrent cerebral infa rct ion with platelet aggregation in the presence of various different antiplatelet drugs . We prospect ively evaluated adenosine diphosphate (ADP)- and collagen-induced platelet aggregation and followed the incidence of recurrent infa rct ion in patients categorized into 3 groups based on treatment ; aspirin ( n = 144 ) , ticlopidine ( n = 100 ) , and aspirin + ticlopidine ( n = 96 ) . The patients in each treatment group were stratified into quartiles according to platelet aggregation , and the association of recurrent infa rct ion with platelet aggregation was investigated . ADP-induced platelet aggregation values were significantly lower in the ticlopidine group and the aspirin + ticlopidine group compared with the aspirin group ( P collagen-induced platelet aggregation values were significantly lower in the aspirin group and the aspirin + ticlopidine group compared with the ticlopidine group ( P recurrence rate was somewhat higher in the higher aggregation quartiles than in the lower aggregation quartiles of 2 μg/mL collagen , the differences were not statistically significantly ( P = .243 ) . In the ticlopidine group , the recurrence rate was significantly higher in the lower aggregation quartiles compared with the higher aggregation quartiles of 1 μmol/L ADP ( P = .025 ) . No tendencies were found in the aspirin + ticlopidine group . Although the study is limited by its small sample size , the results suggest a possible difference between aspirin therapy and ticlopidine therapy in the pattern of association of recurrent infa rct ion with platelet aggregation", "Previous studies have shown that more complete platelet inhibition improves the coronary flow reserve ( CFR ) , a measure of microvascular integrity , in patients undergoing percutaneous coronary intervention ( PCI ) . We hypothesized that patients with aspirin resistance would have impaired CFR after elective PCI . We used VerifyNow Aspirin to determine the response to aspirin in 117 consecutive patients who underwent elective single-lesion PCI . The assay results are expressed quantitatively in Aspirin Reaction Units based on the degree of platelet aggregation . All patients received a 300-mg loading dose of clopidogrel > 12 hours before and a 75-mg maintenance dose the morning of PCI . CFR was estimated using the Thrombolysis In Myocardial Infa rct ion frame count method . Of the 117 patients , 22 ( 18.8 % ) were aspirin resistant . The clinical , angiographic , and procedural characteristics of the aspirin-sensitive and -resistant patients were balanced . All patients underwent successful PCI with CFR than the aspirin-sensitive patients ( 1.42 + /- 0.35 vs 1.80 + /- 0.64 , p = 0.018 ) . Univariate correlates of CFR included the Aspirin Reaction Unit ( r = -0.227 , p = 0.014 ) and post-PCI creatine kinase-MB elevation ( p = 0.048 ) . Multivariate linear regression analysis revealed the Aspirin Reaction Unit to be the only independent determinant of CFR after PCI ( r2 = 0.051 , p = 0.014 ) . Thus , aspirin resistance was associated with impaired CFR in patients who underwent elective PCI , implicating insufficient aspirin-induced platelet inhibition as a cause of microvascular dysfunction by distal atherothrombotic embolization and /or spasm", "OBJECTIVE To investigate the occurrence of aspirin resistance in coronary heart disease ( CHD ) patients and its influence on myonecrosis among patients undergoing non-emergent percutaneous coronary intervention ( PCI ) . METHODS 256 CHD patients who have been on aspirin ( 100 mg/d ) for at least 7 days were recruited based on aspirin responsiveness determination . All the patients were divided into two groups : aspirin-resistant group and aspirin-sensitive group . For all patients scheduled for non-emergent PCI , a loading dose of 300 mg of clopidogrel was given at least 12 h before PCI and a 75 mg maintenance dose was given every morning before and after PCI . The incidence of myonecrosis was evaluated by the levels of creatine kinase-myocardial b and ( CK-MB ) and troponin I ( TnI ) before and after PCI . RESULTS Aspirin resistance was found in 67 ( 26.2 % ) patients and 189 ( 73.8 % ) patients were aspirin-sensitive . There was a significantly higher proportion of female subjects in the aspirin-resistant group . The incidence of any CK-MB elevation was 38 ( 56.7 % ) in aspirin-resistant group and 42 ( 22.2 % ) in aspirin-sensitive group ( P elevation of TnI was observed in 41 ( 61.2 % ) of the aspirin-resistant group and in 67 ( 35.4 % ) of the aspirin-sensitive group ( P CK-MB elevation after PCI ( OR = 2.5 ; 95 % CI 1.5 to 6.5 ; P Aspirin resistance exists in some CHD patients , which increases the risk of myonecrosis following non-emergent PCI", "OBJECTIVE The presence of the glycoprotein IIIa allele PlA2 is associated with enhanced thrombin formation and an impaired antithrombotic action of aspirin , which could favor coronary thrombosis . We wondered whether PlA1/A2 genetic polymorphism could affect the postoperative bleeding in patients undergoing coronary artery bypass grafting . We also aim ed to assess the effects of aspirin pretreatment and to ascertain the value of platelet function studies as predictors of postoperative bleeding . METHODS In a r and omized , double-blind study , patients undergoing coronary artery bypass grafting were pretreated with a 150-mg dose of aspirin orally 12 and 3 hours before surgery ( n = 51 , 41 elective ) or with placebo ( n = 51 , 43 elective ) . The hemostasis was monitored by Simplate ( bioMérieux , Inc , Durham , NC ) bleeding time and capillary closure time ( platelet function analyzer PFA 100 ; Sysmex UK Ltd , Milton Keynes , United Kingdom ) . Postoperative bleeding and blood products transfusions were recorded . The glycoprotein IIIa polymorphism was analyzed . RESULTS Bleeding was significantly greater in PlA1 homozygotes from control group . Blood loss was significantly greater ( by 25 % ) in aspirin group . The volume of blood products transfusions in aspirin patients was significantly larger ( by 137 % ) . When subjects were stratified accordingly to blood platelet glycoprotein IIb/IIIa genotype , in the aspirin group PlA2 carriers had greater blood loss than PlA1 homozygotes ( 1858 + /- 932 mL vs 1216 + /- 525 mL , P perioperative bleeding . Capillary closure time had no advantage relative to Simplate bleeding time in predicting postoperative blood loss . Aspirin pretreatment revealed no beneficial effects and result ed in increased postoperative bleeding and requirement for blood product transfusions after coronary artery bypass grafting in patients with stable angina . It was most unfavorable for PlA2 carriers", "The hypothesis that aspirin resistance is often due to noncompliance was investigated . One hundred ninety patients with a history of myocardial infa rct ion were evaluated using arachidonic acid-stimulated light aggregometry at 3 different time points : while receiving their usual daily aspirin , after not receiving aspirin for 7 days , and 2 hours after the observed ingestion of aspirin 325 mg . At the first time point , 17 patients ( 9 % ) failed to show aspirin inhibition of platelet aggregation , but 2 hours after observed aspirin ingestion , aspirin inhibition was observed in all but 1 patient", "BACKGROUND AND OBJECTIVES Low response to antiplatelet therapy may be a risk factor for the development of ischemic complications in patients with non-ST segment elevation acute coronary syndrome ( NSTE ACS ) undergoing coronary stenting . METHODS We prospect ively studied the platelet response to both clopidogrel and aspirin in 106 NSTE ACS consecutive patients undergoing percutaneous coronary intervention ( PCI ) with stenting . A single post-treatment blood sample was obtained just before PCI and analyzed by platelet aggregometry using both ADP and arachidonic acid ( AA ) as agonists to explore the responses to clopidogrel and aspirin , respectively . Patients were divided into quartiles according to the ADP or AA induced maximal intensity of platelet aggregation . Patients of the highest quartile ( quartile 4 ) were defined as the ' low-responders ' . RESULTS Twelve recurrent cardiovascular ( CV ) events occurred during the 1-month follow-up . Clinical outcome was significantly associated with platelet response to clopidogrel [ Quartile 4 vs. 1 , 2 , 3 : OR ( 95 % CI ) 22.4 ( 4.6 - 109 ) ] . Low platelet response to aspirin was significantly correlated with clopidogrel low response ( P = 0.003 ) but contributed less to CV events [ OR ( 95%CI ) : 5.76 ( 1.54 - 35.61 ) ] . CONCLUSIONS A post-treatment ADP-induced platelet aggregation performed just before PCI identifies low responders to dual antiplatelet therapy with an increased risk of recurrent CV events ", "Low-response to the P2Y12 adenosine diphosphate (ADP)-receptor antagonist clopidogrel was suggested to correspond to a higher incidence of stent thrombosis ( ST ) . This prospect i ve observational study assessed the capability of two platelet function assays , e.g. direct measurement of the phosphorylation status of vasodilator-stimulated phosphoprotein ( VASP ) and ADP-induced platelet aggregation for definition of the individual risk to develop ST . Ninety-nine patients with an elevated high risk to develop ST were enrolled . All patients received a dual antiplatelet therapy consisting of 100 mg aspirin and 75 mg clopidogrel during an observation period of six months . Flow cytometry of VASP phosphorylation and densitometrically-determined measurement of ADP-induced platelet aggregation was performed 72 - 96 hours after stent implantation . These data were related to angiographically confirmed ST . Nine patients suffered from angiographically confirmed ST ( 9.1 % ) . The meanVASP-platelet reactivity indices ( VASP-PRI ) and values for ADP-induced platelet aggregation in the ST group were significantly higher ( 60.8 + /- 13.0 and 60.9 + /- 13.1 , respectively ) compared to patients without ST ( 41.3 + /- 14.0 and 50.8 + /- 14.4 , P VASP was the only independent predictor of ST and was superior to previously identified angiographic parameters . Receiver- operator characteristic ( ROC ) curve analysis revealed a cut-off value for VASP-PRI of VASP phosphorylation is superior to conventional platelet aggregometry and angiographic parameters for assessing the risk of ST . Patients with a VASP-PRI > 48 % seem to have a significantly increased risk", "Objective To assess whether prehospital initiation of high-dose tirofiban in addition to high-dose clopidogrel results in more adequate inhibition of platelet aggregation ( IPA ) and better clinical outcome after primary percutaneous coronary intervention ( PCI ) . Methods Prespecified two-centre sub study of the prospect i ve , international , multicentre , placebo controlled Ongoing Tirofiban in Myocardial Infa rct ion Evaluation trial 2 ( On-TIME-2 trial ) . 648 of 964 ( 67 % ) patients in the On-TIME-2 trial with ST elevation myocardial infa rct ion undergoing primary PCI were studied . Pre-PCI IPA after early prehospital initiation of high-bolus dose ( 25 μg/kg ) tirofiban was compared to placebo in addition to acetylsalicylic acid , unfractionated heparin and 600 mg clopidogrel . Results IPA was measured at a median of 60 min after study medication administration . In all four tests : Fe induced platelet aggregation , ADP induced platelet aggregation , platelet function analyser (PFA)-100 ( collagen – epinephrine and collagen – ADP cartridge ) IPA was higher in patients pretreated with high-dose tirofiban ( p 74 min of pretreatment . Patients in the highest quartile of IPA had less residual ST segment deviation 1 h post-PCI ( p value for trend : p=0.001 , 0.004 , 0.001 , 0.002 respectively ) . There was a significant relationship between PFA-100 ( both cartridges ) and major adverse cardiovascular events ( MACE , p=0.028 , p=0.035 ) and early thrombosis ( p=0.009 , p=0.007 ) . Conclusions 60 min of prehospital initiated antiplatelet treatment including high-dose tirofiban result ed in higher levels of IPA compared to pretreatment with acetylsalicylic acid and high-dose clopidogrel alone , even after longer pretreatment times . Levels of IPA were significantly related to ST resolution and MACE , including stent thrombosis . This sub study confirms the main findings of the On-TIME2 trial that clopidogrel alone is suboptimal , even at high dose and administered well in advance of primary PCI", "Background Long-term success in ventricular assist device ( VAD ) recipients is limited by thromboembolic events , the prediction of which remains elusive . We evaluated the predictive value of aspirin hyporesponsiveness and markers of coagulation and fibrinolysis . Methods We prospect ively enrolled patients scheduled to undergo VAD implantation between June 2004 and March 2006 . Once before surgery , daily during hospitalization , and weekly after discharge we assessed platelet function , measured prothrombin activation fragment 1.2 ( F1.2 ) and plasminogen activator inhibitor-1 ( PAI-1 ) concentrations , and evaluated aspirin hyporesponsiveness by whole-blood aggregometry and thromboelastography . All patients received 325 mg oral aspirin daily from at least 7 days before VAD implantation . Follow-up continued until heart transplantation , death or closure of the data base . Results We included 26 patients ( median follow-up 315 days , range 9–833 days ) . In eight ( 31 % ) patients , 14 thromboembolic events occurred at a median of 42 ( interquartile range 26–131 ) days . Only six ( 43 % ) events based on whole-blood aggregometry and one ( 7 % ) based on thromboelastography coincided with aspirin hyporesponsiveness . Within-patient variability was high for both tests ( 59 % and 567 % , respectively ) . Compared with levels before surgery , PAI-1 concentrations were raised for up to 45 days ( P PAI-1 and F1.2 levels did not rise significantly further before thromboembolic events . Conclusions Aspirin hyporesponsiveness was not associated with raised risk of future clinical thromboembolic events after VAD implantation . Impaired fibrinolysis , demonstrated by raised PAI-1 concentrations , might , however , indicate a predisposition to such events early after surgery", "Objective Previous studies have demonstrated significant heterogeneity in responses to antiplatelet therapy ( APT ) , and high residual platelet reactivity is associated with the risk of ischaemic events , including stent thrombosis ( ST ) . The prevalence of APT hyporesponsiveness in a ‘ real world ’ registry of ST patients and the feasibility of personalising APT are reported . Patients and setting 39 consecutive patients admitted to a single regional cardiothoracic centre with definite ST were prospect ively evaluated . Interventions Response to aspirin and clopidogrel was measured following discharge using short thrombelastography ( TEG ) , a rapid , well vali date d near patient platelet function test . Treatment modification in hyporesponders comprised an increase in aspirin dose and /or changing clopidogrel to prasugrel or ticagrelor . Short TEG was repeated following treatment modification to ensure an adequate response had been achieved . Results 12 ( 31 % ) patients had an adequate response to both aspirin and clopidogrel , 16 ( 41 % ) were hyporesponsive to clopidogrel alone , one ( 3 % ) was hyporesponsive to aspirin alone and 10 ( 26 % ) were hyporesponsive to both aspirin and clopidogrel . Following treatment modification , an adequate response to aspirin and P2Y12 agent was achieved in 10 ( 91 % ) and 22 ( 85 % ) patients , respectively . None has presented with a further ST episode . Conclusions There is a high prevalence of hyporesponsiveness to APT in patients with ST . Improved APT efficacy can be achieved by tailored therapy . Short TEG is a plausible platelet function test that can be used to deliver point of care personalised APT", "The primary objective of this study was to apply a sophisticated coagulation monitoring system including estimation of the concentration of prothrombin fragment 1 + 2 ( PTF 1 + 2 ) and the activity of prothrombin ( coagulation factor II or FII ) to cases of stent implantation and to compare the results with those of st and ard coagulation tests . The secondary objective was to detect the incidence after stenting of subacute thrombosis ( SAT ) and bleeding complications in these patients and to compare the results with those of a group of patients with stent implantation in whom coagulation was monitored exclusively by st and ard tests . SAT several days after coronary stenting occurs in up to 20 % despite aggressive intravenous and overlapping oral anticoagulation . According to a prospect i ve study protocol 120 consecutive patients with implantation of 155 Palmaz-Schatz stents underwent coagulation monitoring including single daily estimation of the concentration of PTF1 + 2 ( target range FII activity ( 15 % to 35 % ) in addition to the st and ard tests of thrombin time ( TT ) , partial thromboplastin time ( aPTT ) , international normalized ratio ( INR ) , antithrombin III ( ATIII ) , and fibrinogen . Adjustment of heparin and phenprocoumon dosages in this study group was based only on the results of PTF1 + 2 and FII measurements . A control group consisted of 53 patients with implantation of 64 stents who were matched for baseline , angiographic , and procedure-related characteristics . After stenting , anticoagulation was monitored by estimation of TT ( target range > 70 seconds ) , aPTT ( > 70 seconds ) , INR ( 3.0 to 4.5 ) , AT III ( > 80 % ) , and fibrinogen ( PTF1 + 2 and aPTT ( r = 0.337 ; PTF1 + 2 = -0.00169aPTT + 0.491 ) and PTF1 + 2 and TT ( r = 0.328 ; PTF1 + 2 = -0.00142TT + 0.494 ) . A better correlation was found between FII and INR ( r = 0.983 ; FII = -23.8 INR + 134 ) . Stable oral anticoagulation was maintained 2.8 + /- 0.9 days later according to an FII concentration of 3 . The incidence of SAT was 3.3 % with 3.0 % for elective versus 3.8 % for nonelective stenting . The sensitivity , specificity , and accuracy of the PTF1 + 2 test were 100 % , 88 % , and 88 % , respectively . In the control group the incidence of SAT was 17 % , with 16.1 % for elective versus 18 % for nonelective stenting . Major bleeding complications occurred in 10 % ( study group ) and in 11.3 % ( control group ) of patients ( no statistical difference ) . ( ABSTRACT TRUNCATED AT 400 WORDS", "Platelet – leukocyte conjugates are increased in patients with coronary artery disease but the relationship between conjugate formation and myocardial ischemic outcome is unknown . We prospect ively evaluated the relationship between conjugate formation and the development of recurrent myocardial ischemia in patients with acute coronary syndromes ( ACS ) . Platelet – leukocyte conjugate formation ( induced by thrombin receptor activating peptide ( TRAP ) ) and platelet aggregation ( induced by ADP and arachidonic acid ) were assessed in 30 patients with unstable angina or non-ST elevation myocardial infa rct ion . All patients were treated with β-blockers , aspirin , heparin , and GPIIb – IIIa antagonists and were followed for in-hospital recurrent myocardial ischemia . Troponin I and C-reactive protein ( CRP ) were also measured . Seven patients ( 23 % ) experienced recurrent ischemia . Platelet – neutrophil conjugates were greater in ischemic patients ( 59 ± 9 and 36 ± 4 % , P = 0.007 , for + ischemia and −ischemia , respectively ) . Platelet aggregation did not differ between ischemic and nonischemic patients , and there was no significant relationship between aspirin resistance and ischemic outcome . Troponin I was greater in patients who developed recurrent ischemia ( 3.04 ± 1.73 vs. 0.70 ± 0.21 ng/ml , P = 0.03 , for + ischemia and −ischemia , respectively ) but CRP was not . TRAP-induced platelet – neutrophil conjugate formation was an independent predictor of ischemic outcome ( OR 1.07 , 95 % CI 1.00–1.15 , for each 1 % increase in conjugate formation ) . Receiver operator characteristic analysis showed platelet – neutrophil conjugates to have good ability to discriminate between ischemic and nonischemic patients ( AUC of 0.84 , P ) . TRAP induced platelet – neutrophil conjugate formation is related to in vivo ischemic risk in ACS patients ", "AIM Previous studies regarding on-treatment platelet reactivity have focused on response variability to individual antiplatelet agents . There are limited data on [ 1 ] response variability to both of these anti-platelet drugs , [ 2 ] efficacy of combining two point-of-care tests ( POCT ) simultaneously and [ 3 ] how it predicts the clinical outcome after percutaneous coronary intervention ( PCI ) . METHODS We analyzed 716 patients , enrolled in the CILON-T prospect i ve r and omized controlled trial , with both VerifyNow P2Y12 ( PRU ) and Aspirin ( ARU ) data at discharge . Patients were classified according to the tertile of PRU , ARU and the sum of the tertiles of PRU and ARU . The primary endpoint was the composite of cardiac death , nonfatal myocardial infa rct ion ( MI ) and ischemic stroke at 6 months post-PCI . RESULTS Ten patients reached the primary endpoint , four of which were nonfatal MI and six ischemic stroke . When analyzed for the primary endpoint , tertiles of ARU and PRU were not able to discriminate patients with future thrombotic events from the remainder ( p= 0.197 for ARU and 0.058 for PRU with the log-rank test , respectively ) , whereas combining the tertiles of ARU and PRU was significantly effective ( p= 0.019 for ARU+PRU with the log-rank test ) . Multivariate analysis showed that the highest tertile of the sum of ARU and PRU tertiles was the only significant predictor of future thrombotic events after PCI ( HR 6.34 , 95 % confidence interval 1.32 - 30.47 , p= 0.021 ) . CONCLUSIONS In this post-hoc analysis of the CILON-T trial , combining the results of ARU and PRU simultaneously had a significant role in discriminating patients at highest risk of future thrombotic events after PCI compared with either assay alone", "BACKGROUND Some data suggest that biological ' resistance ' to aspirin or clopidogrel may influence clinical outcome . OBJECTIVE The aim of this study was to evaluate the relationship between aspirin and clopidogrel responsiveness in healthy subjects . METHODS Ninety-six healthy subjects were r and omly assigned to receive a 1-week course of aspirin 100 mg day(-1 ) followed by a 1-week course of clopidogrel ( 300 mg on day 1 , then 75 mg day(-1 ) ) , or the reverse sequence , separated by a 2-week wash-out period . The drug effects were assessed by means of serum TxB2 assay , platelet aggregation tests , and the PFA -100 and Ultegra RPFA -Verify Now methods . RESULTS Only one subject had true aspirin resistance , defined as a serum TxB2 level > 80 pg microL(-1 ) at the end of aspirin administration and confirmed by platelet incubation with aspirin . PFA-100 values were normal in 29 % of the subjects after aspirin intake , despite a drastic reduction in TxB2 production ; these subjects were considered to have aspirin pseudo-resistance . Clopidogrel responsiveness was not related to aspirin pseudo-resistance . Selected polymorphisms of platelet receptor genes were not associated with either aspirin or clopidogrel responsiveness . CONCLUSIONS In healthy subjects , true aspirin resistance is rare and aspirin pseudo-resistance is not related to clopidogrel responsiveness", "BACKGROUND Decreased responsiveness to oral antiplatelet drug therapy has been associated with an adverse outcome after coronary stenting ( CS ) , but more studies are needed . The purpose of the present study was to prospect ively evaluate this issue . METHODS A total of 612 consecutive patients with stable or unstable coronary artery disease who underwent CS after at least 12 hours of aspirin and clopidogrel loading were studied . The study population was divided into responders and nonresponders to oral antiplatelet therapy , according to the values of preprocedural Platelet Function Analyzer-100 ( Dade Behring , Marburg , Germany ) collagen epinephrine closure time ( CEPI-CT ) . In particular , responders were considered as patients with a CEPI-CT > 193 seconds and nonresponders as those with a CEPI-CT death and rehospitalization for nonfatal myocardial infa rct ion was the prespecified primary study end point . RESULTS At 1 year , 9.1 % of patients reached the primary end point . Nonresponders to oral antiplatelet therapy were at significantly higher risk for the primary end point ( 18.7 % vs 7.6 % ) than responders . Nonresponsiveness to oral antiplatelet therapy was a predictor of the primary end point by both univariate ( hazard ratio 2.7 , 95 % CI 1.6 - 4.5 , P antiplatelet therapy , assessed by Platelet Function Analyzer-100 CEPI-CT , is an independent predictor of long-term outcome after CS", "AIM The relationships between clinical events and acetylsalicylic acid resistance ( AR ) , as well as its frequency , have been established in stable patients with coronary artery disease ( CAD ) . Although acute coronary syndrome ( ACS ) patients taking acetylsalicylic acid have been accepted as a high-risk population , the role of AR has not been investigated in these patient groups . Thus , in the present study , the impact of AR was investigated in patients with ACS who were taking acetylsalicylic acid . METHODS Between January 2001 and February 2003 , 140 ACS patients were included in the present prospect i ve study . All patients had ACS while taking acetylsalicylic acid . Coronary angiographic scores for severity and extent of CAD were determined for all patients . The effect of acetylsalicylic acid on platelet function was assessed by the platelet function analyzer PFA-100 ( Dade Behring , USA ) . The primary end point was the composite of death , myocardial infa rct ion , cerebrovascular accident and revascularization . The mean follow-up period was 20 months . RESULTS Patients with AR were older than patients without AR ( 63.8+/-10.8 years versus 58.3+/-11.2 years ; P=0.005 ) . Moreover , myocardial damage was higher in patients with AR according to cardiac troponin T values ( 1.11+/-1.3 mug/L versus 0.41+/-0.5 mug/L ; P=0.01 ) . The composite end point of death , myocardial infa rct ion , cerebrovascular accident or revascularization was present in 16 of 45 patients ( 35 % ) with AR and in 13 of 79 patients ( 16 % ) without AR ( hazard ratio 2.46 , 95 % CI 1.18 to 5.13 ; P=0.016 ) . After adjustment for age , platelet count , cardiac troponin T value and CAD severity score , AR remained an independent predictor for long-term adverse events ( hazard ratio 3.03 , 95 % CI 1.06 to 8.62 ; P=0.038 ) . CONCLUSIONS The clinical event rate was found to be higher in ACS patients with AR than in those without AR . Thus , it may be concluded that there is a strong correlation between a worse prognosis and AR in these patients", "Abstract Aim : To estimate the cost of treating stroke in the UK . Methods : A cost-of-illness model was constructed to estimate stroke-related costs over a 5-year period . The cost estimates were based on data from a large , r and omised , prospect i ve study comparing alternative strategies of stroke care . The study collected detailed data on re source use in hospital , primary care , healthcare contacts , and utilisation of social services over a period of 1 year following stroke . A Markov framework was used to extrapolate 1-year costs over 5 years . Results : The model estimated that , for every patient who experiences a stroke , the cost to the NHS in the UK is £ 15 306 over 5 years and , when informal care costs are included , the amount increases to £ 29 405 ( 2001/2002 prices ) . The robustness of the cost findings was explored with the use of sensitivity analysis . This focused on the key variables of rates of recurrent stroke , the estimated acute costs , and costs attached to institution and home care . Conclusion : As well as being a considerable cause of morbidity and mortality , stroke is also a huge cost burden to both the UK ’s NHS and the carers of stroke victims", "BACKGROUND AND PURPOSE Biological aspirin resistance ( AR ) has been recognized as an important cause of clinical AR . Recent studies have reported the beneficial effects of cilostazol for the prevention of cardiovascular diseases . This study investigated whether addition of cilostazol to aspirin in ischaemic stroke patients can reduce AR . METHODS In this double-blind multicenter trial , 244 aspirin users with ischaemic stroke were r and omly assigned to receive cilostazol 100 mg twice daily or to placebo . Antiplatelet function was assessed using the VerifyNow Aspirin system . The primary end-point was the incidence of AR , which was measured as aspirin resistance unit ( ARU ) > or = 550 after 4-week treatment . RESULTS The incidence of AR after treatment in cilostazol group was not significantly different from that in placebo ( 8.8 % vs. 10.9 % , P = 0.578 ) . However , AR decreased from 12.8 % to 8.8 % in cilostazol group , whereas it was not changed in the placebo group . The mean ARU after treatment were also lower in the cilostazol group ( 456.9 + /- 56.0 vs. 470.7 + /- 67.2 , P = 0.081 ) . Cilostazol addition did not prolong bleeding time . CONCLUSIONS Although this was a negative study , our findings disclosed a trend toward enhanced antiplatelet effects when cilostazol was added to aspirin in ischaemic stroke patients . Combination of aspirin and cilostazol might be a treatment option in the ischaemic stroke patients with AR", "A group of 100 patients with intermittent claudication ( 70 male , 30 female ) , treated with I00 mg ASA per day , were followed over 18 months after elective percutaneous balloon angioplasty . Platelet function was monitored over a period of 12 months by corrected whole blood aggregometry ( CWBA ) . Upon stimulation by arachidonic acid ( AA ) , adenosine diphosphate ( ADP ) and collagen , CWBA- results were obtained by an electronic acquisition and evaluation system correcting for hematocrit and platelet count of the blood sample . All patients showed a completely inhibited platelet response to AA stimulation . Comparison of the CWBA- results with clinical parameters revealed that reocclusions at the site of angioplasty occurred exclusively in male patients for which CWBA failed to prove an inhibition of aggregation upon both agonists , ADP and collagen , and for these patients the risk of complication is at least 87 % higher ( p = 0.0093 ) . Only 40 % of male patients show the expected effect of ASA on in vitro platelet aggregation at any given point in time and CWBA is capable of predicting those male patients which are at an elevated risk of reocclusion following peripheral angioplasty", "Celecoxib is a novel cyclooxygenase-2-specific inhibitor for the management of acute pain , primary dysmenorrhea , and the signs and symptoms of arthritis . This double-blind , placebo-controlled study in 16 healthy volunteers evaluated whether celecoxib alters the effect of concomitant aspirin on platelet function . Volunteers received celecoxib ( 400 mg/day ) or placebo for 4 days . On day 5 , they also received a single 325 mg dose of aspirin with either 200 mg celecoxib or placebo . Thromboxane and platelet aggregation response to adenosine 5'-diphosphate ( ADP ) , collagen , and arachidonic acid were measured before the first dose of celecoxib or placebo ( baseline ) and before dosing and 2 and 8 hours post dose on day 5 . There was no significant difference in thromboxane inhibition between the two groups ( percent inhibition : placebo 99.4 % , celecoxib 99.0 % ; p = 0.555 ) . There was also no significant difference in the effect of aspirin on platelet aggregation due to ADP , collagen , or arachidonic acid between the groups . Therefore , these data indicate that celecoxib does not alter the effects of aspirin on platelet function", "BACKGROUND Aspirin resistance is a major problem and its incidence and clinical significance in Indian patients with documented coronary artery disease are not known . AIM We sought to study the incidence of aspirin resistance and its clinical significance in a cohort of Indian patients with coronary heart disease on therapy with aspirin using urinary 11-Dehydrothromboxane B2 levels as a surrogate marker for antiplatelet efficacy . SETTING AND DESIGN Non r and omized single center prospect i ve study in cohort of patients with stable cardiovascular disease on chronic aspirin therapy attending the cardiology outpatient clinic of a tertiary care hospital . MATERIAL S AND METHODS Urinary dehydrothromboxane levels were analyzed in a cohort of 63 patients with stable documented coronary artery disease and in 21 healthy volunteers . The cases were followed up prospect ively for a median period of 36 ( 1 - 53 ) months . The clinical endpoint was a composite of acute coronary syndrome , stroke , revascularization and death . STATISTICAL ANALYSIS Comparison of urinary dehydrothromboxane concentration values between various risk factors was done using Mann Whitney U test , a non parametric alternative of independent t test . All statistical analyses were done using SPSS 11.0 ( Chicago , USA ) software . RESULTS The median ( range ) absolute values of urinary11- dehydrothromboxane B2 levels for the healthy volunteers and cases were 440 ( 286 - 2050 ) pg/ml and 320 ( 72 - 2600 ) pg/ml ( P=0.007 ) . The corresponding normalized values were 87.3 ( 43 - 143 ) and 60.8 ( 16.7 - 943 ) ng/mmol of creatinine ( P=0.131 ) . Among the various vascular risk factors , patients who were overweight had higher absolute levels of 11- urinary dehydrothomboxane B2 levels ( P=0.016 ) . There were significantly more clinical events in patients with absolute urinary 11-dehydrothromboxane B2 levels in the upper two quartiles compared to the lower two quartiles ( P=0.04 ) . CONCLUSION The incidence of aspirin resistance in the cohort of patients with documented heart disease was 38.1 % . Patients with elevated absolute urinary dehydrothomboxane levels ( > 320 pg/ml ) on chronic aspirin therapy constitute a high risk subset for recurrent vascular events", "BACKGROUND Platelets , long believed to be incapable of de novo protein synthesis , may retain their ability to form the cyclooxygenase ( COX ) enzyme once it has been inactivated by aspirin . This may explain the inefficacy of the drug to induce sustained platelet inhibition in certain patients . We evaluated the stability of platelet inhibition following once-daily enteric-coated aspirin administration . METHODS Platelet responsiveness to aspirin was evaluated in 11 stable coronary artery disease patients on chronic aspirin therapy before and 1 , 3 , 8 , and 24h after observed ingestion of 80-mg enteric-coated aspirin . Inhibition of the COX pathway was measured pharmacologically through plasma thromboxane ( Tx ) B(2 ) levels , and functionally by light transmission aggregometry in response to arachidonic acid . COX-independent platelet activity was measured in response to adenosine diphosphate , epinephrine and collagen . RESULTS Plasma TxB(2 ) levels showed profound inhibition of TxA(2 ) formation , which was stable throughout 24h , in all but 1 subject . This subject had optimal response to aspirin ( inhibition of platelet TxA(2 ) production within 1h ) , but recovered the ability to synthesize TxA(2 ) within 24h of aspirin ingestion . Arachidonic acid-induced platelet aggregation closely mirrored TxB(2 ) formation in this patient , portraying a functional ability of the platelet to aggregate within 24h of aspirin ingestion . COX-independent platelet aggregation triggered TxA(2 ) production to a similar extent in all patients , likely through signal-dependent protein synthesis . CONCLUSIONS COX-dependent platelet activity is recovered in certain individuals within 24h of aspirin administration . Further research should consider increasing aspirin dosing frequency to twice daily , to allow sustained inhibition in such subjects", "Clinical significance of resistance to aspirin and thienopyridine therapy is poorly defined . The authors aim ed to evaluate whether more effective antiplatelet therapy is associated with better outcome in patients on dual-antiplatelet treatment . Using optical aggregometer , maximal platelet aggregation values were measured with induction of adenosine diphosphate , collagen , and adrenaline 30 ± 5 days after coronary stent implantation in 134 patients . Markers of platelet activation were also analyzed with fluorescent immunoassay in 57 patients . After 10 months of follow-up , 33 patients reached the composite endpoint of cardiovascular death , myocardial infa rct ion , and revascularisation . Adenosine diphosphate-induced maximal aggregation values were in significant relationship with the development of major adverse cardiac events ( P ) . Level of soluble P-selectin proved to be an independent risk factor of adverse outcome ( P of thienopyridine therapy showed significant relation with clinical outcome , the authors conclude that interindividual variability in response to adenosine diphosphate-receptor antagonists may be of substantial clinical importance", "Platelet aggregability and fibrinolytic activity were studied repeatedly in 83 patients with reversible cerebral ischemic attacks over a median follow-up period of 26 months . Platelet hyperaggregability , defined as in vitro secondary aggregation obtained by adenosine diphosphate concentration less than or equal to 1 mumol/l , was demonstrated in 36.1 % or the patients examined 5 - 8 days after the attack , but only in 6 % of age- and sex-matched blood donors ( p less than 0.001 ) . Fibrinolytic activity was reduced in 57.8 % of the patients , as compared with 20.5 % of the controls . At the time of follow-up only 8 % of the survivors showed platelet hyperaggregability , whereas the fibrinolytic activity was still reduced in 44.4 % . Over the observation period 21.7 % of the patients had a stroke or died . No significant correlation was found between abnormalities of platelet aggregability or of fibrinolytic activity , when observed 5 - 8 days after the ischemic episode , and the subsequent risk of stroke or death . It is concluded that in patients with recent cerebral ischemic attacks the demonstration of platelet hyperaggregability or reduced fibrinolytic activity appears to be without prognostic significance", "OBJECTIVE This study was conducted to assess the thromboxane ( TX ) dependence of biochemical and functional indexes used to monitor the effect of low-dose aspirin . BACKGROUND Functional assays of the antiplatelet effects of low-dose aspirin variably reflect the TX-dependent component of platelet aggregation . Previous studies of aspirin resistance were typically based on a single determination of platelet aggregation . METHODS We assessed the TXB(2 ) dependence of biochemical and functional indexes , as well as their intersubject and intrasubject variability during administration of the drug and after its withdrawal in 48 healthy volunteers r and omized to receive aspirin 100 mg daily for 1 to 8 weeks . RESULTS Serum TXB(2 ) was uniformly suppressed by 99 % of baseline . Urinary 11-dehydro-TXB(2 ) , arachidonic acid-induced aggregation , and VerifyNow Aspirin ( Accumetrics Inc. , San Diego , California ) showed stable , incomplete inhibition ( 65 % , 80 % , and 35 % , respectively ) . Adenosine diphosphate- and collagen-induced aggregation was highly variable and poorly affected by aspirin , with an apparent time-dependent reversal . Inhibition of platelet cyclooxygenase activity was nonlinearly related to inhibition of platelet aggregation . Platelet function largely recovered by day 3 post-aspirin , independently of treatment duration . With any functional assay , occasionally \" resistant \" subjects were found to be \" responders \" on previous or subsequent determinations . CONCLUSIONS Platelet cyclooxygenase activity , as reflected by serum TXB(2 ) levels , is uniformly and persistently suppressed by low-dose aspirin in healthy subjects . However , the effect of aspirin is variably detected by functional assays , potentially leading to misclassification of \" responder \" as \" resistant \" phenotypes owing to poor reproducibility of functional measurements . The nonlinearity of the relationship between inhibition of TX production and inhibition of platelet function has important clinical implication", "OBJECTIVES The purpose of this study was to investigate the long-term outcome after elective percutaneous coronary intervention in low-risk patients screened for aspirin and /or clopidogrel responsiveness in the 3T/2R ( Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and /or Resistance to Clopidogrel ) trial . BACKGROUND The impact of aspirin and /or clopidogrel poor response on long-term outcome is debated . METHODS Aspirin and clopidogrel response was measured with the VerifyNow system aspirin and P2Y12 assays . After percutaneous coronary intervention ( PCI ) , death , stroke , and myocardial infa rct ion were assessed up to 1 year . RESULTS Overall , 1,277 patients were screened , and 826 ( 65 % ) were treated with PCI . In all , 124 patients were found to be aspirin poor responders , and there were 179 clopidogrel poor responders ( totally , 278 poor responders ) . The 1-year end point was significantly higher in poor responders as compared to full responders ( 15.8 % vs. 8.6 % , p=0.002 ) , which is principally due to more myocardial infa rct ion occurrence . At multivariable analysis , clopidogrel poor response emerged as an independent predictor ( hazard ratio : 1.15 , 95 % confidence interval : 1.03 to 1.28 ) . Receiver-operator characteristic analysis identifies≤23 of percentage of platelet inhibition and ≥208 of P2Y12 reactivity units as optimal cut offs to predict 1-year end point . Excluding periprocedural events , also peri-PCI myocardial infa rct ion , which is strongly related to aspirin/clopidogrel poor response , was an independent predictor ( hazard ratio : 1.25 , 95 % confidence interval : 1.14 to 1.37 ) . Glycoprotein IIb/IIIa inhibitor administration reduces this risk in poor responders ( 21.2 % vs. 34.7 % , p=0.02 ) , but not in full responders ( 6.3 % vs. 6.5 % , p=0.8 ) . CONCLUSIONS Poor response to clopidogrel is an independent predictor of periprocedural myocardial infa rct ion and worse 1-year outcome in low-risk patients undergoing PCI , whereas poor response to aspirin failed to predict a worse outcome . Contrary to what was observed in poor responders , glycoprotein IIb/IIa inhibitor therapy failed to provide a benefit in aspirin and /or clopidogrel full responders", "Platelets play a central role in the genesis of post-percutaneous coronary intervention ( PCI ) ischemic events . High post-procedural platelet reactivity to adenosine diphosphate ( HPRADP ) may be a risk factor for ischemic events after PCI . The study was design ed to evaluate a cutpoint of platelet reactivity that is associated with the occurrence of ischemic events after PCI . Post-procedural platelet reactivity to ADP was measured by conventional aggregometry in 297 consecutive patients undergoing non-emergent PCI . Patients were prospect ively followed for up to 2 years for post-discharge ischemic events . All patients had received clopidogrel and aspirin therapy at the time of aggregation measurements . Eighty-one patients ( 27 % ) suffered ischemic events . Patients with ischemic events had higher 5 µM ADP-induced platelet aggregation ( 46 ± 14 % vs. 30 ± 17 % , p and 20 µM ADP-induced platelet aggregation ( 60 ± 13 % vs. 43 ± 19 % , p 46 % aggregation following 5 µM ADP stimulation and > 59 % aggregation following 20 µM ADP stimulation ( HPRADP ) were associated with 58 and 54 % of ischemic events , respectively . Multivariate Cox regression demonstrated a significant relation between event occurrence and post-procedural HPRADP cutpoints ( 5 µM ADP , OR=3.9 , and 20 µM ADP , OR=3.8 , p both ) . High post-procedural platelet reactivity to ADP is an independent risk factor for ischemic events within 2 years of non-emergent PCI . These data support a potential therapeutic target for antiplatelet therapy based on the results of an ex vivo platelet function test . The study is a step towards a personalized medicine approach to guide the intensity of antiplatelet therapy", "To determine the prevalence of platelet nonresponsiveness to aspirin treatment for secondary stroke prophylaxis , the authors studied consecutive patients during a 29-month period . Information regarding their ischemic events , risk factors , and medications was collected . Platelet aggregation in response to collagen and arachidonic acid was used to determine platelet responsiveness to aspirin . A total of 653 patients were evaluated . Of these , 129 patients ( 20 % ) were determined to be nonresponsive to aspirin based on continued platelet aggregation in response to collagen , arachidonic acid , or both . A total of 87 ( 13 % ) of the 653 patients were clinical aspirin failures ( ie , presented with new focal cerebral ischemic symptoms while taking aspirin ) . Of the patients with new cerebral ischemic symptoms , 57 ( 66 % ) were determined to be platelet nonresponsive to aspirin . The odds ratio for platelet nonresponsiveness to aspirin in patients who suffered a recurrent ischemic event while taking aspirin was 14.25 ( 95 % confidence interval : 8.5 - 23.7 ; P Continued platelet aggregation despite aspirin treatment occurred in 20 % of ambulatory patients treated for secondary stroke prophylaxis . The prevalence of nonresponsiveness to aspirin was statistically higher in those patients who suffered recurrent cerebral ischemia while taking aspirin ( P < .5 ) compared with patients who remained without new ischemic symptoms" ]

[ "Background —In patients with ischemic heart disease , high thoracic epidural analgesia ( TEA ) has been proposed to improve abnormalities of coronary function by inhibiting cardiac sympathetic tone . We evaluated the effect of TEA on myocardial blood flow in patients with ischemic heart disease . Methods and Results —Twenty male patients with multivessel ischemic heart disease were studied . An epidural catheter was inserted between the second and third thoracic vertebral interspace ( Th2 to Th3 ) . Analgesia was induced by epidural injection of bupivacaine 0.5 % , and a sensory block from the sixth cervical ( C6 to C7 ) to Th10 ( Th8 to Th11 ) vertebral interspace was achieved . Myocardial blood flow was measured with dynamic 13N-ammonia PET with and without TEA at rest , during pharmacological vasodilation with dipyridamole , and during sympathetic stimulation with the cold pressor test . Myocardial blood flow during dipyridamole increased similarly , regardless of TEA , in all regions except in myocardium subtended by collateral arteries in which blood flow increased more with than without TEA ( P TEA , myocardial blood flow during the cold pressor test remained unchanged compared with myocardial blood flow at rest . In contrast , with TEA , myocardial blood flow increased in all vascular territories . Coronary vascular resistance increased during the cold pressor test without TEA , whereas with TEA , coronary resistance decreased in myocardium subtended by nonstenotic and stenotic coronary vessels and remained unchanged in myocardium subtended by occluded vessels . Conclusions —In patients with multivessel ischemic heart disease , TEA partly normalizes the myocardial blood flow response to sympathetic stimulation", "We investigated whether perioperative extensive epidural block ( C3-L ) affects postoperative immune response in patients undergoing radical esophagectomy . Patients undergoing radical esophagectomy were r and omly assigned to either general anesthesia with continuous epidural infusion via 2 epidural catheters that was continued for postoperative analgesia ( group E , n = 15 ) or intraoperative general anesthesia and postoperative IV morphine analgesia ( group G , n = 15 ) . Plasma levels of stress hormones , cytokines , C-reactive protein ( CRP ) , leukocyte counts , and distribution of lymphocyte subsets were assessed before and after surgery and on postoperative days ( PODs ) 1 and 3 . In comparison with group E , significant increases in plasma epinephrine level at the end of surgery ( P in cluster of differentiation ( CD4/CD8 ratio ) at the end of surgery ( P groups , plasma cortisol , adrenocorticotropic hormone , interleukin (IL)-1β , IL-6 , IL-10 , and CRP levels were increased after surgery ( each group P IL-1β , IL-6 , IL-10 , and CRP were still increased on POD1 and POD3 ( each change , each group P were increased on POD1 ( each group P ) . The proportion of lymphocytes decreased from the end of surgery to POD3 ( each group P The proportion of B cells was increased on POD1 ( each group P natural killer cells was decreased at POD1 and POD3 ( each group P < 0.01 ) . We conclude that tissue damage and inflammation apparently overcome the effects of extensive epidural block on stress response and immune function in radical esophagectomy", "The aim of this trial was to compare multimodal optimization with conventional perioperative management in a consecutive series of patients undergoing a wide range of colorectal procedures", "Background Perioperative myocardial ischemia occurs in 35 % of unselected elderly patients undergoing hip fracture surgery . Perioperative epidural analgesia may reduce the incidence of adverse cardiac events . Methods The effect of early administration of epidural analgesia during the stressful presurgical period , on preoperative cardiac events was evaluated in a prospect i ve r and omized study in 68 patients with hip fractures who either had known coronary artery disease or were at high risk for coronary artery disease . On admission to the emergency room , patients were assigned to receive a usual care analgesic regimen ( intramuscular meperidine , control group , n = 34 ) or continuous epidural infusion of local anesthetic and opioid ( epidural group , n = 34 ) . Monitoring in the preoperative period included a preoperative history and physical examination , daily assessment of cardiac adverse events , serial electrocardiograms , cardiac enzymes , and pain scores . Results Preoperative adverse cardiac events were significantly more prevalent in the control group compared with the epidural group ( 7 of 34 vs. 0 of 34;P = 0.01 ) . Adverse cardiac events included fatal myocardial infa rct ion in three , fatal congestive heart failure in one , nonfatal congestive heart failure in one , and new onset atrial fibrillation in two . The incidence of intraoperative and postoperative adverse cardiac events was similar for the two groups . The significant difference between groups in the incidence of preoperative cardiac events prompted interruption of the study after the planned interim analysis . Conclusions The authors ’ data indicate that compared with conventional analgesia , early administration of continuous epidural analgesia is associated with a lower incidence of preoperative adverse cardiac events in elderly patients with hip fracture who have or are at risk for coronary artery disease . Preoperative epidural analgesia may be advantageous for this surgical population", "Background Because general anesthesia with tracheal intubation can elicit life-threatening bronchospasm in patients with bronchial hyperreactivity , epidural anesthesia is often preferred . However , segmental high thoracic epidural anesthesia ( sTEA ) causes pulmonary sympathetic and respiratory motor blockade . Whether it can be safely used for chest wall surgery as a primary anesthetic technique in patients with chronic obstructive pulmonary disease or asthma is unclear . Furthermore , ropivacaine supposedly evokes less motor blockade than bupivacaine and might minimize side effects . To test the feasibility of the technique and the hypotheses that ( 1 ) sTEA with ropivacaine or bupivacaine does not change lung function and ( 2 ) there is no difference between sTEA with ropivacaine or bupivacaine , the authors studied 20 patients with severe chronic obstructive pulmonary disease ( forced expiratory volume in 1 s [ FEV1 ] = 52.1 ± 17.3 % of predicted [ mean ± SD ] ) or asthma who were undergoing breast surgery . Methods In a double-blind , r and omized fashion , sTEA was performed with 6.6 ± 0.5 ml of either ropivacaine , 0.75 % ( n = 10 ) , or bupivacaine , 0.75 % ( n = 10 ) . FEV1 , vital capacity , FEV1 over vital capacity , spread of analgesia ( pin prick ) , h and and foot skin temperatures , mean arterial pressure , heart rate , and local anesthetic plasma concentrations were measured with patients in the sitting and supine positions before and during sTEA . Results Segmental high thoracic epidural anesthesia ( segmental spread C4–T8 [ bupivacaine ] and C5–T9 [ ropivacaine ] ) significantly decreased FEV1 from 1.22 ± 0.54 l ( supine ) to 1.09 ± 0.56 l ( ropivacaine ) and from 1.23 ± 0.49 l to 1.12 ± 0.46 l ( bupivacaine ) . In contrast , FEV1 over vital capacity increased from 64.6 ± 13.5 to 68.2 ± 14.5 % ( ropivacaine ) and from 62.8 ± 12.4 to 66.5 ± 13.6 % ( bupivacaine ) . There was no difference between ropivacaine and bupivacaine . Skin temperatures increased significantly , whereas arterial pressure and heart rate significantly decreased indicating widespread sympathetic blockade . All 20 patients tolerated surgery well . Conclusions Despite sympathetic blockade , sTEA does not increase airway obstruction and evokes only a small decrease in FEV1 as a sign of mild respiratory motor blockade with no difference between ropivacaine and bupivacaine . Therefore , sTEA can be used in patients with severe chronic obstructive pulmonary disease and asthma undergoing chest wall surgery as an alternative technique to general anesthesia", "Optimal analgesia is important after thoracotomy in pulmonary-limited patients to avoid pain-related pulmonary complications . Thoracic epidural anesthesia ( TEA ) can provide excellent pain relief . However , potential paralysis of respiratory muscles and changes in bronchial tone might be unfavorable in patients with end-stage chronic obstructive pulmonary disease ( COPD ) . Therefore , we evaluated the effect of TEA on maximal inspiratory pressure , pattern of breathing , ventilatory mechanics , and gas exchange in 12 end-stage COPD patients . Pulmonary resistance , work of breathing , dynamic intrinsic positive end-expiratory pressure , and peak inspiratory and expiratory flow rates were evaluated by assessing esophageal pressure and airflow . An increase in minute ventilation ( 7.50 ± 2.60 vs 8.70 ± 2.10 L/min;P = 0.04 ) by means of increased tidal volume ( 0.46 ± 0.16 vs 0.53 ± 0.14 L/breath;P = 0.003 ) was detected after TEA . These changes were accompanied by an increase in peak inspiratory flow rate ( 0.48 ± 0.17 vs 0.55 ± 0.14 L/s;P = 0.02 ) and a decrease in pulmonary resistance ( 20.7 ± 9.9 vs 16.6 ± 8.1 cm H2O · L−1 · s−1;P = 0.02 ) . Peak expiratory flow rate , dynamic intrinsic positive end-expiratory pressure , work of breathing , Pao2 , and maximal inspiratory pressure were unchanged ( all P > 0.50 ) . We conclude that TEA with bupivacaine 0.25 % can be used safely in end-stage COPD patients", "BACKGROUND Epidural block is widely used to manage major abdominal surgery and postoperative analgesia , but its risks and benefits are uncertain . We compared adverse outcomes in high-risk patients managed for major surgery with epidural block or alternative analgesic regimens with general anaesthesia in a multicentre r and omised trial . METHODS 915 patients undergoing major abdominal surgery with one of nine defined comorbid states to identify high-risk status were r and omly assigned intraoperative epidural anaesthesia and postoperative epidural analgesia for 72 h with general anaesthesia ( site of epidural selected to provide optimum block ) or control . The primary endpoint was death at 30 days or major postsurgical morbidity . Analysis by intention to treat involved 447 patients assigned epidural and 441 control . FINDINGS 255 patients ( 57.1 % ) in the epidural group and 268 ( 60.7 % ) in the control group had at least one morbidity endpoint or died ( p=0.29 ) . Mortality at 30 days was low in both groups ( epidural 23 [ 5.1 % ] , control 19 [ 4.3 % ] , p=0.67 ) . Only one of eight categories of morbid endpoints in individual systems ( respiratory failure ) occurred less frequently in patients managed with epidural techniques ( 23 % vs 30 % , p=0.02 ) . Postoperative epidural analgesia was associated with lower pain scores during the first 3 postoperative days . There were no major adverse consequences of epidural-catheter insertion . INTERPRETATION Most adverse morbid outcomes in high-risk patients undergoing major abdominal surgery are not reduced by use of combined epidural and general anaesthesia and postoperative epidural analgesia . However , the improvement in analgesia , reduction in respiratory failure , and the low risk of serious adverse consequences suggest that many high-risk patients undergoing major intra-abdominal surgery will receive substantial benefit from combined general and epidural anaesthesia intraoperatively with continuing postoperative epidural analgesia", "It has been suggested that the incidence of early graft occlusion after arterial reconstructive surgery to the leg may be decreased by epidural analgesia . This effect may be mediated by the suppression of the usual cortisol response to surgery , which results in increased circulating plasminogen activator inhibitor-1 with consequent adverse effects on fibrinolysis . To investigate this and other potential mechanisms , 30 patients undergoing arterial reconstructive surgery to the leg were r and omized to receive either general anaesthesia or general anaesthesia plus epidural analgesia . Post-operative analgesia was provided by morphine infusion or epidural analgesia , respectively . Blood sample s were collected at 0 , 2 , 4 , 6 , 12 and 24 h , and 2 , 3 and 5 days and analysed for cortisol , plasminogen activator inhibitor-1 antigen , interleukin-6 and beta thromboglobulin . The incidence of graft-related and systemic complications was recorded for 30 days . Only one patient developed early graft occlusion that required embolectomy and eventually amputation . There were no significant changes from control values in either group of patients in circulating cortisol , plasminogen activator inhibitor-1 and beta thrombogobulin ( a marker for platelet degranulation ) . Interleukin-6 values increased significantly in both groups after 4 h and remained elevated until day 3 . There were no significant differences between the groups in any variable measured . We conclude that any effect of epidural analgesia on early graft patency is unlikely to be mediated by fibrinolysis or platetlet degranulation", "Sodium channel blockers are approved for IV administration in the treatment of neuropathic pain states . Pre clinical studies have suggested antihyperalgesic effects on the peripheral and central nervous system . Our objective in this study was to determine the time course of the analgesic and antihyperalgesic mechanisms of perioperative lidocaine administration . Forty patients undergoing major abdominal surgery participated in this r and omized and double-blinded study . Twenty patients received lidocaine 2 % ( bolus injection of 1.5 mg/kg in 10 min followed by an IV infusion of 1.5 mg · kg−1 · h−1 ) , and 20 patients received saline placebo . The infusion started 30 min before skin incision and was stopped 1 h after the end of surgery . Lidocaine blood concentrations were measured . Postoperative pain ratings ( numeric rating scale of 0–10 ) and morphine consumption ( patient-controlled analgesia ) were assessed up to 72 h after surgery . Mean lidocaine levels during surgery were 1.9 ± 0.7 & mgr;g/mL. Patient-controlled analgesia with morphine produced good postoperative analgesia ( numeric rating scale at rest , ≤3 ; 90%–95 % ; no group differences ) . Patients who received lidocaine reported less pain during movement and needed less morphine during the first 72 h after surgery ( 103.1 ± 72.0 mg versus 159.0 ± 73.3 mg ; Student ’s t-test ; P IV lidocaine may have a true preventive analgesic activity , most likely by preventing the induction of central hyperalgesia in a clinical ly relevant manner", "Background : Laparoscopic colonic surgery has been cl aim ed to hasten recovery and reduce hospital stay compared with open operation . Recently , enforced multimodal rehabilitation ( fast-track surgery ) has improved recovery and reduced hospital stay in both laparoscopic and open colonic surgery . Since no comparative data between laparoscopic and open colonic resection with multimodal rehabilitation are available , the value of laparoscopy per se is unknown . Methods : In a r and omized , observer- and -patient , blinded trial , 60 patients ( median age 75 years ) underwent elective laparoscopic or open colonic resection with fast-track rehabilitation and planned discharge after 48 hours . Functional recovery was assessed in detail during the first postoperative month . Results : Median postoperative hospital stay was 2 days in both groups , with early and similar recovery to normal activities as assessed by hours of mobilization per day , computerized monitoring of motor activity assessed , pulmonary function , cardiovascular response to treadmill exercise , pain , sleep quality , fatigue , and return to normal gastrointestinal function . There were no significant differences in postoperative morbidity , mortality , or readmissions , although 3 patients died in the open versus nil in the laparoscopic group . Conclusion : Functional recovery after colonic resection is rapid with a multimodal rehabilitation regimen and without differences between open and laparoscopic operation . Further large-scale studies are required on potential differences in serious morbidity and mortality", "Background Because of the uncertainty and limitations in available r and omized controlled trials , we performed an analysis of the Medicare cl aims data base to determine whether an association exists between postoperative epidural analgesia and mortality . Methods A 5 % nationally r and om sample of Medicare beneficiaries from 1997 to 2001 was analyzed to identify patients undergoing segmental excision of the lung ( International Statistical Classification of Diseases , Ninth Revision , Clinical Modification codes 32.3 and 32.4 ) , complete pneumonectomy ( code 32.5 ) , partial excision of large intestine ( codes 45.73 and 45.76 ) , anastomosis of the esophagus ( codes 42.5 and 42.6 ) , total knee replacement/revision ( codes 81.54 and 81.55 ) , total/radical abdominal hysterectomy ( codes 68.4 and 68.6 ) , partial/radical pancreaticoduodenectomy ( codes 52.5 and 52.7 ) , partial/complete nephrectomy ( codes 55.4 and 55.5 ) , partial/complete cystectomy ( codes 57.6 and 57.7 ) , hepatotomy/lobectomy of the liver ( codes 50.0 and 50.3 ) , partial/total gastrectomy ( codes 43.5 to 43.9 ) , and radical retropubic prostatectomy ( codes 60.4 and 60.5 ) . Patients were divided into 2 groups , depending on the presence or absence of postoperative epidural analgesia . The rate of major morbidity and death at 7 and 30 days after surgery were compared . Multivariate regression analyses incorporating race , gender , age , comorbidities , hospital size , hospital teaching status , and hospital technology status were performed . Results The presence of epidural analgesia was associated with a significantly lower odds of death at 7 days ( odds ratio [ OR ] , 0.52 ; 95 % confidence interval [ CI ] , 0.38 to 0.73 ; P = .0001 ) and 30 days ( OR , 0.74 ; 95 % CI , 0.63 to 0.89 ; P = .0005 ) after surgery ; however , no difference was seen between the groups with regard to overall major morbidity , with the exception of an increase in pneumonia at 30 days for the epidural group ( OR , 1.91;[95 % CI , 1.09 to 3.34 ; P = .02 ) . Conclusions Postoperative epidural analgesia may contribute to lower odds of death after surgery", "Background Adequate tissue oxygen tension is an essential requirement for surgical-wound healing . The authors tested the hypothesis that epidural anesthesia and analgesia increases wound tissue oxygen tension compared with intravenous morphine analgesia . Methods In a prospect i ve , r and omized , blind clinical study , the authors allocated patients having major abdominal surgery ( n = 32 ) to receive combined general and epidural anesthesia with postoperative patient-controlled epidural analgesia ( epidural group , n = 16 ) , or general anesthesia alone with postoperative patient-controlled intravenous analgesia ( intravenous group , n = 16 ) . An oxygen sensor and a temperature sensor were placed subcutaneously in the wound before closure . Wound oxygen tension ( Pwo2 ) and temperature were measured continuously for 24 h. Other variables affecting wound tissue oxygenation and visual analogue scale ( VAS ) pain scores were also documented . Results Despite epidural patients having lower body temperatures at the end of surgery ( 35.7 ± 0.3 ) versus 36.3 ± 0.5 ° C , P = 0.004 ) , they had significantly higher mean Pwo2 over the 24 h period , compared with the intravenous group ( 64.4 ± 14 vs. 50.7 ± 15 ) mmHg , mean ( SD ) , 95 % CI difference , −22 to −5 , P = 0.002 ) . Area under the Pwo2 −24 h time curve was also significantly higher in the epidural group ( 930 ± 278 vs. 749 ± 257 ) mmHg × h , 95 % CI difference −344 to −18 , P = 0.03 ) . VAS pain scores at rest and moving were significantly lower in the epidural group at all times . Conclusion Epidural anesthesia and postoperative analgesia for major abdominal surgery increases wound tissue oxygen tension compared with general anesthesia and intravenous morphine analgesia", "There is still controversy concerning the beneficial aspects of ' dynamic analgesia ' ( i.e. pain while coughing or moving ) on the reduction of postoperative atelectasis . In this study , we tested the hypothesis that thoracic epidural analgesia ( TEA ) prevents these abnormalities as opposed to multimodal analgesia with i.v . patient controlled analgesia ( i.v . PCA ) after thoracotomy . Fifty-four patients undergoing thoracotomy ( lung cancer ) were r and omly assigned to one of the two groups . Clinical respiratory characteristics , arterial blood gas , and pulmonary function tests ( forced vital capacity and forced expiratory volume in 1 s ) were obtained before surgery and on the next 3 postoperative days . Atelectasis was compared between the two groups by performing computed tomography ( CT ) scan of the chest at day 3 . Postoperative respiratory function and arterial blood gas values were reduced compared with preoperative values ( mean ( SD ) FEV1 day 0 : 1.1 ( 0.3 ) litre ; 1.3 ( 0.4 ) litre ) but there was no significant difference between groups at any time . PCA and TEA provided a good level of analgesia at rest ( VAS day 0 : 21 ( 15/100 ) ; 8 ( 9/100 ) ) , but TEA was more effective for analgesia during mobilization ( VAS day 0 : 52 ( 3/100 ) ; 25 ( 17/100 ) ) . CT scans revealed comparable amounts of atelectasis ( expressed as a percentage of total lung volume ) in the TEA ( 7.1 (2.8)% ) and in the i.v . PCA group ( 6.71 (3.2)% ) . There was no statistical difference in the number of patients presenting with at least one atelectasis of various types ( lamellar , plate , segmental , lobar )", "Surgery is associated with immune alterations , which are the combined result of tissue damage , anesthesia , postoperative pain , and psychological stress . In the present study , we compared the effects of several postoperative pain management techniques on postoperative immune function . Patients hospitalized for abdominal surgery were r and omly assigned to one of three postoperative pain management techniques : opiates on dem and ( intermittent opiate regimen [ IOR ] ) , patient-controlled analgesia ( PCA ) , and patient-controlled epidural analgesia ( PCEA ) . Postoperative pain was assessed . Blood sample s were collected before and 24 , 48 , and 72 h after surgery . Production of interleukin (IL)-1&bgr ; , IL-2 , and IL-6 , natural killer cell cytotoxicity , and lymphocyte mitogenic responses were assessed . Patients of the PCEA group exhibited lower pain scores in the first 24 h after surgery compared with patients of the IOR and PCA groups . Mitogenic responses were suppressed in all groups in the first 24 h , returned to preoperative values by 72 h in the PCEA group , but remained suppressed in the PCA group . Production of IL-1&bgr ; and IL-6 increased in the IOR and PCA groups , whereas it remained almost unchanged in the PCEA group . Patients receiving an epidural mixture of opiate and local anesthetics ( PCEA group ) exhibited reduced suppression of lymphocyte proliferation and attenuated proinflammatory cytokine response in the postoperative period", "Background and Objectives : The effect of postoperative epidural analgesia ( vs. systemic analgesia ) on patient outcomes is unclear . Available r and omized controlled trials ( RCTs ) have focused on the intraoperative period and not properly examined the effect of postoperative epidural analgesia ( EA ) on outcomes . Methods : A 5 % nationally r and om sample of Medicare beneficiaries from 1994 to 1999 was analyzed to identify patients undergoing total hip arthroplasty ( Common Procedural Terminology [ CPT ] code 27130 , 27132 , 27134 , 27137 , 27138 ) . Patients were divided into 2 groups depending on the presence or absence of postoperative EA based on the CPT coding ( 01996 ) . The rate of major morbidity ( acute myocardial infa rct ion , deep venous thrombosis , pulmonary embolism , angina , respiratory failure , heart failure , cardiac dysrhythmias , pneumonia , pulmonary edema , sepsis , acute renal failure , paralytic ileus , acute cerebrovascular event ) and death at 7 and 30 days after the procedure were compared . Multivariate regression analysis was performed to determine if the presence of postoperative ( EA ) had an independent effect on mortality or major morbidity . Data were reported as an odds ratio with 95 % confidence intervals ( CI ) when appropriate . Results : The unadjusted 7‐ and 30‐day death rate was significantly lower for EA versus no EA ( 1.9/1000 [ 95 % CI : 0.2‐3.6 ] vs. 3.9/1000 [ 95 % CI : 3.0‐6.2 ] at 7 days [ P = .04 ] and 5.8/1000 [ 95 % CI : 2.9‐8.7 ] vs. 9.9/1000 [ 95 % CI : 8.6‐11.3 ] at 30 days [ P = 0.01 ] ) . However , multivariate regression analysis revealed that there was no difference between the groups with regard to mortality or major morbidity with the exception of an increase in deep venous thrombosis in patients who received EA . Conclusions : The use of postoperative EA was not associated a lower incidence of mortality and major morbidity in Medicare patients undergoing total hip arthroplasty . However , the results should be interpreted with caution because of limitations in using the Medicare cl aims data for analysis . Further trials using other properly conducted and design ed studies ( e.g. , RCTs ) would be ideal to vali date these results", "In a primary analysis of a large recently completed r and omized trial in 915 high-risk patients undergoing major abdominal surgery , we found no difference in outcome between patients receiving perioperative epidural analgesia and those receiving IV opioids , apart from the incidence of respiratory failure . Therefore , we performed a selected number of predetermined subgroup analyses to identify specific types of patients who may have derived benefit from epidural analgesia . We found no difference in outcome between epidural and control groups in subgroups at increased risk of respiratory or cardiac complications or undergoing aortic surgery , nor in a subgroup with failed epidural block ( all P > 0.05 ) . There was a small reduction in the duration of postoperative ventilation ( geometric mean [ SD ] : control group , 0.3 [ 6.5 ] h , versus epidural group , 0.2 [ 4.8 ] h ; P = 0.048 ) . No differences were found in length of stay in intensive care or in the hospital . There was no relationship between frequency of use of epidural analgesia in routine practice outside the trial and benefit from epidural analgesia in the trial . We found no evidence that perioperative epidural analgesia significantly influences major morbidity or mortality after major abdominal surgery", "Background : Meta-analyses report similar numbers needed to treat for nonsteroidal antiinflammatory drugs ( NSAIDs ) and opioids . Differences in baseline pain intensity among the studies from which these numbers needed to treat were derived may have confounded the results . NSAIDs have an opioid-sparing effect , but the importance of this effect is unclear . Therefore , the authors sought to compare the proportions of subjects who obtain pain relief with ketorolac versus morphine after surgery and to determine whether the opioid-sparing effect of an NSAID reduces the magnitude of opioid side effects . Methods : The study was a double-blind , r and omized controlled trial . The authors r and omly assigned 1,003 adult patients to receive 30 mg ketorolac or 0.1 mg/kg morphine intravenously . They calculated the proportion of subjects who achieved at least 50 % reduction in pain intensity 30 min after analgesic administration . Further , so long as pain intensity 30 min after analgesic administration was 5 or more out of 10 , patients received 2.5 mg morphine every 10 min until pain intensity was 4 or less out of 10 . The authors assessed the presence of opioid-related side effects . Results : Five hundred patients received morphine and 503 received ketorolac . Fifty percent of patients in the morphine group achieved pain relief , compared with 31 % in the ketorolac group ( difference , 19 % ; 95 % confidence interval , 13–25 % ) . The ketorolac – morphine group required less morphine ( difference , 6.5 mg ; 95 % confidence interval , −5.8 to −7.2 ) and had a lower incidence of side effects ( difference , 11 % ; 95 % confidence interval , 5–16 % ) than the morphine group . Conclusions : Opioids are more efficacious analgesics than NSAIDs , although historic data for these two drugs yield similar numbers needed to treat . Adding NSAIDs to the opioid treatment reduces morphine requirements and opioid-related side effects in the early postoperative period", "OBJECTIVE The purpose of this study was to assess prospect ively the incidence , health care re source utilization , and economic burden associated with perioperative myocardial ischemic injury ( PMII ) in high-risk patients undergoing noncardiac vascular surgery . METHODS Two hundred thirty-six patients consented to participate in a pharmacoeconomic sub study as part of a r and omized , multicenter clinical trial . Patients were assessed for myocardial ischemic injury by using clinical , biochemical , and electrocardiographic criteria . PMII was defined as fatal or nonfatal myocardial infa rct ion , new or worsened congestive heart failure , or new arrhythmias . Re source utilization parameters were compared for patients with and without PMII . Patients underwent the following index procedures : open abdominal aortic aneurysm repair ( n = 44 ) , bypass for aortoiliac disease ( n = 29 ) , bypass for femoropopliteal disease ( n = 62 ) , bypass for femorotibial disease ( n = 71 ) , extra-anatomic bypass ( n = 23 ) , and miscellaneous ( n = 7 ) . Patients undergoing carotid endarterectomy or only endovascular interventions were excluded . The incremental cost of PMII was estimated by applying the average costs ( adjusted to 2004 US dollars ) of the hospital ward ( dollar 700.00/d ) or intensive care unit ( dollar 2500.00/d ) to the length of stay differences for patients with and without PMII . RESULTS The overall mortality was 3.4 % ( 8/236 ) , and 7 of 8 deaths were related to PMII . PMII occurred in 42 ( 17.8 % ) of 236 patients : 22 myocardial infa rct ions , 11 congestive heart failures , and 12 new arrhythmias ( 3 patients had 2 PMII events ) . There was no evidence of differences in the incidence of PMII among the various index procedures . PMII was associated with a dramatic increase in re source utilization . The mean length of stay was 16.8 and 10.0 days for patients with and without PMII , respectively ( P Intensive care unit care was required by 35 ( 83.3 % ) of 42 patients with and 121 ( 62.4 % ) of 194 patients without PMII ( P mean intensive care unit length of stay was 6.6 and 3.7 days for patients with and without PMII , respectively ( P re source utilization and cost . The increase in re source utilization associated with PMII result ed in an estimated incremental cost per patient of dollar 9980.00 . If 250,000 high-risk open vascular operations are performed annually in the United States , the economic burden of PMII in these procedures alone approximates dollar 444 million . Strategies to decrease PMII incidence and severity should be evaluated in large-scale prospect i ve trials", "Twenty-four adults who were undergoing operations on the abdominal aorta were enrolled in a r and omized , double-blind , placebo-controlled study in which epidural morphine sulfate ( 6 mg ) was employed to attenuate the sympathoadrenal response to surgery to evaluate the possible contribution of sympathetic nervous system hyperactivity to postoperative hypertension . Patients who received epidural morphine required less parenteral morphine in the 24 hours following surgery , had lower analogue pain scores , and had markedly lower plasma norepinephrine levels when compared with patients in the control group who received an identical volume of saline in the epidural space . Epidural morphine had no effect on plasma epinephrine or arginine vasopressin levels . Fewer patients in the morphine group ( 4 of 12 vs 9 of 12 patients in the saline group ) required treatment for hypertension ( mean arterial blood pressure , greater than or equal to 110 mm Hg ) in the 24 hours following surgery . In addition , patients in the morphine group had lower blood pressures in the 24 hours following surgery . These data suggest that sympathetic nervous system activity and not adrenal epinephrine or pituitary secretion of arginine vasopressin is responsible for the development of hypertension following aortic surgery . Furthermore , epidural narcotics appear to provide a means of attenuating this response", "Objective To test the hypothesis that epidural anesthesia and postoperative epidural analgesia decrease the incidence of death and major complications during and after four types of intraabdominal surgical procedures . Summary Background Data Even though many beneficial aspects of epidural anesthesia have been reported , clinical trials of epidural anesthesia for outcome of surgical patients have shown conflicting results . Methods The authors studied 1,021 patients who required anesthesia for one of the intraabdominal aortic , gastric , biliary , or colon operations . They were assigned r and omly to receive either general anesthesia and postoperative analgesia with parenteral opioids ( group 1 ) or epidural plus light general anesthesia and postoperative epidural morphine ( group 2 ) . The patients were monitored for death and major complications during and for 30 days after surgery , as well as for postoperative pain , time of ambulation , and length of hospital stay . Results Overall , there was no significant difference in the incidence of death and major complications between the two groups . For abdominal aortic surgical patients , unlike the other three types of surgical patients , the overall incidence of death and major complications was significantly lower in group 2 patients ( 22 % ) than in group 1 patients ( 37 % ) , stemming from differences in the incidence of new myocardial infa rct ion , stroke , and respiratory failure between the two groups . Overall , group 2 patients received significantly less analgesic medication but had better pain relief than group 1 patients . In group 2 aortic patients , endotracheal intubation time was 13 hours shorter and surgical intensive care stay was 3.5 hours shorter . Conclusions The effect of anesthetic and postoperative analgesic techniques on perioperative outcome varies with the type of operation performed . Overall , epidural analgesia provides better postoperative pain relief . Epidural anesthesia and epidural analgesia improve the overall outcome and shorten the intubation time and intensive care stay in patients undergoing abdominal aortic operations", "Postoperative ileus is a concern among surgical patients .Epidural anesthesia and analgesia with local anesthetics can decrease the duration of ileus . Significant systemic absorption of local anesthesia occurs during epidural use . In this study , we examined whether many of the beneficial effects on bowel function seen with epidural lidocaine are also present when the drug is given parenterally . Forty patients undergoing radical retropubic prostatectomy were studied with one half of the patients receiving a lidocaine bolus ( 1.5 mg/kg ) and infusion ( 3 mg/min , unless weight saline infusion . A blind observer recorded the patient 's daily pain score , the time the patient first experienced flatulence and had the first bowel movement , and the total use of analgesics . Lidocaine-treated patients first experienced flatulence in a significantly shorter time ( P Lidocaine patients ' hospital stay was also significantly shorter ( P lidocaine initiated before anesthesia and continued 1 h postoperatively significantly sped up the return of bowel function . Lidocaine patients were also more comfortable postoperatively . Many of the bowel function benefits attributed to epidural lidocaine are also present when the drug is administered parenterally . Additionally , the length of hospital stay was reduced in lidocaine-treated patients . Implication s : This study prospect ively examined whether IV lidocaine could affect the return of bowel function after radical prostate surgery . Lidocaine-treated patients had shorter hospital stays , less pain , and faster return of bowel function . In this population , lidocaine infusion can be a useful adjunct in anesthetic management . ( Anesth Analg 1998;86:235 - 9", "Background : Cardiovascular function was assessed in 20 ASA I‐II patients , scheduled for elective orthopaedic surgery with tourniquet in order to compare the haemodynamic changes induced by unilateral spinal anaesthesia and combined sciaticofemoral nerve block ", "OBJECTIVE The objective of this study was to determine whether st and ard deviations ( SDs ) used in sample size calculations are smaller than those found in the result ing study sample , thereby leading to underpowered studies . METHOD The predicted SD used in the sample size calculation and the actual SD of the study sample were recorded for r and omized trials recently published in one of four major journals . RESULTS Sample SD was greater than predicted SD for 80 % of endpoints . About one quarter of trials required five times as many patients as specified in the sample size calculation . CONCLUSION Trials reporting sample size calculations for continuous endpoints published in the most reputable medical journals are often underpowered . There seems to be insufficient underst and ing that the SD of a sample of patients is a r and om variable , associated with imprecision , that can not easily be extrapolated from one population to another" ]

[ "A new ambulatory method of monitoring physical activities in Parkinson 's disease ( PD ) patients is proposed based on a portable data -logger with three body-fixed inertial sensors . A group of ten PD patients treated with subthalamic nucleus deep brain stimulation ( STN-DBS ) and ten normal control subjects followed a protocol of typical daily activities and the whole period of the measurement was recorded by video . Walking periods were recognized using two sensors on shanks and lying periods were detected using a sensor on trunk . By calculating kinematics features of the trunk movements during the transitions between sitting and st and ing postures and using a statistical classifier , sit-to-st and ( SiSt ) and st and -to-sit ( StSi ) transitions were detected and separated from other body movements . Finally , a fuzzy classifier used this information to detect periods of sitting and st and ing . The proposed method showed a high sensitivity and specificity for the detection of basic body postures allocations : sitting , st and ing , lying , and walking periods , both in PD patients and healthy subjects . We found significant differences in parameters related to SiSt and StSi transitions between PD patients and controls and also between PD patients with and without STN-DBS turned on . We concluded that our method provides a simple , accurate , and effective means to objective ly quantify physical activities in both normal and PD patients and may prove useful to assess the level of motor functions in the latter", "Background Patients with Parkinson 's disease ( PD ) suffer from a high fall risk . Previous approaches for evaluating fall risk are based on self-report or testing at a given time point and may , therefore , be insufficient to optimally capture fall risk . We tested , for the first time , whether metrics derived from 3 day continuous recordings are associated with fall risk in PD . Methods and Material s 107 patients ( Hoehn & Yahr Stage : 2.6±0.7 ) wore a small , body-fixed sensor ( 3D accelerometer ) on lower back for 3 days . Walking quantity ( e.g. , steps per 3-days ) and quality ( e.g. , frequency-derived measures of gait variability ) were determined . Subjects were classified as fallers or non-fallers based on fall history . Subjects were also followed for one year to evaluate predictors of the transition from non-faller to faller . Results The 3 day acceleration derived measures were significantly different in fallers and non-fallers and were significantly correlated with previously vali date d measures of fall risk . Walking quantity was similar in the two groups . In contrast , the fallers walked with higher step-to-step variability , e.g. , anterior-posterior width of the dominant frequency was larger ( p = 0.012 ) in the fallers ( 0.78±0.17 Hz ) compared to the non-fallers ( 0.71±0.07 Hz ) . Among subjects who reported no falls in the year prior to testing , sensor-derived measures predicted the time to first fall ( p = 0.0034 ) , whereas many traditional measures did not . Cox regression analysis showed that anterior-posterior width was significantly ( p = 0.0039 ) associated with time to fall during the follow-up period , even after adjusting for traditional measures . Conclusions / Significance These findings indicate that a body-fixed sensor worn continuously can evaluate fall risk in PD . This sensor-based approach was able to identify transition from non-faller to faller , whereas many traditional metrics were not successful . This approach may facilitate earlier detection of fall risk and may in the future , help reduce high costs associated with falls", "An ambulatory gait analysis method using body-attached gyroscopes to estimate spatio-temporal parameters of gait has been proposed and vali date d against a reference system for normal and pathologic gait . Later , ten Parkinson 's disease ( PD ) patients with subthalamic nucleus deep brain stimulation ( STN-DBS ) implantation participated in gait measurements using our device . They walked one to three times on a 20-m walkway . Patients did the test twice : once STN-DBS was ON and once 180 min after turning it OFF . A group of ten age-matched normal subjects were also measured as controls . For each gait cycle , spatio-temporal parameters such as stride length ( SL ) , stride velocity ( SV ) , stance ( ST ) , double support ( DS ) , and gait cycle time ( GC ) were calculated . We found that PD patients had significantly different gait parameters comparing to controls . They had 52 % less SV , 60 % less SL , and 40 % longer GC . Also they had significantly longer ST and DS ( 11 % and 59 % more , respectively ) than controls . STN-DBS significantly improved gait parameters . During the stim ON period , PD patients had 31 % faster SV , 26 % longer SL , 6 % shorter ST , and 26 % shorter DS . GC , however , was not significantly different . Some of the gait parameters had high correlation with Unified Parkinson 's Disease Rating Scale ( UPDRS ) subscores including SL with a significant correlation ( r=-0.90 ) with UPDRS gait subscore . We concluded that our method provides a simple yet effective way of ambulatory gait analysis in PD patients with results confirming those obtained from much more complex and expensive methods used in gait labs", "Background and Purpose : Relatively little is known about the natural evolution of physical activity – related participation restrictions associated with Parkinson 's disease ( PD ) . We examined this issue prospect ively , using continuous monitoring technology to capture the free-living ambulatory activity of persons with PD engaging in life situations . We specifically sought ( 1 ) to explore natural , long-term changes in daily ambulatory activity and ( 2 ) to compare the responsiveness of ambulatory activity parameters to clinical measures of gait and disease severity . Methods : Thirty-three persons with PD participated ( Hoehn and Yahr range of 1–3 ) . Participants wore a step activity monitor for up to 7 days at baseline and again at 1-year follow-up . Mean daily values were calculated for parameters indicative of amount , intensity , frequency , and duration of ambulatory activity . Clinical measures included the Unified Parkinson Disease Rating Scale , the 6-Minute Walk , and Maximal Gait Speed . Parametric tests for paired sample s were used to investigate changes in ambulatory activity parameters and clinical measures . Results : Participants had significant declines in the amount and intensity of daily ambulatory activity but not in its frequency and duration ( P number of daily minutes participants spent engaging in at least moderate-intensity ambulatory activity . Conclusion : Continuous monitoring of ambulatory activity beyond mere step counts may serve as a distinct and important means of quantifying declining ambulatory behavior associated with disease progression or improved ambulatory behavior result ing from rehabilitation and medical and /or surgical interventions in persons with PD", "OBJECTIVES To explore the potential of using step activity monitoring to detect differences in ambulatory activity associated with advancing age and declining function in community-dwelling seniors . DESIGN Cross-sectional pilot study . SETTING General communities of Seattle , Washington ; Catonsville , Maryl and ; and Durham , North Carolina . PARTICIPANTS Thirty healthy younger adults , 28 healthy older adults , and 12 older adults reporting functional limitations . MEASUREMENTS Ambulatory activity data were collected over 6 days with the StepWatch 3 . Average daily values were calculated for number of steps , number of minutes of activity , number of activity bouts , variability of minute-to-minute activity , and r and omness of minute-to-minute activity fluctuations . RESULTS Healthy older adults engaged in fewer bouts of activity ( P=.03 ) and displayed less-variable activity ( P=.02 ) than younger adults . Older adults reporting functional limitations not only engaged in fewer bouts of activity ( P=.009 ) and less variable activity ( P total steps ( P=.003 ) and minutes of activity ( P=.008 ) and had less-r and om minute-to-minute activity fluctuations ( P=.02 ) . CONCLUSION Step activity monitoring data were useful for detecting differences in ambulatory activity according to age and functional limitation . Monitor-based measures reflecting patterns of ambulatory activity show promise for use in studies of physical functioning", "OBJECTIVE To examine the reliability , validity , and responsiveness of a continuous ambulatory activity monitor in patients with rheumatoid arthritis ( RA ) . METHODS Forty-one patients with RA , participating in a r and omized controlled trial examining the effect of an intensive exercise program , were assessed by means of the Dynaport ADL ( activities of daily living ) monitor ( AM ) . The time spent on activities ( locomotion , st and ing , and active sitting ) during 24 hours and the intensity of trunk movement during these activities were recorded . To determine test-retest reliability 20 patients were reassessed with the AM one week after the first assessment . Construct validity of the AM was determined by comparing the AM results with physical fitness measures ( muscle strength , endurance , joint mobility ) , disease activity , and functional status . As well , 37 patients were assessed 18 months after the first assessment to determine responsiveness . RESULTS All AM measurements showed satisfactory test-retest reliability ( ICC 0.63 - 0.76 ) . AM measures were significantly associated with physical fitness , functional status , and disease activity , indicating construct validity of the AM . The AM could discriminate between patients with improvement and deterioration in physical fitness , indicating sufficient responsiveness of AM variables . CONCLUSION This study shows the value of an ambulatory activity monitor to quantify both the amount and intensity of physical activity of patients with RA during a day in their own environment . The ambulatory activity monitor seems to be a promising instrument for research into rehabilitation of patients with RA", "The aim of this study was to assess whether the GAITRite gait analysis system an effective tool in evaluating parkinsonian bradykinesia . In their best ON and worst OFF states , 13 parkinsonian patients were asked to perform walking trail at their fastest velocity , and to su bmi t to traditional timed tests . Significant correlations existed between OFF-ON improvement in gait parameters and in UPDRS III score ( r(2)=0.59 - 0.78 ) except cadence . Among the gait parameters , stride length is the most effective indicator of timed test and UPDRS III score improvements . The GAITRite system is an efficient , yet effective device in evaluating parkinsonian bradykinesia and can be used as a substitute for the traditional timed test", "Background : Impaired postural stability places individuals with Parkinson ’s at an increased risk for falls . Given the high incidence of fall-related injuries within this population , ongoing assessment of postural stability is important . Objective : To evaluate the validity of the Nintendo Wii ® balance board as a measurement tool for the assessment of postural stability in individuals with Parkinson ’s . Subjects : Twenty individuals with Parkinson ’s participated . Intervention : Subjects completed testing on two balance tasks with eyes open and closed on a Wii ® balance board and biomechanical force platform . Main Measures : Bl and –Altman plots and a two-way , r and om-effects , single measure intraclass correlation coefficient model were used to assess concurrent validity of centre-of-pressure data . Results : Concurrent validity was demonstrated to be excellent across balance tasks ( intraclass correlation coefficients = 0.96 , 0.98 , 0.92 , 0.94 ) . Conclusions : This study suggests that the Wii ® balance board is a valid tool for the quantification of postural stability among individuals with Parkinson ’s" ]

[ "In a r and omized , cross-over feeding trial involving 10 men with polygenic hypercholesterolemia , a control , Mediterranean-type cholesterol-lowering diet , and a diet of similar composition in which walnuts replaced approximately 35 % of energy from unsaturated fat , were given for 6 weeks each . Compared with the control diet , the walnut diet reduced serum total and LDL cholesterol by 4.2 % ( P = 0.176 ) , and 6.0 % ( P = 0.087 ) , respectively . No changes were observed in HDL cholesterol , triglycerides , and apolipoprotein A-I levels or in the relative proportion of protein , triglycerides , phospholipids , and cholesteryl esters in LDL particles . The apolipoprotein B level declined in parallel with LDL cholesterol ( 6.0 % reduction ) . Whole LDL , particularly the triglyceride fraction , was enriched in polyunsaturated fatty acids from walnuts ( linoleic and alpha-linolenic acids ) . In comparison with LDL obtained during the control diet , LDL obtained during the walnut diet showed a 50 % increase in association rates to the LDL receptor in human hepatoma HepG2 cells . LDL uptake by HepG2 cells was correlated with alpha-linolenic acid content of the triglyceride plus cholesteryl ester fractions of LDL particles ( r(2 ) = 0.42 , P LDL lipid fatty acids after a walnut-enriched diet facilitate receptor-mediated LDL clearance and may contribute to the cholesterol-lowering effect of walnut consumption", "BACKGROUND Elevated serum cholesterol levels play an important role in the development of coronary artery disease . Previous studies have suggested that nut consumption benefits lipid profile . Pistachio nuts are widely available , inexpensive and frequently consumed by the general population . OBJECTIVE To determine whether substituting 20 % of the daily caloric intake in the form of pistachio nuts will improve the lipid profiles of humans with primary , moderate hypercholesterolemia . DESIGN Controlled , r and omized crossover design . SETTING Outpatient dietary modification , counseling and blood analysis . PATIENTS Ten patients with moderate hypercholesterolemia . INTERVENTION Three weeks of dietary modification with 20 % caloric intake from pistachio nuts . MEASUREMENTS Body weight , blood pressure , total cholesterol , LDL , HDL , and triglycerides were monitored . Lipid profiles were analyzed prior to , during and after dietary modification . RESULTS After three weeks , there was a decrease in total cholesterol ( p HDL ( p total cholesterol/HDL ratio ( p LDL/HDL ratio ( p Triglycerides and LDL levels decreased , but not significantly . Body weight and blood pressure remained constant throughout the study . CONCLUSIONS Results suggest that eating pistachio nuts instead of other dietary fat calories can improve lipid profiles , thereby decreasing coronary risk . Further studies will be required to confirm these results and to determine the mechanism of this effect", "BACKGROUND AND AIMS Virgin olive oil ( VOO ) and nuts are basic components of the Mediterranean diet , a heart-healthy dietary pattern . Nuts have well known cholesterol lowering effects , while evidence is unclear for VOO . We design ed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40 % of the fat in the background diet with VOO , walnuts or almonds . METHODS AND RESULTS After a 4 week run-in period with a healthy diet , eligible c and i date s were r and omized into three diet sequences in a crossover design , with a common background diet enriched with VOO , walnuts or almonds , lasting 4 weeks each . Outcomes were changes of serum lipids and oxidation and inflammation markers , measured by st and ard methods . Plasma fatty acids were determined by gas chromatography to assess compliance . In 18 participants completing the study ( 9 women , mean age 56 y , BMI 25.7 kg/m(2 ) ) , LDL-cholesterol was reduced from baseline by 7.3 % , 10.8 % and 13.4 % after the VOO , walnut and almond diets , respectively ( P = 0.001 , Friedman test ) . Total cholesterol and LDL/HDL ratios decreased in parallel . LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets . No changes of other lipid fractions , oxidation analytes or inflammatory biomarkers were observed . Plasma fatty acid changes after each diet sequence supported good compliance . CONCLUSION The results confirm the cholesterol lowering properties of nut-enriched diets . They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content , which clearly deserves further study", "Nut consumption reduces cardiovascular risk , and reductions in blood pressure and peripheral vascular resistance may be important mediators of this relationship . We evaluated effects of pistachios on flow-mediated dilation and blood pressure response to acute stress . Twenty-eight adults with dyslipidemia completed a r and omized , crossover , controlled-feeding study . All of the meals were provided and calories were controlled . After 2 weeks on a typical Western diet ( 35 % total fat and 11 % saturated fat ) , test diets were presented in counterbalanced order for 4 weeks each , a low-fat control diet ( 25 % total fat and 8 % saturated fat ) , a diet containing 10 % of energy from pistachios ( on average , 1 serving per day ; 30 % total fat and 8 % saturated fat ) , and a diet containing 20 % of energy from pistachios ( on average , 2 servings per day , 34 % total fat and 8 % saturated fat ) . None of the resting hemodynamic measures significantly differed from pretreatment values . When resting and stress levels were included in the repeated- measures analysis , average reductions in systolic blood pressure were greater after the diet containing 1 serving per day versus 2 servings per day of pistachios ( mean change in systolic blood pressure , −4.8 vs −2.4 mm Hg , respectively ; P reductions in peripheral resistance ( −62.1 dyne·s × cm−5 ) and heart rate ( −3 bpm ) versus the control diet ( P increases in cardiac output . There was no effect of diet on fasting flow-mediated dilation . Reductions in peripheral vascular constriction and the result ing decrease in hemodynamic load may be important contributors to lower risk in nut consumers", "BACKGROUND Dietary guidelines recommend interchanging protein foods ( e.g. , chicken for red meat ) , but they may be exchanged for carbohydrate-rich foods varying in quality [ glycemic load ( GL ) ] . Whether such exchanges occur and how they influence long-term weight gain are not established . OBJECTIVE Our objective was to determine how changes in intake of protein foods , GL , and their interrelationship influence long-term weight gain . DESIGN We investigated the association between 4-y changes in consumption of protein foods , GL , and their interaction with 4-y weight change over a 16- to 24-y follow-up , adjusted for other lifestyle changes ( smoking , physical activity , television watching , sleep duration ) , body mass index , and all dietary factors simultaneously in 3 prospect i ve US cohorts ( Nurses ' Health Study , Nurses ' Health Study II , and Health Professionals Follow-Up Study ) comprising 120,784 men and women free of chronic disease or obesity at baseline . RESULTS Protein foods were not interchanged with each other ( intercorrelations typically long-term weight gain , with positive associations for meats , chicken with skin , and regular cheese ( per increased serving/d , 0.13 - 1.17 kg ; P = 0.02 to P 0.40 for each ) ; and relative weight loss for yogurt , peanut butter , walnuts , other nuts , chicken without skin , low-fat cheese , and seafood ( -0.14 to -0.71 kg ; P = 0.01 to P ) . Increases in GL were independently associated with a 0.42-kg greater weight gain per 50-unit increase ( P weight gain when GL increased , with weight stability when GL did not change , and with weight loss when exchanged for GL ( i.e. , decrease in GL ) . CONCLUSION Protein foods were commonly interchanged with carbohydrate , and changes in protein foods and GL interacted to influence long-term weight gain", "Frequent consumption of nuts is associated with decreased risk of cardiovascular disease . We investigated the effect of pecans rich in monounsaturated fat as an alternative to the Step 1 diet in modifying serum lipids and lipoproteins in men and women with normal to moderately high serum cholesterol . In a single-blind , r and omized , controlled , crossover feeding study , we assigned 23 subjects ( mean age : 38 y ; 9 women , 14 men ) to follow two diets , each for 4 wk : a Step I diet and a pecan-enriched diet ( accomplished by proportionately reducing all food items in a Step I diet by one fifth for a 20 % isoenergetic replacement with pecans ) . The percentage of energy from fat in the two diets was 28.3 and 39.6 % , respectively . Both diets improved the lipid profile ; however , the pecan-enriched diet decreased both serum total and LDL cholesterol by 0.32 mmol/L ( 6.7 and 10.4 % , respectively ) and triglyceride by 0.14 mmol/L ( 11.1 % ) beyond the Step I diet , while increasing HDL cholesterol by 0.06 mmol/L ( 2.5 mg/dL ) . Serum apolipoprotein B and lipoprotein(a ) decreased by 11.6 and 11.1 % , respectively , and apolipoprotein A1 increased by 2.2 % when subjects consumed the pecan compared with the Step I diet . These differences were all significant ( P serum lipid profile beyond the Step I diet , without increasing body weight . Nuts such as pecans that are rich in monounsaturated fat may therefore be recommended as part of prescribed cholesterol-lowering diet of patients or habitual diet of healthy individuals", "BACKGROUND Frequent consumption of nuts may lower the risk of cardiovascular disease by favorably altering serum lipid and lipoprotein concentrations . OBJECTIVE We compared the effects of 2 amounts of almond intake with those of a National Cholesterol Education Program Step I diet on serum lipids , lipoproteins , apolipoproteins , and glucose in healthy and mildly hypercholesterolemic adults . DESIGN In a r and omized crossover design , 25 healthy subjects ( 14 men , 11 women ) with a mean ( + /- SD ) age of 41 + /- 13 y were fed 3 isoenergetic diets for 4 wk each after being fed a 2-wk run-in diet ( containing 34 % of energy from fat ) . The experimental diets included a Step I diet , a low-almond diet , and a high-almond diet , in which almonds contributed 0 % , 10 % , and 20 % of total energy , respectively . RESULTS Inverse relations were observed between the percentage of energy in the diet from almonds and the subject 's total cholesterol ( P value for trend LDL-cholesterol ( P apolipoprotein B ( P ratios of LDL to HDL cholesterol ( P apolipoprotein B to apolipoprotein A ( P high-almond diet reduced total cholesterol ( 0.24 mmol/L or 4.4 % ; P = 0.001 ) , LDL cholesterol ( 0.26 mmol/L or 7.0 % ; P apolipoprotein B ( 6.6 mg/dL or 6.6 % ; P HDL cholesterol ( 0.02 mmol/L or 1.7 % ; P = 0.08 ) ; and decreased the ratio of LDL to HDL cholesterol ( 8.8 % ; P serum lipid profile of healthy and mildly hypercholesterolemic adults . Total and LDL-cholesterol concentrations declined with progressively higher intakes of almonds , which suggests a dose-response relation", "BACKGROUND Atherosclerosis is a chronic inflammatory disease . We previously reported that a diet high in alpha-linolenic acid ( ALA ) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects . OBJECTIVE The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells ( P BMC s ) from subjects fed the experimental diets . DESIGN A r and omized , controlled , 3-diet , 3-period crossover study design was used . Hypercholesterolemic subjects ( n = 23 ) were assigned to 3 experimental diets : a diet high in ALA ( ALA diet ; 6.5 % of energy ) , a diet high in linoleic acid ( LA diet ; 12.6 % of energy ) , and an average American diet ( AAD ) for 6 wk . Serum interleukin (IL)-6 , IL-1beta , and tumor necrosis factor-alpha ( TNF-alpha ) concentrations and the production of IL-6 , IL-1beta , and TNF-alpha by P BMC s were measured . RESULTS IL-6 , IL-1beta , and TNF-alpha production by P BMC s and serum TNF-alpha concentrations were lower ( P ALA diet than with the LA diet or AAD . P BMC production of TNF-alpha was inversely correlated with ALA ( r = -0.402 , P = 0.07 ) and with eicosapentaenoic acid ( r = -0.476 , P = 0.03 ) concentrations in P BMC lipids with the ALA diet . Changes in serum ALA were inversely correlated with changes in TNF-alpha produced by P BMC s ( r = -0.423 , P antiinflammatory effects by inhibiting IL-6 , IL-1beta , and TNF-alpha production in cultured P BMC s. Changes in P BMC ALA and eicosapentaenoic acid ( derived from dietary ALA ) are associated with beneficial changes in TNF-alpha release . Thus , the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines", "This study was conducted to assess the cholesterol-lowering potential of macadamia nuts . Seventeen hypercholesterolemic men ( mean age 54 y ) were given macadamia nuts ( 40 - 90 g/d ) , equivalent to 15 % energy intake , for 4 wk . Plasma total cholesterol , LDL cholesterol , HDL cholesterol , triglycerides and homocysteine concentrations and the fatty acid composition of plasma lipids were determined before and after treatment . Plasma MUFA 16:1(n-7 ) , 18:1(n-7 ) and 20:1(n-9 ) were elevated after intervention with macadamia nuts . Plasma ( n-6 ) and ( n-3 ) PUFA concentrations were unaffected by macadamia nut consumption . Plasma total cholesterol and LDL cholesterol concentrations decreased by 3.0 and 5.3 % , respectively , and HDL cholesterol levels increased by 7.9 % in hypercholesterolemic men after macadamia nut consumption . Plasma triglyceride and homocysteine concentrations were not affected by treatment . Macadamia nut consumption was associated with a significant increase in the relative intake of MUFA and a reduced relative intake of saturated fatty acids and PUFA . This study demonstrates that macadamia nut consumption as part of a healthy diet favorably modifies the plasma lipid profile in hypercholesterolemic men despite their diet being high in fat", "BACKGROUND Nuts appear to have cardiovascular benefits but their effect in diabetic patients is unclear . OBJECTIVE The objective was to assess effects of almond-enriched diets on insulin sensitivity and lipids in patients with normoglycemia or type 2 diabetes . DESIGN Study 1 assessed the effect of almonds on insulin sensitivity in 20 free-living healthy volunteers who received 100 g almonds/d for 4 wk . Study 2 was a r and omized crossover study that compared 4 diets in 30 volunteers with type 2 diabetes : 1 ) high-fat , high-almond ( HFA ; 37 % total fat , 10 % from almonds ) ; 2 ) low-fat , high-almond ( LFA ; 25 % total fat , 10 % from almonds ) ; 3 ) high-fat control ( HFC ; 37 % total fat , 10 % from olive or canola oil ) ; and 4 ) low-fat control ( LFC ; 25 % total fat , 10 % from olive or canola oil ) . After each 4-wk diet , serum lipids and oral glucose tolerance were measured . RESULTS In study 1 , almond consumption did not change insulin sensitivity significantly , although body weight increased and total and LDL cholesterol decreased by 21 % and 29 % , respectively ( P total cholesterol was lowest with the HFA diet ( 4.46 + /- 0.14 , 4.52 + /- 0.14 , 4.63 + /- 0.14 , and 4.63 + /- 0.14 mmol/L with the HFA , HFC , LFA , and LFC diets , respectively ; P = 0.0004 for fat level ) . HDL cholesterol was significantly lower with the almond diets ( P = 0.002 ) ; however , no significant effect of fat source on LDL : HDL was observed . Glycemia was unaffected . CONCLUSIONS Almond-enriched diets do not alter insulin sensitivity in healthy adults or glycemia in patients with diabetes . Almonds had beneficial effects on serum lipids in healthy adults and produced changes similar to high monounsaturated fat oils in diabetic patients", "Epidemiologic and clinical studies have shown that nut consumption is associated with favorable plasma lipid profiles and reduced cardiovascular risk . These effects may result from their high monounsaturated fat ( MUFA ) content but nuts contain constituents other than fatty acids that might be cardioprotective . We conducted a study to compare the effects of whole-almond vs. almond oil consumption on plasma lipids and LDL oxidation in healthy men and women . Using a r and omized crossover trial design , 22 normolipemic men and women replaced half of their habitual fat ( approximately 14 % of approximately 29 % energy ) with either whole almonds ( WA ) or almond oil ( AO ) for 6-wk periods . Compliance was ascertained by monitoring dietary intake via biweekly 5-d food records , return of empty almond product packages and weekly meetings with a registered dietitian . Fat replacement with either WA and AO result ed in a 54 % increase in percentage of energy as MUFA with declines in both saturated fat and cholesterol intake and no significant changes in total energy , total or polyunsaturated fat intake . The effects of WA and AO on plasma lipids did not differ compared with baseline ; plasma triglyceride , total and LDL cholesterol significantly decreased , 14 , 4 and 6 % respectively , whereas HDL cholesterol increased 6 % . Neither treatment affected in vitro LDL oxidizability . We conclude that WA and AO do not differ in their beneficial effects on the plasma lipid variables measured and that this suggests that the favorable effect of almonds is mediated by components in the oil fraction of these nuts", "Epidemiologic studies and clinical trials have demonstrated that the unique fatty acid profile of nuts beneficially affects serum lipids/lipoproteins , reducing cardiovascular disease ( CVD ) risk . Nuts are low in SFA and high in PUFA and monounsaturated fatty acids ( MUFA ) . Macadamia nuts are a rich source of MUFA . A r and omized , crossover , controlled feeding study ( 5-wk diet periods ) compared a Macadamia nut-rich diet [ 42.5 g ( 1.5 ounces)/8.79 MJ ( 2100 kcal ) ] [ MAC ; 33 % total fat ( 7 % SFA , 18 % MUFA , 5 % PUFA ) ] vs. an average American diet [ AAD ; 33 % total fat ( 13 % SFA , 11 % MUFA , 5 % PUFA ) ] on the lipid/lipoprotein profile of mildly hypercholesterolemic ( n = 25 ; 15 female , 10 male ) subjects . Serum concentrations of total cholesterol ( TC ) and LDL cholesterol ( LDL-C ) following the MAC ( 4.94 + /- 0.17 mmol/L , 3.14 + /- 0.14 mmol/L ) were lower than the AAD ( 5.45 + /- 0.17 mmol/L , 3.44 + /- 0.14 mmol/L ; P serum non-HDL cholesterol ( HDL-C ) concentration and the ratios of TC : HDL-C and LDL-C : HDL-C were reduced following consumption of the MAC diet ( 3.83 + /- 0.17 , 4.60 + /- 0.24 , and 2.91 + /- 0.17 , respectively ) compared with the AAD ( 4.26 + /- 0.17 , 4.89 + /- 0.24 , and 3.09 + /- 0.18 , respectively ; P serum triglyceride concentration . Thus , macadamia nuts can be included in a heart-healthy dietary pattern that reduces lipid/lipoprotein CVD risk factors . Nuts as an isocaloric substitute for high SFA foods increase the proportion of unsaturated fatty acids and decrease SFA , thereby lowering CVD risk", "BACKGROUND Nut consumption lowers cardiovascular disease ( CVD ) risk . Studies are lacking about the effects of pistachios , a nutrient-dense nut , on CVD risk factors , dose-response relations , and lipid-lowering mechanisms . OBJECTIVE We evaluated the effects of 2 doses of pistachios , added to a lower-fat diet , on lipids and lipoproteins , apolipoprotein (apo)-defined lipoprotein subclasses , and plasma fatty acids . To investigate the mechanisms of action , we measured cholesteryl ester transfer protein and indexes of plasma stearoyl-CoA desaturase activity ( SCD ) . DESIGN In a r and omized crossover controlled-feeding study , 28 individuals with LDL cholesterol > or = 2.86 mmol/L consumed 3 isoenergetic diets for 4 wk each . Baseline measures were assessed after 2 wk of a typical Western diet . The experimental diets included a lower-fat control diet with no pistachios [ 25 % total fat ; 8 % saturated fatty acids ( SFAs ) , 9 % monounsaturated fatty acids ( MUFAs ) , and 5 % polyunsaturated fatty acids ( PUFAs ) ] , 1 serving/d of a pistachio diet ( 1 PD ; 10 % of energy from pistachios ; 30 % total fat ; 8 % SFAs , 12 % MUFAs , and 6 % PUFAs ) , and 2 servings/d of a pistachio diet ( 2 PD ; 20 % of energy from pistachios ; 34 % total fat ; 8 % SFAs , 15 % MUFAs , and 8 % PUFAs ) . RESULTS The 2 PD decreased ( P total cholesterol ( -8 % ) , LDL cholesterol ( -11.6 % ) , non-HDL cholesterol ( -11 % ) , apo B ( -4 % ) , apo B/apo A-I ( -4 % ) , and plasma SCD activity ( -1 % ) . The 1 PD and 2 PD , respectively , elicited a dose-dependent lowering ( P total cholesterol/HDL cholesterol ( -1 % and -8 % ) , LDL cholesterol/HDL cholesterol ( -3 % and -11 % ) , and non-HDL cholesterol/HDL cholesterol ( -2 % and -10 % ) . CONCLUSIONS Inclusion of pistachios in a healthy diet beneficially affects CVD risk factors in a dose-dependent manner , which may reflect effects on SCD", "Lifestyle modification is the cornerstone of population -based strategies for prevention of coronary heart disease and is the first line of therapy in patients with hypercholesterolemia . Diets low in saturated fatty acids and cholesterol have long been recommended to decrease low-density lipoprotein ( LDL ) cholesterol levels and reduce cardiovascular risk ( 1 ) . Ample evidence suggests that polyunsaturated fatty acids and monounsaturated fatty acids have a similar cholesterol-lowering effect when substituted for saturated fatty acids ( 2 - 4 ) . However , most studies of fatty acids and blood lipids have been done with fats and oils , rarely with whole fatty foods . Because people usually buy and consume whole food products , it is desirable to know the effects of specific foods on risk factors for coronary heart disease . Recent reports suggest that the regular consumption of nuts might reduce cardiovascular risk ( 5 ) . Walnuts are particularly rich in polyunsaturated fatty acids ( 6 ) , and epidemiologic evidence suggests that frequent walnut consumption protects against coronary heart disease ( 7 ) . In a controlled feeding trial by Sabat and colleagues ( 8) , a diet in which walnuts represented 55 % of the energy from fat reduced blood cholesterol levels in normal young men when compared with a st and ard low-fat diet . However , the results can not easily be extrapolated to the population at risk for coronary heart disease because women , older age groups , and hypercholesterolemic persons were not studied ( 8) . In addition , because meals were served at a metabolic kitchen , the study did not address the question of whether free-living persons would incorporate substantial quantities of walnuts into their diets . Because oxidized LDL plays a key role in atherogenesis ( 9 ) and oxidative damage involves peroxidation of polyunsaturated fatty acids in LDL lipids ( 10 ) , there is concern that walnut intake may promote LDL oxidation . Therefore , we design ed a dietary intervention study in free-living adult men and women with polygenic hypercholesterolemia to compare the effects of a walnut-rich diet with those of a cholesterol-lowering Mediterranean diet on serum lipid levels , lipoprotein levels , and LDL resistance to oxidation . Methods Patients Adult men and women with polygenic hypercholesterolemia attending the Lipid Clinic of the Hospital Clnic of Barcelona were eligible if they had serum LDL cholesterol concentrations greater than 3.36 mmol/L ( 130 mg/dL ) and triglyceride concentrations less than 2.82 mmol/L ( 250 mg/dL ) ; no evidence of alcohol , tobacco , or drug abuse ; absence of diabetes mellitus and liver , kidney , thyroid , or other endocrine diseases , as assessed by medical history , a complete physical examination , and laboratory tests ; no intake in the previous 8 weeks of medications known to affect lipid metabolism , including hypolipidemic agents and estrogen compounds in women ; infrequent consumption of nuts and no known history of allergy to them ; and no use of multivitamin or vitamin E supplements . Because the target population had common ( polygenic ) hypercholesterolemia , we excluded persons whose elevated blood cholesterol levels had a strong genetic basis ( such as heterozygous familial hypercholesterolemia or familial combined hyperlipidemia ) , as established by st and ard criteria . On admission to the Lipid Clinic , all patients were advised to follow a Mediterranean-type hypolipidemic diet ( 11 ) . For a crossover design , statistical power calculations indicated that to detect mean differences of 0.39 mmol/L ( 15 mg/dL ) , 34 patients would need to complete the two treatment periods ( statistic , 0.05 ; power>0.8 ) . From a computerized register of clinical records , 75 hypercholesterolemic patients ( 35 women and 40 men ) who initially met the eligibility criteria were selected for screening and were asked to participate in the study . They were offered free walnuts but no monetary compensation . Study Design A crossover design was used . Patients were r and omly assigned to the two diet sequences by using a computer-generated r and om-number table , with stratification by sex . Because patients followed each diet for 6 weeks and lipoprotein changes due to dietary intervention stabilize in less than 4 weeks ( 12 ) , we did not incorporate a washout period between diets . In their crossover feeding study with walnuts , Sabat and colleagues ( 8) did not observe a carryover effect . In the week before the trial began , patients received expert dietary counseling individually and in a group class . Twice during the pretrial week and on weeks 5 and 6 of each one of the two dietary periods , patients came to the clinic for a medical visit , an interview with the dietitian , anthropometric measurements , and blood extraction . The main outcomes of the study were changes in serum levels of total and LDL cholesterol from the control diet period to the walnut diet period . Secondary outcomes were changes in other lipid variables and oxidizability of LDL particles . The study protocol was approved by the institutional review board of the Hospital Clnic of Barcelona , and all patients gave informed consent . Diets The experimental diets were individually prescribed and were based on estimated energy requirements . Because participants ate on their own , detailed dietary information was provided to them and , if appropriate , to their partners . Diets were calculated in increments of 200 kcal to cover the range from 1600 to 2200 kcal . The control diet was Mediterranean and was composed of natural foodstuffs . Red meat and eggs were limited , vegetable products and fish were emphasized , olive oil was indicated for culinary use , and no nuts were allowed . The walnut diet was similar to the control diet , but walnuts partially replaced olive oil and other fatty foods . Prepackaged daily allowances of raw , shelled walnuts were provided daily in amounts varying from 41 g to 56 g ( the equivalent of 8 to 11 walnuts ) , according to the participants ' total energy intake . Walnuts were consumed as snacks or with meals in desserts or salads . In the walnut diet , walnuts contributed approximately 18 % of the total energy and 35 % of the total fat . To improve compliance , each family unit was given 1000-g packs of walnuts at the beginning of the walnut diet period . Adherence to the study diets was carefully monitored . Unannounced 24-hour diet recalls were performed weekly by telephone during the two dietary periods , for a total of 12 recalls per patient . This method allows reliable estimations of food intake ( 13 ) . The nutrient composition of the diets was calculated with Food Processor Plus software , version 5.0 ( ESHA Research , Salem , Oregon ) , which was adapted to nutrient data bases of specific Mediterranean foods when appropriate . We defined noncompliance as at least 20 % deviation from dietary instructions regarding walnut or nutrient intake . Compliance during the walnut diet was also assessed at each clinic visit by a count of the empty walnut packages . The fatty acid content of LDL lipids was analyzed as a biological measure of adherence to the prescribed diets . Laboratory Measurements Blood sample s were obtained after an overnight fast , and serum and EDTA plasma were collected and processed immediately . Serum lipid and apolipoprotein levels were determined as described elsewhere ( 11 ) . In brief , serum cholesterol and triglyceride levels were measured by using enzymatic reagents ( Trinder , Bayer Diagnostics , Tarrytown , New York ) adapted to a Cobas Mira automated analyzer ( Hoffmann-LaRoche , Basel , Switzerl and ) . High-density lipoprotein ( HDL ) cholesterol was quantified after precipitation with phosphotungstic acid and magnesium chloride . Levels of apolipoprotein A-I and apolipoprotein B were determined by an immunoturbidimetric method ( Unimate 3 , Roche Diagnostic Systems , Basel , Switzerl and ) . Measurements of the cholesterol content of very-low-density lipoprotein particles and LDL particles were based on preparative ultracentrifugation ( 11 ) . Lipoprotein(a ) levels were measured by using an immunoturbidimetric method ( Lipoprotein[a ] SPQ II Test Kit , DiaSorin , Stillwater , Minnesota ) . To obtain the LDL fraction for fatty acid and oxidizability studies , lipoproteins were fractionated by sequential centrifugation adjusting with NaBr to separate very-low-density lipoprotein particles ( d=1.006 g/mL ) and to obtain LDL particles ( d=1.063 g/mL ) , as described elsewhere ( 14 ) . Low-density lipoprotein fatty acids were measured by capillary gas chromatography in the cholesteryl ester , phospholipid , and triglyceride lipid fractions ( 14 ) . Low-density lipoprotein susceptibility to oxidation was determined by measuring the -tocopherol content of LDL particles and conjugated diene kinetics after incubation of 50 g of LDL protein with 5 mol of copper sulfate at 37 C ( 15 , 16 ) . Statistical Analysis The two measurements obtained at baseline and at the end of each dietary period were averaged . Means and SDs are presented for each measurement . With methods described by Fleiss ( 17 ) , two-tailed t-tests were used to compare changes in outcome variables in response to dietary treatment and diet period and carryover effects for the two-period crossover design . Differences between the walnut and control diets were also tested by analysis of covariance using general linear models ; baseline values or sex were used as covariates . Analyses were performed by using SAS software ( SAS , Inc. , Cary , North Carolina ) ( 18 ) . Role of the Funding Sources The California Walnut Commission provided funding and walnuts . Research grants were also obtained from national and local nonprofit agencies . The funding sources were not involved in the design of the study and had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . None of the authors has any financial interest in the nut food industry . Results Patient Characteristics Of the 75 eligible patients , 20 left the study before r and omization for", "Background —Epidemiological studies suggest that nut intake decreases coronary artery disease ( CAD ) risk . Nuts have a cholesterol-lowering effect that partly explains this benefit . Endothelial dysfunction is associated with CAD and its risk factors and is reversed by antioxidants and marine n-3 fatty acids . Walnuts are a rich source of both antioxidants and & agr;-linolenic acid , a plant n-3 fatty acid . Methods and Results —To test the hypothesis that walnut intake will reverse endothelial dysfunction , we r and omized in a crossover design 21 hypercholesterolemic men and women to a cholesterol-lowering Mediterranean diet and a diet of similar energy and fat content in which walnuts replaced ≈32 % of the energy from monounsaturated fat . Participants followed each diet for 4 weeks . After each intervention , we obtained fasting blood and performed ultrasound measurements of brachial artery vasomotor function . Eighteen subjects completing the protocol had suitable ultrasound studies . Compared with the Mediterranean diet , the walnut diet improved endothelium-dependent vasodilation and reduced levels of vascular cell adhesion molecule-1 ( P both ) . Endothelium-independent vasodilation and levels of intercellular adhesion molecule-1 , C-reactive protein , homocysteine , and oxidation biomarkers were similar after each diet . The walnut diet significantly reduced total cholesterol ( −4.4±7.4 % ) and LDL cholesterol ( −6.4±10.0 % ) ( P 0.05 for both ) . Cholesterol reductions correlated with increases of both dietary & agr;-linolenic acid and LDL & ggr;-tocopherol content , and changes of endothelium-dependent vasodilation correlated with those of cholesterol-to-HDL ratios ( P improves endothelium-dependent vasodilation in hypercholesterolemic subjects . This finding might explain the cardioprotective effect of nut intake beyond cholesterol lowering", "Background Tocopherols may protect against prostate cancer and cardiovascular disease ( CVD ) . Methods We assessed the effect of walnuts , which are rich in tocopherols , on markers of prostate and vascular health in men at risk for prostate cancer . We conducted an 8-week walnut supplement study to examine effects of walnuts on serum tocopherols and prostate specific antigen ( PSA ) . Subjects ( n = 21 ) consumed ( in r and om order ) their usual diet + /- a walnut supplement ( 75 g/d ) that was isocalorically incorporated in their habitual diets . Prior to the supplement study , 5 fasted subjects participated in an acute timecourse experiment and had blood taken at baseline and 1 , 2 , 4 , and 8 h after consuming walnuts ( 75 g ) . Results During the timecourse experiment , triglycerides peaked at 4 h , and gamma-tocopherol ( γ-T ) increased from 4 to 8 h. Triglyceride – normalized γ-T was two-fold higher ( P = 0.01 ) after 8 versus 4 h. In the supplement study , change from baseline was + 0.83 ± 0.52 μmol/L for γ-T , -2.65 ± 1.30 μmol/L for alpha-tocopherol ( α-T ) and -3.49 ± 1.99 for the tocopherol ratio ( α-T : γ-T ) . A linear mixed model showed that , although PSA did not change , the ratio of free PSA : total PSA increased and approached significance ( P = 0.07 ) . The α-T : γ-T ratio decreased significantly ( P = 0.01 ) , partly reflecting an increase in serum γ-T , which approached significance ( P = 0.08 ) . Conclusion The significant decrease in the α-T : γ-T ratio with an increase in serum γ-T and a trend towards an increase in the ratio of free PSA : total PSA following the 8-week supplement study suggest that walnuts may improve biomarkers of prostate and vascular status", "Frequent consumption of nuts lowers the risk of CHD . While lowering blood lipids is one of the mechanisms for cardioprotection , the present study sought to determine whether monounsaturated fat-rich almonds also influence other CHD risk factors such as inflammation and haemostasis . This was a r and omised , controlled , crossover feeding study with twenty-five healthy adults ( eleven men ; fourteen women ) , age 22 - 53 years . Following a 2 week run-in phase ( 34 % energy from fat ) , subjects were assigned in r and om order to three diets for 4 weeks each : a heart-healthy control diet with no nuts ( , respectively ) . Serum E-selectin was significantly lower on the high-almond diet compared with the control diet . E-selectin decreased as the percentage of energy from almonds increased ( P C-reactive protein ( CRP ) was lower in both the almond diets compared with the control diet . A clear dose response was not observed for either E-selectin or CRP . There was no effect of diet on IL-6 or fibrinogen . Tissue plasminogen activator antigen was significantly lower on the control and high-almond diets compared with the low-almond diet , although the values were within normal range . In conclusion , consumption of almonds influenced a few but not all of the markers of inflammation and haemostasis . A clear dose response was not observed for any of the markers studied", "Background Compared with other common plant foods , walnuts ( Juglans regia ) are consistently ranked among the highest in antioxidant capacity . In vitro , walnut polyphenols inhibit plasma and LDL oxidation , while in animal models they lower biomarkers of oxidative stress and raise antioxidant capacity . A limited number of human feeding trials indicate that walnuts improve some measures of antioxidant status , but not others . Methods A 19 wk , r and omized crossover trial was conducted in 21 generally healthy men and postmenopausal women ≥50 y to study the dose-response effects of walnut intake on biomarkers of antioxidant activity , oxidative stress , and nutrient status . Subjects were r and omized to receive either 21 or 42 g raw walnuts/d during each 6 wk intervention phase with a 6 wk washout between phases . Subjects were instructed to consume their usual diet , but refrain from eating any other tree nuts , seeds , peanuts , or ellagitannin-rich foods during the entire study , and other polyphenol-rich foods for 2 d prior to each study visit . Results Compared to baseline levels , red blood cell ( RBC ) linoleic acid and plasma pyridoxal phosphate ( PLP ) were significantly higher after 6 wk with 42 g/d walnuts ( P , changes in plasma total thiols , and other antioxidant biomarkers , were not significant with either walnut dose . However , when compared to fasting levels , plasma total thiols were elevated within 1 h of walnut consumption with both doses during the baseline and end visits for each intervention phase ( P increase in RBC linoleic and linolenic acids associated with walnut consumption , this substrate for lipid peroxidation only minimally affected malondialdehyde ( MDA ) and antioxidant capacity . The proportional changes in MDA and Oxygen Radical Absorbance Capacity ( ORAC ) were consistent with a dose-response effect , although no significant within- or between-group differences were observed for these measures . Conclusions Walnut consumption did not significantly change the plasma antioxidant capacity of healthy , well-nourished older adults in this pilot study . However , improvements in linoleic acid and pyridoxal phosphate were observed with chronic consumption , while total plasma thiols were enhanced acutely . Future studies investigating the antioxidant effects of walnuts in humans are warranted , but should include either a larger sample size or a controlled feeding intervention . Trial Registration Clinical Trials.gov :", "Background : Increased consumption of nuts has been advocated because of their health benefits , but the role of nuts in the treatment of obesity is unclear given their high energy density . Objective : This study was design ed to evaluate the effects of a hypocaloric , almond-enriched diet ( AED ) compared with a hypocaloric nut-free diet ( NFD ) on body weight and cardiovascular disease risk factors in the context of an 18-mo behavioral weight-management program . Design : Overweight and obese individuals [ n = 123 ; age = 46.8 y , BMI ( in kg/m2 ) = 34.0 ] were r and omly assigned to consume an AED or NFD and instructed in traditional behavioral methods of weight control . Anthropometric and metabolic measurements were made at baseline , 6 mo , and 18 mo . Results : Those in the AED group lost slightly but significantly less weight than did those in the NFD group at 6 mo ( −5.5 compared with −7.4 kg ; P = 0.04 ) , but there were no differences at 18 mo . No significant differences in body composition were found between the groups at 6 or 18 mo . The AED , compared with the NFD , was associated with greater reductions in total cholesterol ( P = 0.03 ) , total : HDL cholesterol ( P = 0.02 ) , and triglycerides ( P = 0.048 ) at 6 mo , and no differences were observed between the groups at 18 mo . Conclusions : The AED and NFD groups experienced clinical ly significant and comparable weight loss at 18 mo . Despite smaller weight loss in the AED group at 6 mo , the AED group experienced greater improvements in lipid profiles . This trial was registered at clinical trials.gov as NCT00194428", "Background Cocoa , mixed with other food ingredients , intake can have beneficial effects on cardiovascular disease ( CVD ) biomarkers . We compared the effects of 4 cocoa cream products on some of these biomarkers . Methods and Findings In this multi-centered , r and omized , controlled , double-blind , parallel trial , volunteers ( n = 113 ; age range : 43–65 years ) who were pre-hypertensive , stage-1 hypertensive and hypercholesterolemic received one of 4 cocoa cream products ( 13 g/unit ; 1 g cocoa/unit , 6 units/d ; 465 Kcal/d ) added to a low saturated fat diet for 4 weeks . The groups were : A ) ( n = 28 ) , cocoa cream considered as control ; B ) ( n = 28 ) , cocoa+hazelnut cream ( 30 g/d hazelnuts ) ; C ) ( n = 30 ) , cocoa+hazelnuts+phytosterols ( 2 g/d ) ; and D ) ( n = 27 ) , cocoa+hazelnuts+phytosterols+soluble fiber ( 20 g/d ) the patented “ LMN product ” . Primary outcome measures were BP , LDL-c , apolipoprotein B-100 ( Apo B ) , ApoB/ApoA ratio , oxidized LDL ( oxLDL ) and high-sensitive C-reactive protein ( hsCRP ) determined at baseline and post-cocoa cream product intake . Statistical analysis used was ANCOVA or mixed models ( in case of repeated measurements ) , with baseline observation included as a covariate . After 4 weeks , compared to product A , product C reduced LDL-c by 11.2 % , Apo B by 8.1 % and ApoB/ApoA ratio by 7.8 % ( P = 0.01 ) . LMN decreased LDL-c by 9.2 % , Apo B-100 by 8.5 % , ApoB/ApoA ratio by 10.5 % , hsCRP by 33.4 % and oxLDL by 5.9 % ( P = 0.01 ) . Surprisingly , even “ control ” product A reduced systolic BP ( −7.89 mmHg ; 95%CI : −11.45 to −4.3 ) and diastolic BP ( −5.54 mmHg ; 95%CI : −7.79 to −3.29 ) . The BP reductions were similar with the other 3 products . Limitations of the study are that the trial period was relatively short and that a better “ BP control ” product would have been preferable . Conclusion The creams ( particularly the LMN ) have anti-inflammatory and antioxidant effects in addition to lowering LDL-c , Apo B and ApoB/ApoA ratio . Thus , the soluble fiber effects amplified with sterols ( as contained in the cocoa creams ) provide new dietary therapeutic perspectives . Trial Registration Clinical trials.gov", "Objective : Clinical and epidemiological studies have reported the beneficial effects of tree nuts and peanuts on serum lipid levels . We studied the effects of consuming 15 % of the daily caloric intake in the form of pistachio nuts on the lipid profiles of free-living human subjects with primary , moderate hypercholesterolemia ( serum cholesterol greater than 210 mg/dL ) . Methods : Design : R and omized crossover trial . Setting : Outpatient dietary counseling and blood analysis . Subjects : 15 subjects with moderate hypercholesterolemia . Intervention : Fours weeks of dietary modification with 15 % caloric intake from pistachio nuts . Measures of Outcome : Endpoints were serum lipid levels of total cholesterol , HDL-C , LDL-C , VLDL-C , triglycerides and apolipoproteins A-1 and B-100 . BMI , blood pressure , and nutrient intake ( total energy , fat , protein , and fiber ) were also measured at baseline , during , and after dietary intervention . Results : No statistically significant differences were observed for total energy or percent of energy from protein , carbohydrate or fat . On the pistachio nut diet , a statistically significant decrease was seen for percent energy from saturated fat ( mean difference , −2.7 % ; 95 % CI , −5.4 % to −0.08 % ; p = 0.04 ) . On the pistachio nut diet , statistically significant increases were seen for percent energy from polyunsaturated fat ( mean difference , 6.5 % ; 95 % CI , 4.2 % to 8.9 % ; p and fiber intake ( mean difference , 15 g ; 95 % CI , 8.4 g to 22 g ; p = 0.0003 ) . On the pistachio diet , statistically significant reductions were seen in TC/HDL-C ( mean difference , −0.38 ; 95 % CI , −0.57 to −0.19 ; p = 0.001 ) , LDL-C/HDL-C ( mean difference , −0.40 ; 95 % CI , −0.66 to −0.15 ; p = 0.004 ) , B-100/A-1 ( mean difference , −0.11 ; 95 % CI , −0.19 to −0.03 ; p = 0.009 ) and a statistically significant increase was seen in HDL-C ( mean difference , 2.3 ; 95 % CI , 0.48 to 4.0 ; p = 0.02 ) . No statistically significant differences were seen for total cholesterol , triglycerides , LDL-C , VLDL-C , apolipoprotein A-1 or apolipoprotein B-100 . No changes were observed in BMI or blood pressure . Conclusion : A diet consisting of 15 % of calories as pistachio nuts ( about 2–3 ounces per day ) over a four week period can favorably improve some lipid profiles in subjects with moderate hypercholesterolemia and may reduce risk of coronary disease", "Background / Objectives : A large intake of walnuts may improve lipid profile and endothelial function . The effect of moderate walnut consumption is not known . We investigated whether a moderate intake of walnuts would affect lipid profile , arterial stiffness and platelet activation in healthy volunteers . Subjects/ Methods : A total of 30 healthy males were recruited into a single-blind r and omized controlled crossover trial of 4 weeks of dietary walnut supplementation ( 15 g/day ) and 4 weeks of control ( no walnuts ) . Arterial stiffness was assessed using pulse waveform analysis to determine the augmentation index and augmented pressure . Platelet activation was determined using flow cytometry to measure circulating platelet – monocyte aggregates . Results : There were no differences in lipid profile after 4 weeks of walnut supplementation compared with control . Dietary intake of α-linolenic acid was increased during the walnut diet ( 2.1±0.4 g/day versus 0.7±0.4 g/day , P differences in augmentation index or augmented pressure during walnut supplementation . Walnut supplementation did not affect platelet – monocyte aggregation . Conclusions : Dietary intervention with a moderate intake of walnuts does not affect lipid profile , arterial stiffness or platelet activation in man . Our results suggest that the potentially beneficial cardiac effects of walnuts may not be apparent at lower and more practical levels of consumption", "OBJECTIVE Recent studies have suggested that nuts have favorable effects beyond lipid lowering . We aim ed to investigate effect of the Antep pistachio ( Pistacia vera L. ) on blood glucose , lipid parameters , endothelial function , inflammation , and oxidation in healthy young men living in a controlled environment . METHODS A Mediterranean diet was administered to normolipidemic 32 healthy young men ( mean age 22 y , range 21 - 24 ) for 4 wk . After 4 wk , participants continued to receive the Mediterranean diet but pistachio was added for 4 wk by replacing the monounsaturated fat content constituting approximately 20 % of daily caloric intake . Fasting blood sample s and brachial endothelial function measurements were performed at baseline and after each diet . RESULTS Compared with the Mediterranean diet , the pistachio diet decreased glucose ( P low-density lipoprotein ( P total cholesterol ( P triacylglycerol ( P=0.008 , -13.8+/-33.8 % ) significantly and high-density lipoprotein ( P=0.069 , -3.1+/-11.7 % ) non-significantly . Total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios decreased significantly ( P pistachio diet significantly improved endothelium-dependent vasodilation ( P=0.002 , 30 % relative increase ) , decreased serum interleukin-6 , total oxidant status , lipid hydroperoxide , and malondialdehyde and increased superoxide dismutase ( P C-reactive protein and tumor necrosis factor-alpha levels . CONCLUSION In this trial , we demonstrated that a pistachio diet improved blood glucose level , endothelial function , and some indices of inflammation and oxidative status in healthy young men . These findings are in accordance with the idea that nuts , in particular pistachio nuts , have favorable effects beyond lipid lowering that deserve to be evaluated with prospect i ve follow-up studies", "OBJECTIVE To compare serum lipid profiles and dietary intakes of people with normal lipid levels who consumed pecans and those who did not consume nuts . DESIGN Eight-week , r and omized , controlled study of pecan treatment group vs control group . SUBJECT Nineteen people with normal lipid levels completed the study ; 10 had been r and omly assigned to the pecan treatment group ( 7 women , 3 men , mean age = 45 + /- 10 years ) and 9 to the control group ( 8 women , 1 man , mean age = 37 + /- 12 years ) . INTERVENTION The pecan treatment group consumed 68 g pecans per day for 8 weeks plus self-selected diets . The pecans contributed 459 kcal and 44 g fat daily . The control group avoided nuts and consumed self-selected diets . MAIN OUTCOME MEASURES Total serum cholesterol , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , and total triglyceride levels were measured at the time of entrance to the study ( baseline ) , week 4 , and week 8 . Computer analyses were done on five 3-day food records . STATISTICAL ANALYSIS Comparisons were made using analysis of variance or paired t test . RESULTS LDL-C was lowered in the pecan treatment group from 2.61 + /- 0.49 mmol/L at baseline to 2.35 + /- 0.49 at week 4 ( P total cholesterol and HDL-C in the pecan treatment group were significantly lower ( P Dietary fat , monounsaturated fat , polyunsaturated fat , insoluble fiber , magnesium , and energy were significantly higher in the pecan treatment group than in the control group . Body mass indexes and body weights were unchanged in both groups . APPLICATIONS Pecans can be included in a healthful diet when energy intake and potential weight gain are addressed", "OBJECTIVES Oxidation and level of plasma lipids are closely implicated in the development of coronary heart disease ( CHD ) . Dietary almond supplementation may participate in beneficial effects on CHD lipid risk factor levels and their susceptibility to oxidative modification . The aim of this study was to evaluate the effects of dietary supplementation with almond on serum lipid levels and their relation to lipid oxidation parameters in men with mild hyperlipidemia . DESIGN Thirty ( 30 ) healthy volunteer men ( age 45.57 ± 7.14 years and body-mass index 24.29 ± 2.15 kg/m(2 ) ) with mild hyperlipidemia received 60 g almond daily for 4 weeks . OUTCOME MEASURES Overnight fasting blood sample s were obtained before and after supplementation . Serum levels of lipids , lipoproteins , and apolipoproteins and copper-induced serum lipid oxidation were determined . Lipid oxidation was followed by monitoring of the change of conjugated dienes in diluted serum after addition of Cu(2 + ) . A number of quantitative parameters including lag-time , maximal rate of oxidation ( V-max ) , and maximal amount of lipid peroxide products ( OD-max ) were evaluated . RESULTS After 4 weeks , almond supplementation significantly decreased low-density lipoprotein cholesterol , total cholesterol ( TC ) , and apolipoprotein B100 ( apo-B100 ) . At baseline , there was little correlation between lipid risk factors and lipid oxidation parameters , but a positive correlation was observed between TC and lag-time ( r = 0.6 , p = 0.001 ) , negative correlation between TC with V-max and OD-max ( r = -0.65 , p between apo-B100 with V-max and OD-max ( r = 0.48 , p = 0.01 and r = 0.54 , p = 0.003 ) after almond supplementation . CONCLUSIONS These results demonstrated that almond supplementation , in addition to lowering effects on serum levels of CHD lipid risk factors , may contribute to a dramatic change in the relation of lipid risk factors and susceptibility of serum lipids to oxidative modification . This may be due to the distribution of different almond phenolic antioxidants in different components of serum including nonlipoprotein molecules such as serum albumin", "Abstract : The effects of almond consumption on DNA damage and oxidative stress among cigarette smokers were studied . Thirty healthy adult male regular smokers were r and omly divided into three groups , 10 subjects per group . Group A ( control group ) did not receive any almonds . Subjects in Groups B and C received 3 oz and 6 oz ( 84 g and 168 g ) of almonds each day respectively for 4 wk . Two known biomarkers for DNA damage , urinary 8-hydroxy-2’-deoxyguanosine ( 8-OH-dG ) and single str and DNA breaks of peripheral blood lymphocytes , were measured by enzyme-linked immunosorbent assay and comet assay , respectively . In addition , plasma malondialdehyde ( MDA ) level , superoxide dismutase ( SOD ) , and glutathione peroxidase ( GSH-Px ) activities were measured as biomarkers for oxidative stress . The results showed lower levels of urinary 8-OH-dG and single str and DNA breaks in the two almond-treated groups as compared with the control group . Furthermore , MDA levels in the almond-treated groups were lower than the controls . However , no significant effects of almonds on SOD and GSH-Px activities were found . In conclusion , results from this pilot study indicate that almond consumption has preventive effects on oxidative stress and DNA damage caused by smoking . A larger , r and omized , placebo-controlled clinical trial on almonds will be initiated in the near future", "BACKGROUND Increased consumption of n-3 ( omega-3 ) fatty acids decreases the incidence of coronary heart disease ( CHD ) . OBJECTIVE The objective was to determine whether walnuts ( plant n-3 fatty acid ) and fatty fish ( marine n-3 fatty acid ) have similar effects on serum lipid markers at intakes recommended for primary prevention of CHD . DESIGN In a r and omized crossover feeding trial , 25 normal to mildly hyperlipidemic adults consumed 3 isoenergetic diets ( approximately 30 % total fat and a control diet ( no nuts or fish ) , a walnut diet ( 42.5 g walnuts/10.1 mJ ) , or a fish diet ( 113 g salmon , twice/wk ) . Fasting blood was drawn at baseline and at the end of each diet period and analyzed for serum lipids . RESULTS Serum total cholesterol and LDL cholesterol concentrations in adults who followed the walnut diet ( 4.87 + /- 0.18 and 2.77 + /- 0.15 mmol/L , respectively ) were lower than in those who followed the control diet ( 5.14 + /- 0.18 and 3.06 + /- 0.15 mmol/L , respectively ) and those who followed the fish diet ( 5.33 + /- 0.18 and 3.2 + /- 0.15 mmol/L , respectively ; P fish diet result ed in decreased serum triglyceride and increased HDL-cholesterol concentrations ( 1.0 + /- 0.11 and 1.23 + /- 0.05 mmol/L , respectively ) compared with the control diet ( 1.12 + /- 0.11 and 1.19 + /- 0.05 mmol/L , respectively ) and the walnut diet ( 1.11 + /- 0.11 mmol/L , P ratios of total cholesterol : HDL cholesterol , LDL cholesterol : HDL cholesterol , and apolipoprotein B : apolipoprotein A-I were lower ( P fish diets . CONCLUSION Including walnuts and fatty fish in a healthy diet lowered serum cholesterol and triglyceride concentrations , respectively , which affects CHD risk favorably", "Objective : To determine the serum cholesterol , apolipoproteins and LDL oxidizability in young Japanese women and men during walnut consumption and to evaluate its active principle . Design : Experimental study with a r and omized design .Subjects : Twenty healthy women and 20 healthy men . Interventions : Subjects were r and omly assigned to consume each of two mixed natural diets for 4 weeks in a cross-over design . Reference and walnut diets were design ed and the walnut diet had 12.5 % of the energy derived from walnuts ( 44–58 g/day ) . Results : The total cholesterol and serum apolipoprotein B concentrations , and the ratio of LDL cholesterol to HDL cholesterol was significantly lowered in women and men when fed on the walnut diet , than when on the reference diet ( P≤0.05 ) . The LDL cholesterol concentration was significantly lowered in women on the walnut diet ( 0.22 mmol/l , P=0.0008 ) , whereas this decrease was not significant in men ( 0.18 mmol/l , P=0.078 ) . The most prominent change in the fatty acid composition of the cholesteryl esters from serum after the walnut diet was an elevation of α-linolenic acid in women ( 76 % , P change in LDL cholesterol in women ( r=0.496 , P=0.019 ) and men ( r=0.326 , P=0.138 ) . The LDL oxidizability in women was not influenced by the diets ( P=0.19 ) . Conclusions : α-Linolenic acid in the walnut diet appears to be responsible for the lowering of LDL cholesterol in women . Sponsorship : Kyushu University ( Fukuoka , Japan ) and the California Walnut Commission ( California , USA )", "Almond consumption is associated with ameliorations in obesity , hyperlipidemia , hypertension , and hyperglycemia . The hypothesis of this 12-week r and omized crossover clinical trial was that almond consumption would improve glycemic control and decrease the risk for cardiovascular disease in 20 Chinese patients with type 2 diabetes mellitus ( T2DM ) ( 9 male , 11 female ; 58 years old ; body mass index , 26 kg/m² ) with mild hyperlipidemia . After a 2-week run-in period , patients were assigned to either a control National Cholesterol Education Program step II diet ( control diet ) or an almond diet for 4 weeks , with a 2-week washout period between alternative diets . Almonds were added to the control diet to replace 20 % of total daily calorie intake . Addition of approximately 60 g almonds per day increased dietary intakes of fiber , magnesium , polyunsaturated fatty acid , monounsaturated fatty acid , and vitamin E. Body fat determined with bioelectrical impedance analysis was significantly lower in patients consuming almonds ( almonds vs control : 29.6 % vs 30.4 % ) . The almond diet enhanced plasma α-tocopherol level by a median 26.8 % ( 95 % confidence intervals , 15.1 - 36.6 ) compared with control diet . Furthermore , almond intake decreased total cholesterol , low-density lipoprotein cholesterol , and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol by 6.0 % ( 1.6 - 9.4 ) , 11.6 % ( 2.8 - 19.1 ) , and 9.7 % ( 0.3 - 20.9 ) , respectively . Plasma apolipoprotein ( apo ) B levels , apo B/apo A-1 ratio , and nonesterified fatty acid also decreased significantly by 15.6 % ( 5.1 - 25.4 ) , 17.4 % ( 2.8 - 19.9 ) , and 5.5 % ( 3.0 - 14.4 ) , respectively . Compared with subjects in the control diet , those in the almond diet had 4.1 % ( 0.9 - 12.5 ) , 0.8 % ( 0.4 - 6.3 ) , and 9.2 % ( 4.4 - 13.2 ) lower levels of fasting insulin , fasting glucose , and homeostasis model assessment of insulin resistance index , respectively . Our results suggested that incorporation of almonds into a healthy diet has beneficial effects on adiposity , glycemic control , and the lipid profile , thereby potentially decreasing the risk for cardiovascular disease in patients with type 2 diabetes mellitus", "Objective : To compare two low fat diets one rich in walnuts on parameters of lipid metabolism in a group of hyperlipidaemic subjects . Design : A r and omised cross over study . Setting : Department of Human Nutrition , University of Otago , Dunedin , New Zeal and Subjects : Twenty one men with mean ( s.d ) levels of total and LDL cholesterol of 6.58 ( 0.60 ) and 4.63 ( 0.58 ) respectively . Interventions : For two periods of four weeks subjects were asked to consume two low fat diets ( fat 30 % total energy ) , one containing , on average , 78 g/d walnuts . Walnuts obtained through Lincoln University and the Walnut Growers Group ( South Canterbury ) . Results : Participants reported a higher total fat intake on the walnut diet ( 38 % compared with 30 % on the low fat diet P fatty acid profile of triacylglycerol , phospholipid and cholesterol ester on the walnut diet was a significant ( P acid . Triacylglycerol linolenate also increased significantly ( P Total and LDL cholesterol were lower on both experimental diets than at baseline , 0.25 mmol/l and 0.36 mmol/l respectively on the walnut diet and 0.13 mmol/l and 0.20 mmol/l respectively on the low fat diet . High density lipoprotein cholesterol was higher on both the walnut and low fat diets when compared to baseline ( 0.15 mmol/l and 0.12 mmol/l , respectively ) . When comparing the walnut and low fat diets only apo B was significantly lower ( P apolipoprotein B suggests a reduction in lipoprotein mediated risk , the relatively low myristic acid content of both diets perhaps explaining the absence of more extensive differences in lipoprotein levels on the two diets . Sponsorship : Nutrition Department University of Otago , New Zeal and", "OBJECTIVE The aim of this study was to examine the effect of a moderate-fat diet inclusive of walnuts on blood lipid profiles in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS This was a parallel r and omized controlled trial comparing three dietary advice groups each with 30 % energy as fat : low fat , modified low fat , and modified low fat inclusive of 30 g of walnuts per day . Fifty-eight men and women , mean age 59.3 + /- 8.1 years , started the trial . Dietary advice was given at baseline with monthly follow-up and fortnightly phone calls for support . Body weight , percent body fat , blood lipids , HbA1c , total antioxidant capacity , and erythrocyte fatty acid levels were measured at 0 , 3 , and 6 months . Data were assessed by repeated- measures ANOVA with an intention-to-treat model . RESULTS The walnut group achieved a significantly greater increase in HDL cholesterol-to-total cholesterol ratio ( P=0.049 ) and HDL ( P=0.046 ) than the two other treatment groups . A 10 % reduction in LDL cholesterol was also achieved in the walnut group , reflecting a significant effect by group ( P=0.032 ) and time ( P=0.036 ) . There were no significant differences between groups for changes in body weight , percent body fat , total antioxidant capacity , or HbA1c levels . The higher dietary polyunsaturated fat-to-saturated fat ratio and intakes of omega-3 fatty acids in the walnut group were confirmed by erythrocyte biomarkers of dietary intake . CONCLUSIONS Structured \" whole of diet \" advice that included 30 g of walnuts/day delivering substantial amounts of polyunsaturated fatty acid improved the lipid profile of patients with type 2 diabetes", "1 . Recent studies have identified potential beneficial effects of eating nuts , most of which have substantial amounts of monounsaturated fatty acids ( MUFA ) . Macadamia nuts consist of 75 % fat by weight , 80 % of which is MUFA ( palmitoleic acid )", "We investigated the effects of Antep pistachio on International Index of Erectile Function ( IIEF ) scores , penile color Doppler ultrasound ( PCDU ) parameters and serum lipid levels in patients with ED . A total of 17 married male patients with ED for at least 12 months were included in this prospect i ve study . Patients were put on a 100 g pistachio nuts diet for 3 weeks . IIEF and PCDU were evaluated before and after the pistachio diet . In addition , plasma total cholesterol ( TC ) , low-density lipoprotein ( LDL ) , high-density lipoprotein ( HDL ) and triglyceride were measured before and after dietary modifications from all subjects . Mean IIEF-15 score was 36±7.5 before the diet and 54.2±4.9 after the diet ( P=0.001 ) . Similarly , an increase in all five domains of IIEF was observed after the diet ( P ) . Mean peak systolic velocity values before and after the pistachio diet were 35.5±15.2 and 43.3±12.4 cm s–1 , respectively ( P=0.018 ) . After the pistachio diet , TC and LDL levels decreased significantly , whereas HDL level increased ( P=0.008 , 0.007 and 0.001 , respectively ) . We demonstrated that a pistachio diet improved IIEF scores and PCDU parameters without any associated side effects in patients with ED . Furthermore , the lipid parameters showed statistically significant improvements after this diet", "The objective of this study was to assess the dose-response effect of almond intake on plasma and red blood cell tocopherol concentrations in healthy adults enrolled in a r and omized , crossover feeding trial . Participants were 16 healthy men and women , aged 41+/-13 years . After a 2-week run-in period , participants were fed three diets for 4 weeks each : a control diet , a low-almond diet , and a high-almond diet , in which almonds contributed 0 % , 10 % , and 20 % of total energy , respectively . Changes in blood tocopherol levels were assayed by high pressure liquid chromatography . Incorporating almonds into the diet helped meet the revised Recommended Dietary Allowance of 15 mg/day alpha-tocopherol and increased lipid-adjusted plasma and red blood cell alpha-tocopherol concentrations . A significant dose-response effect was observed between percent energy in the diet from almonds and plasma ratio of alpha-tocopherol to total cholesterol", "Objective : There is a widely held view that , due to high fat content , snacking on nuts will lead to weight gain , ultimately causing unhealthy changes in lipid profiles . This study is design ed to study the effects of pistachio snack consumption on body weight and lipid levels in obese participants under real-world conditions . Methods : Participants were r and omly assigned to consume 1 of 2 isocaloric weight reduction diets for 12 weeks , with each providing 500 cal per day less than resting metabolic rate . Each diet included an afternoon snack of either 53 g ( 240 cal ) of salted pistachios ( n = 31 ) or 56 g of salted pretzels ( 220 cal ; n = 28 ) . Results : Both groups lost weight during the 12-week study ( time trend , p in body mass index between the pretzel and pistachio groups ( pistachio , 30.1 ± 0.4 to 28.8 ± 0.4 vs. pretzel , 30.9 ± 0.4 to 30.3 ± 0.5 ) . At 6 and 12 weeks , triglycerides were significantly lower in the pistachio group compared with the pretzel group ( 88.04 ± 9.80 mg/dL vs. 144.56 ± 18.86 mg/dL , p = 0.01 at 6 weeks and 88.10 ± 6.78 mg/dL vs. 132.15 ± 16.76 mg/dL , p = 0.02 at 12 weeks ) , and there was a time trend difference between the 2 groups over the 12 weeks ( p in total cholesterol , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol , insulin , or glucose between the 2 groups . Conclusion : Pistachios can be consumed as a portion-controlled snack for individuals restricting calories to lose weight without concern that pistachios will cause weight gain . By comparison to refined carbohydrate snacks such as pretzels , pistachios may have beneficial effects on triglycerides as well", "Objective : To compare the lipid-altering effect of roasted salted almonds and roasted almond butter with that of raw almonds , as part of a plant-based diet . Methods : Thirty-eight free-living , hypercholesterolemic men ( n = 12 ) and women ( n = 26 ) with a mean total serum cholesterol ( TC ) of 245 + 29 mg/dL ( mean + SD ) followed a heart-healthy diet including 100 g of one of three forms of almonds : roasted salted almonds , roasted almond butter or raw almonds for four weeks . Measurements of serum TC , triglycerides ( TG ) , selected lipoproteins and blood pressure were taken at baseline and after four weeks . Results : All three forms of almonds in the context of a heart-healthy diet significantly lowered low-density lipoprotein-cholesterol ( LDL ) from baseline to the completion of the study . Both raw and roasted almonds significantly lowered TC , whereas the decrease by almond butter ( in a smaller cohort ) did not reach statistical significance . High-density lipoprotein-cholesterol ( HDL ) did not significantly change with raw or roasted almonds but slightly increased with almond butter . At the end of the study , blood pressure did not change significantly from baseline values for any of the groups . Conclusion : These results suggest that unblanched almonds — whether raw , dry roasted , or in roasted butter form — can play an effective role in cholesterol-lowering , plant-based diets", "BACKGROUND In a recent six-year follow-up study , we found that frequent consumption of nuts was associated with a reduced risk of ischemic heart disease . To explore possible explanations for this finding , we studied the effects of nut consumption on serum lipids and blood pressure . METHODS We r and omly placed 18 healthy men on two mixed natural diets , each diet to be followed for four weeks . Both diets conformed to the National Cholesterol Education Program Step 1 diet and contained identical foods and macronutrients , except that 20 percent of the calories of one diet ( the walnut diet ) were derived from walnuts ( offset by lesser amounts of fatty foods , meat , and visible fat [ oils , margarine , and butter ] ) . RESULTS With the reference diet , the mean ( + /- SD ) serum values for total , low-density lipoprotein ( LDL ) , and high-density lipoprotein ( HDL ) cholesterol were , respectively , 182 + /- 23 , 112 + /- 16 , and 47 + /- 11 mg per deciliter ( 4.71 + /- 0.59 , 2.90 + /- 0.41 , and 1.22 + /- 0.28 mmol per liter ) . With the walnut diet , the mean total cholesterol level was 22.4 mg per deciliter ( 0.58 mmol per liter ) lower than the mean level with the reference diet ( 95 percent confidence interval , 28 to 17 mg per deciliter [ 0.72 to 0.44 mmol per liter ] ) ; the LDL and HDL cholesterol levels were , respectively , 18.2 mg per deciliter ( 0.47 mmol per liter ) ( P total , LDL , and HDL cholesterol , respectively . The ratio of LDL cholesterol to HDL cholesterol was also lowered ( P . Mean blood-pressure values did not change during either dietary period . CONCLUSIONS Incorporating moderate quantities of walnuts into the recommended cholesterol-lowering diet while maintaining the intake of total dietary fat and calories decreases serum levels of total cholesterol and favorably modifies the lipoprotein profile in normal men . The long-term effects of walnut consumption and the extension of this finding to other population groups deserve further study", "Objective : The authors tested the hypothesis that in adults with prediabetes , an almond-enriched American Diabetes Association ( ADA ) diet improves measures of insulin sensitivity and other cardiovascular risk factors compared with an ADA nut-free diet . Methods : Design : R and omized parallel-group trial . Setting : Outpatient dietary counseling and blood analysis . Subjects : Sixty-five adult participants with prediabetes . Intervention : Sixteen weeks of dietary modification featuring an ADA diet containing 20 % of energy from almonds ( approximately 2 oz per day ) . Measures of Outcome : Outcomes included fasting glucose , insulin , total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , triglycerides , TC : HDL-C , and HbA1c , which were measured at weeks 0 , 8 , and 16 . Body weight , body mass index ( BMI ) , waist circumference , blood pressure , and nutrient intake were measured at weeks 0 , 4 , 8 , 12 , and 16 . Results : The almond-enriched intervention group exhibited greater reductions in insulin ( −1.78 µU/ml vs. + 1.47 µU/ml , p = 0.002 ) , homeostasis model analysis for insulin resistance ( −0.48 vs. + 0.30 , p = 0.007 ) , and homeostasis model analysis for beta-cell function ( −13.2 vs. + 22.3 , p = 0.001 ) compared with the nut-free control group . Clinical ly significant declines in LDL-C were found in the almond-enriched intervention group ( −12.4 mg/dl vs. −0.4 mg/dl ) as compared with the nut-free control group . No changes were observed in BMI ( −0.4 vs. −0.7 kg/m2 , p = 0.191 ) , systolic blood pressure ( −4.4 mm Hg vs. −3.5 mm Hg , p = 0.773 ) , or for the other measured cardiovascular risk factors . Conclusions : An ADA diet consisting of 20 % of calories as almonds over a 16-week period is effective in improving markers of insulin sensitivity and yields clinical ly significant improvements in LDL-C in adults with prediabetes", "Walnut ( Juglans regia L. ) is described as an anticancer , tonic , blood purifier , and detoxifier agent . It is said that nuts have favorable fatty acids and nutrients . This study was performed to determine the lipid-lowering properties of walnut in a population in Shiraz , Southern Iran . In a r and omized case-control study , 52 volunteers were divided into 2 groups : Group A consumed walnuts , 20 grams per day for 8 weeks and the control group ( group B ) consumed no walnuts . Triglycerides , total high-density lipoprotein ( HDL ) , and low-density lipoprotein ( LDL ) levels were checked for each subject prior to , after 4 weeks , and at 8 weeks after the beginning of the study . In group A , the mean plasma TG level dropped by 17.1 % from the baseline and HDL cholesterol also increased significantly by 9 % . It was shown that frequent consumption of nuts in the daily diet was associated with a potentially decreased risk of coronary artery disease by decreasing the level of triglyceride and increasing the level of HDL", "Background : A number of recent studies indicate that antioxidants reduce the oxidative stress associated with the development of coronary heart diseases ( CHD ) . Objective : ( i ) To investigate whether the erythrocyte catalase ( CAT ) , superoxide dismutase ( SOD ) , total glutathione , reduced glutathione ( GSH ) , oxidized glutathione ( GSSG ) , and lipid peroxidation ( LPO ) , and serum uric acid and paraoxonase-1 ( PON1 ) are modified at increased CHD-risk individuals consuming walnut-enriched meat ( WM ) , ( ii ) to evaluate whether these changes were influenced by basal serum cholesterol , body mass index or smoking habit . Design : The study was a non blinded , cross-over , placebo-controlled trial in which 22 volunteers ( 60 % overweight and 40 % obese ) with increased CHD-risk were r and omly assigned to receive WM or control meat ( CM ) during two different periods of 5 weeks . Results : A significant interaction time*treatment ( p enzymes and substrates tested except HDL-C , uric acid and LPO . The treatment significantly increased CAT activity , total glutathione and GSSG ( p total glutathione was found increasing at the end of the WM period in male but not changing in female . Total glutathione and GSH/GSSG ratio ( p Hypercholesterolemics presented higher uric acid ( p enzyme activities or substrate concentrations were different from those of normocholesterolemics . Conclusions : The WM tested appears to be a functional food as it improved the antioxidant status of increased CHD-risk volunteers . Despite its high energy content , it also appears adequate for overweight and obese people because did not exert negative effect upon body weight", "BACKGROUND AND AIM Effects of pistachio nuts consumption on plasma lipid profile and oxidative status were investigated in healthy volunteers with normal lipid levels . METHODS AND RESULTS The study was conducted in 24 healthy men and 20 healthy women . All subjects consumed their regular diets during a 1-week period . After this period , half of the subjects ( 12 men and 10 women , mean age 32.8 + /- 6.7 years ) were r and omized to a regular diet group and the other half ( 12 men and 10 women , mean age 33.4 + /- 7.2 years ) were r and omized to a pistachio group which involved substituting pistachio nuts for 20 % of their daily caloric intake for 3 weeks . Plasma total cholesterol , low-density lipoprotein ( LDL ) , high-density lipoprotein ( HDL ) , triglyceride , malondialdehyde ( MDA ) and antioxidant potential ( AOP ) were measured before and after the dietary modification from all the subjects . After 3 weeks , with the pistachio diet , the mean plasma total cholesterol , MDA levels and , total cholesterol/HDL and LDL/HDL ratios were found to be significantly decreased ( P HDL and AOP levels , and AOP/MDA ratios were significantly increased ( P Triglyceride and LDL levels also decreased but this was not statistically significant ( P > 0.05 ) . CONCLUSION These results indicated that consumption of pistachio nuts decreased oxidative stress , and improved total cholesterol and HDL levels in healthy volunteers", "BACKGROUND AND AIM Small quantities of nuts protect against subsequent cardiovascular risk . There is speculation that the cholesterol lowering effect associated with nut consumption arises primarily from the fatty acid composition of nuts but may be caused by some other component . To evaluate this possibility we compared the effect of various nuts , against a Canola oil based cereal with a comparable fatty acid profile , on lipids , lipoproteins and fatty acids to determine whether the fatty acid profile of nuts explains their cholesterol lowering effects . METHODS AND RESULTS Twenty-eight men and women with mean ( s.d . ) levels of total and low density lipoprotein cholesterol of 6.0 ( 1.1 ) mmol/L , and 4.1 ( 1.0 ) mmol/L , respectively and a mean body mass index ( BMI ) of 26.9 ( 3.2 ) kg/m2 took part in a r and omised cross over trial . For two periods of six weeks , separated by a four-week washout , participants were asked to consume a low saturated fat diet , which included either 30 g/d nuts ( nut diet ) or one serving of a cereal containing Canola oil ( cereal diet ) . There were no significant differences in the lipids , lipoproteins , plasma fatty acids or other variables between the two diets at the end of the study . Total cholesterol ( TC ) and low density lipoprotein cholesterol ( LDL-C ) were lower on both experimental diets than at baseline , 0.51 mmol/L and 0.40 mmol/L ( p . CONCLUSION A 30 g serving of nuts , or a serving of a Canola oil enriched cereal with a similar fatty acid composition reduced total and LDL cholesterol to a similar extent when consumed as part of a lipid lowering diet . Results suggest that foods with a similar fatty acid composition to nuts can produce comparable decreases in lipoprotein mediated cardiovascular risk", "CONTEXT Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified . OBJECTIVE To assess major lipids and apolipoproteins in vascular risk . DESIGN , SETTING , AND PARTICIPANTS Individual records were supplied on 302,430 people without initial vascular disease from 68 long-term prospect i ve studies , mostly in Europe and North America . During 2.79 million person-years of follow-up , there were 8857 nonfatal myocardial infa rct ions , 3928 coronary heart disease [ CHD ] deaths , 2534 ischemic strokes , 513 hemorrhagic strokes , and 2536 unclassified strokes . MAIN OUTCOME MEASURES Hazard ratios ( HRs ) , adjusted for several conventional factors , were calculated for 1-SD higher values : 0.52 log(e ) triglyceride , 15 mg/dL high-density lipoprotein cholesterol ( HDL-C ) , 43 mg/dL non-HDL-C , 29 mg/dL apolipoprotein AI , 29 mg/dL apolipoprotein B , and 33 mg/dL directly measured low-density lipoprotein cholesterol ( LDL-C ) . Within- study regression analyses were adjusted for within-person variation and combined using meta- analysis . RESULTS The rates of CHD per 1000 person-years in the bottom and top thirds of baseline lipid distributions , respectively , were 2.6 and 6.2 with triglyceride , 6.4 and 2.4 with HDL-C , and 2.3 and 6.7 with non-HDL-C. Adjusted HRs for CHD were 0.99 ( 95 % CI , 0.94 - 1.05 ) with triglyceride , 0.78 ( 95 % CI , 0.74 - 0.82 ) with HDL-C , and 1.50 ( 95 % CI , 1.39 - 1.61 ) with non-HDL-C. Hazard ratios were at least as strong in participants who did not fast as in those who did . The HR for CHD was 0.35 ( 95 % CI , 0.30 - 0.42 ) with a combination of 80 mg/dL lower non-HDL-C and 15 mg/dL higher HDL-C. For the subset with apolipoproteins or directly measured LDL-C , HRs were 1.50 ( 95 % CI , 1.38 - 1.62 ) with the ratio non-HDL-C/HDL-C , 1.49 ( 95 % CI , 1.39 - 1.60 ) with the ratio apo B/apo AI , 1.42 ( 95 % CI , 1.06 - 1.91 ) with non-HDL-C , and 1.38 ( 95 % CI , 1.09 - 1.73 ) with directly measured LDL-C. Hazard ratios for ischemic stroke were 1.02 ( 95 % CI , 0.94 - 1.11 ) with triglyceride , 0.93 ( 95 % CI , 0.84 - 1.02 ) with HDL-C , and 1.12 ( 95 % CI , 1.04 - 1.20 ) with non-HDL-C. CONCLUSION Lipid assessment in vascular disease can be simplified by measurement of either total and HDL cholesterol levels or apolipoproteins without the need to fast and without regard to triglyceride", "Background / Objectives : Diets high in nuts reduce cholesterol , probably due to their favorable lipid profile and other bioactive substances . However , the physical form of the nut may be important as the cell wall of intact nuts may limit the hypocholesterolemic effect of nuts by reducing lipid bioavailability . Therefore , we investigated the effects on blood lipids of incorporating three different forms of hazelnuts ( ground , sliced and whole ) into the usual diet . Subjects/ Methods : In a r and omized crossover study with three phases , 48 mildly hypercholesterolemic participants were asked to consume 30 g of ground , sliced or whole hazelnuts for 4 weeks . Body weight , plasma total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , triacylglycerol ( TAG ) , apolipoprotein ( apo ) A1 , apo B100 and α-tocopherol were measured at baseline and at the end of each dietary phase . Results : There were no significant differences in any outcome variable between the different forms of nuts ( all P⩾0.159 ) . However , compared with baseline , mean values at the end of each hazelnut intervention were significantly higher for HDL-C ( P=0.023 ) and α-tocopherol ( P=0.005 ) , and significantly lower for TC ( P ( P ) , TC : HDL-C ratio ( P ) , apo B100 ( P=0.002 ) and apo B100:apo A1 ratio ( P in body weight ( P=0.813 ) . Conclusions : The ingestion of three different forms of hazelnuts equally improved the lipoprotein profile and α-tocopherol concentrations in mildly hypercholesterolemic individuals . Hazelnuts can therefore be incorporated into the usual diet as a means of reducing cardiovascular disease risk" ]

[ "Study design : This was a multicentre , prospect i ve , r and omised study . Objectives : To compare the outcomes of intradetrusor and suburothelial onabotulinumtoxinA injections in patients with spinal cord injury and refractory neurogenic detrusor overactivity ( NDO ) . Setting : Urology departments of two tertiary hospitals in the Czech Republic . Methods : A total of 32 spinal cord injury patients with severe NDO refractory to the st and ard anticholinergic treatment were r and omised to receive either intradetrusor or suburothelial 300 IU onabotulinumtoxinA injections . Subjective satisfaction , bladder diary data and urodynamic data were compared in both groups before treatment and at 3 months post treatment . Results : In all , 64.3 % patients in the intradetrusor group and 88.8 % patients in the suburothelial group were subjectively satisfied with the treatment . There was a significant post-treatment improvement in both groups regarding the number of catheterisations over 24 h , number of incontinence episodes over 24 h , catheterised volume , cystometric capacity , volume at first involuntary detrusor contraction , maximal detrusor pressure during filling and detrusor compliance . No significant differences between the groups were observed , with the exception of improvement of detrusor compliance , which was better in the intradetrusor group . There was one adverse effect comprising transient muscle weakness that was reported by one patient in the intradetrusor group . Conclusion : Results in both groups were comparable . The authors favour suburothelial onabotulinumtoxinA injection because this method allows more precise toxin localisation", "Chornic spinal cord injury ( SCI ) will induce bladder urothelium dysfunction . This study investigated the therapeutic effects on urothelial dysfunction after repeated detrusor injections of onabotulinumtoxinA ( BoNT-A ) in SCI patients with neurogenic detrusor overactivity ( NDO ) . Twenty chronic suprasacral SCI patients with NDO were enrolled . The patients received 300 U BoNT-A injection into the detrusor every six months . The urothelium was assessed by cystoscopic biopsy at baseline and six months after each BoNT-A treatment . Immunofluorescence staining for urothelial dysfunction , including E-cadherin , zonula occludens-1 ( ZO-1 ) , tryptase for mast cell activity , and urothelial apoptosis were investigated . The outcome of urothelial dysfunction parameters after BoNT-A injection were compared between baseline and six months after each treatment . Repeated 300 U BoNT-A injections showed a sustained decrease of detrusor pressure compared with baseline . After three repeated BoNT-A detrusor injections , significantly greater distributions of E-cadherin ( p = 0.042 ) and ZO-1 ( p = 0.003 ) expressions , but no significant changes , of urothelial apoptosis and mast cell activation were found after repeated BoNT-A therapy . Urothelial dysfunction , such as adhesive and junction protein concentrations in SCI patients ’ bladders , recovered after three repeated cycles of BoNT-A treatment . The therapeutic effects sustained . However , urothelial inflammation and apoptosis after SCI were not significantly improved after three repeated BoNT-A injections", "Background The control of the lower urinary tract is a complex , multilevel process involving both the peripheral and central nervous system . Due to lesions of the neuraxis , most spinal cord injury patients suffer from neurogenic lower urinary tract dysfunction , which may jeopardise upper urinary tract function and has a negative impact on health-related quality of life . However , the alterations to the nervous system following spinal cord injury causing neurogenic lower urinary tract dysfunction and potential effects of treatments such as intradetrusor onabotulinumtoxinA injections on lower urinary tract control are poorly understood . Methods / Design This is a prospect i ve structural and functional magnetic resonance imaging study investigating the supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity . Neuroimaging data will include structural magnetic resonance imaging ( T1-weighted imaging and diffusion tensor imaging ) as well as functional , i.e. blood oxygen level-dependent sensitive magnetic resonance imaging using a 3 T magnetic resonance scanner . The functional magnetic resonance imaging will be performed simultaneously to three different bladder stimulation paradigms using an automated magnetic resonance compatible and synchronised pump system . All subjects will undergo two consecutive and identical magnetic resonance imaging measurements . Healthy subjects will not undergo any intervention between measurements but spinal cord injury patients will receive intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity . Parameters of the clinical assessment including bladder diary , urinalysis , medical history , neuro-urological examination , urodynamic investigation as well as st and ardised question naires regarding lower urinary tract function and quality of life will serve as co-variates in the magnetic resonance imaging analysis . Discussion This study will identify structural and functional alterations in supraspinal networks of lower urinary tract control in spinal cord injury patients with neurogenic detrusor overactivity compared to healthy controls . Post-treatment magnetic resonance imaging measurements in spinal cord injury patients will provide further insights into the mechanism of action of treatments such as intradetrusor onabotulinumtoxinA injections and the effect on supraspinal lower urinary tract control . Trial registration Clinical Trials.gov NCT01768910", "Study design : The study was design ed as a single-arm clinical trial . Objectives : To investigate the effect of detrusor botulinum toxin A ( BoNTA ) injection on urinary tract infection ( UTI ) in patients with spinal cord injury ( SCI ) . Setting : The study was performed in a national rehabilitation research center of China . Methods : Between September 2010 and May 2012 , 41 male in patients with neurogenic detrusor overactivity ( NDO ) caused by traumatic SCI , mean age 36.0±8.8 years , duration of SCI since inclusion 21.5±17.3 months , received an injection of 300 U BoNTA into detrusor . Before and 3 months after injection , each patient kept a bladder diary , underwent video-urodynamic investigation and urine culture . All UTIs occurring in the 6 months before and the 6 months after injection were recorded . Results : Before injection , the mean number of UTI over 6 months was 1.39±1.36 . After injection , the mean significantly decreased to 0.78±0.96 ( P=0.023 ) . The mean maximum detrusor pressure during filling decreased significantly in the patients of detrusor overactivity ( n=24 ) compared with patients of normo-active detrusor ( n=17 ) after injection ( 35.4±12.2 vs 20.9±7.9 cmH2O , P=0.000 ) , meantime , the decrease of UTI was significant in the former ( 1.29±1.21 vs 0.41±0.62 cmH2O , P=0.015 ) while no significant in the latter ( 1.46±1.47 vs 1.04±1.08 , P=0.319 ) . Conclusion : Detrusor BoNTA injection significantly decreased UTI in SCI patients with NDO . This effect seems to be related to the decrease of detrusor pressure ", "Purpose To explore the dose response to onabotulinumtoxinA 50 , 100 , and 200 U in patients with spinal cord injury ( SCI ) with urinary incontinence ( UI ) due to neurogenic detrusor overactivity ( NDO ) . Methods Patients ( N = 73 ) with SCI ( level T1 or lower ) with NDO and UI ( ≥14 UI episodes/week ) received 30 intradetrusor injections of onabotulinumtoxinA ( 50 U [ n = 19 ] , 100 U [ n = 21 ] , or 200 U [ n = 17 ] ) or placebo ( n = 16 ) via cystoscopy , avoiding the trigone . Changes from baseline in UI episodes/week , volume voided/micturition , maximum cystometric capacity , and maximum detrusor pressure ( MDP ) during first involuntary detrusor contraction ( IDC ) were evaluated . Adverse events ( AEs ) were assessed . Results A significant linear dose response for UI episodes/week was identified at weeks 18 , 30 , 36 , 42 , and 54 ( P in volume/void at all post-treatment time points up to week 54 ( P in MDP during first IDC at week 6 ( P = 0.034 ) . The proportion of patients who achieved continence at week 6 was highest in the 200 U group . Duration of effect was longest with the 200 U dose , compared with other treatment groups . The AEs were comparable across groups ; urinary tract infection was the most common AE across all treatment groups . Conclusions In this exploratory dose – response study of SCI patients with UI due to NDO , onabotulinumtoxinA 200 U was the most effective dose . The AE profile was comparable across all groups", "OBJECTIVE To assess the reliability , validity , responsiveness , and minimally important difference ( MID ) of the Incontinence Quality of Life ( I-QOL ) question naire in patients with urinary incontinence due to neurogenic detrusor overactivity . DESIGN R and omized , double-blind , multicenter , placebo-controlled study . SETTING Eight centers across Belgium , France , and Switzerl and . PARTICIPANTS Patients with urinary incontinence due to neurogenic detrusor overactivity inadequately managed on oral anticholinergics . Fifty-nine patients ( spinal cord injury , n=53 ; multiple sclerosis , n=6 ) were enrolled . INTERVENTION Single dose of botulinum toxin type A ( Botox ) ( 200 or 300 U ) or placebo . MAIN OUTCOME MEASURES I-QOL question naire completed at screening and over a 24-week post-treatment period . RESULTS The Cronbach alpha ranged from .79 to .93 , indicating that I-QOL is a reliable measure of QOL in neurogenic urinary incontinence patients . No item had more than 5.1 % missing or out of range values . With the exception of 2 items , questions showed acceptable item-scale correlation and scaling success results varied by domain . Post-treatment correlations indicated acceptable construct validity . The I-QOL was responsive to improvements in symptoms . MID values ranged from 4 to 11 points . CONCLUSIONS Results suggest that I-QOL is a reliable , valid , and responsive measure of incontinence-related QOL in neurogenic patients", "Introduction : Apart from the st and ard intramural administration of botulinum neurotoxin A ( BoNT/A ) to the detrusor , intense research is taking place into new means of administration in view of the complex mechanism of action of BoNT/A. Methods : An open , r and omised , prospect i ve study was performed on a total of 23 patients with neurogenic detrusor overactivity . Following r and omisation , patients were treated with 300 U of onabotulinumtoxinA ( onaBoNT/A ) in either the submucosa or the detrusor . Urodynamic examinations were carried out , and a bladder diary was kept both prior to and 12 weeks after the treatment . All patients stopped taking anticholinergics 1 week prior to the treatment . Results : In both the submucosa and detrusor groups , we recorded a significant improvement in the monitored urodynamic parameters and significant decreases in the frequency of urinary incontinence episodes following the treatment . A comparison of the two groups showed no significant difference between the two forms of application , with the exception of voided volume ( p = 0.007 ) . Conclusion : A comparison of the two administration methods did not show any significant difference between onaBoNT/A administration to the submucosa and to the detrusor . Thus , the submucosal injection of onaBoNT/A represents an equally effective approach for its administration to patients", "Introduction To evaluate the efficacy and safety of onabotulinumtoxinA for the treatment of neurogenic detrusor overactivity ( NDO ) in sub population s of etiology ( multiple sclerosis [ MS ] or spinal cord injury [ SCI ] ) and concomitant anticholinergics ( use/non-use ) . Methods Data were pooled from two double-blind , placebo-controlled , pivotal , phase 3 studies including a total of 691 patients with ≥14 urinary incontinence ( UI ) episodes/week due to MS ( n = 381 ) or SCI ( n = 310 ) . Patients received intradetrusor injections of onabotulinumtoxinA 200U ( n = 227 ) , 300U ( n = 223 ) , or placebo ( n = 241 ) . Change from baseline at week 6 in UI episodes/week ( primary endpoint ) , urodynamics , quality of life ( QOL ) , and adverse events ( AEs ) were assessed . Results Significant and similar reductions in UI episodes were observed regardless of etiology or anticholinergic use : at week 6 , mean weekly decreases of −22.6 and −19.6 were seen in MS and SCI patients , respectively , and −20.3 and −22.5 in anticholinergic users and non-users , respectively , treated with onabotulinumtoxinA 200U . The 300U dose did not add to the clinical efficacy in any sub population . Similar proportions of patients achieved ≥50 % or 100 % reductions in UI episodes in all subgroups . Improvements in maximum cystometric capacity , maximum detrusor pressure during first involuntary detrusor contraction , and QOL were significant in both etiologies and were independent of anticholinergic use . The most common AEs in all groups were urinary tract infection and urinary retention . Conclusion Regardless of concomitant anticholinergic use or etiology , onabotulinumtoxinA significantly improved UI symptoms , urodynamics , and QOL in patients with UI due to NDO . OnabotulinumtoxinA was well tolerated in all groups", "PURPOSE We determined the safety and efficacy of each of 2 doses of botulinum toxin type A ( BTX-A ) ( 200 or 300 U BOTOX ) injected into the detrusor for urinary incontinence caused by neurogenic detrusor overactivity of predominantly spinal cord origin . MATERIAL S AND METHODS A total of 59 patients with urinary incontinence caused by neurogenic detrusor overactivity ( due to spinal cord injury in 53 and multiple sclerosis in 6 ) requiring clean intermittent self-catheterization were r and omized to receive a single dose into the detrusor of BTX-A ( 200 U or 300 U ) or placebo . Changes in daily frequency of urinary incontinence episodes were monitored via a patient bladder diary during 24 weeks . Key urodynamic assessment s ( maximum cystometric capacity , reflex detrusor volume and maximum detrusor pressure during bladder contraction ) were used to provide objective measures of the treatment effect on bladder function . The impact of treatment on quality of life was assessed using the Incontinence Quality of Life question naire . RESULTS There were significant posttreatment decreases in incontinence episodes from baseline in the 2 BTX-A groups ( p placebo group . In addition , more patients who received BTX-A reported no incontinence episodes during at least 1 posttreatment evaluation period . Positive treatment effects were also reflected by significant improvements in bladder function in the BTX-A groups , as assessed by urodynamics and in patient quality of life . Benefits were observed from the first evaluation at week 2 to the end of the 24-week study . No safety concerns were raised . CONCLUSIONS Intramuscular injections of BTX-A into the detrusor can provide rapid , well tolerated , clinical ly significant decreases in the signs and symptoms of urinary incontinence caused by neurogenic detrusor overactivity during a 24-week study period", "OBJECTIVES To investigate the therapeutic effects of repeated detrusor onabotulinumtoxinA injections on treatment outcomes , quality of life ( QoL ) , and glomerular filtration rate ( GFR ) in chronic spinal cord injured ( SCI ) patients with neurogenic lower urinary tract dysfunction and urinary incontinence . MATERIAL S AND METHODS Patients with SCI who failed antimuscarinic treatment were enrolled . All patients had urodynamic detrusor overactivity ( DO ) or increased detrusor tonicity without anatomical bladder outlet obstruction or intrinsic sphincter deficiency . They were r and omly assigned to receive 200-U or 300-U onabotulinumtoxinA detrusor injections every 6 months . The primary endpoint was 6 months after the second injection . The urodynamic parameters , QoL measures , and 99mTc renal scans were evaluated at baseline and every 3 months and compared between dosages . RESULTS A total of 72 patients were enrolled , including 43 men and 29 women and mean injury duration of 8.7 years . Among them , 38 patients received 200-U and 34 received 300-U onabotulinumtoxinA injections . At the end-point , the urodynamic parameters and incontinence severity improved significantly , without a significant difference between the two groups . QoL also improved in both groups , without differences between groups . Uninhibited DO improved more in 300-U group compared to 200-U group at end-point ( P = 0.01 ) . The GFR did not change significantly in either group . The most common complication was urinary tract infection , which occurred in one third of patients . CONCLUSIONS Either 200-U or 300-U repeated detrusor onabotulinumtoxinA injections improved incontinence , urodynamic parameters , and QoL in SCI patients with neurogenic DO . Renal function was maintained in patients receiving both dosage of repeated injections", "OBJECTIVE To evaluate botulinum toxin type A ( BTX-A ) for treating neurogenic detrusor overactivity in patients with spinal cord lesions , including those with abnormally low bladder compliance . DESIGN Nonr and omized , before-after trial ( 9-mo follow-up ) . SETTING Hospitalized care . PARTICIPANTS Ten patients with high detrusor contraction pressure and /or poor response to oxyphencyclimine with incontinence selected as a consecutive sample . INTERVENTION BTX-A ( Botox ; 300U ) was injected into the detrusor muscle . MAIN OUTCOME MEASURES Urinary continence , functional bladder capacity , bladder compliance , detrusor contraction pressure , and volume at first reflex voiding . Measurements were taken before and 6 , 16 , and 36 weeks posttreatment . RESULTS Six weeks after treatment , complete continence was restored in 7 patients without oxyphencyclimine . Mean functional bladder capacity ( P=.008 ) , compliance ( P=.012 ) , and reflex volume ( P=.045 ) significantly increased , whereas maximal detrusor contraction pressure significantly decreased ( P Urodynamic variables remained significantly improved at 16 weeks , but values were returning toward baseline levels by 36 weeks . The procedure was generally uneventful , without any serious side effects . CONCLUSIONS BTX-A injections are an effective , well-tolerated treatment for neurogenic detrusor overactivity in patients with spinal cord lesions , even in patients with abnormally low bladder compliance . Patients may require repeat injections after 16 weeks to remain continent", "PURPOSE The short-term outcomes of initial detrusor injections vs combined detrusor-trigone botulinum toxin-A injections were determined in patients with spinal cord injury-neurogenic detrusor overactivity . MATERIAL S AND METHODS Adults with refractory spinal cord injury-neurogenic detrusor overactivity who strictly discontinued anticholinergics were recruited for the study . At a 1:1 ratio patients r and omly received 300 U botulinum toxin-A intradetrusor injections excluding the trigone ( detrusor arm ) or 200 U intradetrusor plus 100 U intratrigonal injections ( combined arm ) . Study end points were determination of the impact on incontinence episodes , complete dryness , quality of life , reusing anticholinergics , maximum detrusor pressure , reflex volume , maximum cystometric capacity , vesicoureteral reflux and adverse events . Patients were evaluated at baseline , and 2 , 8 , 12 and 18 weeks after injection . Statistical significance was considered at p 18 patients per arm with no significant baseline differences . On within group analysis all parameters improved significantly compared to baseline . On between group analysis in the detrusor vs the combined arm at week 8 incontinence decreased by 52.4 % vs 80.9 % ( number needed to treat 1.91 vs 1.23 patients , p complete dryness was achieved in 33.3 % vs 66.7 % of patients ( number needed to treat 3 vs 1.5 , p quality of life score was decreased by 46.76 % vs 48.13 % ( number needed to treat 2.14 vs 2.08 , p reflex volume ( p maximum cystometric capacity ( p maximum detrusor pressure ( p grade d vesicoureteral reflux or reported significant adverse events . CONCLUSIONS In the short term all parameters improved significantly in each arm . The superiority of including rather than excluding the trigone was significant", "AIMS OnabotulinumtoxinA significantly reduces urinary incontinence ( UI ) and improves bladder management in patients with neurogenic detrusor overactivity ( NDO ) . We evaluated the impact of onabotulinumtoxinA on patient-reported outcomes ( PROs ) in patients with UI due to NDO in a double-blind , placebo-controlled study . METHODS Patients with UI due to NDO ( from multiple sclerosis or spinal cord injury ) were r and omized to intradetrusor placebo ( n = 92 ) or onabotulinumtoxinA 200 U ( n = 92 ) or 300 U ( n = 91 ) . PROs included Incontinence Quality of Life ( I-QOL ) Question naire to assess health-related quality of life ( HRQoL ) , the 16-item modified Overactive Bladder-Patient Satisfaction with Treatment Question naire ( OAB-PSTQ ) to assess treatment satisfaction , and Patient Global Assessment to assess treatment goal achievement . RESULTS Mean improvement in I-QOL total score at weeks 6 and 12 was significantly greater with both onabotulinumtoxinA 200 U and 300 U versus placebo ( Δ12.3 for 200 U and Δ14.9 for 300 U vs. placebo ; P improvement in satisfaction at weeks 6 and 12 was significantly greater for onabotulinumtoxinA versus placebo ( P somewhat or very satisfied ( 200 U , 77.5 % and 300 U , 67.8 % vs. placebo , 39.5 % ) , and significant progress toward or complete achievement of primary treatment goal ( 200 U , 62.9 % and 300 U , 61.6 % vs. placebo , 16.5 % ) . CONCLUSIONS NDO patients treated with onabotulinumtoxinA 200 or 300 U had significantly greater improvement in HRQoL and greater treatment satisfaction compared with placebo-treated patients , with no clinical ly relevant differences between onabotulinumtoxinA doses", "BACKGROUND Neurogenic detrusor overactivity ( NDO ) frequently results in urinary incontinence ( UI ) which impairs quality of life ( QOL ) and puts the upper urinary tract at risk . OBJECTIVE To assess the effects of onabotulinumtoxinA ( BOTOX ( ® ) , Allergan , Inc. ) on UI , urodynamic variables , and QOL in incontinent patients with NDO . DESIGN , SETTING , AND PARTICIPANTS This multicentre , r and omised , double-blind , placebo-controlled study enrolled patients with multiple sclerosis ( MS ; n=154 ) or spinal cord injury ( SCI ; n=121 ) with UI due to NDO ( ≥14 UI episodes per week ) . INTERVENTION Patients received 30 intradetrusor injections of onabotulinumtoxinA 200 U ( n=92 ) , 300 U ( n=91 ) , or placebo ( n=92 ) , avoiding the trigone . MEASUREMENTS Primary end point was change from baseline in UI episodes per week ( week 6 ) . Secondary end points included urodynamics ( maximum cystometric capacity [ MCC ] , maximum detrusor pressure during first involuntary detrusor contraction [ P(detmaxIDC ) ] ) , and Incontinence Quality of Life ( I-QOL ) total score . Adverse events ( AEs ) were assessed . RESULTS AND LIMITATIONS At baseline , mean UI episodes per week ( 33.5 ) were similar across groups . At week 6 , onabotulinumtoxinA 200 U and 300 U significantly reduced UI episodes per week ( -21.8 and -19.4 , respectively ) compared with placebo ( -13.2 ; p Improvements in MCC , P(detmaxIDC ) , and I-QOL at week 6 were significantly greater with both onabotulinumtoxinA doses than with placebo ( p The median time to patient request for retreatment was the same for both onabotulinumtoxinA doses ( 42.1 wk ) and greater than placebo ( 13.1 wk ; p were localised urologic events ( urinary tract infections and urinary retention , which were dose related in patients not using clean intermittent catheterisation [ CIC ] at baseline ) . Significant increases in postvoid residual were observed in patients not using CIC prior to treatment , and 12 % , 30 % , and 42 % of patients in the placebo , 200-U , and 300-U groups , respectively , initiated CIC posttreatment . CONCLUSIONS OnabotulinumtoxinA significantly reduced UI and improved urodynamics and QOL in MS and SCI patients with NDO . Both doses were well tolerated with no clinical ly relevant differences in efficacy or duration of effect between the two doses ( http://www . clinical trials.gov ; NCT00461292 )", "PURPOSE We assessed the efficacy , safety and effects on quality of life of onabotulinumtoxinA in patients with neurogenic detrusor overactivity . MATERIAL S AND METHODS In this 52-week , international , multicenter , double-blind , r and omized , placebo controlled trial 416 patients with neurogenic detrusor overactivity and urinary incontinence ( 14 or more episodes per week ) result ing from multiple sclerosis ( 227 ) and spinal cord injury ( 189 ) were treated with intradetrusor injections of onabotulinumtoxinA ( 200 or 300 U ) or placebo . The primary end point was the change from baseline in the mean number of urinary incontinence episodes per week at week 6 . Maximum cystometric capacity , maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life total score were secondary end points . Adverse events were monitored . RESULTS OnabotulinumtoxinA at a dose of 200 U in 135 patients and 300 U in 132 decreased mean urinary incontinence at week 6 by 21 and 23 episodes per week , respectively , vs 9 episodes per week in 149 on placebo ( each dose p maximum cystometric capacity , maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life score were significantly improved over values in the placebo group ( each dose p Median time to patient re-treatment request was greater for onabotulinumtoxinA 200 and 300 U than for placebo ( 256 and 254 days , respectively , vs 92 ) . The most common adverse events were urinary tract infection and urinary retention . Of patients who did not catheterize at baseline 10 % on placebo , 35 % on 200 U and 42 % on 300 U initiated catheterization due to urinary retention . CONCLUSIONS OnabotulinumtoxinA significantly improved neurogenic detrusor overactivity symptoms vs placebo . Clean intermittent catheterization initiation due to urinary retention appeared to increase in a dose dependent fashion . No clinical ly relevant benefit in efficacy or duration was identified for the 300 U dose over the 200 U dose", "AIM To vali date a self-administered instrument , the Medication Adherence Self-Report Inventory ( MASRI ) for measuring adherence to anti-cholinergic medication for overactive bladder ( OAB ) . METHODS Prospect i ve study in 131 women with OAB treated with fesoterodine . Adherence was measured at 8 and 12 weeks using an interviewer administered brief medication question naire ( BMQ ) that assesses barriers to adherence ( criterion st and ard ) , the MASRI , and pill count . Construct , concurrent and discriminant validity of the MASRI was assessed . We hypothesized that women who were non-adherent as measured by the MASRI would be more likely to have a belief barrier than women who were adherent to medication . RESULTS Women diagnosed as non-adherent by the MASRI were more likely to report a belief barrier to taking medication as compared to adherent women at 8 weeks ( 80 % vs. 38 % , P adherence rates measured by the MASRI and the BMQ at 8 weeks ( r = 0.87 , P adherence rate as measured by the MASRI and pill count at 8 weeks ( r = 0.49 , P = 0.02 ) but not at 12 weeks ( r = 0.05 , P = 0.87 ) . The MASRI correctly identified 93 % and 96 % of non-adherent women at 8 and 12 weeks , respectively . Sensitivity , specificity , and positive likelihood ratio of the MASRI for predicting non-adherence was 91 % , 82 % , and 5.1 at 8 weeks and 90 % , 85 % and 6.1 at 12 weeks . CONCLUSIONS The MASRI is a valid self-administered tool for measuring adherence to anti-cholinergic medication in women with OAB", "Study design : The study was design ed as a single-arm clinical trial . Objectives : To investigate the therapeutic effects of detrusor botulinum toxin A ( BoNT-A ) treatment in patients with different levels of spinal cord injury ( SCI ) and types of detrusor sphincter dyssynergia ( DSD ) . Setting : Patients with chronic suprasacral SCI and neurogenic detrusor overactivity ( NDO ) were treated with 200-U BoNT-A detrusor injection in a tertiary university hospital in Taiwan . Methods : Outcome assessment of urodynamic parameters and therapeutic satisfaction were performed at 3 and 6 months among patients with different demographics , SCI levels and types of DSD . The treatment outcomes were assessed by changes in Urogenital Distress Inventory 6-item short form ( UDI-6 ) , quality of life ( QoL ) index and detrusor pressure at maximum flow rate ( Pdet . Qmax ) . Results : A total of 38 patients with a mean age of 40.1±12.4 years and median duration of SCI of 10.3 years were enrolled . Satisfactory response was reported in 23 ( 60 % ) patients . Significant improvements in the UDI-6 and QoL were reported and significant increases of cystometric bladder capacity and post-void residual were noted in overall patients after treatment . Patients with different clinical demographics and urodynamic parameters had similar treatment outcomes and UDI-6 scores . In 11 patients receiving repeat injections of 300 U of BoNT-A after failure of a previous 200 U injection , the treatment outcomes were not significantly different , except that the PdetQmax at 6 months were higher in the group that received 200 U of BoNT-A. Conclusion : Patients with different SCI levels or DSD types had similar treatment outcomes after detrusor 200 U BoNT-A injections for NDO", "OBJECTIVES To study the effect of botulinum toxin A ( BoNTA ) injections into the detrusor muscle on the incidence of symptomatic urinary infections in patients with neurogenic detrusor overactivity . METHODS Between February 2004 and June 2005 , 30 patients ( 18 men , 12 women ) , mean age 39.4+/-12.1 yr , with neurogenic detrusor overactivity received an injection of 300 U Botox ( Allergan Inc. , Irvine , CA , USA ) into the detrusor . Fifteen patients had multiple sclerosis , 14 had spinal cord injury , and 1 had myelitis . Twenty-two patients had urinary incontinence . Patients were either resistant to anticholinergic medications , had discontinued treatment because of adverse effects , or had contraindications to anticholinergic drugs . Before and 6 wk after injection , each patient kept a bladder diary and underwent urodynamic investigation , retro grade and voiding cystourethrography , and urine culture . All symptomatic urinary infections ( pyelonephritis , orchitis , prostatitis ) occurring in the 6 mo before and the 6 mo after injection were recorded . RESULTS Before injection , the mean number of symptomatic urinary infections over 6 mo was 1.75+/-1.87 . After injection , the mean was 0.2+/-0.41 ( p=0.003 ) , and only 3 patients presented symptomatic urinary infections . These patients were those who showed less improvement in their urodynamic parameters after injection ( volume of the first uninhibited contraction , maximum bladder pressure , and maximum cystometric capacity , respectively ; p=0.0037 , p=0.0002 , p=0.0027 , ANOVA ) . CONCLUSIONS BoNTA injections into the detrusor muscle significantly decreased the incidence of symptomatic urinary infections . This effect seems to be related to improvement in urodynamic parameters , reflecting improved reservoir capacity at low pressure", "OBJECTIVE To evaluate the impact of botulinum toxin type A ( BoNTA ) on health-related quality of life in patients with neurogenic urinary incontinence ( UI ) using the Incontinence Quality of Life question naire ( I-QOL ) . METHODS R and omized , double-blind , multicenter , placebo-controlled study involving eight centers across Belgium , France , and Switzerl and . Patients ( n = 59 ) with UI due to neurogenic detrusor overactivity ( spinal cord injury , n = 53 ; multiple sclerosis , n = 6 ) who were inadequately managed on oral anticholinergics received a single dose of BoNTA ( 200U or 300U , Botox ) or placebo . I-QOL scores at screening and after treatment at weeks 2 , 6 , 12 , 18 , and 24 were recorded . RESULTS Median total and subscale I-QOL scores increased significantly from screening with BoNTA 300U compared with placebo at all time points ( p BoNTA 200U compared with placebo at all time points for total score and the Avoidance Limiting Behavior subscale ( p Psychosocial Impact and Social Embarrassment subscales . Approximately twice as many BoNTA recipients as placebo recipients achieved at least a minimal important difference in total I-QOL score at 2 , 6 , 12 , and 24 wk . CONCLUSIONS BoNTA significantly improves UI-associated health-related quality of life in patients with neurogenic UI", "PURPOSE We determined the efficacy of onabotulinumtoxinA for neurogenic detrusor overactivity secondary to spinal cord injury or multiple sclerosis . MATERIAL S AND METHODS In a prospect i ve , double-blind , multicenter study 57 patients 18 to 75 years old with neurogenic detrusor overactivity secondary to spinal cord injury or multiple sclerosis and urinary incontinence ( defined as 1 or more occurrences daily ) despite current antimuscarinic treatment were r and omized to onabotulinumtoxinA 300 U ( 28 ) or placebo ( 29 ) via cystoscopic injection at 30 intradetrusor sites , sparing the trigone . Patients were offered open label onabotulinumtoxinA 300 U at week 36 and followed a further 6 months while 24 each in the treatment and placebo groups received open label therapy . The primary efficacy parameter was daily urinary incontinence frequency on 3-day voiding diary at week 6 . Secondary parameters were changes in the International Consultation on Incontinence Question naire and the urinary incontinence quality of life scale at week 6 . Diary and quality of life evaluations were also done after open label treatment . RESULTS The mean daily frequency of urinary incontinence episodes was significantly lower for onabotulinumtoxinA than for placebo at week 6 ( 1.31 vs 4.76 , p urodynamic and quality of life parameters for treatment vs placebo were evident at week 6 and persisted to weeks 24 to 36 . The most common adverse event in each group was urinary tract infection . CONCLUSIONS In adults with antimuscarinic refractory neurogenic detrusor overactivity and multiple sclerosis onabotulinumtoxinA is well tolerated and provides clinical ly beneficial improvement for up to 9 months" ]

[ "We have compared the biomechanical nature of the reconstruction of the hip in conventional total hip arthroplasty ( THA ) and surface replacement arthroplasty ( SRA ) in a r and omised study involving 120 patients undergoing unilateral primary hip replacement . The contralateral hip was used as a control . Post-operatively , the femoral offset was significantly increased with THA ( mean 5.1 mm ; -2.8 to 11.6 ) and decreased with SRA ( mean -3.3 mm ; -8.9 to 8.2 ) . Femoral offset was restored within sd 4 mm in 14 ( 25 % ) of those with THA and in 28 ( 57 % ) of the patients receiving SRA ( p leg was lengthened by a mean of 2.6 mm ( -6.04 to + 12.9 ) , whereas it was shortened by a mean of 1.9 mm ( -7.1 to + 2.05 ) in the SRA group , compared with the contralateral side . Leg-length ine quality was restored within sd 4 mm in 42 ( 86 % ) of the SRA and 33 ( 60 % ) of the THA patients . The radiological parameters of acetabular reconstruction were similar in both groups . Restoration of the normal proximal femoral anatomy was more precise with SRA . The enhanced stability afforded by the use of a large-diameter femoral head avoided over-lengthening of the limb or increased offset to improve soft-tissue tension as occurs sometimes in THA . In a subgroup of patients with significant pre-operative deformity , restoration of the normal hip anatomy with lower pre-operative femoral offset or significant shortening of the leg was still possible with SRA", "The purpose of this study was to compare conventional and navigated technique and a recently developed straight hip stem for uncemented primary total hip arthroplasty . The results of two consecutive implantation series of 42 patients ( nonnavigated ) and 42 patients ( navigated ) were analysed for implant positioning and complications . All surgeries were performed by the investigator . Radiographic analysis of cup position showed a significant improvement with reduced radiologic inclination ( 53 degrees nonnavigated /44 degrees navigated ; P mean postoperative limb length difference was 6.2 mm ( SD , 9.0 for nonnavigated ) and 4.4 mm ( SD , 6.4 for navigated ) . Intraoperative and early postoperative complications were not different . No dislocation occurred in either group . There was one intraoperative trochanter fracture that was not revised ( nonnavigated ) and one revision because of a periprosthetic fracture caused by fall down during rehabilitation ( navigated ) . We conclude that acetabular implant positioning can be significantly improved by the use of navigated surgery technique . The data for postoperative limb length difference were still similar but within the expected range in both groups . The effect of improved cup positioning on mid and longterm results for both groups has to be investigated further", "We prospect ively evaluated acetabular cup placement in total hip arthroplasty with an imageless computer navigation system or using conventional manual technique . The achieved cup orientation in the manual group had substantially larger variances and greater placement error than the navigation cases . The use of navigation was ab and oned in 3 cases because of excessive pelvic tilt and unreliable registration of the pelvis . Computer navigation system helped improve the accuracy of the acetabular cup placement for total hip arthroplasty in this study . The variation between the intraoperative navigation readings and the computed tomographic values suggests that relying on palpation of bony l and marks through drapes and tissue is a limitation of this method . Further , the variation in pelvic tilt has an effect on cup placement that requires further studies", "We report the kinematic and early clinical results of a patient- and observer-blinded r and omised controlled trial in which CT scans were used to compare potential impingement-free range of movement ( ROM ) and acetabular component cover between patients treated with either the navigated ' femur-first ' total hip arthroplasty ( THA ) method ( n = 66 ; male/female 29/37 , mean age 62.5 years ; 50 to 74 ) or conventional THA ( n = 69 ; male/female 35/34 , mean age 62.9 years ; 50 to 75 ) . The Hip Osteoarthritis Outcome Score , the Harris hip score , the Euro-Qol-5D and the Mancuso THA patient expectations score were assessed at six weeks , six months and one year after surgery . A total of 48 of the patients ( 84 % ) in the navigated ' femur-first ' group and 43 ( 65 % ) in the conventional group reached all the desirable potential ROM boundaries without prosthetic impingement for activities of daily living ( ADL ) in flexion , extension , abduction , adduction and rotation ( p = 0.016 ) . Acetabular component cover and surface contact with the host bone were > 87 % in both groups . There was a significant difference between the navigated and the conventional groups ' Harris hip scores six weeks after surgery ( p = 0.010 ) . There were no significant differences with respect to any clinical outcome at six months and one year of follow-up . The navigated ' femur-first ' technique improves the potential ROM for ADL without prosthetic impingement , although there was no observed clinical difference between the two treatment groups", "Background This study compared the efficacy and safety of 3 different anesthesia techniques used in total hip arthroplasty ( THA ) . Material / Methods We allocated 198 patients preparing to undertake THA into 3 groups : general anesthesia group ( GA group , n=66 ) , caudal epidural anesthesia group ( CEA group , n=66 ) , and spinal-epidural anesthesia group ( SEA group , n=66 ) . We compared postoperative adverse effects occurring in patients of the 3 anesthesia groups . The Visual Analog Scale ( VAS ) score , Minimum Mental State Examination ( MMSE ) score , and β-amyloid ( Aβ ) expression were calculated to determine the effects of different anesthesia on the postoperative pain and cognitive dysfunction of patients . Results The CEA and SEA groups had lower rates of perioperative adverse effects than in the GA group . Patients in the GA group required significantly higher administration of analgesics after the surgery than those in CEA and SEA groups . Higher Aβ expression levels and VAS scores , as well as lower MMSE scores , were also seen in the GA group compared with the other 2 groups . Conclusions CEA and SEA were more effective than GA in THA , and CEA seemed to be a better anesthesia technique than SEA", "Background Restoration of biomechanics is a major goal in THA . Imageless navigation enables intraoperative control of leg length equalization and offset reconstruction . However , the effect of navigation compared with intraoperative fluoroscopy is unclear . Questions / purpose sWe asked whether intraoperative use of imageless navigation ( 1 ) improves the relative accuracy of leg length and global and femoral offset restoration ; ( 2 ) increases the absolute precision of leg length and global and femoral offset equalization ; and ( 3 ) reduces outliers in a reconstruction zone of ± 5 mm for leg length and global and femoral offset restoration compared with intraoperative fluoroscopy during minimally invasive ( MIS ) THA with the patient in a lateral decubitus position . Methods In this prospect i ve study a consecutive series of 125 patients were r and omized to either navigation-guided or fluoroscopy-controlled THA using sealed , opaque envelopes . All patients received the same cementless prosthetic components through an anterolateral MIS approach while they were in a lateral decubitus position . Leg length , global or total offset ( representing the combination of femoral and acetabular offset ) , and femoral offset differences were restored using either navigation or fluoroscopy . Postoperatively , residual leg length and global and femoral offset discrepancies were analyzed on magnification-corrected radiographs of the pelvis by an independent and blinded examiner using digital planning software . Accuracy was defined as the relative postoperative difference between the surgically treated and the unaffected contralateral side for leg length and offset , respectively ; precision was defined as the absolute postoperative deviation of leg length and global and femoral offset regardless of lengthening or shortening of leg length and offset throughout the THA . All analyses were performed per intention-to-treat . Results Analyzing the relative accuracy of leg length restoration we found a mean difference of 0.2 mm ( 95 % CI , −1.0 to + 1.4 mm ; p = 0.729 ) between fluoroscopy and navigation , 0.2 mm ( 95 % CI , −0.9 to + 1.3 mm ; p = 0.740 ) for global offset and 1.7 mm ( 95 % CI , + 0.4 to + 2.9 mm ; p = 0.008 ) for femoral offset . For the absolute precision of leg length and global and femoral offset equalization , there was a mean difference of 1.7 ± 0.3 mm ( p a residual leg length and global and femoral offset discrepancy less than 5 mm and less than 8 mm , respectively , succeeded in 93 % and 98 % , respectively , in the navigation group and in 54 % and 95 % , respectively , in the fluoroscopy group . Conclusions Intraoperative fluoroscopy and imageless navigation seem equivalent in accuracy and precision to reconstruct leg length and global and femoral offset during MIS THA with the patient in the lateral decubitus position . Level of Evidence Level I , therapeutic study . See the Instructions for Authors for a complete description of levels of evidence", "We present a match-paired study between computer-assisted and freeh and techniques using a short modular femoral stem ( Metha ; B. Braun Aesculap , Tuttlingen , Germany ) in total hip replacement ( THR ) . Surgical time , clinical outcome , dislocation rate , limb length , and offset in 44 patients with ideal indication for this more conservative implant were assessed . Despite both longer surgical time and similar early outcomes , the results showed how computer-assisted techniques allow easier management of limb length discrepancy and offset restoring . We believe that navigated short modular stems are safe for less invasive THR", "Navigation in primary total hip arthroplasty has a history of over 20 years . During this process , imageless computer navigation can be particularly helpful in optimally restoring the hip ’s biomechanics . This involves the accurate placement of the acetabular component with the determination of the anteversion and abduction , whereby the navigated femur-first technique also allows for a calculation of the combined anteversion . Additional critical parameters such as the reconstruction of the rotation centre , as well as the femoral and acetabular offset , can also be optimally adjusted . Last but not least , an intra-operative evaluation and equalisation of the leg length is possible . Nonetheless , the disadvantages of this surgical technique in terms of the high costs in the acquisition and preservation of the necessary devices , as well as the longer operation time , must be taken into account . However , economic aspects are not the only thing preventing widespread use of the navigation technique . Determining the plane of reference ( APP ) for the optimal orientation of the implants is based on palpation of the bony l and marks – and this is influenced by the thickness of the soft tissue layer . Furthermore , the experience of the surgeon constitutes a variable that influences the accuracy of navigation . In summary , hip navigation certainly offers an interesting technique for the optimisation of total hip arthroplasty with reconstruction of proper biomechanics . At the same time , there is currently a lack of high- quality r and omised controlled long-term trials that evaluate the clinical advantage for the patients , together with cost utility and survival rates . Cite this article : Renner L , Janz V , Perka C , Wassilew GI . What do we get from navigation in primary THA ? EFORT Open Rev 2016;1:205 - 210 . 10.1302/2058 - 5241.1.000034" ]

[ "OBJECTIVE To pilot , among women with gestational diabetes mellitus ( GDM ) , the feasibility of a prenatal/postpartum intervention to modify diet and physical activity similar to the Diabetes Prevention Program . The intervention was delivered by telephone , and support for breastfeeding was addressed . RESEARCH DESIGN AND METHODS The goal was to help women return to their prepregnancy weight , if it was normal , or achieve a 5 % reduction from prepregnancy weight if overweight . Eligible participants were identified shortly after a GDM diagnosis ; 83.8 % consented to be r and omly assigned to intervention or usual medical care ( 96 and 101 women , respectively ) . The retention was 85.2 % at 12 months postpartum . RESULTS The proportion of women who reached the postpartum weight goal was higher , although not statistically significant , in the intervention condition than among usual care ( 37.5 vs. 21.4 % , absolute difference 16.1 % , P = 0.07 ) . The intervention was more effective among women who did not exceed the recommended gestational weight gain ( difference in the proportion of women meeting the weight goals : 22.5 % , P = 0.04 ) . The intervention condition decreased dietary fat intake more than the usual care ( condition difference in the mean change in percent of calories from fat : −3.6 % , P = 0.002 ) and increased breastfeeding , although not significantly ( condition difference in proportion : 15.0 % , P = 0.09 ) . No differences in postpartum physical activity were observed between conditions . CONCLUSIONS This study suggests that a lifestyle intervention that starts during pregnancy and continues postpartum is feasible and may prevent pregnancy weight retention and help overweight women lose weight . Strategies to help postpartum women overcome barriers to increasing physical activity are needed", "OBJECTIVE —We evaluated whether participation in a community-based group diabetes prevention program might lead to relative changes in composite 10-year coronary heart disease ( CHD ) risk for overweight adults with abnormal glucose metabolism . RESEARCH DESIGN AND METHODS —We used the UK Prospect i ve Diabetes Study engine to estimate CHD risk for group-lifestyle and brief counseling ( control ) groups . Between-group risk changes after 4 and 12 months were compared using ANCOVA . RESULTS —Baseline 10-year risk was similar between treatment groups ( P = 0.667 ) . At 4 and 12 months , the intervention group experienced significant decreases in 10-year risk from baseline ( −3.28 % , P both CHD and type 2 diabetes in adults with pre-diabetes", "BACKGROUND Since the Diabetes Prevention Project ( DPP ) demonstrated that lifestyle weight-loss interventions can reduce the incidence of diabetes by 58 % , several studies have translated the DPP methods to public health-friendly context s. Although these studies have demonstrated short-term effects , no study to date has examined the impact of a translated DPP intervention on blood glucose and adiposity beyond 12 months of follow-up . PURPOSE To examine the impact of a 24-month , community-based diabetes prevention program on fasting blood glucose , insulin , insulin resistance as well as body weight , waist circumference , and BMI in the second year of follow-up . DESIGN An RCT comparing a 24-month lifestyle weight-loss program ( LWL ) to an enhanced usual care condition ( UCC ) in participants with prediabetes ( fasting blood glucose=95 - 125 mg/dL ) . Data were collected in 2007 - 2011 ; analyses were conducted in 2011 - 2012 . SETTING / PARTICIPANTS 301 participants with prediabetes were r and omized ; 261 completed the study . The intervention was held in community-based sites . INTERVENTION The LWL program was led by community health workers and sought to induce 7 % weight loss at 6 months that would be maintained over time through decreased caloric intake and increased physical activity . The UCC received two visits with a registered dietitian and a monthly newsletter . MAIN OUTCOME MEASURES The main measures were fasting blood glucose , insulin , insulin resistance , body weight , waist circumference , and BMI . RESULTS Intent-to-treat analyses of between-group differences in the average of 18- and 24-month measures of outcomes ( controlling for baseline values ) revealed that the LWL participants experienced greater decreases in fasting glucose ( -4.35 mg/dL ) ; insulin ( -3.01 μU/ml ) ; insulin resistance ( -0.97 ) ; body weight ( -4.19 kg ) ; waist circumference ( -3.23 cm ) ; and BMI ( -1.40 ) , all p-values reductions in metabolic indicators and adiposity ", "BACKGROUND The Diabetes Prevention Program ( DPP ) found that an intensive lifestyle intervention can reduce the development of diabetes by more than half in adults with prediabetes , but there is little information about the feasibility of offering such an intervention in community setting s. This study evaluated the delivery of a group-based DPP lifestyle intervention in partnership with the YMCA . METHODS This pilot cluster-r and omized trial was design ed to compare group-based DPP lifestyle intervention delivery by the YMCA to brief counseling alone ( control ) in adults who attended a diabetes risk-screening event at one of two semi-urban YMCA facilities and who had a BMI > or=24 kg/m2 , > or=2 diabetes risk factors , and a r and om capillary blood glucose of 110 - 199 mg/dL. Multivariate regression was used to compare between-group differences in changes in body weight , blood pressures , HbA1c , total cholesterol , and HDL-cholesterol after 6 and 12 months . RESULTS Among 92 participants , controls were more often women ( 61 % vs 50 % ) and of nonwhite race ( 29 % vs 7 % ) . After 6 months , body weight decreased by 6.0 % ( 95 % CI=4.7 , 7.3 ) in intervention participants and 2.0 % ( 95 % CI=0.6 , 3.3 ) in controls ( p total cholesterol ( -22 mg/dL vs + 6 mg/dL controls ; p YMCA sites , it was not possible to adjust for potential clustering by site . CONCLUSIONS The YMCA may be a promising channel for wide-scale dissemination of a low-cost approach to lifestyle diabetes prevention", "Purpose The purpose of the study was to examine the long-term effect of a Group Lifestyle Balance ( GLB ) program on weight , impaired fasting glucose , hypertension , and hyperlipidemia in an urban , medically underserved community . Methods This study was a single-arm prospect i ve intervention study that was design ed to test the effectiveness of a community-based GLB intervention . In sum , 638 residents from 11 targeted neighborhoods were screened for body mass index ≥ 25 kg/m2 and metabolic syndrome . Eligible individuals took part in a 12-week GLB intervention ( n = 105 ) that addressed weight loss and physical activity . Subjects were followed for 24 months . Results The probability of being at risk for diabetes and cardiovascular disease was significantly reduced by 25.7 % over the long-term follow-up . Of the participants who lost at least 5 % of their body weight following the intervention , 52.6 % maintained the 5 % weight loss at their last follow-up time , weighing about 20 lb less than they did at baseline . Conclusion Risk reduction and weight loss maintenance are possible following a GLB intervention and have substantial potential for future public health impact", "Purpose The objective was to take prevention from the clinic to the community by including a high-risk group and working with the community to tailor , enhance , deliver , and evaluate a community-based version of the Diabetes Prevention Program ’s ( DPP ) clinic-based lifestyle intervention . Methods This was a nonr and omized prospect i ve study using a single-group design . Study eligibility included a screening glucose value in the normal to prediabetes range with no current diagnosis of diabetes , overweight , not pregnant nor planning to become pregnant during study period , aged 18 to 65 , Latino , living in the study target communities , and no reported medical restrictions related to the program goals . A total of 69 individuals participated . The Healthy Living Program ( HLP ) was based on the DPP ’s 1-year intensive lifestyle program , was tailored and enhanced for a Latino community , and was delivered by community health workers . Anthropometric and paper and pencil measures were administered to examine program outcome at 6 months and 12 months . Results In general , results indicate statistically significant improvements in anthropometrics and many behavioral outcomes , particularly at 6 months . Participants demonstrated forward movement through the stages of change during the program . Conclusions Results support the effectiveness of the intervention and show that delivery of the translated version of the DPP ’s lifestyle intervention in the community by community residents holds promise as one strategy to reach people at increased risk of developing diabetes . Use of this translation model , including collaboration with community health workers , offers diabetes educators an opportunity to extend their reach into underserved communities", "Asian Americans experience diabetes at a higher rate than non-Hispanic whites . Diabetes prevention programs using lifestyle interventions have been shown to produce beneficial results , yet there have been no culturally-tailored programs for diabetes prevention in the Korean community . We explore the impact and feasibility of a pilot Community Health Worker ( CHW ) intervention to improve health behaviors and promote diabetes prevention among Korean Americans using a r and omized controlled trial . Between 2011 and 2012 , a total of 48 Korean Americans at risk for diabetes living in New York City ( NYC ) participated in the intervention . Participants were allocated to treatment or control groups . A community-based participatory research approach guided development of the intervention , which consisted of 6 workshops held by CHWs on diabetes prevention , nutrition , physical activity , diabetes complications , stress and family support , and access to health care . Changes over 6 months were examined for clinical measurements ( weight , BMI , waist circumference , blood pressure , glucose , and cholesterol ) ; health behaviors ( physical activity , nutrition , food behaviors , diabetes knowledge , self-efficacy , and mental health ) ; and health access ( insurance and self-reported health ) . In this small pilot study , changes were seen in weight , waist circumference , diastolic blood pressure , physical activity nutrition , diabetes knowledge , and mental health . Qualitative findings provide additional context ual information that inform ways in which CHWs may influence health outcomes . These findings demonstrate that a diabetes prevention program can be successful among a Korean American population in NYC , and important insight is provided for ways that programs can be tailored to meet the needs of vulnerable population ", "Purpose . To evaluate the effectiveness of FUEL Your Life , a translation of the Diabetes Prevention Program for worksites . Design . A r and omized control group design was conducted in five worksites of a large transportation company . Measures were collected pretest , posttest ( 6 months ) , and follow-up ( 12 months ) . Setting . Railroad maintenance facilities of Union Pacific Railroad . Subjects . Participants consisted of 362 workers ( 227 treatment , 135 control ) . Intervention . FUEL Your Life was translated from the Diabetes Prevention Program to better fit within the context of the worksite . The primary difference was the use of peer health coaches to provide social support and reinforcement and an occupational nurse to provide lesson content ( six sessions of 10 minutes ) to participants instead of the lifestyle coaches employed by the Diabetes Prevention Program , result ing in a less structured meeting schedule . Measures . The primary outcomes were weight and body mass index ( BMI ) , with secondary outcomes including eating behaviors , physical activity , and social support . Analysis . Latent growth modeling was used to measure changes in the outcomes over time . Results . Participants in the intervention group maintained weight/ BMI ( –.1 pounds/–.1 BMI ) , whereas the control participants gained weight/ BMI ( + 2.6 pounds/+.3 BMI ) , result ing in a statistically significant difference between groups . Fifty-five percent of intervention participants lost some weight , whereas only 35 % of the control group lost weight . Conclusions . FUEL Your Life , a low intensity intervention , was not effective for promoting weight loss , but was effective for helping workers maintain weight over a 12-month period", "Evidence from varied community setting s has shown that the Group Lifestyle Balance ( GLB ) Program and other adaptations of the Diabetes Prevention Program ( DPP ) intervention are effective in lowering diabetes risk . Most DPP data originated from studies of pre-diabetic whites , with only sparse evidence of the effect of DPP in African Americans ( AAs ) in community setting s. This paper describes the design , methods , baseline characteristics and cost effective measures , of a single-blinded , cluster-r and omized trial of a faith-based adaptation of the GLB program , Fit Body and Soul ( FBAS ) . The major aims are to test efficacy and cost utility of FBAS in twenty AA churches . R and omization occurred at the church level and 604 AA overweight/obese ( BMI ≥25kg/m(2 ) ) adults with fasting plasma glucose range from normal to pre-diabetic received either FBAS or a health-education comparison program . FBAS is a group-based , multi-level intervention delivered by trained church health advisors ( health professionals from within the church ) , with the goal of ≥7 % weight loss , achieved through increasing physical activity , healthy eating and behavior modification . The primary outcome is weight change at 12weeks post intervention . Secondary outcomes include hemoglobin A1C , fasting plasma glucose , waist circumference , blood pressure , physical activity level , quality of life measures , and cost-effectiveness . FBAS is the largest known cohort of AAs enrolled in a faith-based DPP translation . Reliance on health professionals from within the church for program implementation and the cost analysis are unique aspects of this trial . The design provides a model for faith-based DPPs and holds promise for program sustainability and widespread dissemination", "Purpose The purpose of this study was to describe the feasibility of using a community-based participatory research ( CBPR ) approach to implement the Power to Prevent ( P2P ) diabetes prevention education curriculum in rural African American ( AA ) setting s. Methods Trained community health workers facilitated the 12-session P2P curriculum across 3 community setting s. Quantitative ( based on the pre- and post-curriculum question naires and changes in blood glucose , blood pressure [ BP ] , and weight at baseline and 6 months ) and qualitative data ( based on semi-structured interviews with facilitators ) were collected . Indicators of feasibility included : dem and , acceptability , implementation fidelity , and limited efficacy testing . Results Across 3 counties , 104 AA participants were recruited ; 43 % completed ≥ 75 % of the sessions . There was great dem and for the program . Fifteen community health ambassadors ( CHAs ) were trained , and 4 served as curriculum facilitators . Content and structure of the intervention was acceptable to facilitators but there were challenges to implementing the program as design ed . Improvements were seen in diabetes knowledge and the impact of healthy eating and physical activity on diabetes prevention , but there were no significant changes in blood glucose , BP , or weight . Conclusion While it is feasible to use a CBPR approach to recruit participants and implement the P2P curriculum in AA community setting s , there are significant challenges that must be overcome", "BACKGROUND The Diabetes Prevention Program ( DPP ) lifestyle intervention reduced the incidence of type 2 diabetes mellitus ( DM ) among high-risk adults by 58 % , with weight loss as the dominant predictor . However , it has not been adequately translated into primary care . METHODS We evaluated 2 adapted DPP lifestyle interventions among overweight or obese adults who were recruited from 1 primary care clinic and had pre-DM and /or metabolic syndrome . Participants were r and omized to ( 1 ) a coach-led group intervention ( n = 79 ) , ( 2 ) a self-directed DVD intervention ( n = 81 ) , or ( 3 ) usual care ( n = 81 ) . During a 3-month intensive intervention phase , the DPP-based behavioral weight-loss curriculum was delivered by lifestyle coach-led small groups or home-based DVD . During the maintenance phase , participants in both interventions received lifestyle change coaching and support remotely-through secure email within an electronic health record system and the American Heart Association Heart360 website for weight and physical activity goal setting and self-monitoring . The primary outcome was change in body mass index ( BMI ) ( calculated as weight in kilograms divided by height in meters squared ) from baseline to 15 months . RESULTS At baseline , participants had a mean ( SD ) age of 52.9 ( 10.6 ) years and a mean BMI of 32.0 ( 5.4 ) ; 47 % were female ; 78 % , non-Hispanic white ; and 17 % , Asian/Pacific Isl and er . At month 15 , the mean ± SE change in BMI from baseline was -2.2 ± 0.3 in the coach-led group vs -0.9 ± 0.3 in the usual care group ( P self-directed group vs usual care ( P = .02 ) . The percentages of participants who achieved the 7 % DPP-based weight-loss goal were 37.0 % ( P = .003 ) and 35.9 % ( P = .004 ) in the coach-led and self-directed groups , respectively , vs 14.4 % in the usual care group . Both interventions also achieved greater net improvements in waist circumference and fasting plasma glucose level . CONCLUSION Proven effective in a primary care setting , the 2 DPP-based lifestyle interventions are readily scalable and exportable with potential for substantial clinical and public health impact . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00842426", "Background : Research on the translation of efficacious lifestyle change programs to prevent type 2 diabetes into community or clinical setting s is needed . Objective : The objective of this study was to examine the reach , implementation , and efficacy of a 6-month lifestyle program implemented in primary care by nurse practitioners ( NPs ) for adults at risk of type 2 diabetes . Methods : The NP sites ( n = 4 ) were r and omized to an enhanced st and ard care program ( one NP and one nutrition session ) or a lifestyle program ( enhanced st and ard care and six NP sessions ) . These NPs recruited adults at risk of diabetes from their practice ( n = 58 ) , with an acceptance rate of 70 % . Results : The program reached a diverse , obese , and moderately low income sample . The NPs were able to successfully implement the protocol s. The average length of the program was 9.3 months . Attendance was high ( 98 % ) , and attrition was low ( 12 % ) . The NPs were able to adopt the educational , behavioral , and psychosocial strategies of the intervention easily . Motivational interviewing was more difficult for NPs . Mixed-model repeated- measures analysis indicated significant trends or improvement in both groups for nutrition and exercise behavior . Participants of the lifestyle program demonstrated trends for better high-density lipoprotein ( HDL ) and exercise behavior compared with the enhanced st and ard care participants . Twenty-five percent of lifestyle participants met treatment goals of 5 % weight loss compared with 11 % of st and ard care participants . Discussion : A lifestyle program can be implemented in primary care by NPs , reach the targeted population , and be modestly successful . Further research is indicated", "Objective To evaluate the use and effectiveness of two “ in-home ” strategies for delivering diabetes prevention programming using cable television . Methods An individually r and omized , two-arm intervention trial including adults with diabetes risk factors living in two US cities . Interventions involved a 16-session lifestyle intervention delivered via “ video-on-dem and ” cable television , offered alone versus in combination with web-based lifestyle support tools . Repeated measures longitudinal linear regression with imputation of missing observations was used to compare changes in body weight . Results A total of 306 individuals were r and omized and offered the interventions . After 5 months , 265 ( 87 % ) participants viewed at least 1 , and 110 ( 36 % ) viewed ≥9 of the video episodes . A total of 262 ( 86 % ) participants completed a 5-month weight measurement . In intention-to-treat analysis with imputation of missing observations , mean weight loss at 5 months for both treatment groups combined was 3.3 % ( 95 % CI 0.7 - 5.0 % ) , regardless of intervention participation ( with no differences between r and omized groups ( P = 0.19 ) ) , and was 4.9 % ( 95 % CI 2.1 - 6.5 % ) for participants who viewed ≥9 episodes . Conclusions In-home delivery of evidence -based diabetes prevention programming in a reality television format , offered with or without online behavioral support tools , can achieve modest weight losses consistent with past implementation studies of face-to-face programs using similar content", "Objective . To examine whether baseline obesity severity modifies the effects of two different , primary care-based , technology-enhanced lifestyle interventions among overweight or obese adults with prediabetes and /or metabolic syndrome . Patients and Methods . We compared mean differences in changes from baseline to 15 months in clinical measures of general and central obesity among participants r and omized to usual care alone ( n = 81 ) or usual care plus a coach-led group ( n = 79 ) or self-directed individual ( n = 81 ) intervention , stratified by baseline body mass index ( BMI ) category . Results . Participants with baseline BMI 35 + had greater reductions in mean BMI , body weight ( as percentage change ) , and waist circumference in the coach-led group intervention , compared to usual care and the self-directed individual intervention ( P BMI s between 25 ≤ 35 . Mean weight loss exceeded 5 % in the coach-led intervention regardless of baseline BMI category , but this was achieved only among self-directed intervention participants with baseline BMI s < 35 . Conclusions . Baseline BMI may influence behavioral weight-loss treatment effectiveness . Research ers and clinicians should take an individual 's baseline BMI into account when developing or recommending lifestyle focused treatment strategy . This trial is registered with Clinical Trials.gov NCT00842426", "OBJECTIVE —The objective of this study was to determine if a community-based modified Diabetes Prevention Program Group Lifestyle Balance ( GLB ) intervention , for individuals with metabolic syndrome , was effective in decreasing risk for type 2 diabetes and cardiovascular disease ( CVD ) in an urban medically underserved community , and subsequently to determine if improvements in clinical outcomes could be sustained in the short term . RESEARCH DESIGN AND METHODS —This nonr and omized prospect i ve intervention study used a one-group design to test the effectiveness of a community-based GLB intervention . Residents from 11 targeted neighborhoods were screened for metabolic syndrome ( n = 573 ) and took part in a 12-week GLB intervention ( n = 88 ) that addressed safe weight loss and physical activity . RESULTS —A marked decline in weight ( 46.4 % lost ≥5 % and 26.1 % lost ≥7 % ) was observed in individuals after completion of the intervention . Of these subjects , 87.5 % ( n = 28 ) and 66.7 % ( n = 12 ) sustained the 5 % and 7 % reduction , respectively , at the 6-month re assessment . Over one-third of the population ( 43.5 % , n = 30 ) experienced improvements in one or more component of metabolic syndrome , and 73.3 % ( n = 22 ) sustained this improvement at the 6-month re assessment . Additional improvements occurred in waist circumference ( P ) and blood pressure levels ( P = 0.04 ) after adjustment for age , sex , race , mean number of GLB classes attended , and time . CONCLUSIONS —Adults in an urban medically underserved community can decrease their risk for type 2 diabetes and CVD through participation in a GLB intervention , and short-term sustainability is feasible . Future research will include long-term follow-up of these subjects", "OBJECTIVE The Diabetes Prevention Program ( DPP ) showed that intensive lifestyle intervention reduced the risk of diabetes by 58 % . This paper examines demographic , psychosocial , and behavioral factors related to achieving weight loss and physical activity goals in the DPP lifestyle participants . RESEARCH METHODS AND PROCEDURES Lifestyle participants ( n = 1079 ; mean age = 50.6 , BMI = 33.9 , 68 % female , and 46 % from minority groups ) had goals of 7 % weight loss and 150 min/wk of physical activity . Goal achievement was assessed at the end of the 16-session core curriculum ( approximately week 24 ) and the final intervention visit ( mean = 3.2 years ) as a function of demographic , psychosocial , and behavioral variables . RESULTS Forty-nine percent met the weight loss goal and 74 % met the activity goal initially , while 37 % and 67 % , respectively , met these goals long-term . Men and those with lower initial BMI were more likely to meet activity but not weight loss goals . Hispanic , Asian , and Native Americans were more likely to meet the long-term activity goals , and whites were more likely to meet the initial weight loss goal . In multivariate analyses , meeting the long-term weight loss goal and both activity goals increased with age , while psychosocial and depression measures were unrelated to goal achievement . Dietary self-monitoring was positively related to meeting both weight loss and activity goals , and meeting the activity goal was positively related to meeting the weight loss goal . Participants who met initial goals were 1.5 to 3.0 times more likely to meet these goals long-term . DISCUSSION Success at meeting the weight loss and activity goals increased with age . Initial success predicted long-term success . Self-monitoring and meeting activity goals were related to achieving and sustaining weight loss", "OBJECTIVES To improve nutrition and physical activity of county employees and promote weight loss . DESIGN R and om assignment to begin the program when first offered or after 3 months ( \" wait control \" group ) . SETTING Worksite . PARTICIPANTS Onondaga County employees ( n = 45 ) at risk for diabetes ( n = 35 ) or with diabetes ( n = 10 ) . Mean ( ±SD ) age = 51.2 ( ± 8.0 ) years and body mass index ( BMI ) = 37.3 ± ( 6.8 kg/m ) . INTERVENTION Twelve weekly healthy lifestyle sessions based on the Diabetes Prevention Program curriculum , followed by monthly sessions for up to 12 months . OUTCOMES Medical : Weight , BMI , waist circumference , blood pressure , fasting glucose , lipid , and hemoglobin A1c levels . Psychosocial/behavioral : Health-related quality of life Short Form-12 , Impact of Weight on Quality of Life Scale ) , physical activity ( International Physical Activity Question naire ) , eating behavior ( 3-Factor Eating Question naire , National Cancer Institute Fat Screener ) , job satisfaction . RESULTS The intervention group lost significant weight compared to the wait control group over the first 3 months ( mean [ 95 % CI ] , -2.23 kg [ -3.5 to 0.97 ] ) vs [ + 0.73 kg ( + 0.17 to + 1.28 ) ] , with a decrease in BMI ( P and waist circumference ( P = .004 ) , an increase in physical activity ( International Physical Activity Question naire , P = .011 ) and lower dietary fat intake ( P = .018 ) . Over 12 months , 22.5 % ( 9/40 ) lost more than 5 % body weight and 12.5 % ( 5/40 ) lost more than 7 % body weight . After the first 3 months , there was gradual partial weight regain but reduction in waist circumference was maintained . The intervention group demonstrated significant improvement in Impact of Weight on Quality of Life Scale ( P , 3-Factor Eating ( cognitive restraint P .003 , and emotional eating P = .001 ) , International Physical Activity Question naire ( P = .011 ) , and Short Form-12 Physical Component Summary ( P = .048 ) . No improvements were observed in blood pressure , lipid , hemoglobin A1c , or glucose levels . Job satisfaction was inversely related to BMI at baseline ( P = .001 ) with a trend for improvement with the modest weight loss . CONCLUSIONS A worksite intervention program can help government employees adopt healthier lifestyles and achieve modest weight loss", "BACKGROUND Older adults have high obesity rates and respond well to evidence -based weight-loss programs , such as the Diabetes Prevention Program ( DPP ) Lifestyle intervention . The goal of this study was to determine whether a translation of the DPP Lifestyle program delivered by lay health educators and conducted in senior centers is effective in promoting weight loss among older adults . DESIGN An RCT with older adults nested within senior centers . Senior centers identified lay health educators to receive training and deliver the intervention program at the senior center . Senior centers were r and omized to DPP Lifestyle program or an attention control intervention ( cognitive training ) . SETTING / PARTICIPANTS Senior centers ( N=15 ) located throughout Arkansas . Participants ( N=228 ) were obese ( BMI = 34.5±4.9 ) older ( aged 71.2±6.6 years ) adults able to engage in moderate exercise . Follow-up data were collected at 4 months on 93 % of the original cohort between February 2009 and July 2010 . INTERVENTIONS A 12-session translation of the Diabetes Prevention Program Lifestyle behavioral weight-control program delivered in group sessions by trained lay health educators . MAIN OUTCOME MEASURES Body weight was assessed by digital scale . Percentage weight loss from baseline and proportion achieving ≥5 % and ≥7 % weight loss were examined . Analyses were completed in March 2011 . RESULTS Participants attending senior centers r and omized to Lifestyle lost a significantly greater percentage of baseline weight ( 3.8 % , 95 % CI=2.9 % , 4.6 % ) than those in the control senior centers ( 0.2 % , 95 % CI= -0.6 % , -0.9 % ) after adjusting for baseline BMI and gender ( p lost ≥5 % of baseline weight compared with 5 % in the control arm ( p lost ≥7 % than did control participants ( 3 % , p=0.001 ) . CONCLUSIONS A behavioral lifestyle weight-loss intervention delivered by a lay health educator offers a promising vehicle for translation of evidence -based obesity treatment programs in underserved areas . TRIAL REGISTRATION This study is registered at Clinical trials.govNCT01377506", "The Diabetes Prevention Program is a r and omized clinical trial testing strategies to prevent or delay the development of type 2 diabetes in high-risk individuals with elevated fasting plasma glucose concentrations and impaired glucose tolerance . The 27 clinical centers in the U.S. are recruiting at least 3,000 participants of both sexes , approximately 50 % of whom are minority patients and 20 % of whom are > or = 65 years old , to be assigned at r and om to one of three intervention groups : an intensive lifestyle intervention focusing on a healthy diet and exercise and two masked medication treatment groups -- metformin or placebo -- combined with st and ard diet and exercise recommendations . Participants are being recruited during a 2 2/3-year period , and all will be followed for an additional 3 1/3 to 5 years after the close of recruitment to a common closing date in 2002 . The primary outcome is the development of diabetes , diagnosed by fasting or post-challenge plasma glucose concentrations meeting the 1997 American Diabetes Association criteria . The 3,000 participants will provide 90 % power to detect a 33 % reduction in an expected diabetes incidence rate of at least 6.5 % per year in the placebo group . Secondary outcomes include cardiovascular disease and its risk factors ; changes in glycemia , beta-cell function , insulin sensitivity , obesity , diet , physical activity , and health-related quality of life ; and occurrence of adverse events . A fourth treatment group -- troglitazone combined with st and ard diet and exercise recommendations --was included initially but discontinued because of the liver toxicity of the drug . This r and omized clinical trial will test the possibility of preventing or delaying the onset of type 2 diabetes in individuals at high risk", "BACKGROUND Although numerous studies have translated the Diabetes Prevention Program lifestyle intervention into various setting s , no study to date has reported a formal cost analysis . PURPOSE To describe costs associated with the Healthy Living Partnerships to Prevent Diabetes ( HELP PD ) trial . DESIGN HELP PD was a 24-month RCT testing the impact of a lifestyle weight-loss intervention administered through a diabetes education program and delivered by community health workers ( CHWs ) on blood glucose and body weight among prediabetics . SETTING / PARTICIPANTS In all , 301 participants with prediabetes were r and omized in Forsyth County NC . Data reported in these analyses were collected in 2007 - 2011 and analyzed in 2011 - 2012 . INTERVENTION The lifestyle weight-loss group had a 7 % weight loss goal achieved and maintained by caloric restriction and increased physical activity . The usual care group received two visits with a registered dietitian and monthly newsletters . MAIN OUTCOME MEASURES Measures are direct medical costs , direct nonmedical costs , and indirect costs over the 2-year study period . Research costs are excluded . RESULTS The direct medical cost ( in 2010 dollars ) to identify one participant was $ 16.85 . Direct medical costs per capita for participants in the usual care group were $ 142 and $ 850 for lifestyle weight-loss participants . Per capita direct costs of care outside the study were $ 7454 for the usual care group and $ 5177 for the lifestyle weight-loss group . Per capita direct nonmedical costs were $ 12,881 for the usual care group and $ 13,836 for the lifestyle weight-loss group . The lifestyle weight-loss group in HELP PD cost $ 850 in direct medical costs for 2 years , compared to $ 2631 in direct medical costs for the first 2 years of DPP . CONCLUSIONS A community-based translation of the DPP can be delivered effectively and with reduced costs", "The Think Health ! study evaluated a behavioral weight loss program adapted from the Diabetes Prevention Program ( DPP ) lifestyle intervention to assist primary care providers ( PCPs ) and auxiliary staff acting as lifestyle coaches ( LCs ) in offering weight loss counseling to their patients . In a r and omized trial conducted at five clinical sites , study participants were r and omly assigned in a 1:1 ratio within each site to either \" Basic Plus \" ( n = 137 ) , which offered PCP counseling every 4 months plus monthly LC visits during the first year of treatment , or \" Basic \" ( n = 124 ) , which offered only PCP counseling every 4 months . Participants were primarily ( 84 % ) female , 65 % African American , 16 % Hispanic American , and 19 % white . In the 72 % of participants in each treatment group with a 12-month weight measurement , mean ( 95 % CI ) 1-year weight changes ( kg ) were -1.61 ( -2.68 , -0.53 ) in Basic Plus and -0.62 ( -1.45 , 0.20 ) in Basic ( difference : 0.98 ( -0.36 , 2.33 ) ; P = 0.15 ) . Results were similar in model-based estimates using all available weight data for r and omized participants , adjusting for potential confounders . More Basic Plus ( 22.5 % ) than Basic ( 10.2 % ) participants lost ≥ 5 % of their baseline weight ( P = 0.022 ) . In a descriptive , nonr and omized analysis that also considered incomplete visit attendance , mean weight change was -3.3 kg in Basic Plus participants who attended ≥ 5 LC visits vs. + 0.53 kg in those attending the Basic Plus approach of moderate-intensity counseling by PCPs and their staff can facilitate modest weight loss , with clinical ly significant weight loss in high program attenders", "OBJECTIVE : To test the feasibility and effectiveness of a Web-based lifestyle intervention based on the Diabetes Prevention Program modified for women with recent gestational diabetes mellitus to reduce postpartum weight retention . METHODS : We r and omly allocated 75 women with recent gestational diabetes mellitus to either a Web-based lifestyle program ( Balance after Baby ) delivered over the first postpartum year or to a control group . Primary outcomes were change in body weight at 12 months from 1 ) first postpartum measured weight ; and 2 ) self-reported prepregnancy weight . RESULTS : There were no significant differences in baseline characteristics between groups including age , body mass index , race , and income status . Women assigned to the Balance after Baby program ( n=36 , three lost to follow-up ) lost a mean of 2.8 kg ( 95 % confidence interval –4.8 to −0.7 ) from 6 weeks to 12 months postpartum , whereas the control group ( n=39 , one lost to follow-up ) gained a mean of 0.5 kg ( −1.4 to + 2.4 ) ( P=.022 ) . Women in the intervention were closer to prepregnancy weight at 12 months postpartum ( mean change −0.7 kg ; −3.5 to + 2.2 ) compared with women in the control arm ( + 4.0 kg ; + 1.3 to + 6.8 ) ( P=.035 ) . CONCLUSION : A Web-based lifestyle modification program for women with recent gestational diabetes mellitus decreased postpartum weight retention . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT01158131 . LEVEL OF EVIDENCE :", "Objective : To investigate whether the effects on weight loss and cardiometabolic risk factor reduction of two technology-mediated lifestyle interventions for 15 months in a primary care-based translation trial sustained at 24 months ( that is , 9 months after the end of intervention ) . Design : This study analyzed data from an extended follow-up of participants in the original ‘ E-LITE ’ ( Evaluation of Lifestyle Interventions to Treat Elevated Cardiometabolic Risk in Primary Care)-r and omized controlled trial , which demonstrated the effectiveness of two adapted Diabetes Prevention Program ( DPP ) lifestyle interventions compared with usual primary care . Subjects : E-LITE r and omized 241 overweight or obese participants with pre-diabetes and /or metabolic syndrome to receive usual care alone ( n=81 ) or usual care plus a coach-led ( n=79 ) or self-directed intervention ( n=81 ) . The interventions provided coach-led group behavioral weight-loss treatment or a take-home , self-directed DVD using the same 12-week curriculum , followed by 12 additional months of technology-mediated coach contact and self-monitoring support . Participants received no further intervention after month 15 . A blinded assessor conducted 24-month visits by following the measurement protocol s of the original trial . Measurements include weight and cardiometabolic risk factors ( waist circumference , fasting plasma glucose , resting blood pressure , triglycerides , high- and low-density lipoprotein cholesterol , total cholesterol and triglyceride to high-density lipoprotein cholesterol ratio ) . Results : At month 24 , mean±s.e . changes in body mass index ( trial primary outcome ) and weight ( kg ) from baseline were –1.9±0.3 ( P=0.001 ) and –5.4±0.9 ( P maintaining ⩾7 % weight loss and sustained improvements in waist circumference and fasting plasma glucose levels than usual care . Conclusion : This study shows sustained benefits of the two primary care-based , technology-mediated DPP lifestyle interventions . The findings warrant replication in long-term studies involving diverse population", "OBJECTIVE To pilot test the feasibility and effectiveness of interactive voice response ( IVR ) calls targeting physical activity and healthful eating as strategies for weight loss for patients with pre-diabetes . METHODS Participants ( N=77 ) who engaged in a 90-min diabetes prevention class were r and omly assigned to receive IVR support targeting physical activity and nutrition weight loss strategies or to a no-contact control . Physical activity , dietary intake , and body weight were assessed prior to and following the 3-month intervention . RESULTS Eighty-five percent of the intervention participants completed at least half of the intervention . Participants assigned to receive the intervention lost an average of 2.6 % of body weight during the 3 months while control participants lost an average of 1.6 % . To determine the effect of the calls when used we found that those who used the system lost approximately 3 % of body weight which approached significance when compared to controls ( p IVR holds promise for follow-up encounters with patients with pre-diabetes . PRACTICE IMPLICATION S IVR can be used to provide physical activity and nutrition counseling that can enhance the potential reach and effectiveness of health professionals working with patients who have diabetes while placing a minimal burden on financial re sources and staff time", "INTRODUCTION Diabetes as a multifactorial disorder requires prevention measures based upon the modification of several risk factors simultaneously ; otherwise , there is insufficient potential for prevention . Following the success of the American Diabetes Prevention Program ( DPP ) , we implemented an intervention program in a large Israeli healthcare organization with an emphasize on Mediterranean Diet ( MedDiet ) and physical activity . The objective was to evaluate the effectiveness of two types of intervention , individual and group therapies , in reducing risk factors and in preventing or delaying the development of type 2 diabetes . METHODS Out of 180 primary care physicians , 85 who agreed to participate , were r and omly assigned , between the years 2005 and 2006 , into two groups : those who would refer pre-diabetes adult patients for individual therapy and those who would refer for group therapy . The two groups of patients consisted of 111 and 112 in each group . The intervention lasted for 6 months and discussed : the benefits of MedDiet , planning nutritional behavior and mindful eating , and the importance of physical activity . All patients were invited to participate in walking groups . Follow up lasted for 24 months and logistic , mixed models , and Cox regressions were employed . RESULTS No statistically significant differences were detected between the two intervention groups in age ; gender and clinical measurements at recruitment . Thirty nine percent of both groups developed diabetes ( entered the DR by 2012 ) , including 38.7 % from the individual therapy and 39.3 % from the group therapy ( P=0.933 ) . The mean time from 2005 until entry to the Diabetes Registry ( DR ) was 2.9 and 2.5 years for the individual and group therapy respectively ( P=0.542 ) . CONCLUSION Both interventions were equally effective in achieving the desired outcomes and time until entry to the DR . For large health organizations with a high number of pre-diabetes patients and scarce re sources , group therapy , where 12 people are reached out by one team member are preferable and more costly effective , than a one on one therapy ", "BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin", "OBJECTIVES The purpose of this study was to determine the feasibility of implementing a diabetes prevention program ( DPP ) in a rural African-American church . METHODS A six-session DPP , modeled after the successful National Institutes of Health ( NIH ) DPP , was implemented in a rural African-American church . Adult members of the church identified as high risk for diabetes , based on results of a risk question naire , were screened with a fasting glucose . Persons with prediabetes , a fasting glucose of 100 - 125 mg/dL , participated in the six-session , Lifestyle Balance Church DPP . The primary outcomes were attendance rates and changes in fasting glucose , weight and body mass index measured at baseline , six- and 12-month follow-up . RESULTS Ninety-nine adult church members were screened for diabetes risk . Eleven had impaired fasting glucose . Ten of 11 participated in the six-session intervention , for an attendance rate of 78 % . After the intervention and 12-month follow-up , there was a mean weight loss of 7.9 lbs and 10.6 lbs , respectively . CONCLUSIONS This pilot project suggests that a modified six-session DPP can be translated to a group format and successfully implemented in a church setting . Further r and omized studies are needed to determine the effectiveness of such an intervention", "OBJECTIVES We tested the effectiveness of a community-based , literacy-sensitive , and culturally tailored lifestyle intervention on weight loss and diabetes risk reduction among low-income , Spanish-speaking Latinos at increased diabetes risk . METHODS Three hundred twelve participants from Lawrence , Massachusetts , were r and omly assigned to lifestyle intervention care ( IC ) or usual care ( UC ) between 2004 and 2007 . The intervention was implemented by trained Spanish-speaking individuals from the community . Each participant was followed for 1 year . RESULTS The participants ' mean age was 52 years ; 59 % had less than a high school education . The 1-year retention rate was 94 % . Compared with the UC group , the IC group had a modest but significant weight reduction ( -2.5 vs 0.63 lb ; P = .04 ) and a clinical ly meaningful reduction in hemoglobin A1c ( -0.10 % vs -0.04 % ; P = .009 ) . Likewise , insulin resistance improved significantly in the IC compared with the UC group . The IC group also had greater reductions in percentage of calories from total and saturated fat . CONCLUSIONS We developed an inexpensive , culturally sensitive diabetes prevention program that result ed in weight loss , improved HbA1c , and improved insulin resistance in a high-risk Latino population", "Objective : The US Diabetes Prevention Program ( DPP ) and other large trials internationally have shown that an intensive lifestyle intervention can reduce the development of type 2 diabetes . We evaluated long-term effects of a lower cost , group-based adaption of the DPP lifestyle intervention offered by the YMCA . Methods : Participants were adults with BMI ≥24 kg/m2 and r and om capillary blood glucose 6.1–11.1 mmol/L who had been previously enrolled in a cluster-r and omized trial comparing a group-based DPP lifestyle intervention versus brief advice alone . Four to 12 months after completion of the initial trial , 72 % of 92 participants enrolled in an extension study , and all were offered a group lifestyle maintenance program at the YMCA . Paired t-tests were used to assess within-group changes ; ANCOVA with adjustment was used for between-group comparisons . Results : At 28 months , after both arms were offered the same 8-month lifestyle maintenance intervention , both arms had statistically significant weight losses compared to baseline ( brief advice controls : −3.6 % ; 95 % CI : −5.8 to −1.4 ; intensive lifestyle : −6.0 % ; 95 % CI : −8.8 to −3.2 ) . Participants initially assigned to the DPP also experienced significant improvements in blood pressure and total cholesterol . Discussion : The YMCA is a promising channel for dissemination of a low-cost model for lifestyle diabetes prevention . Future studies are needed to verify these findings", "OBJECTIVE To up date outcomes of the Diet-Exercise-Activity-Lifestyle ( DEAL ) program , a clinic-based diabetes prevention intervention . METHODS Changes in weight , fasting blood glucose , and 2-hour glucose after a 75-g oral glucose tolerance test were evaluated in patients who enrolled in the DEAL program between January 2007 and August 2009 . RESULTS The 221 qualified participants had a mean age of 62 years , weight of 87.4 kg , body mass index of 31.2 kg/m² , fasting glucose level of 109 mg/dL , and 2-hour glucose value of 138 mg/dL. Among the program participants , 67 % were women and 88 % were white ; 56 % had isolated impaired fasting glucose , 5 % had impaired glucose tolerance only , and 39 % had both . The 6-month follow-up medical appointment was kept by 72 % of program participants , but only 56 % attended the 12-month visit . By 6 months after baseline , 59 % had significantly lower fasting glucose concentrations , 59 % had improvement in 2-hour glucose levels , and 61 % had weight loss . Nearly 40 % , however , were nonresponders and had increased fasting glucose , 2-hour glucose , and weight by 6 months . By the 12-month visit , significant declines in fasting glucose ( P ) , 2-hour glucose ( P ) , and weight ( P = .008 ) occurred in comparison with baseline values ; however , no significant changes occurred in these measures between the 6- and 12-month visits ( P>.30 for all ) . CONCLUSION Most DEAL participants showed improvement in glucose levels and weight , but some patients exhibited worsening glucose intolerance . Factors underlying nonresponse need to be identified . Ongoing experience and analysis should help revise the DEAL program so that outcomes for all participating patients will improve", "The relationship between chronic stress and weight management efforts may be a concern for African American ( AA ) women , who have a high prevalence of obesity , high stress levels , and modest response to obesity treatment . This pilot study r and omly assigned 44 overweight/obese AA women with moderate to high stress levels to either a 12-week adaptation of the Diabetes Prevention Program Lifestyle Balance intervention augmented with stress management strategies ( Lifestyle + Stress ) or Lifestyle Alone . A trend toward greater percentage of baseline weight loss at 3-month data collection was observed in Lifestyle + Stress ( −2.7 ± 3.6 % ) compared with Lifestyle Alone ( −1.4 ± 2.3 % ; p = .17 ) and a greater reduction in salivary cortisol ( Lifestyle + Stress : −0.2461 ± 0.3985 ng/mL ; Lifestyle Alone : −0.0002 ± 0.6275 ng/mL ; p = .20 ) . These promising results suggest that augmenting a behavioral weight control intervention with stress management components may be beneficial for overweight/obese AA women with moderate to high stress levels and merit further investigation with an adequately powered trial", "Purpose This article reports the results of a community-based , culturally tailored diabetes prevention program for overweight Mexican American adults on weight loss , waist circumference , diet and physical activity self-efficacy , and diet behaviors . Methods The intervention used content from the Diabetes Prevention Program but culturally tailored the delivery methods into a community-based program for Spanish-speaking adults of Mexican descent . The design was a r and omized controlled trial ( N = 58 ) comparing the effects of a 5-month educational intervention with an attention control group . The primary study outcome was weight loss . Secondary outcomes included change in waist circumference , body mass index , diet self-efficacy , and physical activity self-efficacy . Results There were significant intervention effects for weight , waist circumference , body mass index , and diet self-efficacy , with the intervention group doing better than the control group . These effects did not change over time . Conclusions Findings support the conclusion that a community-based , culturally tailored intervention is effective in reducing diabetes risk factors in a 5-month program", "BACKGROUND The Diabetes Prevention Program ( DPP ) demonstrated that lifestyle intervention reduces risk for type 2 diabetes and the metabolic syndrome . A universal framework for translation of multiple aspects of the DPP intervention , including training , support , and evaluation is needed to enhance treatment fidelity in a variety of setting s. PURPOSE This study aims to develop a comprehensive model for diabetes prevention translation using a modified DPP lifestyle intervention . METHODS The DPP lifestyle intervention was adapted to a 12-session group-based program called Group Lifestyle Balance for implementation in the community setting . A model for training and support mirroring that of the DPP was developed for prevention professionals administering the program . The process of training/support and program implementation was evaluated for feasibility and effectiveness using a nonr and omized prospect i ve design in two phases ( N=51 , Phase 1 : 2005 - 2006 ; N=42 , Phase 2 : 2007 - 2009 ; data analysis completed 2008 - 2009 ) . A total of 93 nondiabetic individuals with BMI > or=25 kg/m(2 ) and the metabolic syndrome or prediabetes participated . Measures were collected at baseline and post-intervention for all and 6 and 12 months post-intervention for Phase 2 . RESULTS Significant decreases in weight , waist circumference , and BMI were noted in both phases from baseline . Participants in Phase 2 also demonstrated decreases in total cholesterol , non-HDL cholesterol , and systolic and diastolic blood pressure that were maintained at 12 months . Average combined weight loss for both groups over the course of the 3-month intervention was 7.4 pounds ( 3.5 % relative loss , p weight loss , respectively . More than 80 % of those achieving 7 % weight loss in the Phase-2 group maintained their weight loss at 6 months . CONCLUSIONS A comprehensive diabetes prevention model for training , intervention delivery , and support was shown to be successful and was effective in reducing diabetes and cardiovascular disease risk factors in this group of high-risk individuals", "Purpose With growing numbers of people at risk for diabetes and cardiovascular disease , diabetes educators report increasing referrals for intervention in prevention of these conditions . Diabetes educators have expertise in diabetes self-management education ; however , they are generally not prepared for delivery of chronic disease primary prevention . The purpose of this project was to determine if individuals at risk for diabetes who participate in an intervention delivered by trained diabetes educators in existing diabetes self-management education community-based programs can reduce risk factors for diabetes and cardiovascular disease . Methods Diabetes educators in 3 outpatient-hospital programs ( urban , suburban , and rural ) received training and support for implementation of the Group Lifestyle Balance program , an adaptation of the Diabetes Prevention Program lifestyle intervention , from the Diabetes Prevention Support Center of the University of Pittsburgh . Adults with prediabetes and /or the metabolic syndrome were eligible to enroll in the program with physician referral . With use of existing diabetes educator networks , recruitment was completed via on-site physician in-services , informative letters , and e-mail contact as well as participant-directed newspaper advertisement . Results Eighty-one participants enrolled in the study ( 71 women , 10 men ) . Mean overall weight loss was 11.3 lb ( 5.1 % , P fasting plasma glucose , low-density lipoprotein cholesterol , triglycerides , and blood pressure . Conclusions These results suggest that the Group Lifestyle Balance program delivered by diabetes educators was successful in reducing risk for diabetes and cardiovascular disease in high-risk individuals . Furthermore , diabetes educators , already integrated within the existing health care system , provide yet another re source for delivery of primary prevention programs in the community" ]

[ "PURPOSE We investigated the efficacy and safety of intralesional interferon alpha-2b for the treatment of Peyronie 's disease . MATERIAL S AND METHODS A total of 117 consecutive patients with a mean age of 55.1 years who had Peyronie 's disease were enrolled in a single-blind , multicenter , placebo controlled , parallel study to determine the efficacy and safety of intralesional interferon alpha-2b therapy ( Schering , Kenilworth , New Jersey ) , including 62 who received placebo and 55 who received interferon alpha-2b . Saline ( 10 ml ) in controls and interferon alpha-2b ( 5 x 10(6 ) U ) were administered biweekly for 12 weeks . Each patient was evaluated for penile curvature , plaque size and density , penile pain , erectile function and penile hemodynamics before and after study completion . Improvement in these parameters was statistically compared between the groups . RESULTS A total of 53 patients in the control arm and 50 in the interferon alpha-2b arm completed the study . Improvement in penile curvature , plaque size and density , and pain resolution was significantly greater in patients treated with interferon alpha-2b vs placebo . The increase in mean International Index of Erectile Function scores was not significantly different between the groups . Penile blood flow improvement was observed in interferon alpha-2b treated patients but not in those who received placebo . The decrease in the number of penile vascular pathologies was significantly higher in interferon alpha-2b cases . Side effects , mostly flu-like symptoms , which were frequently noted in patients on interferon alpha-2b , were mild to moderate in degree and of short duration . CONCLUSIONS This single-blind , multicenter , placebo controlled , parallel study demonstrates that intralesional interferon alpha-2b at a dose of 5 x 10(6 ) units biweekly for 12 weeks is effective and safe as minimally invasive therapy for Peyronie 's disease", "INTRODUCTION Penile duplex Doppler ultrasound ( PDDU ) is currently the preferred method for the functional evaluation of penile hemodynamics . PDDU may be used to monitor objective ly changes in penile vascular parameters in men who undergo treatment for Peyronie 's disease ( PD ) , including intralesional interferon alpha-2b ( IFN alpha-2b ) . AIM To investigate the impact of intralesional IFN alpha-2b therapy for PD on penile hemodynamics by using PDDU and to assess the objective role of PDDU in monitoring treatment outcomes . MATERIAL S AND METHODS Thirty-nine patients ( 20 in the placebo and 19 in the IFN alpha-2b treatment arm ) were enrolled in this prospect i ve , placebo-controlled , parallel study . Patients received either 10 mL saline or 5 x 10(6 ) units of IFN alpha-2b intralesional injections every other week for a total of six injections . Patients in each group were evaluated at baseline and after completion of treatment regarding changes in penile hemodynamic parameters , penile curvature , plaque size and density , pain on erection , and erectile function . Specific published criteria were used for PDDU measurements . Outcomes were statistically compared between each group by using Mann-Whitney U and chi-square tests . RESULTS The mean age of the patients and the duration of PD were similar in both groups . The improvement in penile blood flow was significantly greater in IFN alpha-2b-treated patients than those in the placebo group . The number with the nonvascular classification increased significantly in the IFN alpha-2b arm from 31.5 % to 57.8 % . Additionally , improvements in penile curvature , plaque size and density , and pain on erection were better in the IFN alpha-2b group compared with the control . No significant improvement was observed in the erectile function domain in either group . CONCLUSION This study reveals that intralesional IFN alpha-2b injections have a significant benefit on penile hemodynamic parameters . Moreover , intralesional IFN alpha-2b is an effective , minimally invasive treatment for PD , and PDDU is a useful adjunct to monitor objective ly changes in penile vascular parameters . interferon alpha-2b injection therapy on penile hemodynamics in men with Peyronie 's disease", "OBJECTIVE To evaluate the efficacy of subcutaneous interferon-alpha 2b in the treatment of Peyronie 's disease . PATIENTS AND METHODS Twenty-three men ( mean age 53 years , range 27 - 69 ) received interferon-alpha 2b in an unr and omized prospect i ve study . The drug was injected subcutaneously adjacent to the plaque three times a week for 3 weeks at a dose of 2 x 106 IU . The effect of interferon-alpha 2b on the extent of penile deviation , plaque size and erectile pain were investigated , and the drug 's side-effects were documented . The mean ( range ) follow-up was 22 ( 4 - 48 ) months RESULTS All patients had pain relief and 13 of 19 with pain before treatment became pain-free . The penile deviation was reduced in one patient ; the deviation increased despite therapy in one patient and remained stable in the others . Plaque size remained unchanged in all patients . Impaired sexual function was improved in seven ( 30 % ) of the patients . Side-effects ( myalgia , fever ) occurred after only four of 207 injections ( 2 % ) . CONCLUSIONS Subcutaneous interferon-alpha 2b is safe , well tolerated and relieves pain . However , with no objective reduction in penile deviation and plaque size , the outcome of interferon-alpha 2b therapy is generally unconvincing and the drug can not be recommended for the conservative treatment of Peyronie 's disease", "CONTEXT Conservative therapies for Peyronie 's disease ( PD ) aim to treat early-stage disease by improving clinical outcomes such as penile curvature , penile length erectile dysfunction , and pain . OBJECTIVE To summarise the available evidence regarding injection and mechanical therapies for PD treatment . EVIDENCE ACQUISITION An extensive search of Medline , Embase , and Scopus data bases retrieved English- language articles up to 15 May 2018 . The systematic review protocol was registered on PROSPERO ( CRD42017077050 ) . Inclusion criteria were as follows : adults with early or chronic PD receiving treatment with injection therapy , penile traction , or a vacuum device . EVIDENCE SYNTHESIS Fifty-two articles were selected according to the inclusion criteria -17 comparative studies and 35 cohort studies -analysing the effects of calcium channel blockers ( verapamil , nicardipine ) , collagenase Clostridium histolyticum ( CCH ) , interferon α-2b ( IFNα-2b ) , hyaluronic acid ( HA ) , onabotulinum toxin A , thiocolchicine , penile extender devices , and vacuum devices . Qualitative data from these studies suggest a clinical ly significant effect of CCH and IFNα-2b injection therapy to decrease penile curvature and conserve penile length . Verapamil and HA performed well in single-arm or case-control studies . Studies of penile traction and vacuum devices in patients with PD demonstrated some benefits in terms of curvature and penile length but only in small , underpowered , nonr and omised studies . Studies of onabotulinum toxin A injections or thiocolchicine showed significant improvements in penile curvature , but only in studies of single-arm or case-control design . CONCLUSIONS CCH and IFNα-2b injected into stable PD plaques can decrease penile curvature ; CCH can also improve penile length . However , based on available data , strong conclusions can not be drawn for other treatments , including calcium channel blockers , HA , or mechanical therapies . PATIENT SUMMARY Our systematic review of injection therapies provides evidence for improvements in penile curvature for patients with Peyronie 's disease . No robust evidence is available to support the use of other local treatments including calcium channel blockers , hyaluronic acid , or mechanical therapies" ]

[ "The British Regional Heart Study ( BRHS ) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol ( HDLC ) and incidence of coronary heart disease was eliminated by covariance adjustment . Using the proportional hazards model and adjusting for age , blood pressure , smoking , body mass index , and low-density lipoprotein cholesterol , we analyzed this relation separately in the Framingham Heart Study ( FHS ) , Lipid Research Clinics Prevalence Mortality Follow-up Study ( LRCF ) and Coronary Primary Prevention Trial ( CPPT ) , and Multiple Risk Factor Intervention Trial ( MRFIT ) . In CPPT and MRFIT ( both r and omized trials in middle-age high-risk men ) , only the control groups were analyzed . A 1-mg/dl ( 0.026 mM ) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2 % in men ( FHS , CPPT , and MRFIT ) and 3 % in women ( FHS ) . In LRCF , where only fatal outcomes were documented , a 1-mg/dl increment in HDLC was associated with significant 3.7 % ( men ) and 4.7 % ( women ) decrements in cardiovascular disease mortality rates . The 95 % confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably , and all contained the range 1.9 - 2.9 % . HDLC levels were essentially unrelated to non-cardiovascular disease mortality . When differences in analytic methodology were eliminated , a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies", "Human plasma platelet-activating factor acetylhydrolase ( PAF-AH ) is a phospholipase A2 that is primarily associated with low density lipoprotein ( LDL ) . PAF-AH activity has also been found in high density lipoprotein ( HDL ) , although it has recently been indicated that there is no PAF-AH protein in HDL . Plasma paraoxonase 1 ( PON1 ) is an HDL-associated esterase , which also exhibits PAF-AH – like activity . The effect of atorvastatin ( 20 mg per day for 4 months ) on PAF-AH and PON1 activities in patients with dyslipidemia of type IIA ( n=55 ) or type IIB ( n=21 ) was studied . In both patient groups , atorvastatin significantly reduced plasma PAF-AH activity because of the decrease in LDL plasma levels and the preferential decrease in PAF-AH activity on dense LDL subfractions ( LDL-4 and LDL-5 ) . Drug therapy did not affect HDL-associated PAF-AH activity or serum PON1 activities toward paraoxon and phenylacetate in either patient group . However , because of the reduction in LDL cholesterol levels , the ratios of HDL-associated PAF-AH and serum PON1 activities to LDL cholesterol levels were significantly increased after drug administration . The reduction of the LDL-associated PAF-AH activity and the elevation in the ratios of HDL-associated PAF-AH and PON1 activities to LDL plasma levels may represent a new dimension in the antiatherogenic effect of atorvastatin", "Objective —Diminished serum paraoxonase and arylesterase activities ( measures of paraoxonase-1 [ PON-1 ] function ) in humans have been linked to heightened systemic oxidative stress and atherosclerosis risk . The clinical prognostic use of measuring distinct PON-1 activities has not been established , and the genetic determinants of PON-1 activities are not known . Methods and Results —We established analytically robust high-throughput assays for serum paraoxonase and arylesterase activities and measured these in 3668 stable subjects undergoing elective coronary angiography without acute coronary syndrome and were prospect ively followed for major adverse cardiovascular events ( MACE= death , myocardial infa rct ion , stroke ) over 3 years . Low serum arylesterase and paraoxonase activities were both associated with increased risk for MACE , with arylesterase activity showing greatest prognostic value ( quartile 4 versus quartile 1 ; hazard ratio 2.63 ; 95 % CI , 1.97–3.50 ; P PON-1 gene that were highly significantly associated with serum paraoxonase ( 1.18 × 10 - 303 ) or arylesterase ( 4.99 × 10−116 ) activity but these variants were not associated with either 3-year MACE risk in an angiographic cohort ( n=2136 ) or history of either coronary artery disease or myocardial infa rct ion in the Coronary Artery Disease Genome-Wide Replication and Meta- Analysis consortium ( n≈80 000 subjects ) . Conclusion —Diminished serum arylesterase activity , but not the genetic determinants of PON-1 functional measures , provides incremental prognostic value and clinical reclassification of stable subjects at risk of developing MACE", "CONTEXT AND OBJECTIVE Paraoxonase 1 ( PON1 ) , an enzyme associated with high-density lipoprotein ( HDL-PON1 ) , is reported to have antioxidant and cardioprotective properties . The aim of the present study was to investigate the effects of anthocyanins on the HDL-PON1 activity and cholesterol efflux capacity in hypercholesterolemic subjects . DESIGN AND PARTICIPANTS A total of 122 hypercholesterolemic subjects were given 160 mg of anthocyanins twice daily or placebo ( n = 61 of each group ) for 24 weeks in a double-blind , r and omized , placebo-controlled trial . Participants and investigators were masked to treatment allocation . RESULTS Anthocyanin consumption significantly increased HDL cholesterol and decreased low -density lipoprotein cholesterol concentrations compared with placebo ( P Anthocyanin supplementation also increased the activity of HDL-PON1 compared with placebo ( P cholesterol efflux capacity was increased more in the anthocyanin group ( 20.0 % increase ) than in the placebo group ( 0.2 % increase ) ( P HDL-PON1 activity and the levels of lipid hydroperoxides associated with HDL confirm the relationship between PON1 activity and lipid peroxidation of lipoproteins . Furthermore , a strong positive correlation was noted between increased HDL-PON1 activity and improved cholesterol efflux capacity both before and after adjustment for HDL cholesterol and apolipoprotein AI in anthocyanin-treated subjects ( both P HDL-PON1 activity strongly prevented the antioxidant ability of HDL and attenuated the cholesterol efflux capacity of subjects from anthocyanin group . CONCLUSIONS Our observations suggest that the alterations of PON1 activity by anthocyanin observed in hypercholesterolemic HDL reflect a shift to an improvement of cholesterol efflux capacity of HDL and may provide a link between anthocyanin and cardioprotective effects", "Type 2 diabetes ( T2D ) is associated with increased oxidative stress as indicated by elevated levels of lipid peroxidation and protein oxidation products . Since reactive oxygen species ( ROS ) can cause damage to biological macromolecules including DNA , this study investigated oxidative damage to DNA using the alkaline ( pH > 13 ) comet assay in peripheral whole blood leukocytes sample d from 15 dyslipidemic T2D patients treated with simvastatin ( 20 mg/day ) , 15 dyslipidemic T2D patients not treated with simvastatin , 20 non‐dyslipidemic T2D patients , and 20 healthy individuals ( controls ) . Our results showed a greater DNA migration in terms of damage index ( DI ) ( p with statin ( DI = 67.70 ± 10.89 ) when compared to the dyslipidemic T2D patients under statin treatment ( DI = 47.56 ± 7.02 ) , non‐dyslipidemic T2D patients ( DI = 52.25 ± 9.14 ) , and controls ( DI = 13.20 ± 6.40 ) . Plasma malondialdehyde ( MDA ) and C‐reactive protein ( CRP ) levels were also increased and total antioxidant reactivity ( TAR ) and paraoxonase activity ( PON1 ) decreased in non‐dyslipidemic T2D patients and dyslipidemic T2D non‐treated with simvastatin . We also found that DI was inversely correlated with TAR ( r = −0.61 , p that simvastatin treatment plays a protective role on oxidative damage to DNA in dyslipidemic T2D patients probably reflecting a general decrease in oxidative stress in these patients . Copyright © 2010 John Wiley & Sons ,", "BACKGROUND AND STUDY AIMS The prevalence of non-alcoholic fatty liver disease ( NAFLD ) appears to be increasing . The aim of the present study was to investigate the relationship between hepatic antioxidant paraoxonase 1 ( PON1 ) activity , lipid peroxidation and antioxidant enzymes in patients with NAFLD and the effect of atorvastatin . PATIENTS AND METHODS This study was conducted on 50 patients with NAFLD and 20 normal subjects matched for age and sex . All of them were subjected to the following investigations : abdominal ultrasonography , serum PON1 activity level , liver function tests , serum lipid profile , fasting and postpr and ial blood glucose and serum levels of malondialdehyde ( MDA ) and glutathione peroxidase ( GP ) . NAFLD patients were further r and omly classified into two groups ( 25 patients each ) , groups Ia and Ib . Only group Ia received atorvastatin 40 mg tablet for 8months . RESULTS Obesity , dyslipidaemia and impaired glucose tolerance were prevalent in group I. There was a significant decrease in serum PON1 activity with a significant increase in MDA and GP activity ( i.e. , there is a significant increase in lipid peroxidation rate ) in group I compared with group II . After atorvastatin therapy , there was a significant increase in serum PNO1 activity and significant decrease in serum MDA levels . CONCLUSION Patients with NAFLD show enhanced oxidative stress which may lead to non-alcoholic steatohepatitis ( NASH ) . Reduced PON1 activity and increased MDA could be considered a biochemical marker for lipid peroxidation , which require follow-up in patients with NAFLD . Atorvastatin may have a role in prevention of , or delay , the transformation of liver steatosis into NASH", "1 Patients with advanced chronic renal disease and anaemia have decreased serum paraoxonase‐1 ( PON1 ) activity and an increased degree of oxidative stress compared with normal subjects . The present study investigated the effects of treatment of anaemia with exogenous recombinant erythropoietin ( EPO ) β and iron on levels of antibodies against oxidized low‐density lipoproteins ( ox‐LDL ) , as well as on serum PON1 activity and concentration , in predialysis patients with chronic renal disease . 2 Forty‐nine patients with chronic renal failure and haemoglobin ( Hb ) were treated over a period of 6 months with EPOβ ( 80–120 U/kg per week , s.c . ) and variable doses of iron . Selected biochemical variables were determined before and after treatment . 3 Treatment with EPOβ and iron was associated with a significant increase in mean ( ±SD ) blood Hb concentration compared with pretreatment values ( 12.8 ± 1.5 vs 9.9 ± 0.6 g/dL , respectively ; P of EPOβ was 6160 ± 3000 U/week . After 6 months of treatment , compared with pretreatment values , the median levels ( 95 % confidence intervals ) of antibodies against ox‐LDL were decreased ( 17.5 ( 10.6–24.4 ) vs 24.8 ( 11.5–38.1 ) U/mL , respectively ; P activity was slightly but significantly increased ( 123.6 ( 76.1–343.6 ) vs 101.0 ( 50.0–332.5 ) U/L , respectively ; P = 0.016 ) and the concentration of PON1 was significantly decreased ( 37.3 ( 11.8–76.2 ) vs 46.7 ( 24.6–98.0 ) mg/L , respectively ; P . There were no significant changes in total cholesterol , triglycerides or cholesterol fraction concentrations before and after treatment . 4 We suggest that EPOβ and iron treatment of anaemia promotes significant changes in serum PON1 activity and concentration and has a beneficial effect on oxidative stress in predialysis patients with chronic renal disease", "The aim of this study was to investigate the modulating effect of atorvastatin on serum paraoxonase 1 enzyme ( PON1 ) activity in type 2 diabetic Egyptian patients with or without nephropathy . The present study was carried out on the following groups : control group , which consisted of 30 healthy persons ; Group I , which consisted of 20 type 2 diabetic patients without nephropathy ; and Group II , which consisted of 20 type 2 diabetic patients with nephropathy . All the patients selected were under an antidiabetic regimen of insulin , and patients receiving antihypertensive agents were excluded from the follow-up study to avoid drug interaction fallacies . Twenty-two patients ( 15 without nephropathy and seven with nephropathy ) received atorvastatin in individually adjusted oral dosage ( range 10 - 20 mg ) once per day for 12 weeks . All cases were subjected to thorough clinical examination and history taking and measurement of serum levels of PON1 activity , malondialdehyde ( MDA ) , glutathione reductase activity , fasting glucose , total cholesterol , triglycerides , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , urea , and creatinine . Urine sample s were collected for determination of proteinuria . The obtained results showed that PON1 activity and HDL significantly decreased and fasting glucose significantly increased in Group I and Group II when compared to the control group , with significant difference in their levels between Group II and Group I. MDA , total cholesterol , and LDL levels significantly increased and glutathione reductase activity significantly decreased in Group I and Group II when compared to the control group . Urea , creatinine , and proteinuria levels showed significant increase in Group II when compared to the control group and Group I , with nonsignificant difference between control group and Group I. Atorvastatin therapy caused a significant increase in PON1 activity , and serum levels of MDA and glutathione reductase activity were significantly decreased and increased , respectively . Also , total cholesterol , triglyceride and LDL-cholesterol levels were significantly reduced with a significant increase in HDL-cholesterol levels . There was a significant modest reduction in serum urea and creatinine levels as well as in proteinuria level . Fasting glucose level was significantly reduced under the antidiabetic regimen of insulin through the follow-up period . PON1 activity showed a significant negative correlation with glucose and LDL , and a significant positive correlation with HDL in all the studied groups . It could be concluded that atorvastatin with its pleiotropic effects could provide optimal therapeutic intervention to control not only dyslipidemia , but also oxidative stress status with consequent improvement in the course of type 2 diabetes and diabetic nephropathy . More specifically , restoration of PON1 activity by atorvastatin opens a window to investigate other drugs that could provide a new adjuvant therapeutic line for better control of diabetes and diabetic nephropathy . Further research is also recommended to study the distribution of PON1 genetic polymorphism among the Egyptian population to explain the variability in its activity and its relationship with other factors that associate diabetes and its complications", "CONTEXT Paraoxonase 1 ( PON1 ) is reported to have antioxidant and cardioprotective properties . The relationship between PON1 genotypes and functional activity with systemic measures of oxidative stress and cardiovascular disease ( CVD ) risk in humans has not been systematic ally investigated . OBJECTIVE To investigate the relationship of genetic and biochemical determinants of PON1 activity with systemic measures of oxidative stress and CVD risk in humans . DESIGN , SETTING , AND PARTICIPANTS The association between systemic PON1 activity measures and a functional polymorphism ( Q192R ) result ing in high PON1 activity with prevalent CVD and future major adverse cardiac events ( myocardial infa rct ion , stroke , or death ) was evaluated in 1399 sequential consenting patients undergoing diagnostic coronary angiography between September 2002 and November 2003 at the Clevel and Clinic . Patients were followed up until December 2006 . Systemic levels of multiple structurally defined fatty acid oxidation products were also measured by mass spectrometry in 150 age- , sex- , and race-matched patients and compared with regard to PON1 genotype and activity . MAIN OUTCOME MEASURES Relationship between a functional PON1 polymorphism and PON1 activity with global indices of systemic oxidative stress and risk of CVD . RESULTS The PON1 genotype demonstrated significant dose-dependent associations ( QQ192 > QR192 > RR192 ) with decreased levels of serum PON1 activity and with increased levels of systemic indices of oxidative stress . Compared with participants with either the PON1 RR192 or QR192 genotype , participants with the QQ192 genotype demonstrated an increased risk of all-cause mortality ( 43/681 deaths [ 6.75 % ] in RR192 and QR192 and 62/584 deaths [ 11.1 % ] in QQ192 ; adjusted hazard ratio , 2.05 ; 95 % confidence interval [ CI ] , 1.32 - 3.18 ) and of major adverse cardiac events ( 88/681 events [ 13.6 % ] in RR192 and QR192 and 102/584 events [ 18.0 % ] in QQ192 ; adjusted hazard ratio , 1.48 ; 95 % CI , 1.09 - 2.03 ; P = .01 ) . The incidence of major adverse cardiac events was significantly lower in participants in the highest PON1 activity quartile ( 23/315 [ 7.3 % ] ) and 235/324 [ 7.7 % ] for paraoxonase and arylesterase , respectively ) compared with those in the lowest activity quartile ( 78/311 [ 25.1 % ] and 75/319 [ 23.5 % ] ; P adjusted hazard ratios for major adverse cardiac events between the highest and lowest PON1 activity quartiles were , for paraoxonase , 3.4 ( 95 % CI , 2.1 - 5.5 ; P < .001 ) and for arylesterase , 2.9 ( 95 % CI , 1.8 - 4.7 ; P < .001 ) and remained independent in multivariate analysis . CONCLUSION This study provides direct evidence for a mechanistic link between genetic determinants and activity of PON1 with systemic oxidative stress and prospect i ve cardiovascular risk , indicating a potential mechanism for the atheroprotective function of PON1", "Human paraoxonase ( PON1 ) is a calcium-dependent esterase closely associated with high density lipoprotein (HDL)-containing apolipoprotein AI ( apoAI ) , which has been shown to confer antioxidant properties to HDL . PON1 has been recently implicated in the pathogenesis of atherosclerosis . Low PON1 activities have been found in familial hypercholesterolemia ( FH ) and diabetes mellitus . We have undertaken a study of the effect of the lipid-lowering drug simvastatin on serum PON1 activity ( in relation to paraoxon and arylesterase activity ) , on apoAI-containing and apolipoprotein B (apoB)-containing lipoproteins , and on lipid peroxide concentrations in 64 ( 39 women and 25 men ) unrelated FH patients . We have also analyzed the influence of the PON1 - 192 and PON1 - 55 genetic polymorphisms on the response of PON1 activity to simvastatin therapy . A venous blood sample for a baseline analysis and another after 4 months of simvastatin therapy at a dosage of 20 mg per day were taken . The major effect of simvastatin on lipid traits was to decrease serum cholesterol , low density lipoprotein ( LDL ) cholesterol , and lipid peroxide concentrations by 19.9 % , 26.3 % , and 37.3 % , respectively . There was also a significant decrease in serum apoB , LDL apoB , and triglyceride concentrations ( 20.5 % , 21.1 % , and 15.6 % , respectively ) . Conversely , simvastatin had no significant influence on very low density lipoprotein – lipid content , HDL cholesterol , apoAI concentrations , and lipoprotein AI and AI : AII particles . Remarkably , serum PON1 activity toward paraoxon significantly increased during treatment with simvastatin ( 168.7±100.3 U/L before therapy versus 189.5±116.5 U/L after therapy , P = 0.005 ) . Arylesterase activity displayed only a nonsignificant trend to increase after therapy . Whereas PON1 activity levels were significantly lower in FH patients before simvastatin therapy compared with those of 124 normolipidemic subjects ( 168.7±100.3 versus 207.6±125.2 U/L , respectively;P after simvastatin therapy . After simvastatin therapy , a significantly negative correlation between PON1 activity and lipid peroxide concentration was observed ( r = −0.35 , P = 0.028 ) . The latter also strongly correlated with LDL cholesterol concentration ( r = 0.64 , P were significantly lower in the low-activity PON1 - 192 QQ and PON1 - 55 M carriers than in R carriers and in LL carriers , respectively . No significant differences were found in the therapeutic response of PON1 activity between genotype groups ( 8.5 % and 11.1 % increase for QQ homozygous and R-carrier FH patients , respectively , and 12.7 % and 9.5 % increase for LL homozygotes and M carriers , respectively ) . We conclude that simvastatin may have important antioxidant properties through increasing serum PON1 activity , perhaps as a consequence of reducing oxidative stress , by a mechanism independent of apoAI-containing lipoprotein concentration and without the influence of PON1 - 192 and PON1 - 55 genetic polymorphisms . Further studies are clearly warranted to clarify the precise mechanism by which simvastatin therapy is associated with increased PON1 activity", "Abstract . We studied the effects of the 3‐hydroxy‐3‐methylglutaryl‐CoA ( HMG‐CoA ) reductase inhibitors simvastatin and pravastatin on the in vitro susceptibility of low‐density lipoprotein ( LDL ) to oxidation . Twenty‐three hypercholesterolaemic patients ( mean serum cholesterol 9.7 mmol 1‐1 ) were treated with increasing doses of either simvastatin or pravastatin for 18 weeks . No significant differences in effect on lipid levels between the two drugs were found . Treatment result ed in lowering of total cholesterol and LDL‐cholesterol by maximally 30 % and 34 % , respectively . Chemical composition analysis showed that LDL particles contained relatively more protein and less free cholesterol and cholesteryl‐ester after treatment . The LDL cholesterol/protein ratio decreased from 1.24 ± 0.21 to 0.97 ± 0.23 ( n = 20 ) . By continuous monitoring of in vitro oxidation it appeared that LDL was less susceptible to oxidation after drug treatment . Maximal rate of diene production was significantly decreased from 19.7 ± 3.1 to 18.5 ± 3.3 nmol min‐1 mg‐1 LDL ; total diene production decreased significantly from 420.3 ± 67.6 to 380.5 ± 49.1 nmol mg‐1 LDL ; the lag time was unchanged throughout the study . These studies show that HMG‐CoA reductase inhibitors reduce the oxidizability of LDL by altering its composition", "Paraoxonase ( PON ) is an enzyme carried by high-density lipoprotein cholesterol ( HDL-C ) . Two gene polymorphisms leading to amino acid substitutions of methionine for leucine at position 55 ( M/L55 ) and arginine for glutamine at position 192 ( R/Q192 ) modulate the activity of the enzyme and possibly also lipid and apolipoprotein concentrations . Our purpose was to examine the effect of the PON genotype on HDL-C and apolipoprotein AI ( apo AI ) responses to pravastatin treatment . Fifty-one mildly hypercholesterolemic male subjects ( mean age 35 + /- 4 years ) were enrolled by this prospect i ve , r and omized , double-blind study . Lipid concentrations were measured at baseline and after 6 months of pravastatin ( n = 25 ) or placebo ( n = 26 ) therapy . Low active ( MM , ML or QQ ) and high active ( LL or RQ , RR ) PON genotype groups were related to lipid and apolipoprotein concentration changes . Pravastatin increased the apo AI concentration 12 % ( P = 0.017 , RANOVA ) and tended to increase the HDL-C concentration ( P = 0.095 , RANOVA ) in R allele carriers but not in QQ homozygotes . Significant predictors of the change in apo AI concentration during pravastatin treatment were R/Q192 genotype ( P = 0.002 ) , apo AI concentration at baseline ( P = 0.002 ) and M/L55 genotype ( P = 0.042 ) . Correspondingly , R/Q192 ( P = 0.009 ) and M/L55 ( P = 0.050 ) genotypes were the statistically significant determinants of HDL-C concentration change . The PON genotype thus modifies the effect of pravastatin on serum HDL-C and apo AI concentrations . This could partly explain the contradictory results obtained from previous studies on the effects of statins on the serum HDL-C concentration", "ABSTRACT Objective : Paraoxonase-1 ( PON-1 ) is a high-density lipoprotein ( HDL ) associated enzyme involved in the protective mechanisms of HDL . Our aim was to compare the effect of treatment with rosuvastatin and atorvastatin on serum PON-1 activity . Methods : We performed a prespecified prospect i ve study in 68 patients , part of a larger , multicentre r and omized study – RADAR ( Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport ) . Patients aged 40–80 years , all men , with established cardiovascular disease and high-density lipoprotein cholesterol ( HDL‑C ) entered a 6-week dietary run-in period before receiving treatment with rosuvastatin 10 mg or atorvastatin 20 mg daily for 6 weeks . Doses were increased after 6 weeks to rosuvastatin 20 mg or atorvastatin 40 mg and after 12 weeks to rosuvastatin 40 mg or atorvastatin 80 mg daily . Serum PON-1 activity and lipid profile were determined at baseline , 6 and 18 weeks . Results : After 18 weeks , the rosuvastatin arm showed a significant increase of PON-1 activity ( 6.39 U/L , p = 0.02 ) whereas this was not observed in the atorvastatin arm ( 1.84 U/L , p = 0.77 ) . The difference between groups did not reach significance ( p = 0.11 ) . Both rosuvastatin and atorvastatin result ed in significant ( p = 0.0001 ) and similar increases in HDL‑C after 6 weeks [ 0.06 mmol/L ( 2.32 mg/dL ) vs. 0.05 mmol/L ( 1.93 mg/dL ) ] and after 18 weeks [ 0.10 mmol/L ( 3.87 mg/dL ) vs. 0.10 mmol/L ( 3.87 mg/dL ) ] . Conclusions : Rosuvastatin treatment result ed in a significant increment of serum PON-1 activity with increasing dose while this was not observed with atorvastatin ", "Objective High-density lipoprotein (HDL)-associated antioxidant paraoxonase ( PON ) may reduce low-density lipoprotein ( LDL ) oxidation and prevent atherosclerosis . The aim of this present study was to investigate the effect of the 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor atorvastatin on hydrogen-peroxide-induced DNA damage by comet assay and the correlation between oxidative DNA damage and antioxidant PON activity . Methods Thirteen type-II/a hyperlipidemic patients were enrolled in the study . We examined the effect of 10 mg/day atorvastatin treatment on lipid levels and the degree of DNA damage in lymphocytes separated from hyperlipidemic patients , nitric oxide ( NO ) , thiobarbituric acid-reactive substances ( TBARS ) , PON levels and activity . Results After 6 months , atorvastatin treatment significantly decreased serum cholesterol and LDL-cholesterol levels . The triglyceride level did not change , and there was no significant change in the HDL cholesterol level . The visual score characteristic to the degree of DNA damage in comet assay was significantly decreased , as well as the TBARS level , while the level of NO was non-significantly increased . PON activity and the PON/HDL ratio were significantly increased after atorvastatin treatment . There was a negative correlation between DNA damage and PON activity , as well as between DNA damage and the PON/HDL ratio before and after atorvastatin treatment . Conclusion These findings show that atorvastatin treatment favorably affected the lipid profile , increasing the activity of HDL-associated PON and decreasing the cytotoxic effect of oxidative stress", "Objective : Mixed dyslipidemia , oxidative stress and inflammation are related to a high risk for cardiovascular events . The aim of this open-label r and omized study was to compare the effects of high-dose rosuvastatin , low-dose rosuvastatin plus fenofibrate and low-dose rosuvastatin plus omega 3 fatty acids on inflammation and oxidative stress indices in patients with mixed dyslipidemia . Methods : Ninety patients with mixed dyslipidemia participated in the study . Patients were r and omly allocated to receive rosuvastatin 40 mg ( n = 30 , group R ) , rosuvastatin 10 mg plus fenofibrate 200 mg ( n = 30 , group RF ) or rosuvastatin 10 mg plus omega 3 fatty acids 2 g daily ( n = 30 , group RΩ ) . Plasma and high-density lipoprotein (HDL)-associated lipoprotein-associated phospholipase A2 ( LpPLA2 ) activities , high-sensitivity C reactive protein ( hsCRP ) , plasma isoprostane and paraoxonase ( PON1 ) activities were measured at baseline and after 3 months of treatment . Results : Serum concentrations of non-HDL cholesterol and low-density lipoprotein cholesterol ( LDL-C ) were significantly reduced in all study groups . However , these changes were more pronounced in the rosuvastatin monotherapy group . In all treatment groups a significant reduction in total plasma LpPLA2 activity was observed ( by 41 , 38 and 30 % for groups R , RF and RΩ , respectively ) . This decrease was greater in the R and RF groups compared with the RΩ combination ( p 0.05 ) . HDL-LpPLA2 activity was increased more in the RF group ( + 43 % ) compared with the R and RΩ groups ( + 18 % and + 35 % , respectively ; p reduction in plasma 8-iso-PGF2α levels . A 53 % reduction of hsCRP levels was observed in the R group , while in the RF and RΩ groups the reduction was 28 and 23 % , respectively ( p in PON activities in all treatment groups . Conclusion : The greater non-HDL-C- and LDL-C-lowering efficiency of rosuvastatin monotherapy along with its more potent effect on LpPLA2 activity and hsCRP levels indicate that this regimen is a better treatment option for patients with mixed dyslipidemia", "ABSTRACT Background : Serum paraoxonase ( PON1 ) , a high density lipoprotein (HDL)-bound antioxidant enzyme , plays a role in atherosclerosis . An increase in PON1 activity has been reported following statin treatment . Objective : In the present study the following factors were evaluated : the influence of PON1 gene Q192R , L55 M and T(–107)C polymorphisms on the response of LDL oxidisability and PON1 activity to atorvastatin treatment . Research design and methods : 205 Sicilian subjects with primary hypercholesterolaemia ( HCh ) and 69 healthy subjects as controls were concurrently enrolled . Hypercholesterolaemic patients were r and omly divided into two groups : an atorvastatin group ( 10 mg/day atorvastatin ) and a placebo group . Lipid profile , markers of LDL resistance to in vitro oxidation ( lag-phase , oxidation rate and thiobarbituric acid-reactive substances ) , vitamin E content in LDL , PON1 activity and genotypes in both HCh and control subjects were determined at baseline . The same parameters were measured again after 3 weeks of treatment in both the atorvastatin and placebo groups . Results : HCh subjects showed significantly lower LDL resistance to oxidation , vitamin E content and PON1 activity levels than controls . A strong association was found among PON1 T(–107)C genotypes , LDL susceptibility to oxidation , vitamin E content and PON1 activity . After treatment , the atorvastatin group displayed a significant decrease in total cholesterol , LDL-cholesterol levels , and LDL susceptibility to oxidation , and an increase in vitamin E content and PON1 activity , compared with baseline values . Unlike PON1 activity levels , no difference among PON1 gene polymorphisms and reduction in markers of LDL oxidisability was observed . Conclusions : These results show , for the first time , that atorvastatin is able to improve the resistance to LDL oxidation independently of PON1 gene polymorphism", "Human serum paraoxonase ( PON1 ) is a high-density lipoprotein (HDL)-associated enzyme that is responsible for the protective effect of HDL against oxidation of low-density lipoprotein ( LDL ) . PON1 has a Glu to Arg polymorphism at codon 192 ( CGA-->CAA ) which is design ated R/Q192 . The R/Q192 polymorphism has been associated with coronary artery disease ( CAD ) in several , but not all , case-control studies . We prospect ively studied the association of the Q/R192 genotypes with the severity , progression and regression of CAD , plasma lipid levels , clinical events and response to treatment with fluvastatin in a well-characterized cohort . Genotypes were determined by polymerase chain reaction ( PCR ) and restriction mapping with AlwI enzyme in 356 subjects in the Lipoprotein and Coronary Atherosclerosis Study ( LCAS ) . Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following r and omization to fluvastatin or placebo . A total of 177 ( 50 % ) , 142 ( 40 % ) and 37 ( 10 % ) subjects had Q/Q , Q/R and R/R genotypes , respectively . Baseline and final plasma levels of HDL , LDL , triglyceride and other lipoproteins , lesion-specific minimum lumen diameters ( MLD ) , mean MLD , number of coronary lesions and total occlusions at baseline and follow-up and clinical event rates were not significantly different among the genotypes . There was no genotype-treatment interaction with respect to plasma lipid levels and angiographic indices of CAD . The Q/R192 variants of PON1 are not associated with severity , progression or regression of coronary atherosclerosis , plasma lipid levels , clinical events , or response to treatment with fluvastatin . Thus , the Q/R192 polymorphism is not a major risk factor in susceptibility to CAD in the LCAS population", "Background —The HDL-associated enzyme paraoxonase protects LDLs from oxidative stress . 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) appear to favorably influence the atherosclerotic process by different mechanisms . The present study examined the influence of simvastatin on paraoxonase expression and serum paraoxonase levels . Methods and Results —Simvastatin upregulated in a dose-dependent manner the activity of the promoter of the paraoxonase gene in expression cassettes transfected into HepG2 cells . Upregulation could be blocked by mevalonate and other intermediates of the cholesterol biosynthetic pathway . Simvastatin increased nuclear factors , notably sterol regulatory element – binding protein-2 , capable of binding to the paraoxonase promoter ; this was also blocked by mevalonate . Sterol regulatory element – binding protein-2 upregulated promoter activity in vitro . Patients treated with statin showed a significant increase in serum concentrations and activities of paraoxonase . Conclusions —The data indicate that simvastatin can modulate expression in vitro of the antioxidant enzyme paraoxonase and is associated with increased serum paraoxonase concentration and activity . It is consistent with effects of simvastatin treatment , which have the potential to influence beneficially antiatherogenic mechanisms at the HDL level . The study provides evidence for 1 molecular mechanism by which paraoxonase gene expression could be regulated", "OBJECTIVES The aim of our study was to examine the influence of atorvastatin on lipid parameters , particularly on HDL , and on the activity of LCAT and CETP and how they affect the activity of the HDL-associated antioxidant enzyme paraoxonase . DESIGN AND METHODS Thirty-three patients with types II.a and II.b primary hyperlipoproteinemia were enrolled into our study . The patients received atorvastatin , 20 mg daily , for 3 months . We measured the serum paraoxonase activity and concentration , oxidized LDL , LCAT and CETP activities . RESULTS Atorvastatin significantly reduced the levels of cholesterol , triglyceride , LDL-C and apoB , while it did not influence the levels of HDL-C and apo A-I. The increases in serum PON-specific activity , PON/HDL ratio and LCAT activity were significant , while oxLDL and CETP activities were significantly decreased . CONCLUSION Atorvastatin may influence the composition and function of HDL , thereby possibly increasing the activity of paraoxonase and preventing atherosclerosis", "SUMMARY Objective : High-density lipoprotein (HDL)-associated paraoxonase ( PON ) activity may play an important role in the inhibition of low-density lipoprotein ( LDL ) oxidation . Previous studies have demonstrated that serum PON activity is decreased in patients with hyperlipoproteinaemia and coronary heart disease . The study presented here examined the effect of short-term treatment with simvastatin and atorvastatin on lipids and PON activity in patients with hyperlipoproteinaemia . Research design and methods : A prospect i ve , non-blinded , single-group , cross-over , comparative trial was performed . Following an 8-week dietary run-in period , 49 patients ( 23 men and 26 women , mean age : 59.8 ± 7.9 years ) with Fredrickson type IIa . and IIb . hyperlipoproteinaemias were r and omized to receive either simvastatin 20 mg/day or atorvastatin 10 mg/day for 3 months . Following an 8-week washout period , patients were crossed-over to receive the other drug for a further 3 months . Serum lipids were measured and serum PON activity was determined spectrophotometrically using paraoxon as a substrate . Results : Simvastatin treatment significantly reduced serum cholesterol , LDL-cholesterol ( LDL-C ) and apolipoprotein ( apo ) B levels ( p had a more pronounced cholesterol , LDL-C- and apo B-lowering effect ( p 0.001 ) compared with simvastatin . Both statins also significantly reduced serum triglyceride levels ( p caused no significant change in the levels of HDL-cholesterol ( HDL-C ) and apo A1 . HDL-associated PON activity did not change significantly after simvastatin therapy , but significantly increased after atorvastatin treatment ( p : Short-term administration of simvastatin did not increase PON activity . Atorvastatin treatment had a favourable effect on lipid profile and increased the activity of HDL-associated PON ", "Although the raising effect of rosuvastatin on high-density lipoprotein cholesterol is well-established , there is a paucity of data regarding the effect of this statin on the high-density lipoprotein subfraction phenotype . A total of 150 participants without evidence of cardiovascular disease were r and omized to therapeutic lifestyle modification ( nonstatin-treated group ) or to therapeutic lifestyle modification plus rosuvastatin at 10 mg/d ( RSV10 group ) or 20 mg/d ( RSV20 group ) . We assessed the effect of rosuvastatin on the cholesterol mass of high-density lipoprotein subfractions at baseline as well as after 12 weeks post-treatment . Rosuvastatin treatment dose-dependently increased the high-density lipoprotein cholesterol ( 3.4 % vs 5.3 % in the RSV10 and RSV20 groups , respectively , P = .02 ) . A dose-related rosuvastatin-induced increase in the cholesterol concentration of large high-density lipoprotein particles was also noted ( by 11.4 % in RSV10 group vs 22.0 % in the RSV20 group , P = .01 ) . Rosuvastatin treatment increases the high-density lipoprotein cholesterol by increasing the cholesterol mass only of the larger high-density lipoprotein particles in a dose-dependent manner" ]

[ "A comparison was made of the growth responses of prepubertal naive GH-deficient children who were r and omly assigned to receive 0.3 mg/kg.week recombinant human GH administered either daily ( QD ) or three times weekly ( TIW ) over 4 yr . The effects of the two regimens on annual growth velocity , change in height SD score , bone maturation , and age at onset of puberty are presented as the mean + /- SD . During each of the 4 yr , the annual growth velocity was significantly greater in the QD vs. TIW group . At 48 months , the mean total gain in height was 9.7 cm greater in the QD group ( 38.4 + /- 5.5 ) than that in the TIW group 28.7 + /- 3.2 ; P = 0.0002 ) . The mean height SD score at the end of each year was significantly greater in the QD group . After 4 yr , the total gain in height SD score was 3.2 + /- 1.2 in the QD group compared to 1.5 + /- 0.5 in the TIW group ( P = 0.0003 ) . The height SD score at 4 yr was 0.2 in the QD group ( pretreatment , -2.9 ) compared to -1.4 in the TIW group ( pretreatment , -2.9 ) . After 4 yr of rhGH treatment , the increment in bone age was similar in the QD ( 4.9 + /- 1.0 yr ) and TIW ( 4.8 + /- 1.1 yr ) groups . The change in height age minus the change in bone age was more favorable in the QD ( 1.2 + /- 0.8 yr ) than in the TIW ( 0.0 + /- 0.9 yr ) group ( P = 0.003 ) . The mean age at onset of puberty in boys was the same in the QD ( 13.2 yr ) and TIW ( 13.0 yr ) groups ( P = 0.71 ) , and the mean bone age at the start of puberty was also similar ( 11.5 in QD and 11.3 in TIW groups ; P = 0.66 ) . The advantages of QD rhGH treatment in prepubertal GH-deficient children after 4 yr were additional gains of 1.7 height SD score and 9.7 cm in height over those treated with the TIW regimen ( P = 0.0002 )", "OBJECTIVE . The goal was to determine how often common laboratory tests yield normal results at the time of diagnosis for children with inflammatory bowel disease . METHODS . Data were obtained from a registry of children with newly diagnosed inflammatory bowel disease who were enrolled prospect ively in 18 US/Canadian centers . Laboratory values investigated included hemoglobin level , platelet count , albumin level , and erythrocyte sedimentation rate . Disease severity was categorized by physician global assessment . RESULTS . A total of 526 children ( mean age : 11.6 years ; 58 % male ; 392 with Crohn disease and 134 with ulcerative colitis ) were studied . All 4 values were normal for 21 % of patients with mild Crohn disease and 54 % with mild ulcerative colitis . In contrast , only 3.8 % of children with moderate/severe Crohn disease and 4.3 % with moderate/severe ulcerative colitis had normal results for all 4 tests . The erythrocyte sedimentation rate was least likely to be normal ; overall , 26 % of patients with inflammatory bowel disease had a normal erythrocyte sedimentation rate , including 18 % with moderate/severe disease . Hemoglobin levels were normal for 32 % , platelet counts for 50 % , and albumin levels for 60 % . There was no clear association between Crohn disease location and either severity or number of normal laboratory values . In contrast , there were direct correlations between ulcerative colitis disease severity and both the extent of bowel inflammation and the number of abnormal laboratory tests . CONCLUSION . The presence of normal screening laboratory studies should not dissuade clinicians from considering a diagnosis of inflammatory bowel disease", "GH is often used to treat children with idiopathic short stature despite the lack of definitive , long-term studies of efficacy . We performed a r and omized , double-blind , placebo-controlled trial to determine the effect of GH on adult height in peripubertal children . Subjects ( n = 68 ; 53 males and 15 females ) , 9 - 16 yr old , with marked , idiopathic short stature [ height or predicted height received either GH ( 0.074 mg/kg ) or placebo sc three times per week until they were near adult height . At study termination , adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr . Adult height was greater in the GH-treated group ( -1.81 + /- 0.11 SDS , least squares mean + /- sem ) than in the placebo-treated group ( -2.32 + /- 0.17 SDS ) by 0.51 SDS ( 3.7 cm ; P GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS . Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS ( 0.52 SDS ; 3.8 cm ; P GH treatment increases adult height in peripubertal children with marked idiopathic short stature", "OBJECTIVE Our objective was to assess final height ( FH ) and adverse effects of combined GH and GnRH agonist ( GnRHa ) treatment in short adolescents born small for gestational age or with normal birth size ( idiopathic short stature ) . DESIGN AND PATIENTS Thirty-two adolescents with Tanner stage 2 - 3 , age and bone age ( BA ) less than 12 yr for girls or less than 13 yr for boys , height sd score ( SDS ) less than -2.0 SDS or between -1.0 and -2.0 SDS plus a predicted adult height ( PAH0 ) less than -2.0 SDS were r and omly allocated to receive GH plus GnRHa ( n=17 ) or no treatment ( n=15 ) for 3 yr . FH was assessed at the age of 18 yr or older in girls or 19 yr or older in boys . RESULTS FH was not different between treatment and control groups . Treated children had a larger height gain ( FH-PAH0 ) than controls : 4.4 ( 4.9 ) and -0.5 ( 6.4 ) cm , respectively ( P height gain at treatment withdrawal was lost , result ing in a mean gain of 4.9 cm ( range , -4.0 to 12.3 cm ) compared with controls . Treatment did not affect body mass index or hip bone mineral density . Mean lumbar spine bone mineral density and bone mineral apparent density tended to be lower in treated boys , albeit statistically not significant . CONCLUSION Given the expensive and intensive treatment regimen , its modest height gain results , and the possible adverse effect on peak bone mineralization in males , GH plus GnRHa can not be considered routine treatment for children with idiopathic short stature or persistent short stature after being born small for gestational age", "BACKGROUND Short-term studies have demonstrated acceleration of growth rate following administration of biosynthetic human growth hormone ( r-hGH ) to short normal children . We describe the effect of such treatment on final height . METHODS This was an open study of consecutive referrals to a growth disorder clinic from which 16 short children ( height st and ard deviation score [ SDS ] -2.17 [ range -1.8 to -3.3 ] ; height velocity SDS -0.44 [ 0.33 ] ; peak serum GH response to stimulation 27.9 mU/L [ 9.2 ] were treated with r-hGH , and 7 short children who declined treatment ( height SDS -2.34 [ 0.61 ] ; height velocity SDS -0.36 [ 0.28 ] ; peak serum GH response 28.2 mU/L [ 6.8 ] ) acted as an observation group . Subcutaneous r-hGH dose ranged between 12.2 and 21.0 U/m2 per week ( 0.02 - 0.04 mg/kg per day ) for the first 2 years of treatment and 20 U/m2 per week thereafter , 3 untreated children were lost to long-term follow-up . FINDINGS r-hGH significantly increased the difference in final height compared with pretreatment predicted height ( + 0.42 SDS [ 0.79 ] , p = 0.03 ) but this change was not significantly greater than that of the observation group ( + 0.16 SDS [ 0.20 ] ) . Treatment had no effect on the timing of puberty . Boys progressed slightly faster through puberty , associated with an acceleration in bone-age maturation . No untoward effects on glucose metabolism were observed . Long-term therapy did not alter body-fat distribution or blood pressure . INTERPRETATION Long-term therapy in this group of children appears safe but the small increment in final height , approximately 2.8 cm in boys and 2.5 cm in girls , does not justify the widespread use of r-hGH for short normal children", "OBJECTIVES To investigate in an open-label r and omized study , the effect of two doses of growth hormone ( GH ) on final height and height velocity during the first 2 years of treatment of children with idiopathic short stature ( mean baseline height st and ard deviation score [ SDS ] -3.2 ) . STUDY DESIGN Patients were treated with GH at 0.24 mg/kg/week , 0.24 mg/kg/week for the first year and at 0.37 mg/kg/week thereafter ( 0.24 - ->0.37 ) , or 0.37 mg/kg/week . Final height was evaluated in 50 patients at study completion ( mean treatment duration , 6.5 years ) . RESULTS Patients who received 0.37 mg/kg/week ( n = 72 ) experienced a significantly greater increase in height velocity than those who received 0.24 mg/kg/week ( n = 70 ) ( treatment difference = 0.8 cm/year ; P = .003 ) or 0.24 - ->0.37 mg/kg/week ( n = 67 ) ( treatment difference = 0.9 cm/year ; P = .001 ) . For the 50 patients for whom final height measurements were available , mean height SDS increased by 1.55 , 1.52 , and 1.85 SDS , respectively , for the three dose groups . For the primary comparison between the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups , the mean treatment difference ( adjusted for differences in baseline predicted height SDS ) was 0.57 SDS ( 3.6 cm ; P = .025 ) . Mean overall height gains ( final height minus baseline predicted height ) were 7.2 cm and 5.4 cm for the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups , respectively , without dose effects on safety parameters . Final height measurements were within the normal adult height range for 94 % of patients r and omized to 0.37 mg/kg/week who continued to final height . CONCLUSION GH treatment dose-dependently increases height velocity and final height in children with idiopathic short stature", "CONTEXT The effect of GH therapy in short non-GH-deficient children , especially those with idiopathic short stature ( ISS ) , has not been clearly established owing to the lack of controlled trials continuing until final height ( FH ) . OBJECTIVE The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children , mainly with ISS , compared with untreated controls . DESIGN AND SETTING A r and omized , controlled , long-term multicenter trial was conducted in Sweden . INTERVENTION Two doses of GH ( Genotropin ) were administered , 33 or 67 microg/kg.d ; control subjects were untreated . SUBJECTS A total of 177 subjects with short stature were enrolled . Of these , 151 were included in the intent to treat ( AllITT ) population , and 108 in the per protocol ( AllPP ) population . Analysis of ISS subjects included 126 children in the ITT ( ISSITT ) population and 68 subjects in the PP ( ISSPP ) population . MAIN OUTCOME MEASURES We measured FH sd score ( SDS ) , difference in SDS to midparenteral height ( diff MPHSDS ) , and gain in heightSDS . RESULTS After 5.9+/-1.1 yr on GH therapy , the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 ( 33 microg/kg.d , -1.7+/-0.70 ; and 67 microg/kg.d , -1.4+/-0.86 ; P MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 ( P gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 ( P GH therapy was safe and had no impact on time to onset of puberty . A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four population s. CONCLUSION GH treatment significantly increased FH in ISS children in a dose-dependent manner , with a mean gain of 1.3 SDS ( 8 cm ) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls", "Background / Aims : The effects of biosynthetic human growth hormone ( r-hGH ) in children with familial short stature ( FSS ) are varied . We determined whether responsivity to r-hGH in FSS is dose-dependent . Method : R and omised trial of two doses ( 20 or 40 IU/m2 body surface area/week by daily subcutaneous injection ) of r-hGH in 29 ( 24 male , 5 female ) FSS children with assessment at adult height . Results : Age range at presentation was 5.1–10.5 years , height less than 1.5 st and ard deviation scores ( SDS ) below the mean , height velocity SDS greater than –1.5 and peak growth hormone response to provocative testing over 13.5 mU/l . Adult height data ( SDS ) at 16.5 ± 2.1 years for the low-dose group and 16.1 ± 1.1 years for the high-dose group ( p = 0.62 ) were similar [ low dose –1.06 ( SD 0.75 ) , high dose –1.02 ( SD 0.83 ) ; p = 0.88 ] . The incremental effect of both doses on stature was minimal [ low-dose difference in height actual-predicted 0.79 ( SD 0.94 ) , high dose 1.27 ( SD 0.88 ) ; p = 0.12 ] . Conclusion : Using this r-hGH dosing schedule there were little short- or long-term effects on height in children with FSS", "We measured adult heights ( Ht ) of 94 healthy GH-sufficient children ( peak GH > 10 ng/mL , polyclonal RIA ) whose Ht at presentation were more than 2 SD below the mean for chronological age , with normal weight-to-Ht ratios , normal body proportions , and pathologic growth velocity for chronological age . Group 1 ( n 36 , 6 females ) received st and ardized doses ( 0.3 mg/kg x week ) of GH ( mean duration = 41 months ) , while group 2 ( n = 58 , 17 females ) received no treatment . Our conclusion was that the mean final Ht SD score in the GH-treated group ( -1.5 ) was significantly greater than in the untreated group ( -2.1 ) ; P short stature was evident in both groups : the midparental Ht SD score was -1.1 in the treated and -1.0 in the untreated group . Midparental Ht was met or exceeded by 42 % of the GH-treated group but only 15 % of the untreated group . Final Ht was not significantly different from predicted Ht , except from GH-treated girls , who exceeded their predicted Ht . Although the mean Ht gains ( 6.8 cm in girls and 3 cm in boys ) were modest and variable , GH treatment provided significantly better Ht outcomes for the majority of children with idiopathic growth failure", "Idiopathic short stature ( ISS ) includes a heterogeneous group of patients with common characteristics to those of familial short stature and constitutional delay . Some authors state that these children can often respond to GH treatment , thus increasing their adult height . The aims of this study were to determine the effect of GH treatment ( 0.5 - 0.7 IU/kg/week ) and the influence of some initial variables on adult height in patients with ISS . It was a non-r and omized , observational study of 30 boys with ISS and a historical control group of 42 patients . The patients were followed until achieving their adult height . The mean height gain of the treated group attributable to GH was 4.5 cm . A stepwise regression model considering predicted adult height and target height as independent variables and final height as dependent variable gave an R2 coefficient of 0.38 . We conclude that GH significantly increases final height in boys with ISS", "Recombinant human growth hormone ( rhGH ) is approved in the United States for treatment of idiopathic short stature ( ISS ) . The occurrence of adverse events ( AEs ) and the long-term safety of rhGH treatment in this patient population are review ed . Data were analyzed from postmarketing surveillance studies that included ISS patients , prospect i ve ISS treatment trials and studies of specific AEs in smaller groups of rhGH-treated children . Frequency rates of targeted AEs ( i.e. , scoliosis , slipped capital femoral epiphysis , intracranial hypertension , pancreatitis ) in patients with ISS are similar to or lower than the rates observed in other rhGH-treated conditions . At dosages of 0.24–0.37 mg/kg/week , rhGH treatment in children with ISS does not adversely affect blood glucose levels . At dosages ≧0.3 mg/kg/week , a dose-dependent increase in mean fasting and stimulated insulin levels is observed . Current evidence derived from ‘ on-treatment ’ surveillance studies suggests that rhGH does not increase the risk for new malignancies in children with ISS.The safety profile of rhGH at doses ≤0.37 mg/kg/week for the treatment of children with ISS is similar to or better than the profile seen in other rhGH-treated conditions and is not associated with any predictable AEs . Due to a continuing trend toward dose escalation to achieve greater height-promoting effects and the possibility of delayed post-treatment effects of hyperinsulinemia and /or heightened GH and insulin-like growth factor I exposure on cancer risk , caution and ongoing scrutiny of risks versus benefits are warranted", "Many children with idiopathic short stature ( ISS ) remain short as adults . Height can be improved permanently by growth hormone ( GH ) treatment , as in children with Turner syndrome or born small for gestational age . Although GH treatment for ISS is an approved indication in the United States , there is ongoing controversy in Europe about approving GH treatment for this indication as well as determining the optimal mode of treatment . In addition to data from r and omized controlled trials , data from pharmacoepidemiological surveys such as the Pfizer International Growth Study Data base ( KIGS ) have provided substantial information about the short-term and long-term effects of GH on growth and adult height in children with ISS . Based on published articles and a recent survey from KIGS on 454 patients who have reached adult height , we attempted to categorize those children with ISS who have the greatest chances of achieving a normal adult height , or at least gain the most height following GH treatment . This analysis provides a rational basis for discussion about the most efficacious and cost-effective uses of GH treatment in children with ISS", "Recombinant human GH therapy to children with idiopathic short stature ( ISS ) increases growth velocity , but its effect on final height ( FH ) is still uncertain . The aim of this study was to investigate the effect of recombinant human GH on FH of patients with ISS who were treated according to two protocol s in comparison to untreated historical controls . In study 1 ( n = 24 ) , all patients were treated with 14 IU ( 4.6 mg)/m(2 ) body surface x wk in the first year ; thereafter the dosage was doubled if the growth response was insufficient . In study 2 ( n = 34 ) , patients were r and omized into three arms : 18 IU ( 6 mg)/m(2 ) x wk ; 27 IU ( 9 mg)/m(2 ) x wk ; and 18 IU/m(2 ) x wk in the first year , followed by 27 IU/m(2 ) x wk thereafter . Observed or estimated FH was available for 53 patients . Thirty-four untreated controls from the same centers were available for comparison . Mean FH SD score in GH-treated children was -2.1 , vs. -2.4 in controls ( -2.4 ) ( NS ) , but height SD score gain ( 1.3 vs. 0.7 ) and the difference between FH and predicted adult height ( 4.0 vs. 0.8 cm ) were significantly greater . The growth response on an initial dosage of 27 IU/m(2 ) x wk ( 6.9 cm ) was significantly better than on other regimens ( 2.8 cm ) . We conclude that a GH dosage of 27 IU ( 9 mg)/m(2 ) x wk to prepubertal children with ISS leads to a mean FH gain of approximately 7 cm , whereas regimens starting on lower dosages are less efficacious", "BACKGROUND There are few data on the long-term outcome of growth-hormone treatment in short normal children . We assessed the impact of growth-hormone treatment on pubertal development and near-final height in girls . METHODS In a r and omised controlled trial , we studied ten girls , with a mean age of 8.07 years and height 2 SDs or more below the mean for their age , and eight short untreated controls matched for age , and 20 short untreated girls who did not give consent for r and omisation . The girls received either 30 IU/m2 somatropin per week as daily subcutaneous injections or no treatment . We assessed pubertal staging and height gain every 6 months . FINDINGS Eight treated girls completed a mean of 6.2 years ' therapy . By a mean age of 16.4 years , their mean height SD score had changed significantly from -2.42 to -1.14 ( p=0.008 ) and they were , on average , 7.5 cm taller than the girls in the control group ( height SD scores did not change significantly from -2.55 ) and 6.0 cm taller than the non-consent group . The timing of each pubertal stage , and the age and amplitude of peak height velocity were similar for all groups . INTERPRETATION Growth-hormone therapy effectively increased height SD score among short normal girls started on treatment in early to mid childhood , with no untoward effect on pubertal progression", "Background : C and i date s for specialty drugs , the fastest growing and costliest pharmaceuticals , typically originate with primary care referrals . However , little is known about what drives such referrals — especially for large population s such as short , otherwise normal children ( idiopathic short stature ) . Recent exp and ed approval of growth hormone ( GH ) makes more than 585,000 US children eligible for such treatment , potentially costing over $ 11 billion/y . Methods : To quantify the relative impact of patient physiological indicators , physician characteristics , and consumer preferences on referrals to endocrinologists ( and potential access to GH ) for short children , a national study of 1268 r and omly selected US pediatricians was conducted , based on a full factorial experimental design in a structured survey . Results : While patient indicators ( height , growth pattern ) influenced referrals ( P drivers ( family concern ) and physician attitudes had almost as great an impact — especially for children with less severe growth impairment ( P short stature impairs emotional well-being and physician characteristics ( female , older , shorter , beliefs about drug company information ) increased referrals ( P children with short stature strikingly susceptible to nonphysiological influences on referrals that render them c and i date s for this specialty drug . Only 1 additional referral per US pediatrician would likely increase GH costs by over $ 100 million/y" ]

[ "A study was made of the effect of high or low intake of sucrose for periods of 14 days in a group of nineteen apparently healthy men . The high sucrose diet produced no change in blood levels of cholesterol or phospholipids , or in glucose tolerance , but it produced a significant rise in triglycerides in all nineteen men . In six of them , there was in addition a rise in serum immunoreactive insulin , especially during the glucose tolerance test , and these same six subjects also showed a considerable increase in weight and a significant increase in platelet adhesiveness . There was no difference between the six subjects and the remaining thirteen in any of the other measurements , or in the diets they consumed during the experiment . The changes produced by sucrose had disappeared , or nearly so , after 14 days of normal diet . It is suggested that the effect of sucrose in producing hyperinsulinism may be more relevant to its possible role in the aetiology of ischaemic heart disease than its effect on blood lipids . It is further suggested that only some individuals are susceptible to the development of ischaemic heart disease by dietary sucrose , and that these may be identified as those that show ‘ sucrose-induced hyperinsulinism ’", "The effects of several high carbohydrate foods on fasting serum cholesterol , phospholipids , and triglyceride levels were tested in 12 young men . The men were distributed into four groups , each of which was given a diet containing a different supplement . The four supplements ( 500 kcal of carbohydrate each ) contained , respectively , sucrose , wheat flour , mixed fruits , and mixed vegetables . Egg white was added as needed to equalize protein in all the supplements . In consecutive 2-week periods , the supplements were exchanged so that in four periods each group received every supplement . Fasting blood sample s were taken on the last 3 days of each period . There was no significant difference in serum cholesterol levels except for the vegetable diet , which produced much lower serum cholesterol than any of the other three diets . The serum phospholipids were also lower with the vegetable diet than with any of the other diets . No significant difference in serum triglycerides was found between the four diets . In a second similar experiment , diets containing sucrose , wheat flour , chickpeas , and a mixture of dry peas and beans were compared . No significant between-diets difference was found for either cholesterol , phospholipids , or triglycerides in this experiment . These results indicate that in 2-week dietary periods sucrose does not cause higher fasting serum cholesterol , phospholipids , or triglycerides than either wheat flour or dry leguminous seeds in amounts containing isocaloric quantities of starch . Am . J. Clin . Nutr . 27 : 1043 - 105 1 , 1974", " Twelve carbohydrate-sensitive men selected due to their abnormally high insulin responses to a sucrose load and 12 men with normal insulin responses were fed diets containing 0 , 7.5 , and 15 % fructose for 5 wk each in a cross-over design . The diets contained 43 % total carbohydrate , 42 % fat , and 15 % protein . Initial fasting total cholesterol and low-density lipoprotein cholesterol were higher in the hyperinsulinemic men than in the controls . Diastolic blood pressure was not affected by diet , but systolic blood pressure was slightly higher after the men consumed the 0 % fructose diet . Free fatty acids were not different . Total plasma cholesterol and low-density lipoprotein cholesterol were higher after the men consumed 7.5 and 15 % fructose than when they consumed the 0 % fructose diet . Plasma triglyceride increased significantly as fructose in the diets of the hyperinsulinemics increased , but was not affected in the controls . These changes in blood lipids are associated with heart disease", "Ten hyperinsulinemic and 11 nonhyperinsulinemic men consumed for 5 wk each in a cross-over design a diet , similar to one currently consumed in the United States , with 20 % of the kilocalories from either fructose or high-amylose cornstarch to determine the effects of the two diets on various blood metabolites considered to be risk factors associated with heart disease . In the hyperinsulinemic men the intake of fructose as compared with cornstarch significantly increased total triglycerides and their lipoprotein distribution ; total and very-low-density lipoprotein cholesterol ; apoproteins B-100 , C-II , C-III ; and uric acid . In the nonhyperinsulinemic men total triglycerides , total and low-density lipoprotein cholesterol and uric acid were significantly greater after the consumption of fructose than after cornstarch . The results indicate that in a diet high in saturated fatty acids and cholesterol , fructose increases the levels of risk factors associated with heart disease , especially in hyperinsulinemic men", "OBJECTIVE To test the hypothesis that family dietary coaching would improve nutritional intakes and weight control in free-living ( noninstitutionalized ) children and parents . DESIGN R and omized controlled trial . SETTING Fifty-four elementary schools in Paris , France . PARTICIPANTS One thous and thirteen children ( mean age , 7.7 years ) and 1013 parents ( mean age , 40.5 years ) . INTERVENTION Families were r and omly assigned to group A ( advised to reduce fat and to increase complex carbohydrate intake ) , group B ( advised to reduce both fat and sugar and to increase complex carbohydrate intake ) , or a control group ( given no advice ) . Groups A and B received monthly phone counseling and Internet-based monitoring for 8 months . OUTCOME MEASURES Changes in nutritional intake , body mass index ( calculated as weight in kilograms divided by height in meters squared ) , fat mass , physical activity , blood indicators , and quality of life . RESULTS Compared with controls , participants in the intervention groups achieved their nutritional targets for fat intake and to a smaller extent for sugar and complex carbohydrate intake , leading to a decrease in energy intake ( children , P Mean changes in body mass index were similar among children ( group A , + 0.05 , 95 % confidence interval [ CI ] , - 0.06 to 0.16 ; group B , + 0.10 , 95 % CI , - 0.03 to 0.23 ; control group , + 0.13 , 95 % CI , 0.04 - 0.22 ; P = .45 ) , but differed in parents ( group A , + 0.13 , 95 % CI , - 0.01 to 0.27 ; group B , - 0.02 , 95 % CI , - 0.14 to 0.11 ; control group , + 0.24 , 95 % CI , 0.13 - 0.34 ; P = .001 ) , with a significant difference between group B and the control group ( P = .01 ) . CONCLUSIONS Family dietary coaching improves nutritional intake in free-living children and parents , with beneficial effects on weight control in parents . Trial Registration clinical trials.gov Identifier : NCT00456911", "BACKGROUND The consumption of sucrose-sweetened soft drinks ( SSSDs ) has been associated with obesity , the metabolic syndrome , and cardiovascular disorders in observational and short-term intervention studies . Too few long-term intervention studies in humans have examined the effects of soft drinks . OBJECTIVE We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition ( in liver and muscle tissue ) . DESIGN Overweight subjects ( n = 47 ) were r and omly assigned to 4 different test drinks ( 1 L/d for 6 mo ) : SSSD ( regular cola ) , isocaloric semiskim milk , aspartame-sweetened diet cola , and water . The amount of intrahepatic fat and intramyocellular fat was measured with (1)H-magnetic resonance spectroscopy . Other endpoints were fat mass , fat distribution ( dual-energy X-ray absorptiometry and magnetic resonance imaging ) , and metabolic risk factors . RESULTS The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat ( 132 - 143 % , sex-adjusted mean ; P skeletal muscle fat ( 117 - 221 % ; P visceral fat ( 24 - 31 % ; P blood triglycerides ( 32 % ; P total cholesterol ( 11 % ; P Total fat mass was not significantly different between the 4 beverage groups . Milk and diet cola reduced systolic blood pressure by 10 - 15 % compared with regular cola ( P diet cola had effects similar to those of water . CONCLUSION Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk , diet cola , and water . Thus , daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases . This trial is registered at clinical trials.gov as NCT00777647", "IMPORTANCE Epidemiologic studies have suggested that higher intake of added sugar is associated with cardiovascular disease ( CVD ) risk factors . Few prospect i ve studies have examined the association of added sugar intake with CVD mortality . OBJECTIVE To examine time trends of added sugar consumption as percentage of daily calories in the United States and investigate the association of this consumption with CVD mortality . DESIGN , SETTING , AND PARTICIPANTS National Health and Nutrition Examination Survey ( NHANES , 1988 - 1994 [ III ] , 1999 - 2004 , and 2005 - 2010 [ n = 31,147 ] ) for the time trend analysis and NHANES III Linked Mortality cohort ( 1988 - 2006 [ n = 11 733 ] ) , a prospect i ve cohort of a nationally representative sample of US adults for the association study . MAIN OUTCOMES AND MEASURES Cardiovascular disease mortality . RESULTS Among US adults , the adjusted mean percentage of daily calories from added sugar increased from 15.7 % ( 95 % CI , 15.0%-16.4 % ) in 1988 - 1994 to 16.8 % ( 16.0%-17.7 % ; P = .02 ) in 1999 - 2004 and decreased to 14.9 % ( 14.2%-15.5 % ; P added sugar ( 71.4 % ) and approximately 10 % consumed 25 % or more in 2005 - 2010 . During a median follow-up period of 14.6 years , we documented 831 CVD deaths during 163,039 person-years . Age- , sex- , and race/ethnicity-adjusted hazard ratios ( HRs ) of CVD mortality across quintiles of the percentage of daily calories consumed from added sugar were 1.00 ( reference ) , 1.09 ( 95 % CI , 1.05 - 1.13 ) , 1.23 ( 1.12 - 1.34 ) , 1.49 ( 1.24 - 1.78 ) , and 2.43 ( 1.63 - 3.62 ; P added sugar with those who consumed less than 10.0 % of calories from added sugar . These findings were largely consistent across age group , sex , race/ethnicity ( except among non-Hispanic blacks ) , educational attainment , physical activity , health eating index , and body mass index . CONCLUSIONS AND RELEVANCE Most US adults consume more added sugar than is recommended for a healthy diet . We observed a significant relationship between added sugar consumption and increased risk for CVD mortality", "Background The replacement of sucrose with HFCS in food products has been suggested as playing a role in the development of obesity as a public health issue . The objective of this study was to examine the effects of four equally hypocaloric diets containing different levels of sucrose or high fructose corn syrup ( HFCS ) . Methods This was a r and omized , prospect i ve , double blind trial , with overweight/obese participants measured for body composition and blood chemistry before and after the completion of 12 weeks following a hypocaloric diet . The average caloric deficit achieved on the hypocaloric diets was 309 kcal . Results Reductions were observed in all measures of adiposity including body mass , BMI , % body fat , waist circumference and fat mass for all four hypocaloric groups , as well as reductions in the exercise only group for body mass , BMI and waist circumference . Conclusions Similar decreases in weight and indices of adiposity are observed when overweight or obese individuals are fed hypocaloric diets containing levels of sucrose or high fructose corn syrup typically consumed by adults in the United States", "The long-term impact of dietary carbohydrate type , in particular sucrose , on insulin resistance and the development of diabetes and atherosclerosis is not established . Current guidelines for the healthy population advise restriction of sucrose intake . We investigated the effect of high- versus low-sucrose diet ( 25 vs. 10 % , respectively , of total energy intake ) in 13 healthy subjects aged 33 ± 3 years ( mean ± SE ) , BMI 26.6 ± 0.9 kg/m2 , in a r and omized crossover design with sequential 6-week dietary interventions separated by a 4-week washout . Weight maintenance , eucaloric diets with identical macronutrient profiles and fiber content were design ed . All food was weighed and distributed . Insulin action was assessed using a two-step euglycemic clamp ; glycemic profiles were assessed by the continuous glucose monitoring system and vascular compliance by pulse-wave analysis . There was no change in weight across the study . Peripheral glucose uptake and suppression of endogenous glucose production were similar after each diet . Glycemic profiles and measures of vascular compliance did not change . A rise in total and LDL cholesterol was observed . In this study , a high-sucrose intake as part of an eucaloric , weight-maintaining diet had no detrimental effect on insulin sensitivity , glycemic profiles , or measures of vascular compliance in healthy nondiabetic subjects", "The effect of dietary fructose ( 20 % of carbohydrate calories , 45 - 65 g day-1 for 4 weeks ) on glycaemic control , serum lipid , lipoprotein and apoprotein A-I and A-II concentrations and on insulin sensitivity was studied in 10 type 2 diabetic patients . The study was done in a r and omized , double-blind fashion with crystalline fructose or placebo administered evenly during 4 meals or snacks per day . The patients were hospitalized throughout the study periods . The fasting plasma glucose concentration decreased during the fructose ( from 10.7 + /- 1.4 mmol l-1 to 8.0 + /- 0.8 mmol l-1 , P control diet ( from 10.1 + /- 0.9 mmol l-1 to 8.0 + /- 0.7 mmol l-1 , P mean diurnal blood glucose concentration also fell both during the fructose ( from 10.8 + /- 0.5 mmol l-1 to 8.4 + /- 0.3 mmol l-1 , P HbA1 concentration improved ( P Insulin sensitivity increased by 34 % ( P Serum insulin , triglyceride , apoprotein A-I and A-II concentrations , body weight , blood pressure and blood lactate remained unchanged during both diets . In conclusion , substitution of moderate amounts of fructose for complex carbohydrates can improve glycaemic control and insulin sensitivity in patients with type 2 diabetes", "OBJECTIVE To examine the effect on plasma triglycerides of removing most of the extrinsic sugar from the diet of free living hypertriglyceridaemic individuals while controlling weight loss . DESIGN Free living subjects were r and omly assigned to intervention and control groups . The intervention group undertook to consume a \" sugar free ' diet for six months after a three month baseline period . The control group maintained their usual diets for the nine month period . The results from the two groups were compared using repeated measures ANOVA . SUBJECTS Thirty two hypertriglyceridaemic individuals , selected from members of the public in Dunedin , New Zeal and . RESULTS Subjects in the intervention group were able to achieve a mean reduction in sucrose intake of > 70 % , largely extrinsic sucrose , result ing in a group mean reduction in plasma triglyceride levels of > 20 % and a mean weight loss over the six month period of about 2 % . Repeated measures ANOVA on the mean triglyceride figures after the individual figures had been adjusted for this small weight loss , showed that there was a significant fall in triglyceride levels over the study period compared with the baseline . CONCLUSIONS Hypertriglyceridaemia can be reduced in some individuals by the reduction of extrinsic sucrose in the diet . When allowance is made for weight loss the reduction is still significant", "Summary The effects of regularly eating sucrose were studied in 23 diabetic patients , 12 Type 1 ( insulin-dependent ) and 11 Type 2 ( non-insulin-dependent ) , with differing degrees of glycaemic control . Two diets , each lasting 6 weeks , were compared in a r and omised cross-over study . Both diets were high in fibre and low in fat . In one diet 45 g of complex carbohydrate was replaced by 45 g of sucrose taken at mealtimes . There were no significant biochemical differences between the two diets in either Type 1 or Type 2 patients . In Type 1 patients the mean ( ±SEM ) fasting plasma glucose was 10.5 ( 1.8 ) mmol/1 on the control diet and 10.3 ( 1.5 ) mmol/1 on sucrose . In Type 2 patients the levels were 9.1 ( 0.8 ) mmol/1 and 8.9 ( 0.8 ) mmol/l respectively . Glycosylated haemoglobin for the Type 1 patients was 9.9 % on control and 10.3 % on sucrose ; for Type 2 patients the figures were 9.3 % and 9.0 % respectively . There were no differences in mean daily plasma glucose levels or diurnal glucose profiles . Cholesterol ( total and in lipoprotein fractions ) was unchanged , as were diurnal triglyceride profiles and plasma insulin profiles in the Type 2 patients . There were no changes in medication or body weight . We conclude that a moderate amount of sucrose taken daily at mealtimes does not cause deterioration in metabolic control in diabetic patients following a high fibre/low fat diet", "Objectives We investigated the effect of natural honey on body weight and some blood biochemical indices of diabetic subjects . Methods Forty-eight diabetic type 2 patients were r and omly assigned into two groups : the honey group received oral natural honey for 8 weeks , and the control group did not take honey . Before the onset of the study ( week 0 ) and after 8 weeks , weight measurements were taken and fasting blood sample s were drawn . Results After adjustment for the baseline values , there were no significant differences in the fasting blood sugars between the two groups . Body weight , total cholesterol , low-density lipoprotein-cholesterol and triglyceride decreased ( P = 0.000 ) , and high-density lipoprotein-cholesterol increased significantly ( P levels of hemoglobin A1C increased significantly in this group ( P body weight and blood lipids of diabetic patients . However , since an increase in the hemoglobin A1C levels was observed , cautious consumption of this food by diabetic patients is recommended", "People are advised to reduce their intake of saturated fat and replace it by carbohydrate to avoid coronary heart disease . It is unknown whether sucrose and starchy foods , two major sources of carbohydrates , have similar effects on cardiovascular risk markers if incorporated as a replacement for saturated fat into diets eaten ad libitum . We served 20 healthy , normal-weight women aged 21 to 52 years three strictly controlled diets ad libitum : FAT , high in total fat ( 46 % of total energy [ E% ] ) and saturated fat ( 21 E% ) ; STARCH , high in total carbohydrates ( 59 E% ) and low in sucrose ( 2.5 E% ) ; and SUCROSE , high in total carbohydrates ( 59 E% ) and sucrose ( 23.2 E% ) . The diets were eaten in r and omized order for a period of 2 weeks . Blood lipids , factor VII coagulant activity ( FVIIc ) , and fibrinogen concentrations were measured with subjects in the fasted state ( 9:45 AM ) and the postabsorptive state ( 6:00 PM ) . STARCH was associated with lower total cholesterol ( mean difference , 0.34 mmol/L ; 95 % confidence interval [ CI ] , 0.18 to 0.50 ) , low-density lipoprotein ( LDL ) cholesterol ( 0.25 mmol/L ; 95 % CI , 0.13 to 0.37 ) , fasting triglycerides ( 0.15 mmol/L ; 95 % CI , 0.07 to 0.23 ) , nonfasting triglycerides ( 0.44 mmol/L ; 95 % CI , 0.30 to 0.58 ) , and nonfasting FVIIc ( 9.8 % ; 95 % CI , 3.8 to 15.8 ) than SUCROSE . Compared with FAT , STARCH result ed in a desirable decrease of LDL cholesterol and nonfasting FVIIc . STARCH was also associated with a minor weight loss ( 0.7 kg ) that was not found on the other 2 diets . We conclude that starchy foods with a natural content of dietary fiber can be recommended as substitutes for saturated fat in the dietary prevention of coronary heart disease . According to the present short-term findings in healthy females , substitution with sucrose is not advisable", "Twelve subjects with radiolucent gall stones and bile supersaturated with cholesterol were studied after six weeks each on diets which contained 112 g and 16 g respectively of refined ( fibre depleted ) sucrose but which allowed free access to other foods . Energy intake was 24.5 % higher on the high sugar diet and body weight ended 1.4 kg higher than on the low sugar diet . Biliary secretion rates of cholesterol , phospholipid and bile acid , measured by a perfusion technique , were similar on the two diets , as were the bile acid pool sizes measured by isotope dilution . Cholesterol saturation index of fasting ' gall bladder ' bile was 1.30 + /- 0.11 and 1.37 + /- 0.14 on high and low sugar respectively ( NS ) . Plasma triglycerides were 36 % higher and plasma high density lipoprotein cholesterol concentrations were 9 % lower on the high sugar diet . These findings indicate that over a six week period refined sugar in normally consumed amounts does not adversely affect the lipid composition of bile", "Some properties of the two-period change-over design are investigated . It is shown that if the effect of subjects is assumed to be a r and om variable , the difference between the direct effects and the differenice between the residual effects of treatments are estimable , but the difference between periods is not . The amount of experimentation necessary to achieve a specified power of the test of e quality of the direct effects of treatments result ing from a two-period change-over design is compared to the amount required for a design in which the subjects are assigned r and omly to a single treatment . This comparison shows that the two-period changeover design is preferable when the residual effects of the treatments are equal and the correlation between the response to the two tieatments is positive . Otherwise the design in which there is r and om assignment to a single treatment is preferable", "BACKGROUND Studies of cocoa suggest an array of cardiovascular benefits ; however , the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function ( EF ) have yet to be established . METHODS 44 adults ( BMI 25 - 35 kg/m2 ) participated in a r and omized , controlled , crossover trial . Participants were r and omly assigned to a treatment sequence : sugar-free cocoa beverage , sugar-sweetened cocoa beverage , and sugar-sweetened cocoa-free placebo . Treatments were administered daily for 6 weeks , with a 4-week washout period . RESULTS Cocoa ingestion improved EF measured as flow-mediated dilation ( FMD ) compared to placebo ( sugar-free cocoa : change , 2.4 % [ 95 % CI , 1.5 to 3.2 ] vs. -0.8 % [ 95 % CI , -1.9 to 0.3 ] ; difference , 3.2 % [ 95 % CI , 1.8 to 4.6 ] ; p : change , 1.5 % [ 95 % CI , 0.6 to 2.4 ] vs. -0.8 % [ 95 % CI , -1.9 to 0.3 ] ; difference , 2.3 % [ 95 % CI , 0.9 to 3.7 ] ; p=0.002 ) . The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater , but not significantly . Other biomarkers of cardiac risk did not change appreciably from baseline . BMI remained stable throughout the study . CONCLUSIONS Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk , and does not cause weight gain . Sugar-free preparations may further augment endothelial function" ]

[ "The aim of the study was to determine whether a recommendation to walk 10000 steps per day would result in significant improvements in glycemic control , insulin sensitivity , and cardiovascular risk in patients with type 2 diabetes mellitus . The study was a 6-week r and omized controlled trial that included 30 patients with type 2 diabetes mellitus . After 10 days of baseline activity , patients were r and omized into 2 groups : control and active . The control group ( n = 15 ) was instructed to continue with their baseline activity for 6 weeks . The active group ( n = 15 ) was instructed to walk at least 10000 steps per day 5 or more days per week , for 6 weeks . Data relevant to glycemic control and other parameters of health were collected at study weeks 0 and 6 . There were no differences in the baseline activity between groups ( P = .36 ) . Subjects in the active group significantly increased physical activity by 69 % during the intervention phase of the study ( P = .002 ) , whereas there was no change in the physical activity of the control group ( P > .05 ) . High-density lipoprotein cholesterol and resting energy expenditure significantly increased in the active group ( P plasminogen activator inhibitor 1 ( PAI-1 ) activity was reduced by exercise relative to the control group ( P = .03 ) . There were no differences in any other study parameters during the 6-week study . In conclusion , short-term intervention with a pedometer increased physical activity and positively affected plasminogen activator inhibitor 1 activity in previously inactive patients with type 2 diabetes mellitus . The use of a pedometer may prove to be an effective tool for promoting healthy lifestyle changes that include daily physical activity and self-monitoring of therapeutic goals", "PURPOSE The American College of Sports Medicine and the Centers for Disease Control and Prevention ( ACSM-CDC ) recommend 30 min of daily moderate-intensity physical activity for health ; however , the effectiveness of this recommendation in lowering blood pressure ( BP ) in hypertensives is unclear . The present study tested the hypothesis that walking activity following the ACSM-CDC physical activity recommendation would lower BP in postmenopausal women with high BP . METHODS Resting BP was measured in 24 postmenopausal women with borderline to stage 1 hypertension at baseline , 12 wk , and 24 wk . Fifteen women in the exercise ( EX ) group walked 3 km.d-1 above their daily lifestyle walking , whereas 9 women in the control ( CON ) group did not change their activity . Walking activity was self-measured with a pedometer in both groups . RESULTS Resting systolic BP was reduced in the EX group after 12 wk by 6 mm Hg ( P diastolic BP with walking . The CON group experienced no change in BP at either 12 or 24 wk . Body mass was modestly reduced by 1.3 kg in the EX group after 24 wk ( P BP . There were no changes in selected variables known to impact BP including percent body fat , fasting plasma insulin , or dietary intake . CONCLUSION In conclusion , a 24-wk walking program meeting the ACSM-CDC physical activity recommendation is effective in lowering systolic BP in postmenopausal women with borderline to stage 1 hypertension", "OBJECTIVE : To conduct a r and omised trial of a physical activity ( PA ) intervention , The First Step Program ( FSP ) for adults with type II diabetes . DESIGN : A 16-week intervention study and 24-week follow-up assessment . PARTICIPANTS : A total of 47 overweight/obese , sedentary individuals ( age=52.7±5.2 y ; BMI = 33.3±5.6 kg/m2 ) recruited through a diabetes education centre . MEASUREMENTS : Primary outcome : daily PA assessed by pedometer ( steps/day ) . Secondary outcomes : anthropometric measures ( weight , BMI , waist girth , hip girth ) ; indicators of cardiovascular health ( resting heart rate and blood pressure ) ; glycemic control ( fasting glucose , insulin , HbA1c , glucose concentration 120 min postglucose load ) ; plasma lipid status ( total cholesterol , HDL cholesterol , LDL cholesterol , and triglycerides ) . RESULTS : Relative to the CONTROL group , FSP participants increased their PA > 3000 steps/day ( approximately 30 min/day ) during the intervention ( P decreased ( approximately 2–3 cm ) , but did not differ significantly between groups . Significant changes did not emerge for any of the other variables . CONCLUSIONS : The FSP is a practical intervention that elicits an immediate and profound change in walking behaviour . Such change is an important ‘ first step ’ towards increasing the volume and /or intensity of PA necessary to improve long-term health outcomes in this largely sedentary and overweight or obese population . Relapse by 24 weeks indicates that other strategies such as booster sessions are needed to maintain lifestyle change . Further research must determine realistic and responsive health outcomes for this population that are achievable through practical , real-world programming", "BACKGROUND It is currently unclear how physical activity and diet interact within the ranges of activity seen in the general population . This study aim ed to establish whether a small , acute , increase in physical activity would lead to compensatory change in energy intake and nutrient balance , and to provide power analysis data for future research in this field . METHOD Twelve participants were studied over 7 days of habitual activity and 2 weeks after instruction to increase physical activity by 2000 steps per day . Physical activity was assessed using a diary , the ' activPAL ' activity monitor and a pedometer . Dietary analyses from prospect i ve food diaries were compared between the first and third weeks . RESULTS Participants increased step-counts ( + 2600 steps per day , P = 0.008 ) and estimated energy expenditure ( + 300 - 1000 kJ day(-1 ) , P = 0.002 ) but did not significantly change their energy intake , dietary composition or number of meals per day . From reverse power analysis 38 participants would be needed to exclude a change in energy intake of 400 kJ day(-1 ) with 90 % power at P activity . CONCLUSION These results did not demonstrate any compensatory increase in food consumption when physical activity was increased by walking an average of 2600 additional steps per day . Power analysis indicates that a larger study ( n = 38 ) will be necessary to exclude such an effect with confidence", "PURPOSE This study examined the effects of walking speed on the accuracy and reliability of 10 pedometers : Yamasa Skeletone ( SK ) , Sportline 330 ( SL330 ) and 345 ( SL345 ) , Omron ( OM ) , Yamax Digiwalker SW-701 ( DW ) , Kenz Lifecorder ( KZ ) , New Lifestyles 2000 ( NL ) , Oregon Scientific ( OR ) , Freestyle Pacer Pro ( FR ) , and Walk4Life LS 2525 ( WL ) . METHODS Ten subjects ( 33 + /- 12 yr ) walked on a treadmill at various speeds ( 54 , 67 , 80 , 94 , and 107 m x min-1 ) for 5-min stages . Simultaneously , an investigator determined steps by a h and counter and energy expenditure ( kcal ) by indirect calorimetry . Each br and was measured on the right and left sides . RESULTS Correlation coefficients between right and left sides exceeded 0.81 for all pedometers except OR ( 0.76 ) and SL345 ( 0.57 ) . Most pedometers underestimated steps at 54 m x min-1 , but accuracy for step counting improved at faster speeds . At 80 m x min-1 and above , six models ( SK , OM , DW , KZ , NL , and WL ) gave mean values that were within + /- 1 % of actual steps . Six pedometers displayed the distance traveled . Most of them estimated mean distance to within + /- 10 % at 80 m x min-1 but overestimated distance at slower speeds and underestimated distance at faster speeds . Eight pedometers displayed kilocalories , but except for KZ and NL , it is unclear whether this should reflect net or gross kilocalories . If one assumes they display net kilocalories , the general trend was an overestimation of kilocalories at every speed . If one assumes they display gross kilocalorie , then seven of the eight pedometers were accurate to within + /-30 % at all speeds . CONCLUSION In general , pedometers are most accurate for assessing steps , less accurate for assessing distance , and even less accurate for assessing kilocalories", "OBJECTIVES To determine whether a home-based pedometer-driven walking program with arthritis self-management education ( Walk + ) would increase physical activity , muscle strength , and functional performance in older adults with osteoarthritis ( OA ) of the knee as opposed to arthritis self-management education alone ( EDU ) . DESIGN A r and omized two-by-three ( group-by-time ) design with participants assigned to Walk + ( n = 17 , mean age + /- st and ard deviation = 69.6 + /- 6.7 ) or EDU ( n = 17 , age = 70.8 + /- 4.7 ) . SETTING Community located in the Baltimore-Washington area . PARTICIPANTS Thirty-four community-dwelling adults , aged 60 and older with symptomatic knee OA and self-reported functional impairment . INTERVENTIONS Both groups received 12 hours of the Arthritis Self-Management program over 12 weeks and were followed for an additional 12 weeks . In addition , the Walk + group received individualized instruction in the use of a pedometer , with the goal of increasing their step count by 30 % of their baseline step count . MEASUREMENTS The outcome measures were physical activity ( daily step counts and total activity vector magnitude as measured by a pedometer and Tritrac-R3D accelerometer ) , quadriceps femoris strength ( isometric peak torque ) , and functional performance tasks ( 100-foot walk-turn-walk , timed stair climb , timed chair rise , and pain status ) . RESULTS Daily steps walked showed a significant group-by-time interaction ( P = .04 ) after controlling for age . From baseline to completion of training , a 23 % increase in daily steps occurred in the Walk + group and a 15 % decrease in the EDU group . Although steps increased in the Walk + group , total activity vector magnitude was maintained , suggesting a more efficient gait . The Walk + group became quicker than the EDU group in the normal-pace walk-turn-walk ( P = .04 ) . An isometric strength gain of 21 % postintervention was seen in the Walk + group , compared with a loss of 3.5 % in the EDU group . CONCLUSION In older adults with symptomatic knee OA , Walk + appears to increase walking , with improvements in muscle strength and walking performance . The use of a home-based pedometer-driven program to increase physical activity , strength , and function in this population warrants further research", "Izawa KP , Watanabe S , Omiya K , Hirano Y , Oka K , Osada N , Iijima S : Effect of the self-monitoring approach on exercise maintenance during cardiac rehabilitation : A r and omized , controlled trial . Am J Phys Med Rehabil 2005;84:313–321 . Objective : To evaluate the effect of the self-monitoring approach ( SMA ) on self-efficacy for physical activity ( SEPA ) , exercise maintenance , and objective physical activity level over a 6-mo period after a supervised 6-mo cardiac rehabilitation ( CR ) program . Design : We conducted a r and omized , controlled trial with 45 myocardial infa rct ion patients ( 38 men , seven women ; mean age , 64.2 yrs ) recruited after completion of an acute-phase , exercise-based CR program . Patients were r and omly assigned to an SMA group ( n = 24 ) or control group ( n = 21 ) . Along with CR , the subjects in the SMA group self-monitored their weight and physical activity for 6 mos . The SMA used in this study was based on B and ura ’s self-efficacy theory and was design ed to enhance confidence for exercise maintenance . The control group participated in CR only . All patients were evaluated with the SEPA assessment tool . Exercise maintenance , SEPA scores , and objective physical activity ( average steps per week ) as a caloric expenditure were assessed at baseline and during a 6-mo period after the supervised CR program . Results : Mean period from myocardial infa rct ion onset did not differ significantly between the SMA and control groups ( 12.1 ± 1.3 vs. 12.2 ± 1.2 mos , P = 0.692 ) . All patients maintained their exercise routine in the SMA group . Mean SEPA score ( 90.5 vs. 72.7 points , P mean objective physical activity ( 10,458.7 vs. 6922.5 steps/wk , P SEPA showed significant positive correlation with objective physical activity ( r = 0.642 , P increase exercise maintenance , SEPA , and objective physical activity at 12 mos after myocardial infa rct ion onset", "OBJECTIVE To determine whether a home-based activity and dietary intervention can increase activity level , reduce caloric intake , and impact positively components of metabolic syndrome in a disabled population . DESIGN Testing occurred at 3 points during the 6-month intervention period ( baseline , 3mo , 6mo ) and at 6 months postintervention . Each test point included laboratory testing of anthropometric and metabolic variables and 3 days of home-based activity and dietary monitoring . A personally tailored activity and dietary prescription based on baseline testing was implemented during the 6-month intervention period . SETTING Human performance laboratory of a university and each subject 's home . PARTICIPANTS Twenty adult volunteer ambulatory subjects with several types of slowly progressive neuromuscular disease ( NMD ) . INTERVENTION Using a pedometer , subjects were instructed to increase number of steps by 25 % over their baseline determined from home monitoring . An individualized dietary prescription was provided focusing on problematic issues identified from the baseline dietary profile . MAIN OUTCOME MEASURES Body composition , physical activity , dietary intake , energy expenditure , gait efficiency , metabolic variables , and quality of life . RESULTS At the end of the protocol , mean step count increased approximately 27 % above baseline ( P=.001 ) and caloric intake decreased over 300kcal/d ( P=.002 ) . Body fat percentage significantly decreased ( from 33.3%+/-1.5 % to 32.6%+/-1.6 % , P=.032 ) . Gait efficiency did not change , and metabolic variables did not show statistically significant improvement , although 2 of the 5 subjects originally meeting the criteria for metabolic syndrome at baseline no longer met the criteria at the end of the intervention period . Six months after completing the protocol , caloric intake remained significantly reduced ( P=.02 ) , but although mean step count remained elevated , it was not statistically significant . CONCLUSIONS Using a home-based protocol , people with NMD can increase activity and reduce caloric intake . Although this 6-month program showed positive changes , it was insufficient to affect risk factors associated with metabolic syndrome . It remains to be seen if a program longer than 6 months or a more rigorous program could lead to a reduction in the risk factors associated with metabolic syndrome", "PURPOSE To compare the number of steps accumulated by women instructed to walk 10,000 steps per day ( 10 K group ) with those told to take a brisk 30-min walk on most , preferably all , days of the week ( 30-min group ) . METHODS Daily steps were compared for 58 sedentary women ( mean age 45.0+/-6.0 yr ) r and omly assigned to either the 10 K or the 30-min group . Subjects wore a sealed pedometer for 2 wk for baseline physical activity assessment . Those averaging sealed pedometer capable of storing 7 d of data , and reported to the laboratory each week so that investigators could gather step counts . The 10 K group wore a second pedometer for viewing their daily steps . RESULTS There were no differences ( P>0.05 ) between the groups for baseline steps . During the intervention , there was a significant difference ( P daily steps . The 30-min group walked 8270+/-354 steps per day , and the 10 K group walked 10,159+/-292 steps per day . The 30-min group averaged 9505+/-326 steps per day on the days that a 30-min walk occurred , and 5597+/-363 steps per day when no walk occurred ( P walk more when told to take 10,000 steps per day compared with those instructed to take a brisk 30-min walk . On days when women took a 30-min walk , their average step count was near 10,000", "BACKGROUND Physical activity ( PA ) has been shown to benefit glucose tolerance . Walking is a convenient low-impact mode of PA and is reported to be the most commonly performed activity for those with diabetes . The purpose of this study was to determine whether a recommendation to accumulate 10,000 steps/day for 8 weeks was effective at improving glucose tolerance in overweight , inactive women . METHODS Eighteen women ( 53.3 + /- 7.0 years old , 35.0 + /- 5.1 kg/m(2 ) ) with a family history of type 2 diabetes completed a 4-week control period followed by an 8-week walking program with no changes in diet . The walking program provided a goal of accumulating at least 10,000 steps/day , monitored by a pedometer . RESULTS During the control period , participants walked 4972 steps/day . During the intervention period , the participants increased their accumulated steps/day by 85 % to 9213 , which result ed in beneficial changes in 2-h postload glucose levels ( P AUC(glucose ) ( P = 0.025 ) , systolic blood pressure ( P diastolic blood pressure ( P = 0.002 ) . There were no changes in body mass , body fat percentage , and waist circumference during the walking intervention . CONCLUSIONS The 10,000 steps/day recommendation result ed in improved glucose tolerance and a reduction in systolic and diastolic blood pressure in overweight women at risk for type 2 diabetes . This demonstrates that activity can be accumulated throughout the day and does not have to result in weight loss to benefit this population", "OBJECTIVE To study the effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation . METHODS Twenty-one chronic obstructive pulmonary disease ( COPD ) patients were r and omized to an experimental group that followed a regular rehabilitation program plus the counseling intervention or to a control group that only followed rehabilitation . The primary outcome was daily physical activity assessed by pedometers . Secondary outcomes were physical fitness , health-related quality of life , activities of daily living , depression and self-efficacy . RESULTS The experimental group showed an increase of 1,430 steps/day ( + 69 % from baseline ) , whereas the control group showed an increase of 455 steps/day ( + 19 % ) ( p = 0.11 for group x time interaction ) . The secondary outcomes showed no differences . CONCLUSION AND PRACTICE IMPLICATION S This study showed that the use of the pedometer , in combination with exercise counseling and the stimulation of lifestyle physical activity , is a feasible addition to pulmonary rehabilitation which may improve outcome and maintenance of rehabilitation results", "Because of their frequent encounters with sedentary patients , family physicians are poised to be on the forefront of the medical community 's response to physical inactivity . The purpose of this pilot study was to examine whether the addition of a pedometer to brief physician counseling could help patients increase their ambulatory activity . Ninety four participants recruited from a family medicine clinic were r and omly assigned to 2 groups . Both groups received a brief physician endorsement of regular physical activity , a h and out on the benefits of an active lifestyle , and 3 follow-up phone calls from a health educator . In addition , the intervention group received a pedometer and was instructed to record their steps daily over the 9-week study period . Measurements were taken for self-reported walking , walking stage-of-change , walking self-efficacy , and pedometer steps ( intervention group only ) . Among completers , mean daily step counts in the pedometer group rose from 6779 at baseline to 8855 at study end . Average individual improvement was 41 % over the study period . Both groups significantly increased blocks walked per day , stair climbing versus using the elevator , days per week walking > or = 30 minutes , and walking for fun/leisure . The frequency of walking short trips improved significantly more in the pedometer group relative to the comparison group . The results of this pilot study highlight the need for further research on the use of pedometers as a motivational tool in the context of medical encounters with inactive patients ", "This study investigated whether feedback from pedometers motivated adults to increase their walking behavior . Participants ( n = 26 ) were enrolled in one of two 8-wk . “ Walking for Fitness ” classes . The study used a crossover design , such that Group 1 wore pedometers for the first 3 weeks ( Feedback Condition ) and sealed “ disguised ” pedometers for the last 3 weeks ( No-feedback Condition ) . The order of feedback was reversed for Group 2 . Analysis indicated that ( a ) neither group increased their walking behavior significantly over time and , ( b ) interactions between groups were not significant at Week 3 or 6 , indicating that groups did not respond differently to feedback from the pedometers . If a motivational effect from pedometers exists , it may be small , dissipate before 3 wk . , only work in combination with goal setting , or only motivate certain types of individuals", "Background Effective interventions to increase physical activity levels are critical in a nation where inactivity is a national public health problem . Objective This pilot study examined whether a minimal intervention ( daily records of physical activity ) increased activity levels in a community sample of working women . Methods In a longitudinal , pretest-posttest design , 49 working women were r and omly assigned at the work site level to the control ( n = 25 ) or intervention group ( n = 24 ) . At pretest and posttest , subjects completed self-report question naires that measured psychological , social-environmental , physical activity , and demographic variables . Subjects in the intervention group kept daily records of their physical activities during the 12-week study , while those in the control group kept no records . In order to compare activity in the two groups , all subjects wore pedometers daily that recorded number of steps . Results There was a significant difference between groups in the pedometer values ( mean number of daily steps ) at the end of the study period ( mean difference ±SE : 2147 ± 636 , p = .022 ) ( 2000 steps = approximately 1 mile ) . Multiple regression analysis showed that only the intervention ( p = .003 ) was a significant predictor of the pedometer values . Hierarchical data analysis was used to account for the intra-class correlation of 0.48 within work site . Conclusion Results from this sample of 49 women indicated that mean activity was greater in the intervention group compared to the control group . Recording daily activity is a cost-effective and acceptable intervention that may increase activity levels in women . However , more research is recommended to study the dual role of activity records as a data collection method as well as a potential intervention to increase physical activity ", "ABSTRACT A 6-month home-based ( HB ) physical activity program was compared to a control ( CTL ) condition in terms of effect on physical activity and health-related fitness in three generations of women ( daughter/mother/maternal gr and mother ) . Volunteers were r and omly assigned to a HB or CTL condition . HB participants ( n = 28 ) were asked to participate in lifestyle , aerobic , muscular strength , and flexibility activities at least 3 times per week and they completed 73 % of the recommended PA bouts . CTL condition participants ( n = 9 ) were asked to continue their usual pattern of physical activity . Changes in physical activity were measured pre- and post-intervention using the Physical Best question naire and pedometer step counts ( 3-day average ) . Changes in health-related fitness were assessed using Fitnessgram tests . Group × Time interactions were significant for changes in participation in flexibility activity ( d/wk ) and steps/day , indicating that the HB group experienced significant positive changes in the expected direction ( + 305 % and + 37 % , respectively ) , while the CTL group regressed ( −15 % and −13 % , respectively ) . The G × T interaction for mile time was significant , although not in the expected direction ( CTL group < by 14 % and HB group < by 5 % ) . Findings should be interpreted with caution due to several limitations of the study , but several suggestions are made for more effectively study ing this topic in the future", "BACKGROUND Inactivity is a leading contributor to chronic health problems . Here , we examined the effects of a pedometer-based physical activity intervention ( Prince Edward Isl and -First Step Program , PEI-FSP ) on activity and specific health indices in 106 sedentary workers . METHODS Participants were recruited from five workplaces where most jobs were moderately-highly sedentary . Using subjects as their own control , physical activity ( pedometer-determined steps per day ) was compared before and after a 12-week intervention . Changes in body mass index ( BMI ) , waist girth , resting heart rate , and blood pressure were evaluated . RESULTS The PEI-FSP was completed by 59 % of participants . Steps per day increased from 7,029 + /- 3,100 ( SD ) at baseline to a plateau of 10,480 + /- 3,224 steps/day by 3.96 + /- 3.28 weeks of the intervention . The amount that participants were able to increase their steps per day was not related to their baseline BMI . On average , participants experienced significant decreases in BMI , waist girth , and resting heart rate . Reductions in waist girth and heart rate were significantly related to the increase in steps per day . In contrast , reductions in BMI were predicted by the initial steps per day . CONCLUSIONS The PEI-FSP increased physical activity in a sedentary population . Importantly , those with a higher BMI at baseline achieved relatively similar increases in their physical activity as participants with a lower BMI", "This pilot study assessed possible changes in Life Satisfaction across three generations of women after a 6-mo . physical activity intervention . The primary purpose of the study was to test the study design and discover critical issues that should be controlled for or changed in a follow-up study . A quasi-experimental design was used to assign r and omly a convenience sample of participant triads into two groups : a home-based group ( n = 27 ) and a control group ( n = 9 ) . Daughters were premenarcheal ( n = 13 , M = 10.1 yr . , SD = 1.5 ) , mothers were premenopausal ( n = 13 , M = 37.2 yr . , SD = 4.2 ) , and gr and mothers were postmenopausal ( n = 11 , M = 61.5 yr . , SD = 4.4 ) . Life Satisfaction was measured using the Satisfaction with Life Scale . Participation in physical activity was measured using the Physical Best Physical Activity Question naire and a pedometer to count the number of steps taken per day . Compared with the control group , participants in the home-based group generally increased physical activity but their scores for Life Satisfaction did not increase . Recommendations concerning the study design , reducing limitations , and hypotheses for further study are given", "Purpose . This study was design ed ( 1 ) to examine the effects of a 10,000 steps·d−1 exercise prescription on sedentary , overweight/obese adults , and ( 2 ) to examine the effects of adherence on body composition and cardiovascular risk factors . Methods . Fifty-six overweight/obese adults participated in the study . Body composition and cardiovascular risk factors were determined at baseline , 20 weeks , and 36 weeks . Adherence was defined as averaging ≥ 9500 steps·d−1 from week 4 to week 36 . Results . 38 participants ( 68 % ) wore pedometers daily for 36 weeks and were available for posttesting . Significant improvements were noted in mean values for walking volume ( 3994 steps·d−1 ) , body weight ( –2.4 kg ) , body mass index ( –0.8 kg·m−2 ) , percentage body fat ( –1.9 % ) , fat mass ( –2.7 kg ) , waist circumference ( –1.8 cm ) , hip circumference ( –1.9 cm ) and high-density lipoprotein ( 3 mg/dl ) . The adherers had large improvements in body composition measures , whereas the nonadherers showed little or no change in these variables . Discussion . A 10,000 steps·d−1 exercise prescription result ed in weight loss over 36 weeks in previously sedentary , overweight/obese adults . Adherence to the step goal had a marked effect on the outcome" ]

[ "Abdominal obesity is associated with blunted GH secretion and a cluster of cardiovascular risk factors that characterize the metabolic syndrome . GH treatment in abdominally obese men reduces visceral adipose tissue and has beneficial effects on the metabolic profile . There are no long-term data on the effects of GH treatment on postmenopausal women with abdominal obesity . Forty postmenopausal women with abdominal obesity participated in a r and omized , double-blind , placebo-controlled , 12-month trial with GH ( 0.67 mg/d ) . The primary aim was to study the effect of GH treatment on insulin sensitivity . Measurements of glucose disposal rate ( GDR ) using a euglycemic , hyperinsulinemic glucose clamp ; abdominal fat , hepatic fat content , and thigh muscle area using computed tomography ; and total body fat and fat-free mass derived from (40)K measurements were performed at baseline and at 6 and 12 months . GH treatment reduced visceral fat mass , increased thigh muscle area , and reduced total and low-density lipoprotein cholesterol compared with placebo . Insulin sensitivity was increased at 12 months compared with baseline values in the GH-treated group . In the GH-treated group only , a low baseline GDR was correlated with a more marked improvement in insulin sensitivity ( r = -0.68 ; P GDR and liver attenuation as a measure of hepatic fat content between baseline and 12 months ( r = 0.7 ; P postmenopausal women with abdominal obesity , 1 yr of GH treatment improved insulin sensitivity and reduced abdominal visceral fat and total and low-density lipoprotein cholesterol concentrations . The improvement in insulin sensitivity was associated with reduced hepatic fat content", "Background — Statins are important in vascular disease prevention in the elderly . However , the best method of selecting older patients for treatment is uncertain . We assessed the role of plasma lipoproteins as predictors of risk and of treatment benefit in the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) . Method and Results — The association of LDLc and HDLc with risk was examined in the 5804 70- to 82-year-old subjects of PROSPER . Baseline LDLc showed no relation to risk of the primary end point in the placebo group ( P=0.27 ) , nor did on-treatment LDLc in the pravastatin group ( P=0.12 ) . HDLc was inversely associated with risk in subjects on placebo ( P=0.0019 ) but not in those on pravastatin ( P=0.24 ) . Risk reduction on pravastatin treatment was unrelated to baseline LDLc ( P=0.38 ) but exhibited a significant interaction with HDLc ( P=0.012 ) . Subjects in the lowest 2 quintiles of HDLc ( risk reduction of 33 % ( hazard ratio , 0.67 ; 95 % confidence limits , 0.55 , 0.81 ; P level of LDLc or HDLc and risk . However , the change in the LDLc/HDLc ratio on statin treatment appeared to account for the effects of therapy . Conclusions — In people > 70 years old , HDLc appears to be a key predictor of risk and of treatment benefit . Findings in PROSPER suggest that statin therapy could usefully be targeted to those with HDLc 3.3", "OBJECTIVE Young adults with childhood-onset GH deficiency ( GHD ) have reduced memory and attention , which can be improved by treatment with GH . Little information is available on cognitive function in elderly GHD patients . DESIGN Single center , double-blind , r and omized , placebo-controlled study of 52-week duration . METHODS Elderly GH therapy naïve GHD patients ( n=34 ; age range 60 - 77 years ) were enrolled and r and omized to receive placebo or GH therapy which was titrated to achieve a target IGF-I level of + 1 to + 2 s.d . of the normal mean for age . Cognitive function was assessed at baseline and after 24 and 52 weeks , using a computerized psychometric test package ( Neurobehavioral Examination System-2 ) . RESULTS The mean GH dose was 0.16+/-0.06 mg/day ; mean IGF-I increased from 135+/-59 ng/ml at baseline to 213+/-77 ng/ml during active treatment . The GH-treated group had better mean serial digit learning scores compared with placebo group ( P effect sizes showed that improvements in memory occurred with GH after 24 weeks . The overall adverse event rates were similar in the GH and the placebo group . CONCLUSION This study indicates that GH replacement may be accompanied by improvement in certain measures of cognitive function in elderly patients with GHD", "Aging is associated with alterations in body composition and a decline in functional status . Healthy older persons have decreased muscle mass , increased fat mass , and decreased strength [ 1 - 3 ] . The muscle strength of 70-year-old men is about half that of young adults [ 3 ] . The risk for falls , fractures , and frailty increases with age-related decreases in muscle strength [ 4 - 6 ] . Pituitary secretion of growth hormone and circulating levels of insulin-like growth factor 1 decrease with aging [ 7 ] ; these events are called somatopause . Growth hormone is both anabolic and lipolytic [ 8 - 10 ] , and the action of growth hormone on peripheral tissues is mediated , in part , by circulating insulin-like growth factor 1 [ 11 ] . Growth hormone deficiency results in body composition changes that are similar to the changes seen with aging [ 1 , 7 ] . Growth hormone replacement in patients with hypopituitarism and in older men reverses some of the body composition changes associated with both growth hormone deficiency and aging [ 12 - 14 ] . In a study by Rudman and colleagues [ 14 ] on the effects of growth hormone replacement therapy on body composition , the administration of growth hormone to 12 men 61 to 73 years of age for 6 months increased lean body mass by 9 % and decreased adipose tissue mass by 15 % ( P Circulating insulin-like growth factor 1 levels increase similarly in young and old men after exogenous administration of either growth hormone or growth hormone-releasing hormone [ 7 , 11 ] . Therefore , low insulin-like growth factor 1 levels reflect decreased growth hormone secretion rather than a loss of hepatic responsiveness to the hormone . On the basis of these data , it has been proposed that diminished secretion of growth hormone is responsible , in part , for the somatic changes of aging [ 14 ] . Growth hormone replacement has been shown to improve muscle volume , isometric strength , and exercise capacity in young adults with hypopituitarism [ 12 , 13 ] . In one study of growth hormone-deficient young adults treated with growth hormone [ 12 ] , thigh muscle volume increased by 6 % ( P isometric strength increased by 8 % ( P = 0.08 ) compared with controls . Increases in isometric strength were associated with increases in muscle volume ( r = 0.75 ; P Exercise capacity also increased by 12 % ( P growth hormone replacement therapy on strength or function are not available for older persons . To test the hypothesis that the muscle weakness and functional decline associated with aging are in part due to decreased growth hormone secretion , we conducted a 6-month r and omized , controlled , double-blind trial comparing recombinant human growth hormone therapy with placebo in 56 elderly men whose baseline insulin-like growth factor 1 levels were less than the tenth percentile found in younger healthy adults . Methods Participants We recruited healthy , ambulatory , community-dwelling men older than 69 years of age . Because growth hormone secretion is pulsatile and diurnal , a more convenient measure of growth hormone secretion is insulin-like growth factor 1 , which has constant and nonpulsatile plasma levels [ 1 , 7 , 15 , 16 ] . Inclusion criteria included two fasting morning plasma insulin-like growth factor 1 levels ( assayed after plasma was extracted with acid ethanol by the Nichols Institute [ 17 ] ) less than 161 ng/mL that were obtained at least 2 weeks apart , a fasting blood glucose level less than 8.4 mmol/L ( 140 mg/dL ) , stable body weight between 80 % and 120 % of ideal body weight [ 18 ] during the previous year , and a normal complete blood count at baseline . Participants had to be able to follow the study instructions and perform the strength measurements . Exclusion criteria included diseases that might contraindicate the use of growth hormone ( such as carcinoma within the previous 5 years , diabetes mellitus , and the carpal tunnel syndrome ) , uncontrolled hypertension ( blood pressure more than 180/100 mm Hg ) , oral corticosteroid use within the previous year , or a recent change in ambulatory status ( for example , as the result of a stroke ) . Design After the participants gave informed written consent , the following baseline measurements were obtained : question naires ( demographic characteristics and medical conditions ) ; fasting blood chemistry ( levels of electrolytes , urea nitrogen , creatinine , glucose , calcium , phosphate , and albumin ) ; complete blood count ; serum and rogen levels ( total and free testosterone and dehydroepi and rosterone ) ; fasting lipoprotein levels ( total cholesterol , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol , and triglycerides ) and thyroid-stimulating hormone and free thyroxine levels ; 24-hour urinary calcium excretion ; and creatinine clearance . At baseline , we also measured the body composition , strength , and functional ability of all participants . We then used a computer-generated r and omization table to assign each participant to receive either growth hormone or placebo . Participants , investigators who had contact with the participants , and laboratory personnel were blinded to treatment status . Treatment consisted of recombinant human growth hormone ( somatropin [ Nutropin , Genentech ] ) , 0.03 mg/kg of body weight , or an equivalent placebo volume ( supplied in identical vials by Genentech ) injected subcutaneously three times per week in the morning for 6 months . We evaluated the participants after 2 , 4 , 8 , 12 , 18 , and 24 weeks of treatment to determine whether side effects developed and to ensure compliance . Participants were examined and specifically asked about the presence of the following side effects : malaise , fatigue , edema , arthralgias , arthritis , the carpal tunnel syndrome , muscle discomfort , dyspnea , depression , polydipsia , polyuria , nocturia , and tender or enlarged breasts . At each visit , we measured fasting morning plasma insulin-like growth factor 1 levels 48 hours after the last treatment dose and repeated most of the baseline blood and urinary tests . We adjusted the dose of recombinant human growth hormone to maintain serum insulin-like growth factor 1 levels between 190 and 350 ng/mL ( the 25th to 75th percentiles of a young adult population ) 48 hours after a dose . To preserve blinding , each growth hormone recipient was paired with a placebo recipient . An unblinded physician who had not had contact with the participants review ed insulin-like growth factor 1 levels during the trial . If the levels were less than 190 ng/mL or greater than 350 ng/mL , the unblinded physician instructed study personnel to make identical dose adjustments for both participants in the pair . The dose was also decreased in any participant who reported troublesome side effects that were potentially attributable to growth hormone . We repeated all study outcome measurements after 6 months of treatment . We also measured fasting plasma renin activity , cortisol and aldosterone levels , and 24-hour urine aldosterone excretion . The investigational review boards of the University of California , San Francisco , and the Department of Veterans Affairs Medical Center , San Francisco , approved the study protocol . Measurements Body Composition We used dual-energy x-ray absorptiometry ( Lunar DPX-Plus , Madison , Wisconsin ) total-body composition scans to measure lean tissue mass and fat mass , and we used anterior-posterior lumbar scans to measure bone mineral content . We measured skin thickness using ultrasonography with a 10-MHz transducer ( Diasonics , Milpitas , California ) that was positioned transversely 5 cm below the umbilicus . Using the same transducer , we made two ultrasonographic measurements on each participant . The average of the two measurements was used for analysis . The study radiologist , who was blinded to the participants ' treatment status , interpreted all test results . Muscle Strength The study 's physical therapist measured the muscle strength of the participants ' knee flexor and extensor muscles using an isokinetic dynamometer ( Cybex 340 , Lumex , Bay Shore , New York ) . Using a st and ard protocol , we measured peak torque of knee flexion and extension at joint speeds of 90 , 120 , and 180 degrees per second . We measured h and grip strength according to a st and ardized protocol using a grip dynamometer ( Smedley Grip Dynamometer , JA Preston , Jackson , Mississippi ) . The greater of the two measurements was used for analysis . Systemic Endurance To assess systemic endurance , we measured maximal oxygen consumption ( Vo 2 max ) during exercise cycle testing . Upright exercise testing was done using an electronically braked cycle ergometer ( Erich Jaeger , Rockford , Illinois ) . Exercise was initially done unloaded and was then increased by 25 watts every 2 minutes . Participants continued to exercise until they were exhausted or unable to maintain critical pedal frequency ( greater than 50 revolutions per minute ) . During exercise cycle testing , we continuously measured respiratory gas exchange to determine Vo 2 max ( Ergopneumotest , Erich Jaeger ) . Physical Performance The study 's physical therapist used the Physical Performance Test [ 19 ] to assess the participants ' performance on nine physical functions . Participants were asked to write a prescribed sentence , transfer kidney beans using a teaspoon , place a heavy book on a shelf , remove a jacket , pick up a penny from the floor , turn 360 degrees , walk a 50-foot walking test course , and climb stairs to determine speed and the number of flights climbed before the development of fatigue . The test score is based on the time required to complete each task . Higher scores ( the best performance is a maximum score of 36 ) are associated with the shortest time required to complete a task and with better functional status . Cognitive Function and Mood Each participant completed the Trails B Test , the Mini-Mental State Examination , the Digit Symbol Substitution Test , and the Geriatric Depression Scale [ 20 - 23 ] . The Trails B Test ( from the Halstead-Reitan Neuropsychological Test ", "In 134 males and 242 females , aged 20 - 70 years , most of them r and omly selected from population studies , the body composition was estimated from the measurements of body height ( BH ) , body weight ( BW ) , total body potassium ( TBK ) and total body water ( TBW ) . TBK was measured with isotope dilution technique using 42 K or determined as 40 K in a whole body counter . TBW was determined with an isotope dilution technique using tritiated water , assayed in urine or plasma . From these data , body cell mass ( BCM ) , intra- and extra-cellular water ( ICW and ECW , resp . ) and body fat ( BF ) were calculated for each individual . Significant correlations were found between age versus TBK , ECW , BF and ECW/ICW ; between BW versus TBK , TBW , ECW , BF and ECW/ICW ; ( females only ) and between BH versus TBK , TBW , ECW ( females only ) and ECW/ICW . For the prediction of TBK , TBW and BF , multiple regression equations based on BW , BH and age are given . These equations are also presented diagrammatically . The problems with the methods used are considered as well as the applicability of the formulas for the calculation of BCM etc . The predictive value of the results when both TBW and TBK are used for the calculation of body composition data is discussed and compared with similar results , based on TBW or TBK only . It is concluded , that the most reliable method for calculation of BF is to estimate both TBW and TBK", "objectives To assess effects of GH replacement therapy on cardiac structure and function , exercise capacity as well as serum lipids in elderly patients with GH deficiency ( GHD )", "CONTEXT The effects of GH replacement in elderly GH-deficient ( GHD ) adults are not well known . OBJECTIVE / DESIGN / PATIENTS In this prospect i ve , single-center , open-label study , baseline characteristics and the effects of 2-yr GH replacement were determined in 24 GHD adults above 65 yr of age and in 24 younger GHD patients ( mean age , 37 yr ; range , 27 - 46 yr ) . All patients had adult onset disease , and both groups were comparable in terms of the number of pituitary hormonal deficiencies , gender , body mass index , and waist/hip ratio . Duration of hypopituitarism was , however , longer in the elderly patients . RESULTS The mean maintenance dose of GH was 0.31 ( sem , 0.03 ) mg/d in the elderly GHD patients and 0.44 ( 0.04 ) mg/d in the younger patients . The less marked response in IGF-I sd score , total body fat , and extracellular water in the elderly patients lost significance when the dose of GH was accounted for in the statistical analyses . Despite the lower dose in the elderly GHD group , these patients had a more marked reduction in waist/hip ratio and serum low-density lipoprotein-cholesterol level , and these differences remained also after correction for duration of hypopituitarism . There was no difference at baseline or in responsiveness in lean mass , bone mineral density , and glucose homeostasis . CONCLUSIONS This study identifies elderly GHD adults as a GH-sensitive group in whom a low dose of GH can improve body composition and serum lipid profile without any significant impairment of glucose metabolism . GH replacement should therefore be considered in elderly GHD adults ", " OBJECTIVE There Is a cllnlcal need for population based reference values for serum Insulin‐like growth factor I ( IGF‐I ) . We have therefore determined serum IGF‐i concentrations In a r and om population sample from Sweden and have related the levels to age , sex , llfe style factors , blood pressure , body composition , blood llplds , plasma fibrlnogen , Parathyroid hormone ( PTH ) and osteocalcin", "Objective Little is known of the long‐term effects of GH replacement therapy on muscle strength in elderly adults with adult onset GH deficiency ( GHD ) . In this study , the effects of 5 years of GH replacement therapy on muscle function were determined in adults over 60 years of age with adult onset GHD", "Although growth hormone ( GH ) replacement therapy is increasingly utilized in the management of adult hypopituitary patients , optimum dosing schedules are poorly defined . The use of weight-based or surface area-based dosing may result in overtreatment , and individual variation in susceptibility on the basis of gender and other factors is now being recognized . To optimize GH replacement and to explore further gender differences in susceptibility , we used a dose titration regimen , starting at the initiation of GH replacement therapy , in 50 consecutive adult-onset hypopituitary patients , and compared the results with those in 21 patients previously treated using a weight-based regimen . Titrated patients commenced GH 0.8 IU/day subcutaneously ( 0.4 IU/day if hypertensive or glucose tolerance impaired ) . Serum insulin-like growth factor I ( IGF-I ) was measured at 0 , 2 , 4 , 6 , 8 , 10 , and 12 weeks in all patients . Serum IGF binding protein 3 and acid labile subunit were measured at the same time points in 17 patients ( 8 male , 9 female ) . Patients were review ed every 4 weeks and the dose of GH increased , if necessary , to achieve a serum IGF-I level between the median and the upper end of the age-related reference range . There was no significant difference between mean serum IGF-I at 2 and 4 weeks , or between 6 and 8 weeks , indicating that the full effects of a change in dose are evident within 2 weeks of that change . Maintenance doses were significantly higher in females than males [ 1.2 ( 0.8 - 2.0 ) vs. 0.8 ( 0.4 - 1.6 ) IU/day ; median ( range ) ; P median time to achieve maintenance dose was significantly shorter in males [ 4 ( 2 - 12 ) vs. 9 ( 2 - 26 ) weeks ; P Median maintenance dose was lower overall than in a group of 21 patients initially commenced on GH using a weight-based dosing schedule , with subsequent adjustment of dose during clinical follow-up [ 1.5 ( 0.4 - 3.2 ) IU/day ; P = 0.02 ] . Reduction in waist measurement and waist to hip ratio at 6 and 12 months was similar in females ( P Well-being improved significantly after 3 months of GH therapy ( 14.2 + /- 5.9 vs. 7.4 + /- 4.5 SD ; P Adult Growth Hormone Deficiency Assessment ( AGHDA ) scores at 6 months were similar to maintenance scores in patients commenced on weight-based regimens . Measurements of ALS and IGFBP-3 added no useful extra information to IGF-I in managing the dose titration . The practical scheme outlined for dose titration of GH replacement result ed in rapid achievement of lower maintenance doses than those achieved using conventional weight-based regimens without loss of efficacy . It was particularly important in female patients who demonstrated decreased overall sensitivity to GH and required higher doses to achieve the same effects as males . This constitutes the first report of a uniform titration regimen based on a defined target range of serum IGF-I in a large patient cohort", "We investigated the effect of 12 weeks of recombinant human GH therapy given in three different doses on serum insulin-like growth factor I ( IGF-I ) and IGF-binding protein-3 ( IGFBP-3 ) in patients with GH deficiency ( GHD ) . We used low doses of recombinant human GH ( Genotropin ) , as we and others recently found a strong decrease in physiological GH production with age in healthy controls , especially in those older than 30 yr . Sixty patients with GHD ( aged 20 - 70 yr ) were r and omized to one of the three dose groups . Group 1 used a dose of 0.6 IU/day for 12 weeks . Group 2 started at a dose of 0.6 IU for 4 weeks followed by 1.2 IU/day for 8 weeks . Group 3 used 0.6 IU for 4 weeks , followed by 1.2 IU/day for 4 weeks and 1.8 IU/day thereafter . IGF-I concentrations ( nanomoles per L ) were determined by RIA after extraction and purification on ODS-silica columns . The measurement of IGFBP-3 ( milligrams per L ) was performed by RIA . The three groups were equal with regard to age , sex and body mass index . At the start of the study , we found lower levels of both serum IGF-I and IGFBP-3 in childhood-onset GHD than in adult-onset GHD . Moreover , there was a gender difference ; female GHD patients had lower serum IGF-I levels than male patients . Serum IGF-I levels were low in both childhood-onset and adult-onset GHD . Serum IGFBP-3 levels , however , were low in patients with childhood-onset GHD , but normal in patients with adult-onset GHD . After 12 weeks of treatment , IGF-I levels were low normal in the low dose group and normal in groups 2 and 3 of both adult-onset and childhood-onset GHD . In adult-onset GHD , serum IGFBP-3 increased to high normal levels in all groups , whereas it increased to low normal levels in childhood-onset GHD . This study demonstrates differences in the biochemical characteristics of childhood-onset and adult-onset GHD . In patients with adult-onset GHD , serum IGFBP-3 levels are not significantly decreased and , therefore , can not be used as a screening method for GHD or as a dose-finding parameter . GH therapy at doses of 0.6 and 1.2 IU/day in male and female patients , respectively , is , in general , able to increase serum IGF-I into the normal range after 12 weeks of treatment , without reaching supranormal levels of serum IGF-I. This dose could , therefore , be a starting dose in GH-deficient adults", "CONTEXT Only few studies have investigated the effects of GH replacement on muscle strength in elderly patients with GH deficiency ( GHD ) . OBJECTIVE , DESIGN , AND PATIENTS : In this prospect i ve open-labeled study , the effects of 10 years of GH replacement on muscle strength and neuromuscular function were followed in 24 elderly GHD adults ( mean age of 65.2 years ; range 61 - 74 years ) . Muscle strength was compared with reference values obtained from the background population . RESULTS The mean initial GH dose of 0.72 mg/day was lowered to 0.37 mg/day . The mean IGF1 SDS increased from -1.10 at baseline to 1.17 at study end . GH replacement induced a sustained increase in lean body mass and a transient increase in isometric knee flexor strength . Isometric knee extensor strength was reduced after 10 years . However , after correction for age and gender , using observed/predicted value ratios , there was sustained and even progressive increase in most variables reflecting muscle strength . Measurements of neuromuscular function showed unchanged voluntary motor unit activation after 10 years . CONCLUSIONS Ten years of GH replacement therapy in elderly GHD adults result ed in a transient increase in isometric knee flexor strength , and provided protection from most of the normal age-related decline in muscle performance and neuromuscular function" ]

[ "Muscle mass decreases with age , leading to \" sarcopenia , \" or low relative muscle mass , in elderly people . Sarcopenia is believed to be associated with metabolic , physiologic , and functional impairments and disability . Methods of estimating the prevalence of sarcopenia and its associated risks in elderly population s are lacking . Data from a population -based survey of 883 elderly Hispanic and non-Hispanic white men and women living in New Mexico ( the New Mexico Elder Health Survey , 1993 - 1995 ) were analyzed to develop a method for estimating the prevalence of sarcopenia . An anthropometric equation for predicting appendicular skeletal muscle mass was developed from a r and om sub sample ( n = 199 ) of participants and was extended to the total sample . Sarcopenia was defined as appendicular skeletal muscle mass (kg)/height2 ( m2 ) being less than two st and ard deviations below the mean of a young reference group . Prevalences increased from 13 - 24 % in persons under 70 years of age to > 50 % in persons over 80 years of age , and were slightly greater in Hispanics than in non-Hispanic whites . Sarcopenia was significantly associated with self-reported physical disability in both men and women , independent of ethnicity , age , morbidity , obesity , income , and health behaviors . This study provides some of the first estimates of the extent of the public health problem posed by sarcopenia", "BACKGROUND The prominent clinical feature of cachexia has traditionally been understood to be weight loss ; however , in recognition of the potential for divergent behavior of muscle and adipose tissue , cachexia was recently defined as loss of muscle with or without loss of fat mass . Detailed assessment s are required to verify body composition in patients with cancer cachexia . DESIGN We adopted a population -based approach to study body composition in patients with cancer , with the use of diagnostic computed tomography images acquired for cancer diagnosis and follow-up . A prospect i ve cohort of 441 patients with non-small cell lung cancer , who were referred consecutively to a regional medical oncology service in Alberta , Canada , was evaluated . RESULTS At referral ( median time to death : 265 d ) , mean body mass index ( BMI ; in kg/m(2 ) ) was 24.9 , with 47.4 % of patients being overweight or obese . Only 7.5 % overall were underweight as conventionally understood ( BMI computed tomography images showed extremely high heterogeneity of muscle mass within all strata of BMI . The overall prevalence of severe muscle depletion ( sarcopenia ) was 46.8 % and was present in patients in all BMI categories . A much higher proportion of men ( 61 % ) than women ( 31 % ) met the criteria for sarcopenia . CONCLUSIONS Wasting of skeletal muscle is a prominent feature of patients with lung cancer , despite normal or heavy body weights . The significance of muscle wasting in normal-weight , overweight , and obese patients as a nutritional risk factor , as a prognostic factor , and as a predictor of cancer treatment toxicity is discussed in this article", "PURPOSE This prospect i ve study was design ed in order to compare the most common subjective measurements of physical function in patients with advanced lung cancer with an objective physical functional test ( Simmonds Functional Assessment Tool [ SFA ] ) . PATIENTS AND METHODS One hundred patients agreed to participate and complete the study before or after their outpatient medical oncology appointment . Patients underwent assessment using the Karnofsky , the Brief fatigue Inventory , The Functional Assessment of Cancer Therapy-Lung patients ( FACT-L ) and the Edmonton Symptom Assessment Scale ( ESAS ) . These results were compared to the SFA tool . The SFA consists of six tasks : tying a belt , putting coins in a cup , reaching above head , st and ing up/sitting down , reaching forward and walking 50 feet . RESULTS Ninety-nine patients completed the study over 8 months : median Karnofsky performance status was 85 ( 70 to 100 ) , Edmonton Symptom Assessment Scale ( ESAS ) score ( 0 to 10 ) was generally low ( 0.5 to 2.8 ) . SFA scores were significantly different in patients compared to a control group . The correlation between the subscales of the SFA and the Karnofsky , the Brief Fatigue Inventory , The FACT-L and the ESAS was generally low to moderate ( r values : 0.22 to 0.38 ) . There was generally a moderate correlation between the different subjective scales ( r values : 0.3 to 0.62 ) . CONCLUSION Adherence to the SFA tool was excellent . The low to moderate correlation between the abnormalities found in the objective SFA and the subjective fatigue tests suggest that objective evaluation of the functional capacity provides a potentially useful and independent end-point for clinical trials and therapeutic interventions . These assessment tools should be used complementary to each other to better assess the functional status of patients with advanced lung cancer . Large trials of objective functional assessment are justified", "The ECOG Scale of Performance Status ( PS ) is widely used to quantify the functional status of cancer patients , and is an important factor determining prognosis in a number of malignant conditions . The PS describes the status of symptoms and functions with respect to ambulatory status and need for care . PS 0 means normal activity , PS 1 means some symptoms , but still near fully ambulatory , PS 2 means less than 50 % , and PS 3 means more than 50 % of daytime in bed , while PS 4 means completely bedridden . An inter-observer variability study of PS assessment has been carried out to evaluate the non-chance agreement among three oncologists rating 100 consecutive cancer patients . Total unanimity was observed in 40 cases , unanimity between two observers in 53 cases , and total disagreement in seven cases . Kappa statistics reveal the ability of the observers compared to change alone and were used to evaluate non-chance agreement . Overall Kappa was 0.44 , ( 95 % confidence limits 0.38 - 0.51 ) . The Kappa for PS 0 was 0.55 ( 0.44 - 0.67 ) , while those for PS 1 , 2 , 3 and four were 0.48 ( 0.37 - 0.60 ) , 0.31 ( 0.19 - 0.42 ) , 0.43 ( 0.32 - 0.55 ) , and 0.33 ( 0.33 - 0.45 ) , respectively . If one observer allocated patients to PS 0 - 2 , then another r and omly selected observed placed the patients in the same category with a probability of 0.92 . For patients with PS 3 - 4 the probability that the same category would be chosen was 0.82 . Overall , the non-chance agreement between observers was only moderate , when all ECOG Performance Status groups were considered . However , agreement with regard to allocation of patients to PS 0 - 2 versus 3 - 4 was high . This is of interest because this cut-off is often used in clinical studies", "Purpose This study aim ed to determine the prevalence of sarcopenia and examine whether sarcopenia was associated with overall and breast-cancer-specific mortality in a cohort of women diagnosed with breast cancer ( stages I – IIIA ) . Methods A total of 471 breast cancer patients from western Washington State and New Mexico who participated in the prospect i ve Health , Eating , Activity , and Lifestyle Study were included in this study . Appendicular lean mass was measured using dual X-ray absorptiometry scans at study inception , on average , 12 months after diagnosis . Sarcopenia was defined as two st and ard deviations below the young healthy adult female mean of appendicular lean mass divided by height squared ( Total and breast-cancer-specific mortality data were obtained from Surveillance Epidemiology and End Results registries . Multivariable Cox proportional hazard models assessed the associations between sarcopenia and mortality . Results Median follow-up was 9.2 years ; 75 women were classified as sarcopenic , and among 92 deaths , 46 were attributed to breast cancer . In multivariable models that included age , race-ethnicity/ study site , treatment type , comorbidities , waist circumference , and total body fat percentage , sarcopenia was independently associated with overall mortality ( hazard ratio ( HR ) = 2.86 ; 95 % CI , 1.67–4.89 ) . Sarcopenic women had increased risk of breast-cancer-specific mortality , although the association was not statistically significant ( HR = 1.95 , 95 % CI , 0.87–4.35 ) . ConclusionS arcopenia is associated with an increased risk of overall mortality in breast cancer survivors and may be associated with breast-cancer-specific mortality . The development of effective interventions to maintain and /or increase skeletal muscle mass to improve prognosis in breast cancer survivors warrants further study . Implication s for Cancer SurvivorsSuch interventions may help breast cancer patients live longer", "Early identification and treatment of nutritional deficiencies can lead to improved outcomes in the quality of life ( QoL ) and survival of patients with nonsmall cell lung cancer ( NSCLC ) . Noninvasive techniques are needed to evaluate changes in body composition as part of determining nutritional status . The aim of the study was to evaluate the association of nutritional parameters in health-related quality of life ( HRQL ) and survival in patients with advanced NSCLC . Chemotherapy-naïve patients with advanced NSCLC with good performance status Eastern Cooperative Oncology Group ( ECOG ) 0–2 were included prospect ively in the study . We evaluated inflammatory parameters such as C-reactive protein , platelet/lymphocyte index , neutrophil/lymphocyte index , serum interleukin (IL)-6 , and tumor necrosis factor-α , and nutritional variables such as body mass index ( BMI ) and serum albumin levels . Bioelectrical impedance analysis including phase angle was obtained before cisplatin-based chemotherapy was started . HRQL was assessed by application of the European Organization for Research and Treatment of Cancer Quality of Life Question naire (QLQ)-C30 and QLQ-LC13 instruments at baseline . Overall survival ( OS ) was calculated with the Kaplan-Meier method and analyzed with log-rank and Cox proportional hazard models . One hundred nineteen patients were included . Mean BMI was 24.8 ± 4.5 kg/m2 , average weight loss of patients was 8.4 % , and median phase angle was 5.8 ° . Malnutrition measured by subjective global assessment ( SGA ) , weight loss > 10 % , BMI > 20 was associated with lower HRQL scales . Patients with ECOG 2 , high content serum IL-6 , lower phase angle , and malnutrition parameters showed lower OS ; however , after multivariate analysis , only ECOG 2 [ Hazard ratio ( HR ) , 2.7 ; 95 % confidence interval ( 95 % CI ) , 1.5–4.7 ; P = 0.001 ] , phase angle ≤5.8 ° ( HR = 3.02 ; 95 % CI : 1.2–7.11 ; P = 0.011 ) , and SGA ( HR = 2.7 ; 95 % CI , 1.31–5.5 ; P = 0.005 ) were associated with poor survival . Patients were divided into low- , intermediate- , and high-risk groups according to regression coefficients ; OS at 1 yr was 78.4 , 53 , and 13.8 % , respectively . Malnutrition is associated with low HRQL and is an independent prognostic factor in advanced NSCLC . The results warrant prospect i ve trials to evaluate the impact of different nutritional interventions on HRQL and survival", "Background A frequent manifestation of advanced NSCLC is malnutrition , even though there are many studies which relate it with a poor survival , its relation with toxicity has not yet been consistently reported . The aim of this study was to associate malnutrition and albumin serum levels with the occurrence of chemotherapy-induced toxicity in cisplatin plus paclitaxel chemotherapy-treated NSCLC . Methods We prospect ively evaluated 100 stage IV NSCLC patients treated with paclitaxel ( 175 mg/m2 ) and cisplatin ( 80 mg/m2 ) . Malnutrition was assessed using SGA prior treatment . Neutrophil Lymphocyte Ratio ( NLR ) and the Platelet Lymphocyte Ratio ( PLR ) were used to determine the presence of systemic inflammatory response ( SIR ) and were related to the development of toxicity . Toxicity was grade d according to NCI CTCAE version 3.0 after two chemotherapy cycles . Results Median age was 58 ± 10 years , 51 % of patients were malnourished , 50 % had albumin ≤3.0 mg/mL. NLR ≥ 5 was associated with basal hypoalbuminemia ( mean ranks , 55.7 vs. 39 p = 0.006 ) , ECOG = 2 ( 47.2 vs. 55.4 p = 0.026 ) and PLR ≥ 150 were significantly related with a basal body mass index ≤20 ( 56.6 vs. 43.5 ; p = 0.02 ) and hypoalbuminemia ( 58.9 vs. 41.3 ; p = 0.02 ) . Main toxicities observed after 2 cycles of chemotherapy were alopecia ( 84 % ) , nausea ( 49 % ) , neuropathy ( 46 % ) , anemia ( 33 % ) , lymphopenia ( 31 % ) , and leukopenia ( 30 % ) . Patients malnourished and with hypoalbuminemia developed more chemotherapy-induced toxicity overall when compared with those without malnutrition ( 31 vs 22 ; p = 0.02 ) and normal albumin ( mean ranks , 62 vs 43 ; p = 0.002 ) , respectively . Hypoalbuminemia was associated with anemia ( 56 vs 47 ; p = 0.05 ) , fatigue ( 58 vs 46 ; p = 0.01 ) , and appetite loss ( 57.1 vs 46.7 ; p = 0.004 ) compared with normal albumin . PLR ≥ 150 was related with the development of toxicity grade III/IV ( 59.27 vs. 47.03 p = 0.008 ) and anemia ( 37.9 vs 53.8 p = 0.004 ) . ConclusionS IR parameters were associated with malnutrition , weight loss and hypoalbuminemia . Chemotherapy-induced toxicity in NSCLC patients treated with paclitaxel and cisplatin was associated with malnutrition and hypoalbuminemia . Early nutritional assessment and support might confer beneficial effects", "BACKGROUND Patients referred for lung cancer operations were reported to be nutritionally depleted . This may be relevant in determining patient outcome after surgical procedures . A study was undertaken to measure a range of nutritional variables including dietary intake of patients referred to a regional cardiothoracic center for curative lung cancer operations . METHODS Anthropometric measurements , grip strength , fat-free mass ( FFM ) , serum protein concentrations , lymphocyte count , creatinine-height index , subjective global assessment , and data on daily intakes of energy , protein , and vitamin C were collected prospect ively . Anthropometric indices were also measured in a group of control patients with mild chronic obstructive pulmonary disease . RESULTS Sixty patients and 22 control patients were recruited . Weight , skin-fold thickness , and grip strength were not significantly different between patients and control patients , and both groups were similar to the general population . However , 8 patients ( 13.3 % ) had a body mass index ( BMI ) less than 20 , and 14 patients ( 24.1 % ) had a fat-free mass index less than 15 . Serum albumin and transferrin concentrations and lymphocyte count were very rarely depressed but prealbumin and retinol-binding protein levels were below normal in 11.9 % and 8.3 % of patients , respectively . Thirty percent of patients reported low energy intake , 13 % reported a low protein intake , and 61.7 % had reduced vitamin C intake . CONCLUSIONS Severe nutritional depletion was uncommon in patients referred for operations for lung cancer and its frequency may have been overestimated in some previous reports . A low intake of vitamin C was common in our patients but its clinical significance is unclear", "Oxidative stress plays a role in the tumor-cytotoxic effect of cancer chemotherapy and radiotherapy and also in certain adverse events . In view of these conflicting aspects , a double-blind trial over a 6-month period was performed to determine whether a cysteine-rich protein ( IMN1207 ) may have a positive or negative effect on the clinical outcome if compared with casein , a widely used protein supplement low in cysteine . Sixty-six patients with stage IIIB-IV non-small cell lung cancer were r and omly assigned to IMN1207 or casein . Included were patients with a previous involuntary weight loss of > or = 3 % , Karnofsky status > or = 70 , and an estimated survival of > 3 months . Thirty-five lung cancer patients remained on study at 6 weeks . Overall compliance was not different between treatment arms ( 42 - 44 % or 13 g/day ) . The patients treated with the cysteine-rich protein had a mean increase of 2.5 % body weight , whereas casein-treated patients lost 2.6 % ( p = 0.049 ) . Differences in secondary endpoints included an increase in survival , h and -grip force , and quality of life . Adverse events were mild or moderate . Further studies will have to show whether the positive clinical effects can be confirmed and related to specific parameters of oxidative stress in the host", "PURPOSE To evaluate the effect of megestrol acetate at a lower dose than previously investigated on the symptoms of cachexia in patients with advanced cancer . METHODS A total of 84 patients with advanced , solid tumours not responsive to hormone therapy were enrolled in this double-blind , crossover study . During phase 1 , patients were r and omly assigned to receive megestrol acetate ( 160 mg 3 times daily ) for 10 days or placebo . During phase 2 , after a 2-day washout period , patients received the alternate treatment for 10 days . Patients underwent daily assessment s of activity , nausea , appetite and well-being by means of a visual analogue scale ( VAS ) . In addition , nutritional status ( weight , tricep skinfold measure , arm muscle circumference ) , energy intake , fatigue ( Piper Fatigue Scale ) and quality of life ( Functional Living Index-Cancer [ FLIC ] ) were assessed . RESULTS Among the 53 evaluable patients megestrol acetate result ed in a significant improvement in appetite ( p = 0.005 ) , activity ( p = 0.007 ) and well-being ( p = 0.03 ) . There was no significant change in the intensity of nausea , nutritional parameters , energy intake or FLIC scores . There was a significant improvement in 2 of the 3 factors measured by the Piper Fatigue Scale and in the overall fatigue score . Upon completion of the study , while still blind to the treatment condition , 30 patients indicated that they felt better overall after megestrol , 15 said they felt better after placebo , and 10 indicated no preference ( p = 0.001 ) . CONCLUSION Treatment with megestrol acetate results in rapid and significant improvement of symptoms in terminally ill patients at lower doses than previously reported . The effects are not secondary to nutritional changes . The FLIC quality -of-life question naire was unable to detect these changes", "PURPOSE In a r and omized clinical trial in patients with advanced non-small-cell lung cancer ( NSCLC ) , infusion with adenosine 5'-triphosphate ( ATP ) inhibited loss of body weight and quality of life . In the present article , the effects of ATP on body composition , energy intake , and energy expenditure as secondary outcome measures in the same patients are reported . PATIENTS AND METHODS Patients with NSCLC , stage IIIB or IV , were r and omized to receive either 10 intravenous , 30-hour ATP infusions every 2 to 4 weeks or no ATP . Fat mass ( FM ) , fat-free mass ( FFM ) , and arm muscle area were assessed at 4-week intervals for 28 weeks . Food intake , body cell mass ( BCM ) , and resting energy expenditure ( REE ) were assessed at 8-week intervals for 16 weeks . Between-group differences were tested for statistical significance by repeated- measures analysis of covariance . RESULTS Fifty-eight patients were r and omized ( 28 ATP , 30 control ) . No change in body composition over the 28-week follow-up period was found in the ATP group , whereas , per 4 weeks , the control group lost 0.6 kg of FM ( P = .004 ) , 0.5 kg of FFM ( P = .02 ) , 1.8 % of arm muscle area ( P = .02 ) , and 0.6 % of BCM/kg body weight ( P = .054 ) and decreased 568 KJ/d in energy intake ( P = .0001 ) . Appetite also remained stable in the ATP group but decreased significantly in the control group ( P = .0004 ) . No significant differences in REE between the ATP and control groups were observed . CONCLUSION The inhibition of weight loss by ATP infusions in patients with advanced NSCLC is attributed to counteracting the loss of both metabolically active and inactive tissues . These effects are partly ascribed to maintenance of energy intake", "PURPOSE Eicosapentaenoic acid ( EPA ) has been proposed to have specific anticachectic effects . This trial compared EPA diethyl ester with placebo in cachectic cancer patients for effects on weight and lean body mass . PATIENTS AND METHODS Five hundred eighteen weight-losing patients with advanced gastrointestinal or lung cancer were studied in a multicenter , double-blind , placebo controlled trial . Patients were r and omly assigned to receive a novel preparation of pure EPA at a dose of 2 g or 4 g daily or placebo ( 2 g EPA , n = 175 ; 4 g EPA , n = 172 ; placebo , n = 171 ) . Patients were assessed at 4 weeks and 8 weeks . RESULTS The groups were well balanced at baseline . Mean weight loss at baseline was 18 % ( n = 518 ) . Over the 8-week treatment period , both intention-to-treat analysis and per protocol analysis revealed no statistically significant improvements in survival , weight , or other nutritional variables . There was , however , a trend in favor of EPA with analysis of the primary end point , weight , at 8 weeks showing a borderline , nonsignificant treatment effect ( P = .066 ) . Relative to placebo , mean weight increased by 1.2 kg with 2 g EPA ( 95 % CI , 0 kg to 2.3 kg ) and by 0.3 kg with 4 g EPA ( -0.9 kg to 1.5 kg ) . CONCLUSION The results indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia . Future studies should concentrate on other agents or combination regimens", "PURPOSE This study tested whether infliximab , a chimeric IgG1kappa monoclonal antibody that blocks tumor necrosis factor ( TNF ) alpha , improves/stabilizes weight loss in elderly and /or poor performance status patients with metastatic non-small cell lung cancer ( NSCLC ) . METHODS This double-blind trial r and omly assigned patients to infliximab/docetaxel ( n=32 ) versus placebo/docetaxel ( n=29 ) . The primary endpoint was > or = 10 % weight gain . RESULTS Groups were balanced with respect to age , number of prior chemotherapy regimens , baseline weight loss , and performance status . No patient gained > or = 10 % baseline weight , and early evidence of the lack of efficacy prompted early trial closure . Appetite improvement was negligible in both arms . However , infliximab-/docetaxel-treated patients developed greater fatigue and worse global quality of life scores . Other outcomes , such as tumor response rate ( overall survival , were not statistically different between groups . There were no statistically significant differences in adverse events , although one death was attributed to infliximab . Genotyping for the TNF alpha -238 and -308 polymorphisms revealed no clinical significance of these genotypes , as relevant to the loss of weight or appetite . CONCLUSIONS This trial closed early because infliximab did not prevent or palliate cancer-associated weight loss . Infliximab was associated with increased fatigue and inferior global quality of life", "Involuntary weight loss is a major contributor to mortality and morbidity in patients with advanced cancer . Nutritional intervention with fish oil (FO)‐derived eicosapentaenoic acid ( EPA ) may prevent deterioration of body composition . This study compared intervention with FO with st and ard of care ( SOC ; no intervention ) with regard to weight , skeletal muscle , and adipose tissue in newly referred patients with nonsmall cell lung cancer from the time of initiation to completion of first‐line chemotherapy", "The aim of the study was to investigate the effect of intravenous infusions of adenosine 5′-triphosphate ( ATP ) on nutritional status and survival in preterminal cancer patients . Ninety-nine preterminal cancer patients ( estimated life expectancy 1–6 months ) with mixed tumor types were r and omly allocated to receive either intravenous ATP weekly ( 8–10 h/week , maximum 50 μg/kg/min ) for 8 weeks , or no ATP ( control group ) . Nutritional status parameters were assessed until 8 weeks , and analyzed by repeated- measures analysis of covariance . Cox proportional hazards models were fitted to assess the effect of ATP on short-term ( 0–8 weeks ) and long-term ( 0–6 months ) survival . Fifty-one patients were r and omized to ATP and 48 to the control group . Results showed a significant favorable effect of ATP on triceps skin fold thickness [ between-group difference per 8 weeks 1.76 mm , 95 % confidence interval ( CI ) : 0.48–3.12 mm ; P = 0.009 ] and on short-term survival [ 0–8 weeks hazard ratio ( HR ) : 0.40 , 95 % CI : 0.17–0.95 ; P = 0.037 ] . In weight-stable patients and in lung cancer patients , long-term survival ( 0–6 months ) was also significantly better in ATP-treated patients ( weight-stable patients HR : 0.40 , 95 % CI : 0.19–0.83 ; P = 0.014 ; patients with lung cancer : HR : 0.35 , 95 % CI : 0.14–0.88 ; P = 0.025 ) . In conclusion , in this population of preterminal cancer patients , ATP infusions , at the dose and schedule studied , had a favorable effect on triceps skin fold thickness and survival , especially in weight-stable patients and patients with lung cancer . Larger studies are warranted to confirm these findings and to further define the effect of ATP on tumor growth and survival", "The authors examined the effect of recombinant-human growth hormone ( r-hGH ) and insulin ( INS ) administration on protein kinetics in cancer patients . Twenty-eight cancer patients either received r-hGH for 3 days ( GH group , n = 12 , weight loss = 6 + /- 2 % ) or were not treated ( control [ CTL ] group , n = 16 , weight loss = 11 + /- 2 % ) before metabolic study . Recombinant-human growth hormone dose was 0.1 mg/kg/day ( n = 6 ) or 0.2 mg/kg/day ( n = 6 ) . Patients then underwent measurement of baseline protein kinetics ( GH/B , CTL/B ) followed by a 2-hour euglycemic insulin infusion ( 1 mU/kg/minute ) and repeat kinetic measurements ( GH/INS , CTL/INS ) . Whole-body protein net balance ( mumol leucine/kg/minute ) was higher ( p less than 0.05 ) in GH/INS ( 0.20 + /- 0.06 ) than in CTL/INS ( 0.06 + /- 0.03 ) or GH/B ( -0.19 + /- 0.03 ) . Skeletal muscle protein net balance ( nmol phenylalanine/100 g/minute ) in GH/INS ( 25 + /- 6 ) and CTL/INS ( 19 + /- 5 ) was higher than CTL/B ( -18 + /- 3 ) . Recombinant-human growth hormone and insulin reduce whole-body and skeletal muscle protein loss in cancer patients . Simultaneous use of these agents during nutritional therapy may benefit the cancer patient", "Objective . To evaluate body composition changes , specifically skeletal muscle mass , in men receiving and rogen deprivation with luteinizing-hormone releasing hormone-agonist ( LHRH-A ) for prostate cancer ( PCa ) in comparison with healthy controls . Design . Retrospective analysis of body composition changes in men with prostate cancer receiving LHRH-A therapy from 2 clinical trials compared to men without prostate cancer serving as a placebo-control in another clinical trial . Setting . Clinical Research Center in Connecticut . Participants . Thirty men ( > 60 years ) receiving 6 months of LHRH-A therapy for PCa were compared to a healthy group of 25 men without PCa . Measurements . Appendicular skeletal muscle/height2 ( ASM/ht2 ) , lean and fat mass were assessed by dual energy x-ray absorptiometry . Total testosterone levels were assessed by enzyme immunoassay . Results . At baseline , 12/30 ( 40 % ) of the treatment group and 7/25 ( 28 % ) of the control group ( p = 0.11 ) met criteria for sarcopenia . There were no differences between control groups in ASM/ht2 or lean mass . The LHRH-A group had a higher percent body fat than the control group , 29.8 ± 6.3 versus 26.3 ± 4.6 ( p = 0.02 ) . ASM/ht2 and lean mass decreased in the LHRH-A group from 7.5 ± 0.9 kg to 7.3 ± 0.9 kg ( −2.3 % ± 0.03 ; p ⩽ 0.001 ) and 53.5 ± 5.4 kg to 52.3 ± 5.3 kg ( −2.1 % ± 0.03 ; p ⩽ 0.001 ) , respectively . There was no muscle loss in the control group . At 6 months , the LHRH-A group had increased percent body fat from 29.8 ± 6.4 to 32.2 ± 5.8 ( 9.5 % ± 0.13 ; p ⩽ 0.001 ) , whereas the control group had decreased in percent body fat from 26.6 ± 4.6 to 25.3 ± 5.0 ( −3.8 % ± 0.08 ; p = 0.02 ) . Conclusions . Men undergoing LHRH-A treatment for PCa decreased appendicular skeletal muscle and lean tissue and increased body fat within 6 months of initiation of therapy . Lifestyle changes or medical interventions to minimize the effects of and rogen deprivation therapy for PCa deserve investigation", "Introduction : A significant proportion of lung cancer patients receive no anticancer treatment . This varies from 19 % in USA , 33 % in Australia , 37 % in Scotl and , and 50 % in Irel and . The aim of this study was to identify the reasons behind this . Methods : The Lung Cancer Multidisciplinary Meeting ( MDM ) in South-West Sydney prospect ively collects data on all patients presented . All new lung cancer patients presented between December 1 , 2005 , and December 31 , 2007 , were review ed . Patients were assigned optimal treatment based on evidence -based guidelines . Those patients in whom guidelines recommended no treatment ( GNT ) were compared with those whom the MDM recommended no treatment ( MNT ) and with those who actually received no treatment ( ANT ) . Results : There were 335 patients with a median age of 69 years . A total of 82 % had non-small cell lung cancer , 14 % had small cell lung cancer , and 4 % had no pathologic diagnosis . Eighty-five percent had locally advanced or metastatic disease . GNT was recommended in 4 % ( n = 13 ) , MNT in 10 % ( n = 32 ) but ANT comprised 20 % ( n = 66 ) . The differences between GNT and MNT were mainly due to patient comorbidities and clinician decision , but the differences between MNT and ANT were due to patient preference and declining performance status . In multivariate analysis , older age , poorer Eastern Cooperative Oncology Group status , non-small cell lung cancer , and non-English language predicted for ANT . Conclusions : The proportion of patients with lung cancer receiving no treatment is greater than that predicted by guidelines or recommended by the MDM but lower than that described in population -based studies suggesting that MDMs can improve treatment utilization in lung cancer" ]

[ "Background . Resistance training research has demonstrated positive effects for persons with Parkinson 's disease ( PD ) , but the number of acute training variables that can be manipulated makes it difficult to determine the optimal resistance training program . Objective . The purpose of this investigation was to examine the effects of an 8-week resistance training intervention on strength and function in persons with PD . Methods . Eighteen men and women were r and omized to training or st and ard care for the 8-week intervention . The training group performed 3 sets of 5–8 repetitions of the leg press , leg curl , and calf press twice weekly . Tests included leg press strength relative to body mass , timed up- and -go , six-minute walk , and Activities-specific Balance Confidence question naire . Results . There was a significant group-by-time effect for maximum leg press strength relative to body mass , with the training group significantly increasing their maximum relative strength ( P .05 ) . Conclusions . Moderate volume , high-load weight training is effective for increasing lower-body strength in persons with PD", "Background and Purpose : Distinguishing between a clinical ly significant change and change due to measurement error can be difficult . The purpose of this study was to determine test-retest reliability and minimal detectable change for the Berg Balance Scale ( BBS ) , forward and backward functional reach , the Romberg Test and the Sharpened Romberg Test ( SRT ) with eyes open and closed , the Activities-specific Balance Confidence ( ABC ) Scale , the Six-Minute Walk Test ( 6MWT ) , comfortable and fast gait speed , the Timed “ Up & Go ” Test ( TUG ) , the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) , and the Unified Parkinson Disease Rating Scale ( UPDRS ) in people with parkinsonism . Subjects : Thirty-seven community-dwelling adults with parkinsonism ( mean age=71 years ) participated . The Hoehn and Yahr Scale median score of 2 was on the lower end of the scale ; however , the scores ranged from 1 to 4 . Methods : Subjects were tested twice by the same raters , with 1 week between tests . Test-retest reliability was calculated using intraclass correlation coefficients ( ICCs ) . Minimal detectable change was calculated using a 95 % confidence interval ( MDC95 ) . Results : The ICCs for test-retest reliability were above .90 for the BBS , ABC Scale , SRT with eyes closed , 6MWT , and comfortable and fast gait speeds . The MDC95 values for those functional tests were : BBS=5/56 , ABC Scale=13 % , SRT with eyes closed=19 seconds , 6MWT=82 m , comfortable gait speed=0.18 m/s , and fast gait speed=0.25 m/s . The ICCs for test-retest reliability of SF-36 scores were above .80 , with the exception of the social functioning subscale . The MDC95 values for the SF-36 ranged between 19 % and 45 % . The MDC95 values for the UPDRS Activities of Daily Living section , Motor Examination section , and total scores were 4/52 , 11/108 , and 13/176 , respectively . Discussion and Conclusion : Minimal detectable change values are useful to therapists in rehabilitation and wellness programs in determining whether change during or after intervention is clinical ly significant . High test-retest reliability of scores for the BBS , ABC Scale , SRT with eyes closed , 6MWT , and gait speed make them trustworthy functional assessment s in people with parkinsonism . The SF-36 and UPDRS provide quality -of-life and disease severity rating values in the ongoing assessment of people with parkinsonism", "This r and omized controlled trial with blinded assessment aim ed to determine the effect of a 6-month minimally supervised exercise program on fall risk factors in people with Parkinson 's disease ( PD ) . Forty-eight participants with PD who had fallen or were at risk of falling were r and omized into exercise or control groups . The exercise group attended a monthly exercise class and exercised at home three times weekly . The intervention targeted leg muscle strength , balance , and freezing . The primary outcome measure was a PD falls risk score . The exercise group had no major adverse events and showed a greater improvement than the control group in the falls risk score , which was not statistically significant ( between group mean difference = -7 % , 95 % CI -20 to 5 , P = 0.26 ) . There were statistically significant improvements in the exercise group compared with the control group for two secondary outcomes : Freezing of Gait Question naire ( P = 0.03 ) and timed sit-to-st and ( P = 0.03 ) . There were statistically nonsignificant trends toward greater improvements in the exercise group for measures of muscle strength , walking , and fear of falling , but not for the measures of st and ing balance . Further investigation of the impact of exercise on falls in people with PD is warranted", "The lower extremity performance in elderly female patients with mild to moderate Parkinson 's disease ( PD ; n = 12 ) and controls ( n = 16 ) was compared . Isometric dynamometry and force-plate measurements were used . PD patients had lower ( p than control participants . BL strength deficit was greater ( p longer chair-rise time and lower maximal rate of vertical-ground-reaction-force development while rising from a chair was found in PD patients than in controls . These findings suggest that elderly women with PD have lowered voluntary isometric force-generation capacity of the leg-extensor muscles . Reduced BL leg-extension strength might contribute to the difficulty of individuals with PD to rise from a chair", "BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from \" fair \" to \" substantial , \" and the reliability of the total PEDro score was \" fair \" to \" good .", "Persons with Parkinson disease ( PD ) often demonstrate bradykinesia during mobility tasks . Bradykinesia combined with other PD-related movement deficits may contribute to self-reported reductions in quality of life . At this time , no studies have examined the effects of resistance exercise as an intervention to reduce bradykinesia and improve self-reported quality of life . Therefore , we examined changes in muscle force production , clinical measures of bradykinesia , and quality of life following 12 weeks of a high intensity eccentric resistance exercise program in persons with mild to moderate PD . Twenty individuals with idiopathic PD were matched into an experimental or an active control group . All participants were tested prior to and following a 12-week intervention period . The experimental group performed high intensity quadriceps contractions on an eccentric ergometer 3 days a week for 12 weeks . The active control group participated in an evidence based exercise program of PD . The outcome variables were quadriceps muscle force , clinical bradykinesia measures ( gait speed , timed up and go ) and disease specific quality of life ( Parkinson 's disease question naire-39 [ PDQ-39 ] ) . Data was analyzed using separate 2 ( group ) x 2 ( time period ) ANOVAs . Results demonstrated significant time by group interaction effects for gait speed , timed up and go , and the composite PDQ-39 score ( p Muscle force , bradykinesia , and QOL were improved to a greater degree in those that performed high intensity eccentric resistance training compared to an active control group . Additional research is needed to determine if this type of training has long-term impact and if it results in an alteration of the natural history of mobility and QOL decline in persons with PD", "OBJECTIVE To assess immediate and near-term effects of 2 exercise training programs for persons with idiopathic Parkinson 's disease ( IPD ) . DESIGN R and omized control trial . SETTING Public health facility and medical center . PARTICIPANTS Fifteen persons with IPD . INTERVENTION Combined group ( balance and resistance training ) and balance group ( balance training only ) underwent 10 weeks of high-intensity resistance training ( knee extensors and flexors , ankle plantarflexion ) and /or balance training under altered visual and somatosensory sensory conditions , 3 times a week on nonconsecutive days . Groups were assessed before , immediately after training , and 4 weeks later . MAIN OUTCOME MEASURES Balance was assessed by computerized dynamic posturography , which determined the subject 's response to reduced or altered visual and somatosensory orientation cues ( Sensory Orientation Test [ SOT ] ) . Muscle strength was assessed by measuring the amount of weight a participant could lift , by using a st and ardized weight- and -pulley system , during a 4-repetition-maximum test of knee extension , knee flexion , and ankle plantarflexion . RESULTS Both types of training improved SOT performance . This effect was larger in the combined group . Both groups could balance longer before falling , and this effect persisted for at least 4 weeks . Muscle strength increased marginally in the balance group and substantially in the combined group , and this effect persisted for at least 4 weeks . CONCLUSION Muscle strength and balance can be improved in persons with IPD by high-intensity resistance training and balance training" ]

[ "Selective serotonin reuptake inhibitors ( SSRIs ) are increasingly used to treat premature ejaculation . We report a large prospect i ve placebo-controlled crossover study of sertraline in premature ejaculation ( PE ) using Arabic Index of Premature Ejaculation ( AIPE ) . One hundred and forty-seven men suffering from PE were enrolled in a r and omized single-blinded crossover study of sertraline hydrochloride and placebo . Patients were r and omized into group 1 ( n=77 ) and group 2 ( n=70 ) . Both groups received sertraline and placebo interchangeably for 4 weeks . Overall , 127 ( 81 % ) of 157 subjects experienced a significant increase in their AIPE total score after sertraline treatment . Sixty-six ( 66 % ) of 100 patients available for follow-up experienced relapse of PE within 6 months after sertraline withdrawal . The active drug was generally well tolerated . Our relatively large study , using a vali date d question naire ( AIPE ) , confirmed the useful effect of sertraline on PE", "Abstract Objectives : To compare the clinical efficacy of the on-dem and use of four drugs in the management of patients with premature ejaculation ( PE ) , as the off-label use of selective serotonin-reuptake inhibitors and topical penile anaesthetics is frequently indicated for the management of patients with PE , and tramadol HCl and sildenafil citrate were also tried for managing this disorder , but with recommendations based on weak evidence . Patients and methods : This was a single-centre , single-blind , placebo-controlled clinical trial conducted on 150 patients who had PE for > 1 year . Patients were r and omised equally into five groups . On-dem and tramadol , sildenafil , paroxetine , local lidocaine gel or placebo was given for patients in groups 1–5 , respectively . During the month before treatment , the intravaginal ejaculation latency time ( IELT ) and sexual satisfaction scores ( on a 0–5-point scale ) were measured and compared to the mean IELT and sexual satisfaction scores recorded during 4 weeks of on-dem and drug administration , with monitoring of any possible side-effects . Results : Tramadol-treated patients had a significantly longer mean ( SD ) IELT , of 351 ( 119 ) s , than the other groups . Local anaesthetic was significantly better than paroxetine in prolonging the IELT , at 278 ( 111 ) vs. 186 ( 65 ) s , respectively . The improvement in sexual satisfaction was significantly better in the sildenafil group , with a mean ( SD ) improvement of 2.9 ( 1 ) points , than in the paroxetine and local anaesthetic groups , at 2.2 ( 0.9 ) and 1.9 ( 0.9 ) points , respectively . Conclusions : The four drugs significantly improved IELT values over placebo . Tramadol was associated with significantly longer IELT values , whilst sildenafil induced significantly better sexual satisfaction than the other drugs . The four drugs had tolerable side-effects", "BACKGROUND No drugs are approved for treatment of premature ejaculation . Our aim was to determine the efficacy and tolerability of on-dem and dapoxetine in patients with severe premature ejaculation . METHODS We determined the efficacy of dapoxetine in a prospect ively predefined integrated analysis of two 12-week r and omised , double-blind , placebo-controlled , phase III trials of identical design done independently , in parallel , at 121 sites in the USA . Men with moderate-to-severe premature ejaculation in stable , heterosexual relationships took placebo ( n=870 ) , 30 mg dapoxetine ( 874 ) , or 60 mg dapoxetine ( 870 ) on-dem and ( as needed , 1 - 3 h before anticipated sexual activity ) . The primary endpoint was intravaginal ejaculatory latency time ( IELT ) measured by stopwatch . Safety and tolerability were assessed . All analyses were done on an intention-to-treat basis . The trials are registered at Clinical Trials.gov , numbers NCT00211107 and NCT00211094 . FINDINGS 672 , 676 , and 610 patients completed in the placebo , 30 mg dapoxetine , and 60 mg dapoxetine groups , respectively . Dapoxetine significantly prolonged IELT ( p Mean IELT at baseline was 0.90 ( SD 0.47 ) minute , 0.92 ( 0.50 ) minute , and 0.91 ( 0.48 ) minute , and at study endpoint ( week 12 or final visit ) was 1.75 ( 2.21 ) minutes for placebo , 2.78 ( 3.48 ) minutes for 30 mg dapoxetine , and 3.32 ( 3.68 ) minutes for 60 mg dapoxetine . Both dapoxetine doses were effective on the first dose . Common adverse events ( 30 mg and 60 mg dapoxetine , respectively ) were nausea ( 8.7 % , 20.1 % ) , diarrhoea ( 3.9 % , 6.8 % ) , headache ( 5.9 % , 6.8 % ) , and dizziness ( 3.0 % , 6.2 % ) . INTERPRETATION On-dem and dapoxetine is an effective and generally well tolerated treatment for men with moderate-to-severe premature ejaculation", "The aim of the study was to compare the clinical efficacy and safety of the on‐dem and use of paroxetine , dapoxetine , sildenafil and combined dapoxetine with sildenafil in treatment of patients with premature ejaculation ( PE ) . In a single‐blind placebo‐controlled clinical study , 150 PE patients without erectile dysfunction ( ED ) were included during the period of March 2015 to May 2016 . Patients were r and omly divided into five groups ( 30 patients each ) . On dem and placebo , paroxetine ( 30 mg ) , dapoxetine ( 30 mg ) , sildenafil citrate ( 50 mg ) and combined dapoxetine ( 30 mg ) with sildenafil citrate ( 50 mg ) were given for patients for 6 weeks in each group respectively . All patients were instructed to record intravaginal ejaculatory latency time ( IELT ) and evaluated with Premature Ejaculation Diagnostic Tool ( PEDT ) and the patient satisfaction score before and after treatment . The mean of IELT , satisfaction score and PEDT in all groups was significantly improved after treatment ( p value = .001 ) . Combined dapoxetine with sildenafil group had the best values of IELT , satisfaction scores and PEDT in comparison with other treatment groups ( p value .001 ) . The combined dapoxetine with sildenafil therapy could significantly improve PE patients without ED as compared to paroxetine alone or dapoxetine alone or sildenafil alone with tolerated adverse effects", "OBJECTIVES To determine the efficacy of tramadol in premature ejaculation ( PE ) treatment compared with placebo . METHODS A single-blind , placebo-controlled , crossover study was conducted with 60 lifelong ( primary ) patients with PE . The patients were r and omized into 2 groups , each consisting of 30 patients , who took tramadol or placebo on dem and . PE was defined as an intravaginal ejaculation latency time of ≤60 seconds in 90 % of intercourse episodes . The efficacy of the drugs was assessed using the intravaginal ejaculation latency time , ability of ejaculation control , and sexual satisfaction scores after an 8-week treatment period . RESULTS All participants completed the study voluntarily . Two groups were similar in terms of the patient demographics . Increases in the intravaginal ejaculation latency time , ability of ejaculation control , and sexual satisfaction score between the placebo and tramadol groups were compared with the baseline values in both groups . At the end of study period , the tramadol group had significantly ( P tramadol is effective for lifelong PE . Currently , selective seratonin reuptake inhibitors such as dapoxetine , are a more popular treatment option for PE . However , tramadol might be considered an alternative agent for primary PE treatment", "PURPOSE Fluoxetine , a selective serotonin re-uptake inhibitor , has been shown to increase the intravaginal latency of patients with premature ejaculation . We demonstrated the effects of fluoxetine on intravaginal latency , penile sensory threshold , and variables of sacral evoked response and cortical somatosensorial evoked potential in patients with premature ejaculation . MATERIAL S AND METHODS Of 48 patients 40 who presented to our clinic with premature ejaculation met the study criteria , gave written or oral consent , and were divided r and omly in a double-blind fashion into 2 groups of 20 patients . The study group received 20 mg . fluoxetine daily and the control group received placebo for 1 month . The patients were evaluated during visits before and after treatment for intravaginal latency , penile sensory threshold values , and the variables of sacral evoked response and cortical somatosensory evoked potential tests . RESULTS Patient ages , intravaginal latencies , penile sensory threshold values , and amplitudes and latencies of sacral evoked response and cortical somatosensory evoked potential tests in both groups were not significantly different at the beginning of treatment ( p > 0.05 ) . At the end of treatment intravaginal latencies and penile sensory threshold values were increased in the study group compared to before treatment and the control group ( p amplitudes and latencies of sacral evoked response and cortical somatosensory evoked potential tests ( p > 0.05 ) . CONCLUSIONS These findings suggest that fluoxetine is effective treatment for premature ejaculation probably due to its effect of increasing the penile sensory threshold , without changing the amplitudes and latencies of sacral evoked response and cortical somatosensory evoked potential", "INTRODUCTION Dapoxetine is a short-acting selective serotonin reuptake inhibitor that was recently approved for the on-dem and treatment of premature ejaculation ( PE ) . AIM To evaluate the efficacy and safety of dapoxetine 30 mg and 60 mg on dem and ( prn ) in men with PE from the Asia-Pacific region . METHODS This r and omized , double-blind , parallel-group , placebo-controlled trial enrolled men who were 18 years or older ; in a monogamous , heterosexual relationship for at least 6 months ; met the Diagnostic and Statistical Manual of Mental Disorders , fourth edition , text revision , criteria for PE for at least 6 months ; and had an intravaginal ejaculatory latency time ( IELT ) of 2 minutes or less in at least 75 % of sexual intercourse episodes . Subjects received placebo , dapoxetine 30 mg , or dapoxetine 60 mg prn ( 1 - 3 hours before intercourse ) for 12 weeks . MAIN OUTCOME MEASURES Stopwatch-measured Average IELT , the Premature Ejaculation Profile ( PEP ) , Clinical Global Impression ( CGI ) of change in PE , treatment-emergent adverse events ( TEAEs ) . RESULTS Of the 1,067 subjects r and omized , 858 completed the study . Mean Average IELT increased from approximately 1.1 minutes at baseline ( across groups ) to 2.4 , 3.9 , and 4.2 minutes with placebo , dapoxetine 30 mg , and dapoxetine 60 mg , respectively , and geometric mean Average IELT increased from approximately 0.9 minutes at baseline ( across groups ) to 1.8 , 2.7 , and 3.1 minutes , respectively ( fold-increases of 2.0 , 2.8 , and 3.3 , respectively ) . All PEP measures and the CGI of change were significantly improved with dapoxetine vs. placebo at study endpoint ( P dapoxetine included nausea , dizziness , somnolence , headache , vomiting , diarrhea , and nasopharyngitis ; TEAEs led to discontinuation in 0.3 % , 1.7 % , and 5.1 % of subjects with placebo , dapoxetine 30 mg , and dapoxetine 60 mg , respectively . CONCLUSIONS Dapoxetine treatment significantly prolonged IELT and improved PEP measures and was generally well tolerated in men with PE in the Asia-Pacific region", "BACKGROUND Dapoxetine is being developed for the on-dem and treatment of premature ejaculation ( PE ) . Previous clinical trials have demonstrated its safety and efficacy . OBJECTIVE To evaluate the long-term efficacy and safety of dapoxetine in men with PE . DESIGN , SETTING , AND PARTICIPANTS This r and omized , double-blind , parallel-group , placebo-controlled , phase 3 trial , conducted in 22 countries , enrolled men ( N=1162 ) > or = 18 yr of age who met the Diagnostic and Statistical Manual of Mental Disorders , fourth edition , text revision criteria for PE for > or = 6 mo , with an intravaginal ejaculatory latency time ( IELT ) or = 75 % of intercourse episodes at baseline . INTERVENTION Dapoxetine 30 mg or dapoxetine 60 mg or placebo on dem and ( 1 - 3 h before intercourse ) for 24 wk . MEASUREMENTS Stopwatch-measured IELT , Premature Ejaculation Profile ( PEP ) , Clinical Global Impression ( CGI ) of change , adverse events ( AEs ) . RESULTS AND LIMITATIONS The study was completed by 618 men . Mean average IELT increased from 0.9 min at baseline ( all groups ) to 1.9 min , 3.2 min , and 3.5 min with placebo and dapoxetine 30 mg and dapoxetine 60 mg , respectively , at study end point ; geometric mean IELT increased from 0.7 min at baseline to 1.1 min , 1.8 min , and 2.3 min , respectively , at study end point . All PEP measures and IELTs improved significantly with dapoxetine versus placebo at week 12 and week 24 ( p nausea , dizziness , diarrhea , and headache . AEs led to discontinuation in 1.3 % , 3.9 % , and 8.2 % of subjects with placebo and dapoxetine 30 mg and dapoxetine 60 mg , respectively . Limitations of this study included the exclusion of men who were not in long-term monogamous relationships . CONCLUSIONS Dapoxetine significantly improved all aspects of PE and was generally well tolerated in this broad population", " Seventeen male out patients with premature ejaculation were r and omly assigned to treatment with paroxetine ( N = 8) or placebo ( N = 9 ) . After a first week dose of 20 mg/day , the paroxetine regimen was increased to 40 mg/day for 5 weeks . Patients and their female partners were interviewed separately . Patients treated with paroxetine had significantly greater clinical improvement than the patients given placebo", "Background : Several recent studies have investigated the therapeutic role of phosphodiesterase type 5 ( PDE5 ) inhibitors in premature ejaculation ( PE ) used in the treatment of erectile dysfunction . Objectives : In the present research , the efficacy of paroxetine alone and paroxetine plus tadalafil was compared in patients referred because of premature ejaculation . Patients and Methods : This quasi-experimental study was performed on 100 consecutive 17 to 49-year-old potent men with premature ejaculation and without any clear organic disease . All patients had lifelong PE with an intravaginal ejaculation latency time ( IELT ) shorter than 1.5 minutes . Informed consent was obtained from all patients who were r and omly divided into two groups using a computer-generated r and om tabulation list . In group A , patients received 10 mg paroxetine daily , in addition to four hours before planned sexual activity . In group B , 10 mg paroxetine was taken daily , plus 10 mg tadalafil one hour before planned sexual activity . The duration of the intervention was six months and patients were evaluated for IELT three and six months after the beginning of therapy . Results : The mean age of patients in groups A and B were 33 ± 9.6 and 31.2 ± 9.3 years , respectively ( P = 0.368 ) . The mean number of intercourses were 1.08 ± 0.6 and 1.12 ± 0.6 per week in groups A and B , respectively ( P = 0.791 ) . Mean IELT at the 3-month follow up in groups A and B was 4.5 ± 1.5 and 5 ± 2.4 minutes , respectively ( P = 0.285 ) and at the 6-month follow up was 4.8 ± 1 and 5.3 ± 2 minutes , respectively ( P = 0.278 ) . Conclusions : The results of the study show that tadalafil can increase the mean IELT and can be used for treatment of premature ejaculation in combination with paroxetine", "PURPOSE The efficacy of the selective serotonin re-uptake inhibitor fluoxetine in the treatment of premature ejaculation was examined . MATERIAL S AND METHODS The study comprised 17 patients with premature ejaculation who presented to the urology clinic of our medical school . In this double-blind study the patients were r and omized into treatment groups receiving 20 mg . fluoxetine daily for 1 week and 40 mg . daily afterward ( group 1 ) or 1 capsule placebo daily for 1 week and 2 capsules daily afterward ( group 2 ) . The groups were evaluated according to the latent period of intravaginal ejaculation . RESULTS The latent period of intravaginal ejaculation in group 1 was significantly longer than that in group 2 . Nausea , headache and insomnia were reported side effects . CONCLUSIONS Fluoxetine may be regarded as a safe and effective alternative in the treatment of premature ejaculation", "Depression is a common cause of sexual dysfunction , but also antidepressant medication is often associated with sexual side effects . This article includes two related studies . The first double-blind , placebo-controlled study was conducted in men with lifelong rapid ejaculation and aim ed to assess putative differences between the major selective serotonin reuptake inhibitors ( SSRIs ) ( fluoxetine , fluvoxamine , paroxetine , and sertraline ) with regard to their ejaculation-delaying effect . Sixty men with an intravaginal ejaculation latency time ( IELT ) of 1 minute or less were r and omly assigned to receive fluoxetine 20 mg/day , fluvoxamine 100 mg/day , paroxetine 20 mg/day , sertraline 50 mg/day , or placebo for 6 weeks . During the 1-month baseline and 6-week treatment periods , the men measured their IELT at home using a stopwatch . The trial was completed by 51 men . During the 6-week treatment period , the geometric mean IELT in the placebo group was constant at approximately 20 seconds . Analysis of variance revealed a between-groups difference in the evolution of IELT delay ( p = 0.0004 ) ; in the paroxetine , fluoxetine , and sertraline groups there was a gradual increase to about 110 seconds , whereas in the fluvoxamine group , IELT was increased to only approximately 40 seconds . The paroxetine , fluoxetine , and sertraline groups differed significantly ( p placebo but the fluvoxamine group did not ( p = 0.38 ) . Compared with baseline , paroxetine exerted the strongest delay in ejaculation , followed by fluoxetine and sertraline . There was no clinical ly relevant delay in ejaculation with fluvoxamine . In men with lifelong rapid ejaculation , paroxetine delayed ejaculation most strongly , whereas fluvoxamine delayed ejaculation the least . The second double-blind , placebo-controlled study was carried out in men with lifelong rapid ejaculation ( IELT 1 minute ) to investigate whether data about SSRI-induced delayed ejaculation in men with rapid ejaculation may be extrapolated to men with less-rapid ejaculation . After measurement of IELT at home ( using a stopwatch ) during a 1-month baseline assessment , 32 men with an IELT of 1 minute or less ( group 1 ) or more than 1 minute ( group 2 ) were r and omly assigned to receive paroxetine 20 mg/day or placebo for 6 weeks in a double-blind manner . Patients continued to measure their IELTs at home during the 6 weeks of the study . At baseline , 24 patients consistently had IELTs of one minute or less ( group 1 ) , and eight patients had IELTs of more than 1 minute ( group 2 ) . The geometric mean IELT was 14 seconds in group 1 and 83 seconds in group 2 . Twelve patients in group 1 and five in group 2 were r and omized to the paroxetine 20 mg/day . The percentage increase in the geometric mean IELT compared with baseline in patients treated with paroxetine was 420 % ( 95 % confidence interval [ CI ] , 216 - 758 % ) in group 1 and 480 % ( 95 % CI , 177 - 1,118 % ) in group 2 ( p = 0.81 ) . After 6 weeks of treatment with paroxetine , the geometric mean IELT was 92 seconds in group 1 and 602 seconds in group 2 ( p paroxetine-induced percentage increase in IELT seems to be independent of the baseline IELT . This suggests that ejaculation-delaying side effects of some SSRIs investigated in men with lifelong rapid ejaculation may be generalized to men with less-rapid ejaculation", "PURPOSE We evaluate the efficacy of paroxetine hydrochloride as needed for the treatment of premature ejaculation . MATERIAL S AND METHOD Study 1 comprised 26 potent men with a mean age of 39.5 years with premature ejaculation who were r and omized to receive 20 mg . oral paroxetine ( group A ) or placebo ( group B ) as needed 3 to 4 hours before planned intercourse in a controlled single-blind crossover trial . Study 2 comprised 42 potent men with a mean age of 40.5 years with premature ejaculation who were r and omized to receive 10 mg . paroxetine daily for 3 weeks and then 20 mg . paroxetine as needed ( group C ) for 4 weeks or placebo daily for 3 weeks and then placebo as needed ( group D ) for 4 weeks . RESULTS Mean pretreatment ejaculatory latency time was 0.3 minute for study 1 . At 4 weeks mean ejaculatory latency time was 3.2 minutes in the paroxetine as needed and 0.45 in the placebo as needed phase for group A ( p placebo as needed and 3.5 in the paroxetine as needed phase for group B ( p adverse effects with paroxetine or placebo in study 1 . Mean pretreatment ejaculatory latency time was 0.5 minute for study 2 . At 3 weeks mean ejaculatory latency time was 4.3 minutes in the paroxetine daily and 5.8 in the paroxetine as needed phase , and 0.9 in the placebo daily and 0.6 in the placebo as needed phase for group C ( p ejaculatory latency time was 0.8 minutes in the placebo daily and 1.1 in the placebo as needed phase , and 3.3 in the paroxetine daily and 6.1 in the paroxetine as needed phase for group D ( p Adverse effects in 7 of 42 men ( 17 % ) given paroxetine daily included an ejaculation in 3 , anorexia in 1 , gastrointestinal upset in 3 and reduced libido in 2 . Mean ejaculatory latency time was greater in the paroxetine as needed phase of study 2 than that of study 1 ( p paroxetine as needed is significantly better if patients are initially treated with the drug daily . CONCLUSIONS Paroxetine appears to be superior to placebo in the pharmacological treatment of premature ejaculation when administered on a chronic or as needed basis", "Purpose : To evaluate the efficacy and safety of most selective serotonin reuptake inhibitor drug , escitalopram , in delaying ejaculation in patients with premature ejaculation ( PE ) . Material s and Methods : A total of 276 married men ( mean age , 34.4 years ) with PE were r and omly assigned to receive 10 mg of escitalopram ( n = 138 ; Group 1 ) or placebo ( n = 138 ; Group 2 ) for 12 weeks . Pretreatment evaluation included history and physical examination , intravaginal ejaculatory latency time ( IELT ) , International Index of Erectile Function ( IIEF ) , and Meares-Stamey test . The efficacy of 2 treatments was assessed every 2 weeks during treatment , at the end of study , and in 3- and 6-month follow-up after cessation of treatment . Results : At the end of 12-week treatment , the escitalopram group had a 4.9-fold ( 95 % confidence interval [ CI ] , 3.14 - 6.12 ) increase of the geometric mean IELT , whereas after placebo , the geometric mean IELT did not increase significantly ( 1.4-fold increase ; 95 % CI , 0.86 - 1.68 ; P = 0.001 ) . Baseline mean intercourse satisfaction domain values of IIEF 10 and 11 reached to 16 and 10 at 12-week treatment in Groups 1 and 2 , respectively ( P = 0.01 ) . At the end of 6-month follow-up period , the geometric mean IELT in escitalopram and placebo group demonstrated 3.1- ( 95 % CI , 2.16 - 4.4 ) and 1.3-fold ( 95 % CI , 0.78 - 1.62 ) increase , respectively ( P = 0.001 ) . Three- and 6-month intercourse satisfaction domain values of IIEF were 15 and 14 in Groups 1 and 10 and 10 ( P = 0.01 ) in Group 2 , respectively . Mean number of adverse events was 22 for escitalopram and 9 for placebo ( P = 0.04 ) . Conclusions : Oral escitalopram is an effective treatment for PE with long-term benefit for the patient after it is withdrawn . Further studies are required to draw final conclusions on the efficacy of this drug in PE", "We investigated safety and efficacy of vardenafil and sertraline in premature ejaculation ( PE ) . Seventy‐two men grade d their primary PE on a scale of 0–8 ( 0 = almost never , 8 = almost always ) . Intravaginal ejaculatory latency time ( IELT ) was measured . Patients were included if they scored their PE as 4 or greater and their IELTs were less than 1.30 min . After 6 weeks of behavioural psychosexual therapy , 49 patients still had a PE of 4 or greater and an IELT less than 1.30 min and they were r and omised : 6 weeks vardenafil ( 10 mg ) or sertraline ( 50 mg ) . After a wash‐out phase for 1 week , medication was changed in a cross‐over design . Initially , all 72 men with PE received behavioural therapy . Twenty‐three men were satisfied with treatment and excluded . The remaining 49 men grade d their PE as 5.94 ± 1.6 and IELT was 0.59 min and patients were r and omised . Four men discontinued the study . Vardenafil improved PE grading : 2.7 ± 2.1 ( P increased to 5.01 ± 3.69 ( P grading improved 1.92 ± 1.32 , ( P IELT 3.12 ± 1.89 ( P 0.001 ) with sertraline . It is concluded that vardenafil and sertraline are useful agents in the pharmacological treatment of PE ", "Summary . Premature ejaculation is a common male sexual disorder in which orgasm and ejaculation occur before the desired moment . The primary therapeutic approach to premature ejaculation has been behavioural and pharmacotherapy . In this study , we evaluated the efficacy and optimum usage of lidocaine‐prilocaine cream 5 % in preventing premature ejaculation . Forty patients were examined in the study group and r and omized into four groups , each comprising 10 patients . Patients in group 1 applied lidocaine‐prilocaine cream 5 % for 20 min , the patients in group 2 applied it for 30 min , and the patients in group 3 applied the cream for 45 min before sexual contact , with all patients covering the penis with a condom . Patients in the fourth group applied a base cream as placebo . In group 1 , the pre‐ejaculation period increased to 6.71 ± 2.54 min without any adverse effects . In group 2 , although the pre‐ejaculation period increased in four patients up to 8.70 ± 1.70 min , six patients in this group and all patients in group 3 had erection loss because of numbness . In the placebo group , there was no change in their pre‐ejaculation period . Therefore , lidocaine‐prilocaine cream 5 % is effective in premature ejaculation and 20 min of application time before sexual contact is the optimum period", "Objectives : The objective of this study is to assess the dose-related effects of tramadol on a group of patients with premature ejaculation ( PE ) . Subjects and Methods : During the period of months between June 2010 and July 2012 , 180 PE patients presented to outpatient clinic of our hospital . Patients were r and omized in a 1:1:1 fashion to receive different sequences of the three medications : placebo , 50 mg of tramadol and 100 mg of tramadol . Every patient received 10 doses of each medication for 2 months . Intra-vaginal ejaculatory latency time ( IELT ) was recorded in seconds initially and for each arm . Successful treatment of PE is defined if IELT exceeded 120 s. Side-effects of medications were reported . Results : Of patients enrolled , 125 ( 69.4 % ) continued the study . Patients ′ age range was 20 - 55 years with PE complaint of 1 to 10 years duration . Mean IELT was 72 at presentation , 82 for placebo , 150 for tramadol 50 mg , and 272 for tramadol 100 mg ( P PE was successfully treated in only 2.4 % of patients with placebo , in contrast to 53.6 % and 85.6 % with 50 and 100 mg tramadol , respectively ( P baseline IELT was the only predictor of successful treatment of PE with both tramadol 50 mg ( odds ratio [ OR ] : 1.05 , 95 % confidence interval [ CI ] : 1.03 - 1.07 , P tramadol 100 mg ( OR : 1.07 , 95 % CI : 1.04 - 1.11 , P 12.8 % of those who received 50 mg tramadol and 33.6 % of those who received 100 mg tramadol ( P Weak scanty ejaculation was the main complaint in 7.2 % versus 21.6 % of those using 50 and 100 mg tramadol , respectively ( P = 0.002 ) . Two patients discontinued tramadol 100 mg due to side-effects . Conclusion : Tramadol hydrochloride exhibits a significant dose-related efficacy and side-effects over placebo for treatment of PE", "Background : Despite the limited number of available study comparing of their efficacy , selective serotonin re-uptake inhibitors ( SSRI ) have been thought to have beneficial effects for the patients with premature ejaculation . In the present study , we decided to examine the efficacy of citalopram , an SSRI , in the treatment of premature ejaculation . Method : The study was consisted of 26 married patients diagnosed with premature ejaculation according to Diagnostic and Statistical Manual of Mental Disorders Third Revised Version ( DSM-III-R ) . The patients were r and omly assigned to two groups , citalopram ( group I ) and placebo ( group II ) , each consisting of 13 patients . The effects of drug on the ejaculatory function were assessed by the intravaginal ejaculation latency time . Additionally , all patients were screened by using Clinical Global Impression-Improvement Scale ( CGI-I ) and Yonsei Sexual Function Inventory-II ( YSFI-II ) . Results : The increase in the intravaginal ejaculation latency time in the citalopram group was statistically significant than that of placebo group . In addition , with respect to the subscales of the YSFI-II scale , similar overall significant improvements were seen in the patients given citalopram compared to those given placebo . Of group I patients , five ( 38.5 % ) were considered as ‘ very much improved ’ and four ( 30.8 % ) ‘ much improved ’ by CGI-I and only one of group II patients ( 7.7 % ) showed ‘ much improved ’ . Conclusion : The patients treated with citalopram showed significantly greater improvement compared to the patients receiving placebo", "INTRODUCTION There is partial evidence to support the use of phophodiesterase-5 inhibitor ( PDE5-I ) for the treatment of premature ejaculation ( PE ) . AIM We compared on-dem and dosing of dapoxetine alone and combined with mirodenafil in subjects with lifelong PE and without erectile dysfunction ( ED ) . METHODS Our prospect i ve , r and omized , double-blind , placebo-controlled , multicenter trial enrolled 118 subjects with lifelong PE without ED . PE was diagnosed using Diagnostic and Statistical Manual of Mental Disorders , fourth edition , text revision . Patients were divided into two groups : dapoxetine 30 mg plus placebo ( group A , n=56 ) and dapoxetine 30 mg plus mirodenafil 50 mg ( group B , n=62 ) . MAIN OUTCOME MEASURES During 12 weeks , intravaginal ejaculatory latency time ( IELT ) and the time from foreplay to beginning intercourse ( FTIT ) with a stopwatch , and Premature Ejaculation Profile ( PEP ) were measured . Overall sexual act time ( OSAT ; sum of FTIT and IELT ) was calculated . Any treatment-emergent adverse events ( TEAEs ) were also recorded . RESULTS Over 12 weeks , IELT , OSAT , and PEP index score significantly improved in group B compared with group A ( increased geometric mean IELT in group A and B=3.6 and 6.1 minutes , P=0.026 ; increased geometric mean OSAT in group A and B=5.5 and 9.9 minutes , P=0.012 ; increased median PEP index score in group A and B=1.0 and 1.3 , P=0.046 ) . However , there was no significant difference between two groups with respect to improvement of FTIT ( P=0.147 ) . TEAEs did not differ between groups ( all P>0.05 ) , and there was no serious adverse event in any subjects . CONCLUSIONS Low dose of dapoxetine combined with mirodenafil showed better results in terms of IELT , OSAT , and PEP index score , and similar TEAEs , compared with that of dapoxetine only . Our results support the suggestion that the PDE5-Is have a potential role in the treatment of PE without ED", "Antidepressant medication is often associated with sexual side effects . A double-blind , placebo-controlled study in men with lifelong rapid ejaculation was performed to assess the effects of two selective serotonin ( 5-HT ) reuptake inhibitors — paroxetine and sertraline— and the 5-HT 2 antagonist and 5-HT/noradrenaline reuptake inhibitor nefazodone on the latency to ejaculate . Forty-eight men with an intravaginal ejaculation latency time ( IELT ) of a maximum of 1 minute were r and omly assigned to receive paroxetine ( 20 mg/day ) , sertraline ( 50 mg/day ) , nefazodone ( 400 mg/day ) , or placebo for 6 weeks . During the 1-month baseline and 6-week treatment period , IELTs were measured at home with a stopwatch . The trial was completed by 40 men . During the 6-week treatment period , the geometric mean IELT in the placebo group was stable at approximately 20 seconds . Analysis of variance revealed a between-group difference in the evolution of IELT delay over time ( p = 0.002 ) ; the IELT after paroxetine and sertraline gradually increased to approximately 146 and 58 seconds , respectively , compared with 28 seconds in the nefazodone group . The paroxetine and sertraline groups differed significantly ( p placebo , but the nefazodone group did not ( p = 0.85 ) . Compared with baseline , paroxetine exerted the strongest delay in ejaculation , whereas sertraline delayed it only moderately . There was no clinical ly relevant delay in ejaculation with nefazodone", "INTRODUCTION Men with comorbid erectile dysfunction ( ED ) and premature ejaculation ( PE ) may be concomitantly prescribed a phosphodiesterase type 5 ( PDE5 ) inhibitor and dapoxetine . AIM Evaluate efficacy and safety of dapoxetine 30 mg and 60 mg on dem and ( prn ) in men with PE and ED who were being treated with PDE5 inhibitors . METHODS This r and omized , double-blind , placebo-controlled , flexible-dose , multicenter study enrolled men ≥18 years who met diagnostic criteria for PE including intravaginal ejaculatory latency time ( IELT ) of ≤2 minutes in ≥75 % of sexual intercourse episodes ; were on stable regimen of a PDE5 inhibitor ; and had International Index of Erectile Function-erectile function domain score ≥21 . Subjects received placebo , dapoxetine 30 mg , or dapoxetine 60 mg prn ( 1 - 3 hours before intercourse ) for 12 weeks . MAIN OUTCOME MEASURE Stopwatch-measured average IELT , Clinical Global Impression of Change ( CGIC ) in PE , Premature Ejaculation Profile ( PEP ) , and treatment-emergent adverse events ( TEAEs ) . RESULTS Of 495 subjects r and omized , 429 completed the study . Arithmetic mean average IELT significantly increased with dapoxetine vs. placebo at end point ( 5.2 vs. 3.4 minutes ) and weeks 4 , 8 , and 12 ( P ≤ 0.002 for all ) . Men who described their PE at least \" better \" using the CGIC were significantly greater with dapoxetine vs. placebo at end point ( 56.5 % vs. 35.4 % ) and weeks 4 , 8 , and 12 ( P ≤ 0.001 for all ) . Significantly better outcomes were also reported with dapoxetine vs. placebo on PEP measures . Incidence of TEAEs was 20.0 % and 29.6 % in placebo- and dapoxetine-treated subjects , respectively ( P = 0.0135 ) . TEAEs led to discontinuation in 1.6 % of subjects in both groups . Most frequent TEAEs were known adverse drug reactions of dapoxetine treatment including nausea ( 9.2 % ) , headache ( 4.4 % ) , diarrhea ( 3.6 % ) , dizziness ( 2.4 % ) , and dizziness postural ( 2.4 % ) . CONCLUSIONS In men with PE and comorbid ED on a stable regimen of PDE5 inhibitor , dapoxetine provided meaningful treatment benefit and was generally well tolerated", "INTRODUCTION Premature ejaculation ( PE ) is the most common male sexual dysfunction with many lines of treatment that show conflicting results . Paroxetine and tramadol were both reported to be effective in treatment of PE . AIM To investigate the effectiveness of long-term daily paroxetine vs. on-dem and tramadol HCl in treatment of PE . MAIN OUTCOME MEASURES Intravaginal ejaculatory latency time ( IELT ) and Arabic Index of PE ( AIPE ) were used to assess the efficacy of investigated drugs . METHODS Thirty-five cases with lifelong PE were enrolled in this study . Baseline recording of IELT using a stop watch and AIPE was done . Patients were r and omized to take tramadol HCl on-dem and or daily paroxetine . Re assessment was done after 6 and 12 weeks . A wash-out period for 2 weeks was given before cross-over to the other medication . Assessment of the effect of the second medication after 6 and 12 weeks was done . RESULTS Tramadol and paroxetine increased IELT significantly after 6 weeks by seven- and 11-folds , respectively , compared with baseline . After 12 weeks , a decline of IELT to fivefolds was recorded with tramadol whereas further increase of IELT to 22-folds was recorded with paroxetine compared with baseline ( P Tramadol improved AIPE score significantly after 6 weeks but not after 12 weeks vs. baseline , whereas paroxetine increased the AIPE score after 6 and 12 weeks vs. baseline ( P paroxetine is more effective than on-dem and tramadol for treatment of lifelong PE . Tramadol is not recommended as a long-term treatment of lifelong PE", "BACKGROUND Premature ejaculation ( PE ) is a widely observed male sexual dysfunction with a major impact on quality of life for many men and their sexual partners . OBJECTIVE To assess the safety of tramadol orally disintegrating tablet ( ODT ) ( Zertane ) and its efficacy in prolonging intravaginal ejaculation latency time ( IELT ) and improving Premature Ejaculation Profile ( PEP ) scores . DESIGN , SETTING , AND PARTICIPANTS We conducted an integrated analysis of two identical 12-wk r and omized double-blind , placebo-controlled phase 3 trials across 62 sites in Europe . Healthy men 18 - 65 yr of age with a history of lifelong PE according to the Diagnostic and Statistical Manual of Mental Disorders , 4th Edition , Text Revision , and an IELT ≤ 120 s were included . There were 604 intent-to-treat subjects included in the analysis . INTERVENTION Subjects were r and omized to receive 1:1:1 placebo ( n=200 ) , 62 mg tramadol ODT ( n=206 ) , or 89 mg tramadol ODT ( n=198 ) . MEASUREMENTS We measured overall change and fold increase in median IELT and the mean change in all four measures of the PEP . Differences across treatment groups were analyzed using Wilcoxon rank-sum tests , analysis of variance , and chi-square analyses . RESULTS AND LIMITATIONS Tramadol ODT result ed in significant increases in median IELT compared with placebo ; increases were 0.6 min ( 1.6 fold ) , 1.2 min ( 2.4 fold ) , and 1.5 min ( 2.5 fold ) for placebo , 62 mg tramadol ODT , and 89 mg tramadol ODT , respectively ( p all four measures of the PEP in both doses compared with placebo ( p comparisons ) . Tramadol ODT was well tolerated ; study discontinuation occurred in 0 % , 1.0 % , and 1.6 % of subjects in placebo , 62 mg , and 89 mg tramadol ODT groups , respectively . Limitations include study inclusion for men with IELT up to 120 s. CONCLUSIONS On-dem and 62 mg tramadol ODT is an effective treatment for PE in a low and safe therapeutic dose and provides a new option for managing mild to severe PE", "This study investigated the efficacy and the adverse effects of sertraline in the treatment of premature ejaculation ( PE ) . Thirty-seven patients with PE were r and omly assigned to receive either sertraline or a placebo . Of them 22 were given 50 mg of sertraline per day and the other 15 patients were given an identical placebo one per day . After 4 weeks , the latency to ejaculation in the sertraline group was found to be significantly longer than that of the placebo group ( p adverse effects . These results indicate that sertraline is an effective therapy for PE ", "PURPOSE The efficacy of sertraline hydrochloride for the treatment of premature ejaculation is evaluated . MATERIAL S AND METHODS A total of 37 potent men , 19 to 70 years old ( mean age 41 ) , with premature ejaculation were treated with 50 mg . oral sertraline and placebo in a controlled r and omized single-blind crossover trial . All men were either married or in a stable relationship . None of the patients received any formal psychosexual therapy . Chronic open label treatment with sertraline was continued in 29 patients who had achieved an increase in ejaculatory latency times over pretreatment levels with active drug in the initial crossover study . In an attempt to identify which patients could maintain the improved ejaculatory control after withdrawal of the active drug , serial drug withdrawal was conducted every 4 weeks with drug initiation after a further 2 weeks if improved ejaculatory control was not maintained . RESULTS The mean pretreatment ejaculatory latency time was 0.3 minute ( range 0 to 1 ) . The mean ejaculatory interval after 4 weeks of treatment was 3.2 minutes ( range 1 minute to anejaculation ) with sertraline and 0.5 minute ( range 0 to 1 ) with placebo ( p Intravaginal ejaculation was achieved for the first time in 5 patients with primary premature ejaculation and 2 patients experienced anejaculation . One patient described minor drowsiness and anorexia , and 2 patients described mild , transient gastrointestinal upset . Staged drug withdrawal allowed 20 of the 29 patients ( 67 % ) on chronic open label treatment with sertraline to discontinue the drug after a mean interval of 7.3 months with a mean ejaculatory latency time of 4.1 minutes ( range 1 to 12 ) . CONCLUSIONS Sertraline appears to be a useful agent in the pharmacological treatment of premature ejaculation", "We aim ed to evaluate the effectiveness of paroxetine and tadalafil combination in the treatment of premature ejaculation ( PE ) . A total of 150 primary (lifelong)PE patients were r and omly distributed into three groups of 50 patients each . Group 1 received 20 mg paroxetine every day for 1 month , Group 2 received 20 mg tadalafil on dem and 2 h before intercourse , and Group 3 received paroxetine and tadalafil on dem and 2 h before intercourse . Intravaginal ejaculatory latency times ( IELT ) scores were evaluated at baseline , at the end of the first month of therapy and 1 month after discontinuation of the treatment , while International Index of Erectile Function ( IIEF ) question naire scores were evaluated both prior to and after the treatment . At the end of the first month of therapy , IELT scores were compared with the basal values and statistically significant changes were detected ( 60.6 ± 30.2–117.3 ± 67.3 , 68.5 ± 21.4–110.2 ± 37.3 , 71.56 ± 40.23–175.2 ± 60.2)(P discontinuation of treatment were found to be close to the baseline IELT scores ( P > 0.05 ) . IIEF scores were evaluated both prior to and after the treatment , and no statistically significant difference was detected ( P > 0.05 ) . It is concluded that utilisation of selective serotonin reuptake inhibitors ( SSRI ) and phosphodiesterase‐5 inhibitors ( PDE5i ) combination before intercourse seems to provide significantly longer ejaculatory latency times as compared with SSRI alone for a long time in patients with PE", "Aim : Premature ejaculation ( PME ) is defined as ejaculation with the minimal sexual stimulation before , on or shortly after penetration and or before a person wishes it . It is a function of the time between intra-vaginal penetration and intra-vaginal ejaculation . Tramadol has shown efficacy in PME when used as sporadic basis . In this study , we compared the use of 100 mg of tramadol as sporadic treatment ( administered 6 - 8 h before coitus ) versus continued treatment with the objective of evaluating the therapeutic results of both modalities . We assumed our alternative hypothesis that they have similar effects . Material s and Methods : A prospect i ve study was carried out on 60 patients divided into two groups of 30 patients each . Intra-vaginal ejaculation latency time ( IELT ) and coital frequency were measured both prior to and after the treatment . Group A received tramadol 100 mg daily for 4 weeks and on request ( sporadically ) for 4 weeks more . Group B was given placebo in the same manner . Results were statistically analyzed using the Student t-test . Results : Mean IELT prior to treatment was 59.2 s in Group A and 58.7 s in Group B. Mean pre-treatment coital frequency was 2.44 times/week for Group A and 2.13 times/week for Group B. Mean IELT was 202.5 s after continued tramadol treatment and 238.2 s after sporadic treatment in Group A. Mean IELT with daily placebo was 94.8 s and with sporadic placebo was 96.6 s. Coital frequency increased to 4.32 times/week with daily tramadol treatment and 4.86 times with sporadic treatment . Coital frequency increased to 2.88 times/week with daily placebo treatment and 3.23 times with sporadic treatment . Conclusions : The results of PME treatment with tramadol are similar with both continued and sporadic administration . The sex life of patients improved and they reported greater satisfaction with the sporadic treatment", "Objective The aim of this study is to measure the ejaculation latency time ( ELT ) and to evaluate the effects of vardenafil on ELT and rigidity parameters of patients with lifelong premature ejaculation ( PE ) in a laboratory setting . Material s and methods Double-blind , placebo-controlled , cross-over laboratory study was performed with 40 males with lifelong PE . As the subject ingested the placebo or vardenafil , real-time penile tumescence and rigidity monitoring began . Audiovisual sexual stimulation ( AVSS ) was performed 45 min later . The patient began vibratory stimulation to the frenular area at 8th minute of AVSS till ejaculation . A button has been placed under the cover where the patient presses to operate the vibrator . ELT was calculated in seconds with a chronometer . Following ejaculation , AVSS was stopped . The test was repeated with second medication in 7–15 days . Results Among 40 patients , the results of 17 could be evaluated . When the patient took placebo and vardenafil , mean ELTs were 62.7 and 189.5 s , respectively . When compared with placebo , vardenafil improved ELT significantly ( P = 0.04 ) . After the beginning of AVSS , time to first recorded base or tip rigidities was shorter and time to last recorded tip or base rigidities following ejaculation was longer than placebo ; however , these differences were not significant ( P > 0.05 for each ) . Conclusions This laboratory design might be used to evaluate the effects of drugs on patients with ejaculation disorders . In this laboratory setting study , vardenafil exerted a threefold increase in ejaculation delay outside the vagina in patients with lifelong PE ", "Introduction : Premature ejaculation ( PE ) is a common male sexual disorder . An ideal , reliable and effective treatment is desired by many men and couples affected by this condition . Aim : Evaluate if the association of a phosphodiesterase-5 inhibitor , tadalafil , and a selective serotonin reuptake inhibitor , fluoxetine , can prolong the intravaginal ejaculatory latency time ( IELT ) in men with lifelong premature ejaculation . Methods : Sixty patients with lifelong premature ejaculation and without erectile dysfunction ( ED ) with IELT less than 90 s were enrolled in the protocol and r and omized into 4 groups to use a combination of medications : ( 1 ) tadalafil 20 mg plus fluoxetine 90 mg , ( 2 ) fluoxetine 90 mg plus placebo , ( 3 ) tadalafil 20 mg plus placebo , and ( 4 ) two different placebo capsules ( control ) . Before starting the medications , each man timed his IELT with a stopwatch , and likewise during the treatment period . Fluoxetine 90 mg or placebo was taken once a week plus tadalafil 20 mg or placebo within a 36-hour frame of intended sexual intercourse with a steady partner . Patients were prospect ively followed for 12 weeks . One-way ANOVA was used for statistical comparisons of IELT results in each group . Results : Mean IELT before starting treatment was 51.3 ± 23 s. Withone-way ANOVA , a statistically significant difference in post-treatment IELT was seen with combination treatment compared to placebo ( p increases in IELT from baseline in patients using fluoxetine plus tadalafil ( 49.57 ± 25.87 to 336.13 ± 224.77 ) ( p tadalafil ( 49.26 ± 19.43 to 186.53 ± 159.05 ) ( p = 0.001 ) . The increases in each group were statistically significant compared to the placebo ( 49.86 ± 19.43 to 67.82 ± 46.18 ) ( p = 0.042 ) . Conclusion : Fluoxetine plus tadalafil significantly increased the IELT from baseline in men with lifelong premature ejaculation when compared to placebo , tadalafil or fluoxetine", "PURPOSE We compared the efficacy and safety of fluoxetine , sertraline , clomipramine and placebo for the oral pharmacotherapy of premature ejaculation . MATERIAL S AND METHODS The study included 36 men ( mean age 44 years ) who had intravaginal ejaculation latency of less than 2 minutes . Patients took each of 3 drugs and the placebo consecutively during a 4-week period per each agent . Efficacy and side effects data were obtained by a self-reported patient question naire that rated intravaginal ejaculation latency , sexual satisfaction of patient and partner , and possible side effects . RESULTS After 4 weeks of treatment with placebo , fluoxetine , sertraline and clomipramine the mean intravaginal ejaculation latency time was significantly increased from 46 seconds to 2.27 minutes , 2.30 minutes , 4.27 minutes and 5.75 minutes , respectively ( all p clomipramine or sertraline caused a greater increase in mean intravaginal ejaculation latency time than fluoxetine or placebo ( p Patient sexual satisfaction rate after treatment with clomipramine was significantly higher ( p sertraline , fluoxetine or placebo . Partner sexual satisfaction rate was also higher with clomipramine than with sertraline or fluoxetine but no statistical difference was found . The incidence of side effects with clomipramine was significantly higher ( p fluoxetine , sertraline and placebo , while no significant difference among sertraline , fluoxetine and placebo was noted . CONCLUSIONS In men with premature ejaculation clomipramine was the most useful drug in terms of efficacy . Treatment with sertraline was nearly as effective and had a lower incidence of side effects", "Introduction : The aim of this study was to compare the efficacy of fluoxetine alone and combined with sildenafil in patients complaining of premature ejaculation . Patients and Methods : Ninety-one married potent men , 21–43 years old , with premature ejaculation but without any obvious organic cause were enrolled . Pretreatment evaluation included history , physical examination , and self-administration of the International Index of Erectile Function question naire . The patients were r and omly divided into two groups : group A patients ( n = 48 ) received 20 mg fluoxetine daily for 4 weeks and then 20 mg as needed 2–3 h before sexual activity for 4 months , and group B patients ( n = 43 ) received group A regimen plus 50 mg sildenafil as needed 1 h before sexual activity for 4 months . Results : Ejaculatory latency time and intercourse satisfaction significantly improved in group B as compared with group A ( p Fluoxetine combined with sildenafil seems to provide significantly better ejaculatory latency time and intercourse satisfaction as compared with fluoxetine alone in patients with premature ejaculation", "To assess the use of a topical anaesthetic mixture to improve premature ejaculation ( PE ) , for which penile hypersensitivity might be a cause", "Premature ejaculation ( PE ) is the most common sexual disorder . It affects 20%-30 % of adult men ; the aetiology of this condition has not yet been eluci date d. The aim of this study is to evaluate the efficacy , safety , tolerability , undesirable effects and improved satisfaction with sexual intercourse with tramadol hydrochloride at different dosages for the treatment of PE . A total of 300 patients who presented with lifelong ( primary ) PE were included in this study . The study was performed for 28 weeks , in which placebo ( starch tablet ) was given for 4 weeks , and active ingredient ( tramadol hydrochloride ) was administered at different therapeutic dosages for 24 weeks . Patients were divided into three equal groups , each consisting of 100 patients . The first group ( A ) was given tramadol hydrochloride capsule 25 mg . The second group ( B ) was given tramadol hydrochloride capsule 50 mg . The third group ( C ) was given tramadol hydrochloride capsule 100 mg . All of the 300 participants included completed the study voluntarily . The age of the patients varied from 25 to 50 years . After the treatment period , the recorded data were collected for each group and analysed . The results showed a highly significant increase in the mean intravaginal ejaculatory latency time ( IELT ) in all groups compared to baseline data ( P tramadol hydrochloride at different doses on dem and for the treatment of PE is effective , safe and tolerable , with minimal undesirable effects , and approval for this indication should be sought", "BACKGROUND Recently , sildenafil has been demonstrated to be effective in treating premature ejaculation ( PE ) . However , these studies ignored female factors and could not exclude the probability of drug interaction when combined with paroxetine . Therefore , the aim of this study was to evaluate the efficacy and safety of sildenafil alone in the treatment of primary PE , taking female factors into consideration . METHODS One hundred and eighty potent men with primary PE were r and omly divided into three groups and followed up for 6 months . Group A were treated with 50 mg sildenafil as needed , group B with 20 mg paroxetine daily and group C with squeeze technique daily . Intravaginal ejaculatory latency time ( IELT ) , PE grade , intercourse satisfactory score ( ISS ) , frequency of intercourse , and adverse effects of drugs were recorded before treatment , and 3 and 6 months after treatment . RESULTS Compared with pretreatment , the three groups had significant differences in all the parameters after 3 or 6 months treatment , except the frequency of intercourse in Group C ( all P = 0.00 ) . However , there were no significant differences between 3 and 6 months . Compared with paroxetine and squeeze technique , after 3 or 6 months , sildenafil had significant differences in all the parameters ( all P = 0.00 ) . After 6 months , 1.7 % , 18.3 % and 36.7 % patients in groups A , B and C , respectively , withdrew from the study and 86.7 % , 60.0 % and 45.0 % patients , respectively , wanted to be treated further with the original administration , and this was statistically significant ( both P = 0.00 ) . CONCLUSION Sildenafil is very effective and safe to treat PE , and has much higher efficacy than paroxetine and squeeze technique", "To evaluate , in a phase II study , the efficacy and safety of a topical eutectic mixture for premature ejaculation ( TEMPE ) , a metered‐dose aerosol spray containing a eutectic mixture of lidocaine and prilocaine , as a treatment for PE", "INTRODUCTION PSD502 is a novel aerosolized , lidocaine-prilocaine , spray being developed for the treatment of lifelong premature ejaculation . The clinical profile of PSD502 is described in one of two double-blind , placebo-controlled , phase III studies . AIM To determine the effect of PSD502 on the Index of Premature Ejaculation ( IPE ) and intravaginal ejaculatory latency ( IELT ) of men with lifelong PE . METHODS Men with lifelong PE who documented an IELT ≤ 1 minute with two or more of the first three sexual encounters during a 4-week baseline period were r and omized to receive double-blind treatment with PSD502 or placebo for 3 months . Patients completed IPE and Premature Ejaculation Profile question naires at entry and monthly visits , and recorded stop-watch timed IELT during each encounter . Safety was assessed by collecting adverse event data and st and ard safety measures . MAIN OUTCOME MEASURES Stopwatch timed IELT recordings and a patient-reported outcome question naire the IPE were used in this study to determine the effect of PSD502 applied topically 5 minutes before intercourse . RESULTS Two hundred fifty-six men with PE were r and omized from 38 centers in the U.S. , Canada , and Pol and . The geometric mean IELT over the 3-month treatment period increased from a baseline of 0.56 minute and 0.53 minute in the PSD502 and placebo group respectively to 2.60 and 0.80 minute . There were significantly greater increases in the scores for the IPE domains of ejaculatory control , sexual satisfaction and distress in the PSD502 group than in the placebo group , with a mean 5.0 point difference between treatments in change from baseline in the IPE domain for ejaculatory control , 4.6 point difference in change from baseline in the IPE domain for sexual satisfaction , and a 2.5 point difference in change from baseline in the IPE domain for distress . This was supported by improvements in all secondary endpoints . CONCLUSION In this study , PSD502 applied topically to the glans penis 5 minutes before intercourse showed significantly improved ejaculatory latency , ejaculatory control , sexual satisfaction and distress and was shown to be well tolerated by patients and partners", "Background : Several medical therapies have been proposed for the treatment of premature ejaculation ( PE ) . Paroxetine and tramadol were both reported to be effective in treatment of PE . In this study , the therapeutic effects of tramadol , paroxetine and placebo were compared in treatment of primary PE . Methods : In this r and omized , double-blind , placebo-controlled clinical trial , 150 patients were divided into 3 groups . One group was treated with tramadol 50 mg ondem and , the other group took paroxetine 20 mg on-dem and and the third group was treated with placebo . Before starting treatment and after 12 weeks , patients were asked to measure their average intravaginal ejaculation latency time ( IELT ) and fill the PEP ( Premature Ejaculation Profile ) question naire . Results : At the end of the 12th week , the mean IELT and average of PEP scores improved in all 3 groups . The increase in tramadol group was significantly higher than the paroxetine and placebo groups ( p side effects between the 3 groups . Conclusion : The results showed that despite an increase in mean IELT and PEP scores in all 3 groups , the rate of improvement in tramadol group was significantly more than the others . Thus , tramadol may be considered as an appropriate alternative therapeutic option for lifelong PE", "Background : This r and omized clinical trial was aim ed to evaluate the effect of oral use of tamarind seed powder as an herbal product in patients affected by premature ejaculation ( PE ) . Material s and Methods : In this study , 75 patients r and omized in tamarind group ( 25 patients received daily 130 mg tamarind seed powder ) , paroxetine group ( 25 patients received daily 20 mg paroxetine ) , and placebo group ( 25 patients ) . Patients received the treatment regimen for 4 weeks . The primary outcome was intravaginal ejaculatory latency time ( IELT ) . The secondary outcomes were PE diagnostic tool score , sexual function using International Index of Erectile Function ( IIEF ) , and complications . Studied sexual functions include erectile function , orgasmic function , sexual desire , intercourse satisfaction , and overall satisfaction . Results : The mean of IELT in tamarind , paroxetine , and placebo groups at baseline was 35.2 ± 26.5 , 38 ± 27.6 , and 44 ± 34.9 s and at the end of study was 49.5 ± 48.2 , 147.4 ± 209.6 , and 46.9 ± 37.6 s , respectively , which in paroxetine group significantly increased compared to other groups . IIEF scores for orgasmic function and intercourse satisfaction for paroxetine after treatment significantly increased than that of other groups . The differences between tamarind and placebo groups for studied variables were not statistically significant . The mean of increases in IELT for tamarind , paroxetine , and placebo groups was 14.35 ± 34.3 , 109.4 ± 213.4 , and 2.9 ± 9.3 s , respectively , which in paroxetine group was significantly higher than other groups and in tamarind group was significantly higher than placebo . Conclusions : Paroxetine was significantly better than tamarind seed powder and placebo although side effect in paroxetine was more frequent . IELT significantly more increased in tamarind group compared to placebo", "To determine the effect of PSD502 applied topically 5 min before intercourse on the Index of Premature Ejaculation ( IPE ) and intravaginal ejaculatory latency time ( IELT ) of men with lifelong premature ejaculation ( PE ) defined according to the International Society of Sexual Medicine ( ISSM ) definition ; secondary objectives were to evaluate the safety and tolerability of PSD502 in patients with PE , and their sexual partners" ]

[ "OBJECTIVE Physical activity improves function in adults with arthritis , but it is unknown if there is a grade d relationship between physical activity and functional benefit . This study was undertaken to examine the cross-sectional and longitudinal relationship between self-reported physical activity and observed functional performance in adults with knee osteoarthritis ( OA ) . METHODS The Osteoarthritis Initiative cohort included 2,589 patients with knee OA ( 2,301 with longitudinal followup data ) who were ages 45 - 79 years at baseline . Prospect i ve annual functional performance was assessed for 2 years using timed 20-meter walk tests . We used linear regression to estimate differences across physical activity quartiles in subsequent function ( baseline and 1-year activity predicts 1-year and 2-year function , respectively ) adjusted for demographic factors ( age , sex , race/ethnicity , education level , and marital status ) and health factors ( OA severity , knee symptoms , knee pain , knee injury , body mass index , comorbidity , depression , smoking , alcohol use , and other joint pain ) . RESULTS Increasing physical activity levels had a significant grade d relationship to functional performance . Adults in physical activity quartile groups from least active to most active had an average gait speed of 4.0 , 4.2 , 4.3 , and 4.5 feet/second , respectively , at baseline ( P for trend physical activity level and better performance in adults with knee OA . These findings support guidelines that encourage patients with arthritis who can not attain minimum recommended physical activity to be as active as possible" ]

[ "This paper provides an up-to- date overview of the occurrence , diagnosis , risk factors , prognostic indicators and outcome of shoulder disorder ( SD ) , and of the validity and reproducibility of diagnostic classifications and diagnostic imaging techniques for SD . Furthermore , the available evidence on the effectiveness of non-steroidal anti-inflammatory drugs ( NSAIDs ) , corticosteroid injections and physiotherapy for SD is summarized on the basis of r and omized controlled trials with an acceptable quality of their methods . The annual incidence of SD is estimated at about 7 % , its 1-year period prevalence at about 51 % and its lifetime prevalence at about 10 % . While approximately 50 % of all patients with SD seek medical care , about 95 % are treated in primary health care . Of all new episodes of SD presenting to primary care , approximately 50 % seem to resolve within 6 months , while about 40 % seem to persist for up to 12 months . Several prognostic indicators for a favourable or a poor outcome of SD have been identified , but a comprehensive prognostic model is not available . While evidence for the prognostic validity of popular diagnostic classifications of SD is lacking , their reproducibility has been shown to be poor . The accuracy and clinical usefulness of diagnostic imaging techniques appear to be sufficiently verified for SD in secondary care , while their clinical usefulness in primary care and prognostic validity are not . NSAIDs and steroid injections for SD have been shown to be effective within 6 weeks , but their effect on long-term outcome remains unclear . There is very limited evidence for the effectiveness in SD of physiotherapy , including exercise therapy , ultrasound , electrotherapy , laser , mobilization and manipulation", "Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials", "The Shoulder Disability Question naire ( SDQ ) is a measure covering 16 items design ed to evaluate functional status limitation in patients with shoulder disorders . The responsiveness of the SDQ was evaluated for 180 patients with soft tissue shoulder disorders , without underlying systemic disorders . These patients participated in a r and omized placebo-controlled trial , in which ultrasound and electrotherapy appeared to be ineffective as adjuvants to st and ardized exercise therapy . At baseline and at 6-week follow-up , patients completed the SDQ and rated severity of shoulder pain and their chief complaint , while a research physiotherapist rated severity of symptoms and restriction of mobility . At the 6-week follow-up , patients also rated overall change since baseline . According to the calibrated responsiveness ratio ( CRR ) and the area under the receiver-operator characteristic curve ( AUC ) the SDQ discriminates accurately between self-rated clinical ly stable and improved subjects . The presented results suggest that the SDQ is as responsive as the compared outcome measures , and therefore is ready for use in clinical trials", "As the natural history of frozen shoulder is poorly documented , a prospect i ve study of 40 patients followed up for 40 - 48 months ( mean 44 months ) is described . The range of movement was significantly less than age- and sex-matched controls . Objective restriction was severe in five patients and mild in a further 11 . Patients were often unaware that shoulder range was impaired . Dominant arm involvement , manual labour , and mobilisation physiotherapy were associated with a less satisfactory outcome . We conclude that , while objective restriction persists , there is little functional impairment in the late stage of frozen shoulder", "Background Painful shoulders pose a substantial socioeconomic burden . A prospect i ve cost-of-illness study was performed to assess the costs associated with healthcare use and loss of productivity in patients with shoulder pain in primary health care in Sweden . Methods The study was performed in western Sweden , in a region with 24 000 inhabitants . Data were collected during six months from electronic patient records at three primary healthcare centres in two municipalities . All patients between 20 and 64 years of age who presented with shoulder pain to a general practitioner or a physiotherapist were included . Diagnostic codes were used for selection , and the cases were manually controlled . The cost for sick leave was calculated according to the human capital approach . Sensitivity analysis was used to explore uncertainty in various factors used in the model . Results 204 ( 103 women ) patients , mean age 48 ( SD 11 ) years , were registered . Half of the cases were closed within six weeks , whereas 32 patients ( 16 % ) remained in the system for more than six months . A fifth of the patients were responsible for 91 % of the total costs , and for 44 % of the healthcare costs . The mean healthcare cost per patient was € 326 ( SD 389 ) during six months . Physiotherapy treatments accounted for 60 % . The costs for sick leave contributed to 84 % of the total costs . The mean annual total cost was € 4139 per patient . Estimated costs for secondary care increased the total costs by one third . Conclusions The model applied in this study provides valuable information that can be used in cost evaluations . Costs for secondary care and particularly for sick leave have a major influence on total costs and interventions that can reduce long periods of sick leave are warranted", "OBJECTIVES To estimate the national prevalence and incidence of adults consulting for a shoulder condition and to investigate patterns of diagnosis , treatment , consultation and referral 3 yr after initial presentation . METHODS Prevalence and incidence rates were estimated for 658469 patients aged 18 and over in the year 2000 using a primary care data base , the IMS Disease Analyzer-Mediplus UK . A cohort of 9215 incident cases was followed-up prospect ively for 3 yr beyond the initial consultation . RESULTS The annual prevalence and incidence of people consulting for a shoulder condition was 2.36 % [ 95 % confidence interval ( CI ) 2.32 - 2.40 % ] and 1.47 % ( 95 % CI 1.44 - 1.50 % ) , respectively . Prevalence increased linearly with age whilst incidence peaked at around 50 yr then remained static at around 2 % . Around half of the incident cases consulted once only , while 13.6 % were still consulting with a shoulder problem during the third year of follow-up . During the 3 yr following initial presentation , 22.4 % of patients were referred to secondary care , 30.8 % were prescribed non-steroidal anti-inflammatory drugs and 10.6 % were given an injection by their general practitioner ( GP ) . GPs tended to use a limited number of generalized codes when recording a diagnosis ; just five of 426 possible Read codes relating to shoulder conditions accounted for 74.6 % of the diagnoses of new cases recorded by GPs . CONCLUSIONS The prevalence of people consulting for shoulder problems in primary care is substantially lower than community-based estimates of shoulder pain . Most referrals occur within 3 months of initial presentation , but only a minority of patients are referred to orthopaedic specialists or rheumatologists . GPs may lack confidence in applying precise diagnoses to shoulder conditions", "Objective To determine the extent and nature of selective non-reporting of harm outcomes in clinical studies that were eligible for inclusion in a cohort of systematic review s. Design Cohort study of systematic review s from two data bases . Setting Outcome reporting bias in trials for harm outcomes ( ORBIT II ) in systematic review s from the Cochrane Library and a separate cohort of systematic review s of adverse events . Participants 92 systematic review s of r and omised controlled trials and non-r and omised studies published in the Cochrane Library between issue 9 , 2012 and issue 2 , 2013 ( Cochrane cohort ) and 230 systematic review s published between 1 January 2007 and 31 December 2011 in other publications , synthesis ing data on harm outcomes ( adverse event cohort ) . Methods A 13 point classification system for missing outcome data on harm was developed and applied to the studies . Results 86 % ( 79/92 ) of review s in the Cochrane cohort did not include full data from the main harm outcome of interest of each review for all of the eligible studies included within that review ; 76 % ( 173/230 ) for the adverse event cohort . Overall , the single primary harm outcome was inadequately reported in 76 % ( 705/931 ) of the studies included in the 92 review s from the Cochrane cohort and not reported in 47 % ( 4159/8837 ) of the 230 review s in the adverse event cohort . In a sample of primary studies not reporting on the single primary harm outcome in the review , scrutiny of the study publication revealed that outcome reporting bias was suspected in nearly two thirds ( 63 % , 248/393 ) . Conclusions The number of review s suspected of outcome reporting bias as a result of missing or partially reported harm related outcomes from at least one eligible study is high . The declaration of important harms and the quality of the reporting of harm outcomes must be improved in both primary studies and systematic review", "BACKGROUND The risk , injury , failure , loss-of-function , end-stage-renal-failure ( RIFLE ) and acute kidney injury network ( AKIN ) consensus definitions of acute kidney injury ( AKI ) were established in part to facilitate comparison of trials . Contrast-induced nephropathy ( CIN ) has traditionally used a less dem and ing definition . OBJECTIVES To review use of RIFLE and AKIN as AKI trial outcome variables and contrast these with outcomes for CIN . METHODS We conducted a search of PubMed from 1 January 2005 to 31 December 2008 and 9 trial registries for r and omized control trials for preventional or interventional treatment of AKI and CIN . RESULTS RIFLE or AKIN were outcome variables in 36 % ( n = 8) of the published ( n = 22 ) and 18 % ( n = 4 ) of the current ( n = 22 ) AKI trials . RIFLE was used to triage to intervention in three trials . The urine output definition of RIFLE and AKIN was an outcome in only two trials . In 18 % ( n = 8) of AKI trials , the CIN definition ( increase in serum creatinine of > or = 25 % and /or > or = 44 micromol/l ) was the primary outcome . This was also the primary outcome in 56 % ( n = 13 ) of published ( n = 12 ) and current ( n = 11 ) CIN trials . Three published CIN trials used RIFLE or AKIN as an outcome ( 13 % ) . The duration over which outcomes were determined varied from 24 h to 7 days . CONCLUSIONS Considerable heterogeneity remains in outcome variables of AKI and CIN clinical trials . Even when the RIFLE or AKIN criteria were used , they were not applied consistently . There is a need for further consensus on surrogate outcome variables", "A prospect i ve study has been made of 49 patients with the frozen shoulder syndrome ( as distinct from tendinitis , calcific deposits and frozen shoulders occurring after coronary infa rct ion or with pulmonary tuberculosis ) of whom forty-one have been followed up for 5 - 10 years , always to their greatest recovery . There were three consecutive stages : pain , stiffness , and recovery . The stiffness stage was usually related to the duration of the recovery stage . The total duration was longer than is generally supposed ( an average total of 30.1 months in contrast to about 18 months as often postulated ) . Generally speaking , the longer the stiffness stage is , the longer is the recovery stage . In 4 patients the second shoulder became similarly affected , 6 months to 7 years after the first , and followed a similar chronological sequence to the first . After greatest recovery , slight restriction of movement was found in more than half the cases , but in only 3 , all of long duration , was the restriction a h and icap . Arthrography , carried out on both shoulders in all patients during the recovery stage , showed in the affected shoulder fewer rotator cuff defects than expected at this age and fewer ( four ) than in the contralateral one ( twenty-three ) ; seemingly , the condition leads to the obliteration of some defects", "PURPOSE R and omized clinical trials can provide strong evidence regarding effective treatment options . The quality of reporting and the type of outcome measures used are important when judging whether results justify change in clinical practice . The aim of this study was to assess the quality of reporting of r and omized clinical trials related to treatment of upper-extremity disorders , published in 4 h and surgical and orthopedic journals during an 11-year period , and assess the type of outcome measures used in the trials . METHODS Eligible articles were identified by review ing all abstract s published in the 4 journals from 1992 through 2002 . The quality of reporting was assessed by a modified Jadad scale that consisted of 3 items ( r and omization , blinding , and withdrawals/dropouts ) . A higher score ( 0 - 5 ) indicated higher quality . The outcome measures were classified according to the International Classification of Functioning , Disability and Health into the levels of body function and structure , activity , and participation . RESULTS Of 92 articles reporting r and omized clinical trials , 40 articles described appropriate r and omization method that implied they were truly r and omized studies , 31 articles did not describe the r and omization method , and 21 articles ( 23 % ) described inappropriate r and omization methods . Double or single blinding was reported in 33 articles . Absence or description of withdrawals/dropouts was shown in 77 articles . The median quality score calculated for all 92 articles was 2 ( range , 0 - 5 ) points . The median score for the 28 articles published 1992 through 1996 was 1 ( range , 0 - 5 ) points and for the 64 articles published from 1997 through 2002 was 3 ( range , 0 - 5 ) points . All trials used outcome measures on body function and structure level ; 41 % used measures of activity and /or participation . CONCLUSIONS There is a need to improve the quality of reporting of upper-extremity r and omized clinical trials and to increase the use of outcome measures covering different aspects of disability", "OBJECTIVE --To develop and vali date a question naire to quantify disability associated with shoulder symptoms . METHODS --A set of questions relevant to shoulder symptoms from a general disability interview was developed and the question naire applied to a cross-sectional population survey and a prospect i ve study of general practice attenders . Subjects included adults who reported current shoulder pain in a population survey and patients from three general practice s who attended with shoulder symptoms during a six month period . The main outcome measures were : frequency of problems with daily living related to shoulder symptoms , total score on 22-item disability question naire , and measures of shoulder movement . RESULTS --A higher proportion ( 80 % ) of patients attending their general practitioner with shoulder symptoms had five or more disabilities compared with subjects reporting shoulder pain in a community survey ( 34 % ) . The ranked frequency with which each disability was reported was similar in the two groups , although sleep disturbance was the most common problem in consulters . Self-reported disability is correlated with measures of restricted shoulder movement . CONCLUSION --This disability question naire was simple to complete and should prove useful for both general practice and population -based studies of shoulder pain", "There is a growing recognition that insufficient attention has been paid to the selection of the outcomes to measure in clinical trials and clinical audit . Outcomes need to be relevant to patients , clinicians , purchasers and policy-makers if the findings of research are to influence practice and future research . In addition , st and ardization of outcomes is needed to combine data from different studies to allow evidence synthesis and to compare data sets . Inconsistent choice of outcome measures means that many meta-analyses are unable to include data from all the relevant studies . For example , the five most accessed Cochrane review s in 2009 , together with the top cited review in that year , all described inconsistencies in the outcomes reported in eligible trials . A call for the st and ardization of outcomes is a regular conclusion of systematic review s. Furthermore , outcome reporting bias , defined as the bias arising from selecting outcomes for publication based on the results , affects many r and omized trials and ‘ is an under-recognized problem that affects the conclusions in a substantial proportion of Cochrane review s ’ . That bias is likely to affect systematic review s more widely as well as affecting individual studies when considered on their own . Similar problems occur with clinical audit , highlighting the importance of establishing national audits that use and report the same outcomes for all participants . All these issues could be addressed with the development and application of agreed st and ardized sets of outcomes that have been termed ‘ core outcome sets ’ . These should be measured and reported , as a minimum , in all relevant clinical trials and national clinical audits for a specific condition . Adopting a core outcome set does not imply that a particular study , review or audit should be restricted to only those outcomes . Rather , the expectation is that , as a minimum , core outcomes will always be collected and reported to allow the results of trials to be compared , contrasted and combined as appropriate . The adoption of core outcomes would have implication s across all areas of research in health and health care , reduce heterogeneity between trials , and lead to research that is more likely to have measured relevant outcomes . Importantly , they would enhance the value of evidence synthesis by reducing the risk of outcome reporting bias and ensuring that all trials contribute usable information . In addition , they will increase the efficiency and value of research . An important rationale for core outcome sets is that outcomes currently reported for trials do not consistently reflect endpoints that are meaningful for patients . Examples exist where trials failed to include all outcomes important to patients and where involvement of patients has identified an outcome that might not have been considered by practitioners on their own . Despite increasing recognition of the importance of incorporating patients ’ opinions , their involvement has been limited . Recent regulatory guidance in the USA requires documented evidence of patient input during the development of instruments to measure patient reported outcomes ( PROs ) . However , measurement of PROs in clinical trials is hampered by the multiplicity and heterogeneity of tools currently available . Many generic , disease and domain-specific instruments have been developed and vali date d , each containing multiple scales and items . As a result , synthesis of PRO data from trials is difficult and review s aim ing to summarize treatment effect according to PROs may fail . There is synergy between the development of core outcome sets for trials and work to select up to seven outcomes that are important to patients for inclusion in Summary of Findings tables in systematic review s. Developed by the GRADE group ( http://www . grade workinggroup.org ) , Cochrane review s have featured such tables since 2008 , and they play a key role in presenting research in guidelines , such as those produced by the World Health Organization ( WHO ) . The development of core outcome sets needs to be accelerated and undertaken in ways that maximize efficiency . The COMET ( Core Outcome Measures in Effectiveness Trials , http://www.comet-initiative.org ) Initiative in the UK brings together research ers interested in the development and application of core outcome sets . These include key participants in a collaboration of research ers in rheumatology who have done the most notable work to date in this area . The COMET Initiative was launched in January 2010 , with a second meeting in July 2011 . Attendees included trialists , systematic review ers , patients , clinicians , journal editors , research funders , policy-makers , people responsible for trials registries and regulators . Data on individual studies , both published and ongoing , are being included in a free , publically available internet-based re source . This will be up date d periodically , to minimize the risk of duplication . Seventy-eight published or ongoing studies have already been entered into the repository . In addition , published review s of outcomes used in clinical trials or studies examining patients ’ views , will be entered", "A shoulder pain and disability index ( SPADI ) was developed to measure the pain and disability associated with shoulder pathology . The SPADI is a self-administered index consisting of 13 items divided into two subscales : pain and disability . Thirty-seven male patients with shoulder pain were used in a study to examine the measurement characteristics of the SPADI . Test-retest reliability of the SPADI total and subscale scores ranged from 0.6377 to 0.6552 . Internal consistency ranged from 0.8604 to 0.9507 . SPADI total and subscale scores were highly negatively correlated with shoulder range of motion ( ROM ) supporting the criterion validity of the index . Principal components factor analysis with and without varimax rotation supported the construct validity of the total SPADI and its subscales . High negative correlations between changes in SPADI scores and changes in shoulder ROM indicated the SPADI detected changes in clinical status over short time intervals . The SPADI should prove useful for both clinical and research purpose" ]

[ "Most studies on lipid lowering diets have focused on the total content of saturated , polyunsaturated and monounsaturated fatty acids . However , the distribution of these fatty acids on the triacylglycerol ( TAG ) molecule and the molecular TAG species generated by this stereospecificity are characteristic for various native dietary TAGs . Fat r and omization or interesterification is a process involving the positional redistribution of fatty acids , which leads to the generation of new TAG molecular species . A comparison between native and r and omized TAGs is the subject of this review with regards to the role of stereospecificity of fatty acids in metabolic processing and effects on fasting lipids and postpr and ial lipemia . The positioning of unsaturated versus saturated fatty acids in the sn-2 position of TAGs indicate differences in early metabolic processing and postpr and ial clearance , which may explain modulatory effects on atherogenecity and thrombogenecity . Both human and animal studies are discussed with implication s for human health", "Purpose The association between dietary saturated fatty acids ( SFA ) intake and type 2 diabetes ( T2D ) remains unclear . This study aim ed at investigating the association between SFA intake and T2D risk based on ( 1 ) individual SFA ( differing in carbon chain length ) , ( 2 ) food sources of SFA and ( 3 ) the substituting macronutrients . Methods 37,421 participants from the European Prospect i ve Investigation into Cancer and Nutrition-Netherl and s ( EPIC-NL ) cohort were included in this study . Baseline dietary intake was assessed by a vali date d food frequency question naire . T2D risks were estimated by Cox regression models adjusted for non-dietary and dietary covariates . Results 893 incident T2D cases were documented during 10.1-year follow-up . We observed no association between total SFA and T2D risk . Marginally inverse associations were found for lauric acid ( HR per 1 SD of energy% , 95 % CI 0.92 , 0.85–0.99 ) , myristic acid ( 0.89 , 0.79–0.99 ) , margaric acid ( 0.84 , 0.73–0.97 ) , odd-chain SFA ( pentadecylic plus margaric acids ; 0.88 , 0.79–0.99 ) , and cheese derived SFA ( 0.90 , 0.83–0.98 ) . Soft and liquid fats derived SFA was found related to higher T2D risk ( 1.08 , 1.01–1.17 ) . When substituting SFA by proteins , carbohydrates and polyunsaturated fatty acids , significantly higher risks of T2D were observed ( HRs per 1 energy% ranging from 1.05 to 1.15 ) . Conclusion In this Dutch population , total SFA does not relate to T2D risk . Rather , the association may depend on the types and food sources of SFA . Cheese-derived SFA and individual SFA that are commonly found in cheese , were significantly related to lower T2D risks . We can not exclude the higher T2D risks found for soft and liquid fats derived SFA and for substituting SFA with other macronutrients are influenced by residual confounding by trans fatty acids or limited intake variation in polyunsaturated fatty acids and vegetable protein", "Summary Background Conflicting evidence exists regarding the association between saturated fatty acids ( SFAs ) and type 2 diabetes . In this longitudinal case-cohort study , we aim ed to investigate the prospect i ve associations between objective ly measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants . Methods The EPIC-InterAct case-cohort study includes 12 403 people with incident type 2 diabetes and a representative subcohort of 16 154 individuals who were selected from a cohort of 340 234 European participants with 3·99 million person-years of follow-up ( the EPIC study ) . Incident type 2 diabetes was ascertained until Dec 31 , 2007 , by a review of several sources of evidence . Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids ( mol% ) ; sample s from people with type 2 diabetes and subcohort participants were processed in a r and om order by centre , and laboratory staff were masked to participant characteristics . We estimated country-specific hazard ratios ( HRs ) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression , which is weighted for case-cohort sampling , and pooled our findings using r and om-effects meta- analysis . Findings SFAs accounted for 46 % of total plasma phospholipid fatty acids . In adjusted analyses , different individual SFAs were associated with incident type 2 diabetes in opposing directions . Even-chain SFAs that were measured ( 14:0 [ myristic acid ] , 16:0 [ palmitic acid ] , and 18:0 [ stearic acid ] ) were positively associated with incident type 2 diabetes ( HR [ 95 % CI ] per SD difference : myristic acid 1·15 [ 95 % CI 1·09–1·22 ] , palmitic acid 1·26 [ 1·15–1·37 ] , and stearic acid 1·06 [ 1·00–1·13 ] ) . By contrast , measured odd-chain SFAs ( 15:0 [ pentadecanoic acid ] and 17:0 [ heptadecanoic acid ] ) were inversely associated with incident type 2 diabetes ( HR [ 95 % CI ] per 1 SD difference : 0·79 [ 0·73–0·85 ] for pentadecanoic acid and 0·67 [ 0·63–0·71 ] for heptadecanoic acid ) , as were measured longer-chain SFAs ( 20:0 [ arachidic acid ] , 22:0 [ behenic acid ] , 23:0 [ tricosanoic acid ] , and 24:0 [ lignoceric acid ] ) , with HRs ranging from 0·72 to 0·81 ( 95 % CIs ranging between 0·61 and 0·92 ) . Our findings were robust to a range of sensitivity analyses . Interpretation Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions , which suggests that SFAs are not homogeneous in their effects . Our findings emphasise the importance of the recognition of subtypes of these fatty acids . An improved underst and ing of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed . Funding EU FP6 programme , Medical Research Council Epidemiology Unit , Medical Research Council Human Nutrition Research , and Cambridge Lipidomics Biomarker Research Initiative", "Background It is possible that cross-over studies included in current systematic review s are being inadequately assessed , because the current risk of bias tools do not consider possible biases specific to cross-over design . We performed this study to evaluate whether this was being done in cross-over studies included in Cochrane Systematic Review s ( CSRs ) . Methods We search ed the Cochrane Library ( up to 2013 issue 5 ) for CSRs that included at least one cross-over trial . Two authors independently undertook the study selection and data extraction . A r and om sample of the CSRs was selected and we evaluated whether the cross-over trials in these CSRs were assessed according to criteria suggested by the Cochrane h and book . In addition we reassessed the risk of bias of these cross-over trials by a checklist developed form the Cochrane h and book . Results We identified 688 CSRs that included one or more cross-over studies . We chose a r and om sample of 60 CSRs and these included 139 cross-over studies . None of these CSRs undertook a risk of bias assessment specific for cross-over studies . In fact items specific for cross-over studies were seldom considered anywhere in quality assessment of these CSRs . When we reassessed the risk of bias , including the 3 items specific to cross-over trials , of these 139 studies , a low risk of bias was judged for appropriate cross-over design in 110(79 % ) , carry-over effects in 48(34 % ) and for reporting data in all stages of the trial in 114(82 % ) . Assessment of biases in cross-over trials could affect the GRADE assessment of a review ’s findings . Conclusion The current Cochrane risk of bias tool is not adequate to assess cross-over studies . Items specific to cross-over trials leading to potential risk of bias are generally neglected in CSRs . A proposed check list for the evaluation of cross-over trials is provided", "Background Mayonnaise is used widely in contemporary human diet with widespread use as a salad dressing or spread on breads . Vegetable oils used in its formulation may be a rich source of ω-6 PUFAs and the higher-PUFA content of mayonnaise may be beneficial in mediating a hypocholesterolemic effect . This study , therefore , evaluated the functionality of mayonnaise on cardiometabolic risk within a regular human consumption scenario . Methods Subjects underwent a r and omized double-blind crossover trial , consuming diets supplemented with 20 g/day of either soybean oil-based mayonnaise ( SB-mayo ) or palm olein-based mayonnaise ( PO-mayo ) for 4 weeks each with a 2-week wash-out period . The magnitude of changes for metabolic outcomes between dietary treatments was compared with PO-mayo serving as the control . The data was analyzed by ANCOVA using the GLM model . Analysis was adjusted for weight changes . Results Treatments result ed in significant reductions in TC ( diff = −0.25 mmol/L ; P = 0.001 ) , LDL-C ( diff = −0.17 mmol/L ; P = 0.016 ) and HDL-C ( diff = −0.12 mmol/L ; P affecting LDL-C : HDL-C ratio ( P > 0.05 ) . Lipoprotein particle change was significant with large LDL particles increasing after PO-mayo ( diff = + 63.2 nmol/L ; P = 0.007 ) compared to SB-mayo but small LDL particles remained unaffected . Plasma glucose , apolipoproteins and oxidative stress markers remained unchanged . Conclusions Daily use with 20 g of linoleic acid-rich SB-mayo elicited reductions in TC and LDL-C concentrations without significantly changing LDL-C : HDL-C ratio or small LDL particle distributions compared to the PO-mayo diet . Trial registration This clinical trial was retrospectively registered with the National Medical Research Register , National Institute of Health , Ministry of Health Malaysia , ( NMRR-15 - 40 - 24035 ; registered on 29/01/2015 ; https://www.nmrr.gov.my/fwbPage.jsp?fwbPageId= Research ISRForm&fwbAction = Up date & fwbStep=10&pk . research ID=24035&fwbVMenu=3&fwb Research Action = Up date ) . Ethical approval was obtained from the National University of Malaysia ’s Medical Ethics Committee ( UKM 1.5.3.5/244/SPP/NN-054-2011 , approved on 25/05/2011 )", "BACKGROUND Despite the high content of palmitic acid , palm olein has been shown to have a neutral effect on plasma cholesterol concentrations when compared with olive oil , which is suggested to be attributable to palmitic acid in the sn-1 and sn-3 position . In contrast , palmitic acid is in the sn-2 position in lard . OBJECTIVE The objective was to investigate the effects of a diet rich in palm olein , fractionated palm oil , olive oil , and lard on plasma blood lipids , inflammatory markers , glucose , and insulin . DESIGN A controlled double-blinded , r and omized 3 × 3 wk crossover dietary intervention study included 32 healthy men who daily replaced part of their habitual dietary fat intake with ~ 17 % of energy from palm olein , olive oil , or lard , respectively . RESULTS Compared with intake of olive oil , palm olein and lard increased total cholesterol and LDL cholesterol ( P ) . Palm olein result ed in a lower plasma triacylglycerol concentration than did olive oil ( P in plasma HDL-cholesterol , high-sensitivity C-reactive protein , plasminogen activator-1 , insulin , and glucose concentrations . CONCLUSIONS The current study did not support the previous finding that the effect of palm olein on total plasma cholesterol and LDL cholesterol in healthy individuals with normal plasma cholesterol concentrations is neutral compared with that of olive oil . Thus , sn-positioning was not confirmed to be important with regard to the effect on plasma cholesterol . The relatively lower plasma triacylglycerol concentration after the palm olein diet than after the olive oil diet was unexpected . This trial is registered at clinical trials.gov as NCT00743301", "BACKGROUND AND OBJECTIVES As the most widely produced edible vegetable oil , palm oil is known as to contain a high level of saturated fatty acid , which was thought to adversely affect serum lipid profiles . However , recent studies have shown no influence or benefits of palm oil on serum lipids . The potential nutritional value of palm oil is attributed to the high mono-unsaturation at the crucial sn2-position of the oil 's triacylglycerols , as with the so-called ' healthy ' olive oil ( OO ) . The aim of this study was to further test this hypothesis and evaluate the effects of consuming palm olein versus olive oil on serum lipid profiles in a Chinese population . METHODS AND STUDY DESIGN In total , 120 participants were recruited from a spinnery in Yixing city and r and omly divided into two groups ( palm olein or olive oil ) to conduct a 2 × 2 crossover trial for 2 months ' intervention with 2-week washout periods . Each participant was provided 48 g of test oil per day . At the end of each period , anthropometry , and blood lipid indices were measured to determine the effects of palm olein and olive oil . RESULTS Palm olein and olive oil consumption had no significantly different effect on BMI , on serum total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , triacylglycerol ( TG ) , Apo B , fasting glucose , or insulin concentrations ( all p>0.05 ) . CONCLUSIONS In a dietary crossover trial , palm olein and olive oil had no recognisably different effects on body fatness or blood lipids in a healthy Chinese population", "Background Dietary trans-rich and interesterified fats were compared to an unmodified saturated fat for their relative impact on blood lipids and plasma glucose . Each fat had melting characteristics , plasticity and solids fat content suitable for use as hardstock in margarine and other solid fat formulations . Methods Thirty human volunteers were fed complete , whole food diets during 4 wk periods , where total fat ( ~31 % daily energy , > 70 % from the test fats ) and fatty acid composition were tightly controlled . A crossover design was used with 3 r and omly-assigned diet rotations and repeated- measures analysis . One test fat rotation was based on palm olein ( POL ) and provided 12.0 percent of energy ( % en ) as palmitic acid ( 16:0 ) ; a second contained trans-rich partially hydrogenated soybean oil ( PHSO ) and provided 3.2 % en as trans fatty acids plus 6.5 % en as 16:0 , while the third used an interesterified fat ( IE ) and provided 12.5 % en as stearic acid ( 18:0 ) . After 4 wk the plasma lipoproteins , fatty acid profile , as well as fasting glucose and insulin were assessed . In addition , after 2 wk into each period an 8 h postpr and ial challenge was initiated in a subset of 19 subjects who consumed a meal containing 53 g of test fat . Results After 4 wk , both PHSO and IE fats significantly elevated both the LDL/HDL ratio and fasting blood glucose , the latter almost 20 % in the IE group relative to POL . Fasting 4 wk insulin was 10 % lower after PHSO ( p > 0.05 ) and 22 % lower after IE ( p the glucose incremental area under the curve ( IAUC ) following the IE meal was 40 % greater than after either other meal ( p depressed insulin and C-peptide ( p PHSO and IE fats altered the metabolism of lipoproteins and glucose relative to an unmodified saturated fat when fed to humans under identical circumstances", "Excess ectopic fat storage is linked to type 2 diabetes . The importance of dietary fat composition for ectopic fat storage in humans is unknown . We investigated liver fat accumulation and body composition during overfeeding saturated fatty acids ( SFAs ) or polyunsaturated fatty acids ( PUFAs ) . LIPOGAIN was a double-blind , parallel-group , r and omized trial . Thirty-nine young and normal-weight individuals were overfed muffins high in SFAs ( palm oil ) or n-6 PUFAs ( sunflower oil ) for 7 weeks . Liver fat , visceral adipose tissue ( VAT ) , abdominal subcutaneous adipose tissue ( SAT ) , total adipose tissue , pancreatic fat , and lean tissue were assessed by magnetic resonance imaging . Transcriptomics were performed in SAT . Both groups gained similar weight . SFAs , however , markedly increased liver fat compared with PUFAs and caused a twofold larger increase in VAT than PUFAs . Conversely , PUFAs caused a nearly threefold larger increase in lean tissue than SFAs . Increase in liver fat directly correlated with changes in plasma SFAs and inversely with PUFAs . Genes involved in regulating energy dissipation , insulin resistance , body composition , and fat-cell differentiation in SAT were differentially regulated between diets , and associated with increased PUFAs in SAT . In conclusion , overeating SFAs promotes hepatic and visceral fat storage , whereas excess energy from PUFAs may instead promote lean tissue in healthy humans", "1 . Three studies were carried out in each of six normal volunteers to investigate how lipid , when given at different stages during the course of a meal , affects gastric emptying and postpr and ial blood glucose and insulin concentrations . 2 . The control meal consisted of 300 ml beef consommé ( 50 kJ , 12 kcal ) , followed 20 min later by 300 g mashed potato ( 908 kJ , 217 kcal ) . In the two test meals , 60 g margarine were incorporated into either the soup or the mashed potato . 3 . The addition of margarine to either component of the meal delayed gastric emptying of the mashed potato ( P less than 0.05 ) , but the pattern varied according to the component to which the fat was added . 4 . Incorporation of fat into the soup increased the lag phase ( P less than 0.05 ) but did not influence the slope of emptying of the mashed potato , while incorporation of fat into the mashed potato reduced the slope of emptying of the mashed potato ( P less than 0.05 ) but did not influence the lag phase . 5 . Addition of fat to either component of the meal reduced postpr and ial blood glucose ( P less than 0.05 ) and insulin responses , but when the fat was incorporated in the soup , peak glucose and insulin responses were delayed as well ( P less than 0.05 ) . 6 . The results show that the effect of fat on gastric emptying and absorption of nutrients depends on when , in relation to the other components of the meal , the fat is consumed", "Background : Many studies have shown that trans fatty acids have unfavorable effects on the serum lipoprotein profile . In general , however , fats were compared with different functional characteristics , which lower the practical applications of the results . Objective : The major aim of this study was to compare the effects of a high-palmitic acid , trans-free semiliquid fat with those of a high-oleic acid , low-trans semiliquid fat on the serum lipoprotein profile of healthy subjects . Subjects and design : Forty-four subjects ( 33 women and 11 men ) consumed , in r and om order , two experimental diets , each for 3 weeks . Diets provided 40 energy percent ( En% ) from fat , while 15 En% was supplied by the experimental fats . At the end of each intervention period , concentrations of serum lipoproteins , C-reactive protein , glucose and insulin were measured . Results : When subjects consumed the high-oleic acid , low-trans semiliquid fat , intakes of stearic acid ( + 1.3 En% ) , oleic acid ( + 2.9 En% ) , α-linolenic acid ( + 0.1 En% ) and trans fatty acids ( + 0.6 En% ) were higher and that of palmitic acid ( −4.2 En% ) lower . Serum concentration of low-density lipoprotein cholesterol decreased by 0.34±0.39 mmol/l ( mean±s.d . ; 95 % confidence interval ( CI ) , −0.46 to −0.23 mmol/l ; P ) and high-density lipoprotein ( HDL ) cholesterol by −0.06±0.17 mmol/l ( 95 % CI , −0.11 to −0.01 mmol/l ; P=0.021 ) . Also , the total to HDL cholesterol ratio was lower ( −0.15±0.34 ; 95 % CI , −0.25 to −0.05 ; P=0.006 ) . Other parameters did not change . Conclusions : A high-oleic acid , low-trans semiliquid fat has a more favorable effect on the serum lipoprotein profile than a trans-free semiliquid fat with comparable functional characteristics , but high in palmitic acid", "Dietary trans fatty acids/partially-hydrogenated fat has been associated with increased risk of developing cardiovascular disease ( CVD ) , possibly greater than predicted from changes in lipoprotein levels . To explore this issue further potential risk factors were assessed in subjects provided with each of six diets in r and omized order containing as the major source of fat : soybean oil , semi-liquid margarine , soft margarine , shortening , traditional stick margarine or butter . Plasma fatty acid profiles reflected diet , with triglyceride and phospholipid subfractions affected to a greater extent than cholesteryl ester . Non-fasting LDL-cholesterol levels were 144+/-27 , 141+/-27 , 146+/-26 , 148+/-30 , 151+/-29 and 165+/-31 mg/dl ( P total cholesterol/HDL-cholesterol ratios were 5.50+/-1.25 , 5.54+/-1.50 , 5.69+/-1.29 , 5.82+/-1.40 , 6.11+/-1.30 and 5.94+/-1.43 ( P=0.011 ) , respectively , whereas other lipoprotein levels were not significantly different . Remnant-like particles levels were unaffected by dietary fat , either in the fasting or non-fasting state . Differences in fasting insulin and glucose levels were small and would not be predicted to have a large impact on glucose homeostasis . There was no significant effect of dietary fat type on C-reactive protein levels or blood pressure . These data suggest that , as previously demonstrated , the major CVD risk factor adversely affected by dietary trans fatty acids/partially-hydrogenated fat is LDL-cholesterol levels and total cholesterol/HDL-cholesterol ratios", "OBJECTIVE Diets high in total and saturated fat are associated with insulin resistance . This study examined the effects of feeding monounsaturated , saturated , and trans fatty acids on insulin action in healthy adults . RESEARCH DESIGN AND METHODS A r and omized , double-blind , crossover study was conducted comparing three controlled 4-week diets ( 57 % carbohydrate , 28 % fat , and 15 % protein ) enriched with different fatty acids in 25 healthy men and women . The monounsaturated fat diet ( M ) had 9 % of energy as C18:1cis ( oleic acid ) . The saturated fat diet ( S ) had 9 % of energy as palmitic acid , and the trans fatty acid diet ( T ) had 9 % as C18:1trans . Body weight was kept constant throughout the study . After each diet period , insulin pulsatile secretion , insulin sensitivity index ( S(I ) ) by the minimal model method , serum lipids , and fat oxidation by indirect calorimetry were measured . RESULTS Mean S(I ) for the M , S , and T diets was 3.44 + /- 0.26 , 3.20 + /- 0.26 , and 3.40 + /- 0.26 x 10(-4 ) min(-1 ) . microU(-1 ) . ml(-1 ) , respectively ( NS ) . S(I ) decreased by 24 % on the S versus M diet in overweight subjects but was unchanged in lean subjects ( NS ) . Insulin secretion was unaffected by diet , whereas total and HDL cholesterol increased significantly on the S diet . Subjects oxidized the least fat on the M diet ( 26.0 + /- 1.5 g/day ) and the most fat on the T diet ( 31.4 + /- 1.5 g/day ) ( P = 0.02 ) . CONCLUSIONS Dietary fatty acid composition significantly influenced fat oxidation but did not impact insulin sensitivity or secretion in lean individuals . Overweight individuals were more susceptible to developing insulin resistance on high-saturated fat diets" ]

[ "Low vitamin D status increases the risk of death . Magnesium plays an essential role in vitamin D metabolism and low magnesium intake may predispose to vitamin D deficiency and potentiate the health problems . We investigated whether magnesium intake modifies the serum 25(OH)D3 concentration and its associations with mortality in middle-aged and older men . We included 1892 men aged 42–60 years without cardiovascular disease or cancer at baseline in 1984–1989 from the prospect i ve , population -based Kuopio Ischaemic Heart Disease Risk Factor Study . Serum 25(OH)D3 was measured with the high-performance liquid chromatography using coulometric electrode array detection . Magnesium intake was assessed with 4-day food recording . Deaths were ascertained by a computer linkage to the national cause of death register . Deaths due accidents and suicides were excluded . Cox proportional hazards regression models were used to analyze the associations . The multivariate-adjusted hazard ratio ( HR ) for death in the lowest ( 49.4 nmol/L ) serum 25(OH)D3 tertile was 1.31 ( 95 % CI 1.07–1.60 , Ptrend = 0.01 ) . Stratified by the magnesium intake , the higher risk was observed only in the lower magnesium intake median ( cohort of middle-aged and older men low serum 25(OH)D3 concentration was associated with increased risk of death mainly in those with lower magnesium intake", "Background Evidence of an inverse association between serum 25-hydoroxyvitamin D [ 25(OH)D ] and the risk of all-cause death and cardiovascular disease from prospect i ve studies is inconsistent . We tested the relationship between 25(OH)D and the risk among adult ethnic Chinese in Taiwan . Methods We conducted a community-based cohort study of 1816 participants ( age 60.2±10.2 yrs , 45.0 % women ) in the Chin-Shan Community Cardiovascular Cohort Study who were free of cardiovascular diseases at baseline and provided 25(OH)D measurements . Results During a median 9.6 ( interquartile range , 8.8- 10.5 ) years ’ follow-up period , totally 263 cases developed cardiovascular death events and 559 participants were documented to death from any cause . As 25(OH)D concentration increased , the incidence rates of cardiovascular events and all-cause death decreased progressively . 25(OH)D was inversely associated with all-cause death : the adjusted hazard ratio was 0.49 ( 95 % confidence interval [ CI ] , 0.25 - 0.97 ) for the third quartile and a significant J-shape relationship was found . The performance measures by integrated discriminative improvement showed significant improvement after adding 25(OH)D information ( 0.14 % , 95 % CI , 0.03 - 0.31 , P=0.050 , for all-cause death and 0.32 % , 95 % CI , 0.02 - 0.62 , P=0.018 for cardiovascular events ) . Conclusion These findings suggested a modest inverse association between 25(OH)D and the risk of all-cause death among diabetic participants and a good predictive factor in the community . Further studies to investigate the mechanism of vitamin D role on health effect are warranted", "CONTEXT Observational studies relating circulating 25-hydroxyvitamin D ( 25OHD ) and dietary vitamin D intake to cardiovascular disease ( CVD ) have reported conflicting results . OBJECTIVE Our objective was to investigate the association of 25OHD , dietary vitamin D , PTH , and adjusted calcium with CVD and mortality in a Scottish cohort . DESIGN AND SETTING The MIDSPAN Family Study is a prospect i ve study of 1040 men and 1298 women from the West of Scotl and recruited in 1996 and followed up for a median 14.4 yr . PARTICIPANTS Locally resident adult offspring of a general population cohort were recruited from 1972 - 1976 . MAIN OUTCOME MEASURES CVD events ( n = 416 ) and all-cause mortality ( n = 100 ) were evaluated . RESULTS 25OHD was measured using liquid chromatography-t and em mass spectrometry in available plasma ( n = 2081 ) . Median plasma 25OHD was 18.6 ng/ml , and median vitamin D intake was 3.2 μg/d ( 128 IU/d ) . Vitamin D deficiency ( 25OHD dietary vitamin D intake , PTH , or adjusted calcium were associated with CVD events or with mortality . Vitamin D deficiency was not associated with CVD ( fully adjusted hazard ratio = 1.00 ; 95 % confidence interval = 0.77 - 1.31 ) . Results were similar after excluding patients who reported an activity-limiting longst and ing illness at baseline ( 18.8 % ) and those taking any vitamin supplements ( 21.7 % ) . However , there was some evidence vitamin D deficiency was associated with all-cause mortality ( fully adjusted hazard ratio = 2.02 ; 95 % confidence interval = 1.17 - 3.51 ) . CONCLUSION Vitamin D deficiency was not associated with risk of CVD in this cohort with very low 25OHD . Future trials of vitamin D supplementation in middle-aged cohorts should be powered to detect differences in mortality outcomes as well as CVD", "BACKGROUND AND AIMS Emerging evidence suggests that low levels of vitamin D may be an important risk factor for multiple chronic diseases and mortality , but the evidence is mixed . Vitamin D levels are associated with sun exposure , diet , and metabolic status . One potential explanation for the lack of consistent findings amongst various studies is that low vitamin levels may be associated with poor diets or other risk factors that we were not adequately controlled for in different analyses . METHODS Prospect i ve analysis of adults over the age of 35 in NHANES III data ( 1988 - 1994 ) with 20 year mortality follow-up . Sequential Cox proportional hazard models quartiles of 25OH vitamin D adjusted for age , season , geography , sociodemographic ( SD ) , CVD risk factors ( CVD ) and nutritional factors ( NF ) were performed . RESULTS Gender , race , diabetes , anti-hypertensive meds , income , taking vitamin D supplements , physical activity , alcohol consumption , region , body mass index , blood pressure , creatinine , albumin , CRP , thyroxine , iron , RBC folate , vitamin A , E , alpha-carotene , and lycopene were all associated with different quartiles of vitamin D and as well as CHD and all-cause mortality and thus are important potential confounders of this relationship . Adjusting for the confounding factors , higher levels of vitamin D demonstrate an inverse relationship with all-cause mortality , but only the top quartile of vitamin D shows an inverse relationship with CHD mortality . CONCLUSIONS The highest quartile compared to the lowest quartile of 25OH vitamin D levels is inversely associated with CHD and all-cause mortality adjusting for multiple confounders . Whether supplementation of individuals with low vitamin D will result in similar benefits will require a r and omized clinical trial", "Evidence continues to mount that vitamin D reduces the risk and mortality rates of many types of disease . However , evidence from prospect i ve cohort studies is sometimes weaker than that from case – control and ecological studies . A suggested reason for this discrepancy is that , because serum levels of 25-hydroxyvitamin D [ 25(OH)D ] change over time , a single 25(OH)D concentration measurement taken at study enrollment does not reliably indicate 25(OH)D concentration related to the health outcome . To evaluate this suggestion further , this paper plots results from 12 prospect i ve cohort studies of all-cause mortality rate vs. follow-up time . The regression fit to the hazard ratio per 20-nmol/l increase in serum 25(OH)D concentration vs. time increased from 0.82 ( 95 % CI , 0.67–1.02 ) for 6 y to 0.96 ( 95 % CI , 0.90–1.01 ) for 14 y. The value extrapolated for zero follow-up time was 0.72 ( 95 % CI , 0.50–1.03 ) , giving a hazard ratio reduction 3.5 times higher than the st and ard result from the meta- analysis [ 0.92 ( 95 % CI , 0.89–0.95 ) ] . Using the example of the Vitamin D Pooling Project of Rarer Cancers , this paper also discusses follow-up time ’s effect in interpreting prospect i ve cohort studies of cancer outcome . This paper recommends that meta-analyses of prospect i ve cohort studies account for follow-up time and , if possible , that studies measure serum 25(OH)D concentration every 2–4", "Background / Objectives : Vitamin D deficiency is associated with cardiovascular disease , osteoporosis , poor muscle strength , falls , fractures and mortality . Although older adults are at a higher risk of vitamin D deficiency , the relationship of serum 25-hydroxyvitamin D ( 25(OH)D ) with all-cause and cardiovascular disease mortality has not been well characterized in the elderly . We hypothesized that low serum 25(OH)D levels predicted mortality in older adults . Subjects/ Methods : Serum 25(OH)D as well as all-cause and cardiovascular disease mortality were examined in 1006 adults , aged ⩾65 years , who participated in the InCHIANTI ( Invecchiare in Chianti , Aging in the Chianti Area ) study , a population -based , prospect i ve cohort study of aging in Tuscany , Italy . Serum 25(OH)D levels were measured at the time of enrollment in 1998–1999 , and participants were followed up for mortality . Results : During 6.5 years of follow-up , 228 ( 22.7 % ) participants died , of whom 107 died due to cardiovascular diseases . Compared with participants in the highest quartile of serum 25(OH)D ( > 26.5 ng/ml ) ( to convert to nmol/l , multiply by 2.496 ) , those in the lowest quartile ( increased risk of all-cause mortality ( Hazard Ratio ( H.R. ) 2.11 , 95 % Confidence Interval ( 95 % C.I. ) : 1.22–3.64 , P=0.007 ) and cardiovascular disease mortality ( H.R. 2.64 , 95 % C.I. : 1.14–4.79 , P=0.02 ) , in multivariate Cox proportional hazards models that adjusted for age , sex , education , season , physical activity and other potential confounders . Conclusions : Older community-dwelling adults with low serum 25(OH)D levels are at higher risk of all-cause and cardiovascular disease mortality ", "BACKGROUND / OBJECTIVES : Although both frailty and low vitamin D have been separately associated with an increased risk for adverse health , their joined effects on mortality have not been reported . The current study examined prospect ively the effects of frailty and vitamin D status on mortality in US older adults . SUBJECTS/ METHODS : Participants aged ⩾60 years in The Third National Health and Nutrition Examination Survey with 12 years of mortality follow-up were included in the analysis ( n=4731 ) . Frailty was defined as meeting three or more criteria and pre-frailty as meeting one or two of the five frailty criteria ( low body mass index ( BMI ) , slow walking , weakness , exhaustion and low physical activity ) . Vitamin D status was assessed by serum 25-hydroxyvitamin D ( 25(OH)D ) and categorized into quartiles . Analyses were adjusted for gender , race , age , smoking , education , latitude and other comorbid conditions . RESULTS : Serum 25(OH)D concentrations were lowest in participants with frailty , intermediate in participants with pre-frailty and highest in participants without frailty . The odds of frailty in the lowest quartile of serum 25(OH)D was 1.94 times the odds in the highest quartile ( 95 % confidence interval ( CI ) : 1.09–3.44 ) . Mortality was positively associated with frailty , with the risk among participants who were frail and had low serum 25(OH)D being significantly higher than those who were not frail and who had high concentrations of serum 25(OH)D ( hazards ratio 2.98 ; 95 % CI : 2.01–4.42 ) . CONCLUSION : Our results suggest that low serum 25(OH)D is associated with frailty , and there is additive joint effects of serum 25(OH)D and frailty on all-cause mortality in older adults", "Purpose To investigate the association between serum 25-hydroxyvitamin D [ 25(OH)D ] concentration , a marker of vitamin D status , and risk of all-cause and cardiovascular mortality in a general older population with relatively low average serum 25(OH)D concentrations . Methods The study population included 552 men and 584 women aged 53–73 years who were free of CVD and cancer at baseline in 1998–2001 from the prospect i ve , population -based Kuopio Ischaemic Heart Disease Risk Factor ( KIHD ) Study . Deaths were ascertained by a computer linkage to the national cause of death register . All deaths that occurred from the study entry to December 31 , 2008 , were included . Cox proportional hazards regression models were used to analyze the association between serum 25(OH)D and risk of death . Results The mean serum 25(OH)D concentration was 43.7 nmol/L ( SD 17.8 ) , with a strong seasonal variation . During the average follow-up of 9.1 years , 87 participants died , 35 from cardiovascular disease ( CVD ) . After multivariable-adjustments , the hazard ratios ( HR ) for all cause death in the tertiles of serum 25(OH)D were 1 , 1.68 ( 95 % CI : 0.92 , 3.07 ) and 2.06 ( 95 % CI : 1.12 , 3.80 ) , p for trend = 0.02 . Conclusions Our study supports the accumulating evidence from epidemiological studies that vitamin D deficiency is associated with increased risk of death . Large-scale primary prevention trials with vitamin D supplementation are warranted", "Prospect i ve epidemiologic data on the association between vitamin D and mortality are limited , particularly in Asian population s. Among subjects in Linxian , China , the authors aim ed to test whether baseline serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations in a prospect i ve cohort were associated with all-cause mortality and cause-specific mortality rates over 24 years of follow-up ( 1986 - 2010 ) . Serum 25(OH)D concentrations were measured in 1,101 subjects using an immunoassay . Hazard ratios and 95 % confidence intervals were calculated using Cox regression models that were adjusted for age , sex , tobacco smoking , alcohol drinking , and hypertension . The 25th , 50th , and 75th percentile concentrations of 25(OH)D were 19.6 , 31.9 , and 48.4 nmol/L , respectively . During follow-up , 793 subjects died , including 279 who died of cerebrovascular accident , 217 who died of cancer , and 200 cardiovascular disease deaths . All-cause mortality was not associated with 25(OH)D concentrations using continuous models ( for every 15 nmol/L , hazard ratio = 1.01 , 95 % confidence interval : 0.97 , 1.05 ) or quartile models ( fourth vs. first quartiles , hazard ratio = 1.06 , 95 % confidence interval : 0.87 , 1.30 ; P for trend = 0.731 ) . The authors also found no association with the cause-specific mortality outcomes . Results were similar for men and women . This study showed that prediagnostic serum 25(OH)D concentrations were not associated with all-cause or cause-specific mortality rates in this Chinese population who had low levels of vitamin", "Objective To investigate the association of vitamin D status with all-cause mortality in a Norwegian population and the potential influences of existing chronic diseases on the association . Design A population -based prospect i ve cohort study . Setting Nord-Trøndelag County , Norway . Participants A r and om sample ( n=6613 ) of adults aged 20 years or older in a cohort . Methods Serum 25-hydroxyvitamin D ( 25(OH)D ) levels were measured in blood sample s collected at baseline ( n=6377 ) . Mortality was ascertained from the Norwegian National Registry . Cox regression models were applied to estimate the HRs with 95 % CIs for all-cause mortality in association with serum 25(OH)D levels after adjustment for a wide spectrum of confounding factors as well as chronic diseases at baseline . Results The median follow-up time was 18.5 years , during which 1539 subjects died . The HRs for all-cause mortality associated with the first quartile level of 25(OH)D ( Low serum 25(OH)D level was associated with increased all-cause mortality in a general Norwegian population . The association was not notably influenced by existing chronic diseases", "The beneficial biologic effects attributed to vitamin D suggest a potential to influence overall mortality . Evidence addressing this hypothesis is limited , especially for African Americans who have a high prevalence of vitamin D insufficiency . The authors conducted a nested case-control study within the prospect i ve Southern Community Cohort Study to relate baseline serum levels of 25-hydroxyvitamin D ( 25(OH)D ) with subsequent mortality . Cases were 1,852 participants who enrolled from 2002 to 2009 and died > 12 months postenrollment . Controls ( n = 1,852 ) were matched on race , sex , age , enrollment site , and blood collection date . The odds ratios for quartile 1 ( 21.64 ng/mL ) levels of 25(OH)D were 1.60 ( 95 % confidence interval ( CI ) : 1.20 , 2.14 ) for African Americans and 2.11 ( 95 % CI : 1.39 , 3.21 ) for non-African Americans . The effects were strongest for circulatory disease death , where quartile 1 versus quartile 4 odds ratios were 2.53 ( 95 % CI : 1.44 , 4.46 ) and 3.25 ( 95 % CI : 1.33 , 7.93 ) for African Americans and non-African Americans , respectively . The estimated odds of total mortality were minimized in the 25(OH)D range of 35 - 40 ng/mL. These findings provide support for the hypothesis that vitamin D status may have an important influence on mortality for both African Americans and non-African Americans", "BACKGROUND Evidence is accumulating that vitamin D supplementation of patients with low 25-hydroxyvitamin D concentrations is associated with lower cardiovascular morbidity and total mortality during long-term follow-up . Little is known , however , about the effect of low concentrations of the vitamin D hormone calcitriol on total mortality . We therefore evaluated the predictive value of circulating calcitriol for midterm mortality in patients of a specialized heart center . METHODS This prospect i ve cohort study included 510 patients , 67.7 % with heart failure ( two-thirds in end stage ) , 64.3 % hypertension , 33.7 % coronary heart disease , 20.2 % diabetes , and 17.3 % renal failure . We followed the patients for up to 1 year after blood collection . For data analysis , the study cohort was stratified into quintiles of circulating calcitriol concentrations . RESULTS Patients in the lowest calcitriol quintile were more likely to have coronary heart disease , heart failure , hypertension , diabetes , and renal failure compared to other patients . They also had low 25-hydroxyvitamin D concentrations and high concentrations of creatinine , C-reactive protein , and tumor necrosis factor alpha . Eighty-two patients ( 16.0 % ) died during follow-up . Probability of 1-year survival was 66.7 % in the lowest calcitriol quintile , 82.2 % in the second quintile , 86.7 % in the intermediate quintile , 88.8 % in the fourth quintile , and 96.1 % in the highest quintile ( P survivors and nonsurvivors was best when a cutoff value of 25 ng/L was applied ( area under the ROC curve 0.72 ; 95 % CI 0.66 - 0.78 ) . CONCLUSIONS Decreased calcitriol levels are linked to excess midterm mortality in patients of a specialized heart center", "BACKGROUND vitamin D deficiency has been associated with an increased risk of mortality , but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain . Our objective was to determine whether endogenous 25-hydroxyvitamin D ( 25(OH)D ) , 1,25-dihydroxyvitamin D ( 1,25(OH)2D ) and parathyroid hormone ( PTH ) levels predicted all-cause , cardiovascular and cancer mortality independently of health and lifestyle factors . SETTING : prospect i ve cohort analysis within the European Male Ageing Study . PARTICIPANTS : 2,816 community-dwelling men aged 40 - 79 years at baseline . METHODS : Cox regression was used to examine the association of all-cause mortality with 25(OH)D , 1,25(OH)2D and PTH ; cardiovascular and cancer mortality were modelled using competing-risks regression . Results were expressed as hazard ratios ( HR ) and 95 % confidence intervals ( CIs ) for Cox models ; sub-hazard ratios ( SHR ) and 95 % CIs for competing-risks models . RESULTS : a total of 187 men died during a median of 4.3 years of follow-up . Serum levels of 25(OH)D ( per 1 SD decrease : HR = 1.45 ; 95 % CI = 1.16 , 1.81 ) and 1,25(OH)2D ( per 1 SD decrease : HR = 1.20 ; 95 % CI = 1.00 , 1.44 ) were associated with an increased risk of all-cause mortality after adjusting for age , centre , smoking , self-reported morbidities , physical activity and functional performance . Only levels of 25(OH)D predicted cancer mortality ( SHR = 3.33 ; 95 % CI = 1.38 , 8.04 ) . CONCLUSION : lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men . Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here", "Objective To test the hypothesis that genetically low 25-hydroxyvitamin D concentrations are associated with increased mortality . Design Mendelian r and omisation analysis . Setting Copenhagen City Heart Study , Copenhagen General Population Study , and Copenhagen Ischemic Heart Disease Study . Participants 95 766 white participants of Danish descent from three cohorts , with median follow-up times of 19.1 , 5.8 , and 7.9 years , genotyped for genetic variants in DHCR7 and CYP2R1 affecting plasma 25-hydroxyvitamin D concentrations ; 35 334 also had plasma 25-hydroxyvitamin D measurements . Participants were followed from study entry through 2013 , during which time 10 349 died . Main outcome measures All cause mortality and cause specific mortality , adjusted for common risk factors for all cause mortality based on the World Health Organization ’s global health status . Results The multivariable adjusted hazard ratios for a 20 nmol/L lower plasma 25-hydroxyvitamin D concentration were 1.19 ( 95 % confidence interval 1.14 to 1.25 ) for all cause mortality , 1.18 ( 1.09 to 1.28 ) for cardiovascular mortality , 1.12 ( 1.03 to 1.22 ) for cancer mortality , and 1.27 ( 1.15 to 1.40 ) for other mortality . Each increase in DHCR7/CYP2R1 allele score was associated with a 1.9 nmol/L lower plasma 25-hydroxyvitamin D concentration and with increased all cause , cancer , and other mortality but not with cardiovascular mortality . The odds ratio for a genetically determined 20 nmol/L lower plasma 25-hydroxyvitamin D concentration was 1.30 ( 1.05 to 1.61 ) for all cause mortality , with a corresponding observational multivariable adjusted odds ratio of 1.21 ( 1.11 to 1.31 ) . Corresponding genetic and observational odds ratios were 0.77 ( 0.55 to 1.08 ) and 1.13 ( 1.03 to 1.24 ) for cardiovascular mortality , 1.43 ( 1.02 to 1.99 ) and 1.10 ( 1.02 to 1.19 ) for cancer mortality , and 1.44 ( 1.01 to 2.04 ) and 1.17 ( 1.06 to 1.29 ) for other mortality . The results were robust in sensitivity analyses . Conclusions Genetically low 25-hydroxyvitamin D concentrations were associated with increased all cause mortality , cancer mortality , and other mortality but not with increased cardiovascular mortality . These findings are compatible with the notion that genetically low 25-hydroxyvitamin D concentrations may be causally associated with cancer and other mortality but also suggest that the observational association with cardiovascular mortality could be the result of confounding", "CONTEXT Vitamin D deficiency contributes to skeletal diseases and is highly prevalent among institutionalized elderly patients . Whether low 25-hydroxyvitamin D ( 25[OH]D ) concentrations are an independent risk factor for mortality in these patients is , however , unclear . OBJECTIVE We aim ed to evaluate whether 25(OH)D concentrations are associated with mortality . DESIGN , SETTING , AND PARTICIPANTS This is a prospect i ve cohort study among elderly female patients ( age > 70 yr ) recruited from 95 nursing homes in Austria . MAIN OUTCOME MEASURES We calculated Cox proportional hazard ratios ( HR ) for all-cause mortality according to 25(OH)D quartiles . RESULTS We examined 961 study participants ( age 83.7 ± 6.1 yr ) . Median 25(OH)D concentration was 17.5 ( interquartile range 13.7 - 25.5 ) nmol/liter , and 93 % of our cohort had 25(OH)D levels below 50 nmol/liter . During a mean follow-up time of 27 ± 8 months , 284 patients died . Compared with the fourth quartile ( 25[OH]D > 25.5 nmol/liter ) , the age-adjusted HR ( with 95 % confidence interval ) was 1.49 ( 1.07 - 2.10 ) in the first 25(OH)D quartile ( 25[OH]D Austrian study suggests that the majority of institutionalized female patients are vitamin D deficient during winter and that there was an inverse association of 25(OH)D and mortality . These data underscore the urgent need for effective strategies for the prevention and treatment of vitamin D deficiency , in particular in the setting of nursing homes", "Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases . The authors aim ed to investigate whether serum 25-hydroxyvitamin D ( 25(OH)D ) level predicts mortality from cardiovascular disease ( CVD ) . The study was based on the Mini-Finl and Health Survey and included 6,219 men and women aged > or = 30 years who were free from CVD at baseline ( 1978 - 1980 ) . During follow-up through 2006 , 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified . Levels of 25(OH)D were determined from serum collected at baseline . Cox 's proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death . After adjustment for potential confounders , the hazard ratio for total CVD death was 0.76 ( 95 % confidence interval ( 95 % CI ) : 0.60 , 0.95 ) for the highest quintile of 25(OH)D level versus the lowest . The association was evident for cerebrovascular death ( hazard ratio = 0.48 , 95 % CI : 0.31 , 0.75 ) but not coronary death ( hazard ratio = 0.91 , 95 % CI : 0.70 , 1.18 ) . A low vitamin D level may be associated with higher risk of a fatal CVD event , particularly cerebrovascular death . These findings need to be replicated in other population s. To demonstrate a causal link between vitamin D and CVD , r and omized controlled trials are required", "Objective To investigate the associations between low and high concentrations of baseline serum 25-hydroxyvitamin D [ 25(OH)D ] and all-cause mortality in very old ( ≥85 years ) men and women over 6 years . Design , setting and subjects Prospect i ve mortality data from 775 participants in the Newcastle 85 + Study were analysed for survival in relation to 25(OH)D ( season-specific quartiles and predefined cut-off values ) and sex using Cox proportional hazards models . The models were fitted to the entire and restricted ( nonusers of vitamin D-containing supplements and medication ) cohorts . Results For the entire cohort , mortality was higher in both the lowest and highest 25(OH)D season-specific quartiles [ SQ1 : hazard ratio ( HR ) 1.31 , 95 % confidence interval ( CI ) 1.01–1.69 , P = 0.04 ; SQ4 : HR 1.44 , 95 % CI 1.12–1.85 , P = 0.004 ] compared with the combined middle quartiles ( SQ2 + SQ3 ) , after adjustment for sociodemographic factors . The increased risk for the highest quartile remained significant after further adjustment for lifestyle variables ( SQ4 : HR 1.37 , 95 % CI 1.06–1.77 , P = 0.02 ) and was seen only in women in sex-specific analyses . Similarly , in sensitivity analyses with predefined 25(OH)D cut-off values , the highest 25(OH)D concentration ( ≥75 nmol L−1 ) was associated with a 2.4-fold increased risk of mortality in women ( restricted cohort ) after adjusting for all covariates . Conclusion Low and high season-specific 25(OH)D quartiles were associated with increased risks of mortality over 6 years in the very old ; this effect was particularly noticeable in women , including those who reported taking vitamin D-containing supplements/medication ", "CONTEXT Cardiovascular disease is the major cause of death in the Western world , but the association between 25-hydroxyvitamin D [ 25(OH)D ] levels and the risk of cardiovascular disease mortality remains unclear . OBJECTIVE The objective of the study was to determine the association between cardiovascular , stroke , and acute myocardial infa rct mortality and serum levels of 25(OH)D. DESIGN This was an observational cohort study , the Copenhagen vitamin D study , data from a single laboratory center in Copenhagen , Denmark . Follow-up was from 2004 to 2011 . SETTING Serum 25(OH)D was analyzed from 247 574 subjects from the Copenhagen general practice sector . PARTICIPANTS Examination of the association 25(OH)D levels and mortality from cardiovascular disease , stroke , and acute myocardial infa rct was performed among 161 428 women and 86 146 men . MAIN OUTCOME MEASURES A multivariate Cox regression analysis was used to compute hazard ratios for cardiovascular , stroke , and acute myocardial infa rct mortality . RESULTS Of 247 574 subjects , a total of 16 645 subjects died in the ensuing 0 - 7 years . A total of 5454 died from cardiovascular disease including 1574 from stroke and 702 from acute myocardial infa rct . The 25(OH)D level of 70 nmol/L was associated with the lowest cardiovascular disease mortality risk . Compared with that level , the hazard ratio for cardiovascular disease mortality was 2.0 [ 95 % confidence interval ( CI ) 1.8 - 2.1 ] at the lower extreme ( ∼ 12.5 nmol/L ) with a higher risk for men [ 2.5 ( 95 % CI 2.2 - 2.9 ) ] than for women [ 1.7 ( 95 % CI 1.5 - 1.9 ) ] . At the higher extreme ( ∼ 125 nmol/L ) , the hazard ratio of cardiovascular disease mortality was 1.3 ( 95 % CI 1.2 - 1.4 ) , with a similar risk among men and women . Results were similar for stroke and acute myocardial subgroups . CONCLUSIONS In this large observational study , low and high levels of 25(OH)D were associated with cardiovascular disease , stroke , and acute myocardial mortality in a nonlinear , reverse J-shaped manner , with the highest risk at lower levels . Whether this was a causal or associational finding can not be determined from our data . There is a need for r and omized clinical trials that include information on the effects of 25(OH)D levels greater than 100", "BACKGROUND recent systematic review s have cast doubt on the association between vitamin D and cardiovascular disease . No prior studies have investigated the association between 25-hydroxyvitamin D ( 25[OH]D ) , 1,25-dihydroxyvitamin D ( 1,25[OH](2)D ) , or intact parathyroid hormone and cardiovascular mortality in a temperate climate . METHODS a total of 1073 community-dwelling older adults were evaluated in 1997 - 1999 ; serum levels of 25(OH)D ( mean 42 ng/mL ) , 1,25(OH)(2)D ( median 29 pg/mL ) , and intact parathyroid hormone ( median 46 pg/mL ) were measured ; mean estimated glomerular filtration rate was 74 mL/min/1.73 m(2 ) . Participants were followed up to 10.4 ( mean 6.4 ) years with 111 cardiovascular deaths . RESULTS in unadjusted Cox proportional hazards models , higher levels of 1,25(OH)(2)D were protective against cardiovascular mortality , whereas higher levels of intact parathyroid hormone predicted increased risk of cardiovascular death . After adjusting for age alone or multiple covariates , there was no significant association between 25(OH)D , 1,25(OH)(2)D , or intact parathyroid hormone and cardiovascular mortality ; results did not differ by an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m(2 ) or Caucasian , middle-income , community-dwelling older adults living in sunny southern California , serum levels of 25(OH)D , 1,25(OH)(2)D , and intact parathyroid hormone were not independently associated with cardiovascular mortality", "CONTEXT Previous 25-hydroxyvitamin D [ 25(OH)D ] and mortality studies have included mostly individuals of European descent . Whether the relationship is similar in Blacks and to what extent differences in 25(OH)D explain racial disparities in mortality is unclear . OBJECTIVE The objective of the study was to examine the relationship between 25(OH)D , PTH , and mortality in Black and white community-dwelling older adults over 8.5 yr of follow-up . DESIGN AND SETTING Health ABC is a prospect i ve cohort study conducted in Memphis , TN , and Pittsburgh , PA . PARTICIPANTS Well-functioning Blacks and whites aged 71 - 80 yr with measured 25(OH)D and PTH ( n = 2638 ; 49 % male , 39 % Black ) were included in the study . MAIN OUTCOME MEASURE Multivariate-adjusted proportional hazards models estimated the hazard ratios ( HR ) for all-cause , cardiovascular , cancer , and noncancer , noncardiovascular mortality ( n = 691 deaths ) . RESULTS Mean 25(OH)D concentrations were higher in whites than in Blacks [ mean ( sd ) : 29.0 ( 9.9 ) and 20.8 ( 8.7 ) ng/ml , respectively ; P . Serum 25(OH)D by race interactions were not significant , however . Lower 25(OH)D concentrations were associated with higher mortality in Blacks and whites combined [ HR ( 95 % confidence interval [ CI ] 2.27 ( 1.59 - 3.24 ) , 1.48 ( 1.20 - 1.84 ) , and 1.25 ( 1.02 - 1.52 ) for higher mortality than whites [ HR ( 95 % CI ) 1.22 ( 1.01 , 1.48 ) ] ; after including 25(OH)D in the model , the association was attenuated [ 1.09 ( 0.90 - 1.33 ) ] . The mortality population attributable risks ( 95 % CI ) for 25(OH)D concentrations less than 20 ng/ml and less than 30 ng/ml in Blacks were 16.4 % ( 3.1 - 26.6 % ) and 37.7 % ( 11.6 - 55.1 % ) and in whites were 8.9 % ( 3.9 - 12.7 % ) and 11.1 % ( -2.7 to 22.0 % ) , respectively . PTH was also associated with mortality [ HR ( 95 % CI ) 1.80 ( 1.33 - 2.43 ) for ≥70 vs. increased mortality in Black and white community-dwelling older adults . Because 25(OH)D concentrations were much lower in Blacks , the potential impact of remediating low 25(OH)D concentrations was greater in Blacks than whites", "OBJECTIVE To assess the prospect i ve association of serum 25-hydroxyvitamin D [ 25(OH)D ] levels with frailty status and all-cause mortality in a cohort of community-dwelling participants of the population -based KORA [ Cooperative Health Research in the Region of Augsburg]-Age Study . METHODS 727 non-frail participants , aged ≥65years , with 25(OH)D measurement at baseline in 2009 , were followed for 2.9±0.1years . Participants were classified as pre-frail or frail if they met 1 - 2 or ≥3 , respectively , of the following five criteria : weight loss , exhaustion , physical inactivity , low walking speed , weakness . The association between 25(OH)D and mortality was assessed in 954 participants . Multivariable adjusted logistic regression models were calculated for each outcome . RESULTS The incidence of pre-frailty and frailty was 21.2 % and 3.9 % respectively . After multivariable adjustment , participants with very low 25(OH)D levels ( pre-frailty ( OR=2.43 [ 95 % CI : 1.17 - 5.03 ] ) and pre-frailty/frailty combined ( OR=2.53 [ 95 % CI : 1.23 - 5.22 ] ) , but not for frailty alone ( OR=2.63 [ 95 % CI : 0.39 - 17.67 ] ) . The association between 25(OH)D and mortality ( OR=3.39 [ 95 % CI : 1.08 - 10.65 ] ) was partly mediated by frailty status . CONCLUSION Very low 25(OH)D levels were independently associated with incident pre-frailty , pre-frailty/frailty combined and all-cause mortality", "CONTEXT AND OBJECTIVE Hypovitaminosis D and frailty are common in the older population . We aim ed to determine whether 25-hydroxyvitamin D [ 25(OH)D ] concentrations are associated with frailty and mortality . DESIGN We conducted a prospect i ve cohort study . SETTING AND PARTICIPANTS Participants included 4203 older men aged 70 - 88 years in Perth , Western Australia . MAIN OUTCOME MEASURES 25(OH)D was measured by immunoassay . Frailty was assessed with the 5-point FRAIL ( fatigue , resistance , ambulation , illness , and loss of weight ) scale . Mortality was determined from the death registry via the Western Australian Data Linkage System . RESULTS At baseline , 676 ( 16.1 % ) men were frail , as defined by having ≥3 deficits ( FRAIL scale ≥ 3 ) . In multivariate cross-sectional analysis , low vitamin D status , defined by the lowest quartile of 25(OH)D values ( prevalent frailty ( odds ratio , 1.96 ; 95 % confidence interval [ CI ] , 1.52 to 2.52 ) in comparison to the highest quartile of 25(OH)D values ( > 81.6 nmol/L ) . After a mean period of 5.3 years , the adjusted odds ratio of being frail at follow-up for men with low vitamin D and having zero deficit at baseline ( FRAIL scale = 0 ) was 1.56 ( 95 % CI , 1.07 to 2.27 ) . Low vitamin D also predicted all-cause mortality over a period of up to 9.2 years ( hazard ratio , 1.20 ; 95 % CI , 1.02 to 1.42 ) , independent of baseline frailty and other covariates . CONCLUSION Hypovitaminosis D is associated with prevalent and incident frailty in older men . Hypovitaminosis D also predicts all-cause mortality , independent of frailty . The association between vitamin D and mortality is not solely dependent on the occurrence of frailty", "BACKGROUND Vitamin D , specifically serum 25(OH)D has been associated with mortality , cancer and multiple other health endpoints in observational studies , but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population -wide supplementation . We have therefore launched the D-Health Trial , a r and omized trial of vitamin D supplementation for prevention of mortality and cancer . Here we report the methods and describe the trial cohort . METHODS The D-Health Trial is a r and omized placebo-controlled trial , with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers . Participants aged 65 - 84years were recruited from the general population of Australia . The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo . The primary outcome is all-cause mortality . Secondary outcomes are total cancer incidence and colorectal cancer incidence . RESULTS We recruited 21,315 participants to the trial between February 2014 and May 2015 . The participants in the two arms of the trial were well-balanced at baseline . Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health , to be current smokers or to have diabetes than the Australian population . However , the proportion overweight or with health conditions such as arthritis and angina was similar . CONCLUSIONS Observational data can not be considered sufficient to support interventions delivered at a population level . Large-scale r and omized trials such as the D-Health Trial are needed to inform public health policy and practice", "Despite continued appreciation of the potential role of vitamin D and omega-3 fatty acids in the prevention of cancer and cardiovascular disease ( CVD ) , there remain no completed large-scale , r and omized trials of these agents for the primary prevention of cancer or CVD in a population that has not been selected on the basis of elevated risk . The VITamin D and OmegA-3 TriaL ( VITAL ) is a 2 × 2 factorial r and omized , double-blind , placebo-controlled trial of the benefits and risks of vitamin D ( vitamin D3 [ cholecalciferol ] , 2000 IU/d ) and marine omega-3 fatty acids ( Omacor ( ® ) fish oil , a 1 g/d ) in the primary prevention of cancer and CVD among 25,875 men and women , aged ≥50 and ≥55 years , respectively . R and omization began in November 2011 and was completed in March 2014 . This report will describe the rationale for the trial and currently available r and omized trial data , summarize related ongoing large-scale trials , and provide a brief overview of study design , and an up date on r and omization milestones , racial/ethnic diversity , biorepository activities , in-depth phenotyping of a subcohort , and ancillary studies", "OBJECTIVE Institutionalised elderly people at northern latitudes may be at elevated risk for vitamin D deficiency . In addition to osteoporosis-related disorders , vitamin D deficiency may influence several medical conditions conferring an increased mortality risk . The aim of this study was to explore the prevalence of vitamin D deficiency and its association with mortality . DESIGN The Study of Health and Drugs in the Elderly ( SHADES ) is a prospect i ve cohort study among elderly people ( > 65 years ) in 11 nursing homes in Sweden . METHODS We analysed the levels of 25-hydroxyvitamin D₃ ( 25(OH)D₃ ) at baseline . Vital status of the subjects was ascertained and hazard ratios ( HRs ) for mortality according to 25(OH)D₃ quartiles were calculated . RESULTS We examined 333 study participants with a mean follow-up of 3 years . A total of 147 ( 44 % ) patients died within this period . Compared with the subjects in Q4 ( 25(OH)D₃ > 48 nmol/l ) , HR ( with 95 % CI ) for mortality was 2.02 ( 1.31 - 3.12 ) in Q1 ( 25(OH)D₃ ) . The mean 25(OH)D₃ concentration was 40.2 nmol/l ( S.D. 16.0 ) and 80 % had 25(OH)D₃ below 50 nmol/l . The vitamin D levels decreased from baseline to the second and third measurements . CONCLUSIONS Vitamin D deficiency was highly prevalent and associated with increased mortality among the elderly in Swedish nursing homes . Strategies are needed to prevent , and maybe treat , vitamin D deficiency in the elderly in nursing homes and the benefit of vitamin D supplementation should be evaluated in r and omised clinical trials", "BACKGROUND In cross-sectional studies , low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease . This study aim ed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality . METHODS Prospect i ve cohort study of 3258 consecutive male and female patients ( mean [ SD ] age , 62 [ 10 ] years ) scheduled for coronary angiography at a single tertiary center . We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings . The main outcome measures were all-cause and cardiovascular deaths . RESULTS During a median follow-up period of 7.7 years , 737 patients ( 22.6 % ) died , including 463 deaths from cardiovascular causes . Multivariate-adjusted hazard ratios ( HRs ) for patients in the lower two 25-hydroxyvitamin D quartiles ( median , 7.6 and 13.3 ng/mL [ to convert 25-hydroxyvitamin D levels to nanomoles per liter , multiply by 2.496 ] ) were higher for all-cause mortality ( HR , 2.08 ; 95 % confidence interval [ CI ] , 1.60 - 2.70 ; and HR , 1.53 ; 95 % CI , 1.17 - 2.01 ; respectively ) and for cardiovascular mortality ( HR , 2.22 ; 95 % CI , 1.57 - 3.13 ; and HR , 1.82 ; 95 % CI , 1.29 - 2.58 ; respectively ) compared with patients in the highest 25-hydroxyvitamin D quartile ( median , 28.4 ng/mL ) . Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile . These effects were independent of coronary artery disease , physical activity level , Charlson Comorbidity Index , variables of mineral metabolism , and New York Heart Association functional class . Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation ( C-reactive protein and interleukin 6 levels ) , oxidative burden ( serum phospholipid and glutathione levels ) , and cell adhesion ( vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels ) . CONCLUSIONS Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality . A causal relationship has yet to be proved by intervention trials using vitamin", "OBJECTIVES To explore associations between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and a wide range of health conditions , physical performance measures , disability , and mortality in a large epidemiological study to identify an optimum range for 25(OH)D concentrations . DESIGN Cross-sectional study , with additional prospect i ve data on falls and mortality . SETTING Concord Health and Ageing in Men Project , Sydney , Australia . PARTICIPANTS Community-dwelling men aged 70 and older ( N = 1,659 ) . MEASUREMENTS Serum 25(OH)D levels , general health status , self-reported diseases , physical performance measures , disability ( activities of daily living and instrumental activities of daily living ) and falls . RESULTS Fair , poor , and very poor health ; self-reported diabetes mellitus ; hyperglycemia ; depression ; muscle weakness ; poor balance ; and all-cause mortality were all associated with serum 25(OH)D levels less than 50 nmol/L , even after adjustment for confounding . The findings also suggest that , in older men , for a wide range of health conditions , physical performance measures , disability , falls , and mortality , the optimum range of 25(OH)D is between 50.0 and 74.9 nmol/L , with no additional benefit for 25(OH)D levels of 75.0 nmol/L or greater . CONCLUSION Programs aim ed at achieving an optimum range of serum 25(OH)D at levels between 50.0 and 74.9 nmol/L may have overall health benefits and such levels are adequate for older men", "OBJECTIVES To investigate the association between low vitamin D levels ( 10-year mortality in women aged 75 and older . DESIGN Prospect i ve with 15 years of follow-up . SETTING Malmö , Sweden . PARTICIPANTS Population -based cohort of 75-year-old women ( N = 1,044 ) . MEASUREMENTS Serum 25-hydroxyvitamin D ( 25(OH)D ) levels at age 75 ( n = 1,011 ) , 80 ( n = 642 ) , and 85 ( n = 348 ) were categorized as low ( 75 nmol/L ) at all ages . Hazard ratios ( HRs ) for all-cause mortality between ages 75 and 90 were calculated according to 25(OH)D category . RESULTS Between ages 80 and 90 , all-cause mortality ( HR = 1.8 , 95 % confidence interval ( CI ) = 1.3 - 2.4 , P mortality , but even after excluding women with osteoporotic fracture during the risk of dying associated with low 25(OH)D remained greater ( HR = 1.8 , 95 % CI = 1.2 - 2.7 , P = .002 ; aHR = 1.7 , 95 % CI = 1.2 - 2.5 , P = .006 ) . CONCLUSION In this observational study of women aged 75 and older , 25(OH)D levels of less than 50 nmol/L were associated with greater all-cause mortality for up to 10 years . This difference was at least partially independent of comorbidities and fracture , indicating that low 25(OH)D not only is an indicator of impaired health , but also plays a role in disease outcome", "Prospect i ve studies , mostly from Europe and North America , suggest that serum 25‐hydroxyvitamin D ( 25(OH)D ) is inversely associated with mortality and cardiovascular disease ( CVD ) risk . Data from other regions are limited , and threshold levels for adverse cardiovascular outcomes are uncertain . We examined serum 25(OH)D as a predictor of total mortality and cardiovascular outcomes in an Australian cohort", "OBJECTIVE To investigate relationships between mortality and circulating 25-hydroxyvitamin D ( 25(OH)D ) , 25-hydroxycholecalciferol ( 25(OH)D3 ) and 25-hydroxyergocalciferol ( 25(OH)D2 ) . DESIGN Case-cohort study within the Melbourne Collaborative Cohort Study ( MCCS ) . We measured 25(OH)D2 and 25(OH)D3 in archived dried blood spots by LC-MS/MS . Cox regression was used to estimate mortality hazard ratios ( HR ) , with adjustment for confounders . SETTING General community . SUBJECTS The MCCS included 29 206 participants , who at recruitment in 1990 - 1994 were aged 40 - 69 years , had dried blood spots collected and no history of cancer . For the present study we selected participants who died by 31 December 2007 ( n 2410 ) and a r and om sample ( sub-cohort , n 2996 ) . RESULTS The HR per 25 nmol/l increment in concentration of 25(OH)D and 25(OH)D3 were 0·86 ( 95 % CI 0·78 , 0·96 ; P=0·007 ) and 0·85 ( 95 % CI 0·77 , 0·95 ; P=0·003 ) , respectively . Of 5108 participants , sixty-three ( 1·2 % ) had detectable 25(OH)D2 ; their mean 25(OH)D concentration was 11·9 ( 95 % CI 7·3 , 16·6 ) nmol/l higher ( P The HR for detectable 25(OH)D2 was 1·80 ( 95 % CI 1·09 , 2·97 ; P=0·023 ) ; for those with detectable 25(OH)D2 , the HR per 25 nmol/l increment in 25(OH)D was 1·06 ( 95 % CI 0·87 , 1·29 ; P interaction=0·02 ) . HR were similar for participants who reported being in good , very good or excellent health four years after recruitment . CONCLUSIONS Total 25(OH)D and 25(OH)D3 concentrations were inversely associated with mortality . The finding that the inverse association for 25(OH)D was restricted to those with no detectable 25(OH)D2 requires confirmation in population s with higher exposure to ergocalciferol", "Background : Poor vitamin D status , i.e. low serum levels of 25-hydroxyvitamin D [ 25(OH)D ] , is common in the general population . Prospect i ve epidemiologic data on the association between vitamin D and mortality in oldest old subjects are limited . Objective : This study aim ed to determine whether 25(OH)D concentrations were prospect ively and independently associated with cardiovascular disease ( CVD ) mortality and all-cause mortality in oldest old subjects . Methods : A total of 312 subjects aged 85 years old at baseline ( Octabaix study ) were followed for 3 years . Sociodemographic and overall geriatric assessment data were collected . Serum 25(OH)D concentrations were used to assess vitamin D status . Data on overall and cardiovascular mortality were collected . Results : The mean serum 25(OH)D levels were 28 ± 30 ng/ml . During the follow-up period , 58 subjects ( 18.5 % ) died . Twenty-five of the deaths ( 8 % ) were related to CVD . There were no differences in mortality rates according to the different quartiles of vitamin D ( p = 0.41 for total mortality and p = 0.86 for CVD mortality ) . Conclusion : In community-dwelling oldest old subjects , serum 25(OH)D levels were not associated with overall or CVD mortality after a 3-year follow-up", "CONTEXT Low 25-hydroxyvitamin D [ 25(OH)D ] and high PTH may contribute to increased mortality risk in older adults . OBJECTIVE The aim of the study was to test the association between 25(OH)D , PTH , and mortality in older men . DESIGN AND SETTING The prospect i ve Osteoporotic Fractures in Men ( MrOS ) study was conducted at six U.S. clinical centers . PARTICIPANTS We studied community-dwelling men at least 65 yr old ( n = 1490 ) . MAIN OUTCOME MEASURE Multivariate-adjusted proportional hazards models estimated the hazard ratio ( HR ) for mortality ; cause of death was classified as cancer , cardiovascular , and other by central review of death certificates . RESULTS During 7.3 yr of follow-up , 330 ( 22.2 % ) participants died : 97 from cancer , 110 from cardiovascular disease , and 106 from other causes . The adjusted HR per sd decrease in 25(OH)D for all-cause mortality was 1.01 ( 95 % CI , 0.89 , 1.14 ) ; no association between 25(OH)D and cardiovascular or other-cause mortality was seen . Unexpectedly , lower 25(OH)D levels were modestly associated with a decreased risk of cancer mortality ( adjusted HR per sd decrease , 0.80 ; 95 % CI , 0.64 , 0.99 ) . Analyzing 25(OH)D as a categorical variable did not alter these results . Higher PTH levels ( log-transformed ) were associated with an increased risk of all-cause mortality ( adjusted HR per sd increase , 1.15 ; 95 % CI , 1.03 , 1.29 ) and cardiovascular mortality ( adjusted HR per sd increase in PTH , 1.21 ; 95 % CI , 1.00 , 1.45 ) . CONCLUSIONS In contrast to previous studies , lower 25(OH)D levels were not associated with an increased risk of all-cause or cause-specific mortality in older men . Higher PTH levels were associated with a modest increase in mortality risk", "Highlights • The BEST-D ( Biochemical Efficacy and Safety Trial of vitamin D ) trial will compare the biochemical and other effects of daily dietary supplementation with 100 μg or 50 μg vitamin D3 or placebo , when administered for 12 months , in 305 ambulant community-dwelling older people living in Oxfordshire , Engl and .• The primary analyses will compare 12-month mean plasma concentrations of 25(OH)D as well as the proportion of participants with a 12-month concentration > 90 nmol/L between participants allocated 100 μg and participants allocated 50 μg daily . Secondary analyses will compare the two active doses ( both separately and when combined ) with placebo.• Additional end-points include biochemical assessment s of safety , blood pressure , arterial stiffness , falls , fractures , heel and wrist bone density , grip strength and physical performance and echocardiographic assessment s of cardiac function in a r and om sample of participants .• The results of this trial will help determine the optimum dose of vitamin D to test in a larger trial investigating whether vitamin D supplementation can reduce the risk of fractures , cardiovascular disease or cancer", "Observational studies suggest that low concentrations of serum 25-hydroxyvitamin D ( 25(OH)D ) and high concentrations of parathyroid hormone ( PTH ) are associated with a higher risk of mortality . The aim of this study was to examine whether 25(OH)D and PTH concentrations are independently associated with overall and disease-specific ( cardiovascular and cancer-related ) mortality in a large , prospect i ve population -based cohort of older adults . Data from 1317 men and women ( 65 - 85 years ) of the Longitudinal Aging Study Amsterdam were used . Cox proportional hazard analyses were used to examine whether 25(OH)D and PTH at baseline were associated with overall mortality ( with a follow-up of 18 years ) and disease-specific mortality ( with a follow-up of 13 years ) . Compared to persons in the reference category of ≥75nmol/L , persons with serum 25(OH)D higher risk of overall mortality , as well as men with baseline PTH concentrations ≥7pmol/L ( HR 2.54 ( 95 % CI : 1.58 - 4.08 ) ) , compared to the reference category of with overall mortality was partly mediated by PTH . Furthermore , men with PTH concentrations of ≥7pmol/L ( HR 3.22 ; 95 % CI : 1.40 - 7.42 ) had a higher risk of cardiovascular mortality , compared to the reference category . No significant associations of 25(OH)D or PTH with cancer-related mortality were observed . Both 25(OH)D and PTH should be considered as important health markers", "OBJECTIVES To evaluate the association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and mortality in a representative U.S. sample of older adults . DESIGN Prospect i ve cohort from the Third National Health and Nutrition Examination Survey ( NHANES III ) and linked mortality files . SETTING Noninstitutionalized U.S. civilian population . PARTICIPANTS Three thous and four hundred eight NHANES III participants aged 65 and older enrolled from 1988 to 1994 and followed for mortality through 2000 . MEASUREMENTS Primary exposure was serum 25(OH)D level at enrollment . Primary and secondary outcomes were all-cause and cardiovascular disease ( CVD ) mortality , respectively . RESULTS During the median 7.3 years of follow-up , there were 1,493 ( 44 % ) deaths , including 767 CVD-related deaths . Median 25(OH)D level was 66 nmol/L. Adjusting for demographics , season , and cardiovascular risk factors , baseline 25(OH)D levels were inversely associated with all-cause mortality risk ( adjusted hazard ratio (HR)=0.95 , 95 % confidence interval (CI)=0.92 - 0.98 , per 10 nmol/L 25[OH]D ) . Compared with subjects with 25(OH)D levels of 100 nmol/L or higher , the adjusted HR for subjects with levels less than 25.0 nmol/L was 1.83 ( 95 % CI=1.14 - 2.94 ) and for levels of 25.0 to 49.9 nmol/L was 1.47 ( 95 % CI=1.09 - 1.97 ) . The association appeared stronger for CVD mortality ( adjusted HR=2.36 , 95 % CI=1.17 - 4.75 , for subjects with 25[OH]D levels or = 100.0 nmol/L ) than for non-CVD mortality ( adjusted HR=1.42 , 95 % CI=0.73 - 2.79 , for subjects with 25[OH]D levels or = 100.0 nmol/L ) . CONCLUSION In noninstitutionalized older adults , a group at high risk for all-cause mortality , serum 25(OH)D levels had an independent , inverse association with CVD and all-cause mortality . R and omized controlled trials of vitamin D supplementation in older adults are warranted to determine whether this association is causal and reversible", "It is now generally accepted that vitamin D deficiency is a worldwide health problem that affects not only musculoskeletal health but also a wide range of acute and chronic diseases . However , there remains cynicism about the lack of r and omized controlled trials to support the association studies regarding the nonskeletal health benefits of vitamin D. This review was obtained by search ing English- language studies published up to April 1 , 2013 , in PubMed , MEDLINE , and the Cochrane Central Register of Controlled Trials ( search terms : vitamin D and supplementation ) and focuses on recent challenges regarding the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D concentrations from dietary sources , supplements , and sun exposure . The effect of vitamin D on fetal programming epigenetics and gene regulation could potentially explain why vitamin D has been reported to have such wide-ranging health benefits throughout life . There is potentially a great upside to increasing the vitamin D status of children and adults worldwide for improving musculoskeletal health and reducing the risk of chronic illnesses , including some cancers , autoimmune diseases , infectious diseases , type 2 diabetes mellitus , neurocognitive disorders , and mortality ", "PURPOSE Several observational studies have linked vitamin D deficiency with an increased risk of all cause mortality . Vitamin D deficiency is common among patients with liver diseases . In a r and om sample of the general population , we investigated whether the inverse association between vitamin D status and all-cause mortality could be explained by liver damage as reflected by increased levels of liver enzymes . METHODS We included a total of 2649 persons examined in 1993e1994 . Vitamin D status was assessed as serum 25-hydroxyvitamin D and liver enzyme levels were measured . Information on all-cause mortality was obtained from the Danish Central Personal Register until July 2011 . Median follow-up time was 17.0 years , and there were 736 deaths . RESULTS Multivariable Cox regression analyses with age as underlying time axis and delayed entry showed lower mortality risk with higher vitamin D levels and this was essentially unaffected by adjustment for liver enzyme levels with hazard ratio , 0.96 ( 95 % confidence interval , 0.93e0.99 ) for a 10 nmol/L higher vitamin D level . CONCLUSIONS The present study did not support our hypothesis that the well-known association between low vitamin D status and mortality is explained by liver damage as reflected by levels of liver enzymes", "Vitamin D deficiency is associated with osteoporosis , poor muscle strength , falls , and fractures . The relationship between serum vitamin D concentrations and mortality in older community-dwelling women has not been well characterized . We hypothesized that women with lower 25-hydroxyvitamin D ( 25[OH]D ) concentrations were at higher risk of mortality . We examined the association between serum 25[OH]D concentrations and all-cause mortality in a prospect i ve , population -based study of 714 community-dwelling women , aged 70 to 79 years , the Women 's Health and Aging Studies I and II in Baltimore , Md. The studies were originally design ed to evaluate the causes and course of physical disability in older women living in the community . Vital status was determined through follow-up interviews and matching with the National Death Index . During a median of 72 months of follow-up , 100 ( 14 % ) of 714 women died . Women in the lowest quartile of 25(OH)D ( risk of death ( hazards ratio , 2.45 ; 95 % confidence interval , 1.12 - 5.36 ; P = .02 ) compared to women in the highest quartile ( > 27.0 ng/mL or 67.4 nmol/L ) of 25(OH)D in a multivariate Cox proportional hazards model adjusting for demographics , season , and conventional risk factors . Older community-dwelling women with low 25(OH)D levels are at an increased risk of death", "Background Low serum 25-hydroxyvitamin D [ 25(OH)D ] levels have been associated with higher risk of many diseases that affect mortality , including cardiovascular disease ( CVD ) and cancer . The inverse association between serum 25(OH)D and mortality may be modified by excess circulating vitamin A , due to interactions of vitamin A at the level of the vitamin D nuclear receptor . In this prospect i ve cohort study , we investigated whether the association of 25(OH)D with all-cause , cancer , and CVD mortality was modified by circulating vitamin A or preformed vitamin A intake from supplements . Methods We analyzed 15,998 adults in the Third National Health and Nutrition Examination Survey ( NHANES III ) , 1988–1994 . Mortality data for all-cause ( n = 3890 ) , cancer ( n = 844 ) , and CVD mortality ( n = 1715 ) were assessed through December 2006 . Serum 25(OH)D was measured using a radioimmunoassay kit , vitamin A biomarkers were measured by HPLC , and information on supplement use was obtained by self-report . Multivariable hazard ratios ( HRs ) and corresponding 95 % confidence intervals ( CI ) were estimated by proportional hazards regression . Results Serum 25(OH)D was significantly inversely associated with all-cause mortality ( HR 0.93 , 95 % CI 0.89 , 0.97 , per 10 ng/mL increase ) and also with CVD mortality and mortality due to non-cancer/non-cardiovascular causes , but not with cancer mortality . The observed inverse associations remained statistically significant only among participants with serum retinyl esters 5000 IU/day ) of preformed vitamin A from supplements attenuated the inverse association of 25(OH)D with overall mortality . The observed interactions were not statistically significant . Conclusions 25(OH)D was inversely associated with overall mortality , CVD mortality , and mortality due to non-cancer/non-CVD causes , but not with cancer mortality . A possible interaction between vitamin A exposure and 25(OH)D concentration appears to be associated with an attenuation of the inverse association between risk of death and quartile of 25(OH)D concentration", "Previous studies have shown a relationship between osteoporosis and increased mortality risk . However , none of these studies performed a concomitant evaluation of the parathyroid hormone (PTH)-calcium-vitamin D axis and bone mass to accurately determine the contribution of each of these parameters to survival in older subjects . Thus , we sought to investigate the association between bone parameters and mortality in a longitudinal , prospect i ve , population -based cohort of 839 elderly subjects . Clinical data ( including history of fractures and cardiovascular events ) were assessed using a specific question naire . Laboratory exams , including serum 25OHD and PTH , were also performed . Bone mineral density ( BMD ) at the lumbar spine and hip were evaluated using DXA . All analyses were performed at baseline ( 2005 to 2007 ) . Mortality was recorded during follow-up . Multivariate Cox proportional regression was used to compute hazard ratios for all-cause and cardiovascular mortality . Over a mean 4.06 ± 1.07 years , there were 132 ( 15.7 % ) deaths . These individuals were compared to 707 subjects who were alive at the end of the coverage period for mortality data collection . In a multivariate Cox proportional hazards model , age ( HR 1.32 ; 95 % CI , 1.13 to 1.55 ; p = 0.001 , for each 5-year increase ) , male gender ( HR 1.90 ; 95 % CI , 1.30 to 2.79 ; p = 0.001 ) , recurrent falls ( more than two in the previous year ; HR 1.65 ; 95 % CI , 1.06 to 2.56 ; p = 0.026 ) , diabetes mellitus ( HR 2.17 ; 95 % CI , 1.46 to 3.21 ; p low physical activity score ( HR 1.78 ; 95 % CI , 1.14 to 2.79 ; p = 0.011 ) , prior cardiovascular event ( HR 1.76 ; 95 % CI , 1.18 to 2.63 ; p = 0.006 ) , total hip BMD ( HR 1.41 ; 95 % CI , 1.15 to 1.72 ; p = 0.001 , per each 1 SD decrease ) , and intact PTH ( iPTH ) ( HR 1.06 ; 95 % CI , 1.04 to 1.08 ; p with all-cause mortality . The subjects in the highest quartile of PTH ( > 49 pg/mL ) were at a higher risk of cardiovascular death ( HR 3.09 ; 95 % CI , 1.36 to 6.99 ; p = 0.007 ) compared with the subjects in the lowest quartile ( Low BMD and higher PTH were significantly associated with mortality in community-dwelling older adults . These findings support the notion that careful screening of these bone parameters might lead to better management of older patients and improve outcomes in this population . © 2016 American Society for Bone and Mineral Research", "BACKGROUND Prospect i ve epidemiologic data on the association between vitamin D and all-cause and cause-specific mortality are limited . OBJECTIVE This study aim ed to determine whether 25-hydroxyvitamin D [ 25(OH)D ] concentrations were prospect ively and independently associated with cardiovascular disease ( CVD ) , cancer , and all-cause mortality in postmenopausal women . DESIGN A sub study in 2429 postmenopausal women within the Women 's Health Initiative ( WHI ) with measured baseline 25(OH)D concentrations were followed for 10 y for death from CVD , cancer , and all-cause mortality . Proportional hazards models were performed to evaluate quartiles of month-adjusted 25(OH)D concentrations , with adjustment for potential confounders . Sequential model building and analysis for multiplicative interaction were performed to evaluate the effects of central adiposity on the association of low 25(OH)D with all-cause mortality . RESULTS Of the 2429 women , 224 deaths occurred , with 79 deaths from CVD and 62 deaths from cancer . Multivariate-adjusted HRs that compared quartiles 1 ( lowest ) to 4 ( highest ) of 25(OH)D for all-cause mortality ( HR : 1.25 ; 95 % CI : 0.80 , 1.95 ) , CVD mortality ( HR : 1.27 ; 95 % CI : 0.81 , 1.99 ) , and cancer mortality ( HR : 1.39 ; 95 % CI : 0.88 , 2.19 ) were not significant . There was a potential interaction ( P = 0.08 ) between abdominal obesity and low 25(OH)D concentrations that showed an increased risk of the lowest quartile of 25(OH)D concentrations ( HR : 1.85 ; 95 % CI : 1.00 , 3.44 ) with increased mortality in women with a normal waist circumference but no increased risk in women with abdominal obesity ( HR : 0.96 ; 95 % CI : 0.52 , 1.76 ) . CONCLUSION Body fat distribution may play an important role in the modulation of the effect of low vitamin D concentrations on health . This trial was registered at clinical trials.gov as NCT 00000611", "We prospect ively investigated relationships between blood markers of Fe , vitamin B12 , folate , vitamin C and vitamin D status and subsequent all-cause mortality in 208 men and 191 women aged 75 years or over living in the community in Aberdeen , Scotl and . The participants had been recruited for a cross-sectional study in 1999 - 2000 when they completed health and lifestyle question naires and had blood sample s taken for analysis of serum ferritin , serum vitamin B12 , erythrocyte folate , plasma vitamin C and serum 25-hydroxycholecalciferol . Mortality was ascertained on national data bases up to December 2005 , with a median time of follow up of 69.2 ( range 1.0 - 79.9 ) months . Participants were divided into sex-specific quintiles of baseline levels for each nutrient , and hazard ratios were estimated with Cox proportional hazard models adjusted for age and sex with the significance of linear trends in the associations assessed by logistic regression . There was no significant association between blood markers of Fe , vitamin B12 or folate status at baseline and mortality , but vitamin D status at baseline was inversely related to mortality ( P for trend C there was no evidence of a linear trend but participants in the lowest quintile of plasma levels had a significantly higher risk of death than those in the highest quintile . R and omized controlled trials of lifestyle changes which improve vitamin status are needed to assess whether these associations could be causal", "It was reported that low bone mineral density ( BMD ) , osteoporotic fractures and low serum 25-hydroxyvitamin D ( 25-OHVD ) levels increase the risk of mortality in elderly Caucasian people . However , there is no data available on the relationship between bone mineral density or 25-OHVD levels and mortality in elderly Asian women . To determine whether or not low bone mineral density ( BMD ) or low 25-OHVD levels contribute to increased mortality risk , we conducted a prospect i ve observational study in 1232 ambulatory postmenopausal female volunteers . Information was obtained from the subjects on baseline BMD , the serum levels of biochemical indices including 25-OHVD , prevalent fractures , co-morbidities and lifestyle variables . The participants were observed for a total of 6.9+/-3.6 years ( mean+/-SD ) and a total of 107 participants ( 8.7 % ) were dead during the observation . Mortality was assessed and confirmed on the certificates or hospital records or information from their family . In addition to traditional risks for mortality , such as age ( Hazard ratio , 1.73 , 95 % CI , 1.51 - 1.98 , P 25-OHVD level all-cause mortality by using multivariate Cox 's regression analysis . It is suggested that prevalent osteoporosis , prevalent malignancy or lower levels of 25-OHVD represent powerful risk factors for mortality", "Importance Previous r and omized clinical trials have reported inconsistent results on the effect of vitamin D supplementation on cancer incidence . Objective To examine whether high-dose vitamin D supplementation received monthly , without calcium , is associated with a reduction in cancer incidence and cancer mortality in the general population . Design , Setting , and Participants This is a post hoc analysis of data from the Vitamin D Assessment ( ViDA ) study , a r and omized , double-blind , placebo-controlled trial that recruited participants from family practice s and community groups in Auckl and , New Zeal and , from April 5 , 2011 , through November 6 , 2012 , with follow-up completed December 31 , 2015 . Participants were adult community residents aged 50 to 84 years . Of 47 905 adults invited from family practice s and 163 from community groups , 5110 participants were r and omized to receive vitamin D3 ( n = 2558 ) or placebo ( n = 2552 ) . Two participants withdrew consent , and all others ( n = 5108 ) were included in the primary analysis . Data analysis was by intention to treat . Interventions Oral vitamin D3 , in an initial bolus dose of 200 000 IU and followed by monthly doses of 100 000 IU , or placebo for a median of 3.3 years ( range , 2.5 - 4.2 years ) . Main Outcomes and Measures Post hoc primary outcome was the number of all primary invasive and in situ malignant neoplasms ( excluding nonmelanoma skin cancers ) diagnosed from r and omization until the study medication was discontinued on July 31 , 2015 . Results Of the 5108 participants included in the analysis , the mean ( SD ) age was 65.9 ( 8.3 ) years , 58.1 % were male , and 4253 ( 83.3 % ) were of European or another race/ethnicity , with the remainder being Polynesian or South Asian . Mean ( SD ) baseline deseasonalized 25-hydroxyvitamin D concentration was 26.5 ( 9.0 ) ng/mL. In a r and om sample of 438 participants , the mean follow-up 25-hydroxyvitamin D concentration consistently was greater than 20 ng/mL higher in the vitamin D group than in the placebo group . The primary outcome of cancer comprised 328 total cases of cancer ( 259 invasive and 69 in situ malignant neoplasms ) and occurred in 165 of 2558 participants ( 6.5 % ) in the vitamin D group and 163 of 2550 ( 6.4 % ) in the placebo group , yielding an adjusted hazard ratio of 1.01 ( 95 % CI , 0.81 - 1.25 ; P = .95 ) . Conclusions and Relevance High-dose vitamin D supplementation prescribed monthly for up to 4 years without calcium may not prevent cancer . This study suggests that daily or weekly dosing for a longer period may require further study . Trial Registration anzctr.org.au Identifier :", "BACKGROUND It is unclear whether supplementation with vitamin D reduces the risk of cancer or cardiovascular disease , and data from r and omized trials are limited . METHODS We conducted a nationwide , r and omized , placebo‐controlled trial , with a two‐by‐two factorial design , of vitamin D3 ( cholecalciferol ) at a dose of 2000 IU per day and marine n‐3 ( also called omega‐3 ) fatty acids at a dose of 1 g per day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States . Primary end points were invasive cancer of any type and major cardiovascular events ( a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes ) . Secondary end points included site‐specific cancers , death from cancer , and additional cardiovascular events . This article reports the results of the comparison of vitamin D with placebo . RESULTS A total of 25,871 participants , including 5106 black participants , underwent r and omization . Supplementation with vitamin D was not associated with a lower risk of either of the primary end points . During a median follow‐up of 5.3 years , cancer was diagnosed in 1617 participants ( 793 in the vitamin D group and 824 in the placebo group ; hazard ratio , 0.96 ; 95 % confidence interval [ CI ] , 0.88 to 1.06 ; P=0.47 ) . A major cardiovascular event occurred in 805 participants ( 396 in the vitamin D group and 409 in the placebo group ; hazard ratio , 0.97 ; 95 % CI , 0.85 to 1.12 ; P=0.69 ) . In the analyses of secondary end points , the hazard ratios were as follows : for death from cancer ( 341 deaths ) , 0.83 ( 95 % CI , 0.67 to 1.02 ) ; for breast cancer , 1.02 ( 95 % CI , 0.79 to 1.31 ) ; for prostate cancer , 0.88 ( 95 % CI , 0.72 to 1.07 ) ; for colorectal cancer , 1.09 ( 95 % CI , 0.73 to 1.62 ) ; for the exp and ed composite end point of major cardiovascular events plus coronary revascularization , 0.96 ( 95 % CI , 0.86 to 1.08 ) ; for myocardial infa rct ion , 0.96 ( 95 % CI , 0.78 to 1.19 ) ; for stroke , 0.95 ( 95 % CI , 0.76 to 1.20 ) ; and for death from cardiovascular causes , 1.11 ( 95 % CI , 0.88 to 1.40 ) . In the analysis of death from any cause ( 978 deaths ) , the hazard ratio was 0.99 ( 95 % CI , 0.87 to 1.12 ) . No excess risks of hypercalcemia or other adverse events were identified . CONCLUSIONS Supplementation with vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo . ( Funded by the National Institutes of Health and others ; VITAL Clinical Trials.gov number , NCT01169259 .", "& NA ; There is considerable debate regarding the role that 25‐hydroxyvitamin D [ 25(OH)D ] concentrations play in cancer risk or mortality , with earlier studies drawing mixed conclusions . Using data from the UK Biobank ( UKB ) , we evaluate whether genetically predicted 25(OH)D concentrations are associated with overall cancer susceptibility and cancer mortality using five 25(OH)D genetic markers . Data comprised 438 870 white British UKB participants aged 37‐73 , including 46 155 cancer cases and 6998 cancer‐specific deaths . Participants with keratinocyte cancers and /or benign tumors were excluded from the analysis . Odds ratios were calculated per 20 nmol/L increase in genetically predicted 25(OH)D for cancer risk and cancer mortality . For individual cancer risks , estimates were meta‐analyzed with publicly available data using a fixed‐effect inverse‐variance‐weighted model . We demonstrated that genetically low plasma 25(OH)D concentrations were not associated with increased cancer risk nor cancer mortality . Stratification by sex or cancer types did not reveal any meaningful differences albeit wider confidence intervals . Fixed‐effect meta‐ analysis of our individual cancer risk estimates with those derived from publicly available cancer consortia data and previous studies further reinforced our None Mendelian r and omization findings on prostate , lung , colorectal and breast cancers with tight confidence intervals ; for ovarian and pancreatic cancers , our estimates were less precise despite being not statistically significant . Taken altogether , our results provide no genetic evidence for an association between vitamin D and overall cancer outcomes , with tight confidence intervals to exclude all but very small effect sizes", "OBJECTIVE Ecologic and observational studies have suggested an association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and cardiovascular disease ( CVD ) risk factors , CVD mortality , and cancer mortality . Based on this , low serum 25(OH)D levels should be associated with higher all-cause mortality in a general population . This hypothesis was tested in the present study . DESIGN The Tromsø study is a longitudinal population -based multi purpose study initiated in 1974 with focus on lifestyle-related diseases . Our data are based on the fourth Tromsø study carried out in 1994 - 1995 . METHODS Information about death and cause of death was registered by obtaining information from the National Directory of Residents and the Death Cause Registry . Serum 25(OH)D was measured in 7161 participants in the fourth Tromsø study . Results are presented for smokers ( n=2410 ) and non-smokers ( n=4751 ) separately as our immunoassay seems to overestimate 25(OH)D levels for smokers . RESULTS During a mean 11.7 years of follow-up , 1359 ( 19.0 % ) participants died . In multivariate regression models , there was a significantly increased risk of all-cause mortality ( hazard ratio ( HR ) 1.32 , confidence interval ( CI ) 1.07 - 1.62 ) among non-smoking participants in the lowest 25(OH)D quartile when compared with participants in the highest quartile . Equivalent results for smokers were not significant ( HR 1.06 , CI 0.83 - 1.35 ) . CONCLUSIONS Low serum 25(OH)D levels were associated with increased all-cause mortality for non-smokers , but the results did not reach statistical significance for smokers . However , low 25(OH)D levels are known to be associated with impaired general health , and r and omized controlled studies are needed to address the question of causality", "BACKGROUND Vitamin D insufficiency was shown to be associated with adverse musculoskeletal and nonskeletal outcomes in numerous observational studies . However , some studies did not control for confounding factors such as age or seasonal variation of 25-hydroxyvitamin D [ 25(OH)D ] . OBJECTIVE We sought to determine the effect of vitamin D status on health outcomes . DESIGN Healthy community-dwelling women ( n = 1471 ) with a mean age of 74 y were followed in a 5-y trial of calcium supplementation . 25(OH)D was measured at baseline in all women . Skeletal and nonskeletal outcomes were evaluated according to seasonally adjusted vitamin D status at baseline . RESULTS Fifty percent of women had a seasonally adjusted 25(OH)D concentration or = 50 nmol/L. Women with a seasonally adjusted 25(OH)D concentration incidence of stroke and cardiovascular events that did not persist after adjustment for between-group differences in age or comorbidities . Women with a seasonally adjusted 25(OH)D concentration adverse consequences for any musculoskeletal outcome , including fracture , falls , bone density , or grip strength or any nonskeletal outcomes , including death , myocardial infa rct ion , cancer , heart failure , diabetes , or adverse changes in blood pressure , weight , body composition , cholesterol , or glucose . CONCLUSIONS Vitamin D insufficiency is more common in older , frailer women . Community-dwelling older women with a seasonally adjusted 25(OH)D concentration placebo-controlled trials are needed to determine whether vitamin D supplementation in individuals with vitamin D insufficiency influences health outcomes . This trial was registered at www.anzctr.org.au as ACTRN 012605000242628" ]

[ "Objective This study aims to determine the efficacy of yoga in alleviating vasomotor symptoms ( VMS ) frequency and bother . Methods This study was a three-by-two factorial , r and omized controlled trial . Eligible women were r and omized to yoga ( n = 107 ) , exercise ( n = 106 ) , or usual activity ( n = 142 ) , and were simultaneously r and omized to a double-blind comparison of & ohgr;-3 fatty acid ( n = 177 ) or placebo ( n = 178 ) capsules . Yoga intervention consisted of 12 weekly 90-minute yoga classes with daily home practice . Primary outcomes were VMS frequency and bother assessed by daily diaries at baseline , 6 weeks , and 12 weeks . Secondary outcomes included insomnia symptoms ( Insomnia Severity Index ) at baseline and 12 weeks . Results Among 249 r and omized women , 237 ( 95 % ) completed 12-week assessment s. The mean baseline VMS frequency was 7.4 per day ( 95 % CI , 6.6 to 8.1 ) in the yoga group and 8.0 per day ( 95 % CI , 7.3 to 8.7 ) in the usual activity group . Intent-to-treat analyses included all participants with response data ( n = 237 ) . There was no difference between intervention groups in the change in VMS frequency from baseline to 6 and 12 weeks ( mean difference [ yoga − usual activity ] from baseline at 6 wk , −0.3 [ 95 % CI , −1.1 to 0.5 ] ; mean difference [ yoga − usual activity ] from baseline at 12 wk , −0.3 [ 95 % CI , −1.2 to 0.6 ] ; P = 0.119 across both time points ) . Results were similar for VMS bother . At week 12 , yoga was associated with an improvement in insomnia symptoms ( mean difference [ yoga − usual activity ] in the change in Insomnia Severity Index , 1.3 [ 95 % CI , −2.5 to −0.1 ] ; P = 0.007 ) . Conclusions Among healthy women , 12 weeks of yoga class plus home practice , compared with usual activity , do not improve VMS frequency or bother but reduce insomnia symptoms", "Objective The aim of this study was to assess whether aerobic training affects menopausal symptoms in recently postmenopausal sedentary women . Methods Symptomatic women aged 45 to 63 years ( N = 176 ; 3 - 36 months since last menstruation ) were r and omly assigned to an aerobic training or a control group . The intervention included unsupervised aerobic training for 50 minutes four times weekly for 24 weeks , whereas the control group attended health lectures twice a month . Symptoms were reported twice a day using a mobile phone . The perceived disturbance of menopausal symptoms ( night sweats , mood swings , irritability , depressive mood , headache , vaginal dryness , and urinary symptoms ) was evaluated on a scale from 1 ( low ) to 5 ( high ) . Multilevel mixed-effect ordinal regression models were based on 17,000 responses during 24 weeks . Results One hundred fifty-four women continued until the end of the study ( 88 % compliance rate ) . Baseline prevalence was as follows : night sweats , 50 % to 60 % ; irritability and depression , 20 % to 25 % ; mood swings , 25 % to 30 % ; headache and urinary problems , 15 % to 20 % ; and vaginal dryness , 10 % to 15 % . The prevalence of all symptoms except vaginal dryness decreased among intervention groups . According to multilevel mixed-effect ordinal regression analysis , night sweats and mood swings ( P disturbance of the mood swings ( P irritability ( P sedentary women , aerobic training for 6 months may decrease the typical menopausal symptoms , especially night sweats , mood swings , and irritability", "Objective The practice of yoga has been proven to have positive effects on reducing insomnia . Studies have also shown its effects on reducing climacteric symptoms . To date , however , no studies that evaluate the effects of yoga on postmenopausal women with a diagnosis of insomnia in a r and omized clinical trial have been conducted . The aim of this study was to evaluate the effect of yoga practice on the physical and mental health and climacteric symptoms of postmenopausal women with a diagnosis of insomnia . Methods Postmenopausal women not undergoing hormone therapy , who were 50 to 65 years old , who had an apnea-hypopnea index less than 15 , and who had a diagnosis of insomnia were r and omly assigned to one of three groups , as follows : control , passive stretching , and yoga . Question naires were administered before and 4 months after the intervention to evaluate quality of life , anxiety and depression symptoms , climacteric symptoms , insomnia severity , daytime sleepiness , and stress . The volunteers also underwent polysomnography . The study lasted 4 months . Results There were 44 volunteers at the end of the study . When compared with the control group , the yoga group had significantly lower posttreatment scores for climacteric symptoms and insomnia severity and higher scores for quality of life and resistance phase of stress . The reduction in insomnia severity in the yoga group was significantly higher than that in the control and passive-stretching groups . Conclusions This study showed that a specific sequence of yoga might be effective in reducing insomnia and menopausal symptoms as well as improving quality of life in postmenopausal women with insomnia", "In the present study , 40- to 60-year-old women with climacteric symptoms were placed on a 12-week structured education and exercise program to ascertain the effects of this program on climacteric symptoms , quality of life ( QOL ) , and attitude towards exercise . A total of 35 women served as subjects . Twenty women were enrolled in an educational and exercise program that involved learning about menopause and participating in physical activity at least three times a week ( Group E ) . For comparison , the other 15 women did not participate in this program and were instructed to refrain from exercising during study period ( Group C ) . The effects of the 12-week interventional program on climacteric symptoms , QOL , and attitude towards exercise were thereby investigated . The program demonstrated significant effects on climacteric symptoms in terms of Kupperman index and psychosomatic symptoms , especially paresthesia and nervousness . In other words , climacteric symptoms improved significantly in Group E. Furthermore , scores for QOL and attitude towards exercise improved in Group E after the 12-week program ; however , these trends did not reach statistical significance . Hence , the 12-week structured education and exercise program was shown to be effective in alleviating climacteric symptoms", "BACKGROUND The relationship between menopausal symptoms and bone mineral density ( BMD ) was examined in 290 premenopausal women , ages 44 - 50 years , participating in a r and omized clinical trial of a dietary and exercise intervention : The Women 's Healthy Lifestyle Project . METHODS Information on hot flashes ( presence , absence ) , menstrual cycles ( irregular , regular ) and menstrual flow per period ( variable , same ) over the past 6 months was collected at entry . Participants reporting at least one menopausal symptom were classified as symptomatic and compared to those having no symptoms . Bone mineral density ( BMD ) at the lumbar spine ( L1-L4 ) , total hip and whole-body were made at baseline and at 30 months using a dual-energy X-ray absorptiometer ( Hologic QDR 2000 densitometer ) . RESULTS Baseline BMD at the spine , hip and whole-body were significantly reduced in women reporting menopausal symptoms compared to asymptomatic women , after adjustment for age , weight and intervention status ( all p Women with irregular menstrual cycles had greater annualized rates of bone loss at the spine and hip than asymptomatic women ( spine , -0.77 (1.6)% per year vs. -0.19 (1.0)% per year , p = 0.0043 ; hip , -0.37 (1.1)% per year vs. -0.04 (1.0)% per year , p = 0.061 ) , after adjustments for age , percent change in weight , intervention status , and baseline BMD . Similar findings were not found for whole-body BMD . CONCLUSIONS These results suggest that menopausal symptoms are useful for the effective identification of premenopausal women at higher risk of low BMD and perhaps , of osteoporosis", "In the 1990s , two r and omised clinical trials started in Sc and inavia addressing whether hormone replacement therapy ( HRT ) is safe for women with previous breast cancer . We report the findings of the safety analysis in HABITS ( hormonal replacement therapy after breast cancer -- is it safe ? ) , an open r and omised clinical trial with allocation to either HRT or best treatment without hormones . The main endpoint was any new breast cancer event . All analyses were done according to intention-to-treat . Until September , 2003 , 434 women were r and omised ; 345 had at least one follow-up report . After a median follow-up of 2.1 years , 26 women in the HRT group and seven in the non-HRT group had a new breast-cancer event . All women with an event in the HRT group and two of those in the non-HRT group were exposed to HRT and most women had their event when on treatment . We decided that these findings indicated an unacceptable risk for women exposed to HRT in the HABITS trial , and the trial was terminated on Dec 17 , 2003", "Background : Many women experience detriments in mental health during the menopausal transition . Physical activity may attenuate these adverse outcomes but few studies investigating such effects exist . Purpose : This study examined the effects of a 4-month r and omized controlled exercise trial on mental health outcomes in 164 previously low-active middle-aged women ( M age=49.9 ; SD=3.6 ) . Methods and Results : Participants completed body composition and fitness assessment and a battery of psychological measures at the beginning and end of a 4-month r and omized controlled exercise trial with three arms : walking , yoga , control . The results indicated that walking and yoga were effective in enhancing positive affect and menopause-related QOL and reducing negative affect . Women who experienced decreases in menopausal symptoms across the trial also experienced improvements in all positive mental health and QOL outcomes and reductions in negative mental health outcomes . Whether menopausal symptoms increased or decreased across the trial appeared to be determined in part by whether there were increases or decreases in cardiorespiratory fitness . Conclusions : Physical activity appears to enhance mood and menopause-related QOL during menopause , however , other aspects of mental health may be affected only as a result of reduction in menopausal symptoms . Increasing cardiorespiratory fitness could be one way to reduce menopausal symptoms", "INTRODUCTION Women in the menopausal stage of life usually have climacteric symptoms of hot flashes , back pain , sleeplessness , night sweats and increased risk of cardiovascular disorders . Although physical exercises have been documented to favourably alleviate some of these problems , there 's a paucity of knowledge of their effects on menopausal women in Nigeria . OBJECTIVES This study investigated the effect of a twelve-week Endurance Exercise Programme ( EEP ) on quality of life(QOL ) and menopausal symptoms in these women . METHODS Participants were purposively recruited and assigned into perimenopausal and postmenopausal groups based on history of thier last menstrual period and from each of these groups r and omized into : perimenopausal exercise group ( PEMEG ) , postmenopausal exercise group ( POMEG ) , perimenopausal control group ( PEMCG ) postmenopausal control group ( POMCG ) . Quality of life ( QOL ) , Menopausal symptoms - Back Pain ( BP ) and hot flashes ( HF ) among other variables , were evaluated at baseline and 4 weekly intervals . EEP consisted of a 10-station circuit of muscular and cardiovascular endurance , flexibility , coordination , abdominal and pelvic floor muscle exercises . RESULTS One hundred and seventy five menopausal women , mean age 52.3 + /- 4.1 years . Significant changes occurred between baseline and end of 12th week mean values of PEMEG for QOL : 565.9 + /- 108.8 vs 725.0 + /- 42.9 and BP 4.42 + /- 1.7 vs 1.00 + /- 0.0 . ( p= 0.000 ) . Also , in POMEG : QOL 558.3 + /- 127.7 vs 736.5 + /- 44.8 ; and BP 5.37 + /- 1.48 vs 1.88 + /- 1.18 ( p=0.000 ) . Significant changes in QOL and BP did not occur in the control groups . CONCLUSION Routine participation in endurance exercise programme is recommended for menopausal women for improved QOL", "Abstract Background and objective . To estimate whether aerobic training has an effect on frequency of hot flushes or quality of life . Design . A r and omized controlled trial . Participants and setting . Symptomatic , sedentary women ( n = 176 ) , 43–63 years , no current use of hormone therapy . Intervention . Unsupervised aerobic training for 50 minutes four times per week during 6 months . Outcomes . Hot flushes as measured with Women 's Health Question naire ( WHQ ) and Health-Related Quality of Life ( HRQoL , SF-36 ) , daily reported hot flushes on phone-based diary , cardiorespiratory fitness ( CRF ) , and body composition . Results . Intervention group had larger decrease in the frequency of night-time hot flushes based on phone diary ( P for month × group = 0.012 ) , but not on WHQ scale . Intervention group had less depressed mood ( P = 0.01 ) than control women according to change in WHQ score . Changes in WHQ score in depressed mood ( P = 0.03 ) and menstrual symptoms ( P = 0.01 ) in the intervention group were significantly dependent on frequency of training sessions . HRQoL was improved among the intervention group women in physical functioning ( P = 0.049 ) and physical role limitation ( P = 0.017 ) . CRF improved ( P = 0.008 ) , and lean muscle mass increased ( P = 0.046 ) significantly in the intervention group as compared to controls . Conclusions . Aerobic training may decrease the frequency of hot flushes and improve quality of life among slightly overweight women", "OBJECTIVE To determine the feasibility and acceptability of a restorative yoga intervention for the treatment of hot flushes in postmenopausal women . METHODS A pilot trial in 14 postmenopausal women experiencing > or = 4 moderate to severe hot flushes per day or > or = 30 moderate to severe hot flushes per week . The intervention consisted of eight restorative yoga poses taught in a 3-h introductory session and 8 weekly 90-min sessions . Feasibility was measured by recruitment rates , subject retention and adherence . Acceptability was assessed by subject interview and question naires . Efficacy measures included change in frequency and severity of hot flushes as recorded on a 7-day diary . RESULTS Recruitment was accomplished as planned . The majority of study subjects ( 93 % ) completed the trial . Of those who completed the trial , 92 % attended seven or more of the eight yoga sessions . The majority of the subjects were satisfied with the study and 75 % continued to practice yoga 3 months after the study . Mean number of hot flushes per week decreased by 30.8 % ( 95 % CI 15.6 - 45.9 % ) and mean hot flush score decreased 34.2 % ( 95 % CI 16.0 - 52.5 % ) from baseline to week 8 . No adverse events were observed . CONCLUSIONS This pilot trial demonstrates that it is feasible to teach restorative yoga to middle-aged women without prior yoga experience . The high rates of subject retention and satisfaction suggest that yoga is an acceptable intervention in this population . Our results indicate that a larger , r and omized controlled trial to explore the efficacy of restorative yoga for treatment of menopausal symptoms would be safe and feasible", "Many women approach menopause with uncertainty about what will happen and how to deal with changes that occur . The current study aim ed to evaluate the short-term outcome of a health education intervention devised to prepare 45-year old women in general practice s. One hundred and seventy-eight 45-year old women registered at five general practice s in south London were targeted for the research ; 106 of the women responded and 86 of these women formed a usable pre-menopausal sample which was r and omly allocated to the preparation intervention and control conditions . Preparation involved two health education sessions carried out in small groups and covering information and discussion of the normal menopause transition in the context of mid-life . The women completed pre- and post-intervention ( 3 and 15 months ) question naires which assessed knowledge and beliefs about menopause and a number of health-related behaviours . Knowledge improved significantly at the follow-up assessment s for the preparation group but not for the control group . On the whole , the prepared women 's beliefs about menopause became less negative following the intervention , although there were also some changes reported by the control group . The proportion of smokers decreased from 25 to 20 % for the prepared women although this did not reach statistical significance . There was no change in the prevalence of regular exercise . There was also a decrease in the intention to take hormonal treatments following the intervention . Suggestions for further development of health promotion services for mid-aged women and more holistic health care practice s are proposed", "BACKGROUND Observational studies have suggested that estrogen-replacement therapy may reduce a woman 's risk of stroke and death . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of estrogen therapy ( 1 mg of estradiol-17beta per day ) in 664 postmenopausal women ( mean age , 71 years ) who had recently had an ischemic stroke or transient ischemic attack . Women were recruited from 21 hospitals in the United States and were followed for the occurrence of stroke or death . RESULTS During a mean follow-up period of 2.8 years , there were 99 strokes or deaths among the women in the estradiol group , and 93 among those in the placebo group ( relative risk in the estradiol group , 1.1 ; 95 percent confidence interval , 0.8 to 1.4 ) . Estrogen therapy did not reduce the risk of death alone ( relative risk , 1.2 ; 95 percent confidence interval , 0.8 to 1.8 ) or the risk of nonfatal stroke ( relative risk , 1.0 ; 95 percent confidence interval , 0.7 to 1.4 ) . The women who were r and omly assigned to receive estrogen therapy had a higher risk of fatal stroke ( relative risk , 2.9 ; 95 percent confidence interval , 0.9 to 9.0 ) , and their nonfatal strokes were associated with slightly worse neurologic and functional deficits . CONCLUSIONS Estradiol does not reduce mortality orthe recurrence of stroke in postmenopausal women with cerebrovascular disease . This therapy should not be prescribed for the secondary prevention of cerebrovascular disease", "Objective : Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women , including decreases in perceived quality of life ( QoL ) . A number of trials with hormone therapy showed beneficial effects of the intervention on parameters of quality of life . However , because of known or suspected serious side-effects of conventional hormone therapy there is a need for alternatives . Design : We conducted a double-blind r and omized placebo-controlled trial with soy protein , containing 52 mg genistein , 41 mg daidzein , and 6 mg glycitein ( aglycone weights ) , or milk protein ( placebo ) daily for 1 year . For this trial , we recruited 202 postmenopausal women aged 60 to 75 years . Results : At baseline and at final visit , participants filled in the Short Form of 36 questions ( SF-36 ) , the Question naire on Life Satisfaction Modules ( QLSM ) , and the Geriatric Depression Scale ( GDS ) . For the placebo group scores on all dimensions of the SF-36 and the QLSM decreased during the intervention year , except for the dimension \" role limitations caused by physical problems . \" The soy group showed increases on two dimensions of the SF-36 ( \" social functioning \" and \" role limitations caused by physical problems \" ) and on one dimension of the QLSM . There were however no statistically significant differences in changes of scores between the two intervention groups . For the GDS similarly , no significant differences were found between the groups . Conclusions : In conclusion , the findings in this r and omized trial do not support the presence of a marked effect of soy protein substitution on quality of life ( health status , life satisfaction , and depression ) in elderly postmenopausal women", "OBJECTIVE To assess if regular physical exercise or oral oestradiol therapy decreased vasomotor symptoms and increased quality of life in previously sedentary postmenopausal women . SETTING A prospect i ve , r and omised trial at a University Hospital . METHODS 75 postmenopausal , sedentary women with vasomotor symptoms were r and omised to : exercise three-times weekly over 12 weeks ( 15 women ) , oral oestradiol therapy for 12 weeks ( 15 women ) and 45 women to three other treatment arms . Results from the exercise and oestradiol groups are presented here . The effects on vasomotor symptoms and wellbeing were assessed with logbooks and vali date d question naires . RESULTS Ten women fulfilled 12 weeks of exercise . The number of flushes was rather unchanged in five women and decreased to 28 % ( range 18 - 42 % ) of baseline in the other five women . Five of the ten women continued to exercise another 24 weeks , thus in all 36 weeks . The mean number of flushes decreased by about 50 % in these five women ( from 6.2/24 to 3.2 flushes/24 h at 36 weeks ) . In the same group a score made as the product of reduction in number and severity of flushes decreased by 92 % at 12 weeks , 75 % at 24 weeks and 72 % at 36 weeks compared with baseline . In the estrogen group flushes decreased from 8.4 to 0.8 ( P Well-being according to different measurements improved significantly in both groups , albeit more markedly in the estrogen group . CONCLUSIONS Apart from many other health benefits regular physical exercise may decrease vasomotor symptoms and increase quality of life in postmenopausal women , but this has to be further evaluated scientifically . Exercise should be introduced gradually to ensure compliance", "OBJECTIVE The aim was to evaluate and compare the effects of applied relaxation and oral estradiol treatment on hot flushes , mood and psychological wellbeing in postmenopausal women . PATIENTS AND METHODS In a prospect i ve study , 30 postmenopausal women with vasomotor symptoms were r and omized to applied relaxation or oral estradiol treatment during 12 weeks with 6 months follow-up . Number and severity of flushes were registered daily and Kupperman 's Index and a general estimate of climacteric symptoms , Mood Scale and Symptom Check List were completed at baseline , 4 , 8 and 12 weeks of treatment , and 3 and 6 months after therapy . RESULTS After 12 weeks of treatment , the number of flushes/24 h decreased significantly over time in both treatment groups . In the group receiving applied relaxation , the mean number of flushes/24 h decreased from 6.0 ( 95 % CI 4.5 - 7.6 ) to 3.0 ( 95 % CI 2.1 - 3.9 ) after 12 weeks of treatment . The mean number of flushes/24 h was 1.7 ( 95 % CI 0.7 - 2.5 ) at 6 months follow-up ; i.e. a 72 % decrease . In the estrogen group , the mean number of flushes/24h decreased from 8.4 to 0.8 ; i.e a 90 % decrease in the number of flushes after 12 weeks of treatment . The significant change in flushes reached after 12 weeks of treatment and remained to 6 months after end of treatment in both groups . Estrogen therapy reduced flushes significantly faster than applied relaxation . General climacteric symptoms according to the Visual Analogue Scale and the Kupperman 's Index decreased significantly over time in both groups . General mood ( Mood Scale ) increased significantly in the estrogen group , but not in the group receiving applied relaxation . Psychological wellbeing according to Symptom Checklist , increased significantly from baseline to 12 weeks in both groups . CONCLUSIONS We suggest that applied relaxation may be used as an alternative treatment of vasomotor symptoms for postmenopausal women but should be further evaluated", "Objective : To evaluate the effect of moderate-intensity exercise on the occurrence and severity of menopause symptoms . Design : A yearlong , r and omized , clinical trial , conducted in Seattle , WA , with 173 overweight , postmenopausal women not taking hormone therapy in the previous 6 months . The intervention was a moderate-intensity exercise intervention ( n = 87 ) versus stretching control group ( n = 86 ) . Using logistic regression , odds ratios comparing exercise with controls were calculated at 3 , 6 , 9 , and 12 months for menopause symptoms and their severity . Results : There was a significant increase in hot flash severity and decreased risk of memory problems in exercisers versus controls over 12 months , although the numbers affected were small . No other significant changes in symptoms were observed . Conclusions : Exercise does not seem to decrease the risk of having menopause symptoms in overweight , postmenopausal women not taking hormone therapy and may increase the severity of some symptoms in a small number of women", "Objective This study aims to determine the efficacy of exercise training for alleviating vasomotor and other menopausal symptoms . Methods Late perimenopausal and postmenopausal sedentary women with frequent vasomotor symptoms ( VMS ) participated in a r and omized controlled trial conducted in three sites : 106 women r and omized to exercise and 142 women r and omized to usual activity . The exercise intervention consisted of individual facility-based aerobic exercise training three times per week for 12 weeks . VMS frequency and bother were recorded on daily diaries at baseline and on weeks 6 and 12 . Intent-to-treat analyses compared between-group differences in changes in VMS frequency and bother , sleep symptoms ( Insomnia Severity Index and Pittsburgh Sleep Quality Index ) , and mood ( Patient Health Question naire-8 and Generalized Anxiety Disorder-7 question naire ) . Results At the end of week 12 , changes in VMS frequency in the exercise group ( mean change , −2.4 VMS/d ; 95 % CI , −3.0 to −1.7 ) and VMS bother ( mean change on a four-point scale , −0.5 ; 95 % CI , −0.6 to −0.4 ) were not significantly different from those in the control group ( −2.6 VMS/d ; 95 % CI , −3.2 to −2.0 ; P = 0.43 ; −0.5 points ; 95 % CI , −0.6 to −0.4 ; P = 0.75 ) . The exercise group reported greater improvement in insomnia symptoms ( P = 0.03 ) , subjective sleep quality ( P = 0.01 ) , and depressive symptoms ( P = 0.04 ) , but differences were small and not statistically significant when P values were adjusted for multiple comparisons . Results were similar when considering treatment-adherent women only . Conclusions These findings provide strong evidence that 12 weeks of moderate-intensity aerobic exercise do not alleviate VMS but may result in small improvements in sleep quality , insomnia , and depression in midlife sedentary women", "Objective To investigate whether a dose – response relationship existed between exercise and subjective sleep quality in postmenopausal women . This objective represents a post hoc assessment that was not previously considered . Design Parallel-group r and omised controlled trial . Setting Clinical exercise physiology laboratory in Dallas , Texas . Participants 437 sedentary overweight/obese postmenopausal women . Intervention Participants were r and omised to one of four treatments , each of 6 months of duration : a non-exercise control treatment ( n=92 ) or one of three dosages of moderate-intensity exercise ( 50 % of VO2peak ) , design ed to meet 50 % ( n=151 ) , 100 % ( n=99 ) or 150 % ( n=95 ) of the National Institutes of Health Consensus Development Panel physical activity recommendations . Exercise dosages were structured to elicit energy expenditures of 4 , 8 or 12 kilocalories per kilogram of body weight per week ( KKW ) , respectively . Analyses were intent to treat . Primary outcome measures Continuous scores and odds of having significant sleep disturbance , as assessed by the Sleep Problems Index from the 6-item Medical Outcomes Study Sleep Scale . Outcome assessors were blinded to participant r and omisation assignment . Results Change in the Medical Outcomes Study Sleep Problems Index score at 6 months significantly differed by treatment group ( control : −2.09 ( 95 % CI −4.58 to 0.40 ) , 4 KKW : −3.93 ( −5.87 to −1.99 ) , 8 KKW : −4.06 ( −6.45 to −1.67 ) , 12 KKW : −6.22 ( −8.68 to −3.77 ) ; p=0.04 ) , with a significant dose – response trend observed ( p=0.02 ) . Exercise training participants had lower odds of having significant sleep disturbance at postintervention compared with control ( 4 KKW : OR 0.37 ( 95 % CI 0.19 to 0.73 ) , 8 KKW : 0.36 ( 0.17 to 0.77 ) , 12 KKW : 0.34 ( 0.16 to 0.72 ) ) . The magnitude of weight loss did not differ between treatment conditions . Improvements in sleep quality were not related to changes in body weight , resting parasympathetic control or cardiorespiratory fitness . Conclusion Exercise training induced significant improvement in subjective sleep quality in postmenopausal women , with even a low dose of exercise result ing in greatly reduced odds of having significant sleep disturbance . Trial registration number clinical trials.gov identifier : NCT00011193", "Objective : We investigated the influence of hormone therapy ( HT ) on submaximal central and peripheral function in healthy postmenopausal women after 12 weeks of endurance training . Methods : A r and omized , double-blind , placebo-controlled study in a research and clinical facility was conducted . All participants ( N = 23 ) underwent 12 weeks of aerobic exercise training ( walking 5 d/wk at 70%-80 % peak heart rate [ HR ] ) . Eleven participants received HT ; 12 received placebo . HT consisted of daily 17&bgr;-estradiol ( 1 mg ) with cyclic micronized progesterone ( 200 mg ) or placebo for 10 days per month . Participants were tested before and after exercise training . Primary outcome measures were submaximal stroke volume , cardiac output , and total peripheral resistance measured during cycling at 30W , 45W , and 60W . Secondary outcome measures were ventilatory threshold , peak oxygen uptake ( VO2 peak ) , and resting and peak-ischemic calf blood flow . Results : At baseline , HT and placebo groups were similar ( P > 0.05 ) in age ( mean ± SEM , 57 ± 1 y ) , height ( 162 ± 2 cm ) , weight ( 72 ± 4 kg ) , VO2 peak ( 21.5 ± 1.4 mL · kg−1 · min−1 ) , and all cardiovascular measures . Posttraining oxygen consumption and HR decreased ( P submaximal exercise workload . Stroke volume , cardiac output , and total peripheral resistance remained unaltered ( P > 0.05 ) . VO2 peak and oxygen consumption at the ventilatory threshold increased ( P groups . Resting and postischemic blood flow were unaltered . HT did not influence any of the cardiovascular responses . Conclusions : These findings suggest that in healthy postmenopausal women , 12 weeks of aerobic training is effective in eliciting favorable cardiovascular adaptations , regardless of the presence of short-term HT", "AIM This paper reports a study examining the effects of physical exercise on the quality of life of menopausal women . BACKGROUND People who perform no type of physical activity have poorer physical and mental health . Despite the well-documented benefits of exercise , ageing women remain largely sedentary , and interventions design ed to help them to maintain exercise programmes may prove particularly valuable . Measures should focus on increasing women 's confidence so that they can overcome barriers to exercise . Conflicting results have been reported in intervention studies to promote exercise in postmenopausal women . METHODS Forty-eight menopausal women aged 55 - 72 years were recruited at a primary care centre as voluntary participants in a quasi-experimental study . They were r and omly assigned to one of two groups : control ( n = 24 ) and experimental ( n = 24 ) . The experimental group participated in a 12-month programme of cardiorespiratory , stretching , muscle-strengthening and relaxation exercises carried out during two fully supervised exercise sessions per week ( total of 3 hours weekly ) . Health-related quality of life was assessed by using the Quality of Life Profile for Chronically Ill Patients , a generic question naire widely used in epidemiological and clinical studies to measure well-being and function , incorporating as an optional module the Kupperman Index of Menopausal Symptomatology . RESULTS There was a statistically significant improvement in the health-related quality of life of the experimental group , whereas the health-related quality of life of the control group significantly worsened . Menopausal symptoms also significantly improved in the experimental group and significantly worsened in the control group over the 12-month study period . CONCLUSIONS A customized exercise programme is valuable for improving the health-related quality of life of menopausal women", "CONTEXT The timing of initiation of hormone therapy may influence its effect on cardiovascular disease . OBJECTIVE To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began . DESIGN , SETTING , AND PARTICIPANTS Secondary analysis of the Women 's Health Initiative ( WHI ) r and omized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were r and omized to conjugated equine estrogens ( CEE ) or placebo and 16,608 postmenopausal women who had not had a hysterectomy were r and omized to CEE plus medroxyprogesterone acetate ( CEE + MPA ) or placebo . Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998 . MAIN OUTCOME MEASURES Statistical test for trend of the effect of hormone therapy on coronary heart disease ( CHD ) and stroke across categories of age and years since menopause in the combined trials . RESULTS In the combined trials , there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [ corrected ] cases of CHD and 239 cases of stroke in the placebo group . For women with less than 10 years since menopause began , the hazard ratio ( HR ) for CHD was 0.76 ( 95 % confidence interval [ CI ] , 0.50 - 1.16 ) ; 10 to 19 years , 1.10 ( 95 % CI , 0.84 - 1.45 ) ; and 20 or more years , 1.28 ( 95 % CI , 1.03 - 1.58 ) ( P for trend = .02 ) . The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10,000 person-years ; for women 10 to 19 years since menopause began , 4 per 10,000 person-years ; and for women 20 or more years from menopause onset , 17 per 10,000 person-years . For the age group of 50 to 59 years , the HR for CHD was 0.93 ( 95 % CI , 0.65 - 1.33 ) and the absolute excess risk was -2 per 10,000 person-years ; 60 to 69 years , 0.98 ( 95 % CI , 0.79 - 1.21 ) and -1 per 10,000 person-years ; and 70 to 79 years , 1.26 ( 95 % CI , 1.00 - 1.59 ) and 19 per 10,000 person-years ( P for trend = .16 ) . Hormone therapy increased the risk of stroke ( HR , 1.32 ; 95 % CI , 1.12 - 1.56 ) . Risk did not vary significantly by age or time since menopause . There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women ( HR of 0.70 for 50 - 59 years ; 1.05 for 60 - 69 years , and 1.14 for 70 - 79 years ; P for trend = .06 ) . CONCLUSIONS Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause , but this trend test did not meet our criterion for statistical significance . A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause . These data should be considered in regard to the short-term treatment of menopausal symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611", "CONTEXT Postmenopausal hormone therapy use increased dramatically during the past 2 decades because of a prevailing belief in its health benefits . Recent evidence from r and omized trials published in July 2002 demonstrated adverse cardiovascular disease events and other risks with hormone therapy in the form of oral estrogen combined with progestin . OBJECTIVE To describe patterns of hormone therapy use from 1995 until July 2003 , including the impact of recent evidence . DESIGN , SETTING , AND POPULATION Two data bases were used to describe national trends in hormone therapy use from January 1995 to July 2003 . The National Prescription Audit data base provided data on the number of hormone therapy prescriptions filled by retail pharmacies and the National Disease and Therapeutic Index data base provided data on patient visits to office-based physicians during which hormone therapy was prescribed . MAIN OUTCOME MEASURES Annual number of hormone therapy prescriptions and characteristics of visits to physicians during which hormone therapy was prescribed . RESULTS Annual hormone therapy prescriptions increased from 58 million in 1995 to 90 million in 1999 , representing approximately 15 million women per year , then remained stable through June 2002 . Adoption of new oral estrogen/progestin combinations , primarily Prempro , accounted for most of this growth . Obstetrician/gynecologists provided more than 70 % of hormone therapy prescriptions , and more than one third of patients were older than 60 years . Following the publication of trial results in July 2002 , hormone therapy prescriptions declined in successive months . Relative to January-June 2002 , prescriptions from January-June 2003 declined by 66 % for Prempro and 33 % for Premarin . Small increases were observed in vaginal formulations and in new prescriptions for low-dose Premarin . If prescription rates observed through July 2003 remain stable , a decline to 57 million prescriptions for 2003 , similar to the rate in 1995 , is projected . CONCLUSIONS Clinical practice responded rapidly to recent evidence of harms associated with hormone therapy . Since July 2002 , many patients have discontinued hormone therapy or are tapering to lower doses", "Objective To compare the effects of electro-acupuncture with oral estradiol and superficial needle insertion on hot flushes in postmenopausal women . Material and methods Forty-five postmenopausal women with vasomotor symptoms were r and omized to electro-acupuncture , superficial needle insertion or oral estradiol treatment during 12 weeks , with 6 months ' follow-up . The number and severity of flushes were registered daily and the Kupperman index and a general estimate of climacteric symptoms were completed before , during and after therapy . Results In the electro-acupuncture group , the mean number of flushes/24 h decreased from 7.3 to 3.5 ( ANOVA , p number of flushes ( with a mean decrease of 82 % ) . Superficial needle insertion decreased the number of flushes/24 h from 8.1 to 3.8 ( p number of flushes decreased by at least 50 % ( mean decrease 83 % ) . In the estrogen group , the number of flushes decreased from 8.4 to 0.8 ( p number of flushes persisted during the 24-week follow-up period in all treatment groups . The Kupperman index and the general climacteric symptom score decreased , and remained unchanged 24 weeks after treatment in all groups ( p Electro-acupuncture decreased the number of flushes/24 h significantly over time , but not to the same extent as the estrogen treatment . No significant difference in effect was found between electro-acupuncture and the superficial needle insertion . Conclusion We suggest that acupuncture is a viable alternative treatment of vasomotor symptoms in postmenopausal women and can not recommend superficial needle insertion as an inactive control treatment", "BACKGROUND Menopausal symptoms can affect women 's health and wellbeing . It is important to develop interventions to alleviate symptoms , especially given recent evidence result ing in many women no longer choosing to take hormone replacement therapy . Exercise may prove useful in alleviating symptoms , although evidence on its effectiveness has been conflicting . AIM To examine the association between exercise participation , body mass index ( BMI ) , and health-related quality of life in women of menopausal-age . DESIGN OF STUDY Survey of women of menopausal age . SETTING West Midl and s , Engl and . METHOD Women aged 46 - 55 years ( n = 2399 ) registered with six general practice s in the West Midl and s were sent a question naire containing items relating to demographics , lifestyle factors , weight , height , exercise participation , menopausal bleeding patterns , and health-related quality of life ( including vasomotor symptoms ) . RESULTS One thous and two hundred and six ( 50.3 % ) women replied . Women who were regularly active reported better health-related quality of life scores than women who were not regularly active ( P vasomotor symptoms was recorded for exercise status . Women who were obese reported significantly higher vasomotor symptom scores than women of normal weight ( P Women who were obese reported significantly higher somatic symptoms ( P attractiveness concern scores ( P somatic and psychological dimensions of health-related quality of life and participation in regular exercise . Women with BMI scores in the normal range reported lower vasomotor symptom scores and better health-related quality of life scores than heavier women . Further evidence from high- quality r and omised controlled trials is required to assess whether exercise interventions are effective for management of menopausal symptoms", "CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women . All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD", "OBJECTIVES Evaluate the effect of diet , physical exercise , and a daily oral intake of a soy isoflavones extract ( Fisiogen ( ® ) ) contained 200 mg of Glycine max , which corresponded to 80 mg of isoflavone ( 60.8 mg of genistein , 16 mg of daidzein and 3.2 mg of glicitein ) on leptin and other adipokines plasma levels in healthy obese postmenopausal women . METHODS A multicentric r and omized longitudinal prospect i ve cohort study was conducted in a sample of 87 healthy obese postmenopausal women . Patients were r and omly assigned to a 1200 kcal diet and exercise group ( control group ) or a group of 1200 kcal diet , exercise , and daily oral intake of daily oral intake of a soy isoflavones extract ( Fisiogen ( ® ) ) contained 200 mg of Glycine max , which corresponded to 80 mg of isoflavone ( 60.8 mg of genistein , 16 mg of daidzein and 3.2 mg of glicitein ) ( soy isoflavones group ) along 6 months . Main outcome measures were : anthropometric measures , body composition , leptin , adiponectin , TNF-alpha , homocysteine , C-reactive protein , glucose , insulin , lipid profile and oestradiol serum levels , Kupperman index and Cervantes Scale . RESULTS Mean serum leptin and TNF-alpha levels declined after 6 months in both groups of the study , but only women in the soy isoflavones group showed a significant increase of mean serum levels of adiponectin . CONCLUSIONS Diet , physical exercise and daily oral intake of a soy isoflavones extract ( Fisiogen ( ® ) ) contained 200 mg of Glycine max , which corresponded to 80 mg of isoflavone ( 60.8 mg of genistein , 16 mg of daidzein and 3.2 mg of glicitein ) have a beneficial effect on serum leptin , adiponectin and TNF-α in healthy obese postmenopausal women after 6 months of treatment", "Objective : The purpose of this study was to evaluate the isolated and associated effects of estrogen therapy ( estradiol valerate 1 mg/d orally ) and physical exercise ( moderate aerobic exercise , 3 h/wk ) on health-related quality of life ( HRQOL ) and menopausal symptoms among women who had undergone hysterectomy . Design : A 6-month , r and omized , double-blind , placebo-controlled clinical trial with 44 postmenopausal women who had undergone hysterectomy . The interventions were physical exercise and hormone therapy ( n = 9 ) , being sedentary and hormone therapy ( n = 14 ) , physical exercise and placebo ( n = 11 ) , and being sedentary and placebo ( n = 10 ) . HRQOL was assessed by a Brazilian st and ard version of the Medical Outcome Study Short-Form Health Survey and symptoms by Kupperman Index at baseline and after 6 months . Results : There was a decrease in symptoms in all groups , but only groups who performed physical exercise showed an increase in quality of life . Analysis of variance showed that changes in physical functioning ( P = 0.001 ) and bodily pain ( P = 0.012 ) scores over the 6-month period differed significantly between women who exercised and women who were sedentary , regardless of hormone therapy . Hormone therapy had no effect , and there was also no significant association between physical exercise and hormone therapy in HRQOL . Conclusions : Physical exercises can reduce menopausal symptoms and enhance HRQOL , independent of whether hormone therapy is taken", "The purpose of this r and omized clinical trial study was to determine the effectiveness of a 24-week , home-based , moderate-intensity , walking intervention in improving symptoms ( vasomotor , uro-genital/sexual , sleep , psychological , cognitive , physical ) experienced by midlife women . One hundred and seventy-three Caucasian and African American women aged 45 to 65 who were not on hormone therapy , had no major signs or symptoms of cardiovascular disease , and were sedentary in their leisure activity were r and omly assigned to the moderate-intensity walking group or the nonexercise control group . The exercise prescription was walking at a frequency of 4 times a week for a duration of 20 to 30 minutes . The symptom impact inventory included the frequency , intensity , and bothersomeness of 33 symptoms collected at baseline and 24 weeks . Adherence was measured with a heart rate monitor and exercise log . Average adherence to frequency of walking was 71.6 % of the expected walks . After 24 weeks , there were no differences between the walking and control group on change in symptoms . However , multiple regression revealed that frequency of adherence to walking along with change in physical symptoms and menopausal status were significant predictors of change in sleep symptoms . While walking did not improve most symptoms experienced by midlife women , frequency of walking may improve sleep", "With advancing age , the postural balance function deteriorates as a consequence of decreased functional capacity . Deteriorating balance is a risk factor for bone fractures due to increased risks of falls . It has been suggested that the loss of estrogen , which occurs in relation to the menopause , may be associated with loss of balance . Regular physical exercise without balance training has , in some studies , been shown to have positive effects on the postural balance . The aim of the present study was to examine balance function during the perimenopausal period , and evaluate the effect of estrogen plus progesterone therapy ( EPT ) or aerobic training on balance . Sixty perimenopausal women were recruited to the study . The subjects were then r and omised to either physical training ( n = 20 ) , EPT ( n = 20 ) , or to a control group ( n = 20 ) . The study period was 18 months . Postural stability was measured every third month using a custom‐made force platform . The women using EPT achieved better results in 3 of 6 parameters , after 18 months", "Menopause is associated with a considerable variety of physical , psychological and social symptoms that can be treated using cognitive-behavioral techniques . In the present study , 21 women took part in an eight-week group intervention consisting of weekly two-hour sessions to address their slight symptoms related to the climacteric stage of life . The intervention included : psycho education on menopause , relaxation techniques , nutrition and fitness exercises , Kegel exercises , and problem-solving techniques . A control group was included that did not receive treatment and consisted of 28 women . The results revealed a significant reduction in most symptoms ( including depression and anxiety ) after intervention as compared to the baseline period . No changes appeared in the control group . The relevance of this work lies in the potential element of prevention this therapeutic package could offer to relieve various symptoms , slight and incipient , during the perimenopausal stage", "The effects of physical training and hormone replacement therapy ( HRT ) on bone mineral density in perimenopausal women were studied . Sixty perimenopausal women were r and omized to either physical training ( n=20 ) , HRT ( n=20 ) , or control group ( n=20 ) . The study period was 18 months . Bone mineral density ( BMD ) in the femoral neck and lumbar spine was measured using dual-energy X-ray absorptiometry ( DXA ) . DXA was performed before treatment and after 6 and 18 months . Blood sample s for analysis of the bone markers U-deoxypyridinoline and osteocalcin were collected at the same time points . After 18 months , BMD in the spine had not decreased in either the training group or in the HRT group . In the control group , spine BMD had significantly decreased ( p=0.0014 ) . U-Deoxypyridinoline and osteocalcin were increased significantly in the control group ( p=0.0198 , p=0.0295 , respectively ) . No significant changes in bone marker levels were found in the training group or the HRT group . We found that both HRT and physical training can prevent loss of spine BMD in perimenopausal women over a period of 18 months . HRT remains a cornerstone in the treatment of vasomotor symptoms and preservation of BMD . However , HRT can only be used for limited periods of time due to the potential serious adverse effects . This study indicates a beneficial effect of physical activity on spine BMD in the perimenopausal period , and highlights its potential as an alternative to HRT during this period", "OBJECTIVE To assess the feasibility and efficacy of a yoga treatment for menopausal symptoms . Both physiologic and self-reported measures of hot flashes were included . METHODS A prospect i ve within-group pilot study was conducted . Participants were 12 peri- and post-menopausal women experiencing at least 4 menopausal hot flashes per day , at least 4 days per week . Assessment s were administered before and after completion of a 10-week yoga program . Pre- and post-treatment measures included : Severity of question naire-rated menopausal symptoms ( Wiklund Symptom Check List ) , frequency , duration , and severity of hot flashes ( 24-h ambulatory skin-conductance monitoring ; hot-flash diary ) , interference of hot flashes with daily life ( Hot Flash Related Daily Interference Scale ) , and subjective sleep quality ( Pittsburgh Sleep Quality Index ) . Yoga classes included breathing techniques , postures , and relaxation poses design ed specifically for menopausal symptoms . Participants were asked to practice at home 15 min each day in addition to weekly classes . RESULTS Eleven women completed the study and attended a mean of 7.45 ( S.D. 1.63 ) classes . Significant pre- to post-treatment improvements were found for severity of question naire-rated total menopausal symptoms , hot-flash daily interference ; and sleep efficiency , disturbances , and quality . Neither 24-h monitoring nor accompanying diaries yielded significant changes in hot flashes . CONCLUSIONS The yoga treatment and study procedures were feasible for midlife women . Improvement in symptom perceptions and well being warrant further study of yoga for menopausal symptoms , with a larger number of women and including a control group", "Lifestyle interventions for weight loss are the cornerstone of obesity therapy , yet their optimal design is debated . This is particularly true for postmenopausal women ; a population with a high prevalence of obesity yet toward whom fewer studies are targeted . We conducted a year-long , 4-arm r and omized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced , low-fat diet ( D ) , a moderate-intensity , facility-based aerobic exercise program ( E ) , or the combination of both interventions ( D+E ) , vs. a no-lifestyle-change control ( C ) on change in body weight and composition . The group-based dietary intervention had a weight-reduction goal of ≥10 % , and the exercise intervention consisted of a gradual escalation to 45-min aerobic exercise 5 day/week . Participants were predominantly non-Hispanic whites ( 85 % ) with a mean age of 58.0 ± 5.0 years , a mean BMI of 30.9 ± 4.0 kg/m(2 ) and an average of 47.8 ± 4.4 % body fat . Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants ' intervention assignment . Three hundred and ninety nine women completed the trial ( 91 % retention ) . Using an intention-to-treat analysis , average weight loss at 12 months was -8.5 % for the D group ( P decrease . BMI , waist circumference , and % body fat were also similarly reduced . Among postmenopausal women , lifestyle-change involving diet , exercise , or both combined over 1 year improves body weight and adiposity , with the greatest change arising from the combined intervention", "OBJECTIVES this paper aims to report the prevalence of symptoms in the Hong Kong Chinese perimenopausal women ; to construct reported symptoms into symptom groupings ; and to clarify whether the symptom groups are associated with menopausal status . METHODS a r and om telephone survey of perimenopausal women aged 44 - 55 years was conducted in 1996 . Eligible subjects were identified through telephone dialing of a r and om sample of the numbers listed in the residents ' telephone directory . St and ardized question naire , including a 22-item symptom check list , was administered over the telephone . The principal component analysis method followed by varimax rotation was used to examine the relations among the symptoms . RESULTS differences in the prevalence of menstrual problems across the menopausal status were noted with perimenopausal women having the most complaints . Musculoskeletal conditions were the top complaints reported by the respondents , followed by headaches and psychological symptoms . About 10 % of the women complained of hot flushes , and less than 5 % of cold sweats . Five symptom clusters , namely psychological , musculoskeletal/gastrointestinal , non-specific somatic , respiratory , and vasomotor , have been identified . After adjustment for age , the analysis of variance showed that psychological , non-specific somatic and vasomotor symptoms were significantly associated with menopausal status , while musculoskeletal and respiratory were of borderline statistical significance . CONCLUSIONS compared with pre- and post-menopausal women , perimenopausal women had the highest reports of symptom complaints . Musculoskeletal complaints were the most prevalent complaints , followed by psychological symptoms . While vasomotor symptoms were significantly associated with menopausal status , their prevalence was comparatively lower than that reported in Caucasian population ", "INTRODUCTION Current controversies involve the adverse effects of hysterectomy on women 's psychosocial functioning and whether subtotal as opposed to total hysterectomy mitigates these effects . AIM To investigate the psychosocial effects of hysterectomy by examining sexual , pain , and psychological outcomes of total vs. subtotal hysterectomy in a r and omized controlled trial . METHODS Patients suffering from benign gynecological conditions were r and omly assigned to one of two groups : ( i ) total hysterectomy , that is , laparoscopic assisted vaginal hysterectomy ( TOT , N = 32 ) ; or ( ii ) subtotal hysterectomy , that is , supracervical laparoscopic hysterectomy ( SUB , N = 31 ) . Both groups were premenopausal and underwent hysterectomy without concurrent oophorectomy . Two premenopausal control groups : ( i ) minor gynecological surgery ( SURG-CON , N = 30 ) ; and ( ii ) healthy nonsurgical controls ( NORM-CON , N = 40 ) , were also tested . All surgical groups were assessed 2 - 3 weeks before surgery and then 6 - 7 months afterward ; the nonsurgical control group was assessed at the time of recruitment and 6 - 7 months later . OUTCOME MEASURES Assessment s included semistructured interviews , st and ardized question naires , and st and ardized gynecological examinations . RESULTS For the TOT group , sexual drive , arousal , and sexual behavior significantly improved postoperatively . For the SUB group , sexual behavior and overall sexual functioning significantly improved . For both TOT and SUB groups , unprovoked pain in the abdomen and pain in the abdomen during gynecological examinations was significantly reduced . For both TOT and SUB groups , overall psychological functioning did not significantly change postoperatively . Although between 3 % and 16 % of women undergoing hysterectomy reported adverse changes in psychosocial well-being after surgery , similar percentages of women in the control groups reported such effects . CONCLUSIONS Hysterectomy result ed in a consistent reduction in abdominal pain , some improvement in sexual functioning , but no change in overall psychological functioning . There was no evidence supporting the idea that subtotal hysterectomy produced more favorable psychosocial outcomes than total hysterectomy nor was there any evidence that either type of hysterectomy result ed in adverse effects", "OBJECTIVE To assess the effect of soy protein and progressive resistance training on body composition and lipids in postmenopausal women . DESIGN In a controlled trial , 46 postmenopausal women were r and omized to one of four groups : 25 g of soy protein ( SP , n=10 ) , 25 g of soy protein plus resistance exercise ( SPE , n=14 ) , 25 g of maltodextrine ( placebo ) ( PL , n=11 ) , or placebo plus resistance exercise ( PLE , n=11 ) . Progressive resistance training was held three times a week for 16 weeks and included 8 exercises ( 3 series of 8 - 12 repetitions ) . At baseline and after 16 weeks , body mass index , waist circumference ( WC ) , body fat , muscle mass and serum lipid levels were measured . To confirm isoflavone absorption , urinary concentrations were determined . The t-test of Student and ANOVA were used in the statistical analysis . RESULTS Subjects were classified as overweight and showed and roid fat distribution . Urinary isoflavone excretion indicated compliance to soy protein treatment . After 16 weeks of intervention , both SPE and PLE groups showed a significant increase of 1.3 kg in muscle mass and reduction in WC of -1.4 and -2.1 cm , respectively ( p mean values of total cholesterol and LDL ( -29.0 and -24.0 mg/dL , p Soy protein supplementation did not influence the indicators of body composition . However , it exerted possible favorable effects on lipid profile in postmenopausal women . The increase in muscle mass and reduction in abdominal fat were correlated with resistance training", "BACKGROUND The decision to take hormone replacement therapy ( HRT ) is a choice many women encounter when entering menopause . The purpose of this study was to examine the choice to take HRT while participating in a lifestyle intervention to reduce cardiovascular risk through the menopause . METHODS The Women 's Healthy Lifestyle Project is a r and omized clinical trial design ed to examine whether a behavioral lifestyle intervention can decrease the expected rise in cardiovascular risk through the menopause . Participants ( N = 535 ) completed question naires and were interviewed regarding menopausal symptoms , menopausal status , hot flashes , and HRT use at baseline and 54 months . RESULTS The intervention was successful in preventing risk elevation through the 54-month visit . At the final visit , there was no difference between the intervention and control groups in the percentage who had become postmenopausal ( 32.9 % vs 35.0 % , respectively ) , there was no difference between control and intervention with HRT use , with 31.2 % reporting use of HRT , and there was no difference between groups with menopausal symptoms . The women started HRT an average of 6 months after they missed a period . Baseline risk factors did not predict HRT use at the 54-month visit . CONCLUSIONS A sizable number of women reported HRT use . The decision to use HRT was not influenced by the lifestyle intervention or their baseline cardiovascular risk , and these women started HRT very early in the peri- to postmenopause . Further , weight loss in the perimenopause did not affect menopausal symptoms", "Objective : To study the effect of yoga on the climacteric symptoms , perceived stress , and personality in perimenopausal women . Design : One hundred twenty participants ( ages 40 - 55 y ) were r and omly divided into two study arms , ie , yoga and control . The yoga group practice d an integrated approach to yoga therapy comprising surya namaskara ( sun salutation ) with 12 postures , pranayama ( breathing practice s ) , and avartan dhyan ( cyclic meditation ) , whereas the control group practice d a set of simple physical exercises under supervision of trained teachers for 8 weeks ( 1 h daily , 5 days per week ) . The assessment s were made by Greene Climacteric Scale , Perceived Stress Scale , and Eysenck 's Personality Inventory before and after the intervention . Results : Of the three factors of the Greene Climacteric Scale , the Mann-Whitney test showed a significant difference between groups ( P vasomotor symptoms , a marginally significant difference ( P = 0.06 ) in psychological factors but not in the somatic component . Effect sizes were higher in the yoga group for all factors . There was a significantly greater degree of decrease in Perceived Stress Scale scores ( P Eysenck 's Personality Inventory , the decrease in neuroticism was greater ( P extroversion in either the yoga or control group . Conclusions : Eight weeks of an integrated approach to yoga therapy decreases climacteric symptoms , perceived stress , and neuroticism in perimenopausal women better than physical exercise", "BACKGROUND Higher body mass index is associated with worse hot flushes during menopause but the effect of weight loss on flushing is unclear . METHODS Self-administered question naires were used to assess bothersome hot flushes in a 6-month r and omized controlled trial of an intensive behavioral weight loss program ( intervention ) vs a structured health education program ( control ) in 338 women who were overweight or obese and had urinary incontinence . Weight , body mass index , abdominal circumference , physical activity , calorie intake , blood pressure , and physical and mental functioning were assessed at baseline and at 6 months . Repeated- measures proportional odds models examined intervention effects on bothersome hot flushes and potential mediating factors . RESULTS Approximately half of participants ( n = 154 ) were at least slightly bothered by hot flushes at baseline . Among these women , the intervention was associated with greater improvement in bothersome flushes vs control ( odds ratio [ OR ] for improvement by 1 Likert category , 2.25 ; 95 % confidence interval [ CI ] , 1.20 - 4.21 ) . Reductions in weight ( OR , 1.32 ; 95 % CI , 1.08 - 1.61 ; per 5-kg decrease ) , body mass index ( 1.17 ; 1.05 - 1.30 ; per 1-point decrease ) , and abdominal circumference ( 1.32 ; 1.07 - 1.64 ; per 5-cm decrease ) were each associated with improvement in flushing , but changes in physical activity , calorie intake , blood pressure , and physical and mental functioning were not related . The effect of the intervention on flushing was modestly diminished after adjustment for multiple potential mediators ( OR , 1.92 ; 95 % CI , 0.95 - 3.89 ) . CONCLUSION Among women who were overweight or obese and had bothersome hot flushes , an intensive behavioral weight loss intervention result ed in improvement in flushing relative to control . Trial Registration clinical trials.gov Identifier : NCT00091988", "Objectives . To observe the effect of yoga on menopausal symptoms using a prospect i ve , r and omized , controlled and interventional study . Main outcome measures . Total Menopause Rating Scale ( MRS ) score and three subscale scores ( somatovegetative , psychological and urogenital ) were measured on day 1 and day 90 in the study group which performed yoga ( asana , pranayam and meditation ) under supervision for three months , and were compared with the control group that did not perform yoga . MRS has been design ed to measure health-related quality of life of ageing women . It consists of 11 symptoms and three subscales . Results . It was observed that on day 1 the scores in both the groups were comparable . On day 90 , the scores in the yoga group showed a reduction in score on all the subscales , which was statistically significant . No significant difference was noted in the control group . Conclusion . Yoga is effective in reducing menopausal symptoms and should be considered as alternative therapy for the management of menopausal symptoms", "ABSTRACT Background Postmenopausal women seem to favor alternative therapies such as exercise and phytoestrogens as a substitute for potentially harmful hormone replacement therapy . Based on previous research , we hypothesized that phytoestrogens combined with exercise could have a synergic effect on women 's health . Objective To verify whether phytoestrogens enhance the response to mixed training regarding menopausal symptoms and quality of life in postmenopausal women . Methods From a pool of women participating in a 6-month r and omized , controlled exercise study , 21 received a placebo ( mean age 58.3 ± 5.4 years , body mass index 29.8 ± 5.1 kg/m2 ) and 19 received phytoestrogen supplements ( mean age 60.1 ± 3.4 years ; body mass index 30.3 ± 4.6 kg/m2 ) . Body weight , fat mass and lean body mass ( dual-energy X-ray absorptiometry ) were assessed . Quality of life was estimated by the Short Form-36 ( SF-36 ) and Perceived Stress Scale-10 ( PSS-10 ) question naires , and menopausal symptoms by the Kupperman index . All measurements were performed before and after the intervention . Results Although the Kupperman index and PSS-10 remained unchanged in both groups , the SF-36 Physical Component Summary and almost all the SF-36 subscales ( except for role-emotional and mental health ) increased only in the exercise group taking phytoestrogens ( 0.001 While phytoestrogens combined with mixed exercise were not sufficient to improve menopausal symptoms , it seemed to be a better strategy than exercise alone to improve the general quality of life in postmenopausal women", "AIM AND OBJECTIVE To evaluate the influence of an exercise programme on postmenopausal women with symptoms of anxiety and depression . BACKGROUND The menopause is a period of hormonal changes when mood variations are probably more severe than at any other period of women 's lives . DESIGN Prospect i ve study with control group and pre- and post-treatment measures , after six months treatment . Conducted at two healthcare clinics , in the province of Granada ( Spain ) . METHODS A convenience sample of 60 postmenopausal women aged 60 - 70 years , with symptoms of depression and anxiety , was recruited . The women were r and omly divided into two groups : ( 1 ) control group , no treatment ( n = 30 ) ; ( 2 ) exercise group , which carried out a programme of mixed physical exercises with musical support ( n = 30 ) . All subjects answered question naires for the Hamilton Anxiety Scale and the Brink and Yesavage Geriatric Depression Scale before and after treatment . RESULTS In the exercise group , statistically significant improvements were observed in subjects with moderate and severe depression ( 18 and 22 % , respectively ) and in those with symptoms of anxiety . No such changes were observed in the control group . CONCLUSIONS A controlled programme of physical exercise for postmenopausal women alleviates symptoms of anxiety and depression , and its inclusion in primary healthcare programmes should be considered . RELEVANCE TO CLINICAL PRACTICE Menopausal women may benefit from physical exercise , which attenuates the effects of the physiological and psychological changes associated with the menopause and prevents pathologic changes", "Objective : To test the hypothesis that physical leisure time activities reduce the risk of developing persistent fatigue . Methods : The hypothesis was tested in a sample that was homogeneous with respect to sex and occupation , with a prospect i ve cohort design . Of 6234 vocationally active , female , Norwegian nurses ’ aides , not on leave because of illness or pregnancy when they completed a mailed question naire in 1999 , 5341 ( 85.7 % ) completed a second question naire 15 months later . The main outcome measure was the prevalence of persistent fatigue — that is , always or usually feeling fatigued in the daytime during the preceding 14 days . Results : In participants without persistent fatigue at baseline , reported engagement in physical leisure time activities for 20 minutes or more at least once a week during the three months before baseline was associated with a reduced risk of persistent fatigue at the follow up ( odds ratio = 0.70 ; 95 % confidence interval 0.55 to 0.89 ) , after adjustments for age , affective symptoms , sleeping problems , musculoskeletal pain , long term health problems of any kind , smoking , marital status , tasks of a caring nature during leisure time , and work factors at baseline . Conclusion : The study supports the hypothesis that physical leisure time activities reduce the risk of developing persistent fatigue", "OBJECTIVES To describe Australian-born women 's experience of symptoms during the natural menopause transition and the relative contribution of menopausal and health status , social factors and lifestyle behaviours . DESIGN A community based cross-sectional survey by telephone interview was carried out on a r and omly derived sample of Melbourne women . PARTICIPANTS The participants were 2000 Australian-born women , aged between 45 and 55 years . OUTCOME MEASURES A list of 22 symptoms was used . Explanatory variables were : sociodemographic variables ; menopausal and health status ; lifestyle behaviours ; attitudes to ageing and to menopause . RESULTS A 70 % response rate was achieved for eligible women who could be contacted during the study . Premenopausal women were the least symptomatic and perimenopausal women the most symptomatic . Factor analysis found seven common factors from the 22 symptoms studied . Menopausal status based on menstrual history was significantly related to two groups of symptoms : vasomotor symptoms , which increased through the menopausal transition ; and general somatic symptoms which were more frequent in the perimenopause . Analysis of variance of factor scores found fewer symptoms with increasing years of education , better self-rated health , the use of fewer non-prescription medications , the absence of chronic health conditions , a low level of interpersonal stress , the absence of premenstrual complaints , not currently smoking , exercise at least once a week , and positive attitudes to ageing and menopause . CONCLUSIONS Many factors unrelated to hormonal changes contributed to the symptoms . Longitudinal investigation is needed to determine the relative importance of hormonal , psychosocial and lifestyle variables in the aetiology of mid-life symptoms", "Objective : Physical activity has been shown to enhance quality of life ( QOL ) ; however , few investigations of these effects exist in women undergoing the menopausal transition . The present study examined the long-term effects of physical activity on menopause-related QOL and tested the mediating effects of physical self-worth and positive affect in this relationship . Methods : Middle-aged women previously enrolled in a 4-month r and omized controlled trial involving walking and yoga , and a control group completed a follow-up mail-in survey 2 years after the end of the trial . The survey included a battery of psychological and physical activity measures , including measures of menopausal symptoms and menopause-related QOL . Longitudinal linear panel analysis was conducted within a covariance modeling framework to test whether physical self-worth and positive affect mediated the physical activity-QOL relationship over time . Results : At the end of the trial , physical activity and menopausal symptoms were related to physical self-worth and positive affect , and in turn , greater levels of physical self-worth and positive affect were associated with higher levels of menopause-related QOL . Analyses indicated that increases in physical activity and decreases in menopausal symptoms over the 2-year period were related to increases in physical self-worth ( & bgr;s = 0.23 and −0.52 , physical activity and menopausal symptoms , respectively ) and , for symptoms , also to decreased positive affect ( & bgr ; = −0.47 ) , and both physical self-worth ( & bgr ; = 0.34 ) and affect ( & bgr ; = 0.43 ) directly influenced enhancements in QOL ( R2 = 0.775 ) . Conclusions : The findings support the position that the effects of physical activity on QOL are mediated , in part , by intermediate psychological outcomes and that physical activity can have long-term benefits for women undergoing the menopausal transition", "CONTEXT Observational studies have found lower rates of coronary heart disease ( CHD ) in postmenopausal women who take estrogen than in women who do not , but this potential benefit has not been confirmed in clinical trials . OBJECTIVE To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease . DESIGN R and omized , blinded , placebo-controlled secondary prevention trial . SETTING Outpatient and community setting s at 20 US clinical centers . PARTICIPANTS A total of 2763 women with coronary disease , younger than 80 years , and postmenopausal with an intact uterus . Mean age was 66.7 years . INTERVENTION Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily ( n = 1380 ) or a placebo of identical appearance ( n = 1383 ) . Follow-up averaged 4.1 years ; 82 % of those assigned to hormone treatment were taking it at the end of 1 year , and 75 % at the end of 3 years . MAIN OUTCOME MEASURES The primary outcome was the occurrence of nonfatal myocardial infa rct ion ( MI ) or CHD death . Secondary cardiovascular outcomes included coronary revascularization , unstable angina , congestive heart failure , resuscitated cardiac arrest , stroke or transient ischemic attack , and peripheral arterial disease . All-cause mortality was also considered . RESULTS Overall , there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes : 172 women in the hormone group and 176 women in the placebo group had MI or CHD death ( relative hazard [ RH ] , 0.99 ; 95 % confidence interval [ CI ] , 0.80 - 1.22 ) . The lack of an overall effect occurred despite a net 11 % lower low-density lipoprotein cholesterol level and 10 % higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group ( each P CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5 . More women in the hormone group than in the placebo group experienced venous thromboembolic events ( 34 vs 12 ; RH , 2.89 ; 95 % CI , 1.50 - 5.58 ) and gallbladder disease ( 84 vs 62 ; RH , 1.38 ; 95 % CI , 1.00 - 1.92 ) . There were no significant differences in several other end points for which power was limited , including fracture , cancer , and total mortality ( 131 vs 123 deaths ; RH , 1.08 ; 95 % CI , 0.84 - 1.38 ) . CONCLUSIONS During an average follow-up of 4.1 years , treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease . The treatment did increase the rate of thromboembolic events and gallbladder disease . Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events , we do not recommend starting this treatment for the purpose of secondary prevention of CHD . However , given the favorable pattern of CHD events after several years of therapy , it could be appropriate for women already receiving this treatment to continue", "BACKGROUND Menopause is associated with poor sleep quality and daytime sleepiness , which may lead to impaired quality of life and impaired functioning in daily activities . OBJECTIVE To study whether exercise training improves sleep quality or decreases the amount of night time hot flushes among menopausal women with vasomotor symptoms . STUDY DESIGN A r and omized controlled trial . Sedentary women ( N=176 ) aged 43 - 63 years with menopausal symptoms were r and omized to a six-month unsupervised aerobic training intervention ( 50 min 4 times per week ) or a control group . Both groups attended lectures on physical activity and health once a month . MAIN OUTCOME MEASURES Sleep quality and the amount of hot flushes disturbing sleep . The women reported daily via mobile phone whether hot flushes had disturbed their sleep and how they had slept ( scale 1 - 5 ) . Responses received by mobile phone over the 6-month period totaled on average 125 ( 5.2 per week ) responses per participant . RESULTS At baseline there was no difference between the groups in the demographic variables . Sleep quality improved significantly more in the intervention group than in the control group ( OR 1.02 ; 95 % CI=1.0 - 1.05 , p=0.043 ) . The odds for sleep improvement were 2 % per week in the intervention group and a decrease of 0.5 % per week in the control group . The amount of hot flushes related to sleep diminished ( p=0.004 ) by the end of the intervention . CONCLUSIONS Aerobic training for 6 months may improve sleep quality and reduce hot flushes among symptomatic menopausal women", "OBJECTIVE To determine the effects of moderate-intensity exercise training on self-rated ( subjective ) sleep quality among healthy , sedentary older adults reporting moderate sleep complaints . DESIGN R and omized controlled trial of 16 weeks ' duration . SETTING General community . PARTICIPANTS Volunteer sample of 29 women and 14 men ( of 67 eligible subjects ) aged 50 to 76 years who were sedentary , free of cardiovascular disease , and reported moderate sleep complaints . No participant was withdrawn for adverse effects . INTERVENTION R and omized to 16 weeks of community-based , moderate-intensity exercise training or to a wait-listed control condition . Exercise consisted primarily of four 30- to 40-minute endurance training sessions ( low-impact aerobics ; brisk walking ) prescribed per week at 60 % to 75 % of heart rate reserve based on peak treadmill exercise heart rate . MAIN OUTCOME MEASURE Pittsburgh Sleep Quality Index ( PSQI ) . RESULTS Compared with controls ( C ) , subjects in the exercise training condition ( E ) showed significant improvement in the PSQI global sleep score at 16 weeks ( baseline and posttest values in mean [ SD ] for C=8.93 [ 3.1 ] and 8.8 [ 2.6 ] ; baseline and posttest values for E=8.7 [ 3.0 ] and 5.4 [ 2.8 ] ; mean posttest difference between conditions=3.4 ; P sleep parameters of rated sleep quality , sleep-onset latency ( baseline and posttest values for C=26.1 [ 20.0 ] and 23.8 [ 15.3 ] ; for E=28.4 [ 20.2 ] and 14.6 [ 13.0 ] ; net improvement=11.5 minutes ) , and sleep duration baseline and posttest scores for C=5.8 [ 1.1 ] and 6.0 [ 1.0 ] ; for E=6.0 [ 1.1 ] and 6.8 [ 1.2 ] ; net improvement=42 minutes ) assessed via PSQI and sleep diaries ( P=.05 ) . CONCLUSIONS Older adults with moderate sleep complaints can improve self-rated sleep quality by initiating a regular moderate-intensity exercise program", "An evaluation of the long term impact of a health education intervention in primary care , for premenopausal women ( 45 years of age ) , is presented . The intervention included information and group discussion about menopause , stress management , health behaviours ( smoking , exercise , diet ) and treatment choices . Question naires were sent to 86 women who had been r and omised into two groups ( prepared/control ) and were now aged 50 ( response rate 91 % ) . The prepared group had significantly greater knowledge of menopause and attributed fewer symptoms to the menopause than the controls . There were no group differences in measures of general health or mood , but there was a tendency for the prepared group to report more interest in sexual activity . Subjective evaluation of the intervention was positive in terms of increasing knowledge and helping women to deal with the emotional and practical aspects of the menopause", "Phytoestrogens and training could be effective to reduce cardiovascular and type 2 diabetes mellitus risk factors in postmenopausal women . Nevertheless , the impact of their combination on adipokines and systemic inflammation was never investigated . The objective was to verify if 6 months of mixed training combined with phytoestrogens could have an additional effect on adipokine levels and systemic inflammation in obese postmenopausal women . Fifty-two obese women aged between 50 and 70 years were r and omly assigned to ( 1 ) exercise with placebo ( EX + PL ; n = 25 ) or ( 2 ) exercise with phytoestrogens ( EX + PHY ; n = 27 ) . Body weight , waist circumference , fat mass , and lean body mass ( dual-energy x-ray absorptiometry ) were assessed . Fasting plasma glucose and insulin , adiponectin , leptin , and C-reactive protein ( CRP ) levels were obtained after a 12-hour overnight fast . Total energy intake was measured with a 3-day dietary record . All measurements were performed before and after the 6-month intervention . Although energy intake remained unchanged , body composition was improved in all women ( all Ps Plasma CRP and leptin levels decreased in both groups similarly ( all Ps plasma adiponectin and insulin did not change with exercise combined with placebo or phytoestrogens . Correlation analyses showed that homeostasis model assessment of insulin resistance ( r = -0.58 , P = .02 ) and fasting insulin levels ( r = -0.42 , P = .02 ) at baseline were both correlated with changes in leptin levels . Baseline fasting glucose ( r = -0.36 , P = .03 ) and adiponectin ( r = 0.45 , P = .005 ) levels were associated with changes in CRP concentrations . Although mixed exercise program combined with phytoestrogens does not seem to provide any additional effect , mixed training improves systemic inflammation and leptin concentrations in obese postmenopausal women", "A r and omly selected community cohort of 2000 Australian born women aged 45 to 55 were interviewed on the telephone and information obtained on their health and well-being . These women were divided into pre- , peri- , natural and surgical menopausal groups on their menstrual history . A physical activity question naire was sent to 1181 women in the first three of these groups . These question naires were completed and returned by 61.6 % of the women . The response rate in all groups was significantly associated with the years of education , employment status , body mass index ( BMI ) and self-rated health of the participants . The aim of the study was to test the hypothesis that physical activity is a major contributor to health and well-being by establishing the relationships between physical activity and certain health outcomes , such as menopausal symptoms , psychological well-being , self-rated health and BMI in this cohort of mid-life women . The inter-relationship between physical activity and other variables , including menopausal status , interpersonal stress , health related and preventive health behaviours was examined . Levels of physical activity were significantly associated with better self-rated health , lower BMI measurements , moderate alcohol intake and self-breast examination . There was no significant association between levels of physical activity , psychological well-being and women 's experience of symptoms during the natural menopause transition", "Objective : To investigate factors associated with the presence , severity , and frequency of hot flushes . Design : A 9-year prospect i ve study of 438 Australian-born women , aged 45 to 55 years and menstruating at baseline . Annual fasting blood collection , physical measurements , and interviews including questions about bothersome hot flushes in previous 2 weeks were performed . A “ hot flush index ” score was calculated from the product of the severity and frequency data . Data were analyzed using r and om-effects time-series regression models . Results : A total of 381 women supplied complete data over the follow-up years . A total of 350 women experienced the menopause transition , of whom 60 ( 17 % ) never reported bothersome hot flushes . At baseline , women who reported hot flushes were significantly more likely to have higher negative moods , not be in full- or part-time paid work , smoke , and not report exercising every day . Over the 9-year period of the study , variables significantly associated with reporting bothersome hot flushes were relatively young age ( P low exercise levels ( P low estradiol levels ( P follicle-stimulating hormone ( FSH ) levels ( P smoking ( P the late menopause transition ( P postmenopausal ( P hot flush index score increased as their FSH levels increased ( P age ( P exercise level ( P hot flush index score was greater in women with higher average FSH levels over time ( P FSH and estradiol levels , age , exercise level , and smoking status all contributed to the experience of bothersome hot flushes", "OBJECTIVES The relationship between enhanced physical activity and decreased menopause symptoms is equivocal . In this study we sought to better underst and this relationship by examining the association of physical activity to different symptom domains and by examining mediating and moderating variables . STUDY DESIGN Women participating in a r and omized control trial on physical activity were given a menopause symptom measure ( MENQOL ) at follow-up . Of the 280 women participating , 113 ( mean age=52 ) reported having symptoms they attributed to menopause . Regression analyses were run to examine if change in physical activity predicted fewer symptoms . Exercise self-efficacy was examined as a mediator and depressive symptoms as a moderator . RESULTS An increase in physical activity from baseline was found to be related to reporting fewer total menopause symptoms ( beta=-0.22 , p=.02 ) . When the total menopause symptoms score was examined by domain , increased physical activity was found to be related to reporting fewer general symptoms attributed to menopause ( psychosocial ( beta=-0.18 , p=.05 ) and physical ( beta=-0.23 , p=.01 ) ) , but had no effect on specific symptoms of menopause ( vasomotor and sexual ) . Exercise self-efficacy was found to mediate the relationship between increased physical activity and total , physical and psychosocial menopause symptoms . Finally , for individuals with high depressive symptoms , those who increased physical activity the most reported fewer sexual symptoms of menopause . CONCLUSION This study suggests that physical activity participation is associated with lower general symptom reporting as opposed to specifically impacting menopause symptoms . Further , exercise self-efficacy mediates the relationship between physical activity and general menopause symptoms , suggesting a psychological pathway", "Abstract : Cross – sectional studies and intervention programs have suggested that physical activity is a potential contributor to the health and wellbeing of mid – life and older women . This prospect i ve longitudinal study investigates whether natural changes in physical activity are associated with changes in health outcomes in a population –based cohort of Australian – born women aged 45–55 years living in Melbourne . Of the 352 women from the Melbourne Women 's Midlife Health Project who filled in a base – line physical activity question naire , 292 ( 83 per cent ) were evaluated around three years later with regard to physical activity , psychological wellbeing , self – rated health , symptoms experienced , body mass index ( BMI ) , blood pressure and serum lipids . Mean ( SD ) physical activity measured at base – line was 5.9 ( 5.7 ) hours/week , or 1496 ( 1449 ) kcal/week ; mean ( SD ) change in physical activity per week was 0.05 ( 5.24 ) hours , or 44 ( 1347 ) kcal , indicating that although mean change was small there was substantial variation in change . There were significant increases in BMI ( P , and a decrease in low – density lipoprotein cholesterol ( LDL – C ) levels ( P of physical activity was positively associated with change in HDL – C ( P and change in wellbeing ( P= 0.08 ) and negatively associated with change in coronary heart disease risk score . By increasing physical activity in mid – life , women may reduce at least one risk factor ( HDL – C ) associated with coronary heart disease", "Objective : Exercise and physical activity provide a wide range of health benefits for postmenopausal women , although the impact of maintained exercise participation on psychological well-being is unclear . An exploration of continued exercise participation in psychological well-being after a moderate-intensity exercise program in previously inactive postmenopausal women was therefore undertaken . Design : Twenty-three healthy sedentary postmenopausal women ( age 56 ± 4 years ) were r and omly assigned to two groups . All participants completed the Short Form-36 , Hospital Anxiety and Depression Scale ( HADS ) , and Health Anxiety Question naire ( HAQ ) and then began a 6-week walking program at 50 % heart rate reserve defined by & OV0312;o2 treadmill testing . Post-intervention , all participants underwent repeat & OV0312;o2 treadmill testing and question naires . Group 1 was then instructed to continue exercising , whereas group 2 was instructed to desist for an additional 6-week period . On completion of the 6-week follow-up , participants completed a final set of question naires . Results : Participants performed 97 % of the prescribed 15-hour ( 900 minute ) exercise program ( 875.1 ± 177.4 minutes ) in an average of 26 ± 5 sessions . Total HAQ ( P = 0.001 ) , health worry ( P = 0.001 ) , fear of illness ( P = 0.037 ) , reassurance seeking behavior ( P = 0.037 ) , SF-36 well-being ( P = 0.037 ) , total HADS ( P = 0.019 ) , and HADS depression ( P = 0.015 ) improved significantly following the exercise program . At follow-up , group 1 had lower HADS anxiety ( P = 0.013 ) , total HADS ( P = 0.02 ) , total HAQ ( P = 0.03 ) , and HAQ interference with life ( P = 0.03 ) and significantly higher SF-36 energy ( P = 0.01 ) than group 2 . Conclusions : Healthy postmenopausal women gain significant psychological benefit from moderate-intensity exercise . However , exercise participation must continue to maintain improvements in psychological well-being and quality of life ", "BACKGROUND Evidence suggests that a high proportion of perimenopausal and postmenopausal women experience vasomotor symptoms ( hot flushes/night sweats ) that can be severe and disruptive and which are the principal reason for seeking medical intervention . Hormone therapy ( HT ) is known to be an effective treatment for troublesome hot flushes/night sweats but research has raised questions about the safety of HT and there have been negative high profile media reports about its use . Consequently many women are seeking alternatives and exercise might be one such option but there is a lack of high quality evidence on its effectiveness . AIMS This RCT initially aims to investigate the feasibility/acceptability of two exercise interventions identified from our previous preference study in 165 women , and if found to be feasible/acceptable , continue to recruit sufficient women ( n=261 ) to examine the effect of these interventions on hot flushes/night sweats and other outcomes relevant to menopausal women . METHOD We aim to recruit inactive perimenopausal and menopausal symptomatic women not using HT and r and omise them to one of two exercise interventions or usual care for six months . RESULTS We will assess outcomes at baseline and 6 and 12 months from r and omisation . CONCLUSION We hope this RCT will contribute towards increasing the evidence regarding the question of whether exercise is an effective treatment for vasomotor symptoms in women not taking HT", "BACKGROUND Epidemiological studies suggest a low incidence of hot flashes in population s that consume dietary soy . The present study examined the effect of soy nuts on hot flashes and menopausal symptoms . METHODS Sixty healthy postmenopausal women were r and omized in a crossover design to a therapeutic lifestyle changes ( TLC ) diet alone and a TLC diet of similar energy , fat , and protein content in which one-half cup soy nuts divided into three or four portions spaced throughout the day ( containing 25 g soy protein and 101 mg aglycone isoflavones ) replaced 25 g of nonsoy protein . During each 8-week diet period , subjects recorded the number of hot flashes and amount of exercise daily . At the end of each 8-week diet period , subjects filled out the menopausal symptom quality of life question naire . RESULTS Compared to the TLC diet alone , the TLC diet plus soy nuts was associated with a 45 % decrease in hot flashes ( 7.5 + /- 3.6 vs. 4.1 + /- 2.6 hot flashes day , respectively , p women with > 4.5 hot flashes/day at baseline and 41 % in those with Soy nut intake was also associated with significant improvement in scores on the menopausal symptom quality of life question naire : 19 % decrease in vasomotor score ( p = 0.004 ) , 12.9 % reduction in psychosocial score ( p = 0.01 ) , 9.7 % decrease in physical score ( p = 0.045 ) , and a trend toward improvement in the sexual score , with a 17.7 % reduction in symptoms ( p = 0.129 ) . The amount of exercise had no effect on hot flash reduction . CONCLUSIONS Substituting soy nuts for nonsoy protein in a TLC diet and consumed three or four times throughout the day is associated with a decrease in hot flashes and improvement in menopausal symptoms", "A case-control study design was used to examine whether habitual physical activity prior to the final menstrual period ( FMP ) was associated with reduced risk of vasomotor and other symptoms during the perimenopausal period . Both cases and controls were identified through a screening interview with r and omly selected women members , ages 48 - 52 , of a large health maintenance organization . Cases ( n = 82 ) were defined as women 3 - 12 months past their FMP who reported regularly having hot flashes or night sweats at least once a day or night during the 3 months following their FMP . Controls ( n = 89 ) were of the same biologic age with respect to the FMP but reported vasomotor symptoms less than once a week during the reference time period . Neither cases nor controls had a history of hormone replacement therapy ( HRT ) , hysterectomy , or bilateral oophorectomy . Case-control status , habitual physical activity ( including recreational , housework , child care , and occupational activity ) , and psychological and somatic symptoms were assessed by self-report . Participation in vigorous recreational activity during the year prior to the FMP was not associated with reduced risk of frequent vasomotor symptoms after the FMP ( odds ratio [ OR ] = 1.03 for a 50-unit increase in activity score , 95 % confidence interval [ CI ] = 0.97 - 1.1 ) . This lack of relationship was observed in all domains of activity . Factors that were associated with decreased risk included higher body mass index ( BMI ) ( weight in kg/(height in meters)2 ) ( OR = 0.95 per 1 unit increase in BMI , 95 % CI = 0.90 - 1.00 ) and higher education ( having a college degree relative to less education ) ( OR = 0.56 , 95 % CI = 0.40 - 0.80 ) . Physical activity was also unassociated with reduced risk of psychologic distress , depressive feelings , or somatic symptoms , but , relative to controls , having vasomotor symptoms ( being a case ) was strongly associated with increased risk of experiencing those symptoms ( OR ranging from 1.83 for psychologic distress to 2.84 for depressive feelings ) . These findings suggest that regular physical activity before the FMP may not reduce the likelihood of experiencing symptoms during the perimenopause , although the small sample size may limit the inferences that can be drawn" ]

[ "Objectives The present evidence indicates a reverse correlation between vitamin D status and blood pressure ( BP ) . The present study determined the effect of oral vitamin D supplementation on BP in patients with elevated BP and vitamin D deficiency . Material s and methods In this r and omized , double-blind , placebo-controlled trial , 42 out patients with elevated BP and vitamin D deficiency were assigned r and omly to two groups : the vitamin D-supplemented group ( VDG ) , who received one capsule containing 50 000 IU of cholecalciferol weekly , and the placebo group ( PG ) , who received one similar capsule containing oral liquid paraffin as placebo for 8 weeks . The systolic ( SBP ) and diastolic ( DBP ) blood pressures , mean arterial blood pressure ( MAP ) , pulse pressure , serum 25-hydroxyvitamin D , parathormone , calcium , phosphorus , magnesium , sodium , and potassium were measured before and after the intervention . Results In all , 92.7 % of the VDG recovered from vitamin D deficiency . At the end of the intervention , the mean SBP and DBP , and the MAP decreased significantly in VDG compared with the PG , whereas at the beginning of the intervention , there was no significant difference between the two groups . The mean changes in SBP ( −6.4±5.3 vs. 0.9±3.7 mmHg , PV and MAP ( −3.7±3.6 vs. 0.9±2.5 mmHg , PV patients with vitamin D deficiency could help prevent vitamin D deficiency and aid control of SBP , DBP , and MAP", "Hydroxylation of 25(OH)D to 1,25-dihydroxyvitamin D and signaling through the vitamin D receptor occur in various tissues not traditionally involved in calcium homeostasis . Laboratory studies indicate that 1,25-dihydroxyvitamin D suppresses renin expression and vascular smooth muscle cell proliferation ; clinical studies demonstrate an inverse association between ultraviolet radiation , a surrogate marker for vitamin D synthesis , and blood pressure . We prospect ively studied the independent association between measured plasma 25-hydroxyvitamin D [ 25(OH)D ] levels and risk of incident hypertension and also the association between predicted plasma 25(OH)D levels and risk of incident hypertension . Two prospect i ve cohort studies including 613 men from the Health Professionals ’ Follow-Up Study and 1198 women from the Nurses ’ Health Study with measured 25(OH)D levels were followed for 4 to 8 years . In addition , 2 prospect i ve cohort studies including 38 388 men and 77 531 women with predicted 25(OH)D levels were followed for 16 to 18 years . During 4 years of follow-up , the multivariable relative risk of incident hypertension among men whose measured plasma 25(OH)D levels were relative risk of 2.67 ( 95 % CI : 1.05 to 6.79 ) . The pooled relative risk combining men and women with measured 25(OH)D levels using the r and om-effects model was 3.18 ( 95 % CI : 1.39 to 7.29 ) . Using predicted 25(OH)D levels in the larger cohorts , the multivariable relative risks comparing the lowest to highest deciles were 2.31 ( 95 % CI : 2.03 to 2.63 ) in men and 1.57 ( 95 % CI : 1.44 to 1.72 ) in women . Plasma 25(OH)D levels are inversely associated with risk of incident hypertension", "BACKGROUND Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans . METHODS We assessed prospect ively whether plasma 25-hydroxyvitamin D ( 25[OH]D ) concentrations are associated with risk of coronary heart disease . A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study ; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection . The blood sample s were returned between April 1 , 1993 , and November 30 , 1999 ; 99 % were received between April 1 , 1993 , and November 30 , 1995 . During 10 years of follow-up , 454 men developed nonfatal myocardial infa rct ion or fatal coronary heart disease . Using risk set sampling , controls ( n = 900 ) were selected in a 2:1 ratio and matched for age , date of blood collection , and smoking status . RESULTS After adjustment for matched variables , men deficient in 25(OH)D ( risk for MI compared with those considered to be sufficient in 25(OH)D ( > or=30 ng/mL ) ( relative risk [ RR ] , 2.42 ; 95 % confidence interval [ CI ] , 1.53 - 3.84 ; P elevated risk relative to those with sufficient 25(OH)D levels ( 22.6 - 29.9 ng/mL : RR , 1.60 [ 95 % CI , 1.10 - 2.32 ] ; and 15.0 - 22.5 ng/mL : RR , 1.43 [ 95 % CI , 0.96 - 2.13 ] , respectively ) . CONCLUSION Low levels of 25(OH)D are associated with higher risk of myocardial infa rct ion in a grade d manner , even after controlling for factors known to be associated with coronary artery disease", "Background For adults , vitamin D intake of 100 mcg ( 4000 IU)/day is physiologic and safe . The adequate intake ( AI ) for older adults is 15 mcg ( 600 IU)/day , but there has been no report focusing on use of this dose . Methods We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded , r and omized trial . In Study 1 , 64 out patients ( recruited if summer 2001 25(OH)D 15 or 100 mcg/day vitamin D in December 2001 . Biochemical responses were followed at subsequent visits that were part of clinical care ; 37 patients completed a wellbeing question naire in December 2001 and February 2002 . Subjects for Study 2 were recruited if their 25(OH)D was vitamin D ; 51 completed a wellbeing question naire in both December 2002 and February 2003 . Results In Study 1 , basal summer 25-hydroxyvitamin D [ 25(OH)D ] averaged 48 ± 9 ( SD ) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 ± 30 nmol/L for the 15 mcg/day group , and 112 ± 41 nmol/L for the 100 mcg/day group . Both doses lowered plasma parathyroid hormone with no effect on plasma calcium . Between December and February , wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group ( 1-tail Mann-Whitney p = 0.036 ) . In Study 2 , 25(OH)D averaged 39 ± 9 nmol/L , and winter wellbeing scores improved with both doses of vitamin D ( two-tail p for vitamin D brought summertime 25(OH)D to > 40 nmol/L , lowered PTH , and its use was associated with improved wellbeing . The 100 mcg/day dose produced greater responses . Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients , we can not rule out a placebo wellbeing response , particularly for those on the lower dose . This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin", "Objective To investigate whether vitamin D supplementation can decrease the mortality and morbidity of low birthweight infants in low income countries . Design R and omised controlled trial . Setting Large government hospital in New Delhi , India . Participants 2079 low birthweight infants born at term ( > 37 weeks ’ gestation ) . Main outcome measures Primary outcome was admission to hospital or death during the first six months of life . Main secondary outcome was growth . Interventions Weekly vitamin D supplements for six months at a dose of one recommended nutrient intake per day ( 35 µg/week ) . Infants were visited weekly at home for observed supplementation and were brought to the clinic monthly for clinical examination and anthropometric measurements . Results Between group differences were not significant for death or hospital admissions ( 92 among 1039 infants in the vitamin D group v 99 among 1040 infants in the placebo group ; adjusted rate ratio 0.93 , 95 % confidence interval 0.68 to 1.29 ; P=0.68 ) , or referral to the outpatient clinic for moderate morbidity . Vitamin D supplementation result ed in better vitamin D status as assessed by plasma calcidiol levels at six months . In adjusted analyses , vitamin D treatment significantly increased st and ard deviation ( z ) scores at six months for weight , length , and arm circumference and decreased the proportion of children with stunted growth ( length for age z score ≤2 ) or with arm circumference z scores of 2 or less . Conclusion A weekly dose of vitamin D result ed in better vitamin D status and benefited the classic vitamin D function of bone growth but did not decrease the incidence of severe morbidity or death among young low birthweight infants . Trial registration Clinical Trials.gov NCT00415402", "OBJECTIVE To compare the effects of dydrogesterone and calcium plus vitamin D in women with severe premenstrual syndrome ( PMS ) . METHOD In this r and omized , double-blind , placebo-controlled study , 180 Shiraz University students with PMS used question naires daily to rate their symptoms for 2 menstrual cycles . Then , the students were r and omly assigned to take a tablet containing either 5 mg of dydrogesterone , 500 mg of calcium plus 200 mg of vitamin D , or a placebo twice daily from the 15th to the 24th day of the cycle for 2 more cycles , and to use the same question naires during the intervention cycles . The collected data were then analyzed by repeated-measurement design and multilevel modeling tests . RESULT Treatment with dydrogesterone or calcium plus vitamin D decreased symptom severity in a similar way ( by 4.64 % and 4.20 % , respectively ) and placebo was associated with a 3.42 % decrease . CONCLUSION Treatment with dydrogesterone or calcium plus vitamin D had a similar effect on symptom severity in women with PMS", "Emerging evidence suggests an inverse relation between vitamin D and blood pressure . We examined the independent association between intake of vitamin D and the risk of incident hypertension among participants of 3 large and independent prospect i ve cohorts : Nurses Health Study I ( NHS I ; n=77 436 ) , NHS II ( n=93 803 ) , and Health Professionals ’ Follow-up Study ( HPFS ; n=38 074 ) . Relative risks and 95 % confidence intervals for incident hypertension were computed according to quintiles of vitamin D intake using Cox proportional hazards regression and adjusted for relevant covariates . Each cohort was followed for ≥8 years . Vitamin D intake was not associated with the risk of developing hypertension . The multivariable relative risk estimates for the highest compared with lowest quintile of intake were 0.98 ( 0.93 to 1.04 ) in NHS I , 1.13 ( 0.99 to 1.29 ) in NHS II , and 1.03 ( 0.93 to 1.15 ) in HPFS . When we compared participants who consumed ≥1600 to intake of vitamin D is not associated with a lower risk of incident hypertension ", "Blacks have significantly higher rates of hypertension than whites , and lower circulating levels of 25-hydroxyvitamin D. There are few data about the effect of vitamin D3 ( cholecalciferol ) supplementation on blood pressure in blacks . During 2 winters from 2008 to 2010 , 283 blacks ( median age , 51 years ) were r and omized into a 4-arm , double-blind trial for 3 months of placebo , 1000 , 2000 , or 4000 international units of cholecalciferol per day . At baseline , 3 months , and 6 months , systolic and diastolic pressure and 25-hydroxyvitamin D were measured . The 3-month follow-up was completed in 250 ( 88 % ) participants . The difference in systolic pressure between baseline and 3 months was + 1.7 mm Hg for those receiving placebo , −0.66 mm Hg for 1000 U/d , −3.4 mm Hg for 2000 U/d , and −4.0 mm Hg for 4000 U/d of cholecalciferol ( −1.4 mm Hg for each additional 1000 U/d of cholecalciferol ; P=0.04 ) . For each 1-ng/mL increase in plasma 25-hydroxyvitamin D , there was a significant 0.2-mm Hg reduction in systolic pressure ( P=0.02 ) . There was no effect of cholecalciferol supplementation on diastolic pressure ( P=0.37 ) . Within an unselected population of blacks , 3 months of oral vitamin D3 supplementation significantly , yet modestly , lowered systolic pressure . Future trials of vitamin D supplementation on blood pressure are needed to confirm these promising results , particularly among blacks , a population for whom vitamin D deficiency may play a more specific mechanistic role in the pathogenesis of hypertension", "Background The role of vitamin D in management of depression is unclear . Results from observational and emerging r and omized controlled trials ( RCTs ) investigating the efficacy of vitamin D in depression lack consistency - with some suggesting a positive association while others show a negative or inconclusive association . Methods / Design The primary aim of this study is to conduct a systematic review of RCTs to assess the effect of oral vitamin D supplementation versus placebo on depression symptoms measured by scales and the proportion of patients with symptomatic improvement according to the authors ’ original definition . Secondary aims include assessing the change in quality of life , adverse events and treatment discontinuation . We will conduct the systematic review and meta- analysis according to the recommendations of the Cochrane H and book for Systematic Review s of Interventions . We will search the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE ( 1966 to present ) , EMBASE ( 1980 to present ) , CINAHL ( 1982 to present ) , PsychINFO ( 1967 to present ) and Clinical Trials.gov . Unpublished work will be identified by search ing two major conferences : the International Vitamin Conference , the Anxiety Disorders and Depression Conference , while grey literature will be acquired by contacting authors of included studies . We will use the r and om-effects meta- analysis to synthesize the data by pooling the results of included studies . Discussion The results of this systematic review will be helpful in clarifying the efficacy of vitamin D supplementation and providing evidence to establish guidelines for implementation of vitamin D for depression in general practice and other relevant setting s. Study registration Unique identifier : CRD42013003849", "Vitamin D receptors have been detected in vascular smooth muscle cells , and 1,25-dihydroxyvitamin D inhibits the renin mRNA expression . Epidemiological studies show an inverse relation between serum 25-hydoxyvitamin D levels and blood pressure , and low serum 25-hydoxyvitamin D levels are reported to be predictors of future development of hypertension . This may indicate an important role for vitamin D in blood pressure regulation . In the present study , 25-hydoxyvitamin D was measured in sera collected in 1994 from 4125 subjects who did not use blood pressure medication , and thereafter measurement was repeated in 2008 for 2385 of these subjects . In sera from 1994 there was a significant decrease in age , body mass index , and systolic blood pressure and a significant increase in physical activity score across increasing 25-hydoxyvitamin D quartiles . After adjusting for sex , age , body mass index , and physical activity , the difference in systolic blood pressure between the lowest and highest serum 25-hydoxyvitamin D quartiles was 3.6 mm Hg . After adjustment for confounders , serum 25-hydoxyvitamin D from 1994 did not predict future hypertension or increase in blood pressure , nor was there any significant association between change in serum 25-hydoxyvitamin D from 1994 to 2008 and change in blood pressure . Our results do not support a causal role for vitamin D in blood pressure regulation , and large r and omized clinical trials , preferably including subjects with hypertension and /or low serum 25-hydoxyvitamin D levels , are greatly needed to clarify whether vitamin D supplementation affects the blood pressure", "Increasing evidence describes a possible interplay between vitamin D insufficiency with increased aldosterone . The authors sought to evaluate the effect of vitamin D supplementation on plasma aldosterone concentration ( PAC ) in patients with hypertension and 25-hydroxyvitamin D[25(OH)D ] insufficiency . The Styrian Vitamin D Hypertension Trial was a single-center , double-blind , placebo-controlled r and omized clinical trial conducted from 2011 to 2014 . Two hundred patients with arterial hypertension and 25(OH)D levels to receive either 2800 IU of vitamin D3 or placebo . The present investigation is a post hoc analysis using analysis of covariance adjusting for baseline differences . A total of 188 participants ( mean±st and ard deviation age , 60.1±11.3 years ; 47 % women ; 25(OH)D , 21.2±5.6 ng/mL ) completed the trial . Mean differences between baseline and follow-up PAC in the control and intervention arm were + 3.3 ng/dL and + 0.9 ng/dL , respectively ( P=.04 ) . The findings indicate that vitamin D3 supplementation significantly decreases PAC in patients with arterial hypertension and 25(OH)D insufficiency", "There has been an increased interest in the role of vitamin D in depression ; however , there have been few studies conducted in younger population groups . Our aim was to investigate the association between vitamin D status and depressive symptoms in a non- clinical young adult sample living in Dunedin , New Zeal and . A cross-sectional sample of 615 young adults completed a question naire including demographics and the Centre for Epidemiological Studies Depression Scale ( CES-D ) . Height , weight and a blood sample for 25-hydroxyvitamin D [ 25(OH)D ] was obtained . Serum 25(OH)D was used to predict depression scores , adjusting for potential confounders including time spent outdoors for 13 consecutive days , BMI , age , sex and ethnicity . Prevalence of low vitamin D was high even in this age group , and serum 25(OH)D was negatively associated with depression symptoms before and after adjustment . When investigating the relationship between the presence versus absence of depressive symptoms and quartiles of 25(OH)D , participants in the lowest quartile were more likely to report depressive symptoms compared with those in the highest quartile . Although our findings suggest that vitamin D is a predictor of depression symptomatology , even when controlling for time spent outdoors , a r and omised controlled trial in this young adult target group is needed to confirm the association", "Importance Cohort studies have reported increased incidence of cardiovascular disease ( CVD ) among individuals with low vitamin D status . To date , r and omized clinical trials of vitamin D supplementation have not found an effect , possibly because of using too low a dose of vitamin D. Objective To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population . Design , Setting , and Participants The Vitamin D Assessment Study is a r and omized , double-blind , placebo-controlled trial that recruited participants mostly from family practice s in Auckl and , New Zeal and , from April 5 , 2011 , through November 6 , 2012 , with follow-up until July 2015 . Participants were community-resident adults aged 50 to 84 years . Of 47 905 adults invited from family practice s and 163 from community groups , 5110 participants were r and omized to receive vitamin D3 ( n = 2558 ) or placebo ( n = 2552 ) . Two participants retracted consent , and all others ( n = 5108 ) were included in the primary analysis . Interventions Oral vitamin D3 in an initial dose of 200 000 IU , followed a month later by monthly doses of 100 000 IU , or placebo for a median of 3.3 years ( range , 2.5 - 4.2 years ) . Main Outcomes and Measures The primary outcome was the number of participants with incident CVD and death , including a prespecified subgroup analysis in participants with vitamin D deficiency ( baseline deseasonalized 25-hydroxyvitamin D [ 25(OH)D ] levels myocardial infa rct ion , angina , heart failure , hypertension , arrhythmias , arteriosclerosis , stroke , and venous thrombosis . Results Of the 5108 participants included in the analysis , the mean ( SD ) age was 65.9 ( 8.3 ) years , 2969 ( 58.1 % ) were male , and 4253 ( 83.3 % ) were of European or other ethnicity , with the remainder being Polynesian or South Asian . Mean ( SD ) baseline deseasonalized 25(OH)D concentration was 26.5 ( 9.0 ) ng/mL , with 1270 participants ( 24.9 % ) being vitamin D deficient . In a r and om sample of 438 participants , the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group . The primary outcome of CVD occurred in 303 participants ( 11.8 % ) in the vitamin D group and 293 participants ( 11.5 % ) in the placebo group , yielding an adjusted hazard ratio of 1.02 ( 95 % CI , 0.87 - 1.20 ) . Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes . Conclusions and Relevance Monthly high-dose vitamin D supplementation does not prevent CVD . This result does not support the use of monthly vitamin D supplementation for this purpose . The effects of daily or weekly dosing require further study . Trial Registration clinical trials.gov Identifier :", "Aims Circulating 25-hydroxyvitamin D ( 25OHD ) levels oral vitamin D supplementation reduces mortality in patients with advanced HF . Methods and results Four hundred HF patients with 25OHD levels to receive 4000 IU vitamin D daily or matching placebo for 3 years . Primary endpoint was all-cause mortality . Key secondary outcome measures included hospitalization , resuscitation , mechanical circulatory support ( MCS ) implant , high urgent listing for heart transplantation , heart transplantation , and hypercalcaemia . Initial 25OHD levels were on average Mortality was not different in patients receiving vitamin D ( 19.6 % ; n = 39 ) or placebo ( 17.9 % ; n = 36 ) with a hazard ratio ( HR ) of 1.09 [ 95 % confidence interval ( CI ) : 0.69 - 1.71 ; P = 0.726 ] . The need for MCS implant was however greater in patients assigned to vitamin D ( 15.4 % , n = 28 ) vs. placebo [ 9.0 % , n = 15 ; HR : 1.96 ( 95 % CI : 1.04 - 3.66 ) ; P = 0.031 ] . Other secondary clinical endpoints were similar between groups . The incidence of hypercalcaemia was 6.2 % ( n = 10 ) and 3.1 % ( n = 5 ) in patients receiving vitamin D or placebo ( P = 0.192 ) . Conclusion A daily vitamin D dose of 4000 IU did not reduce mortality in patients with advanced HF but was associated with a greater need for MCS implants . Data indicate caution regarding long-term supplementation with moderately high vitamin D doses . Trial Registration Information clinical trials.gov Idenitfier : NCT01326650", "BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170", "BACKGROUND Epidemiological evidence supports a relationship between vitamin D and mental well-being , although evidence from large-scale placebo-controlled intervention trials is lacking . AIMS To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women ; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms ; and if there is an association between serum 25-hydroxyvitamin D levels and mental health . METHOD A double-blind , r and omised , placebo-controlled trial of women aged 70 or older ( the Vital D Study : IS RCT N83409867 and ACTR12605000658617 ) . Participants were r and omly assigned to receive 500 000 IU vitamin D(3 ) ( cholecalciferol ) orally or placebo every autumn/winter for 3 - 5 consecutive years . The tools utilised at various time points were the General Health Question naire , the 12-item Short Form Health Survey , the Patient Global Impression-Improvement scale and the WHO Well-Being Index . Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants . RESULTS In this non- clinical population , no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health . Serum 25-hydroxyvitamin D levels in the vitamin D group were 41 % higher than the placebo group 12 months following their annual dose . Despite this difference , scores from the question naires did not differ . Furthermore , there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups . CONCLUSIONS The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3 ) is a practical intervention to prevent depressive symptoms in older community-dwelling women", "OBJECTIVES Low vitamin D status has been shown to be associated with hypertension . We planned to research the effect of vitamin D and nifedipine in the treatment of patients with essential hypertension . METHODS Patients with grade s I-II essential hypertension were enrolled in this single-center , double-blind , placebo-controlled trial in Beijing . All patients received a conventional antihypertensive drug ( nifedipine , 30 mg/d ) . One hundred and twenty-six patients were r and omly assigned to receive vitamin D ( n=63 , 2000 IU/d ) or a placebo ( n=63 ) as an add-on to nifedipine , by the method of permutated block r and omization . Ambulatory blood pressure monitoring was performed at baseline ( month 0 ) , at month 3 and at month 6 . RESULTS In vitamin D supplementation group , there was a significant increase in mean 25-hydroxyvitamin D levels from baseline ( 19.4 ± 11.6 ng/ml ) to 6 months ( 34.1 ± 12.2 ng/ml ; p the fall of 24-h mean blood pressure , between the groups was -6.2 mmHg ( 95 % CI -11.2 ; -1.1 ) for systolic blood pressure ( p for diastolic blood pressure ( p patients with vitamin D baseline ( n=113 ) , 24-h mean blood pressure decreased by 7.1/5.7 mmHg ( p were similar among the two groups . CONCLUSIONS Vitamin D supplementation can reduce blood pressure in patients with hypertension , it can be an adjuvant therapy for patients with grade s I-II essential hypertension . CLINICAL TRIAL REGISTRATION This study was registered in the Chinese Clinical Trial Registry , it is available in Website : http://www.chictr.org/cn/ ; REGISTRATION NUMBER ChiCTR-ONC-13003840", "The need , safety , and effectiveness of vitamin D supplementation during pregnancy remain controversial . In this r and omized , controlled trial , women with a singleton pregnancy at 12 to 16 weeks ' gestation received 400 , 2000 , or 4000 IU of vitamin D(3 ) per day until delivery . The primary outcome was maternal/neonatal circulating 25-hydroxyvitamin D [ 25(OH)D ] concentration at delivery , with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25-dihydroxyvitamin D(3 ) [ 1,25(OH)(2)D(3 ) ] production . Of the 494 women enrolled , 350 women continued until delivery : Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different ( p relative risk ( RR ) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000- and the 400-IU groups ( RR = 1.52 , 95 % CI 1.24 - 1.86 ) , the 4000- and the 400-IU groups ( RR = 1.60 , 95 % CI 1.32 - 1.95 ) but not between the 4000- and . 2000-IU groups ( RR = 1.06 , 95 % CI 0.93 - 1.19 ) . Circulating 25(OH)D had a direct influence on circulating 1,25(OH)(2)D(3 ) concentrations throughout pregnancy ( p safety measure . Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels . It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race , whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations , especially in African Americans", "BACKGROUND Ergocalciferol ( vitamin D(2 ) ) supplementation plays a role in fall prevention , but the effect in patients living in the community in sunny climates remains uncertain . We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling . METHODS A 1-year population -based , double-blind , r and omized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth , Australia ( latitude , 32 degrees S ) , with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year . Participants were r and omized to receive ergocalciferol , 1000 IU/d , or identical placebo ( hereinafter , ergocalciferol and control groups , respectively ) . Both groups received calcium citrate , 1000 mg/d . Fall data were collected every 6 weeks . RESULTS Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height , which was significantly different between the 2 groups ( ergocalciferol group , 53.0 % ; control group , 62.9 % ; odds ratio [ OR ] , 0.61 ; 95 % confidence interval [ CI ] , 0.37 - 0.99 ) . When those who fell were grouped by the season of first fall or the number of falls they had , ergocalciferol treatment reduced the risk of having the first fall in winter and spring ( ergocalciferol group , 25.2 % ; control group , 35.8 % ; OR , 0.55 ; 95 % CI , 0.32 - 0.96 ) but not in summer and autumn , and reduced the risk of having 1 fall ( ergocalciferol group , 21.2 % ; control group , 33.8 % ; OR , 0.50 ; 95 % CI , 0.28 - 0.88 ) but not multiple falls . CONCLUSION Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium , which is associated with a 19 % reduction in the relative risk of falling , mostly in winter", "Background Diabetes and vitamin D deficiency are global epidemics . Research ers have long been exploring the role of potentially modifiable factors to manage type 2 diabetes . We conducted a systematic review of prospect i ve studies and r and omized controlled trials that involved vitamin D supplementation and specifically intended to study glycemic outcomes related to type 2 diabetes . Methods Two authors independently search ed Medline and PubMed for longitudinal studies that had assessed the effect of vitamin D supplements on glycemic control , insulin resistance and beta-cell dysfunction in patients with diabetes . Results Seventeen r and omized control trials and seven longitudinal studies with a minimum follow-up of one month were included . Results of the various short-term studies ( follow up ≤ 3 months ) suggested that vitamin D supplementation had a positive impact on glycemic control and metabolic parameters such as insulin resistance and beta cell dysfunction . However , the evidence was weak due to the low method ological quality of the studies . There was no significant effect on HbA1c , beta cell function and insulin resistance in the long-term studies ( follow up > 3 months ) . There existed heterogeneity in the methodology of the studies , inclusion criteria , mode of supplementation of vitamin D and the duration of follow up . Conclusions Current evidence based on r and omized controlled trials and longitudinal studies do not support the notion that vitamin D supplementation can improve hyperglycemia , beta cell secretion or insulin sensitivity in patients with type 2 diabetes . Large-scale trials with proper study design , optimal vitamin D supplementation and longer follow up need to be conducted", "OBJECTIVE The purpose of this study was to prospect ively examine the association between vitamin D and calcium intake and risk of type 2 diabetes . RESEARCH DESIGN AND METHODS In the Nurses ' Health Study , we followed 83,779 women who had no history of diabetes , cardiovascular disease , or cancer at baseline for the development of type 2 diabetes . Vitamin D and calcium intake from diet and supplements was assessed every 2 - 4 years . During 20 years of follow-up , we documented 4,843 incident cases of type 2 diabetes . RESULTS After adjusting for multiple potential confounders , there was no association between total vitamin D intake and type 2 diabetes . However , the relative risk ( RR ) of type 2 diabetes was 0.87 ( 95 % CI 0.75 - 1.00 ; P for trend = 0.04 ) comparing the highest with the lowest category of vitamin D intake from supplements . The multivariate RRs of type 2 diabetes were 0.79 ( 0.70 - 0.90 ; P for trend calcium intake from all sources and 0.82 ( 0.72 - 0.92 ; P for trend 1,200 mg calcium and > 800 IU vitamin D was associated with a 33 % lower risk of type 2 diabetes with RR of 0.67 ( 0.49 - 0.90 ) compared with an intake of vitamin D and calcium intake in reducing the risk of type 2 diabetes", "Background Antenatal vitamin D status may be associated with the risk of adverse pregnancy and neonatal outcomes ; however , the benefits of vitamin D supplementation during pregnancy remain unknown . Methods We conducted a double-blind placebo-controlled r and omized trial to evaluate the effect of high-dose prenatal 3rd trimester vitamin D3 supplementation on maternal and neonatal ( cord blood ) serum 25-hydroxyvitamin D ( 25(OH)D ) concentration ( primary biochemical efficacy outcome ) and maternal serum calcium concentration ( primary safety measure ) . Eligibility criteria were pregnant women aged 18 to 1:1 allocation to one of two parallel intervention groups ; placebo ( n = 80 ) or 35,000 IU/week of vitamin D3 ( n = 80 ) until delivery . All participants , study personnel and study investigators were blind to treatment allocation . Results Mean maternal 25(OH)D concentration was similar in the vitamin D and placebo groups at baseline ( 45 vs. 44 nmol/L ; p = 0.66 ) , but was significantly higher in the vitamin D group vs. placebo group among mothers at delivery ( 134 vs. 38 nmol/L ; p attained 25(OH)D > 50 nmol/L , versus 21 % mothers and 19 % of neonates in the placebo group . No participants met criteria for hypercalcemia , there were no known supplement-related adverse events , and major pregnancy outcomes were similar between groups . Conclusions Antenatal 3rd-trimester vitamin D3 supplementation ( 35,000 IU/week ) significantly raised maternal and cord serum 25(OH)D concentrations above 50 nmol/L in almost all participants without inducing hypercalcemia or other observed safety concerns . Doses up to 35,000 IU/week may be cautiously used in further research aim ed at establishing the clinical effects and safety of vitamin D3 supplementation in pregnancy . Trial registration This trial was registered at Clinical Trials.gov ( NCT01126528 )", "Introduction Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures . A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects . Purpose and Methods Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have review ed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases , providing recommendations and guidelines for future studies in this field . Results and conclusions Robust mechanistic evidence is available from in vitro studies and in vivo animal studies , usually employing cholecalciferol , calcidiol or calcitriol in pharmacologic rather than physiologic doses . Although many cross-sectional and prospect i ve association studies in humans have shown that low 25-hydroxyvitamin D levels ( i.e. , vitamin D are missing , and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels > 50 nmol/L , did not simultaneously assess multiple outcomes , and did not report overall safety ( e.g. , falls ) . Thus , no recommendations can be made to date for the use of vitamin D supplementation in general , parental compounds , or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases . Moreover , attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health can not be recommended based on current evidence , since safety has yet to be confirmed . Finally , the promising findings from mechanistic studies , large cohort studies , and small clinical trials obtained for autoimmune diseases ( including type 1 diabetes , multiple sclerosis , and systemic lupus erythematosus ) , cardiovascular disorders , and overall reduction in mortality require further confirmation", "Background Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections . This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections . Methodology / Findings In this prospect i ve cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009–2010 in 198 healthy adults , blinded to the nature of the substance being measured . The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations . The incidence of infection in participants with different concentrations of vitamin D was determined . One hundred ninety-five ( 98.5 % ) of the enrolled participants completed the study . Light skin pigmentation , lean body mass , and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant ( p developing acute respiratory tract infections and with a marked reduction in the percentages of days ill . Conclusions / Significance Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby , at least during the fall and winter in temperate zones . The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections , including influenza , in the general population and in sub population s with lower 25-hydroxyvitamin D concentrations , such as pregnant women , dark skinned individuals , and the obese", "Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33", "BACKGROUND Vitamin D deficiency is recently speculated to play a role in the development of depression . Nevertheless , few studies have explored the association between blood 25-hydroxyvitamin D [ 25(OH)D ] concentrations and depression in the general population . Therefore , we aim ed to determine this association in middle-aged and elderly Chinese . METHODS We conducted a population -based cross-sectional study in 2005 in Beijing and Shanghai , China . Participants included 3262 community residents aged 50 - 70 . Depressive symptoms were defined as a Center for Epidemiological Studies of Depression Scale ( CES-D ) score of 16 or higher . Circulating 25(OH)D concentrations were measured by radioimmunoassay . RESULTS The prevalence of depressive symptoms was lower in the top tertile of 25(OH)D concentrations compared to the lowest tertile ( 7.2 % vs. 11.1 % ) in the study population ( odds ratio , 0.62 ; 95 % confidence interval , 0.46 - 0.83 ; P for trend=0.002 ) . This association was substantially attenuated after controlling for various confounding factors , and disappeared after including geographic location in the model . Stratified analysis by location did not find any association between depressive symptoms and 25(OH)D levels among participants from either Beijing or Shanghai . LIMITATIONS Due to the cross-sectional study design , causal relation remains unknown . CONCLUSIONS Depressive symptoms are not associated with 25(OH)D concentrations in middle-aged and elderly Chinese . Further prospect i ve studies are required to determine whether they are correlated", "In a double-blind trial of vitamin D supplements in pregnant Asian women calciferol ( ergocalciferol , 1000 IU/day ) was administered to 59 women and placebo to 67 controls during the last trimester . The two groups had similar distributions of maternal age , height , parity , number of vegetarians , countries of origin , and sex and gestation of the infants . At entry to the trial maternal serum 25-hydroxy vitamin D ( 25-OHD ) concentrations were low in both treatment and control groups and significantly lower in vegetarians than non-vegetarians . Mothers in the treatment group gained weight faster in the last trimester than those in the control group , and at term they and their infants all had adequate plasma 25-OHD concentrations , Mothers and infants in the control group , however , had low plasma concentrations of 25-OHD and calcium and raised plasma alkaline phosphatase ( bone isoenzyme ) activity . Five of these infants developed symptomatic hypocalcaemia . Almost twice as many infants in the control group were small for gestational age ( 29 % v 15 % ) , but there were no significant differences between the two groups of infants in antropometric measurements . Infants in the control group , however , had larger fontanelles , suggesting impaired ossification of the skull . Because of the benefits to mothers and infants in the treatment group and the absence of side effects , vitamin D supplements should be given to all pregnant Asian women in the United Kingdom", "Summary Background Vitamin D has a role in regulating immune function , and its deficiency is a suggested risk factor for childhood pneumonia . Our aim was to assess whether oral supplementation of vitamin D3 ( cholecalciferol ) will reduce the incidence and severity of pneumonia in a high-risk infant population . Methods We did a r and omised placebo-controlled trial to compare oral 100 000 IU ( 2·5 mg ) vitamin D3 with placebo given to children aged 1–11 months in Kabul , Afghanistan . R and omisation was by use of a computer-generated list . Vitamin D or placebo was given by fieldworkers once every 3 months for 18 months . Children presenting at the study hospital with signs of pneumonia had their diagnosis confirmed radiographically . Our primary outcome was the first or only episode of radiologically confirmed pneumonia . Our analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00548379 . Findings 1524 children were assigned to receive vitamin D3 and 1522 placebo . There was no significant difference between the incidence of first or only pneumonia between the vitamin D ( 0·145 per child per year , 95 % CI 0·129–0·164 ) and the placebo group ( 0.137 , 0·121–0·155 ) ; the incidence rate ratio was 1·06 ( 95 % CI 0·89–1·27 ) . From 652 children during five separate periods of testing serum calcifediol , only one child in each of two testing periods had results greater than 375 nmol/L in the intervention group — a toxic level . Interpretations Quarterly bolus doses of oral vitamin D3 supplementation to infants are not an effective intervention to reduce the incidence of pneumonia in infants in this setting . Funding Wellcome Trust and British Council", "BACKGROUND Vitamin D has potent anticancer properties , especially against digestive-system cancers . Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure . Here , we considered multiple determinants of vitamin D exposure ( dietary and supplementary vitamin D , skin pigmentation , adiposity , geographic residence , and leisure-time physical activity-to estimate sunlight exposure ) in relation to cancer risk in the Health Professionals Follow-Up Study . METHODS Among 1095 men of this cohort , we quantified the relation of these six determinants to plasma 25-hydroxy-vitamin D [ 25(OH)D ] level by use of a multiple linear regression model . We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics . We then prospect ively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models . RESULTS From 1986 through January 31 , 2000 , we documented 4286 incident cancers ( excluding organ-confined prostate cancer and nonmelanoma skin cancer ) and 2025 deaths from cancer . From multivariable models , an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17 % reduction in total cancer incidence ( multivariable relative risk [ RR ] = 0.83 , 95 % confidence interval [ CI ] = 0.74 to 0.92 ) , a 29 % reduction in total cancer mortality ( RR = 0.71 , 95 % CI = 0.60 to 0.83 ) , and a 45 % reduction in digestive-system cancer mortality ( RR = 0.55 , 95 % CI = 0.41 to 0.74 ) . The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile ; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality . Results were similar when we controlled further for body mass index or physical activity level . CONCLUSIONS Low levels of vitamin D may be associated with increased cancer incidence and mortality in men , particularly for digestive-system cancers . The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day", " Respiratory tract infections ( RTIs ) are very common worldwide . We prospect ively demonstrate an association between low serum 25-hydroxyvitamin D level and increased risk of laboratory-confirmed viral upper RTI in children . Future studies should evaluate the role of supplementation to reduce RTIs", "Most cancer epidemiologists would cite results from a r and omized clinical trial as both the ultimate arbiter of controversial findings from observational studies and the basis for cancer control interventions . Indeed , we consider a trial definitive when its intervention demonstrably lowers", "Background Epidemiological research links vitamin D status to various brain-related outcomes . However , few trials examine whether supplementation can improve such outcomes and none have examined effects on cognition . This study examined whether Vitamin D supplementation led to improvements in diverse measures of cognitive and emotional functioning , and hypothesised that supplementation would lead to improvements in these outcomes compared to placebo . Methods /Principal Findings Healthy young adults were recruited to a parallel-arm , double-blind trial conducted at The University of Queensl and . Participants were r and omly allocated to receive Vitamin D ( one capsule daily , containing 5000 IU cholecalciferol ) or identical placebo capsule for six weeks . All participants and outcome assessors were blinded to group assignment . Primary outcome measures assessed at baseline and 6 weeks were working memory , response inhibition and cognitive flexibility . Secondary outcomes were : hallucination-proneness , psychotic-like experiences , and ratings of depression , anxiety and anger . 128 participants were recruited , r and omised and included in primary analyses ( vitamin D n = 63 ; placebo n = 65 ) . Despite significant increases in vitamin D status in the active group , no significant changes were observed in working memory ( F = 1.09 ; p = 0.30 ) , response inhibition ( F = 0.82 ; p = 0.37 ) , cognitive flexibility ( F = 1.37 ; p = 0.24 ) or secondary outcomes . No serious adverse effects were reported . Conclusions Our findings indicate that vitamin D supplementation does not influence cognitive or emotional functioning in healthy young adults . Future controlled trials in targeted population s of interest are required to determine whether supplementation can improve functioning in these domains . Australian and New Zeal and Clinical Trials Registry ; ACTRN12610000318088", "BACKGROUND Seasonal Affective Disorder ( SAD ) is a sub-type of depression that only occurs during the winter months . A reduction in vitamin D may be linked to SAD . Since vitamin D deficiency has been reported to be common in older people , vitamin D supplementation may be expected to reduce seasonal mood disturbance in this group . OBJECTIVE To assess the effect of vitamin D supplementation on the mental health of older women . SETTING Primary care in three areas of the UK ( Herts , Newcastle , York ) . SUBJECTS Women aged 70 years or more recruited to the trial in the months May-October . INTERVENTION Eligible women were r and omised to receive calcium and vitamin D supplementation or no supplementation . OUTCOME MEASURE At baseline and the six monthly assessment the mental component score ( MCS ) , calculated from the SF-12 question naire was used to assess participants ' subjective psychological well-being . RESULTS A total of 2117 women recruited to the trial had their baseline measures taken between the months of May-October ( 1205 woman in the control group and 912 women in the intervention group ) . Of these women , 1621 had a MCS score at baseline and six months . Comparison of the six month mean MCS scores , adjusting for baseline MCS score and age , showed there was no significant difference between the two scores ( p = 0.262 ) . CONCLUSIONS Supplementing elderly women with 800 IU of vitamin D daily did not lead to an improvement in mental health scores", "BACKGROUND Results of several epidemiologic and clinical studies have suggested that there is an excess risk of hypertension and diabetes mellitus in persons with suboptimal intake of vitamin D. METHODS We examined the association between serum levels of 25-hydroxyvitamin D ( 25[OH]D ) and select cardiovascular disease risk factors in US adults . A secondary analysis was performed with data from the Third National Health and Nutrition Examination Survey , a national probability survey conducted by the National Center for Health Statistics between January 1 , 1988 , and December 31 , 1994 , with oversampling of persons 60 years and older , non-Hispanic black individuals , and Mexican American individuals . RESULTS There were 7186 male and 7902 female adults 20 years and older with available data in the Third National Health and Nutrition Examination Survey . The mean 25(OH)D level in the overall sample was 30 ng/mL ( 75 nmol/L ) . The 25(OH)D levels were lower in women , elderly persons ( > or=60 years ) , racial/ethnic minorities , and participants with obesity , hypertension , and diabetes mellitus . The adjusted prevalence of hypertension ( odds ratio [ OR ] , 1.30 ) , diabetes mellitus ( OR , 1.98 ) , obesity ( OR , 2.29 ) , and high serum triglyceride levels ( OR , 1.47 ) was significantly higher in the first than in the fourth quartile of serum 25(OH)D levels ( P Serum 25(OH)D levels are associated with important cardiovascular disease risk factors in US adults . Prospect i ve studies to assess a direct benefit of cholecalciferol ( vitamin D ) supplementation on cardiovascular disease risk factors are warranted", "OBJECTIVES The objective of the present study was to examine the cross-sectional relation between serum 25-hydroxyvitamin D [ 25-(OH ) D ] levels and depression in overweight and obese subjects and to assess the effect of vitamin D supplementation on depressive symptoms . DESIGN Cross-sectional study and r and omized double blind controlled trial of 20,000 or 40,000 IU vitamin D per week versus placebo for 1 year . SETTING A total of 441 subjects ( body mass index 28 - 47 kg m(-2 ) , 159 men and 282 women , aged 21 - 70 years ) recruited by advertisements or from the out-patient clinic at the University Hospital of North Norway . MAIN OUTCOME MEASURES Beck Depression Inventory ( BDI ) score with subscales 1 - 13 and 14 - 21 . RESULTS Subjects with serum 25(OH)D levels depressive traits ) than those with serum 25(OH)D levels > or = 40 nmol L(-1 ) on the BDI total [ 6.0 ( 0 - 23 ) versus 4.5 ( 0 - 28 ) ( median and range ) ] and the BDI subscale 1 - 13 [ 2.0 ( 0 - 15 ) versus 1.0 ( 0 - 29.5 ) ] ( P vitamin D , but not in the placebo group , there was a significant improvement in BDI scores after 1 year . There was a significant decrease in serum parathyroid hormone in the two vitamin D groups without a concomitant increase in serum calcium . CONCLUSIONS It appears to be a relation between serum levels of 25(OH)D and symptoms of depression . Supplementation with high doses of vitamin D seems to ameliorate these symptoms indicating a possible causal relationship", "Importance Evidence suggests that low vitamin D status may increase the risk of cancer . Objective To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of cancer among older women . Design , Setting , and Participants A 4-year , double-blind , placebo-controlled , population -based r and omized clinical trial in 31 rural counties ( June 24 , 2009 , to August 26 , 2015—the final date of follow-up ) . A total of 2303 healthy postmenopausal women 55 years or older were r and omized , 1156 to the treatment group and 1147 to the placebo group . Duration of treatment was 4 years . Interventions The treatment group ( vitamin D3 + calcium group ) received 2000 IU/d of vitamin D3 and 1500 mg/d of calcium ; the placebo group received identical placebos . Main Outcomes and Measures The primary outcome was the incidence of all-type cancer ( excluding nonmelanoma skin cancers ) , which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling . Results Among 2303 r and omized women ( mean age , 65.2 years [ SD , 7.0 ] ; mean baseline serum 25-hydroxyvitamin D level , 32.8 ng/mL [ SD , 10.5 ] ) , 2064 ( 90 % ) completed the study . At year 1 , serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group . A new diagnosis of cancer was confirmed in 109 participants , 45 ( 3.89 % ) in the vitamin D3 + calcium group and 64 ( 5.58 % ) in the placebo group ( difference , 1.69 % [ 95 % CI , −0.06 % to 3.46 % ] ; P = .06 ) . Kaplan-Meier incidence over 4 years was 0.042 ( 95 % CI , 0.032 to 0.056 ) in the vitamin D3 + calcium group and 0.060 ( 95 % CI , 0.048 to 0.076 ) in the placebo group ; P = .06 . In unadjusted Cox proportional hazards regression , the hazard ratio was 0.70 ( 95 % CI , 0.47 to 1.02 ) . Adverse events potentially related to the study included renal calculi ( 16 participants in the vitamin D3 + calcium group and 10 in the placebo group ) , and elevated serum calcium levels ( 6 in the vitamin D3 + calcium group and 2 in the placebo group ) . Conclusions and Relevance Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL , supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years . Further research is necessary to assess the possible role of vitamin D in cancer prevention . Trial Registration clinical trials.gov Identifier :", "BACKGROUND Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials . However , r and omized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking . METHODS We conducted a r and omized , double-blind , placebo-controlled trial involving 36,282 postmenopausal women from 40 Women 's Health Initiative centers : 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [ corrected ] twice daily ( 1000 mg of elemental calcium and 400 IU of vitamin D3 ) and 18,106 received a matching placebo for an average of 7.0 years . The incidence of pathologically confirmed colorectal cancer was the design ated secondary outcome . Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study . RESULTS The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo ( 168 and 154 cases ; hazard ratio , 1.08 ; 95 percent confidence interval , 0.86 to 1.34 ; P=0.51 ) , and the tumor characteristics were similar in the two groups . The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups . There were no significant treatment interactions with baseline characteristics . CONCLUSIONS Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women . The long latency associated with the development of colorectal cancer , along with the seven-year duration of the trial , may have contributed to this None finding . Ongoing follow-up will assess the longer-term effect of this intervention . ( Clinical Trials.gov number , NCT00000611 . )", "Higher vitamin D concentrations have been proposed as a protective ' seasonal stimulus ' against influenza , and there are suggestions for associations with other aspects of respiratory health . The aim of the present study was to investigate the relationship of current vitamin D status ( measured by 25-hydroxyvitamin D , 25(OH)D ) with respiratory infections and lung function . We used cross-sectional data from 6789 participants in the nationwide 1958 British birth cohort who had measurements of 25(OH)D , lung function ( forced expiratory volume in 1 s ( FEV1 ) and forced vital capacity ( FVC ) ) and respiratory infections available from the age of 45 years . In this population , the prevalence of respiratory infections had a strong seasonal pattern in the opposite direction to the pattern for 25(OH)D concentrations . Each 10 nmol/l increase in 25(OH)D was associated with a 7 % lower risk of infection ( 95 % CI 3 , 11 % ) after adjustment for adiposity , lifestyle and socio-economic factors . For FEV1 and FVC , each 10 nmol/l increase in 25(OH)D was associated with 8 ( 95 % CI 3 , 13 ) ml and 13 ( 95 % CI 7 , 20 ) ml higher volume , respectively , after controlling for covariates . Associations of 25(OH)D with FEV1 and FVC were only slightly attenuated after further adjustment for infection and other respiratory illness . In conclusion , vitamin D status had a linear relationship with respiratory infections and lung function . R and omised controlled trials are warranted to investigate the role of vitamin D supplementation on respiratory health and to establish the underlying mechanisms", "Abstract Mood changes synchronised to the seasons exist on a continuum between individuals , with anxiety and depression increasing during the winter months . An extreme form of seasonality is manifested as the clinical syndrome of seasonal affective disorder ( SAD ) with carbohydrate craving , hypersomnia , lethargy , and changes in circadian rhythms also evident . It has been suggested that seasonality and the symptoms of SAD may be due to changing levels of vitamin D3 , the hormone of sunlight , leading to changes in brain serotonin . Forty-four healthy subjects were given 400 IU , 800 IU , or no vitamin D3 for 5 days during late winter in a r and om double-blind study . Results on a self-report measure showed that vitamin D3 significantly enhanced positive affect and there was some evidence of a reduction in negative affect . Results are discussed in terms of their implication s for seasonality , SAD , serotonin , food preference , sleep , and circadian rhythms", "BACKGROUND Recent studies suggest a role for vitamin D in innate immunity , including the prevention of respiratory tract infections ( RTIs ) . We hypothesize that serum 25-hydroxyvitamin D ( 25[OH]D ) levels are inversely associated with self-reported recent upper RTI ( URTI ) . METHODS We performed a secondary analysis of the Third National Health and Nutrition Examination Survey , a probability survey of the US population conducted between 1988 and 1994 . We examined the association between 25(OH)D level and recent URTI in 18 883 participants 12 years and older . The analysis adjusted for demographics and clinical factors ( season , body mass index , smoking history , asthma , and chronic obstructive pulmonary disease ) . RESULTS The median serum 25(OH)D level was 29 ng/mL ( to convert to nanomoles per liter , multiply by 2.496 ) ( interquartile range , 21 - 37 ng/mL ) , and 19 % ( 95 % confidence interval [ CI ] , 18%-20 % ) of participants reported a recent URTI . Recent URTI was reported by 24 % of participants with 25(OH)D levels less than 10 ng/mL , by 20 % with levels of 10 to less than 30 ng/mL , and by 17 % with levels of 30 ng/mL or more ( P 25(OH)D levels were independently associated with recent URTI ( compared with 25[OH]D levels of > or = 30 ng/mL : odds ratio [ OR ] , 1.36 ; 95 % CI , 1.01 - 1.84 for 25(OH)D level and URTI seemed to be stronger in individuals with asthma and chronic obstructive pulmonary disease ( OR , 5.67 and 2.26 , respectively ) . CONCLUSIONS Serum 25(OH)D levels are inversely associated with recent URTI . This association may be stronger in those with respiratory tract diseases . R and omized controlled trials are warranted to explore the effects of vitamin D supplementation on RTI", "Evidence for a role of supplemental vitamin D and marine omega-3 fatty acids in preventing cancer and cardiovascular disease ( CVD ) remains inconclusive and insufficient to inform nutritional recommendations for primary prevention . The VITamin D and Omega-A 3 TriaL ( VITAL ) is an ongoing nationwide , r and omized , double-blind , placebo-controlled clinical trial design ed to fill this knowledge gap . The study population consists of 25,874 U.S. adults without cancer or CVD at baseline , who were selected only on age ( men aged ≥50 and women aged ≥55 ) , with an oversampling of African Americans ( n=5,107 ) . In a 2 × 2 factorial design , participants were r and omized to one of four supplement groups : [ 1 ] active vitamin D3 ( cholecalciferol ; 2000 IU/d ) and active marine omega-3 fatty acids ( Omacor ® fish oil , eicosapentaenoic acid [ EPA ] and docosahexaenoic acid [ DHA ] , 1g/d ) ; [ 2 ] active vitamin D and omega-3 placebo ; [ 3 ] vitamin D placebo and active marine omega-3 fatty acids ; or [ 4 ] vitamin D placebo and omega-3 placebo . The mean length of the r and omized treatment period will be 5 years . The r and omization was successful , as evidence d by similar distributions of baseline demographic , health , and behavioral characteristics across treatment groups . The similar distribution of known potential confounders across treatment groups strongly suggests that unmeasured or unknown potential confounders are also equally distributed . VITAL is expected to provide important information on the benefit-risk balance of vitamin D and omega-3 fatty acid supplementation when taken for the primary prevention of cancer and CVD", "BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo . Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . )", "Abstract The correlation between vitamin D deficiency and depression has recently been put forward and result ed in controversial findings . The present study was conducted to find out the effect of 2 single injections of 150,000 and 300,000 IU of vitamin D on improving the depression in depressed patients with vitamin D deficiency . This clinical trial study was carried out during 2011–2012 in Yazd , Islamic Republic of Iran . A total of 120 patients who had a Beck Depression Inventory II score of 17 + and were affected with vitamin D deficiency were r and omly assigned to 3 groups of 40 . They included G300 , G150 , and NTG . G300 and G150 received an intramuscular single dose of 300,000 and 150,000 IU of vitamin D , respectively , and the NTG group received nothing . After 3 months of intervention , the depression state , serum vitamin D , calcium , phosphorus , and parathormone were measured . The median of serum vitamin D after intervention were 60.2 , 54.6 , and 28.2 nmol/L ( P Percentages of vitamin D deficiency after intervention were 18 , 20 , and 91.2 for the groups , respectively . The serum calcium mean showed a statistically significant increase in just the 2 test groups receiving vitamin D. There was only significant difference in mean of Beck Depression Inventory II test score between G300 and NTG ( P = 0.003).The results of the study revealed that first , the correction of vitamin D deficiency improved the depression state , and second , a single injection dose of 300,000 IU of vitamin D was safe and more effective than a 150,000-IU dose", "IMPORTANCE Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension . No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension , the most common pattern of hypertension in older people . OBJECTIVE To test whether high-dose , intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension . DESIGN Parallel group , double-blind , placebo-controlled r and omized trial . SETTING Primary care clinics and hospital clinics . PARTICIPANTS Patients 70 years and older with isolated systolic hypertension ( supine systolic blood pressure > 140 mm Hg and supine diastolic blood pressure INTERVENTIONS A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year . MAIN OUTCOMES AND MEASURES Difference in office blood pressure , 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , insulin resistance , and b-type natriuretic peptide level during 12 months . RESULTS A total of 159 participants were r and omized ( mean age , 77 years ) . Mean baseline office systolic blood pressure was 163/78 mm Hg . Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group ( + 8 ng/mL at 1 year , P ) office blood pressure ( −1 [ −6 to 4]/−2 [ −4 to 1 ] mm Hg at 3 months and 1 [ −2 to 4]/0 [ −2 to 2 ] mm Hg overall treatment effect ) . No significant treatment effect was evident for any of the secondary outcomes ( 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , glucose level , and walking distance ) . There was no excess of adverse events in the treatment group , and the total number of falls was nonsignificantly lower in the group receiving vitamin D ( 36 vs 46 , P = .24 ) . CONCLUSIONS AND RELEVANCE Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N92186858", "OBJECTIVES To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation . DESIGN A r and omised controlled trial of cluster design . SETTING AND SUBJECTS 223 Residential units ( mainly identical 30-bedded units ) , within 118 homes for elderly people throughout Britain , with 3,717 participating residents ( 76 % women , average age 85 years ) . The units provided mainly or entirely residential care ( 35 % of residents ) , nursing care ( 42 % ) or care for elderly mentally infirm ( EMI ) residents ( 23 % ) . METHODS Participants were r and omly allocated by residential unit ( cluster design ) to a treated group offered ergocalciferol 2.5 mg every 3 months ( equivalent to a daily dose of 1,100 IU ) , or to a control group . Fractures were reported by staff and confirmed in hospital , and routinely collected data on reported falls were obtained . RESULTS After median follow-up of 10 months ( interquartile range 7 - 14 months ) , 64 ( 3.6 % ) of 1,762 vitamin D-treated residents and 51 ( 2.6 % ) of 1,955 controls had one or more non-vertebral fractures , and 24 ( 1.3 % ) and 20 ( 1.0 % ) , respectively , had a hip fracture . The proportion reporting at least one fall was 44 % in vitamin D-treated and 43 % in control residents . The differences between the vitamin D and control groups were not statistically significant . The incidence of all non-vertebral fractures in the care homes ( 3.2 % per year ) and of hip fractures ( 1.1 % per year ) was low , similar to rates in elderly people in sheltered accommodation , and the pre-treatment serum 25-hydroxy vitamin D concentration was high [ median 47 nmol/l , measured in a 1 % ( n = 18 ) sample ] . CONCLUSIONS We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation", "Calcium supplementation is effective in reducing blood pressure in various states of hypertension , including pregnancy-induced hypertension and preeclampsia . In addition , calcitropic hormones are associated with blood pressure . The hypothesis is that short-term therapy with calcium and vitamin D(3 ) may improve blood pressure as well as secondary hyperparathyroidism more effectively than calcium monotherapy . The effects of 8 weeks of supplementation with vitamin D(3 ) ( cholecalciferol ) and calcium on blood pressure and biochemical measures of bone metabolism were studied . The sample consisted of 148 women ( mean + /- SD age , 74 + /- 1 yr ) with a 25-hydroxycholecalciferol ( 25OHD(3 ) ) level below 50 nmol/L. They received either 1200 mg calcium plus 800 IU vitamin D(3 ) or 1200 mg calcium/day . We measured intact PTH , 25OHD(3 ) , 1,25-dihydroxyvitamin D(3 ) , blood pressure , and heart rate before and after treatment . Compared with calcium , supplementation with vitamin D(3 ) and calcium result ed in an increase in serum 25OHD(3 ) of 72 % ( P serum PTH of 17 % ( P = 0.04 ) , a decrease in systolic blood pressure ( SBP ) of 9.3 % ( P = 0.02 ) , and a decrease in heart rate of 5.4 % ( P = 0.02 ) . Sixty subjects ( 81 % ) in the vitamin D(3 ) and calcium group compared with 35 ( 47 % ) subjects in the calcium group showed a decrease in SBP of 5 mm Hg or more ( P = 0.04 ) . No statistically significant difference was observed in the diastolic blood pressures of the calcium-treated and calcium- plus vitamin D(3)-treated groups ( P = 0.10 ) . Pearson coefficients of correlation between the change in PTH and the change in SBP were 0.49 ( P vitamin D(3 ) plus calcium group and 0.23 ( P calcium group . A short-term supplementation with vitamin D(3 ) and calcium is more effective in reducing SBP than calcium alone . Inadequate vitamin D(3 ) and calcium intake could play a contributory role in the pathogenesis and progression of hypertension and cardiovascular disease in elderly women", "Although geographic ecological studies and observational studies find that ultraviolet B exposure and 25-hydroxyvitamin D [ 25(OH)D ] concentrations are inversely correlated with 15–20 types of cancer , few r and omized controlled trials ( RCTs ) of vitamin D support those findings . The poor design of some RCTs may account for that lack of support . Most vitamin D RCTs to date have considered the vitamin D dose , rather than initial , final , or changes in , serum 25(OH)D concentrations . Here a model is developed for use in design ing and analyzing vitamin D RCTs with application to cancer incidence . The input variables of the model are vitamin D dose , baseline and achieved 25(OH)D concentrations , known rates of cancer for the population , and numbers of participants for the treatment and placebo arms is estimated — vitamin D dosage and numbers of participants are varied to achieve desired hazard ratio significance , using information from two vitamin D RCTs on cancer incidence conducted in Nebraska with good agreement between the model estimates and reported hazard ratios . Further improvements to the conduct of vitamin D RCTs would be to start the trial with a moderate bolus dose to achieve the desired 25(OH)D concentrations , and bloodspot 25(OH)D assay use in summer and winter annually to monitor seasonal and long-term changes in 25(OH)D concentration and compliance , and to allow dosage adjustment for achievement of desired vitamin D status", "Seasonal Affective Disorder ( SAD ) is prevalent when vitamin D stores are typically low . Broad-spectrum light therapy includes wavelengths between 280 - 320 nm which allow the skin to produce vitamin D. This study was design ed to test the hypothesis that vitamin D deficiency might play a role in SAD . A prospect i ve , r and omized controlled trial was conducted in a group of 15 subjects with SAD . Eight subjects received 100,000 I.U. of vitamin D and seven subjects received phototherapy . At the onset of treatment and after 1 month of therapy subjects were administered the Hamilton Depression scale , the SIGH-SAD , and the SAD-8 depression scale . All subjects also had serum levels of 25-hydroxyvitamin D ( 25-OH D ) measured before and 1 week after intervention therapy . All subjects receiving vitamin D improved in all outcome measures . The phototherapy group showed no significant change in depression scale measures . Vitamin D status improved in both groups ( 74 % vitamin D group , p Improvement in 25-OH D was significantly associated with improvement in depression scale scores ( r2=0.26 ; p=0.05 ) . Vitamin D may be an important treatment for SAD . Further studies will be necessary to confirm these findings", "Objective : To compare the therapeutic effects of vitamin D3 plus fluoxetine and fluoxetine alone in patients with major depressive disorder . Methods : In the present double-blind , r and omized , placebo-controlled trial , 42 patients with a diagnosis of major depressive disorder based on DSM-IV criteria were r and omly assigned into two groups to receive daily either 1500 IU vitamin D3 plus 20 mg fluoxetine or fluoxetine alone for 8 weeks . Depression severity was assessed at 2-week intervals using the 24-item Hamilton Depression Rating Scale ( HDRS ) as a primary outcome measure and the 21-item Beck Depression Inventory ( BDI ) as a secondary outcome measure . Serum 25(OH ) vitamin D was measured at baseline and after intervention . Results : Forty patients completed the trial . A two-way repeated- measures analysis of variance showed that depression severity based on HDRS and BDI decreased significantly after intervention , with a significant difference between the two groups . The vitamin D + fluoxetine combination was significantly better than fluoxetine alone from the fourth week of treatment . Conclusions : In the present 8-week trial , the vitamin D + fluoxetine combination was superior to fluoxetine alone in controlling depressive symptoms", "BACKGROUND In cross-sectional studies , low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease . This study aim ed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality . METHODS Prospect i ve cohort study of 3258 consecutive male and female patients ( mean [ SD ] age , 62 [ 10 ] years ) scheduled for coronary angiography at a single tertiary center . We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings . The main outcome measures were all-cause and cardiovascular deaths . RESULTS During a median follow-up period of 7.7 years , 737 patients ( 22.6 % ) died , including 463 deaths from cardiovascular causes . Multivariate-adjusted hazard ratios ( HRs ) for patients in the lower two 25-hydroxyvitamin D quartiles ( median , 7.6 and 13.3 ng/mL [ to convert 25-hydroxyvitamin D levels to nanomoles per liter , multiply by 2.496 ] ) were higher for all-cause mortality ( HR , 2.08 ; 95 % confidence interval [ CI ] , 1.60 - 2.70 ; and HR , 1.53 ; 95 % CI , 1.17 - 2.01 ; respectively ) and for cardiovascular mortality ( HR , 2.22 ; 95 % CI , 1.57 - 3.13 ; and HR , 1.82 ; 95 % CI , 1.29 - 2.58 ; respectively ) compared with patients in the highest 25-hydroxyvitamin D quartile ( median , 28.4 ng/mL ) . Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile . These effects were independent of coronary artery disease , physical activity level , Charlson Comorbidity Index , variables of mineral metabolism , and New York Heart Association functional class . Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation ( C-reactive protein and interleukin 6 levels ) , oxidative burden ( serum phospholipid and glutathione levels ) , and cell adhesion ( vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels ) . CONCLUSIONS Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality . A causal relationship has yet to be proved by intervention trials using vitamin", "Objective : Results from studies examining associations between serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations and depressive symptoms are equivocal . We investigated the relationship between serum 25(OH)D concentrations and symptoms of depression , anxiety and stress in a cross-sectional analysis of a population -based sample of young adults participating in the Western Australian Pregnancy Cohort ( Raine ) Study . Methods : Participants provided a blood sample at the 20-year follow-up ( March 2010-April 2012 ) for the measurement of serum 25(OH)D concentrations . Mental health symptoms were assessed using the 21-item Depression Anxiety Stress Scales ( DASS-21 ) . Associations between serum 25(OH)D concentrations and total DASS-21 scores and subscale scores of depression , anxiety and stress were explored in males and females using negative binomial regression , adjusting for age , race , body mass index ( BMI ) and physical activity ( n=735 ) . Models examining subscale scores were also adjusted for the other subscale scores . Results : After adjusting for confounders , an increase in serum 25(OH)D concentrations of 10 nmol/L decreased total DASS-21 scores in males by 9 % ( rate ratio ( RR ) 0.91 ; 95%CI 0.87,0.95 ; p depression subscale scores in males by 8 % ( RR 0.92 ; 95%CI 0.87,0.96 ; p=0.001 ) . However , in adjusted models there were no significant associations between serum 25(OH)D concentrations and symptoms of anxiety and stress in males . There were no significant associations between serum 25(OH)D concentrations and symptoms of depression , anxiety and stress in females . Conclusions : We found an association between serum 25(OH)D concentrations and symptoms of depression , but not anxiety and stress , in males . R and omised controlled trials are necessary to determine any benefit of vitamin D supplementation in the prevention and treatment of depressive symptoms in young adults", "Data from laboratory studies , observational research , and /or secondary prevention trials suggest that vitamin D and marine omega-3 fatty acids may reduce risk for cancer or cardiovascular disease ( CVD ) , but primary prevention trials with adequate dosing in general population s ( i.e. , unselected for disease risk ) are lacking . The ongoing VITamin D and OmegA-3 TriaL ( VITAL ) is a large r and omized , double-blind , placebo-controlled , 2 x 2 factorial trial of vitamin D ( in the form of vitamin D(3 ) [ cholecalciferol ] , 2000 IU/day ) and marine omega-3 fatty acid ( Omacor fish oil , eicosapentaenoic acid [EPA]+docosahexaenoic acid [ DHA ] , 1g/day ) supplements in the primary prevention of cancer and CVD among a multi-ethnic population of 20,000 U.S. men aged ≥ 50 and women aged ≥ 55 . The mean treatment period will be 5 years . Baseline blood sample s will be collected in at least 16,000 participants , with follow-up blood collection in about 6000 participants . Yearly follow-up question naires will assess treatment compliance ( plasma biomarker measures will also assess compliance in a r and om sample of participants ) , use of non- study drugs or supplements , occurrence of endpoints , and cancer and vascular risk factors . Self-reported endpoints will be confirmed by medical record review by physicians blinded to treatment assignment , and deaths will be ascertained through national registries and other sources . Ancillary studies will investigate whether these agents affect risk for diabetes and glucose intolerance ; hypertension ; cognitive decline ; depression ; osteoporosis and fracture ; physical disability and falls ; asthma and other respiratory diseases ; infections ; and rheumatoid arthritis , systemic lupus erythematosus , thyroid diseases , and other autoimmune disorders", "While observational studies have suggested that vitamin D deficiency increases risk of depression , few clinical trials have tested whether vitamin D supplementation affects the occurrence of depression symptoms . The authors evaluated the impact of daily supplementation with 400 IU of vitamin D(3 ) combined with 1,000 mg of elemental calcium on measures of depression in a r and omized , double-blinded US trial comprising 36,282 postmenopausal women . The Burnam scale and current use of antidepressant medication were used to assess depressive symptoms at r and omization ( 1995 - 2000 ) . Two years later , women again reported on their antidepressant use , and 2,263 completed a second Burnam scale . After 2 years , women r and omized to receive vitamin D and calcium had an odds ratio for experiencing depressive symptoms ( Burnam score ≥0.06 ) of 1.16 ( 95 % confidence interval : 0.86 , 1.56 ) compared with women in the placebo group . Supplementation was not associated with antidepressant use ( odds ratio = 1.01 , 95 % confidence interval : 0.92 , 1.12 ) or continuous depressive symptom score . Results stratified by baseline vitamin D and calcium intake , solar irradiance , and other factors were similar . The findings do not support a relation between supplementation with 400 IU/day of vitamin D(3 ) along with calcium and depression in older women . Additional trials testing higher doses of vitamin D are needed to determine whether this nutrient may help prevent or treat depression ", "& NA ; A r and omized study was conducted to evaluate the effects of single‐dose and daily vitamin D supplementation in pregnant women during the last trimester of a winter pregnancy in the Northwest of France . The women were divided into three r and omized groups : one ( N = 21 ) was given a vitamin D2 supplement of 1000 IU/day during the last three months of pregnancy , one ( N = 27 ) was given a single oral dose of 5 mg at the seventh month of pregnancy , and one ( N = 29 ) acted as a control . Venous plasma sample s were obtained at delivery from the women and from cord blood , and levels of calcium , 25‐OHD , and 1,25(OH)2D were determined . No significant difference in plasma calcium concentration was found among the three groups , but within each group plasma calcium concentrations were higher in the cord sample s than in the respective maternal sample s. The levels of the two metabolites measured were consistently lower in the cord sample s than in the respective maternal sample s. Cord 25‐OHD concentrations correlated with those of maternal plasma . No significant modification of maternal calciuria or of the birth weight of term infants was observed . 25‐OHD concentrations were greater in maternal and cord plasma from treated mothers , but only a slight difference was observed between the supplemented groups . 1,25(OH)2D concentrations were not significantly different in the three groups . A single 5‐mg dose of vitamin D given orally at the seventh month of pregnancy provides effective prophylaxis in the authors ’ region . ( Obstet Gynecol 68:300 , 1986", "CONTEXT Vitamin D or calcium supplementation may have effects on vascular disease and cancer . OBJECTIVE Our objective was to investigate whether vitamin D or calcium supplementation affects mortality , vascular disease , and cancer in older people . DESIGN AND SETTING The study included long-term follow-up of participants in a two by two factorial , r and omized controlled trial from 21 orthopedic centers in the United Kingdom . PARTICIPANTS Participants were 5292 people ( 85 % women ) aged at least 70 yr with previous low-trauma fracture . INTERVENTIONS Participants were r and omly allocated to daily vitamin D(3 ) ( 800 IU ) , calcium ( 1000 mg ) , both , or placebo for 24 - 62 months , with a follow-up of 3 yr after intervention . MAIN OUTCOME MEASURES All-cause mortality , vascular disease mortality , cancer mortality , and cancer incidence were evaluated . RESULTS In intention-to-treat analyses , mortality [ hazard ratio ( HR ) = 0.93 ; 95 % confidence interval ( CI ) = 0.85 - 1.02 ] , vascular disease mortality ( HR = 0.91 ; 95 % CI = 0.79 - 1.05 ) , cancer mortality ( HR = 0.85 ; 95 % CI = 0.68 - 1.06 ) , and cancer incidence ( HR = 1.07 ; 95 % CI = 0.92 - 1.25 ) did not differ significantly between participants allocated vitamin D and those not . All-cause mortality ( HR = 1.03 ; 95 % CI = 0.94 - 1.13 ) , vascular disease mortality ( HR = 1.07 ; 95 % CI = 0.92 - 1.24 ) , cancer mortality ( HR = 1.13 ; 95 % CI = 0.91 - 1.40 ) , and cancer incidence ( HR = 1.06 ; 95 % CI = 0.91 - 1.23 ) also did not differ significantly between participants allocated calcium and those not . In a post hoc statistical analysis adjusting for compliance , thus with fewer participants , trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated , although all results remain nonsignificant . CONCLUSIONS Daily vitamin D or calcium supplementation did not affect mortality , vascular disease , cancer mortality , or cancer incidence", "BACKGROUND Frequent use of personal , non protocol calcium supplements obscured an adverse effect of coadministered calcium and vitamin D ( CaD ) on cardiovascular risk in the Women 's Health Initiative ( WHI ) . OBJECTIVE We investigated the effects of the use of personal calcium or vitamin D supplements on other outcomes in the WHI CaD Study ( WHI CaD ) by using the WHI limited-access clinical trials data set . DESIGN The WHI CaD was a 7-y , r and omized , placebo-controlled trial of CaD ( 1 g Ca/400 IU vitamin D daily ) in 36,282 community-dwelling , postmenopausal women . The incidence of total cancer ( excluding nonmelanoma skin cancers ) , breast and colorectal cancers , hip and total fracture , and mortality was assessed by using Cox proportional hazards models . RESULTS In the WHI CaD , interactions between the use of either personal calcium or vitamin D supplements and CaD were found for total , breast , and colorectal cancers but not for fracture or mortality . In 15,646 women ( 43 % ) who were not taking personal calcium or vitamin D supplements at r and omization , CaD significantly decreased the risk of total , breast , and invasive breast cancers by 14 - 20 % and nonsignificantly reduced the risk of colorectal cancer by 17 % . In women taking personal calcium or vitamin D supplements , CaD did not alter cancer risk ( HR : 1.06 - 1.26 ) . CONCLUSIONS For women in the WHI CaD who were not taking personal calcium or vitamin D supplements at r and omization , CaD decreased the risk of total , breast , and colorectal cancers and did not change the risk of fractures or total mortality . The nonskeletal effects of CaD may be more important than the skeletal effects and should be considered when evaluating these supplements . The WHI CaD trial is registered at clinical trials.gov as NCT00000611", "Observational studies in primary hyperaldosteronism suggest a positive relationship between aldosterone and parathyroid hormone ( PTH ) ; however , interventions to better characterize the physiological relationship between the renin – angiotensin – aldosterone system ( RAAS ) and PTH are needed . We evaluated the effect of individual RAAS components on PTH using 4 interventions in humans without primary hyperaldosteronism . PTH was measured before and after study ( 1 ) low-dose angiotensin II ( Ang II ) infusion ( 1 ng/kg per minute ) and captopril administration ( 25 mg × 1 ) ; study ( 2 ) high-dose Ang II infusion ( 3 ng/kg per minute ) ; study ( 3 ) blinded crossover r and omization to aldosterone infusion ( 0.7 µg/kg per hour ) and vehicle ; and study ( 4 ) blinded r and omization to spironolactone ( 50 mg/daily ) or placebo for 6 weeks . Infusion of Ang II at 1 ng/kg per minute acutely increased aldosterone ( + 148 % ) and PTH ( + 10.3 % ) , whereas Ang II at 3 ng/kg per minute induced larger incremental changes in aldosterone ( + 241 % ) and PTH ( + 36 % ; P ) . Captopril acutely decreased aldosterone ( −12 % ) and PTH ( −9.7 % ; P ) . In contrast , aldosterone infusion robustly raised serum aldosterone ( + 892 % ) without modifying PTH . However , spironolactone therapy during 6 weeks modestly lowered PTH when compared with placebo ( P presence of Ang II type I and mineralocorticoid receptor mRNA and protein expression in normal and adenomatous human parathyroid tissues . We observed novel pleiotropic relationships between RAAS components and the regulation of PTH in individuals without primary hyperaldosteronism : the acute modulation of PTH by the RAAS seems to be mediated by Ang II , whereas the long-term influence of the RAAS on PTH may involve aldosterone . Future studies to evaluate the impact of RAAS inhibitors in treating PTH-mediated disorders are warranted", "OBJECTIVES To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge . DESIGN Multicenter , r and omized , controlled trial with a factorial design . SETTING Five hospitals in Auckl and , New Zeal and , and Sydney , Australia . PARTICIPANTS Two hundred forty-three frail older people . INTERVENTIONS Patients were r and omized to receive a single dose of vitamin D ( calciferol , 300,000 IU ) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits . MEASUREMENTS The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months . Physical performance and self-rated function were secondary endpoints . Assessment s took place in the participants ' homes at 3 and 6 months after r and omization and were performed by blinded assessors . RESULTS There was no effect of either intervention on physical health or falls , but patients in the exercise group were at increased risk of musculoskeletal injury ( risk ratio = 3.6 , 95 % confidence interval = 1.5 - 8.0 ) . Vitamin D supplementation did not improve physical performance , even in those who were vitamin D deficient ( vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization . There was no effect of vitamin D on physical performance , and the exercises increased the risk of musculoskeletal injury . These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people", "A 1-year prospect i ve study of seasonal mood changes was conducted in 250 female Boston area residents , aged 43 to 72 , who were participants in a study of vitamin D supplementation . Each woman completed the Profile of Mood States question naire at four study visits . There were significant changes over the year in scores for Tension-Anxiety , Depression-Dejection , Anger-Hostility , Fatigue-Inertia , and Confusion-Bewilderment . These scores were all highest or \" worst \" in the fall and lowest in the spring or summer . Worse mood scores were associated with fewer hours of sleep . Serum thyroxine was positively associated with higher Depression-Dejection scores in August through November and with higher ( better ) Vigor-Activity scores in February through May. Supplementation with 400 IU of vitamin D did not appear to affect levels or changes in mood scores", "OBJECTIVE The objective of the study was to determine whether vitamin D ( vitD ) supplementation during pregnancy affects obstetric and neonatal outcomes . SETTING The study was conducted at a university hospital in Karachi , Pakistan . METHODS The study was a single-center , open-label , r and omized , controlled trial of routine care ( group A , 200 mg ferrous sulfate and 600 mg calcium daily ) vs vitD supplementation ( group B , 4000 IU vitamin D3 daily ) , started at 20 weeks and continued till delivery . Maternal serum sample s of 25-hydroxyvitamin D ( 25OHD ) were collected at baseline and delivery . Neonatal vitD status was assessed in cord blood or in neonatal serum sample s within 48 hours of birth . Obstetric outcomes included gestational hypertension , gestational diabetes , and preterm labor , and neonatal well-being included small for gestational age , birth weight , length , head circumference , and 1- and 5-minute Apgar scores . RESULTS Of 207 gravidae enrolled , 193 completed the trial . Maternal age , vitD status , and gestational age at enrollment were comparable between the two groups . At delivery , maternal 25OHD was increased in group B ( 18.3 ± 11 ng/dL vs 8.82 ± 11.84 ng/dL ( P = .001 ) compared with group A ( 6.9 ± 7.0 ng/dL vs 6.32 ± 3.97 ng/dL , P = .06 ) . The obstetric outcomes were comparable between the two groups ( P > .05 ) . Neonatal 25OHD levels were significantly higher in group B compared with group A ( 19.22 ± 12.19 ng/dL vs 6.27 ± 5.2 ng/dL ) . There was positive correlation between maternal and neonatal 25OHD levels ( r = 0.83 , P = .001 ) . One- and 5-minute Apgar scores were significantly higher in group B ( 7.10 ± 0.66 vs 6.90 ± 0.50 , P = .026 , and 8.53 ± 0.68 vs 8.33 ± 0.81 , P = .051 , respectively ) . Neonatal anthropometric parameters were comparable between the two groups ( P > .05 ) . CONCLUSION Maternal vitD supplementation improved maternal and neonatal vitD status ", "This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine ( IOM ) . An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes . The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health , consistent with a cause- and -effect relationship and providing a sound basis for determination of intake requirements . For extraskeletal outcomes , including cancer , cardiovascular disease , diabetes , and autoimmune disorders , the evidence was inconsistent , inconclusive as to causality , and insufficient to inform nutritional requirements . R and omized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative . Based on bone health , Recommended Dietary Allowances ( RDAs ; covering requirements of ≥97.5 % of the population ) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age . For vitamin D , RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and older , corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml ( 50 nmol/liter ) , meet the requirements of at least 97.5 % of the population . RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer . Higher values were not consistently associated with greater benefit , and for some outcomes U-shaped associations were observed , with risks at both low and high levels . The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated . Urgent research and clinical priorities were identified , including re assessment of laboratory ranges for 25-hydroxyvitamin D , to avoid problems of both undertreatment and overtreatment", "BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo . Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people", "AIMS To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25-hydroxyvitamin D levels . METHODS Double-blind , parallel group , placebo-controlled r and omized trial . A single dose of 100,000 IU vitamin D2 or placebo was administered to patients with Type 2 diabetes over the winter , when levels of circulating 25-hydroxyvitamin D were likely to be lowest . Patients were enrolled if their baseline 25-hydroxyvitamin D level was Endothelial function and blood pressure were measured and fasting blood sample s were taken at baseline and 8 weeks after administration of vitamin D. RESULTS Forty-nine per cent of subjects screened had 25-hydroxyvitamin D levels Vitamin D supplementation increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to placebo and significantly improved flow mediated vasodilatation ( FMD ) of the brachial artery by 2.3 % . The improvement in FMD remained significant after adjusting for changes in blood pressure . Vitamin D supplementation significantly decreased systolic blood pressure by 14 mmHg compared with placebo ; this did not correlate with change in FMD . CONCLUSIONS Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotl and . A single large dose of oral vitamin D2 improves endothelial function in patients with Type 2 diabetes and vitamin D insufficiency", "OBJECTIVE To examine the association of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment in a r and omized , double-blind , placebo-controlled trial . METHODS Adult primary care patients in Duluth , Minnesota , were screened for vitamin D deficiency in February 2007 . Participants completed question naires pertaining to a variety of symptoms , vitamin D intake , and selected medical conditions . Patients with mild to moderate vitamin D deficiency ( 25-hydroxyvitamin D [ 25(OH)D ] , 10 - 25 ng/mL ) participated in a r and omized controlled trial ( RCT ) of vitamin D replacement and its effect on symptoms . Participants were r and omly assigned to receive 50 000 units of cholecalciferol ( vitamin D3 ) weekly or placebo for 8 weeks . Patients with severe vitamin D deficiency ( 25[OH]D A total of 610 patients underwent initial screening , and 100 patients with mild to moderate vitamin D deficiency participated in the RCT . Thirty-eight severely deficient patients were treated in an unblinded fashion . On initial screening , 46.2 % of participants were deficient in vitamin D. Self-reported vitamin D supplementation , milk intake , celiac disease , gastric bypass , and chronic pancreatitis were predictive of vitamin D status . Severely deficient participants reported increased musculoskeletal symptoms , depression ( including seasonal ) , and higher ( worse ) scores on a fibromyalgia assessment question naire . In the RCT , the treated group showed significant improvement in fibromyalgia assessment scores ( P = 0.03 ) , whereas the placebo-treated participants did not . Severely deficient patients did not show symptom improvement over the 8-week trial period or when followed up 1 year later . CONCLUSIONS Compared with participants in the placebo group , patients in the treatment group showed mild short-term improvement in the overall fibromyalgia impact score , but did not show significant improvement in most musculoskeletal symptoms or in activities of daily living", "Abstract Knowledge about the distributions of serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations in representative population sample s is critical for the quantification of vitamin D deficiency as well as for setting dietary reference values and food-based strategies for its prevention . Such data for the European Union are of variable quality making it difficult to estimate the prevalence of vitamin D deficiency across member states . As a consequence of the widespread , method -related differences in measurements of serum 25(OH)D concentrations , the Vitamin D St and ardization Program ( VDSP ) developed protocol s for st and ardizing existing serum 25(OH)D data from national surveys around the world . The objective of the present work was to apply the VDSP protocol s to existing serum 25(OH)D data from a Danish , a Norwegian , and a Finnish population -based health survey and from a Danish r and omized controlled trial . A specifically-selected subset ( n 100–150 ) of bio-banked serum sample s from each of the studies were reanalyzed for 25(OH)D by LC-MS/MS and a calibration equation developed between old and new 25(OH)D data , and this equation was applied to the entire data -sets from each study . Compared to estimates based on the original serum 25(OH)D data , the percentage vitamin D deficiency ( of serum 25(OH)D concentrations is absolutely necessary in order to compare serum 25(OH)D concentrations across different study population s , which is needed to quantify and prevent vitamin D deficiency", "BACKGROUND Serum 25-hydroxyvitamin D ( 25-[OH]D ) is considered the best biomarker of clinical vitamin D status . OBJECTIVE To determine the effect of increasing oral doses of vitamin D(3 ) on serum 25-(OH)D and serum parathyroid hormone ( PTH ) levels in postmenopausal white women with vitamin D insufficiency ( defined as a 25-[OH]D level ≤50 nmol/L ) in the presence of adequate calcium intake . These results can be used as a guide to estimate the Recommended Dietary Allowance ( RDA ) ( defined as meeting the needs of 97.5 % of the population ) for vitamin D(3 ) . DESIGN R and omized , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00472823 ) SETTING Creighton University Medical Center , Omaha , Nebraska . PARTICIPANTS 163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year . INTERVENTION Participants were r and omly assigned to receive placebo or vitamin D(3 ) , 400 , 800 , 1600 , 2400 , 3200 , 4000 , or 4800 IU once daily . Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg . MEASUREMENTS The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months . RESULTS The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D(3 ) . The RDA of vitamin D(3 ) to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d . A mixed-effects model predicted that 600 IU of vitamin D(3 ) daily could also meet this goal . Compared with participants with a normal body mass index ( 25-(OH)D level that was 17.8 nmol/L lower . Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D(3 ) ( P = 0.012 ) . Depending on the criteria used , hypercalcemia occurred in 2.8 % to 9.0 % and hypercalciuria in 12.0 % to 33.0 % of participants ; events were unrelated to dose . LIMITATION Findings may not be generalizable to other age groups or persons with substantial comorbid conditions . CONCLUSION A vitamin D(3 ) dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5 % of women ; however , a model predicted the same response with a vitamin D(3 ) dosage of 600 IU/d . These results can be used as a guide for the RDA of vitamin D(3 ) , but prospect i ve trials are needed to confirm the clinical significance of these results . PRIMARY FUNDING SOURCE National Institute on Aging", "Objective The aim of this study was to examine the effect of hormone therapy and calcitriol on depression in older postmenopausal women and to determine whether the response was associated with polymorphisms of estrogen receptor & agr ; and vitamin D receptor . Methods In a double-blind placebo-controlled prospect i ve trial involving 489 postmenopausal older women , a secondary analysis of depression was done . The Geriatric Depression Scale was used to screen for depression . We used binary logistic regression to examine the effect of treatment on depression and one-way analysis of variance to find a relationship between gene polymorphisms and depression . Results There was no effect of hormone therapy ( odds ratio [ OR ] , 1.65 ; 95 % CI , 0.66 - 4.12 ; P = 0.277 ) , calcitriol ( OR , 1.15 ; 95 % CI , 0.43 - 3.11 ; P = 0.772 ) , or hormone therapy with calcitriol ( OR , 1.01 ; 95 % CI , 0.36 - 2.80 ; P = 0.979 ) on depression . Neither the polymorphisms of estrogen receptor & agr ; ( XbaI-&bgr ; = 0.093 ; CI , −0.337 to 1.350 ; P = 0.239 and PvuII-&bgr ; = −0.064 ; CI , −1.171 to 0.491 , P = 0.421 ) nor those of vitamin D receptor ( BsmI-&bgr ; = 0.044 , CI −2.546 to 3.030 , P = 0.865 and TaqI-&bgr ; = −0.015 , CI −2.900 to 2.738 , P = 0.955 ) were associated with depression . Conclusion In older postmenopausal women , there was no effect of hormone therapy and calcitriol either individually or in combination with depression . Estrogen receptor & agr ; and vitamin D receptor polymorphisms are not associated with depression or the response to intervention in older postmenopausal women . Additional trials are required to confirm these findings", "OBJECTIVE To determine whether treatment of low serum vitamin D in pregnant women improves fetal growth indices . STUDY DESIGN In this open-label r and omized clinical trial , 130 Iranian pregnant women ( 24 - 26 weeks of gestation ) with vitamin D deficiency or insufficiency [ 25(OH)D were divided at r and om into an intervention group and a control group . The control group received 200 mg calcium plus a multivitamin ( containing vitamin D3 400U ) each day , and the intervention group received 200 mg calcium plus a multivitamin ( containing vitamin D3 400U ) each day , plus vitamin D3 ( 50,000U ) each week for 8 weeks . At delivery , maternal and cord blood 25(OH)D levels , maternal weight gain , neonatal length , neonatal weight and neonatal head circumference were compared between two groups . Serum vitamin D was measured using enzyme-linked immunosorbent assay . A multivariate regression analysis was performed to examine the independent effect of maternal vitamin D level on fetal growth indices . RESULTS Mean ( ±st and ard deviation ) length ( intervention group : 49±1.6 cm ; control group : 48.2±1.7 cm ; p=0.001 ) , head circumference ( intervention group : 35.9±0.7 cm ; control group : 35.3±1.0 cm ; p=0.001 ) and weight ( intervention group : 3429±351.9 g ; control group : 3258.8±328.2 g ; p=0.01 ) were higher in the intervention group compared with the control group . Mean maternal weight gain was higher in the intervention group compared with the control group ( 13.3±2.4 kg vs 11.7±2.7 kg ; p=0.006 ) . Multivariate regression analysis for maternal weight gain , neonatal length , neonatal weight and neonatal head circumference showed an independent correlation with maternal vitamin D level . CONCLUSION Treatment of low serum vitamin D during pregnancy improves fetal growth indices and maternal weight gain " ]

[ "OBJECTIVE this study evaluated the effect of surface treatments ( Nd : YAG laser , CO2 laser , Al203 airborne-particle abrasion , and silica-coating ) on the zirconia-to-resin shear bond strength ( SBS ) . METHOD AND MATERIAL S eighty-one Lava ( 3 M ESPE ) blocks ( 13 x 4 x 2 mm ) were embedded in acrylic resin , polished , and r and omly divided into three groups , which received the following surface treatments : no abrasion , Al203 airborne-particle abrasion ( 50 Μm ) , or silica-coating ( Cojet , 3 M ESPE ) . Each group was divided into three subgroups that were treated with Nd : YAG laser , CO2 laser , or no laser irradiation . Following application of a monomer phosphate-containing primer , cylinders of resin cement ( Panavia F , Kuraray ) ( n = 18 ) were built on the surface . SBS testing was carried out after 24 hours of storage in water . Surface roughness and topography ( SEM ) after treatments were evaluated . RESULTS according to ANOVA and Tukey test ( α = 0.05 ) , mean SBS after Nd : YAG laser treatment ranged from 14.09 to 16.20 MPa and was statistically higher than CO2 laser ( 6.24 to 10.51 MPa ) and no laser treatment ( 4.65 to 8.79 MPa ) . The Nd : YAG laser created more roughness on zirconia when compared to the CO2 laser and abrasion treatments . Silica-coating increased the SBS of lased and nonlased zirconia . Significant microcracks were found on specimens treated with CO2 . CONCLUSION Nd : YAG laser pretreatment , whether associated with abrasion methods or not , created consistent roughness on the zirconia surface and significantly increased zirconia SBS to Panavia F. Silica-coating could potentially increase the SBS of lased and nonlased zirconia . Significant microcracks were found on specimens treated with the CO2 laser ", "Objective : To evaluate the bond stability of resin cements when luted to glass-reinforced alumina and zirconia CAD/CAM dental ceramics . Study design : Eighteen glass-infiltrated alumina and eighteen densely sintered zirconia blocks were r and omly conditioned as follows : Group 1 : No treatment ; Group 2 : S and blasting ( 125 µm Al2O3-particles ) ; and Group 3 : Silica-coating ( 50 µm silica-modified Al2O3-particles ) . Composite sample s were r and omly bonded to the pre-treated ceramic surfaces using different resin cements : Subgroup 1 : Clearfil Esthetic Cement ( CEC ) ; Subgroup 2 : RelyX Unicem ( RXU ) ; and Subgroup 3 : Calibra ( CAL ) . After 24 h , bonded specimens were cut into 1 ± 0.1 mm2 sticks . One-half of the beams were tested for microtensile bond strength ( MTBS ) . The remaining one-half was immersed in 10 % NaOCl aqueous solution ( NaOClaq ) for 5 h before testing . The fracture pattern and morphology of the debonded surfaces were assessed with a field emission gun scanning electron microscope ( FEG-SEM ) . A multiple ANOVA was conducted to analyze the contributions of ceramic composition , surface treatment , resin cement type , and chemical challenging to MTBS . The Tukey test was run for multiple comparisons ( p the highest MTBS . Using RXU , alumina and zirconia registered comparable MTBS . CAL failed prematurely , except when luted to s and blasted zirconia . After NaOClaq storage , CEC significantly lowered MTBS when luted to zirconia or alumina . RXU decreased MTBS only when bonded to silica-coated alumina . CAL recorded 100 % of pre-testing failures . Micromorphological alterations were evident after NaOClaq immersion . Conclusions : Resin-ceramic interfacial longevity depended on cement selection rather than on surface pre-treatments . The MDP-containing and the self-adhesive resin cements were both suitable for luting CAD/CAM ceramics . Despite both cements being prone to degradation , RXU luted to zirconia or untreated or s and blasted alumina showed the most stable interfaces . CAL experimented spontaneous debonding in all tested groups . Key words : CAD/CAM ceramic , alumina , zirconia , resin cement , surface pre-treatment , s and blasting , silica-coating , chemical aging , bond degradation , microtensile bond strength", "This study compares the bond strength of resin cement and yttrium-stabilized tetragonal zirconia polycrystalline ( Y-TZP ) ceramic with different surface conditioning methods . Two hundred presintered Y-TZP ceramic specimens were prepared , sintered ( 4 × 4 × 4 mm ) , and r and omly assigned to four equal groups as control ( C , no conditioning ) ; airborne particle abraded ( APA , air abrasion with 11 μm Al2O3 ) ; tribochemical silica coating/silane coupling system ( TSC , Rocatec , air abrasion with 110 μm Al2O3 , 30 μm silica-coated Al2O3 and silane ) ; and laser ( L , Er : YAG laser irradiation treated at a power setting of 200 mJ ) . After specimen preparation , composite resin cylinders were prepared and cemented with resin cements ( Clearfil Esthetic , Panavia F 2.0 , Rely X-U100 , Super Bond C&B , and Multilink Automix ) on the ceramic surfaces and kept in an incubator at 37 ° C for 60 days . All specimens were tested for shear bond strength with a universal testing machine , and fractured surfaces were evaluated by environmental scanning electron microscopy . Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U-tests ( α=0.05 ) . The bond strengths for C and L groups were not significantly different according to adhesive resin cement . APA and TSC result ed in increased bond strength for Panavia F 2.0 and Rely X-U100 resin cements . Additionally , TSC presented higher bond strength with Multilink Automix . Adhesive fracture between the ceramic and resin cement was the most common failure . Complete cohesive fracture at the ceramic or composite cylinders was not observed . Regardless of the adhesive resin cement used , laser treatment did not improve resin bond strength ", "The present study evaluated the durability of bond strength between zirconia and 3 different resin cements . Thirty stabilized tetragonal zirconium-dioxide blocks were duplicated in dual-curing resin core build-up material specimens . Resin blocks were r and omly luted to zirconium surfaces using 1 ) Clearfil Esthetic Cement ( CLF ) , 2 ) RelyX Unicem Aplicap ( RELX ) , or 3 ) Multilink Automix ( MLA ) . After 24 h , half of the specimens from each of the 3 groups were loaded in tension until fracture ( 0.5 mm/min ) . The remaining half were tested after 6,000 thermal cycles ( 5 to 55 ° C ) . Data were analyzed using 2-way ANOVA and the Tukey test ( α = 0.05 ) . Fractographic analysis was performed using a stereomicroscope . Tensile bond strength values were significantly affected by the luting agent system employed and by thermal aging ( P highest tensile bond strength values in non-thermal-aged groups were observed for specimens from the RELX and CLF groups . In contrast , in the thermal-aged groups , the highest tensile bond strength values were for the MLA and RELX groups . Moreover , while thermocycling significantly affected bond strengths in the RELX and CLF groups , the mean strength of the MLA group did not significantly change after aging . There was little difference in the distribution of failure modes in any group", "Abstract Objective . The purpose of this in vitro study was to evaluate the influence of different power outputs of a carbon dioxide ( CO2 ) laser on shear bond strength of resin cement to zirconium dioxide-based ceramic . Material s and methods . Fifty zirconium dioxide core specimens ( 10 mm diameter and 2 mm thickness ) were produced and they were embedded in the centers of auto-polymerizing acrylic resin blocks . Ten specimens served as control and no surface treatment was applied . Subsequently specimens were r and omly divided into four groups , each containing 10 specimens for surface treatment with CO2 laser with different output power ; laser treated with 2 W ( Group 2 W ) , 3 W ( Group 3 W ) , 4 W ( Group 4 W ) and finally 5 W ( Group 5 W ) . Fifty composite resin discs were fabricated and cemented with adhesive resin cement to the specimen surfaces . A universal test machine was used for shear bond strength test at a crosshead speed 1 mm/min . Data were statistically analyzed by one-way analyses of variance ( ANOVA ) with Post-Hoc Tukey tests ( α = 0.05 ) . Results . It was found that the shear bond strength values were affected by power outputs of laser ( p Highest shear bond strength values were obtained with group 2 W ( 21.0 ± 2.7 ) . Lowest values were obtained with group 5 W ( 14.4 ± 1.6 ) . Conclusion . The current study revealed that there was a relationship between laser output power and shear bond strength for zirconium dioxide ceramics . However , output power of the laser and the energy level is a critical factor on micromechanical retention", "The objective of this study was to evaluate the durability of bond strength between a resin cement and aluminous ceramic su bmi tted to various surface conditioning methods . Twenty-four blocks ( 5 x 5 x 4 mm(3 ) ) of a glass-infiltrated zirconia-alumina ceramic ( In-Ceram Zirconia Classic ) were r and omly divided into three surface treatment groups : ST1-Air-abrasion with 110-mum Al2O3 particles + silanization ; ST2-Laboratory tribochemical silica coating method ( 110-microm Al2O3 , 110-microm silica ) ( Rocatec ) + silanization ; ST3-Chairside tribochemical silica coating method ( 30-microm SiO(x ) ) ( CoJet ) + silanization . Each treated ceramic block was placed in its silicone mold with the treated surface exposed . The resin cement ( Panavia F ) was prepared and injected into the mold over the treated surface . Specimens were sectioned to achieve nontrimmed bar specimens ( 14 sp/block ) that were r and omly divided into two conditions : ( a ) Dry-microtensile test after sectioning ; ( b ) Thermocycling (TC)-(6,000x , 5 - 55 degrees C ) and water storage ( 150 days ) . Thus , six experimental groups were obtained ( n = 50 ) : Gr1-ST1 + dry ; Gr2-ST1 + TC ( ; ) Gr3-ST2 + dry ; Gr4-ST2 + TC ; Gr5-ST3 + dry ; Gr6-ST3 + TC . After microtensile testing , the failure types were noted . ST2 ( 25.1 + /- 11 ) and ST3 ( 24.1 + /- 7.4 ) presented statistically higher bond strength ( MPa ) than that of ST1 ( 17.5 + /- 8) regardless of aging conditions ( p no significant differences ( two-way ANOVA and Tukey 's test , alpha = 0.05 ) . The majority of the failures were mixed ( 82 % ) followed by adhesive failures ( 18 % ) . Gr2 presented significantly higher incidence of ADHESIVE failures ( 54 % ) than those of other groups ( p = 0.0001 ) . Both laboratory and chairside silica coating plus silanization showed durable bond strength . After aging , air-abrasion with 110-microm Al(2)O(3 ) + silanization showed the largest decrease indicating that aging is fundamental for bond strength testing for acid-resistant zirconia ceramics in order to estimate their long-term performance in the mouth", "PURPOSE To evaluate the shear bond strength ( SBS ) to zirconia ceramics using different associations of primers and resin cements . MATERIAL S AND METHODS Two blocks of LAVA zirconia ( 3Y-TZP ) were r and omly su bmi tted to an application of three different commercially available primers : Alloy Primer ( AP ) , Z-Prime Plus ( ZP ) , and Signum Zirconia Bond ( SZB ) . Nonprimed specimens were considered controls . After treatment , the 80 specimens ( 5 mm × 5 mm × 2 mm ) were r and omly cemented with one of the resin cements : Panavia F , Multilink , seT , and NX3 . For cementation , cylinders of resin cement were built on the ceramic surfaces using the SDI SBS apparatus . The specimens were su bmi tted to the SBS test . Fractured surfaces were observed under stereomicroscopy to determine the failure mode , and mean bond strength values were analyzed using the Kruskal-Wallis and Mann-Whitney tests ( α = 0.05 ) . RESULTS Signum Zirconia Bond had the highest SBS compared to all other primers and the control group , regardless of the resin cement used . The highest values were obtained when associating Panavia F with Signum Zirconia Bond . Alloy Primer increased bonding values when associated with seT cement only . When no primer was used , no statistical difference was observed among resin cements . All specimens fractured due to adhesive failure . CONCLUSION Signum Zirconia Bond is capable of increasing bonding values of resin cements to zirconia ceramics . Its association with Panavia F shows enhanced results when considering short-term adhesion to zirconia", "OBJECTIVE We determined that the Er : YAG pulsed 2.94 micron radiation was successful in the removal of caries , cavity preparation , and etching prior to acid etching . SUMMARY BACKGROUND DATA The laser group was compared to a control group in which the high-speed drill was employed . Parameters measured included histological evaluation of the pulp , scanning electron microscopy of the surface morphology of the tooth , dye penetration studies , bond strength measurements , and rating of the laser 's ability to remove caries and form the preparation . METHODS We collectively evaluated 60 patients with 106 teeth in both the laser and control groups over a 1-year period . Teeth were treated in vivo and then extracted immediately , at 2 days , 1 month , and up to 1-year to assess pulpal healing , surface morphology , and the quality of the preparation , restoration , and pain . RESULTS The dental laser was shown to be equal or better than the drill in the tested procedures of caries removal , cavity preparation , and etching prior to acid etching . The scanning electron microscopy revealed no microfracturing , open dentinal tubules , and effective etching with the laser having a mean of 2.7 with an optimum rating of 3 . The histological testing confirmed that the pulp was not compromised using the laser with scores of theta for hemorrhage , 0.47 for hyperemia , and 0.12 for inflammation on a scale of 0 to 3 where 0 is no effect . CONCLUSIONS The FDA has recently cleared the Er : YAG to remove all classes of caries , form the cavity preparation , and modify the enamel and dentin prior to acid etching . In this Phase I study conducted as part of the clinical trials , there were no complications and no tooth was compromised . Patients were consistently treated without anesthesia with the same or better results than the drill as confirmed by scanning electron microscopy and histological studies", "OBJECTIVES The purpose of the current study was to examine the influence of the pre-cementation surface modification techniques , namely alumina abrasion and surface grinding , routinely employed by dental practitioners prior to cementation and placement of crown and bridge restorations on the performance of a Y-TZP dental ceramic . METHODS Twelve sets of 30 Lava ceramic discs ( 13 mm diameter , 1.5 mm thickness ) supplied by the manufacturer were r and omly selected . Six groups were abraded utilising 25 , 50 and 110 microm alumina and stored dry or in a water bath at 37+/-1 degrees C for 24 h. Four groups were ground utilising a fine or a coarse grit diamond bur , specimens were ground dry or while using water as a coolant . The mean bi-axial flexure strengths , st and ard deviations and associated Weibull moduli ( m ) were determined . The surface roughness , hardness and phase composition were assessed utilising profilometry , the Vicker 's hardness indentation and X-ray diffraction , respectively . RESULTS No significant difference ( P > 0.05 ) was identified in the bi-axial flexure strength of the 25 , 50 and 110 microm alumina-abraded and the control specimens stored dry and wet for 24h . However , a significant increase in m was identified for the alumina-abraded specimens stored dry ( 10.7+/-1.9 , 10.6+/-1.9 and 10.6+/-1.9 ) compared with the control ( 7.5+/-1.3 ) and the specimens stored in a water bath . In addition , the alumina abrasion regimes reduced the surface roughness compared with the controls . The coarse grinding regime significantly reduced both the bi-axial flexure strength and the associated m compared with the control whilst no significant difference was identified for the fine grinding regimes . The surface modification techniques initiated a phase transformation mechanism and result ed in the formation of a layer of compressive stresses on the surface of the disc-shaped specimens . CONCLUSIONS The combination of the reduced surface roughness and the formation of a surface layer of compressive stress as a result of the alumina abrasion regimes investigated increased the reliability of the bi-axial flexure strength . The presence of water in the current study did not detrimentally influence the performance of the Y-TZP ceramic under investigation . Coarse grinding significantly reduced the bi-axial flexure strength and m due to the increased surface roughness . The Y-TZP specimens in the current investigation underwent a toughening mechanism as a result of a phase transformation mechanism which generated a transformation compressive stress that opposes the externally applied , crack-propagating tensile stress", "OBJECTIVE To investigate the influence of applying thin intermediary coatings of acid-etchable glasses on the shear bond strength between a methacrylate resin based cement and an yttria-stabilized zirconia dental ceramic substrate . METHODS The upper and lower surfaces of 110 sintered yttria-stabilised tetragonal zirconia polycrystalline disc-shaped specimens were polished using sequential grade s of Silicon Carbide , then air-abraded with 25 μm diameter alumina particles . Specimens were r and omly allocated to 11 groups ( A-K ) ( n=10 ) , group A acting as control . The upper surface of Group A specimens was subjected to a tribochemical coating regime ( CoJet , 3 M ESPE ) . Five glazing ceramics were applied and fired according to the manufacturer 's recommended firing regime . The glaze was etched with 10 % HF acid and all specimens coated with a silane primer . Two differing storage regimes were employed ( wet storage vs thermocycling ) . Shear bond strength testing specimens were created by cementing resin-based composite cylinders to the centre of the prepared ceramic surface using Rely-X Unicem ( 3 M ESPE ) resin based cement . Shear bond strength testing was performed and load at failure recorded . RESULTS A factorial analysis of variance at a 95 % significance level demonstrated that all glazing techniques result ed in a significant increase in the shear bond strength compared with using the resin based cement alone ( P mean shear bond strength ( P=0.008 ) . The differences were a function of the storage state ( wet storage vs thermocycling ( P=0.013 ) ) . CONCLUSION The glazing techniques used in the current investigation result ed in a significantly enhanced shear bond stress to the resin based cement when compared with the current ' gold st and ard ' - tribochemical coating", "OBJECTIVES The aim of this study was to functionalize the surface of yttria partially stabilized tetragonal zirconia ceramics ( Y-TZP ) with a nano-structured alumina coating to improve resin bonding . MATERIAL S AND METHODS A total of 120 densely sintered disc-shaped specimens ( 15.5+/-0.03 mm in diameter and 2.6+/-0.03 mm thick ) were produced from biomedical- grade TZ-3YB-E zirconia powder ( Tosoh , Tokyo , Japan ) , r and omly divided into three groups of 40 and subjected to the following surface treatments : AS - as-sintered ; APA - airborne-particle abraded ; POL - polished . Half of the discs in each group received an alumina coating that was fabricated by exploiting the hydrolysis of aluminium nitride ( AlN ) powder ( groups AS-C , APA-C , POL-C ) . The coating was characterized using scanning electron microscopy ( SEM ) , atomic force microscopy ( AFM ) , and transmission electron microscopy ( TEM ) . The shear-bond strength of the self-etching composite resin ( RelyX Unicem , 3 M ESPE , USA ) was then studied for the coated and uncoated surfaces of the as-sintered , polished and airborne-particle abraded specimens before and after thermocycling ( TC ) . RESULTS The SEM/TEM analyses revealed that the application of an alumina coating to Y-TZP ceramics created a highly retentive surface for resin penetration . The coating showed good surface coverage and a uniform thickness of 240 nm . The resin-bond strength to the groups AS-C , APA-C , POL-C was significantly higher than to the groups AS , APA and POL , both before and after TC ( p debonded spontaneously . In contrast , the TC did not affect the bond strength of the AS-C , POL-C and APA-C groups . SIGNIFICANCE A non-invasive method has been developed that significantly improves resin-bond strength to Y-TZP ceramics . After surface functionalization the bond survives thermocycling without reduction in strength . The method is relatively simple and has the potential to become an effective conditioning method for zirconia ceramics", "This study evaluated the effect of chairside and laboratory types of surface conditioning methods on the adhesion of dual-cure resin cement with MDP functional monomer to zirconia ceramic after thermocycling . Disk-shaped ( diameter : 10 mm , thickness : 2 mm ) Y-TZP ceramics ( Lava , 3 M ESPE ) were used ( N=40 ) and finished with wet 1200-grit silicon carbide abrasive paper . Specimens were r and omly divided into four experimental groups according to the following surface conditioning methods ( n=10 per group ) : Group 1 - -Chairside airborne particle abrasion with 50-microm Al2O2 + Alloy Primer ( Kuraray ) ; Group 2 - -Airborne particle abrasion with 50-microm Al2O3 + Cesead II Opaque Primer ( Kuraray ) ; Group 3 - -Airborne particle abrasion with 50-microm A12O3 + Silano-Pen + silane coupling agent ( Bredent ) ; Group 4 - -Laboratory tribochemical silica coating ( 110-microm Al2O3 + 110-microm SiOx ) ( Rocatec ) + silane coupling agent ( ESPE-Sil ) . Adhesive cement , Panavia F 2.0 ( Kuraray ) , was bonded incrementally to the ceramic surfaces using polyethylene molds ( diameter : 3.6 mm , height : 5 mm ) . All specimens were thermocycled ( 5 and 55 degrees C , 6,000 cycles ) and subjected to shear bond strength test ( 1 mm/min ) . Data were statistically analyzed ( one-way ANOVA , alpha=0.05 ) , whereby no significant differences were found among the four groups ( 8.43+/-1.3 , 8.98+/-3.6 , 12.02+/-6.7 , and 8.23+/-3.8 MPa ) ( p=0.1357 ) . Therefore , the performance of chairside conditioning methods used for zirconia was on par with the laboratory alternative tested", "OBJECTIVES This study aim ed to evaluate the adhesive properties of a MDP-containing resin cement to a colored zirconia ceramic , using an experimental zirconia-silica coating technique with different priming conditions . METHODS 18 zirconia ceramic discs ( Cercon base colored ) were divided into two groups : the control group and the experimental zirconia-silica coating group . Specimens in each group were further divided into 3 subgroups ( n = 3 ) according to the priming conditions : no primer , a MDP-containing primer ( ED Primer II ) or a silane coupling primer ( RelyX ™ Ceramic Primer ) . Then resin-composite discs ( Filtek ™ Z250 ) were bonded to the treated surface using a MDP-containing resin cement ( Panavia F 2.0 ) . The bi-layered specimens were cut into microbars and 20 microbars were r and omly selected from each specimen , half of which were stored in 37 ° C water bath for 24h , and the other half were stored for 30 days . After water storage , the sample s were exposed to a micro tensile bond strength test ( MTBS ) . The results were analyzed by ANOVA , while the fracture surfaces were examined by SEM . RESULTS After 24h water storage , zirconia-silica coating followed by silanization showed a significantly ( P higher MTBS value 45.0 (10.9)MPa . Water storage affected ( P ) MTBS in the control group ( 24.1 - 30.3 MPa to 2.8 - 3.1 MPa ) , but only partially in the zirconia-silica coating group ( 20.0 - 45.1 MPa to 17.4 - 25.9 MPa ) . SEM analysis revealed a failure mode change after water storage . SIGNIFICANCE The combination of zirconia-silica coating with silane coupling can improve the bonding of resin cement to this colored zirconia", "Zirconia-based ceramics offer strong restorations in dentistry , but the adhesive bond strength of resin cements to such ceramics is not optimal . This study evaluated the influence of surface treatments on the bond strength of resin cement to yttrium-stabilized tetragonal zirconia ( Y-TZP ) ceramic . Seventy-five plates of Y-TZP ceramic were r and omly assigned to five groups ( n = 15 ) according to the surface treatments [ airborne particle abrasion , neodymium-doped yttrium aluminum garnet ( Nd : YAG ) laser irradiation ( Fidelis Plus 3 , Fotona ; 2 W , 200 mJ , 10 Hz , with two different pulse duration s 180 or 320 μs ) , glaze applied , and then 9.5 % hydrofluoric acid gel conditioned , control ] . One specimen from each group was r and omly selected , and specimens were evaluated with x-ray diffraction and SEM analysis . The resin cement ( Clearfil Esthetic Cement , Kuraray ) was adhered onto the zirconia surfaces with its corresponding adhesive components . Shear bond strength of each sample was measured using a universal testing machine at a crosshead speed of 1 mm/min . Bond strengths were analyzed through one-way ANOVA/Tukey tests . Surface treatments significantly modified the topography of the Y-TZP ceramic . The Nd : YAG laser-irradiated specimens result ed in both increased surface roughness and bond strength of the resin cement . The highest surface roughness and bond strength values were achieved with short pulse duration . Nd : YAG laser irradiation increased both surface roughness of Y-TZP surfaces and bond strength of resin cement to the zirconia surface", "OBJECTIVE Various chemical interactions can be used to develop ceramic-resin bonding and specific approaches are available for zirconia ceramics . This study evaluated the effect of a new experimental primer , a mixture of organophosphate and carboxylic acid monomers , on the zirconia-to-resin shear bond strength ( SBS ) . METHODS Forty Y-TZP blocks ( 15x4x2 mm ) were embedded in an acrylic resin base , polished , Al(2)O(3)-s and blasted and r and omly divided into eight groups . Three different resin-based luting agents ( BisCem , Duo-Link , Panavia F ) were used to build 2.4mm-diameter cylinders ( n=15 ) onto the zirconia surface with and without the new experimental zirconia primer . The new primer was also tested with Z100 restorative composite resin cylinders . In addition , Panavia was used with its own primer ( Clearfil Ceramic Primer ) . SBS testing was carried out after 24h of storage in water . Scanning electron microscopy ( SEM ) was used to evaluate the zirconia surface topography and failure mode . RESULTS According to ANOVA and Tukey test ( alpha=0.05 ) , the association of the experimental primer with the restorative composite resin Z100 yielded the highest SBS ( 29.35MPa ) followed by DuoLink with the new primer ( 26.68MPa ) . The groups that did not receive the experimental primer presented the lowest SBS values ( from 5.95 to 9.79MPa ) . The failure mode was adhesive for the non-primed specimens and predominantly mixed in the primed groups . SIGNIFICANCE The use of the new zirconia experimental primer based on organophosphate/carboxylic acid monomers increased the bond strength of different resin-based luting agents including Z100 restorative material", "STATEMENT OF PROBLEM The ceramic composition and microstructure surface of all-ceramic restorations are important components of an effective bonding substrate . Both hydrofluoric acid etching and airborne aluminum oxide particle abrasion produce irregular surfaces necessary for micromechanical bonding . Although surface treatments of feldspathic and leucite porcelains have been studied previously , the high alumina-containing and lithium disilicate ceramics have not been fully investigated . PURPOSE The purpose of this study was to assess the surface topography of 6 different ceramics after treatment with either hydrofluoric acid etching or airborne aluminum oxide particle abrasion . MATERIAL AND METHODS Five copings each of IPS Empress , IPS Empress 2 ( 0.8 mm thick ) , Cergogold ( 0.7 mm thick ) , In-Ceram Alumina , In-Ceram Zirconia , and Procera ( 0.8 mm thick ) were fabricated following the manufacturer 's instructions . Each coping was longitudinally sectioned into 4 equal parts by a diamond disk . The result ing sections were then r and omly divided into 3 groups depending on subsequent surface treatments : Group 1 , specimens without additional surface treatments , as received from the laboratory ( control ) ; Group 2 , specimens treated by use of airborne particle abrasion with 50-microm aluminum oxide ; and Group 3 , specimens treated with 10 % hydrofluoric acid etching ( 20 seconds for IPS Empress 2 ; 60 seconds for IPS Empress and Cergogold ; and 2 minutes for In-Ceram Alumina , In-Ceram Zirconia , and Procera ) . RESULTS Airborne particle abrasion changed the morphologic surface of IPS Empress , IPS Empress 2 , and Cergogold ceramics . The surface topography of these ceramics exhibited shallow irregularities not evident in the control group . For Procera , the 50-microm aluminum oxide airborne particle abrasion produced a flattened surface . Airborne particle abrasion of In-Ceram Alumina and In-Ceram Zirconia did not change the morphologic characteristics and the same shallows pits found in the control group remained . For IPS Empress 2 , 10 % hydrofluoric acid etching produced elongated crystals scattered with shallow irregularities . For IPS Empress and Cergogold , the morphologic characteristic was honeycomb-like on the ceramic surface . The surface treatment of In-Ceram Alumina , In-Ceram Zirconia , and Procera did not change their superficial structure . CONCLUSION Hydrofluoric acid etching and airborne particle abrasion with 50-microm aluminum oxide increased the irregularities on the surface of IPS Empress , IPS Empress 2 , and Cergogold ceramics . Similar treatment of In-Ceram Alumina , In-Ceram Zirconia , and Procera did not change their morphologic microstructure", "OBJECTIVES The aim of this study was to compare the effects of three different surface treatments in enhancing porcelain zirconia bonding . METHODS Totally , 160 densely sintered zirconia specimens were prepared and r and omly divided into four study groups : control ( no treatment , Group C ) , s and blasting ( Group S ) , s and blasting followed by regeneration firing ( Group SH ) , and laser irradiation ( pulse mode ) on a CO₂ laser system ( Group L ) . After surface treatment , porcelain powders were veneered on zirconia surface . Half of the specimens in each group were evaluated without aging ( initial shear bond strength - initial SBS ) , and the other half was tested after being stored in water for one month ( aging SBS ) . X-ray diffractometry ( XRD ) was used to observe any crystallographic transformation at zirconia surface . Results were statistically analyzed using analysis of variance ( ANOVA ) and Turkey test ( = 0.05 ) . RESULTS The initial average SBS values of Group S , Group SH , and Group L were 31.3 ± 5.7 MPa , 29.2 ± 7.0 MPa and 32.1 ± 7.5 MPa , respectively . The differences among these three groups were not significant . The control group had significantly lower value , 24.8 ± 6.7 MPa , than those of Group S and Group L. Furthermore , there was no significant difference between initial and aging values in each group . XRD analysis showed that s and blasting caused tetragonal to monoclinic phase transformation . Regeneration firing reversed such a transformation . However , crystallographic transformation could not be detected in laser treated specimens . SIGNIFICANCE Both s and blasting and laser irradiation increased porcelain zirconia bond strength . The presented new modified laser pre-treatment might be an alternative way to s and blasting for improving zirconia/porcelain integration ", "OBJECTIVES This study evaluated the effect of three different surface conditioning methods on the bond strength of a Bis-GMA based luting cement to six commercial dental ceramics . METHODS Six disc shaped ceramic specimens ( glass ceramics , glass infiltrated alumina , glass infiltrated zirconium dioxide reinforced alumina ) were used for each test group yielding a total number of 216 specimens . The specimens in each group were r and omly assigned to one of the each following treatment conditions : ( 1 ) hydrofluoric acid etching , ( 2 ) airborne particle abrasion , ( 3 ) tribochemical silica coating . The resin composite luting cement was bonded to the conditioned and silanized ceramics using polyethylene molds . All specimens were tested at dry and thermocycled ( 6.000 , 5 - 55 degrees C , 30 s ) conditions . The shear bond strength of luting cement to ceramics was measured in a universal testing machine ( 1 mm/min ) . RESULTS In dry conditions , acid etched glass ceramics exhibited significantly higher results ( 26.4 - 29.4 MPa ) than those of glass infiltrated alumina ceramics ( 5.3 - 18.1 MPa ) or zirconium dioxide ( 8.1 MPa ) ( ANOVA , P bond strength significantly for high-alumina ceramics ( 8.5 - 21.8 MPa ) and glass infiltrated zirconium dioxide ceramic ( 17.4 MPa ) compared to that of airborne particle abrasion ( ANOVA , P bond strengths significantly after all of the conditioning methods tested . SIGNIFICANCE Bond strengths of the luting cement tested on the dental ceramics following surface conditioning methods varied in accordance with the ceramic types . Hydrofluoric acid gel was effective mostly on the ceramics having glassy matrix in their structures . Roughening the ceramic surfaces with air particle abrasion provided higher bond strengths for high-alumina ceramics and the values increased more significantly after silica coating/silanization", "STATEMENT OF PROBLEM The influence of different types of adhesive resin cements on the long-term prognosis of aluminum oxide ceramic posterior crowns is unclear . PURPOSE The purpose of this study was to evaluate the fracture resistance of aluminum oxide ceramic on maxillary posterior crowns cemented with different resin luting agents before and after cyclic thermomechanical loading . Material and methods Forty-eight maxillary first molars were prepared and restored with st and ardized aluminum oxide ceramic ( In-Ceram Alumina ) crowns . The test specimens were r and omly divided into 3 groups ( n=16 ) . The crowns were luted with an acrylic resin cement ( Super-Bond C&B , control , Group SB ) and 2 composite luting agents ( Panavia F , Group PV ; and Rely X Unicem , Group RX ) . Half of the specimens were exposed to thermomechanical fatigue in a masticatory simulator . All specimens were tested for fracture strength ( N ) using quasistatic loading . The Wilcoxon rank sum test was used to compare the fracture strength ( alpha=.05 ) . RESULTS All specimens survived the exposure to the simulator . The following median fracture strength values were obtained without/with thermomechanical fatigue loading : Group SB , 2726 N/2673 N ; Group PV , 2520 N/2083 N ; and Group RX , 2036 N/2369 N. The fracture strength in Group PV after thermomechanical fatigue loading was significantly lower compared to the fracture strength in Group PV without artificial aging ( P = .016 ) , as well as significantly lower compared to Group SB with artificial aging ( P = .003 ) . CONCLUSION Within the limitations of this study , all tested cements are capable of successfully luting aluminum oxide ceramic crowns . The fracture strength of Group PV after artificial aging was comparatively low", "Abstract Objective . The purpose of this in-vitro study was to evaluate and compare the effects of different surface treatments and laser irradiation on the shear bond strength of resin cement to zirconia-based ceramic . Material and methods . Forty zirconia core specimens ( 10-mm diameter , 2-mm thickness ) were produced and embedded in the centers of autopolymerizing acrylic resin blocks . Subsequently , specimens were r and omly divided into four groups , each containing 10 specimens , for different surface treatment methods . The details of the groups are as follows : Group C , no treatment applied ( control ) ; Group SB , bonding surfaces of ceramic disks were airborne particle-abraded with 110-μm alumina oxide particles ; Group HF , bonding surfaces of ceramic disks were etched with 9.6 % hydrofluoric acid ; and Group L , bonding surfaces of ceramic disks were irradiated by a CO2 laser . A total of 40 composite resin disks were fabricated and cemented with an adhesive resin cement to the specimen surfaces . A universal test machine was used for the shear bond strength test at a crosshead speed of 1 mm/min . Results . The highest shear bond strength values were obtained with Group L ( 20.99 ± 3.77 MPa ) and the lowest values with Group C ( 13.39 ± 3.10 MPa ) . Although there was no significant difference between Groups C , HF and SB ( P > 0.05 ) , Group L showed a significant difference from all other groups ( p CO2 laser etching may represent an effective method for conditioning zirconia surfaces , enhancing micromechanical retention and improving the bond strength of resin cement on zirconia ceramic", "OBJECTIVE The aim of this study was to evaluate the effect of different surface treatments ; s and blasting , Er : YAG , Nd : YAG , or CO(2 ) laser irradiation on the shear bond strength ( SBS ) of zirconia ceramic to dentin . BACKGROUND DATA Zirconia is not properly luted with resin cements . Various surface treatment methods have been suggested for zirconia to obtain high bond strength to resin cements . There is no study that compared the effect of different laser types ( Er : YAG , Nd : YAG , CO(2 ) ) with s and blasting on SBS between zirconia and dentin . METHODS One hundred and twenty human maxillary third molar teeth were sectioned 3 mm below the occlusal surfaces , embedded in a metal ring with autopolymerizing acrylic resin , and stored in distilled water at 37(0)C. One hundred and twenty disc-shaped zirconia specimens were fabricated ( 6 mm in diameter and 4 mm in thickness ) , and r and omly assigned to six groups ( n=20 ) : Group 1 , untreated ( control ) ; Group 2 , s and blasted ; Group 3 , Er : YAG laser irradiated ; Group 4 , Nd : YAG laser irradiated with contact ; Group 5 , Nd : YAG laser irradiated with non-contact ; Group 6 , CO(2 ) laser irradiated . They were cemented onto the dentin with dual-cured resin cement ( Variolink ( ® ) ) . After they were stored in distilled water at 37(0)C for 24 h , the SBS test was performed at a crosshead speed of 1 mm/min . The fractured specimens were examined under a stereomicroscope to evaluate the fracture pattern . RESULTS Results of this study did not show statistically significant differences between Groups 1 and 2 , or among Groups 3 , 4 and 5 . The lowest SBS was recorded in Group 6 ( CO(2 ) laser ) , and the highest SBS was recorded in Group 4 ( Nd : YAG laser with contact ) , followed by Group 3 ( Er : YAG laser ) . The adhesive failure mode was predominantly observed in Groups 2 , 3 , 5 , and 6 . Group 1 showed 45 % mixed failure and Group 4 showed 50 % mixed failure . CONCLUSIONS This study shows that Er : YAG and Nd : YAG laser treatment increased the bond strength of zirconia compared to s and basting and CO(2 ) laser treatment", "OBJECTIVE To evaluate the influence of different surface treatments on the microtensile bond strength of resin cement to zirconia ceramic . MATERIAL S AND METHODS Twelve cylinder-shaped ( ∅ 12 × 5.25 mm high ) blocks of a commercial zirconium-oxide ceramic ( Cercon ® Zirconia , DENTSPLY ) were r and omly divided into 4 groups ( n=3 ) , based on the surface treatment to be performed : ( 1 ) airborne particle abrasion with 125 μm Al₂O₃ particles ( S ) ; ( 2 ) selective infiltration etching ( SIE ) ; ( 3 ) experimental hot etching solution applied for 30 min ( ST ) and ( 4 ) no treatment ( C ) . Paradigm MZ100 blocks ( 3 M ESPE ) were cut into twelve cylinders of 4 mm in thickness . Composite cylinders were bonded to conditioned ceramics using a resin cement ( Calibra ® , DENTSPLY ) , in combination with the proprietary adhesive system . After 24h bonded specimens were cut into microtensile sticks and loaded in tension until failure . Bond strength data were analyzed with Kruskall-Wallis and Dunn 's Multiple Range test for multiple comparisons ( p was recorded and the interfacial morphology of debonded specimens was analyzed using a scanning electron microscope ( SEM ) . RESULTS Bond strength values achieved after SIE and ST treatment were significantly higher than after S treatment and without any treatment ( p were mostly recorded in the S group . SIGNIFICANCE Conditioning the high-strength ceramic surface with SIE and ST treatments yielded higher bond strengths of the resin cement than when zirconia ceramic was treated with airborne particle abrasion or left untreated", "The current study evaluated the effects of various pretreatments and aging in water on the bond strength to hot isostatic pressed yttrium-oxide partially stabilized zirconia . Sixty zirconia ceramic specimens ( Denzir ) were r and omly divided into three groups of 20 . One group of specimens ( n=10 ) was then bonded to each other using a resin composite cement ( RelyX Unicem ) , the second group ( n=10 ) was bonded with RelyX Unicem and a metal primer ( Metal Primer II ) , while the third group ( n=10 ) was bonded with RelyX Unicem and a ceramic primer ( Ceramic Primer ) . The specimens were then subjected to shear force before and after s and blasting and before and after aging in water for 180 days . Before aging , no significant differences ( p > 0.05 ) were seen within the different groups , either before or after s and blasting . S and blasting and pretreatment with the metal ( p ceramic ( p bond strength compared to that of the non-treated specimens . After aging , the bond strength of the s and blasted specimens with metal primer was significantly higher than that of the s and -blasted specimens with ceramic primer ( p metal primer , the bond strength was not significantly affected after aging ( p > 0.05 ) , whereas , for those specimens with the ceramic primer ( p no primer ( p bond strength significantly decreased . Thus , air abrasion and pretreatment with a metal primer seems to be an appropriate method for improving bond strength", "OBJECTIVES To evaluate the effect of the particle size of s and blasting and the composition of the resin cement on the microtensile bond strength ( MTBS ) to zirconia . METHODS Forty zirconia blocks ( Cercon , Dentsply ) were polished and r and omly treated as follows : Group 1 ( NT ) : no treatment ; Group 2 ( APA-I ) : airborne particle abrasion ( Cobra , Renfert ) using 25-μm aluminium-oxide ( Al(2)O(3))-particles ; Group 3 ( APA-II ) : APA with 50-μm Al(2)O(3)-particles ; and Group 4 ( APA-III ) : APA using 110-μm Al(2)O(3)-particles . Ceramic blocks were duplicated in composite resin . Sample s of each pretreatment group were r and omly divided into two subgroups depending on the resin cement used for bonding the composite disks to the treated zirconia surfaces . Subgroup 1 ( PAN ) , which was a 10-MDP-containing luting system , used Clearfil Ceramic Primer plus Panavia F 2.0 ( Kuraray ) and Subgroup 2 ( BIF ) used Bifix SE ( VOCO ) self-adhesive cement . After 24h , bonded specimens were cut into 1±0.1mm(2 ) sticks . MTBS values were obtained using a universal testing machine ( cross-head speed=0.5mm/min ) . Failure modes were recorded and the interfacial morphology of the debonded microbars was SEM-assessed . Two-way ANOVA , Student-Newman-Keuls tests , and the step-wise linear regression analysis were performed with the MTBS being the dependent variable ( p highest MTBS and frequently showed mixed fractures . BIF recorded no significant differences in MTBS depending on the conditioning method , and registered the highest rates of premature and adhesive failures . CONCLUSIONS The 10-MDP-containing luting system seems to be the most suitable to bond zirconium-oxide ceramic , mainly after s and blasting", "OBJECTIVES To evaluate the effect of mechanical and chemical surface pre-treatment on the bond durability of two composite cements to dental zirconia . METHODS Fully sintered IPS e.max ZirCAD ( Ivoclar-Vivadent ) blocks were either subjected to tribochemical silica s and blasting ( CoJet , 3 M ESPE ) or not mechanically pre-treated . Next , the zirconia sample s were either additionally pre-treated using one of two silane/MDP-combined ceramic primers ( Clearfil Ceramic Primer , Kuraray ; Monobond Plus , Ivoclar-Vivadent ) , or not further chemically pre-treated . Finally , two identically pre-treated zirconia blocks were bonded together using either a conventional BisGMA-based ( Clearfil Esthetic Cement , Kuraray ) or an MDP-based ( Panavia F2.0 , Kuraray ) ' self-etch ' dual-cure composite cement . The specimens were trimmed at the interface to a cylindrical hour-glass shape and stored for 7 days in distilled water ( 37 ° C ) , after which they were r and omly exposed to one of three ageing protocol s : ( 1 ) immersed in 37 ° C water for 10 days ( 10d ) ; ( 2 ) subjected to 10,000 thermo-cycles ( TC ) ; or ( 3 ) immersed in 37 ° C water for 6 months ( 6 m ) . After storage , the micro-tensile bond strength ( μTBS ) was determined in MPa ( n=15 - 21/group ) . Fractographic analysis was performed using SEM . RESULTS Weibull analysis revealed the highest Weibull scale and shape parameters for the ' CoJet/Clearfil Ceramic Primer/Panavia F2.0/10d ' combination . While the BisGMA-based composite cement Clearfil Esthetic Cement ( Kuraray ) bonded equally well to zirconia using either tribochemical silica s and blasting ( CoJet , 3 M ESPE ) or not , s and blasting appeared indispensable for the MDP-based and more hydrophilic composite cement Panavia F2.0 ( Kuraray ) . CONCLUSIONS Combined mechanical and chemical pre-treatment can best be recommended to durably bond to zirconia . CLINICAL SIGNIFICANCE As a st and ard procedure to durable bond zirconia to tooth tissue , both mechanical ( tribochemical silica coating ) and chemical ( silane/MDP-combined ceramic primers ) is clinical ly highly recommended" ]

[ "Background Evidence -based r and omized clinical trials have shown significant benefit of statin treatment with regard to cardiovascular disease . In anticipation of the National Cholesterol Education Program Adult Treatment Panel IV guidelines , we wanted to assess the current state of lipid goal attainment in the high-risk secondary prevention population in the United States . The objectives of the study were to estimate the proportion of high-risk patients treated with statin monotherapy who achieved Adult Treatment Panel III – recommended low-density lipoprotein cholesterol ( LDL-C ) goals ( 3 data sources : electronic medical records ( 2003–September 2010 ) , administrative cl aims data ( 2003–2010 ) , and National Health and Nutrition Examination Survey data ( 2007–2008 ) . High-risk patients ( ≥18 years of age ) were defined as those with a history of coronary heart disease or coronary heart disease risk equivalent who had the latest complete lipid panel measurement and had been treated with statin monotherapy for > 90 days at the time of the lipid panel . Cardiovascular disease , coronary heart disease , and coronary heart disease risk equivalents were defined on the basis of availability , specific to each data source . Across the 3 data sources , 20 % to 26 % of high-risk patients treated with statin monotherapy for > 90 days had LDL-C attaining both LDL-C goals and non – high-density lipoprotein cholesterol goals were quantitatively smaller ( 13.5 % to 19.0 % and 46 % to 70 % ) . Conclusions Across the 3 data sources , there was consistency in the proportion of high-risk patients treated with statin monotherapy who were at LDL-C goal . A significant number of these statin-treated patients had additional dyslipidemias", "A total of 96 patients with moderate elevations of low-density lipoprotein ( LDL ) cholesterol were r and omly assigned to 4 different double-blind treatment regimens : placebo ; colestipol 5 g and lovastatin 20 mg/day ( C5 + L20 ) ; colestipol 10 g and lovastatin 20 mg/day ( C10 + L20 ) ; and lovastatin 40 mg/day ( L40 ) . During 12 weeks of therapy , C10 + L20 achieved the greatest reduction in total cholesterol ( -32 % ) and LDL cholesterol ( -48 % ) levels from baseline . This combination also exhibited significantly greater reductions in LDL cholesterol levels than the C5 + L20 and L40 groups ( p total and LDL cholesterol reduction between the C5 + L20 and L40 groups were not significant . Similar changes and differences between treatments were seen in apolipoprotein B levels . Whereas mean total apolipoprotein A-I levels increased with all treatments ( p lipoprotein particles A-I were significantly increased in the C10 + L20 group ( p lovastatin ( 20 mg/day ) with low-dose colestipol ( 5 or 10 g/day ) produces LDL cholesterol reductions equal to or greater than higher doses of lovastatin ( 40 mg/day ) . In addition , low-dose combinations are > 25 % more cost-effective than high-dose monotherapy", "Background : Patients with coronary artery disease ( CAD ) should be treated with statins to attain very low cholesterol levels , in order to reduce cardiovascular adverse events . More than 70 % of these patients do not reach the appropriate cholesterol goal despite moderate statin doses . However , it is not known whether therapeutic uptitration with different lipid-lowering strategies has a similar “ pleiotropic ” effect on atherosclerotic endothelial dysfunction evaluated by measurement of endothelial progenitor cells ( EPCs ) . Objective : We sought to compare , in patients with stable CAD and with a low-density lipoprotein cholesterol ( LDL-C ) > 70 mg/dL on treatment with simvastatin 20 mg , the effects on EPCs by increasing simvastatin to 80 mg versus adding ezetimibe 10 mg . Methods : Patients ( n = 68 , 63 ± 9 years , 39 % men ) were r and omly allocated to receive ezetimibe 10/simvastatin 20 mg or simvastatin 80 mg for 6 weeks . Circulating EPCs were measured by flow cytometry before and after the treatment . Results : Both strategies presented similar effects on metabolic parameters . The LDLs were equally reduced by ezetimibe 10/simvastatin 20 mg and simvastatin 80 mg ( 28.9 % ± 13 % vs 21.1 % ± 33 % ; P = .46 , respectively ) . The levels of EPCs were unaffected by ezetimibe 10/simvastatin 20 mg ( median [ 25th , 75th ] : pre- vs posttreatment , 7.0 [ 2.3 ; 13.3 ] vs 3.1 [ 0.1 ; 13.2 ] EPCs/104 mononuclear cells ; P = .43 ) or simvastatin 80 mg ( pre- vs posttreatment , 6.1 [ 2.9 ; 15.2 ] vs 4.0 [ 1.4 ; 10.7 ] EPCs/104 mononuclear cells ; P = .5 ) , and there were no differences between the groups on treatment effects ( P = .9 ) . Conclusions : Among stable patients with CAD and with an LDL-C > 70 mg/dL on simvastatin 20 mg , increasing simvastatin dose to 80 mg or adding ezetimibe 10 mg promoted similar further cholesterol reduction but did not have incremental effects on circulating EPCs . These data suggest that the effects of simvastatin moderate doses on EPCs are not increased by intensive lipid-lowering strategies ( clinical trials.gov : NCT00474123 )", "Background Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus , but many of these patients fail to achieve the target LDL-C level . Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin . However , in patients with type 2 diabetes who are already being treated with satins , it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose . Therefore , this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins . Methods The subjects were type 2 diabetic patients under treatment with rosuvastatin ( 2.5 mg daily ) , who had LDL-C levels ≥80 mg/dL. They were r and omly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day ( combination group , n = 40 ) or an increase of the rosuvastatin dose to 5 mg/day ( dose escalation group , n = 39 ) . These two groups were compared at baseline and after 12 weeks of treatment . Results The percent change of LDL-C was −31 % in the combination group and −12 % in the dose escalation group . Both groups showed a significant decrease , but the decrease was greater in the combination group . In both groups , there was a significant decrease in the levels of small dense LDL-C , oxidized LDL and remnant-like lipoprotein cholesterol . For all of these parameters , the percent changes were greater in the combination group . Only the combination group showed a significant decrease of triglycerides . Multivariate analysis was performed to identify factors associated with reaching an LDL-C level with ezetimibe was extracted as a factor related to improvement of LDL-C. Conclusions Compared with increasing the dose of rosuvastatin , the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients , suggesting that this combination could suppress the progression of atherosclerosis . Trial registration", "Summary Background Lowering of LDL cholesterol reduces major vascular events , but whether more intensive therapy safely produces extra benefits is uncertain . We aim ed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk . Methods We undertook a double-blind r and omised trial in 12 064 men and women aged 18–80 years with a history of myocardial infa rct ion . Participants were either currently on or had clear indication for statin therapy , and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not . R and omisation to either 80 mg or 20 mg simvastatin daily was done central ly using a minimisation algorithm . Participants were assessed at 2 , 4 , 8 , and 12 months after r and omisation and then every 6 months until final follow-up . The primary endpoint was major vascular events , defined as coronary death , myocardial infa rct ion , stroke , or arterial revascularisation . Analysis was by intention to treat . This study is registered , number IS RCT N74348595 . Findings 6031 participants were allocated 80 mg simvastatin daily , and 6033 allocated 20 mg simvastatin daily . During a mean follow-up of 6·7 ( SD 1·5 ) years , allocation to 80 mg simvastatin produced an average 0·35 ( SE 0·01 ) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg . Major vascular events occurred in 1477 ( 24·5 % ) participants allocated 80 mg simvastatin versus 1553 ( 25·7 % ) of those allocated 20 mg , corresponding to a 6 % proportional reduction ( risk ratio 0·94 , 95 % CI 0·88–1·01 ; p=0·10 ) . There were no apparent differences in numbers of haemorrhagic strokes ( 24 [ 0·4 % ] vs 25 [ 0·4 % ] ) or deaths attributed to vascular ( 565 [ 9·4 % ] vs 572 [ 9·5 % ] ) or non-vascular ( 399 [ 6·6 % ] vs 398 [ 6·6 % ] ) causes . Compared with two ( 0·03 % ) cases of myopathy in patients taking 20 mg simvastatin daily , there were 53 ( 0·9 % ) cases in the 80 mg group . Interpretation The 6 % ( SE 3·5 % ) reduction in major vascular events with a further 0·35 mmol/L reduction in LDL cholesterol in our trial is consistent with previous trials . Myopathy was increased with 80 mg simvastatin daily , but intensive lowering of LDL cholesterol can be achieved safely with other regimens . Funding Merck ; The Clinical Trial Service Unit also receives funding from the UK Medical Research Council and the British Heart Foundation", "BACKGROUND In patients with established cardiovascular disease , residual cardiovascular risk persists despite the achievement of target low-density lipoprotein ( LDL ) cholesterol levels with statin therapy . It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein ( HDL ) cholesterol is superior to simvastatin alone in reducing such residual risk . METHODS We r and omly assigned eligible patients to receive extended-release niacin , 1500 to 2000 mg per day , or matching placebo . All patients received simvastatin , 40 to 80 mg per day , plus ezetimibe , 10 mg per day , if needed , to maintain an LDL cholesterol level of 40 to 80 mg per deciliter ( 1.03 to 2.07 mmol per liter ) . The primary end point was the first event of the composite of death from coronary heart disease , nonfatal myocardial infa rct ion , ischemic stroke , hospitalization for an acute coronary syndrome , or symptom-driven coronary or cerebral revascularization . RESULTS A total of 3414 patients were r and omly assigned to receive niacin ( 1718 ) or placebo ( 1696 ) . The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy . At 2 years , niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter ( 0.91 mmol per liter ) to 42 mg per deciliter ( 1.08 mmol per liter ) , lowered the triglyceride level from 164 mg per deciliter ( 1.85 mmol per liter ) to 122 mg per deciliter ( 1.38 mmol per liter ) , and lowered the LDL cholesterol level from 74 mg per deciliter ( 1.91 mmol per liter ) to 62 mg per deciliter ( 1.60 mmol per liter ) . The primary end point occurred in 282 patients in the niacin group ( 16.4 % ) and in 274 patients in the placebo group ( 16.2 % ) ( hazard ratio , 1.02 ; 95 % confidence interval , 0.87 to 1.21 ; P=0.79 by the log-rank test ) . CONCLUSIONS Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter ( 1.81 mmol per liter ) , there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period , despite significant improvements in HDL cholesterol and triglyceride levels . ( Funded by the National Heart , Lung , and Blood Institute and Abbott Laboratories ; AIM -HIGH Clinical Trials.gov number , NCT00120289 . )", "OBJECTIVE Lowering LDL-cholesterol by statins has been proven to be associated with reduction of proinflammatory regulators e.g. activation of the transcription factor NF-κB. To our knowledge , anti-inflammatory potential of newer cholesterol lowering agents such as ezetimibe is less intensively studied . Therefore we analyzed the effects of equipotent LDL-lowering therapy with simvastatin alone compared to a combination with ezetimibe on NF-κB activation in peripheral blood mononuclear cells ( P BMC s ) of patients with type 2 diabetes . METHODS Thirty-one patients with type 2 diabetes were included in a double-blind , r and omized trial receiving either 80 mg simvastatin ( sim80 ; n = 10 ) or a combination of 10 mg simvastatin and 10 mg ezetimibe ( sim10eze10 ; n = 11 ) or placebo ( n = 9 ) for eight weeks . NF-κB binding activity and inflammatory markers ( IL-6 , hsCRP ) were analyzed at baseline and after eight weeks of treatment . NF-κB binding activity was analyzed by electrophoretic mobility shift assay . IL-6 and hsCRP were measured by ELISA . RESULTS After eight weeks of treatment LDL-cholesterol was lowered to the same extent in both treatment groups ( p = 0.40 ) but not in placebo . However , patients taking sim80 showed a significant reduction of mononuclear NF-κB binding activity compared to baseline ( p = 0.009 ) while no effect was observed in the sim10eze10 group ( p = 0.79 ) . Similar differences in anti-inflammatory effects were also observed when analyzing hsCRP ( sim80 : p = 0.03 ; sim10eze10 : p = 0.40 ) and IL-6 levels ( sim80 : p = 0.15 ; sim10eze10 : p = 0.95 ) . CONCLUSION High dose simvastatin therapy reduces proinflammatory transcription factor NF-κB binding activity and hsCRP levels , while combination of low dose simvastatin with ezetimibe result ing in a similar LDL-reduction does not affect these inflammatory markers", "Purpose This post hoc analysis assessed switching to ezetimibe/simvastatin 10/20 mg vs doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg in subgroups of obese ( BMI ≥30 kg/m2 ) and non-obese ( BMI Methods This was a r and omized , double-blind , 12-week study of adults 18–79 years with cardiovascular disease with low-density lipoprotein cholesterol ( LDL-C ) ≥70 and ≤160 mg/dl . Percent change in LDL-C and other lipids was estimated . Results In obese subjects ( n = 466 ) , percent changes in LDL-C and most other lipids were greater with ezetimibe/simvastatin vs doubling the baseline statin dose or switching to rosuvastatin . In non-obese subjects ( n = 342 ) , percent changes in LDL-C , total cholesterol , non-HDL-C , Apo B and Apo A-I were greater with ezetimibe/simvastatin vs doubling the baseline statin dose or switching to rosuvastatin ; and treatment with ezetimibe/simvastatin result ed in greater changes in triglycerides vs rosuvastatin and HDL-C vs doubling the baseline statin dose . The safety profiles were generally similar . Conclusions Regardless of baseline obesity status , switching to ezetimibe/simvastatin was more effective at reducing LDL-C , total cholesterol , non-HDL-C , and Apo B vs doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg", "Background Coronary heart disease ( CHD ) risk increases with age ; yet lipid-lowering therapies are significantly under-utilized in patients > 65 years . The objective was to evaluate the safety and efficacy of lipid-lowering therapies in older patients treated with atorvastatin 10 mg + ezetimibe 10 mg ( EZ/Atorva ) vs. increasing the atorvastatin dose to 40 mg . Methods Patients ≥ 65 years with atherosclerotic vascular disease ( LDL-C ≥ 1.81 mmol/L ) or at high risk for coronary heart disease ( LDL-C ≥ 2.59 mmol/L ) were r and omized to EZ/Atorva for 12 wk vs. uptitration to atorvastatin 20 mg for 6 wk followed by atorvastatin 40 mg for 6 wk . The percent change in LDL-C and other lipid parameters and percent patients achieving prespecified LDL-C levels were assessed after 12 wk . Results EZ/Atorva produced greater reductions in most lipid parameters vs. uptitration of atorvastatin in patients ≥ 75 years ( n = 228 ) , generally consistent with patients 65–74 years ( n = 812 ) . More patients achieved LDL-C targets with combination therapy vs. monotherapy in both age groups at 6 wk and in patients ≥ 75 years at 12 wk . At 12 wk , more patients ≥ 75 years achieved LDL-C targets with monotherapy vs. combination therapy . EZ/Atorva produced more favorable improvements in most lipids vs. doubling or quadrupling the atorvastatin dose in patients ≥ 75 years , generally consistent with the findings in patients 65–74 years . Conclusions Our results extended previous findings demonstrating that ezetimibe added to a statin provided a generally well-tolerated therapeutic option for improving the lipid profile in patients 65 to 74 years and ≥ 75 years of age", "Background and Objectives Although recent lipid-lowering therapies are effective in reducing low density lipoprotein-cholesterol ( LDL-C ) levels , many patients treated with lipid-lowering agents do not achieve target LDL-C levels , especially in very high risk patients . The aim of this study is to compare the effect of ezetimibe/simvastatin 10/20 mg and atorvastatin 20 mg on achieving a target LDL-C goal in very high risk patients . Subjects and Methods A total of 74 patients with very high risk were enrolled in the study . Very high risk patients were defined as patients that displayed established cardiovascular disease with multiple major risk factors , poorly controlled risk factors , multiple risk factors of the metabolic syndrome and acute coronary syndromes . Patients were r and omized into two groups : ezetimibe/simvastatin 10/20 mg ( n=36 ) and atorvastatin 20 mg ( n=38 ) . Follow-up lipid profile was obtained 6 weeks later . A target goal of LDL-C was defined as less than 70 mg/dL at follow-up . Results Baseline clinical and laboratory data were similar between the two groups . Achieving a target LDL-C goal was observed in 41.7 % of Group 1 and 44.7 % of Group 2 at 6 weeks ( p=0.82 ) . Changes in other lipid profiles were not significantly different but the tolerability of the two groups was similar . Conclusion Ezetimibe/simvastatin 10/20 mg and atorvastatin 20 mg showed similar effects in achieving target LDL-C levels in patients with very high risk", "Background Statins are frequently administered to reduce low-density lipoprotein cholesterol ( LDL-C ) and vascular inflammation , because LDL-C and high sensitive C-reactive protein ( hs-CRP ) are associated with high risk for cardiovascular events . When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease ( CAD ) , ezetimibe can be added or the statin dose can be increased . However , which strategy is more effective for treating patients with CAD has not been established . The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients . Methods 46 patients with high-risk CAD and LDL-C and hs-CRP levels of > 70 mg/dL and > 1.0 mg/L , respectively , that were not improved by 4 weeks of rosuvastatin ( 2.5 mg/day ) were r and omly assigned to receive 10 mg ( R10 , n = 24 ) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe ( R2.5/E10 , n = 22 ) for 12 weeks . The primary endpoint was a change in hs-CRP . Results Baseline characteristics did not significantly differ between the groups . At 12 weeks , LDL-C and inflammatory markers ( hs-CRP , interleukin-6 , tumour necrosis factor-alpha and pentraxin 3 ) also did not significantly differ between the two groups ( LDL-C : R10 vs. R2.5/E10 : -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL ) . However , high-density lipoprotein cholesterol ( HDL-C ) was significantly improved in the R10 , compared with R2.5/E10 group ( 4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL ; p anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin . However , R10 elevated HDL-C more effectively than R2.5/E10.Trial registration", "BACKGROUND We investigated whether combination therapy with a statin plus a fibrate , as compared with statin monotherapy , would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease . METHODS We r and omly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo . The primary outcome was the first occurrence of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The mean follow-up was 4.7 years . RESULTS The annual rate of the primary outcome was 2.2 % in the fenofibrate group and 2.4 % in the placebo group ( hazard ratio in the fenofibrate group , 0.92 ; 95 % confidence interval [ CI ] , 0.79 to 1.08 ; P=0.32 ) . There were also no significant differences between the two study groups with respect to any secondary outcome . Annual rates of death were 1.5 % in the fenofibrate group and 1.6 % in the placebo group ( hazard ratio , 0.91 ; 95 % CI , 0.75 to 1.10 ; P=0.33 ) . Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex , with a benefit for men and possible harm for women ( P=0.01 for interaction ) , and a possible interaction according to lipid subgroup , with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol ( P=0.057 for interaction ) . CONCLUSIONS The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events , nonfatal myocardial infa rct ion , or nonfatal stroke , as compared with simvastatin alone . These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 .", "International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol ( HDL-C ) and elevated triglycerides for patients at moderately high to high coronary heart disease ( CHD ) risk . Combination therapy is often required to achieve multiple lipid treatment goals , and > or = 50 % reduction in low-density lipoprotein cholesterol ( LDL-C ) is needed in some patients to achieve aggressive LDL-C targets . In this context , we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin ( niacin ER ) , a statin plus ezetimibe , and a highly potent statin alone . This was an open-label , multicenter , 12-week study in 292 patients ( 50 % women ) who qualified for drug therapy based on number of CHD risk factors . Patients were r and omized to four parallel arms , titrated from low to moderate or high doses : atorvastatin/niacin ER , rosuvastatin/niacin ER , simvastatin/ezetimibe , or rosuvastatin alone . Baseline mean values were , for LDL-C 197 mg/dL ( 5.1 mmol/L ) , HDL-C 49 mg/dL ( 1.3 mmol/L ) , triglycerides 168 mg/dL ( 1.9 mmol/L ) . There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment . All groups lowered LDL-C by approximately 50 % or more ( range -49 to -57 % ) , achieving mean levels of 82 - 98 mg/dL ( 2.1 - 2.5 mmol/L ) . Changes in non-HDL-C ( range -46 to -55 % ) mirrored those for LDL-C and did not differ among treatment groups . Statin/niacin ER combination regimens also increased HDL-C and large HDL ( HDL2 ) and lowered triglycerides and lipoprotein ( a ) significantly more than other regimens . No drug-related myopathy or hepatotoxicity was observed . In this study , low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD", "BACKGROUND The aim of this study was to compare the effect on endothelial function of increasing statin dose to add-on ezetimibe in patients with coronary artery disease ( CAD ) already treated with statin . METHODS AND RESULTS Two-hundred and forty-three patients with CAD and low-density lipoprotein cholesterol ( LDL-C ) ≥70 mg/dl even after treatment with atorvastatin ( 10 mg ) were prospect ively r and omized to the ezetimibe addition ( 10 mg ) group ( A10E10 ; n=117 ) or to the double atorvastatin dose ( to 20 mg ; A20 ; n=133 ) group for 12 weeks . Primary endpoint was change in endothelial function measured by logarithmic-scale reactive hyperemia index ( L_RHI ) . After treatment , high-sensitivity C-reactive protein ( hs-CRP ) and all lipids except triglyceride and high-density lipoprotein cholesterol were significantly reduced in both groups . The mean percent changes in LDL-C for the A10E10 and A20 groups were -25.8 % and -9.1 % , respectively ( P 0.48 , P=0.399 ) . Absolute change in L_RHI was significantly higher in the A20 than A10E10 group ( 0.02±0.29 vs. 0.16±0.27 , P CONCLUSIONS Statin and ezetimibe have different effects on endothelial function independent from LDL-C-lowering effects ", "Few clinical studies have focused on the efficacy of lipid-lowering therapies in patients > or = 65 years of age . The percentage of change from baseline in low-density lipoprotein ( LDL ) cholesterol and the percentage of patients achieving prespecified LDL cholesterol levels after 12 weeks of ezetimibe 10 mg plus atorvastatin versus up titration of atorvastatin were assessed in subjects > or = 65 years old with hyperlipidemia and at high risk of coronary heart disease . After stabilization of atorvastatin 10-mg therapy , 1,053 patients , > or = 65 years old , at high risk of coronary heart disease , with and without atherosclerotic vascular disease and a LDL cholesterol level that was not to receive ezetimibe added to atorvastatin 10 mg for 12 weeks versus up titration to atorvastatin 20 mg for 6 weeks followed by up titration to atorvastatin 40 mg for an additional 6 weeks . Ezetimibe added to atorvastatin 10 mg result ed in significantly greater changes at week 6 in LDL cholesterol ( p LDL cholesterol level of LDL cholesterol level of ezetimibe plus atorvastatin 10 mg result ed in significantly greater changes at week 6 in total cholesterol , triglycerides , non-high-density lipoprotein ( HDL ) cholesterol , apolipoprotein B ( all p HDL cholesterol ( p = 0.021 ) compared with atorvastatin 20 mg and significantly greater changes at week 12 in LDL cholesterol , non-HDL cholesterol , apolipoprotein A-I ( p = 0.001 ) , total cholesterol , apolipoprotein B ( p HDL cholesterol ( p tolerated , with comparable safety profiles . In conclusion , adding ezetimibe to atorvastatin 10 mg produced significantly greater favorable changes in most lipids at 6 and 12 weeks and significantly greater attainment of prespecified LDL cholesterol levels than doubling or quadrupling the atorvastatin dose in patients > or = 65 years old at high risk for coronary heart disease", "BACKGROUND Type 2 diabetes mellitus ( T2DM ) is associated with a high risk for coronary heart disease ( CHD ) . A variety of lipoprotein and apolipoprotein ( Apo ) ratios have been proposed that may reflect the balance of cholesterol delivery and removal at the arterial wall and provide an assessment of CHD risk that is supplemental to low-density lipoprotein cholesterol ( LDL-C ) , the primary guide for cholesterol-lowering therapy in patients at risk . OBJECTIVE To examine changes in lipoprotein and apolipoprotein ratios in the VYTAL trial of hypercholesterolemic patients with T2DM . METHODS Changes in the ratios LDL-C/high-density lipoprotein cholesterol ( HDL-C ) , total cholesterol (TC)/HDL-C , non-HDL-C/HDL-C , and ApoB/ApoA-I were assessed in this r and omized , double-blind , parallel-group study that enrolled T2DM patients with LDL-C ≥100 mg/dL for 6-week treatments with either the usual daily starting doses of atorvastatin ( ATORVA ) 10 or 20 mg or ezetimibe/simvastatin ( EZE/SIMVA ) 10/20 mg , or the next highest doses ( ATORVA 40 mg , EZE/SIMVA 10/40 mg ) . Changes in lipoprotein and apolipoprotein ratios , prespecified exploratory endpoints , were analyzed using analysis of variance . RESULTS Efficacy results were based on 1198 patients with sufficient data among 1229 r and omized patients . Baseline lipoproteins , apolipoproteins , and ratios were comparable among treatment groups . EZE/SIMVA produced significantly greater reductions compared with ATORVA in each lipoprotein or apolipoprotein ratio at each dose comparison ( P example , reductions from baseline in TC/HDL-C were ATORVA 10 mg , -30.2 % ; ATORVA 20 mg -34.9 % ; EZE/SIMVA 10/20 mg , -41.6 % ; ATORVA 40 mg , -37.9 % ; and EZE/SIMVA 10/40 mg , -43.5 % . Tolerability of the two treatments was similar . CONCLUSION For the doses assessed , EZE/SIMVA was more effective compared with ATORVA in lowering the lipoprotein and apolipoprotein ratios that might be considered secondary measures of CHD risk", "OBJECTIVES We sought to test the platelet inhibitory and anti-inflammatory effects of a higher statin dosage compared with combined treatment with ezetimibe plus a low statin dose . BACKGROUND Reducing the level of low-density lipoprotein cholesterol ( LDL-C ) with statins induces important pleiotropic effects such as platelet inhibition . An insufficient LDL-C reduction often is treated with ezetimibe , an intestinal cholesterol absorption inhibitor , in combination with a low statin dose . It is not known whether this combination therapy has the same pleiotropic effects as a statin monotherapy . METHODS Fifty-six patients with coronary artery disease were assigned r and omly to receive either 40 mg/day of atorvastatin or 10 mg/day of ezetimibe plus 10 mg/day of atorvastatin for 4 weeks . The levels of LDL-C , platelet activation markers after stimulation , platelet aggregation , and plasma chemokine levels ( i.e. , regulated on activation normally T-cell expressed and secreted [ RANTES ] ) were measured before and after changing lipid-lowering medication . RESULTS Platelet activation markers ( P-selectin ) after stimulation ( adenosine diphosphate ) were reduced by 40 mg/day of atorvastatin ( -5.2 + /- 1.6 arbitrary units ) but not by ezetimibe plus low-dose atorvastatin ( 2.1 + /- 1.8 arbitrary units ; p LDL-C ( atorvastatin -1.01 + /- 0.18 mmol/l vs. ezetimibe plus atorvastatin -1.36 + /- 0.22 mmol/l , p = NS ) . Thrombin receptor-activating peptide-induced platelet aggregation as well as plasma RANTES levels were reduced by 40 mg/day of atorvastatin but not by ezetimibe plus low-dose atorvastatin . CONCLUSIONS Platelet reactivity and a proinflammatory chemokine were reduced more by the higher atorvastatin dose than by ezetimibe plus low-dose atorvastatin . In patients with coronary artery disease , it might be important to combine ezetimibe with higher statin dosages to benefit from cholesterol-independent pleiotropic effects", "PURPOSE To examine the efficacy and safety of colesevelam hydrochloride , a novel , nonsystemic , lipid-lowering agent , when coadministered with starting doses of simvastatin in a multicenter , r and omized , double-blind , placebo-controlled trial . PATIENTS AND METHODS Subjects with hypercholesterolemia ( plasma low density lipoprotein [ LDL ] cholesterol level > 160 mg/dL and triglyceride level were r and omly assigned to receive daily doses of placebo ( n = 33 ) , colesevelam 3.8 g ( recommended dose , n = 37 ) , simvastatin 10 mg ( n = 35 ) , colesevelam 3.8 g with simvastatin 10 mg ( n = 34 ) , colesevelam 2.3 g ( low dose , n = 36 ) , simvastatin 20 mg ( n = 39 ) , or colesevelam 2.3 g with simvastatin 20 mg ( n = 37 ) , for 6 weeks . RESULTS Mean LDL cholesterol levels decreased relative to baseline in the placebo group ( P reduction in LDL cholesterol level was 42 % ( -80 mg/dL ; P simvastatin 10 mg ( -26 % , -48 mg/dL ) or 20 mg ( -34 % , -61 mg/dL ) alone , or for colesevelam 2.3 g ( -8 % , -17 mg/dL ) or 3.8 g ( -16 % , -31 mg/dL ) alone ( P serum HDL cholesterol and triglyceride levels were similar to those for simvastatin alone . Side effects were similar among treatment groups , and there were no clinical ly important changes in laboratory parameters . CONCLUSION Coadministration of colesevelam and simvastatin was effective and well tolerated , providing additive reductions in LDL cholesterol levels compared with either agent alone", " Hypercholesterolemic patients ( n = 1,547 ) at high atherosclerotic cardiovascular disease risk with low-density lipoprotein cholesterol ( LDL-C ) levels ≥100 and ≤160 mg/dl while treated with atorvastatin 10 mg/day entered a multicenter , r and omized , double-blind , active-controlled , clinical trial using two 6-week study periods . Period I compared the efficacy/safety of ( 1 ) adding ezetimibe 10 mg ( ezetimibe ) to stable atorvastatin 10 mg , ( 2 ) doubling atorvastatin to 20 mg , or ( 3 ) switching to rosuvastatin 10 mg . Subjects in the latter 2 groups who persisted with elevated LDL-C levels ( ≥100 and ≤160 mg/dl ) after period I , entered period II ; subjects on atorvastatin 20 mg had ezetimibe added to their atorvastatin 20 mg , or uptitrated their atorvastatin to 40 mg ; subjects on rosuvastatin 10 mg switched to atorvastatin 20 mg plus ezetimibe or uptitrated their rosuvastatin to 20 mg . Some subjects on atorvastatin 10 mg plus ezetimibe continued the same treatment into period II . At the end of period I , ezetimibe plus atorvastatin 10 mg reduced LDL-C significantly more than atorvastatin 20 mg or rosuvastatin 10 mg ( 22.2 % vs 9.5 % or 13.0 % , respectively , p , ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than atorvastatin 40 mg ( 17.4 % vs 6.9 % , p from rosuvastatin 10 mg to ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than uptitrating to rosuvastatin 20 mg ( 17.1 % vs 7.5 % , p treatments , ezetimibe added to atorvastatin 10 mg ( period I ) or atorvastatin 20 mg ( period II ) produced significantly greater percent attainment of LDL-C targets percent reductions in total cholesterol , non-high-density lipoprotein cholesterol , most lipid and lipoprotein ratios , and apolipoprotein B ( except ezetimibe plus atorvastatin 20 vs atorvastatin 40 mg ) . Reports of adverse experiences were generally similar among groups . In conclusion , treatment of hypercholesterolemic subjects at high cardiovascular risk with ezetimibe added to atorvastatin 10 or 20 mg produced significantly greater improvements in key lipid parameters and significantly greater attainment of LDL-C treatment targets than doubling atorvastatin or switching to ( or doubling ) rosuvastatin at the compared doses", "Background : Combination therapy for dyslipidemia holds promise as effective treatment for patients with multiple lipid disorders , especially those at high risk", "BACKGROUND AND AIM The effect of ezetimibe-statin combination on inflammatory markers in acute coronary syndrome is unknown . The aim of our study is to evaluate the effect of this combination on the lipid profile , the CRP hs and the sCD40 lig and levels in acute coronary syndrome ( ACS ) patients . METHODS This is a r and omized , double-blind study including 93 patients admitted for ACS r and omized in 2 groups , ezetimibe 10 mg + atorvastatin 10 mg vs atorvastatin 20 mg + placebo , for 12 weeks follow-up ; blood sample s were collected for lipid profile , ALT , AST , CRP and sCD40L at baseline , 12 hours , 4 weeks , and 12 weeks . RESULTS There was no significant difference in total cholesterol levels , HDL , LDL , CRP , but there was a significant decrease in sCD40L levels in the ezetimibe combination group , with less side effects in the combination group , mainly myalgia ( p = 0.012 ) . CONCLUSION Ezetimibe combination with low dose statin in patients in acute coronary syndrome could be a safe , potent therapy to reduce LDL level with antiinflammatory effect ", "BACKGROUND Reducing low-density lipoprotein cholesterol ( LDL-C ) is the primary goal of therapy in patients with hypercholesterolemia and coronary heart disease ( CHD ) . METHODS This double blind placebo-controlled study enrolled patients 18 to 75 years of age with primary hypercholesterolemia and established CHD who were taking a stable daily dose of simvastatin 20 mg . Patients were r and omized to ezetimibe/simvastatin 10/20 mg ( eze/simva ; n = 56 ) or simvastatin 40 mg ( simva ; n = 56 ) for 6 weeks . Percent change from baseline in LDL-C , total cholesterol , high-density lipoprotein cholesterol ( HDL-C ) , and triglycerides were assessed by use of the Student t test . The percent of patients achieving LDL-C less than 100 mg/dL ( eze/simva combination result ed in significantly greater reductions in LDL-C , total cholesterol , and triglycerides versus doubling the dose of simva to 40 mg ( all P LDL-C less than 100 mg/dL ( ezetimibe/simvastatin versus doubling the dose of simva to 40 mg ( 73.2 % vs 25.0 % ; P simvastatin . Changes in HDL-C were similar between treatments . Both treatments were generally well tolerated . CONCLUSION In high-risk CHD patients with hypercholesterolemia , treatment with eze/simva combination result ed in significantly greater reductions in LDL-C , total cholesterol and triglycerides , as well as greater achievement of recommended LDL-C targets , compared with doubling the simvastatin dose to 40 mg over the 6-week period . ( CLINICAL TRIAL REGISTRATION NUMBER NCT00423579 )", "BACKGROUND Effects independent from cholesterol reduction on vascular function are considered to importantly contribute to the beneficial effects of statin therapy in cardiovascular disease . We aim ed to evaluate the effect of high versus low dose atorvastatin on endothelial dysfunction in patients with coronary artery disease ( CAD ) in a setting of comparable cholesterol reduction . METHODS AND RESULTS Fifty-eight patients with CAD were r and omly assigned to double-blind treatment for 8 weeks with atorvastatin 80 mg per day ( A80 ) or atorvastatin 10mg+ezetimibe 10 mg per day ( A10E10 ) , respectively . Flow-mediated vasodilation ( FMD ) of the brachial artery , nitroglycerin-mediated endothelium-independent vasodilation ( NMD ) , lipid , C-reactive protein ( CRP ) plasma concentrations and urinary 8-iso-prostagl and in F2alpha excretion were measured before and after treatment . Total cholesterol , triglycerides and LDL-cholesterol levels were significantly reduced with no difference between A80 and A10E10 . A80 caused significantly stronger improvement of FMD compared to A10E10 ( absolute change FMD : A80 + 2.7+/-3.0 % ( post vs. pre p NMD was improved by A80 but not by A10E10 ( absolute change NMD : A80 + 2.7+/-4.6 % , A10E10 + 0.7+/-3.5 % , p=0.12 ) . Both treatment groups caused a comparable reduction of CRP and did not effect urinary 8-iso-prostagl and in F2alpha excretion . There was no correlation between FMD or NMD change and LDL-cholesterol change in either treatment group . CONCLUSIONS The present findings clearly suggest that in the presence of comparable LDL-lowering effects of both treatment forms , LDL-cholesterol independent effects of high dose atorvastatin therapy account for the improvement of endothelium-dependent vasodilation in patients with stable CAD", "BACKGROUND Combination therapy to improve the total lipid profile may achieve greater coronary risk reductions than lowering low-density lipoprotein cholesterol ( LDL-C ) alone . A new extended-release niacin ( niacin ER)/lovastatin tablet substantially lowers LDL-C , triglyceride , and lipoprotein(a ) levels and raises high-density lipoprotein cholesterol ( HDL-C ) level . We evaluated these serum lipid responses to niacin ER/lovastatin at all clinical ly reasonable doses . METHODS Men ( n = 85 ) and women ( n = 79 ) with type IIa or IIb primary hyperlipidemia after diet were r and omized among 5 parallel treatment arms . Each arm had 5 sequential 4-week treatment periods : niacin ER ( starting at 500 mg/d , increasing in 500-mg increments to 2500 mg/d ) ; lovastatin ( starting at 10 mg , increasing to 20 mg , then 40 mg/d ) ; and 3 combinations arms , each with a constant lovastatin dose and escalating niacin ER doses . RESULTS For primary comparisons , mean LDL-C level reductions from baseline were greater with niacin ER/lovastatin ( 1500/20 mg ) than with lovastatin ( 20 mg ) ( 35 % vs 22 % , P niacin ER/lovastatin ( 2000/40 mg ) than with lovastatin ( 40 mg ) ( 46 % vs 24 % , P niacin ER , on average , decreased LDL-C levels an additional 4 % and increased HDL-C levels 8 % . The maximum recommended dose ( 2000/40 mg/d ) increased HDL-C levels 29 % and decreased LDL-C levels 46 % , triglyceride levels 38 % , and lipoprotein(a ) levels 14 % . All lipid responses were dose dependent and generally additive . Graphs of the dose-response relationships as 3-dimensional surfaces documented the strength and consistency of these responses . CONCLUSIONS Niacin ER/lovastatin combination therapy substantially improves 4 major lipoprotein levels associated with atherosclerotic disease . Dose-response surfaces provide a practical guide for dose selection", "Background Although the efficacy of ezetimibe/simvastatin and atorvastatin on traditional lipid parameters has been studied extensively , the apolipoprotein B/apolipoprotein A1 ( ApoB/ApoA1 ) ratio , which has a better predictive value for cardiovascular events , has not previously been used as a primary endpoint in these two treatment groups . Objective Our objective was to compare the efficacy and safety of ezetimibe/simvastatin 10/20 mg versus atorvastatin 20 mg once daily in Korean patients with type 2 diabetes mellitus . Study Design This study was an open-label , r and omized , controlled study . Type 2 diabetes patients with high levels of low-density lipoprotein ( LDL ) cholesterol ( > 100 mg/dL ) were r and omized to receive ezetimibe/simvastatin or atorvastatin . Main Outcome MeasureThe primary endpoint was the difference in the percent change of ApoB/ApoA1 at 12 weeks , and secondary endpoints were changes in lipid profiles , glycosylated hemoglobin ( HbA1c ) , homeostatic model assessment ( HOMA ) index , and C-reactive protein . Results In total , 132 patients ( 66 for each group ) were enrolled and r and omized . After 12 weeks of treatment , the ApoB/ApoA1 ratio was significantly reduced in both groups ; however , the difference of changes between the two groups was not statistically significant ( ezetimibe/simvastatin −38.6 ± 18.0 % vs. atorvastatin −34.4 ± 15.5 % ; p = 0.059 ) . There were no significant differences in changes to total cholesterol , LDL cholesterol , high-density lipoprotein cholesterol , triglycerides , ApoB , and ApoB48 between the two groups . However , the increments of ApoA1 were significantly greater in the ezetimibe/simvastatin group than in the atorvastatin group ( 2.8 ± 10.0 vs. −1.8 ± 9.8 % ; p = 0.002 ) . In the per- protocol analysis , improvement in ApoB/ApoA1 was significantly greater in the ezetimibe/simvastatin group ( −42.8 ± 11.8 vs. −36.7 ± 13.2 % ; p = 0.019 ) . The changes in HbA1c , HOMA index , and C-reactive protein were comparable between the two groups . The adverse reaction rate was similar between the two groups ( 24.2 vs. 34.9 % ; p = 0.180 ) . Conclusion Ezetimibe/simvastatin 10/20 mg is comparable to atorvastatin 20 mg for the management of dyslipidemia , and may have more favorable effects on apolipoprotein profiles than atorvastatin 20 mg in Korean patients with type 2 diabetes mellitus", "OBJECTIVE To find out whether the addition of fenofibrate to statin monotherapy produced any synergistic or additive beneficial effects in reducing risk factors , especially plasma fibrinogen , in patients with acute coronary syndrome ( ACS ) requiring percutaneous coronary interventions . METHODS A r and omized , non-blinded , prospect i ve study with parallel group design . One hundred two ACS patients who underwent angioplasty were r and omly assigned to atorvastatin ( 20 mg/day , n=25 ) , simvastatin ( 40 mg/day , n=27 ) , atorvastatin-fenofibrate ( 10 mg/day-200 mg/day ) combination ( n=25 ) or simvastatin-fenofibrate ( 20 mg/day-200 mg/day ) combination ( n=25 ) . The serum lipid profile and plasma fibrinogen were recorded before initiation of therapy and after three months of the respective treatments . RESULTS All patients already had desirable lipid levels as per the National Cholesterol Education Program - Adult Treatment Panel III guidelines . The addition of fenofibrate to statin monotherapy produced further benefits to the reduction in triglyceride and very low-density lipoprotein levels , and caused an increase in high-density lipoprotein levels . All the treatment groups showed a significant decrease in the plasma fibrinogen levels . Plasma fibrinogen did not correlate with study parameters such as age , body weight , hemo-dynamic characteristics and lipoprotein levels . Statin monotherapy as well as its combination with fenofibrate produced a significant decrease in the fibrinogen levels . CONCLUSIONS The addition of fenofibrate to statins seems to be beneficial in patients with ACS . Statins decreased plasma fibrinogen significantly , contrary to results from various reports , and the addition of fenofibrate further enhanced this reduction of the novel risk factor fibrinogen", "Higher than 80 % of coronary heart disease-related mortality occurs in patients ≥65 years of age . Guidelines recommend low-density lipoprotein ( LDL ) cholesterol targets for these at-risk patients ; however , few clinical studies have evaluated lipid-lowering strategies specifically in older adults . This multicenter , 12-week , r and omized , double-blind , parallel-group trial evaluated the efficacy and safety of the usual starting dose of ezetimibe/simvastatin ( 10/20 mg ) versus atorvastatin 10 or 20 mg and the next higher dose of ezetimibe/simvastatin ( 10/40 mg ) versus atorvastatin 40 mg in 1,289 hypercholesterolemic patients ≥65 years of age with or without cardiovascular disease . Patients r and omized to ezetimibe/simvastatin had greater percent decreases in LDL cholesterol ( -54.2 % for 10/20 mg vs -39.5 % and -46.6 % for atorvastatin 10 and 20 mg , respectively ; -59.1 % for 10/40 mg vs -50.8 % for atorvastatin 40 mg ; p LDL cholesterol receiving atorvastatin for all prespecified dose comparisons ( p patients achieved LDL cholesterol ezetimibe/simvastatin 10/20 mg ( 54.3 % ) versus atorvastatin 10 mg ( 10.9 % , p ) and ezetimibe/simvastatin 10/40 mg ( 69.2 % ) versus atorvastatin 40 mg ( 38.2 % , p achieved LDL cholesterol ezetimibe/simvastatin 10/20 mg ( 82.1 % ) versus atorvastatin 10 mg ( 59.3 % , p greater with ezetimibe/simvastatin than atorvastatin for all comparisons ( p 0.001 ) . High-density lipoprotein cholesterol and triglyceride results were variable . All treatments were generally well tolerated . In conclusion , ezetimibe/simvastatin provided significantly greater improvements in key lipid parameters and higher attainment of LDL cholesterol targets than atorvastatin , with comparable tolerability ", "Background Statin – fibrate combinations are very effective in the treatment of familial combined hyperlipidaemia ( FCHL ) . Nonetheless , they have not been extensively used because of the fear of side effects . Thus , a therapeutic alternative is required for this lipid disorder . Objective To compare the long-term ( one-year ) efficacy of atorvastatin monotherapy with those of four statin – fibrate combinations in 675 FCHL patients . Methods Patients were r and omly assigned to atorvastatin monotherapy ( A 20 mg/day ) n=134 , or pravastatin ( P 20 mg/day)+gemfibrozil ( G 1200 mg/day ) n=135 , simvastatin ( S 20 mg/day)+G ( 1200 mg/day ) n=137 , P ( 20 mg/day)+ciciprofibrate ( C 100 mg/day ) n=135 , and S ( 20 mg/day)+C ( 100 mg/day ) n=134 . Results Twelve patients on statin – fibrate combinations were withdrawn from the study because of side effects : Three because of CK elevation , two because of myalgia and seven due to increase in serum transaminase levels . One patient on A was withdrawn because of persistent epigastric discomfort . Atorvastatin reduced low density lipoprotein cholesterol and apoprotein B more than all four combinations ( −45 % vs. maximum −40 % of S+C , and −39 % vs. maximum −32 % of the same combination , respectively , P on triglycerides ( −38 % vs. maximum −53 % of S+C , P=0.0002 ) and high density lipoprotein cholesterol ( 6 % vs. maximum 21 % of S+G , P=0.0003 ) . The effect of A on plasma fibrinogen was analogous to that of G combinations ( −8 % vs. −9 % of P+G and −11 % of S+G , P = NS vs. baseline and among each other ) and inferior to that of the ciprofibrate combinations ( −8 % vs. −24 % of P+C , P=0.0002 and −26 % S+C , P=0.0001 ) . A had a lower treatment cost and better patient compliance , P=0.04 vs. C combinations and P=0.02 vs. G combinations . Conclusions The data suggest that statin – fibrate combinations have a beneficial effect on all lipid parameters . Atorvastatin monotherapy has a better effect on LDL-C and apoprotein B than statin – fibrate combinations , but a lesser effect on HDL-C , TG and in the case of ciprofibrate combinations , fibrinogen . The clinical significance of these findings should be tested in a large , long-term survival study", "OBJECTIVE To compare the efficacy and safety of the recommended usual starting and next highest doses of ezetimibe/ simvastatin and atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia . PATIENTS AND METHODS This double-blind , multicenter study ( June 22 to December 7 , 2005 ) consisted of adult patients r and omized to the recommended usual starting ( ezetimibe/simvastatin , 10/20 mg/d , vs atorvastatin , 10 or 20 mg/d ) or next highest ( ezetimibe/simvastatin , 10/40 mg/d , vs atorvastatin , 40 mg/d ) doses . Efficacy end points included percent changes from baseline in low-density lipoprotein cholesterol ( LDL-C ) levels ( primary ) and proportion of patients attaining LDL-C levels less than 70 mg/dL ( secondary ) . RESULTS A total of 1229 patients participated in the study . Significantly greater mean reductions were found in LDL-C levels with ezetimibe/simvastatin , 10/20 mg/d ( -53.6 % ; 95 % confidence interval [ CI ] , -55.4 % to -51.8 % ) , than with atorvastatin , 10 mg/d ( -38.3 % ; 95 % CI , -40.1 % to -36.5 % ; P ezetimibe/simvastatin , 10/40 mg/d ( -57.6 % ; 95 % CI , -59.4 % to -55.8 % ) , vs atorvastatin , 40 mg/d ( -50.9 % ; 95 % CI , -52.7 % to -49.1 % ; P Ezetimibe/simvastatin was also superior to atorvastatin in attainment of LDL-C levels less than 70 mg/dL ( P ezetimibe/simvastatin than with atorvastatin ( P total cholesterol , high-density lipoprotein cholesterol , and non-high-density lipoprotein cholesterol . Ezetimibe/ simvastatin , 10/20 mg/d , reduced high-sensitivity C-reactive protein and triglyceride levels significantly more than atorvastatin , 10 mg/d ( P = .02 ) , with comparable reductions at other doses . Incidences of clinical adverse events , including serious drug-related and prespecified gastrointestinal- , gallbladder- , and hepatitis-related allergic reactions or rash events , and laboratory adverse events , including repeated elevation of hepatic transaminases or creatine kinase levels , were similar for both treatments . CONCLUSION Ezetimibe/simvastatin provided additional lipid-modifying benefits over atorvastatin monotherapy at the recommended usual starting and next highest doses in patients with type 2 diabetes . Both treatments were generally well tolerated", "Aim : This r and omized , double‐blind study evaluated the efficacy of switching from atorvastatin ( ATV ) 10 mg to ezetimibe/simvastatin ( EZE/SIMVA ) 10/20 mg , EZE/SIMVA 10/40 mg or doubling the dose of ATV from 10 to 20 mg in patients with type 2 diabetes ( T2D )", "BACKGROUND Patients with type 2 diabetes mellitus and mixed hyperlipidemia have an increased cardiovascular risk and may not achieve recommended LDL-C and non-HDL-C goals on statin monotherapy . This study was design ed to obtain regulatory approval of a fenofibrate/pravastatin 160/40 mg fixed-dose combination ( FDC ) capsule . OBJECTIVE The aim of this study was to compare the efficacy and tolerability of this FDC and simvastatin 20 mg in patients with type 2 diabetes . METHODS This multicenter , r and omized , double-blind , parallel-arm study was conducted in patients with type 2 diabetes and mixed hyperlipidemia , without cardiovascular disease , and who were not at lipid goals with simvastatin 20 mg monotherapy . After a 6-week run-in period during which patients received simvastatin 20 mg , those with non-HDL-C concentrations ≥130 mg/dL or LDL-C concentrations ≥100 mg/dL and triglyceride concentrations 150 to 600 mg/dL were enrolled . Eligible patients were r and omly assigned to receive 12-week treatment with fenofibrate/pravastatin 160/40 mg FDC or simvastatin 20 mg once daily , followed by a 12-week open-label tolerability- assessment period during which all patients received the FDC . The primary efficacy outcome was the mean percentage change in non-HDL-C after 12 weeks . Secondary efficacy outcomes included changes in other lipid and lipoprotein parameters , fibrinogen , and high-sensitivity C-reactive protein . Tolerability was assessed based on the prevalence of adverse events and abnormal laboratory data in each treatment group . RESULTS A total of 291 patients were r and omized to receive fenofibrate/pravastatin ( n= 145 ) or simvastatin ( n = 146 ) . The mean ( SD ) age of the participants was 56.6 ( 8.9 ) years , 48.1 % were men , and the body mass index was 31.3 ( 4.6 ) kg/m(2 ) . The FDC was associated with a significantly greater reduction in non-HDL-C ( primary end point ) compared with simvastatin monotherapy ( -12.9 % [ 1.8 ] vs -6.8 % [ 1.8 ] ; P = 0.008 ) . Triglyceride ( -28.6 % [ 3.7 ] vs + 5.0 % [ 3.6 ] ; P 0.001 ) , fibrinogen ( -11.5 % [ 1.6 ] vs + 0.3 % [ 1.6 ] ; P ) , and HDL-C ( + 6.3 % [ 1.3 ] vs + 1.8 % [ 1.3 ] ; P = 0.008 ) concentrations also were significantly improved with the FDC compared with simvastatin monotherapy . The proportions of patients who achieved the LDL-C target ( combined end point of non-HDL-C and LDL-C with fenofibrate/pravastatin compared with simvastatin monotherapy ( 41 [ 28.5 % ] vs 26 [ 17.9 % ] ; P experienced ≥1 adverse event were not statistically different between the fenofibrate/pravastatin and simvastatin groups ( 17.2 % vs 15.1 % ) . However , compared with simvastatin monotherapy , the combination treatment was associated with significantly greater increases in alanine aminotransferase ( + 9.6 % vs + 1.5 % ; P = 0.03 between groups ) , creatinine ( + 13.7 % vs + 6.8 % ; P = 0.002 between groups ) , and homocysteine ( + 36.5 % vs + 1.6 % ; P population of adults with type 2 diabetes , the fenofibrate/pravastatin 160/40 mg FDC was associated with significantly greater changes from baseline in non-HDL-C , triglyceride , and HDL-C concentrations compared with simvastatin 20 mg . Both treatments were well tolerated", "AIM In patients with type 2 diabetes mellitus ( T2DM ) , combination therapy is usually required to optimize glucose metabolism as well as to help patients achieve aggressive targets for low-density lipoprotein cholesterol ( LDL-C ) and other lipid parameters associated with cardiovascular risk . The thiazolidinediones ( TZDs ) are increasingly being used for both their blood glucose-lowering properties and their modest beneficial effects on triglycerides ( TG ) and high-density lipoprotein cholesterol ( HDL-C ) . Ezetimibe , an intestinal cholesterol absorption inhibitor , has a mechanism of action that differs from that of statins , which inhibit hepatic cholesterol synthesis . We compared the lipid-modifying efficacy and safety of adding ezetimibe to simvastatin , vs. doubling the dose of simvastatin , in TZD-treated T2DM patients . METHODS This was a r and omized , double-blind , parallel group , multicentre study in T2DM patients , 30 - 75 years of age , who had been on a stable dose of a TZD for at least 3 months and had LDL-C > 2.6 mmol/l ( 100 mg/dl ) prior to study entry . Other antidiabetic medications were also allowed . Following 6 weeks of open-label simvastatin 20 mg/day , patients were r and omized to the addition of either blinded ezetimibe 10 mg/day ( n = 104 ) or an additional blinded simvastatin 20 mg/day ( total simvastatin 40 mg/day ; n = 110 ) for 24 weeks . Patients were stratified according to TZD type and dose ( pioglitazone 15 - 30 vs. 45 mg/day ; rosiglitazone 2 - 4 vs. 8 mg/day ) . RESULTS LDL-C was reduced more ( p ezetimibe 10 mg to simvastatin 20 mg ( -20.8 % ) than by doubling the dose of simvastatin to 40 mg ( -0.3 % ) . Ezetimibe plus simvastatin 20 mg also produced significant incremental reductions in non-HDL-C ( p very low-density lipoprotein cholesterol ( p apolipoprotein B ( p TG and HDL-C levels , and both treatments were well tolerated . CONCLUSIONS Co-administration of ezetimibe with simvastatin , a dual inhibition treatment strategy targeting both cholesterol synthesis and absorption , is well tolerated and provides greater LDL-C-lowering efficacy than increasing the dose of simvastatin in T2DM patients taking TZDs", "The Lipid Research Clinics Coronary Primary Prevention Trial ( LRC-CPPT ) , a multicenter , r and omized , double-blind study , tested the efficacy of cholesterol lowering in reducing risk of coronary heart disease ( CHD ) in 3,806 asymptomatic middle-aged men with primary hypercholesterolemia ( type II hyperlipoproteinemia ) . The treatment group received the bile acid sequestrant cholestyramine resin and the control group received a placebo for an average of 7.4 years . Both groups followed a moderate cholesterol-lowering diet . The cholestyramine group experienced average plasma total and low-density lipoprotein cholesterol ( LDL-C ) reductions of 13.4 % and 20.3 % , respectively , which were 8.5 % and 12.6 % greater reductions than those obtained in the placebo group . The cholestyramine group experienced a 19 % reduction in risk ( p less than .05 ) of the primary end point -- definite CHD death and /or definite nonfatal myocardial infa rct ion -- reflecting a 24 % reduction in definite CHD death and a 19 % reduction in nonfatal myocardial infa rct ion . The cumulative seven-year incidence of the primary end point was 7 % in the cholestyramine group v 8.6 % in the placebo group . In addition , the incidence rates for new positive exercise tests , angina , and coronary bypass surgery were reduced by 25 % , 20 % , and 21 % , respectively , in the cholestyramine group . The risk of death from all causes was only slightly and not significantly reduced in the cholestyramine group . The magnitude of this decrease ( 7 % ) was less than for CHD end points because of a greater number of violent and accidental deaths in the cholestyramine group . The LRC-CPPT findings show that reducing total cholesterol by lowering LDL-C levels can diminish the incidence of CHD morbidity and mortality in men at high risk for CHD because of raised LDL-C levels . This clinical trial provides strong evidence for a causal role for these lipids in the pathogenesis of CHD", "This r and omised , double-blind study evaluated the efficacy and safety of ezetimibe/simvastatin ( EZE/SIMVA ) 10/20 mg tablet compared to doubling the atorvastatin ( ATV ) dose in hypercholesterolaemic patients with atherosclerotic or coronary heart disease ( CHD ) . The study group included 435 male and female CHD patients ( aged > or=18 years ) who had not achieved their low-density lipoprotein cholesterol ( LDL-C ) goal of ATV 10 mg for > or=6 weeks . After a 1-week diet/stabilisation period , patients with LDL-C > or=2.50 mmol/l and were r and omised ( 1:1 ) to EZE/SIMVA 10/20 mg/day ( n = 221 ) or ATV 20 mg/day ( n = 214 ) for 6 weeks . The primary efficacy objective was to determine the per cent reduction from baseline in LDL-C at week 6 . EZE/SIMVA 10/20 mg produced significantly greater mean per cent changes from baseline in LDL-C compared with ATV 20 mg ( -32.8 vs. -20.3 % ; p LDL-C goal EZE/SIMVA than ATV ( 77.9 vs. 51.9 % ; p total cholesterol ( -20.3 vs. -13.0 % ) , non-high-density lipoprotein cholesterol ( non-HDL-C ) ( -27.9 vs. -17.0 % ) , apolipoprotein B ( -23.4 vs. -14.7 % ) and HDL-C ( 1.8 vs. -0.4 % ) were observed after switching to EZE/SIMVA 10/20 mg for 6 weeks ( p EZE/SIMVA 10/20 mg was generally well tolerated , with an overall safety profile similar to that of ATV 20 mg . EZE/SIMVA 10/20 mg produced superior lipid-altering efficacy by dual inhibition of cholesterol synthesis and intestinal absorption compared with doubling the dose of ATV from 10 to 20 mg", "BACKGROUND Lowering of LDL cholesterol reduces major vascular events , but whether more intensive therapy safely produces extra benefits is uncertain . We aim ed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk . METHODS We undertook a double-blind r and omised trial in 12,064 men and women aged 18 - 80 years with a history of myocardial infa rct ion . Participants were either currently on or had clear indication for statin therapy , and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not . R and omisation to either 80 mg or 20 mg simvastatin daily was done central ly using a minimisation algorithm . Participants were assessed at 2 , 4 , 8 , and 12 months after r and omisation and then every 6 months until final follow-up . The primary endpoint was major vascular events , defined as coronary death , myocardial infa rct ion , stroke , or arterial revascularisation . Analysis was by intention to treat . This study is registered , number IS RCT N74348595 . FINDINGS 6031 participants were allocated 80 mg simvastatin daily , and 6033 allocated 20 mg simvastatin daily . During a mean follow-up of 6·7 ( SD 1·5 ) years , allocation to 80 mg simvastatin produced an average 0·35 ( SE 0·01 ) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg . Major vascular events occurred in 1477 ( 24·5 % ) participants allocated 80 mg simvastatin versus 1553 ( 25·7 % ) of those allocated 20 mg , corresponding to a 6 % proportional reduction ( risk ratio 0·94 , 95 % CI 0·88 - 1·01 ; p=0·10 ) . There were no apparent differences in numbers of haemorrhagic strokes ( 24 [ 0·4 % ] vs 25 [ 0·4 % ] ) or deaths attributed to vascular ( 565 [ 9·4 % ] vs 572 [ 9·5 % ] ) or non-vascular ( 399 [ 6·6 % ] vs 398 [ 6·6 % ] ) causes . Compared with two ( 0·03 % ) cases of myopathy in patients taking 20 mg simvastatin daily , there were 53 ( 0·9 % ) cases in the 80 mg group . INTERPRETATION The 6 % ( SE 3·5 % ) reduction in major vascular events with a further 0·35 mmol/L reduction in LDL cholesterol in our trial is consistent with previous trials . Myopathy was increased with 80 mg simvastatin daily , but intensive lowering of LDL cholesterol can be achieved safely with other regimens . FUNDING Merck ; The Clinical Trial Service Unit also receives funding from the UK Medical Research Council and the British Heart Foundation", "BACKGROUND In the setting of stable coronary artery disease ( CAD ) , it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone . OBJECTIVE We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10mg/simvastatin 20 mg ( E10/S20 ) with simvastatin 80 mg ( S80 ) . METHODS AND RESULTS CAD patients ( n=83 , 63 ± 9 years , 57 % men ) receiving S20 , were r and omly allocated to receive E10/S20 or S80 , for 6 weeks . Lipids , inflammatory markers ( C-reactive protein , interleukin-6 , monocyte chemoattractant protein-1 , soluble CD40 lig and and oxidized LDL ) , and platelet aggregation ( platelet function analyzer [PFA]-100 ) changes were determined . Baseline lipids , inflammatory markers and PFA-100 were similar between groups . After treatment , E10/S20 and S80 patients presented , respectively : ( 1 ) similar reduction in LDL-C ( 29 ± 13 % vs. 28 ± 30 % , p=0.46 ) , apo-B ( 18 ± 17 % vs. 22 ± 15 % , p=0.22 ) and oxidized LDL ( 15 ± 33 % vs. 18 ± 47 % , p=0.30 ) ; ( 2 ) no changes in inflammatory markers ; and , ( 3 ) a higher increase of the PFA-100 with E10/S20 than with S80 ( 27 ± 43 % vs. 8 ± 33 % , p=0.02 ) . CONCLUSIONS These data suggest that among stable CAD patients treated with S20 , ( 1 ) both E10/S20 and S80 were equally effective in further reducing LDL-C ; ( 2 ) neither treatment had any further significant anti-inflammatory effects ; and ( 3 ) E10/S20 was more effective than S80 in inhibiting platelet aggregation . Thus , despite similar lipid lowering and doses 4 × less of simvastatin , E10/S20 induced a greater platelet inhibitory effect than S80", "Background : Coadministration of any statin with ezetimibe is as effective as using high doses of the same statin in the reduction of low-density lipoprotein cholesterol ( LDL-c ) . There may be other effects called pleiotropics . Objective : To compare the effectiveness of 2 different treatments that obtain equivalent LDL-c reductions ( 80 mg of simvastatin , once a day and coadministration of 10 mg of simvastatin and 10 mg of ezetimibe , once a day ) over endothelial function and inflammation . Methods : Twenty-three r and omized patients with hypercholesterolemia in a 2 × 2 crossover protocol were studied . Endothelial function was analyzed by ultrasound assessment of endothelial dependent flow-mediated vasodilation of the brachial artery , and inflammation was estimated by high-sensitivity C-reactive protein ( hs-CRP ) . Results : LDL-c reduction was similar between the 2 treatments with simvastatin/ezetimibe and with simvastatin ( P significantly the endothelial function [ 3.61 % with simvastatin/ezetimibe ( P = 0.003 ) and 5.08 % with simvastatin ( P P = 0.291 ) . hs-CRP had a 23 % reduction with simvastatin/ezetimibe ( P = 0.004 ) and a 30 % reduction with simvastatin alone ( P = 0.01 ) , with no significant difference between the 2 treatments ( P = 0.380 ) . Conclusion : The 2 forms of treatment presented similar pleiotropic effects : improvement in endothelial function and decrease in hs-CRP levels " ]

[ "Abstract Objective : To assess the impact of a social marketing programme for distributing nets treated with insecticide on malarial parasitaemia and anaemia in very young children in an area of high malaria transmission . Design : Community cross sectional study . Annual , cross sectional data were collected at the beginning of the social marketing campaign ( 1997 ) and the subsequent two years . Net ownership and other risk and confounding factors were assessed with a question naire . Blood sample s were taken from the children to assess prevalence of parasitaemia and haemoglobin levels . Setting : 18 villages in the Kilombero and Ulanga districts of southwestern Tanzania . Participants : A r and om sample of children aged under 2 years . Main outcome measures : The presence of any parasitaemia in the peripheral blood sample and the presence of anaemia ( classified as a haemoglobin level of ≤80 g/l ) . Results : Ownership of nets increased rapidly ( treated or not treated nets : from 58 % to 83 % ; treated nets : from 10 % to 61 % ) . The mean haemoglobin level rose from 80 g/l to 89 g/l in the study children in the successive surveys . Overall , the prevalence of anaemia in the study population decreased from 49 % to 26 % in the two years studied . Treated nets had a protective efficacy of 62 % ( 95 % confidence interval 38 % to 77 % ) on the prevalence of parasitaemia and of 63 % ( 27 % to 82 % ) on anaemia . Conclusions : These results show that nets treated with insecticide have a substantial impact on morbidity when distributed in a public health setting", "OBJECTIVES The objective of this study was to assess the effectiveness of government regulation of private pharmacy practice in a low-income country . METHODS The intervention comprised inspections of the pharmacies , information , and distribution of documents to drug sellers and sanctions . It was implemented at two different intensity levels , active and regular intervention . The methods used to assess the effect of the interventions were interviews with the district drug inspectors , drug sellers and customers , inspection of drug purchases , and indicator surveys of pharmacies . Indicators for pharmacy-specific quality as well as for dispensing quality were developed . RESULTS The main finding was one of strong overall improvements from initially low levels . The improvements were particularly marked by increases in the availability of essential material s for dispensing by 34 % and in order in the pharmacy by 19 % . Information given to customers increased from 35 % to 51 % and the mixing of different drugs in the same package went down from 17 % to 9 % . The pharmacies in the active intervention districts showed greater improvements for four of the six indicators , although statistically significant compared with the regular intervention districts only for the essential material s indicator . CONCLUSIONS It was concluded that the regulatory activities have probably been an important factor behind the service quality improvements . It appeared feasible as well as effective to regulate private pharmacy practice in this particular low-income setting", "SETTING Rural and urban areas of Maharashtra , a large state in Western India . OBJECTIVE To underst and tuberculosis ( TB ) management practice s among private medical practitioners ( PPs ) and the treatment behaviour of the patients they manage . DESIGN Prospect i ve study of help-seeking patterns and treatment behaviour among 173 pulmonary TB patients diagnosed in private clinics , and the TB management practice s of 122 PPs treating these patients . RESULTS The first source of help for 86 % of patients was a PP . The diagnostic and treatment practice s of PPs were inadequate ; 15 % did not consider sputum examination to be necessary , and 79 different treatment regimens were prescribed by 105 reporting PPs . Sixty-seven percent of the patients diagnosed in private clinics remained with the private sector , and the rest shifted to public health services within six months of treatment . The treatment adherence rate among the patients in private clinics was 59 % . There were discrepancies between the reported management practice s of the PPs and what their patients actually followed . CONCLUSION The study identifies and highlights the need to educate PPs and their TB patients , and indicates ways in which PPs could be meaningfully involved in efforts to revitalize the national TB control programme", "In just a few years , oral rehydration therapy ( ORT ) has become the st and ard treatment to reduce infant diarrhoeal disease mortality in the developing world . The paper describes an ORT intervention campaign in a rural area in Western Kenya ( Kakamega District ) . After about a year of careful preparation , the campaign was launched in January 1986 and compared the use of a value-added product ( flavoured sachets ) sold through private outlets in addition to primary care distribution of an unflavoured sachet in an experimental cell ( Bukura Division ) . In a control cell ( Novakholo Division ) , only unflavoured sachets were distributed free of charge through primary health care facilities . Using local perceptions of diarrhoeal disease management , the campaign in the experimental cell was carefully design ed and mass communication techniques employed and adapted accordingly . Outcome assessment s of the campaign , which lasted until March 1987 , included the overall ORT utilisation over time . Changes in perceptions towards diarrhoeal disease management , direct assessment s of mixing a ' safe and effective ' solution accurately and other relevant process parameters were evaluated . Comparing several recent ORT intervention projects , the paper concludes that a combination of a commercial approach and mass communication techniques can further ORS use . If a proper incentive system for shopkeepers is installed and message design and ORS product are fully tailored to the perception and preferences of the target population , the commercial availability of ORS will create an extra dem and of the product . However , this will not replace distribution of ORS salts delivered free of charge through primary care sources", "Objectives : To evaluate the training of pharmacists in Accra , Ghana , in the syndromic management of STIs . Methods : We r and omly selected 50 pharmacy outlets that had received the training ( intervention ) and 50 outlets that had not received the training ( no intervention ) . Simulated clients described the symptoms of urethral discharge to the first pharmacy staff encountered and completed a st and ardised question naire after each encounter . Results : Correct drug provision for urethral discharge improved with the educational intervention but remained relatively low ( no intervention 18 % ; intervention 39 % ; p treatment for gonorrhoea was usually correct without the intervention ( 64 % ) and improved further in the intervention outlets ( 76 % ) . The treatment for chlamydia was less often appropriate but also improved ( 31 % and 41 % ) . Condom promotion was poor , with almost no outlets offering condoms . Conclusions : The current training led to improvements in the treatment of urethral discharge . Future training needs to be improved , especially with regard to condom promotion . Moreover , since less than one third of simulated clients were seen by pharmacists , the training should be exp and ed to other pharmacy staff . With enhanced training of all pharmacy staff , the role of pharmacy outlets in STI management and prevention in Ghana and elsewhere can be optimised", "OBJECTIVE To determine whether female adolescents from low-income areas in Managua were satisfied with the sexual and reproductive health ( SRH ) care provided through a competitive voucher programme and to analyse the determinants of their satisfaction . DESIGN A community-based quasi-experimental intervention study from 2000 to 2002 . SETTING Low-income areas of Managua . INTERVENTION Distribution of 28,711 vouchers giving adolescents free-access to SRH care in 19 clinics ; training and support for health care providers . STUDY PARTICIPANTS A r and om sample of 3009 girls from 12 to 20 years completed self-administered question naires : 700 respondents had used this care in the last 15 months , 221 with voucher ( users-with-voucher ) and 479 without voucher ( users-without-voucher ) . MAIN OUTCOME MEASURES User satisfaction ; Satisfaction with clinic reception ; Clarity of doctors ' explanations . RESULTS User satisfaction was significantly higher in users-with-voucher compared with users-without-voucher [ Adjusted odds-ratio ( AOR ) = 2.2 ; 95 % confidence interval ( 95 % CI ) = 1.2 - 4.0 ] . Voucher use was associated with more frequent satisfaction with clinic reception , especially among sexually active girls not yet pregnant or mother ( AOR = 6.9 ; 95 % CI = 1.5 - 31.8 ) . The clarity of doctors ' explanations was not perceived differently ( AOR = 1.4 ; 95 % CI = 0.9 - 2.2 ) . User satisfaction was highly correlated to satisfaction with clinic reception and clarity of doctors ' explanations ( P consultation times , shorter waiting times , older age , and having a female doctor positively influenced user satisfaction . CONCLUSION Voucher use by teenage girls was associated with a better perceived SRH care . This is an important result , given the crucial role user satisfaction plays in adoption and continued use of health care and contraceptives . Though more research is needed , confidential and guaranteed access appear key factors to voucher success", "BACKGROUND The objective of this study was to evaluate a competitive voucher program intended to make sexual and reproductive health care ( SRHC ) accessible to adolescents from disadvantaged areas of Managua . METHODS A quasi-experimental intervention study was performed in which 28,711 vouchers that gave free access to SRHC in 20 health centers , were distributed to adolescents . To evaluate the impact , community sampling took place in markets , neighborhoods , and outside schools where self-administered question naires were distributed . The study comprised a r and om sample of 3,009 female adolescents , ages 12 to 20 years old , 904 voucher receivers and 2,105 nonreceivers . Their use of SRHC , and knowledge and use of contraceptives and condoms were measured . RESULTS Voucher receivers had a significantly higher use of SRHC compared with nonreceivers , 34 % versus 19 % ( adjusted odds ratio , 3.1 ; 95 % confidence interval , 2.5 - 3.8 ) . The highest influence was seen among respondents at schools , where use was 24 % relative to 6 % in nonreceivers ( adjusted odds ratio , 5.9 ; 95 % confidence interval , 3.7 - 9.5 ) . Voucher receivers answered significantly more questions correctly that were related to knowledge of contraceptives and sexually transmitted infections than nonreceivers . At schools , sexually active voucher receivers had a significantly higher use of modern contraceptives than nonreceivers , 48 % versus 33 % ( adjusted odds ratio , 2.3 ; 95 % confidence interval , 1.2 - 4.4 ) ; and in neighborhoods , condom use during last sexual contact was significantly greater among voucher receivers than nonreceivers ( adjusted odds ratio , 2.5 ; 95 % confidence interval , 1.4 - 4.5 ) . CONCLUSION The voucher program succeeded in increasing access to SRHC for poor and underserved girls . The needs of adolescents were met with a relatively simple intervention through existing health facilities . Many adolescents appeared willing to protect themselves against the risks of sexual intercourse . This suggest that access to SRHC can play an important role in changing youth behavior and increase the use of contraceptives and condoms" ]

[ "The long-term physiological effects of refined carbohydrates on appetite and mood remain unclear . Reported effects when subjects are not blind may be due to expectations and have rarely been studied for more than 24 h. The present study compared the effects of supplementary soft drinks added to the diet over 4 weeks on dietary intake , mood and BMI in normal-weight women ( n 133 ) . Subjects were categorised as ' watchers ' or ' non-watchers ' of what they ate then received sucrose or artificially sweetened drinks ( 4 x 250 ml per d ) . Expectancies were varied by labelling drinks ' sugar ' or ' diet ' in a counter-balanced design . Sucrose supplements provided 1800 kJ per d and sweetener supplements provided 67 kJ per d. Food intake was measured with a 7 d diary and mood with ten single Likert scales . By 4 weeks , sucrose supplements significantly reduced total carbohydrate intake ( F(1,129 ) = 53.81 ; P fat ( F(2,250 ) = 33.33 ; P protein intake ( F(2,250 ) = 28.04 ; P sweetener supplements . Mean daily energy intake increased by just under 1000 kJ compared with baseline ( t ( 67 df ) = 3.82 ; P sucrose to gain weight . There were no effects on appetite or mood . Neither dietary restraint status as measured by the Dutch Eating Behaviour Question naire nor the expectancy procedure had effects . Expectancies influenced mood only during baseline week . It is concluded that sucrose satiates , rather than stimulates , appetite or negative mood in normal-weight subjects", "BACKGROUND During the nutrition transition in Chile , dietary changes were marked by increased consumption of high-energy , nutrient-poor products , including sugar-sweetened beverages ( SSBs ) . Obesity is now the primary nutritional problem in posttransitional Chile . OBJECTIVE We conducted a r and omized controlled trial to examine the effects on body composition of delivering milk beverages to the homes of overweight and obese children to displace SSBs . DESIGN We r and omly assigned 98 children aged 8 - 10 y who regularly consumed SSBs to intervention and control groups . During a 16-wk intervention , children were instructed to drink 3 servings/d ( approximately 200 g per serving ) of the milk delivered to their homes and to not consume SSBs . Body composition was measured by dual-energy X-ray absorptiometry . Data were analyzed by multiple regression analysis according to the intention-to-treat principle . RESULTS For the intervention group , milk consumption increased by a mean ( + /- SEM ) of 452.5 + /- 37.7 g/d ( P consumption of SSBs decreased by -711.0 + /- 33.7 g/d ( P milk consumption did not change , and consumption of SSBs increased by 71.9 + /- 33.6 g/d ( P = 0.04 ) . Changes in percentage body fat , the primary endpoint , did not differ between groups . Nevertheless , the mean ( + /- SE ) accretion of lean body mass was greater ( P = 0.04 ) in the intervention ( 0.92 + /- 0.10 kg ) than in the control ( 0.62 + /- 0.11 kg ) group . The increase in height was also greater ( P = 0.01 ) in the intervention group ( 2.50 + /- 0.21 cm ) than in the control group ( 1.77 + /- 0.20 cm ) for boys but not for girls . CONCLUSION Replacing habitual consumption of SSBs with milk may have beneficial effects on lean body mass and growth in children , despite no changes in percentage body fat . This trial was registered at clinical trials.gov as NCT00149695", "To examine whether artificial sweeteners aid in the control of long-term food intake and body weight , we gave free-living , normal-weight subjects 1150 g soda sweetened with aspartame ( APM ) or high-fructose corn syrup ( HFCS ) per day . Relative to when no soda was given , drinking APM-sweetened soda for 3 wk significantly reduced calorie intake of both females ( n = 9 ) and males ( n = 21 ) and decreased the body weight of males but not of females . However , drinking HFCS-sweetened soda for 3 wk significantly increased the calorie intake and body weight of both sexes . Ingesting either type of soda reduced intake of sugar from the diet without affecting intake of other nutrients . Drinking large volumes of APM-sweetened soda , in contrast to drinking HFCS-sweetened soda , reduces sugar intake and thus may facilitate the control of calorie intake and body weight", "Background We investigated the effects of a calcium-fortified beverage supplemented over 12 months on body composition in postmenopausal women ( n = 37 , age = 48–75 y ) . Methods Body composition ( total-body percent fat , % FatTB ; abdominal percent fat , % FatAB ) was measured with dual energy x-ray absorptiometry . After baseline assessment s , subjects were r and omly assigned to a free-living control group ( CTL ) or the supplement group ( 1,125 mg Ca++/d , CAL ) . Dietary intake was assessed with 3-day diet records taken at baseline and 12 months ( POST ) . Physical activity was measured using the Yale Physical Activity Survey . Results At 12 months , the dietary calcium to protein ratio in the CAL group ( 32.3 ± 15.6 mg/g ) was greater than the CTL group ( 15.2 ± 7.5 mg/g ) . There were no differences from baseline to POST between groups for changes in body weight ( CAL = 0.1 ± 3.0 kg ; CTL = 0.0 ± 2.9 kg ) , % FatTB ( CAL = 0.0 ± 2.4 % ; CTL = 0.5 ± 5.4 % ) , % FatAB ( CAL = -0.4 ± 8.7 % ; CTL = 0.6 ± 8.7 % ) , or fat mass ( CAL = 1.3 ± 2.6 kg ; CTL = 1.3 ± 2.7 kg ) . Conclusion These results indicate that increasing the calcium to protein ratio over two-fold by consuming a calcium-fortified beverage for 12 months did not decrease body weight , body fat , or abdominal fat composition in postmenopausal women", "BACKGROUND Baseline data collected on each patient at r and omisation in controlled clinical trials can be used to describe the population of patients , to assess comparability of treatment groups , to achieve balanced r and omisation , to adjust treatment comparisons for prognostic factors , and to undertake subgroup analyses . We assessed the extent and quality of such practice s in major clinical trial reports . METHODS A sample of 50 consecutive clinical -trial reports was obtained from four major medical journals during July to September , 1997 . We tabulated the detailed information on uses of baseline data by use of a st and ard form . FINDINGS Most trials presented baseline comparability in a table . These tables were often unduly large , and about half the trials inappropriately used significance tests for baseline comparison . Methods of r and omisation , including possible stratification , were often poorly described . There was little consistency over whether to use covariate adjustment and the criteria for selecting baseline factors for which to adjust were often unclear . Most trials emphasised the simple unadjusted results and covariate adjustment usually made negligible difference . Two-thirds of the reports presented subgroup findings , but mostly without appropriate statistical tests for interaction . Many reports put too much emphasis on subgroup analyses that commonly lacked statistical power . INTERPRETATION Clinical trials need a predefined statistical analysis plan for uses of baseline data , especially covariate-adjusted analyses and subgroup analyses . Investigators and journals need to adopt improved st and ards of statistical reporting , and exercise caution when drawing conclusions from subgroup findings", "Objective : To examine the effect of various combinations of beverages on hydration status in healthy free-living adult males . Methods : In a counterbalanced , crossover manner , 18 healthy adult males ages 24 to 39 , on four separate occasions , consumed water or water plus varying combinations of beverages . Clinical guidelines were used to determine the fluid allowance for each subject . The beverages were carbonated , caffeinated caloric and non-caloric colas and coffee . Ten of the 18 subjects consumed water and carbonated , non-caffeinated , citrus soft drink during a fifth trial . Body weight , urine and blood assays were measured before and after each treatment . Results : Slight body weight loss was observed on all treatments , with an average of 0.30 % for all treatments . No differences ( p>0.05 ) among treatments were found for body weight changes or any of the biochemical assays . Biochemical assays conducted on first voids and 24-hour urines included electrolytes , creatine , osmolality and specific gravity . Blood sample s were analyzed for hemoglobin , hematocrit , electrolytes , osmolality , urea nitrogen , creatinine and protein . Conclusions : This preliminary study found no significant differences in the effect of various combinations of beverages on hydration status of healthy adult males . Advising people to disregard caffeinated beverages as part of the daily fluid intake is not substantiated by the results of this study . The across-treatment weight loss observed , when combined with data on fluid-disease relationships , suggests that optimal fluid intake may be higher than common recommendations . Further research is needed to confirm these results and to explore optimal fluid intake for healthy individuals", "OBJECTIVE To determine whether an educational programme aim ed at discouraging students from drinking sugar-sweetened beverages could prevent excessive weight gain . DESIGN Forty-seven classes in twenty-two schools were r and omised as intervention or control . SUBJECTS Participants were 1140 , 9 - 12-year-old fourth grade rs ( 435 in the intervention group and 608 in the control group ) . Sugar-sweetened beverages and juice intake were measured through one 24 h recall at baseline and another at the end of the trial . The main outcome was the change in BMI ( BMI = weight (kg)/height ( m2 ) ) , measured at the beginning and at the end of the school year . Intention-to-treat analysis was performed taking into account the cluster ( classes ) effect . RESULTS A statistically significant decrease in the daily consumption of carbonated drinks in the intervention compared to control ( mean difference = -56 ml ; 95 % CI -119 , -7 ml ) was followed by a non-significant overall reduction in BMI , P = 0.33 . However , among those students overweight at baseline , the intervention group showed greater BMI reduction ( -0.4 kg/m2 compared with -0.2 kg/m2 in the control group ( P = 0.11 ) ) , and this difference was statistically significant among girls ( P = 0.009 ) . Fruit juice consumption was slightly increased in the intervention group ( P = 0.08 ) , but not among girls . CONCLUSION Decreasing sugar-sweetened beverages intake significantly reduced BMI among overweight children , and mainly among girls . Efforts to reduce energy intake through liquids need to emphasise overall sweetened beverages and addition of sugar on juices", "Objective To assess the long term effects of an obesity prevention programme in schools . Design Longitudinal results after a cluster r and omised controlled trial . Setting Schools in southwest Engl and . Participants Of the original sample of 644 children aged 7 - 11 , 511 children were tracked and measurements were obtained from 434 children three years after baseline . Intervention The intervention was conducted over one school year , with four sessions of focused education promoting a healthy diet and discouraging the consumption of carbonated drinks . Main outcome measures Anthropometric measures of height , weight , and waist circumference . Body mass index ( BMI ) converted to z scores ( SD scores ) and to centile values with growth reference curves . Waist circumference was also converted to z scores ( SD scores ) . Results At three years after baseline the age and sex specific BMI z scores ( SD scores ) had increased in the control group by 0.10 ( SD 0.53 ) but decreased in the intervention group by −0.01 ( SD 0.58 ) , with a mean difference of 0.10 ( 95 % confidence interval −0.00 to 0.21 , P=0.06 ) . The prevalence of overweight increased in both the intervention and control group at three years and the significant difference between the groups seen at 12 months was no longer evident . The BMI increased in the control group by 2.14 ( SD 1.64 ) and the intervention group by 1.88 ( SD 1.71 ) , with mean difference of 0.26 ( −0.07 to 0.58 , P= 0.12 ) . The waist circumference increased in both groups after three years with a mean difference of 0.09 ( −0.06 to 0.26 , P=0.25 ) . Conclusions These longitudinal results show that after a simple year long intervention the difference in prevalence of overweight in children seen at 12 months was not sustained at three years", "Background Epidemiological studies may be subject to selective reporting , but empirical evidence thereof is limited . We empirically evaluated the extent of selection of significant results and large effect sizes in a large sample of recent articles . Methods and Findings We evaluated 389 articles of epidemiological studies that reported , in their respective abstract s , at least one relative risk for a continuous risk factor in contrasts based on median , tertile , quartile , or quintile categorizations . We examined the proportion and correlates of reporting statistically significant and nonsignificant results in the abstract and whether the magnitude of the relative risks presented ( coined to be consistently ≥1.00 ) differs depending on the type of contrast used for the risk factor . In 342 articles ( 87.9 % ) , ≥1 statistically significant relative risk was reported in the abstract , while only 169 articles ( 43.4 % ) reported ≥1 statistically nonsignificant relative risk in the abstract . Reporting of statistically significant results was more common with structured abstract s , and was less common in US-based studies and in cancer outcomes . Among 50 r and omly selected articles in which the full text was examined , a median of nine ( interquartile range 5–16 ) statistically significant and six ( interquartile range 3–16 ) statistically nonsignificant relative risks were presented ( p = 0.25 ) . Paradoxically , the smallest presented relative risks were based on the contrasts of extreme quintiles ; on average , the relative risk magnitude was 1.41- , 1.42- , and 1.36-fold larger in contrasts of extreme quartiles , extreme tertiles , and above-versus-below median values , respectively ( p < 0.001 ) . Conclusions Published epidemiological investigations almost universally highlight significant associations between risk factors and outcomes . For continuous risk factors , investigators selectively present contrasts between more extreme groups , when relative risks are inherently lower", "This is to cross-over study to assess the effectiveness of fresh young coconut water ( CW ) , and carbohydrate-electrolyte beverage ( CEB ) compared with plain water ( PW ) for whole body rehydration and blood volume ( BV ) restoration during a 2 h rehydration period following exercise-induced dehydration . Eight healthy male volunteers ( mean age and VO2max of 22.4 + /- 3.3 years and 45.8 + /- 1.5 ml min kg-1 respectively ) exercised at 60 % of VO2max in the heat ( 31.1 + /- 0.03 degrees C , 51.4 + /- 0.1 % rh ) until 2.78 + /- 0.06 % ( 1.6 + /- 0.1 kg ) of their body weight ( BW ) was lost . After exercise , the subjects sat for 2 h in a thermoneutral environment ( 22.5 + /- 0.1 degrees C ; 67.0 + /- 1.0 % rh ) and drank a volume of PW , CW and CEB on different occasions representing 120 % of the fluid loss . A blood and urine sample , and the body weight of each subject was taken before and after exercise and at 30 min intervals throughout a rehydration period . Each subject remained fasted throughout rehydration . Each fluid was consumed in three portions in separate trials representing 50 % ( 781 + /- 47 ml ) , 40 % ( 625 + /- 33 ml ) and 30 % ( 469 + /- 28 ml ) of the 120 % fluid loss at 0 , 30 and 60 min of the 2 h rehydration period , respectively . The drinks given were r and omised . In all the trials the subjects were somewhat hypohydrated ( range 0.08 - 0.18 kg BW below euhydrated BW ; p > 0.05 ) after a 2 h rehydration period since additional water and BW were lost as a result of urine formation , respiration , sweat and metabolism . The percent of body weight loss that was regained ( used as index of percent rehydration ) during CW , PW , and CEB trials was 75 + /- 5 % , 73 + /- 5 % and 80 + /- 4 % respectively , but was not statistically different between trials . The rehydration index , which provided an indication of how much of what was actually ingested was used for body weight restoration , was again not different statistically between trials ( 1.56 + /- 0.14 , 1.36 + /- 0.13 and 1.71 + /- 0.21 for CW , CEB and PW respectively ) . Although BV restoration was better with CW , it was not statistically different from CEB and PW . Cumulative urine output was similar in all trials . There were no difference at any time in serum Na+ and Cl- , serum osmolality , and net fluid balance between the three trials . Urine osmolality decreased after 1 h during the rehydration period and it was lowest in the PW trial . Plasma glucose concentrations were significantly higher compared with PW ingestion when CW and CEB were ingested during the rehydration period . CW was significantly sweeter , caused less nausea , fullness and no stomach upset and was also easier to consume in a larger amount compared with CEB and PW ingestion . In conclusion , ingestion of fresh young coconut water , a natural refreshing beverage , could be used for whole body rehydration after exercise", "BACKGROUND Nutritional intake by military personnel is typically inadequate during field exercises , potentially compromising health and performance . HYPOTHESIS Drinking a supplemental carbohydrate ( CHO ) beverage will increase total caloric intake and maintain nutritional status during military training in the desert . METHODS A total of 63 volunteers were r and omly assigned to one of two groups to receive either a CHO or placebo beverage with military rations during an 11-d desert field exercise . Fluid intake was ad libitum and adequate rations were provided . Blood sample s were collected twice to assess nutritional status , and nutrient intake was determined with consumption data . Mood state was examined by question naire . RESULTS Energy intake was significantly higher in the CHO group ( 3050 kcal x d(-1 ) vs. 2631 kcal x d(-1 ) ) , with additional CHO from the beverage providing energy with some compensation by reduced fat and protein intake . Intakes of energy , folacin , calcium , magnesium , iron , and zinc in both groups were inadequate , with intakes significantly lower ( p Blood parameters of nutritional status remained within normal ranges with no differences between groups , but significant decreases were seen in pre-albumin . No changes in mood were seen during the training , nor after exposure to desert conditions . CONCLUSIONS The operational ration supplemented with a CHO beverage significantly increases CHO and energy intakes compared with st and ard rations and maintains nutritional status for short exercises . Fortification with micronutrients most at risk for deficient intake from foods may be needed for longer deployments", "BACKGROUND : Beverages are contributing an increased proportion of energy to the diet . Because they elicit a weak compensatory dietary response , they may increase risk of positive energy balance . OBJECTIVES : This study aim ed to document the differential effects of matched liquid and solid carbohydrate loads on diet and body weight . DESIGN : In a cross-over design , seven males and eight females consumed dietary carbohydrate loads of 1880 kJ/day as a liquid ( soda ) or solid ( jelly beans ) during two 4 week periods separated by a 4 week washout . Subjects were permitted to consume the loads however they chose . In addition to baseline measurements , diet records were obtained on r and om days throughout the study , body composition was measured weekly , physical activity was assessed before and after treatments and hunger was assessed during washout and midway through each treatment . RESULTS : Free-feeding energy intake during the solid period was significantly lower than intake prior to this period . Dietary energy compensation was precise ( 118 % ) . No decrease in free-feeding energy intake occurred during the liquid period . Total daily energy intake increased by an amount equal to the load result ing in dietary compensation of −17 % . Consequently , body weight and BMI increased significantly only during the liquid period . Physical activity and hunger were unchanged . CONCLUSIONS : This study indicates that liquid carbohydrate promotes positive energy balance , whereas a comparable solid carbohydrate elicits precise dietary compensation . Increased consumption of energy-yielding fluids may promote positive energy balance", "OBJECTIVE . The role of sugar-sweetened beverages ( SSBs ) in promoting obesity is controversial . Observational data link SSB consumption with excessive weight gain ; however , r and omized , controlled trials are lacking and necessary to resolve the debate . We conducted a pilot study to examine the effect of decreasing SSB consumption on body weight . METHODS . We r and omly assigned 103 adolescents aged 13 to 18 years who regularly consumed SSBs to intervention and control groups . The intervention , 25 weeks in duration , relied largely on home deliveries of noncaloric beverages to displace SSBs and thereby decrease consumption . Change in SSB consumption was the main process measure , and change in body mass index ( BMI ) was the primary end point . RESULTS . All of the r and omly assigned subjects completed the study . Consumption of SSBs decreased by 82 % in the intervention group and did not change in the control group . Change in BMI , adjusted for gender and age , was 0.07 ± 0.14 kg/m2 ( mean ± SE ) for the intervention group and 0.21 ± 0.15 kg/m2 for the control group . The net difference , −0.14 ± 0.21 kg/m2 , was not significant overall . However , baseline BMI was a significant effect modifier . Among the subjects in the upper baseline- BMI tertile , BMI change differed significantly between the intervention ( −0.63 ± 0.23 kg/m2 ) and control ( + 0.12 ± 0.26 kg/m2 ) groups , a net effect of −0.75 ± 0.34 kg/m2 . The interaction between weight change and baseline BMI was not attributable to baseline consumption of SSBs . CONCLUSIONS . A simple environmental intervention almost completely eliminated SSB consumption in a diverse group of adolescents . The beneficial effect on body weight of reducing SSB consumption increased with increasing baseline body weight , offering additional support for American Academy of Pediatrics guidelines to limit SSB consumption", "In recent years , the prevalence of type 2 diabetes mellitus has dramatically increased in Korea as the diet has rapidly become westernized . We determined the effect of a long-term cola intake for insulin resistance in weaning male Sprague Dawley rats consuming a moderate fat diet . Thirty male pubs born from 6 female rats were r and omized into cola or water drinking groups . The rats of the cola group were freely provided with 33 energy percent fat diets and cola for 28 weeks , while the rats of the control group had the same diet with water instead of cola . The daily caloric intake did not differ between groups , while the rats in the cola group consumed more carbohydrates . However , the mean body weight of the cola group was lower than that of the control group from the second week of the study . Whole body glucose disposal rates measured by euglycemic hyperinsulinemic clamp were higher in the cola group . Compared to the control group , glycogen contents and fraction velocity of glycogen synthase of the quadriceps muscle in the cola group were higher by 39.4 % and 40.3 % , respectively . Uncoupling protein (UCP)-2 and GLUT 4 contents of soleus and quadriceps muscles were higher in the cola group than the control group . In conclusion , insulin action improved with increased peripheral glucose utilization in weaning male rats drinking cola , which was partly due to lower body weight . This latter was possibly as a result of increased thermogenesis in muscles", "BACKGROUND This r and omized , double-blind , placebo-controlled clinical trial is the first study reported from outside China that has examined the general effects of the orally consumed goji berry , Lycium barbarum , as a st and ardized juice ( GoChi ; FreeLife International LLC , Phoenix , AZ ) to healthy adults for 14 days . METHODS Based upon the medicinal properties of Lycium barbarum in traditional Asian medicine , we examined by question naire subjective ratings ( 0 - 5 ) of general feelings of well-being , neurologic/psychologic traits , gastrointestinal , musculoskeletal , and cardiovascular complaints as well as any adverse effects . Also , measures of body weight , body-mass index , blood pressure , pulse rate , and visual acuity were assessed before and after consuming 120 mL of GoChi/day or placebo control solution . Data were statistically analyzed for changes between day 1 and day 15 . RESULTS Significant differences between day 1 and day 15 were found in the GoChi group ( N = 16 ) in increased ratings for energy level , athletic performance , quality of sleep , ease of awakening , ability to focus on activities , mental acuity , calmness , and feelings of health , contentment , and happiness . GoChi also significantly reduced fatigue and stress , and improved regularity of gastrointestinal function . In contrast , the placebo group ( N = 18 ) showed only two significant changes ( heartburn and happiness ) . No significant changes in musculoskeletal or cardiovascular complaints were observed in either group . All parametric data ( body weight , etc . ) were not significantly different between groups or between day 1 and day 15 for either group . CONCLUSIONS These results clearly indicate that daily consumption of GoChi for 14 days increases subjective feelings of general well-being , and improves neurologic/psychologic performance and gastrointestinal functions . The data strongly suggest that further research is indicated to confirm and extend knowledge of the potential effects of Lycium barbarum upon human health", "Objective : To investigate the influence of ingestion of beverages with sucrose or with intense sweeteners on food intake ( FI ) and on hunger ratings in before and after a month of daily consumption of beverages . Design : Experimental study . Setting : Department of Physiology , University Hospital , Dijon , France . Subjects : In all , 12 men and 12 women , aged 20–25 y. Interventions : Four beverages contained either sucrose ( E+:100 g/l , 1672 kJ ) or intense sweeteners ( E− : None energy content ) and were flavoured with either orange ( O ) or raspberry ( R ) . FI was measured in the lab during two 2-consecutive-day periods , carried out on 2 successive weeks ( session 1 ) . The subjects drank 2 l of either E+ or E− beverages on the first day of both weekly periods , according to a balanced r and omised design . E+ was paired with O for 50 % of subjects and with R for the other 50 % . Subjects were then habituated over a 4-week period to both beverages , consuming 1 l of E+ beverage on odd days and 1 l of E– drink on even days . After this period , the measurements of session 1 were repeated ( session 2 , weeks 7–8 ) . Finally , FI was measured for two more 2-day periods ( weeks 9–10 ) after the association between flavour and energy content was reversed ( session 3 ) . Results : The E– drinks were less palatable than the E+ drinks . Besides , we observed that FI was not reduced in response to a liquid extra caloric load and there was no change in hunger ratings after the beverages in any of the sessions . Conclusion : Ingestion of caloric beverages induced a positive energy balance and the continuous exposure phase to these beverages over 1 month did not improve FI adaptation in response to the extra energy provided by the beverages . Sponsorship : This study was sponsored by SEV , Bourg la Reine , France ; the French Ministère de la Recherche et de la Technologie ( Programme AGROBIO-Aliments Demain ) and the Regional Council of Burgundy ( Dijon , France )", "Continuous exposure variables are frequently categorized in epidemiologic data analysis . It has recently been shown that such categorization may transform nondifferential error in measuring continuous exposure variables into differential exposure misclassification . This paper assesses the direction and magnitude of the result ing misclassification bias under a variety of practically relevant forms of nondifferential measurement error . The expected bias of measures of the exposure-disease association is toward the None in the case of purely r and om measurement error with a mean of zero . Systematic nondifferential over- or underestimation of the exposure may bias measures of the exposure-disease association either toward the None or away from the None , depending on the underlying distribution of exposure , the true exposure-disease relation , and the cutpoints employed for categorization . If exposure measurement error has both r and om and systematic components , the direction of the net bias is less predictable than with pure error of either type , but bias toward the None is increasingly likely as the r and om component grows larger . The results indicate the need for careful evaluation of potential effects of nondifferential exposure measurement error in epidemiologic studies in which categories are formed from continuous exposure variables . ( Epidemiology 1994;5:510–517", "OBJECTIVE To examine prospect ively the association between beverage consumption ( fruit juice , fruit drinks , milk , soda , and diet soda ) and changes in weight and body mass index among preschool children . DESIGN A prospect i ve cohort study that collected dietary , anthropometric , and sociodemographic data .Subjects/ Setting The study population included 1,345 children age 2 to 5 years participating in the North Dakota Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) on two visits between 6 to 12 months apart . Statistical analyses We performed linear regression analyses to examine whether beverage consumption was associated with annual change in weight and body mass index . Intakes were measured as continuous ( oz/day ) and we also dichotomized fruit juice , fruit drinks , and milk at high intakes . RESULTS In multivariate regression analyses adjusted for age , sex , energy intake , change in height , and additional sociodemographic variables , weight change was not significantly related to intakes ( per ounce ) of fruit juice ( beta=0.01 lb/year , 95 % CI : -0.01 to 0.20 , P=.28 ) , fruit drinks ( beta=-0.03 lb/year , 95 % CI : -0.07 to 0.01 , P=.28 ) , milk ( beta=0.00 lb/year , 95 % CI : -0.02 to 0.02 , P=.86 ) , soda ( beta=-0.00 lb/year , 95 % CI : -0.08 to 0.08 , P=.95 ) , or diet soda ( beta=0.01 lb/year , 95 % CI : -0.11 to 0.13 , P=.82 ) . Findings remained None when we examined associations with body mass index and when fruit juice , fruit drinks , and milk were dichotomized at high intake levels in both analyses . CONCLUSIONS Our study does not show an association between beverage consumption and changes in weight or body mass index in this population of low-income preschool children in North Dakota", "Objective The present study evaluated weight loss and compliance outcomes for overweight adolescents assigned to one of two dietary interventions differing in the type of snacks allowed . Methods The study was a 12-week , controlled clinical trial , among otherwise healthy but overweight ( body mass index ≥95th percentile ) 11-year-old to 15-year-old girls who were r and omly assigned to either a 1,500 kcal/day free-snack program or a 1,500 kcal/day restricted-snack program . All subjects were counseled to consume three servings of dairy products per day , and were provided with a 500 mg calcium supplement as well . Subjects in the free-snack group could choose any 150-calorie item as one of their two daily snacks , including regular soda if desired ; however , subjects in the restricted-snack group were limited to diet soda . Results Thirty-two adolescent girls completed the 12-week intervention . Both diets were equally effective in achieving a modest amount of weight loss , and were equally acceptable to the subjects . Significant decreases in weight , body mass index , anthropometric measures , total cholesterol and triglycerides were observed . Conclusions A 1,500 kcal/day diet allowing for a free snack of 150 calories was equally as effective as a more restricted snack policy in achieving a modest amount of weight loss among overweight 11-year-old to 15-year-old girls . In addition , results suggest that some soda may be included in a teen weight control diet , as long as caloric intake is maintained at recommended levels , and care is taken to achieve adequate intake of essential nutrients . Calcium intake among subjects was low at baseline , and , although it increased during the study ( due to supplementation ) , further efforts to increase consumption of naturally calcium-rich and calcium-fortified foods and beverages are needed", "Energy compensation following the consumption of caloric beverages is said to be imprecise and incomplete . This study compared the relative impact on satiety and energy intakes of the physical form of foods versus the timing of consumption . Thirty-two volunteers ( 16 men and 16 women ) , aged 18 - 35 years , consumed equal-energy preloads ( 1254 kJ , 300 kcal ) of regular cola ( 710 ml , 24 oz ) or fat-free raspberry cookies ( 87 g , 3 oz ) on two occasions each . The preloads were presented either 2 h or 20 min before the test meal . Their principal ingredient was sugar . Participants rated motivational states prior to ingestion and at 30-min intervals . A tray lunch was presented at 12:30 p.m. , and food consumption was measured . Regular cola and cookies suppressed hunger ratings equally and no temporal difference in satiety was observed . Cola , but not cookies , result ed in lower ratings of thirst . Energy intakes at lunch were lower when the preload was consumed closer to the test meal ( 20 min ) but was not affected by physical form ( liquid vs. solid ) . Cola , but not cookies , reduced water intakes at lunch . There was no satiety deficit following the ingestion of a beverage as compared with a solid food . The timing of consumption may be more important than the physical form of energy consumed", "PURPOSE To determine whether a significant relationship exists between fat mass ( FM ) development and physical activity ( PA ) and /or sugar-sweetened drink ( SD ) consumption in healthy boys and girls aged 8 - 19 yr . METHODS A total of 105 males and 103 females were assessed during childhood and adolescence for a maximum of 7 yr and a median of 5 yr . Height was measured biannually . Fat-free mass ( FFM ) and FM were assessed annually by dual x-ray absorptiometry ( DXA ) . PA was evaluated two to three times annually using the PAQ-C/A. Energy intake and SD were assessed using a 24-h dietary intake question naire also completed two to three times per year . Years from peak height velocity were used as a biological maturity age indicator . Multilevel r and om effects models were used to test the relationship . RESULTS When controlling for maturation , FFM , and energy intake adjusted for SD , PA level was negatively related to FM development in males ( P0.05 ) . In contrast , there was no relationship between SD and FM development of males or females ( P>0.05 ) . There was also no interaction effect between SD and PA ( P>0.05 ) with FM development . CONCLUSION This finding lends support to the idea that increasing PA in male youths aids in the control of FM development . Models employed showed no relationship between SD and FM in either gender" ]

[ "Background The gut microbiota is interlinked with obesity , but direct evidence of effects of its modulation on body fat mass is still scarce . We investigated the possible effects of Bifidobacterium animalisssp . lactis 420 ( B420 ) and the dietary fiber Litesse ® Ultra polydextrose ( LU ) on body fat mass and other obesity-related parameters . Methods 225 healthy volunteers ( healthy , BMI 28–34.9 ) were r and omized into four groups ( 1:1:1:1 ) , using a computer-generated sequence , for 6 months of double-blind , parallel treatment : 1 ) Placebo , microcrystalline cellulose , 12 g/d ; 2 ) LU , 12 g/d ; 3 ) B420 , 1010 CFU/d in microcrystalline cellulose , 12 g/d ; 4 ) LU + B420 , 12 g + 1010 CFU/d . Body composition was monitored with dual-energy X-ray absorptiometry , and the primary outcome was relative change in body fat mass , comparing treatment groups to Placebo . Other outcomes included anthropometric measurements , food intake and blood and fecal biomarkers . The study was registered in Clinical trials.gov ( NCT01978691 ) . Findings There were marked differences in the results of the Intention-To-Treat ( ITT ; n = 209 ) and Per Protocol ( PP ; n = 134 ) study population s. The PP analysis included only those participants who completed the intervention with > 80 % product compliance and no antibiotic use . In addition , three participants were excluded from DXA analyses for PP due to a long delay between the end of intervention and the last DXA measurement . There were no significant differences between groups in body fat mass in the ITT population . However , LU + B420 and B420 seemed to improve weight management in the PP population . For relative change in body fat mass , LU + B420 showed a − 4.5 % ( − 1.4 kg , P = 0.02 , N = 37 ) difference to the Placebo group , whereas LU ( + 0.3 % , P = 1.00 , N = 35 ) and B420 ( − 3.0 % , P = 0.28 , N = 24 ) alone had no effect ( overall ANOVA P = 0.095 , Placebo N = 35 ) . A post-hoc factorial analysis was significant for B420 ( − 4.0 % , P = 0.002 vs. Placebo ) . Changes in fat mass were most pronounced in the abdominal region , and were reflected by similar changes in waist circumference . B420 and LU + B420 also significantly reduced energy intake compared to Placebo . Changes in blood zonulin levels and hsCRP were associated with corresponding changes in trunk fat mass in the LU + B420 group and in the overall population . There were no differences between groups in the incidence of adverse events . Discussion This clinical trial demonstrates that a probiotic product with or without dietary fiber controls body fat mass . B420 and LU + B420 also reduced waist circumference and food intake , whereas LU alone had no effect on the measured outcomes", "Background / Objectives : The population of the obese is increasing worldwide . Prevention and improvement of obesity are indispensable for decreasing the risk of metabolic disorders . We have recently shown that obesity and fatty liver are reduced by a plant-derived lactic acid bacterium , Pediococcus pentosaceus LP28 ( LP28 ) , in high-fat diet-induced obese mice . The aim of the present clinical study is to prove that LP28 is effective for reducing body fat and body weight , as shown in the experiment using mice . Subjects/ Methods : The clinical trial was carried out as a double-blind , r and omized , placebo-controlled study comprising 62 subjects ( 20–70 years of age , BMI 25–30 kg/m2 ) . These subjects were r and omly assigned to three groups that received living LP28 , heat-killed LP28 or a placebo powder , administered orally once a day for 12 weeks . Results : Heat-killed LP28 reduced BMI ( 0.45 kg/m2 , 95 % CI ( 0.04 , 0.86 ) , P=0.035 ) , body fat percentage ( 1.11 % , ( 0.39 , 1.82 ) , P=0.002 ) , body fat mass ( 1.17 kg ( 0.43 , 1.92 ) , P=0.004 ) and waist circumference ( 2.84 cm ( 0.74 , 4.93 ) , P=0.009 ) when compared with a placebo group . Fasting plasma glucose , HbA1c , fasting insulin , HOMA-IR and serum lipids levels did not change by either living LP28 or heat-killed LP28 intake . Conclusions : Heat-killed LP28 displays an antiobesity effect that reduces BMI , body fat and waist circumference , suggesting that the plant-derived lactic acid bacterium LP28 would be a promising preventive of metabolic syndrome", "In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias", "This study evaluated the impact of probiotic supplementation ( Lactobacillus rhamnosus CGMCC1.3724 ( LPR ) ) on appetite sensations and eating behaviors in the context of a weight-reducing program . Obese men ( n = 45 ) and women ( n = 60 ) participated in a double-blind , r and omized , placebo-controlled trial that included a 12-week weight loss period ( Phase 1 ) based on moderate energy restriction , followed by 12 weeks of weight maintenance ( Phase 2 ) . During the two phases of the program , each subject consumed two capsules per day of either a placebo or a LPR formulation ( 10 mg of LPR equivalent to 1.6 108 CFU/capsule , 210 mg of oligofructose , and 90 mg of inulin ) . The LPR supplementation increased weight loss in women that was associated with a greater increase in the fasting desire to eat ( p = 0.03 ) . On the other h and , satiety efficiency ( satiety quotient for desire to eat ) at lunch increased ( p = 0.02 ) , whereas disinhibition ( p = 0.05 ) and hunger ( p = 0.02 ) scores decreased more in the LPR-treated women , when compared with the female control group . Additionally , the LPR female group displayed a more pronounced decrease in food craving ( p = 0.05 ) , and a decrease in the Beck Depression Inventory score ( p = 0.05 ) that was significantly different from the change noted in the placebo group ( p = 0.02 ) , as well as a higher score in the Body Esteem Scale question naire ( p = 0.06 ) . In men , significant benefits of LPR on fasting fullness and cognitive restraint were also observed . Taken together , these observations lend support to the hypothesis that the gut-brain axis may impact appetite control and related behaviors in obesity management", "Objectives : The purpose of this study was to investigate whether probiotics had an effect on proinflammatory markers and cytokines in overweight and obese individuals and whether they could have synergistic effects with weight-loss diets . Methods : A total of 75 healthy overweight and obese individuals completed this r and omized doubled-blind controlled clinical trial . Participants were r and omly assigned to groups consuming regular yogurt with a low-calorie diet ( LCD , RLCD ; n = 25 ) or receiving probiotic yogurt with LCD ( PLCD ; n = 25 ) or consuming probiotic yogurt without LCD ( PWLCD ; n = 25 ) for 8 weeks . The pribiotic regimen contained 200 g/day yogurt , enriched by Lactobacillus acidophilus La5 , Bifidobacterium BB12 , and Lactobacillus casei DN001 108 colony-forming units/g . Body fat percentage , high-sensitive C-reactive protein ( hs-CRP ) , tumor necrosis factor-alpha ( TNF-α ) , leptin , and mRNA levels of inflammation-related genes ( TNF-α and RAR-related orphan receptor gamma [ ROR-γt ] ) in peripheral blood mononuclear cells ( P BMC s ) were measured . Results : A reduction in body mass index ( BMI ) , fat percentage , and leptin level was observed that was more obvious in groups who received the weight-loss diet with probiotic yogurt . Reduction in the gene expression of ROR-γt was significant in the PLCD group ( p The expression of TNF-α did not change among all groups after intervention . The mean concentration of leptin was significantly decreased in all groups after the dietary intervention , but the mean changes in leptin level in the PLCD group was more prominent compared to the other two groups ( −2.38 , p The reduction in serum levels of hs-CRP was more evident in the PWLCD group compared to the PLCD and RLCD groups after the 8-week intervention ( −3.4 , p = 0.03 vs −1.76 , p the weight-loss diet and probiotic yogurt had synergistic effects on T-cells subset specific gene expression in P BMC s , fat percentage , and body weight among overweight and obese individuals", "Background / Objectives : In spite of the much evidence for the beneficial effects of probiotics , their anti-obesity effects have not been well examined . We evaluated the effects of the probiotic Lactobacillus gasseri SBT2055 ( LG2055 ) on abdominal adiposity , body weight and other body measures in adults with obese tendencies . Subjects/ Methods : We conducted a multicenter , double-blind , r and omized , placebo-controlled intervention trial . Subjects ( n=87 ) with higher body mass index ( BMI ) ( 24.2–30.7 kg/m2 ) and abdominal visceral fat area ( 81.2–178.5 cm2 ) were r and omly assigned to receive either fermented milk ( FM ) containing LG2055 ( active FM ; n=43 ) or FM without LG2055 ( control FM ; n=44 ) , and were asked to consume 200 g/day of FM for 12 weeks . Abdominal fat area was determined by computed tomography . Results : In the active FM group , abdominal visceral and subcutaneous fat areas significantly ( P respectively . Body weight and other measures also decreased significantly ( P : body weight , 1.4 % ( −1.1 ( −1.5 , −0.7 ) kg ) ; BMI , 1.5 % ( −0.4 ( −0.5 , −0.2 ) kg/m2 ) ; waist , 1.8 % ( −1.7 ( −2.1 , −1.4 ) cm ) ; hip , 1.5 % ( −1.5 ( −1.8 , −1.1 ) cm ) . In the control group , by contrast , none of these parameters decreased significantly . High-molecular weight adiponectin in serum increased significantly ( P on abdominal adiposity , body weight and other measures , suggesting its beneficial influence on metabolic disorders", "BACKGROUND Controversy exists as to whether the lipid-lowering properties of kefir drink ( a fermented probiotic dairy product ) in animal models could be replicated in humans . OBJECTIVE To assess and compare the potential lipid-lowering effects of kefir drink with low-fat milk in a dairy-rich diet in overweight or obese premenopausal women . METHODS In this 8-week , single-center , multiarm , parallel-group , outpatient , r and omized controlled trial , 75 eligible Iranian women aged 25 to 45 years were r and omly allocated to kefir , milk , or control groups . Women in the control group received a weight-maintenance diet containing 2 servings/d of low-fat dairy products , whereas subjects in the milk and kefir groups received a similar diet containing 2 additional servings/d ( a total of 4 servings/d ) of dairy products from low-fat milk or kefir drink , respectively . At baseline and study end point , serum levels/ratios of total cholesterol ( TC ) , low- and high-density lipoprotein cholesterol ( LDLC and HDLC ) , triglyceride , Non-HDLC , TC/HDLC , LDLC/HDLC , and triglyceride/LDLC were measured as outcome measures . RESULTS After 8 weeks , subjects in the kefir group had significantly lower serum levels/ratios of lipoproteins than those in the control group ( mean between-group differences were -10.4 mg/dL , -9.7 mg/dL , -11.5 mg/dL , -0.4 , and -0.3 for TC , LDLC , non-HDLC , TC/HDLC , and LDLC/HDLC , respectively ; all P kefir and milk groups . CONCLUSION Kefir drink causes a significant yet similar improvement in serum lipid profile , compared with low-fat milk , in a dairy-rich diet in overweight or obese premenopausal women", "Background / objectives : Owing to excess body weight and increased secretion of inflammatory cytokines primarily during the third trimester , pregnancy is associated with elevated insulin resistance . To our knowledge , no report is available indicating the effects of probiotic yoghurt consumption on serum insulin levels in pregnant women . This study was design ed to determine the effects of daily consumption of probiotic yoghurt on insulin resistance and serum insulin levels of Iranian pregnant women . Subjects/ methods : In this r and omized controlled clinical trial , 70 primigravida pregnant women with singleton pregnancy at their third trimester were participated . We r and omly assigned participants to consume 200 g per day of conventional ( n=33 ) or the probiotic group ( n=37 ) for 9 weeks . The probiotic yoghurt was a commercially available product prepared with the starter cultures of Streptococcus thermophilus and Lactobacillus bulgaricus , enriched with probiotic culture of two strains of lactobacilli ( Lactobacillus acidophilus LA5 ) and bifidobacteria ( Bifidobacterium animalis BB12 ) with a total of min 1 × 107 colony-forming units . Fasting blood sample s were taken at baseline and after 9-week intervention to measure fasting plasma glucose and serum insulin levels . Homeostatic model assessment of insulin resistance ( HOMA-IR ) was used to calculate insulin resistance score . Results : Although consumption of probiotic yogurt for 9 weeks did not affect serum insulin levels and HOMA-IR score , significant differences were found comparing changes in these variables between probiotic and conventional yogurts ( changes from baseline in serum insulin levels : + 1.2±1.2 vs + 5.0±1.1 μIU/ml , respectively , P=0.02 ; and in HOMA-IR score : −0.2±0.3 vs 0.7±0.2 , respectively , P=0.01 ) . Conclusions : It is concluded that in contrast to conventional yogurt , daily consumption of probiotic yogurt for 9 weeks maintains serum insulin levels and might help pregnant women prevent developing insulin resistance", "Background Gut lactobacilli can affect the metabolic functions of healthy humans . We tested whether a 1500 kcal/d diet supplemented with cheese containing the probiotic Lactobacillus plantarum TENSIA ( Deutsche Sammlung für Mikroorganismen , DSM 21380 ) could reduce some symptoms of metabolic syndrome in Russian adults with obesity and hypertension . Methods In this 3-week , r and omized , double-blind , placebo-controlled , parallel pilot study , 25 subjects ingested probiotic cheese and 15 ingested control cheese . Fifty grams of each cheese provided 175 kcal of energy . Blood pressure ( BP ) , anthropometric characteristics , markers of liver and kidney function , metabolic indices ( plasma glucose , lipids , and cholesterol ) , and urine polyamines were measured . Counts of fecal lactobacilli and L. plantarum TENSIA were evaluated using molecular methods . The data were analyzed by t-test for independent sample s and Spearman ’s partial correlation analysis . Results The probiotic L. plantarum TENSIA was present in variable amounts ( 529.6 ± 232.5 gene copies ) in 16/25 ( 64 % ) study subjects . Body mass index ( BMI ) was significantly reduced ( p = 0.031 ) in the probiotic cheese group versus the control cheese group . The changes in BMI were closely associated with the water content of the body ( r = 0.570 , p = 0.0007 ) when adjusted for sex and age . Higher values of intestinal lactobacilli after probiotic cheese consumption were associated with higher BMI ( r = 0.383 , p = 0.0305 ) and urinary putrescine content ( r = 0.475 , p = 0.006 ) . In patients simultaneously treated with BP-lowering drugs , similar reductions of BP were observed in both groups . A positive association was detected between TENSIA colonization and the extent of change of morning diastolic BP ( r = 0.617 , p = 0.0248 ) and a trend toward lower values of morning systolic BP ( r = −0.527 , p = 0.0640 ) at the end of the study after adjusting for BMI , age , and sex . Conclusion In a pilot study of obese hypertensive patients , a hypocaloric diet supplemented with a probiotic cheese helps to reduce BMI and arterial BP values , recognized symptoms of metabolic syndrome . Trial registration Current Controlled Trials IS RCT", "OBJECTIVE To investigate whether a probiotic mix has additional effects when compared with an isolated dietary intervention on the body composition , lipid profile , endotoxemia , inflammation , and antioxidant profile . METHODS Women who had excess weight or obesity were recruited to a r and omized , double-blind trial and received a probiotic mix ( Lactobacillus acidophilus and casei ; Lactococcus lactis ; Bifidobacterium bifidum and lactis ; 2 × 1010 colony-forming units/day ) ( n = 21 ) or placebo ( n = 22 ) for 8 weeks . Both groups received a dietary prescription . Body composition was assessed by anthropometry and dual-energy X-ray absorptiometry . The lipid profile , lipid accumulation product , plasma fatty acids , lipopolysaccharide , interleukin-6 , interleukin-10 , tumor necrosis factor-α , adiponectin , and the antioxidant enzymes activities were analyzed . RESULTS In comparison with the dietary intervention group , the dietary intervention + probiotic mix group showed a greater reduction in the waist circumference ( -3.40 % vs. -5.48 % , P = 0.03 ) , waist-height ratio ( -3.27 % vs. -5.00 % , P = 0.02 ) , conicity index ( -2.43 % vs. -4.09 % P = 0.03 ) , and plasma polyunsaturated fatty acids ( 5.65 % vs. -18.63 % , P = 0.04 ) and an increase in the activity of glutathione peroxidase ( -16.67 % vs. 15.62 % , P of a probiotic mix reduced abdominal adiposity and increased antioxidant enzyme activity in a more effective way than an isolated dietary intervention", "Objective : To investigate the effect of a probiotic milk product containing the culture CAUSIDO ® and of two alternative products on risk factors for cardiovascular disease in overweight and obese subjects . Design : An 8 week r and omized , double-blind , placebo- and compliance-controlled , parallel study .Subjects : Seventy healthy , weight-stable , overweight and obese ( 25.0 , were r and omly assigned into five groups . Intervention : Four groups consumed 450 ml fermented milk products ( yoghurt ) daily . Group 1 : a yoghurt fermented with two strains of Streptococcus thermophilus and two strains of Lactobacillus acidophilus ( StLa ) . Group 2 : a placebo yoghurt fermented with delta-acid-lactone ( PY ) . Group 3 : a yoghurt fermented with two strains of Streptococcus thermophilus and one strain of Lactobacillus rhamnosus ( StLr ) . Group 4 : a yoghurt fermented with one strain of Enterococcus faecium and two strains of Streptococcus thermophilus ( CAUSIDO ® culture ) , GAIO ® ( G ) . The dietary composition of the yoghurt was otherwise similar . The fifth group was given two placebo pills ( PP ) daily . Results : When comparing all five treatment groups , unadjusted for changes in body weight , no statistical effects were observed in week 8 in the G-group on low density lipoproteins (LDL)-cholesterol ( P=0.29 ) . After adjustment for small changes in body weight , LDL-cholesterol decreased by 8.4 % ( 0.26±0.10 mmol/l ; P weeks , systolic blood pressure was significantly more reduced in the StLa and G-group compared to StLr . No other differences were found . Conclusion : The CAUSIDO ® culture reduced LDL-cholesterol and increased fibrinogen in the overweight subjects at a 450 ml consumption daily for 8 weeks . The effect on LDL-cholesterol confirms previous studies . An immunostimulation by one of the strains in the product might explain the effect on fibrinogen in the G-group . Sponsorship : MD Foods A/S , Denmark . European Journal of Clinical Nutrition ( 2000 ) 54 ,", "Recent findings on the association of gut microbiota with various diseases , including obesity , prompted us to investigate the possibility of using a certain type of gut bacteria as a safe therapeutic for obesity . Lactobacillus mutants with enhanced capacity in absorption of free fatty acids ( FFAs ) were isolated to show reduced absorption of FFAs by the administered host , attributing to inhibition of body weight gain and body fat accumulation as well as amelioration of blood profiles . Consequently , high throughput screening of natural FFAs‐absorbing intestinal microbes led to the isolation of Lactobacillus reuteri JBD30 l. The administration of Lactobacillus JBD30l lowered the concentration of FFAs in the gut fluid content of small intestine , thus reducing intestinal absorption of FFAs whereas promoting fecal excretion of FFAs . Animal data also confirmed that the efficacy of Lactobacillus JBD30l on body weight similar to that of orlistat , an FDA ‐approved pharmaceutical for long‐term use to treat obesity . In a subsequent r and om , double‐blind , placebo‐controlled clinical trial ( KCT0000452 at Clinical Research Information Service of Korea ) , there was a statistically significant difference in the percentage change in body weight between the Lactobacillus JBD301 and the placebo group ( P = 0.026 ) as well as in the BMI ( P = 0.036 ) from the 0‐week assessment to the 12‐week assessment . Our results show that FFA‐absorbing Lactobacillus JBD301 effectively reduces dietary fat absorption , providing an ideal treatment for obesity with inherent safety", "Purpose Controversy exists regarding whether increasing dairy intake without energy restriction would lead to weight loss . We aim ed to compare the potential weight-reducing effects of kefir drink ( a probiotic dairy product ) and milk in a dairy-rich non-energy-restricted diet in overweight or obese premenopausal women . Methods One hundred and forty-four subjects were assessed for eligibility in this single-center , multi-arm , parallel-group , r and omized controlled trial . Of these , seventy-five eligible women aged 25–45 years were r and omly assigned to three groups , labeled as control , milk , and kefir , to receive an outpatient dietary regimen for 8 weeks . Subjects in the control group received a diet providing a maintenance level of energy intake , containing 2 servings/day of low-fat dairy products , while those in the milk and kefir groups received a weight maintenance diet , containing 2 additional servings/day ( a total of 4 servings/day ) of dairy products from low-fat milk or commercial kefir drink , respectively . Anthropometric outcomes including weight , body mass index ( BMI ) , and waist circumference ( WC ) were measured every 2 weeks . Results Fifty-eight subjects completed the study . Using analysis of covariance models in the intention-to-treat population ( n = 75 ) , we found that at 8 weeks , subjects in the kefir and milk groups had significantly greater reductions in weight , BMI , and WC compared to those in the control group ( all p Conclusions Kefir drink leads to a similar weight loss , compared with milk , in a dairy-rich non-energy-restricted diet in overweight or obese premenopausal women . However , further studies are warranted", "Our previous study showed that supplementation with a combination of Lactobacillus curvatus ( L. curvatus ) HY7601 and Lactobacillus plantarum ( L. plantarum ) KY1032 reduced the body weight , body fat percentage , body fat mass and L1 subcutaneous fat area in overweight subjects . We aim ed to evaluate whether the changes in adiposity after supplementation with Lactobacillus strains were associated with metabolic intermediates . A r and omized , double-blind , placebo-controlled study was conducted on 66 non-diabetic and overweight individuals . Over a 12-week period , the probiotic group consumed 2 g of probiotic powder , whereas the placebo group consumed the same product without the probiotics . To investigate metabolic alterations , we performed plasma metabolomics using ultra-performance liquid chromatography and mass spectrometry ( UPLC-LTQ/Orbitrap MS ) . Probiotic supplementation significantly increased the levels of octenoylcarnitine ( C8:1 ) , tetradecenoylcarnitine ( C14:1 ) , decanoylcarnitine ( C10 ) and dodecenoylcarnitine ( C12:1 ) compared with the levels from placebo supplementation . In the probiotic group , the changes in the body weight , body fat percentage , body fat mass and L1 subcutaneous fat area were negatively associated with changes in the levels of C8:1 , C14:1 , C10 and C12:1 acylcarnitines . In overweight individuals , probiotic-induced weight loss and adiposity reduction from the probiotic supplementation were associated with an increase in medium-chain acylcarnitines", "In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted", "BACKGROUND Despite evidence for the beneficial effects of probiotics and low-fat dairy products , to our knowledge , no study has compared the beneficial effect on weight loss of consuming a probiotic yogurt ( PY ) compared with a st and ard low-fat yogurt ( LF ) during a hypoenergetic program . OBJECTIVE We compared the effect of the PY with LF yogurt consumption on body weight and cardiometabolic risk factors in women during a weight-loss program . DESIGN Overweight and obese women [ body mass index ( in kg/m(2 ) ) : 27 - 40 ; age : 18 - 50 y ) who usually consumed st and ard LFs were asked to consume either PY or LF every day with their main meals for 12 wk while following a weight-loss program . RESULTS A total of 89 participants were r and omly assigned to one of the 2 intervention groups . Baseline variables were not significantly different between groups . A statistically significant reduction in anthropometric measurements and significant improvements in cardiometabolic risk characteristics were observed over the 12 wk in both groups . However , no significant differences in weight loss and anthropometric measurements were seen between groups after the intervention . Compared with the LF group , the PY group had a greater ( mean ± SD ) decrease in total cholesterol ( PY = -0.36 ± 0.10 mmol/L , LF = -0.31 ± 0.10 mmol/L ; P = 0.024 ) , low-density lipoprotein cholesterol ( PY = -0.35 ± 0.10 mmol/L , LF = -0.31 ± 0.11 mmol/L ; P = 0.018 ) , homeostasis model assessment of insulin resistance ( PY = -0.55 ± 0.32 , LF = -0.42 ± 0.20 ; P = 0.002 ) , 2-h postpr and ial glucose ( PY = -0.61 ± 0.24 mmol/L , LF = -0.44 ± 0.19 mmol/L ; P ( PY = -1.76 ± 1.01 mU/mL , LF = -1.32 ± 0.62 mU/mL ; P = 0.002 ) , as secondary endpoints after the study . No significant differences were found for fasting plasma glucose , high-density lipoprotein cholesterol , or triglycerides within both groups after the 12 wk . CONCLUSION Consumption of PY compared with LF with main meals showed no significant effects on weight loss . However , it may have positive effects on lipid profiles and insulin sensitivity during a weight-loss program . This trial was registered at http://www.i rct .ir/ as I RCT 201402177754N8", "Probiotics are believed to have interaction with immune cells through sustained effects on gene expression of different cytokines and transcription factors . The present r and omized doubled-blind controlled clinical trial was performed recruiting 75 individuals with BMI 25 - 35 , who were r and omly assigned to the following three groups : Group 1 ( n = 25 ) who consumed regular yogurt as part of a low calorie diet [ RLCD ] , group 2 ( n = 25 ) who received probiotic yogurt with a LCD [ PLCD ] and group 3 ( n = 25 ) who consumed probiotic yogurt without LCD [ PWLCD ] for 8 week . Participants in PLCD and PWLCD groups received 200 g/day yogurt containing Lactobacillus acidophilus La5 , Bifidobacterium Bb12 , and lactobacillus casei DN001 10(8 ) cfu/gr . The expression of the FOXP3 , T-bet , GATA3 , TNF-α , IFN-γ , TGF-β , and ROR-γt in P BMC s genes were assessed , before and after intervention . In three groups , ROR-γt expression was reduced ( P = 0.007 ) and FOXP3 was increased ( P The expression of TNFα , TGFβ , and GATA3 genes did not change among all groups after intervention . Interestingly , the expression of T-bet gene , which was significantly decreased in PLCD and PWLCD groups ( P whereas gene expression of IFN-γ decreased in all three groups . Our results suggest that weight loss diet and probiotic yogurt had synergistic effects on T-cell subset specific gene expression in peripheral blood mononuclear cells among overweight and obese individuals", "Consumption of fermented milk ( FM ) containing a probiotic , Lactobacillus gasseri SBT2055 ( LG2055 ) , previously showed a reduction in abdominal adiposity in a r and omised controlled trial ( RCT ) using FM with 10(8 ) colony-forming units ( cfu ) of LG2055/g . However , whether the effectiveness is observed at lower concentrations , the recommended minimum or intermediate levels of probiotics ( 10(6 ) or 10(7 ) cfu/g , respectively ) , remains to be examined . A multi-centre , double-blind , parallel-group RCT was conducted using 210 healthy Japanese adults with large visceral fat areas ( 80·2 - 187·8 cm(2 ) ) . They were balanced for their baseline characteristics and r and omly assigned to three groups receiving FM containing 10(7 ) , 10(6 ) or 0 ( control ) cfu LG2055/g of FM , and were asked to consume 200 g FM/d for 12 weeks . Abdominal visceral fat areas , which were determined by computed tomography , at week 12 , changed from baseline by an average of -8·5 % ( 95 % CI -11·9 , -5·1 ; P measures including BMI , waist and hip circumferences , and body fat mass were also significantly decreased from baseline at week 12 in both groups ; interestingly , the cessation of taking FM for 4 weeks attenuated these effects . In the control group , none of these parameters significantly decreased from baseline . These findings demonstrate that consumption of LG2055 at doses as low as the order of 10(8 ) cfu/d exhibited a significant lowering effect on abdominal adiposity , and suggest that constant consumption might be needed to maintain the effect" ]

[ "Purpose Recent trial results are in favor of aggressive lipid lowering using high dose statins in patients needing secondary prevention . It is unclear whether these effects are solely due to more extensive lipid lowering or the result of the potentially anti-inflammatory properties of statins . We aim ed to determine whether aggressive compared with conventional statin therapy is more effective in reducing systemic markers of inflammation and oxidative stress . Material s and methods This was a multi-centre , double-blind , placebo-controlled trial . Patients with previous cardiovascular disease , who did not achieve low density lipoprotein ( LDL ) cholesterol levels conventional statin therapy ( simvastatin 40 mg ) were r and omized to continue with simvastatin 40 mg or to receive atorvastatin 40 mg for 8 weeks and thereafter atorvastatin 80 mg for the final 8 weeks ( aggressive treatment ) . Lipids , C-reactive protein , soluble cellular adhesion molecules , neopterin , von Willebr and Factor , and antibodies against oxidized LDL were measured at baseline and after 16 weeks . Results Lipid levels decreased significantly in the aggressive treatment group ( LDL-C reduction 20.8 % ; P antibodies against oxidized LDL was seen in the aggressive ( 13.4 % ; P inflammatory and oxidative stress contributes to the benefits of aggressive statin therapy", "The present multicenter , 6-week , r and omized , double-blind , parallel-group , clinical trial evaluated the safety and efficacy of ezetimibe ( 10 mg ) added to stable rosuvastatin therapy versus up-titration of rosuvastatin from 5 to 10 mg or from 10 to 20 mg . The study population included 440 subjects at moderately high/high risk of coronary heart disease with low-density lipoprotein ( LDL ) cholesterol levels higher than the National Cholesterol Education Program Adult Treatment Panel III recommendations ( . Pooled data demonstrated that ezetimibe added to stable rosuvastatin 5 mg or 10 mg reduced LDL cholesterol by 21 % . In contrast , doubling rosuvastatin to 10 mg or 20 mg reduced LDL cholesterol by 5.7 % ( between-group difference of 15.2 % , p ezetimibe plus rosuvastatin 5 mg reduced LDL cholesterol more than did rosuvastatin 10 mg ( 12.3 % difference , p ezetimibe plus rosuvastatin 10 mg reduced LDL cholesterol more than did rosuvastatin 20 mg ( 17.5 % difference , p rosuvastatin up-titration , ezetimibe add-on achieved significantly greater attainment of LDL cholesterol levels of reductions in total cholesterol , non-high-density lipoprotein cholesterol , and apolipoprotein B ( p lipid parameters . Adverse experiences were generally comparable among the groups . In conclusion , compared to up-titration doubling of the rosuvastatin dose , ezetimibe 10 mg added to stable rosuvastatin 5 mg or 10 mg produced greater improvements in many lipid parameters and achieved greater attainment of the National Cholesterol Education Program Adult Treatment Panel III recommended LDL cholesterol targets in subjects with elevated LDL cholesterol and at moderately high/high coronary heart disease risk ", "INTRODUCTION We aim ed to assess the efficacy of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia . METHODS A double-blind study was conducted to assess the effect of fixed dose combination of ezetimibe 10 mg plus atorvastatin 10 mg on lipid profile , oxidised low-density lipoprotein ( ox-LDL ) , high-sensitivity C-reactive protein ( hsCRP ) and soluble intercellular cell adhesion molecule ( sICAM ) in dyslipidaemic patients with or at high risk of coronary artery disease , and compare it with atorvastatin 10 mg monotherapy . 30 patients were r and omised to receive ezetimibe plus atorvastatin or atorvastatin once daily for four weeks . RESULTS Of the 30 patients , 10 men and 5 women ( mean age 54.3 ± 1.6 years ) received ezetimibe plus atorvastatin , while 13 men and 2 women ( mean age 53.7 ± 2.8 years ) received only atorvastatin . The combination treatment significantly reduced total cholesterol ( percentage treatment difference -14.4 ± 6.5 , 95 % confidence interval [ CI ] -1.0 to -27.7 ; p = 0.041 ) and LDL cholesterol ( LDL-C ; percentage treatment difference -19.9 ± 6.1 , 95 % CI -7.4 to -32.4 ; p = 0.003 ) compared to atorvastatin monotherapy . 13 patients on combination treament achieved the National Cholesterol Education Program target for LDL-C as compared to 9 patients on atorvastatin monotherapy ( p = 0.032 ) . Significant reductions in very low-density lipoprotein cholesterol , triglyceride , ox-LDL and sICAM were observed with combination treatment compared to atorvastatin monotherapy . However , no significant change was seen in high-density lipoprotein cholesterol or hsCRP levels between the two groups . CONCLUSION Combination treatment with atorvastatin and ezetimibe had relatively better lipid-lowering and anti-inflammatory efficacy than atorvastatin monotherapy ", "ABSTRACT Objective : To evaluate the addition of ezetimibe or placebo to on-going simvastatin treatment on attaining the LDL‐C treatment target of ≤ 2.60 mmol/L ( 100 mg/dL ) in coronary heart disease ( CHD ) patients with hypercholesterolemia . Methods : Patients with documented CHD were recruited if they were on a stable dose of simvastatin 10 mg or 20 mg for at least 6 weeks , had LDL‐C > 2.60 mmol/L and ≤ 4.20 mmol/L ( > 100 mg/dL and ≤ 160 mg/dL ) , triglycerides ≤ 4.00 mmol/L ( 355 mg/dL ) and hepatic transaminases and creatine kinase ≤ 50 % above the upper limit of normal . After a 4-week placebo and diet run-in period , eligible patients were r and omized to a double-blind , placebo-controlled comparative study with ezetimibe 10 mg co-administered with on-going simvastatin 10 mg or 20 mg ( n = 208 ) versus placebo to match ezetimibe co-administered with simvastatin 10 mg or 20 mg for 6 weeks ( n = 210 ) . Results : When ezetimibe was added to on-going simvastatin therapy , a significantly greater percentage of patients attained the LDL‐C target of ≤ 2.60 mmol/L after 6 weeks of treatment compared to placebo added to on-going simvastatin ( 80.4 % vs. 17.4 % , respectively ; p ≤ 0.001 ) . When co-administered with on-going simvastatin therapy , mean percentage reduction in LDL‐C from baseline was significantly larger in the ezetimibe group compared to placebo ( 27.1 % vs. 4.1 % , respectively ; p ≤ 0.001 ) . The co-administration of ezetimibe or placebo to on-going simvastatin treatment was generally well tolerated . Conclusions : Ezetimibe co-administered with on-going simvastatin 10 mg or 20 mg treatment enabled more CHD patients with hypercholesterolemia to attain the LDL‐C treatment target of ≤ 2.60", "OBJECTIVE To assess the effects of inhibited gastrointestinal cholesterol absorption in statin-treated dyslipidemic patients . RESEARCH DESIGN AND METHODS In a multicenter prospect i ve r and omized double-blind placebo-controlled trial , we primarily compared by ANCOVA the effect of 2-month ezetimibe ( 10 mg/day ) or placebo therapy on LDL cholesterol serum levels in 108 type 2 diabetic patients with albuminuria 135 mg/dl despite simvastatin treatment ( 40 mg/day ) . RESULTS Unlike placebo , ezetimibe decreased LDL cholesterol from 99 ± 31 to 66 ± 22 mg/dl , total cholesterol from 162 ± 36 to 124 ± 30 mg/dl , and apolipoprotein B from 83 ± 22 to 64 ± 18 mg/dl ( P on ezetimibe or placebo achieved LDL levels Adding ezetimibe to simvastatin therapy helps to improve the pro-atherogenic lipoprotein profile in type 2 diabetic patients who fail to reach recommended lipid targets with statin therapy alone", "Background A considerable number of patients with severely elevated LDL-C do not achieve recommended treatment targets , despite treatment with statins . Adults at high cardiovascular risk with hypercholesterolemia and LDL-C ≥ 2.59 and ≤ 4.14 mmol/L ( N = 250 ) , pretreated with atorvastatin 20 mg were r and omized to ezetimibe/simvastatin 10/40 mg or atorvastatin 40 mg for 6 weeks . The percent change in LDL-C and other lipids was assessed using a constrained longitudinal data analysis method with terms for treatment , time , time-by-treatment interaction , stratum , and time-by-stratum interaction . Percentage of subjects achieving LDL-C stratum . Tolerability was assessed . Results Switching to ezetimibe/simvastatin result ed in significantly greater changes in LDL-C ( -26.81 % vs.-11.81 % ) , total cholesterol ( -15.97 % vs.-7.73 % ) , non-HDL-C ( -22.50 % vs.-10.88 % ) , Apo B ( -17.23 % vs.-9.53 % ) , and Apo A-I ( 2.56 % vs.-2.69 % ) vs. doubling the atorvastatin dose ( all p ≤ 0.002 ) , but not HDL-C , triglycerides , or hs-CRP . Significantly more subjects achieved LDL-C switching to ezetimibe/simvastatin vs. doubling the atorvastatin dose ( all p profile appeared generally comparable between treatment groups . Conclusions In high cardiovascular risk subjects with hypercholesterolemia already treated with atorvastatin 20 mg but not at LDL-C to combination ezetimibe/simvastatin 10/40 mg provided significantly greater LDL-C lowering and greater achievement of LDL-C targets compared with doubling the atorvastatin dose to 40 mg . Both treatments were generally well-tolerated . Trial registration Registered at clinical trials.gov :", "BACKGROUND In a multinational trial ( 4522IL/0081 ) , we assessed the effects of switching to low doses of rosuvastatin from commonly used doses of atorvastatin , simvastatin , and pravastatin on low-density lipoprotein cholesterol ( LDL-C ) goal achievement in high-risk patients . METHODS Hypercholesterolemic patients ( n = 3140 ) with coronary heart disease , atherosclerosis , or type 2 diabetes were r and omized to open-label rosuvastatin 10 mg , atorvastatin 10 or 20 mg , simvastatin 20 mg , or pravastatin 40 mg for 8 weeks . Patients either remained on these treatments for another 8 weeks or switched treatments from atorvastatin 10 mg , simvastatin 20 mg , and pravastatin 40 mg to rosuvastatin 10 mg or from atorvastatin 20 mg to rosuvastatin 10 or 20 mg . The primary efficacy measure was the proportion of patients reaching the Joint European Societies ' LDL-C goal ( cholesterol goal achievement , treatment arms were compared using logistic-regression analysis . RESULTS Significant improvement in LDL-C goal achievement was found for patients who switched to rosuvastatin 10 mg , compared with patients who remained on atorvastatin 10 mg ( 86 % vs 80 % , P simvastatin 20 mg ( 86 % vs 72 % , P pravastatin 40 mg ( 88 % vs 66 % , P rosuvastatin 20 mg and those who remained on atorvastatin 20 mg ( 90 % vs 84 % , P of the European combined LDL-C and total cholesterol goals and National Cholesterol Education Program Adult Treatment Panel III LDL-C goals . All statins were well tolerated over 16 weeks . CONCLUSIONS We demonstrated that switching to a more efficacious statin is an effective strategy to improve lipid goal achievement in patients requiring lipid-lowering therapy", "Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed", "Background Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus , but many of these patients fail to achieve the target LDL-C level . Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin . However , in patients with type 2 diabetes who are already being treated with satins , it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose . Therefore , this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins . Methods The subjects were type 2 diabetic patients under treatment with rosuvastatin ( 2.5 mg daily ) , who had LDL-C levels ≥80 mg/dL. They were r and omly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day ( combination group , n = 40 ) or an increase of the rosuvastatin dose to 5 mg/day ( dose escalation group , n = 39 ) . These two groups were compared at baseline and after 12 weeks of treatment . Results The percent change of LDL-C was −31 % in the combination group and −12 % in the dose escalation group . Both groups showed a significant decrease , but the decrease was greater in the combination group . In both groups , there was a significant decrease in the levels of small dense LDL-C , oxidized LDL and remnant-like lipoprotein cholesterol . For all of these parameters , the percent changes were greater in the combination group . Only the combination group showed a significant decrease of triglycerides . Multivariate analysis was performed to identify factors associated with reaching an LDL-C level with ezetimibe was extracted as a factor related to improvement of LDL-C. Conclusions Compared with increasing the dose of rosuvastatin , the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients , suggesting that this combination could suppress the progression of atherosclerosis . Trial registration", "The use of atorvastatin is rapidly increasing among statins since the introduction of generics . However , only limited data are available on its current use and the effectiveness outside of r and omised trials . The aim of the study was to assess low-density lipoprotein ( LDL-C ) levels in ambulatory patients at very high cardiovascular risk on atorvastatin therapy in physician ’s offices . A total of 2625 high-risk patients on atorvastatin were included into this cross-sectional study by 539 office-based physicians between June and December 2014 . 47.0 % of the patients had documented coronary heart disease ( CHD ) , 25.1 % type 2 diabetes mellitus ( DM ) , and 27.9 % CHD plus concomitant DM . The mean age was 66.1 ± 10.8 years , 62.1 % were male . Atorvastatin at the dose of 10 , 20 , 40 and 80 mg/day was administered in 15.6 , 45.7 , 33.9 , and 4.8 % of the patients , respectively . The treatment duration was 92.6 ± 109.6 weeks . The mean atorvastatin dose at therapy start was 24.8 ± 15.2 mg/day and at time of documentation 27.9 ± 15.8 mg/day . Low-density lipoprotein cholesterol ( LDL-C ) their individual LDL-C target . In summary , higher doses of atorvastatin are not frequently used in clinical practice . The LDL-C target level of atorvastatin treated patients at very high cardiovascular risk", "The aim of this study was to evaluate the efficacy and safety of ezetimibe 10 mg added to atorvastatin 20 mg compared with doubling atorvastatin to 40 mg in patients with hypercholesterolemia at moderately high risk for coronary heart disease who did not reach low-density lipoprotein ( LDL ) cholesterol levels In this 6-week , multicenter , double-blind , r and omized , parallel-group study , 196 patients treated with atorvastatin 20 mg received atorvastatin 20 mg plus ezetimibe 10 mg or atorvastatin 40 mg for 6 weeks . Adding ezetimibe 10 mg to atorvastatin 20 mg produced significantly greater reductions in LDL cholesterol than increasing atorvastatin to 40 mg ( -31 % vs -11 % , p non-high-density lipoprotein cholesterol , total cholesterol , and apolipoprotein B ( p LDL cholesterol levels atorvastatin 20 mg plus ezetimibe compared with atorvastatin 40 mg ( 84 % vs 49 % , p high-density lipoprotein cholesterol , triglycerides , apolipoprotein A-I , and high-sensitivity C-reactive protein . The incidences of clinical and laboratory adverse experiences were generally similar between groups . In conclusion , the addition of ezetimibe 10 mg to atorvastatin 20 mg was generally well tolerated and result ed in significantly greater lipid-lowering efficacy compared with doubling atorvastatin to 40 mg in patients with hypercholesterolemia at moderately high risk for coronary heart disease", "Background Statins are frequently administered to reduce low-density lipoprotein cholesterol ( LDL-C ) and vascular inflammation , because LDL-C and high sensitive C-reactive protein ( hs-CRP ) are associated with high risk for cardiovascular events . When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease ( CAD ) , ezetimibe can be added or the statin dose can be increased . However , which strategy is more effective for treating patients with CAD has not been established . The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients . Methods 46 patients with high-risk CAD and LDL-C and hs-CRP levels of > 70 mg/dL and > 1.0 mg/L , respectively , that were not improved by 4 weeks of rosuvastatin ( 2.5 mg/day ) were r and omly assigned to receive 10 mg ( R10 , n = 24 ) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe ( R2.5/E10 , n = 22 ) for 12 weeks . The primary endpoint was a change in hs-CRP . Results Baseline characteristics did not significantly differ between the groups . At 12 weeks , LDL-C and inflammatory markers ( hs-CRP , interleukin-6 , tumour necrosis factor-alpha and pentraxin 3 ) also did not significantly differ between the two groups ( LDL-C : R10 vs. R2.5/E10 : -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL ) . However , high-density lipoprotein cholesterol ( HDL-C ) was significantly improved in the R10 , compared with R2.5/E10 group ( 4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL ; p anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin . However , R10 elevated HDL-C more effectively than R2.5/E10.Trial registration", "The percentage of change from baseline in low-density lipoprotein ( LDL ) cholesterol after the addition of ezetimibe 10 mg to atorvastatin 40 mg was compared with uptitration to atorvastatin 80 mg . In this multicenter , double-blind , parallel-group study , adult hypercholesterolemic patients using atorvastatin 40 mg/day were r and omly assigned to atorvastatin 40 mg plus ezetimibe 10 mg or uptitration to atorvastatin 80 mg . After 6 weeks of treatment , compared with atorvastatin 80 mg , atorvastatin 40 mg plus ezetimibe significantly reduced the primary end point of LDL cholesterol by -27 % versus atorvastatin 80 mg by -11 % ( p non-high-density lipoprotein cholesterol , apolipoprotein B , total cholesterol , and triglycerides significantly more than atorvastatin 80 mg ( all p in high-sensitivity C-reactive protein , high-density lipoprotein cholesterol , and apolipoprotein A-I were similar between groups . Significantly more patients treated with atorvastatin 40 mg plus ezetimibe reached LDL cholesterol Safety and tolerability profiles and incidence of liver and muscle adverse experiences were generally similar between groups . In conclusion , these results showed that adding ezetimibe to atorvastatin 40 mg was significantly more effective than uptitrating to atorvastatin 80 mg at lowering LDL cholesterol and other lipid parameters . Both treatments were generally well tolerated ( clinical trial no. NCT00276484 )", "BACKGROUND The aim of this study was to compare the effect on endothelial function of increasing statin dose to add-on ezetimibe in patients with coronary artery disease ( CAD ) already treated with statin . METHODS AND RESULTS Two-hundred and forty-three patients with CAD and low-density lipoprotein cholesterol ( LDL-C ) ≥70 mg/dl even after treatment with atorvastatin ( 10 mg ) were prospect ively r and omized to the ezetimibe addition ( 10 mg ) group ( A10E10 ; n=117 ) or to the double atorvastatin dose ( to 20 mg ; A20 ; n=133 ) group for 12 weeks . Primary endpoint was change in endothelial function measured by logarithmic-scale reactive hyperemia index ( L_RHI ) . After treatment , high-sensitivity C-reactive protein ( hs-CRP ) and all lipids except triglyceride and high-density lipoprotein cholesterol were significantly reduced in both groups . The mean percent changes in LDL-C for the A10E10 and A20 groups were -25.8 % and -9.1 % , respectively ( P 0.48 , P=0.399 ) . Absolute change in L_RHI was significantly higher in the A20 than A10E10 group ( 0.02±0.29 vs. 0.16±0.27 , P CONCLUSIONS Statin and ezetimibe have different effects on endothelial function independent from LDL-C-lowering effects ", "Few clinical studies have focused on the efficacy of lipid-lowering therapies in patients > or = 65 years of age . The percentage of change from baseline in low-density lipoprotein ( LDL ) cholesterol and the percentage of patients achieving prespecified LDL cholesterol levels after 12 weeks of ezetimibe 10 mg plus atorvastatin versus up titration of atorvastatin were assessed in subjects > or = 65 years old with hyperlipidemia and at high risk of coronary heart disease . After stabilization of atorvastatin 10-mg therapy , 1,053 patients , > or = 65 years old , at high risk of coronary heart disease , with and without atherosclerotic vascular disease and a LDL cholesterol level that was not to receive ezetimibe added to atorvastatin 10 mg for 12 weeks versus up titration to atorvastatin 20 mg for 6 weeks followed by up titration to atorvastatin 40 mg for an additional 6 weeks . Ezetimibe added to atorvastatin 10 mg result ed in significantly greater changes at week 6 in LDL cholesterol ( p LDL cholesterol level of LDL cholesterol level of ezetimibe plus atorvastatin 10 mg result ed in significantly greater changes at week 6 in total cholesterol , triglycerides , non-high-density lipoprotein ( HDL ) cholesterol , apolipoprotein B ( all p HDL cholesterol ( p = 0.021 ) compared with atorvastatin 20 mg and significantly greater changes at week 12 in LDL cholesterol , non-HDL cholesterol , apolipoprotein A-I ( p = 0.001 ) , total cholesterol , apolipoprotein B ( p HDL cholesterol ( p tolerated , with comparable safety profiles . In conclusion , adding ezetimibe to atorvastatin 10 mg produced significantly greater favorable changes in most lipids at 6 and 12 weeks and significantly greater attainment of prespecified LDL cholesterol levels than doubling or quadrupling the atorvastatin dose in patients > or = 65 years old at high risk for coronary heart disease", " Hypercholesterolemic patients ( n = 1,547 ) at high atherosclerotic cardiovascular disease risk with low-density lipoprotein cholesterol ( LDL-C ) levels ≥100 and ≤160 mg/dl while treated with atorvastatin 10 mg/day entered a multicenter , r and omized , double-blind , active-controlled , clinical trial using two 6-week study periods . Period I compared the efficacy/safety of ( 1 ) adding ezetimibe 10 mg ( ezetimibe ) to stable atorvastatin 10 mg , ( 2 ) doubling atorvastatin to 20 mg , or ( 3 ) switching to rosuvastatin 10 mg . Subjects in the latter 2 groups who persisted with elevated LDL-C levels ( ≥100 and ≤160 mg/dl ) after period I , entered period II ; subjects on atorvastatin 20 mg had ezetimibe added to their atorvastatin 20 mg , or uptitrated their atorvastatin to 40 mg ; subjects on rosuvastatin 10 mg switched to atorvastatin 20 mg plus ezetimibe or uptitrated their rosuvastatin to 20 mg . Some subjects on atorvastatin 10 mg plus ezetimibe continued the same treatment into period II . At the end of period I , ezetimibe plus atorvastatin 10 mg reduced LDL-C significantly more than atorvastatin 20 mg or rosuvastatin 10 mg ( 22.2 % vs 9.5 % or 13.0 % , respectively , p , ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than atorvastatin 40 mg ( 17.4 % vs 6.9 % , p from rosuvastatin 10 mg to ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than uptitrating to rosuvastatin 20 mg ( 17.1 % vs 7.5 % , p treatments , ezetimibe added to atorvastatin 10 mg ( period I ) or atorvastatin 20 mg ( period II ) produced significantly greater percent attainment of LDL-C targets percent reductions in total cholesterol , non-high-density lipoprotein cholesterol , most lipid and lipoprotein ratios , and apolipoprotein B ( except ezetimibe plus atorvastatin 20 vs atorvastatin 40 mg ) . Reports of adverse experiences were generally similar among groups . In conclusion , treatment of hypercholesterolemic subjects at high cardiovascular risk with ezetimibe added to atorvastatin 10 or 20 mg produced significantly greater improvements in key lipid parameters and significantly greater attainment of LDL-C treatment targets than doubling atorvastatin or switching to ( or doubling ) rosuvastatin at the compared doses", "AIM There have been few comparisons between rosuvastatin and other statins in Japanese patients . This open-label , r and omized , parallel-group comparative study was performed to compare the efficacy and safety of rosuvastatin ( 5 mg ) and atorvastatin ( 10 mg ) once daily in Japanese patients with hypercholesterolemia . METHODS Patients with hypercholesterolemia who had received atorvastatin ( 10 mg/day ) for at least 4 weeks and were in category B3 , B4 , or C according to the Japan Atherosclerosis Society Guidelines for Diagnosis and Treatment of Atherosclerotic Cardiovascular Diseases 2002 ( JAS2002GL ) were r and omly assigned to rosuvastatin at 5 mg/day ( switched treatment ) or atorvastatin at 10 mg/day ( continued treatment ) . The primary endpoint was the achievement of JAS2002GL LDL-C goals at 8 weeks . RESULTS LDL-C goals were reached by 80.3 % of the rosuvastatin group and 67.3 % of the atorvastatin group at 8 weeks ( p change of the LDL-C and LDL-C/HDL-C ratio at 8 weeks was significantly greater in the rosuvastatin group than in the atorvastatin group ( both p Furthermore , rosuvastatin improved fasting plasma glucose ( p tolerated . CONCLUSION Rosuvastatin ( 5 mg/day ) is a useful treatment option for high-risk patients with hypercholesterolemia", "BACKGROUND Despite the efficacy of statins in lowering low-density lipoprotein cholesterol ( LDL-C ) levels , many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction . The cholesterol absorption inhibitor , ezetimibe , has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins . This study was performed to compare the efficacy and safety of ezetimibe ( 10 mg ) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease ( CHD ) and are not at their LDL-C goal on the starting dose of atorvastatin . METHODS This was a 14-week , multicenter , r and omized , double-blind , active-controlled study conducted in 113 clinical research centers in 21 countries . Participants were adults with heterozygous familial hypercholesterolemia ( HeFH ) , CHD , or multiple ( > or = 2 ) cardiovascular risk factors , and a LDL-C level > or = 130 mg/dL after a 6- to 10-week dietary stabilization and atorvastatin ( 10 mg/day ) open-label run-in period . Eligible subjects continued to receive atorvastatin ( 10 mg ) and were r and omized to receive blinded treatment with ezetimibe ( 10 mg/day ; n = 305 ) or an additional 10 mg/day of atorvastatin ( n = 316 ) . The atorvastatin dose in both groups was doubled after 4 weeks , 9 weeks , or both when the LDL-C level was not at its goal ( atorvastatin alone could reach 80 mg/day . The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14 . A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy . RESULTS The proportion of subjects reaching their target LDL-C level goal of atorvastatin monotherapy group ( 22 % vs 7 % ; P levels of LDL-C , triglycerides , and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin ( LDL-C -22.8 % versus -8.6 % ; P safety and tolerability profile similar to that of atorvastatin alone . CONCLUSIONS The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone", "BACKGROUND Reducing low-density lipoprotein cholesterol ( LDL-C ) is the primary goal of therapy in patients with hypercholesterolemia and coronary heart disease ( CHD ) . METHODS This double blind placebo-controlled study enrolled patients 18 to 75 years of age with primary hypercholesterolemia and established CHD who were taking a stable daily dose of simvastatin 20 mg . Patients were r and omized to ezetimibe/simvastatin 10/20 mg ( eze/simva ; n = 56 ) or simvastatin 40 mg ( simva ; n = 56 ) for 6 weeks . Percent change from baseline in LDL-C , total cholesterol , high-density lipoprotein cholesterol ( HDL-C ) , and triglycerides were assessed by use of the Student t test . The percent of patients achieving LDL-C less than 100 mg/dL ( eze/simva combination result ed in significantly greater reductions in LDL-C , total cholesterol , and triglycerides versus doubling the dose of simva to 40 mg ( all P LDL-C less than 100 mg/dL ( ezetimibe/simvastatin versus doubling the dose of simva to 40 mg ( 73.2 % vs 25.0 % ; P simvastatin . Changes in HDL-C were similar between treatments . Both treatments were generally well tolerated . CONCLUSION In high-risk CHD patients with hypercholesterolemia , treatment with eze/simva combination result ed in significantly greater reductions in LDL-C , total cholesterol and triglycerides , as well as greater achievement of recommended LDL-C targets , compared with doubling the simvastatin dose to 40 mg over the 6-week period . ( CLINICAL TRIAL REGISTRATION NUMBER NCT00423579 )", "AIM The aim of this study was to compare ezetimibe/simvastatin combination therapy with intensified statin monotherapy as alternative treatment strategies to achieve the Joint British Societies (JBS)-2 and National Institute for Health and Clinical Excellence low-density-lipoprotein cholesterol ( LDL-C ) target of high-risk patients who have failed to reach target with simvastatin 40 mg . METHODS This is a prospect i ve , double-blind study conducted in 34 UK primary care centres ; 1748 patients with established cardiovascular disease ( CVD ) , diabetes or high risk of CVD who had been taking simvastatin 40 mg for > or = 6 weeks were screened and 786 ( 45 % ) with fasting LDL-C > or = 2.0 mmol/l ( and and after a further 6-week run-in period on simvastatin 40 mg were r and omised to ezetimibe/simvastatin 10/40 mg ( as a combination tablet ; n = 261 ) , atorvastatin 40 mg ( n = 263 ) or rosuvastatin 5 mg ( n = 73 ) or 10 mg ( n = 189 ) once daily for 6 weeks . Rosuvastatin dose was based on UK prescribing instructions . The primary outcome measure was the proportion of patients achieving LDL-C at the end of the study . RESULTS The percentage of patients ( adjusted for baseline differences ) achieving LDL-C ezetimibe/simvastatin 10/40 mg , compared with 33.5 % for atorvastatin 40 mg [ odds ratio 4.5 ( 95 % CI : 3.0 - 6.8 ) ; p rosuvastatin 5 or 10 mg [ odds ratio 13.6 ( 95 % CI : 8.6 - 21.6 ) ; p total cholesterol All study treatments were well tolerated . CONCLUSION Approximately 45 % of patients screened had not achieved LDL-C or = 12 weeks of treatment with simvastatin 40 mg . In this group , treatment with ezetimibe/simvastatin 10/40 mg achieved target LDL-C levels in a significantly higher proportion of patients during a 6-week period than switching to either atorvastatin 40 mg or rosuvastatin 5 - 10 mg", "OBJECTIVE To determine the extent of reduction in low-density lipoprotein cholesterol ( LDL-C ) level and improvement in National Cholesterol Education Program Adult Treatment Panel III ( NCEP ATP III ) LDL-C goal attainment when ezetimibe was added to ongoing statin therapy in a diverse population of community-based patients . PATIENTS AND METHODS In this multicenter , double-blind , placebo-controlled trial ( from January 2003 to August 2003 ) , hypercholesterolemic patients ( from 299 US primary care and specialty practice s ) with LDL-C levels exceeding NCEP ATP III goals were r and omized ( 2:1 ) to receive ezetimibe ( 10 mg/d ) or placebo in addition to their ongoing statin therapy for 6 weeks . RESULTS In a study of 3030 r and omized patients , ezetimibe added to statin therapy significantly reduced the LDL-C level by an additional 25.8 % in the total population , compared with an additional 2.7 % reduction with placebo plus statin ( treatment difference , -23.1 % ; P ezetimibe added to statin reached their NCEP ATP III target LDL-C level compared with those treated with placebo plus statin ( 20.6 % ) . The addition of ezetimibe also result ed in improvement in other lipid parameters and high-sensitivity C-reactive protein levels . These benefits were consistent across sex , race , age , statin br and , and dose subgroups . Ezetimibe plus statin therapy was well tolerated , with a safety profile similar to placebo plus statin . CONCLUSION Across multiple subgroups , ezetimibe added to statin therapy consistently produced significant additional improvements in LDL-C levels and goal attainment , as well as in other lipoproteins , compared with addition of placebo . The addition of ezetimibe to statin therapy should be considered for patients not achieving their NCEP ATP III LDL-C goals while receiving statin therapy alone", "Aim : This r and omized , double‐blind study evaluated the efficacy of switching from atorvastatin ( ATV ) 10 mg to ezetimibe/simvastatin ( EZE/SIMVA ) 10/20 mg , EZE/SIMVA 10/40 mg or doubling the dose of ATV from 10 to 20 mg in patients with type 2 diabetes ( T2D )", "This r and omised , double-blind , placebo (PBO)-controlled study evaluated the efficacy and safety of ezetimibe ( EZE ) co-administered with ongoing atorvastatin ( ATV ) therapy in 450 hypercholesterolemic patients with coronary heart disease ( CHD ) who had not achieved their low-density lipoprotein cholesterol ( LDL-C ) goal ATV 10 or 20 mg/day for > or = 6 weeks . After a 4-week diet/baseline active run-in period , patients with LDL-C > 2.60 mmol/l and were stratified by ATV dose and r and omised ( 1 : 1 ) to EZE 10 mg or PBO for 6 weeks while continuing open-label ATV . Significantly more patients achieved an LDL-C goal EZE than PBO ( 81.3 vs. 21.8 % ; p PBO , co-administration of EZE with ongoing ATV led to significantly ( p LDL-C , total cholesterol , triglycerides , non-high-density lipoprotein cholesterol ( non-HDL-C ) , and apolipoprotein B ; HDL-C was significantly ( p EZE and ATV was well tolerated , with an overall safety profile similar to ATV alone", "BACKGROUND National Cholesterol Education Program Adult Treatment Panel III guidelines for patients at a high risk of coronary heart disease set a low-density lipoprotein cholesterol ( LDL-C ) target of 1993 high-risk patients were r and omized to rosuvastatin 20 mg , atorvastatin 10 mg , atorvastatin 20 mg , simvastatin 20 mg , or simvastatin 40 mg for 8 weeks . Patients either remained on starting treatment or switched to lower or milligram-equivalent doses of rosuvastatin for 8 more weeks . RESULTS At 16 weeks , more patients achieved their LDL-C target by switching to rosuvastatin 10 mg than staying on atorvastatin 10 mg ( 66 % vs 42 % , P simvastatin 20 mg ( 73 % vs 32 % , P rosuvastatin 20 mg brought more patients to their LDL-C target than staying on atorvastatin 20 mg ( 79 % vs 64 % , P simvastatin 40 mg ( 84 % vs 56 % , P LDL-C target of rosuvastatin from atorvastatin or simvastatin ( within-arm comparisons P or = 200 mg/dL ) met LDL-C , non-high-density lipoprotein cholesterol ( non-HDL-C ) , and apolipoprotein B targets by changing to rosuvastatin . Switching to rosuvastatin produced greater reductions in LDL-C , total cholesterol , non-HDL-C , apolipoprotein B , and lipid ratios . All treatments were well tolerated , with no differences among treatment groups in skeletal muscle , hepatic , or renal toxicity . CONCLUSION Rosuvastatin 10 or 20 mg is an effective and safe therapeutic option for high-risk patients to achieve their lipid and apolipoprotein targets", "This r and omised , double-blind study evaluated the efficacy and safety of ezetimibe/simvastatin ( EZE/SIMVA ) 10/20 mg tablet compared to doubling the atorvastatin ( ATV ) dose in hypercholesterolaemic patients with atherosclerotic or coronary heart disease ( CHD ) . The study group included 435 male and female CHD patients ( aged > or=18 years ) who had not achieved their low-density lipoprotein cholesterol ( LDL-C ) goal of ATV 10 mg for > or=6 weeks . After a 1-week diet/stabilisation period , patients with LDL-C > or=2.50 mmol/l and were r and omised ( 1:1 ) to EZE/SIMVA 10/20 mg/day ( n = 221 ) or ATV 20 mg/day ( n = 214 ) for 6 weeks . The primary efficacy objective was to determine the per cent reduction from baseline in LDL-C at week 6 . EZE/SIMVA 10/20 mg produced significantly greater mean per cent changes from baseline in LDL-C compared with ATV 20 mg ( -32.8 vs. -20.3 % ; p LDL-C goal EZE/SIMVA than ATV ( 77.9 vs. 51.9 % ; p total cholesterol ( -20.3 vs. -13.0 % ) , non-high-density lipoprotein cholesterol ( non-HDL-C ) ( -27.9 vs. -17.0 % ) , apolipoprotein B ( -23.4 vs. -14.7 % ) and HDL-C ( 1.8 vs. -0.4 % ) were observed after switching to EZE/SIMVA 10/20 mg for 6 weeks ( p EZE/SIMVA 10/20 mg was generally well tolerated , with an overall safety profile similar to that of ATV 20 mg . EZE/SIMVA 10/20 mg produced superior lipid-altering efficacy by dual inhibition of cholesterol synthesis and intestinal absorption compared with doubling the dose of ATV from 10 to 20 mg", "BACKGROUND In the setting of stable coronary artery disease ( CAD ) , it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone . OBJECTIVE We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10mg/simvastatin 20 mg ( E10/S20 ) with simvastatin 80 mg ( S80 ) . METHODS AND RESULTS CAD patients ( n=83 , 63 ± 9 years , 57 % men ) receiving S20 , were r and omly allocated to receive E10/S20 or S80 , for 6 weeks . Lipids , inflammatory markers ( C-reactive protein , interleukin-6 , monocyte chemoattractant protein-1 , soluble CD40 lig and and oxidized LDL ) , and platelet aggregation ( platelet function analyzer [PFA]-100 ) changes were determined . Baseline lipids , inflammatory markers and PFA-100 were similar between groups . After treatment , E10/S20 and S80 patients presented , respectively : ( 1 ) similar reduction in LDL-C ( 29 ± 13 % vs. 28 ± 30 % , p=0.46 ) , apo-B ( 18 ± 17 % vs. 22 ± 15 % , p=0.22 ) and oxidized LDL ( 15 ± 33 % vs. 18 ± 47 % , p=0.30 ) ; ( 2 ) no changes in inflammatory markers ; and , ( 3 ) a higher increase of the PFA-100 with E10/S20 than with S80 ( 27 ± 43 % vs. 8 ± 33 % , p=0.02 ) . CONCLUSIONS These data suggest that among stable CAD patients treated with S20 , ( 1 ) both E10/S20 and S80 were equally effective in further reducing LDL-C ; ( 2 ) neither treatment had any further significant anti-inflammatory effects ; and ( 3 ) E10/S20 was more effective than S80 in inhibiting platelet aggregation . Thus , despite similar lipid lowering and doses 4 × less of simvastatin , E10/S20 induced a greater platelet inhibitory effect than S80", "OBJECTIVE Evaluate the lipid-altering effects of ezetimibe added to ongoing statin therapy , statin titration , switching from statin monotherapy to a more potent statin or to ezetimibe/simvastatin . METHODS A pooled analysis of patient-level data from 17 double-blind , active or placebo-controlled studies of 8667 hypercholesterolemic adults r and omized to ezetimibe 10 mg added to ongoing statins , statin titration ( doubling ) , or switching from ongoing statins to rosuvastatin ( 10 mg ) or to ezetimibe/simvastatin ( 10/20 and 40 mg ) . Percent change from baseline in low-density lipoprotein cholesterol ( LDL-C ) was estimated by analysis of variance . Percent of patients who achieved LDL-C and other guideline -recommended targets , and target lipid levels by baseline distance to goal were evaluated . RESULTS LDL-C percent change from baseline was -26.0 for ezetimibe added to ongoing statin therapy , -27.6 for switching from ongoing statin to ezetimibe/simvastatin , -19.7 for switching to rosuvastatin 10 mg , and -9.7 for dose doubling of the ongoing statin . For patients within 0.8 mmol/L ( 30 mg/dL ) of the target at baseline , LDL-C target attainment rates were 75.9 % for adding ezetimibe to ongoing statin , 72.8 % for switching to ezetimibe/simvastatin , 61.8 % for switching to rosuvastatin , and 44.3 % for statin dose-doubling . Similarly , improvements in other lipids and achievement of non-high-density lipoprotein cholesterol and apolipoprotein B targets among this patient group were largest for ezetimibe added to ongoing statins and switching to ezetimibe/simvastatin ; switching to rosuvastatin 10 mg and statin dose-doubling were less effective . CONCLUSIONS Adding ezetimibe to ongoing statin therapy appeared to be an effective option for patients who do not achieve lipid-lowering goals on statins alone", "AIMS High-risk subjects with elevated C-reactive protein ( CRP ) are at high risk for cardiovascular events and frequently require potent statins or combined lipid-lowering therapy to achieve lipid targets and decrease inflammation . Our study aim ed at evaluating the effects of three lipid-modifying therapies on LDL-cholesterol , CRP levels and markers of cholesterol absorption and synthesis . MAIN METHODS A prospect i ve intervention study was performed in high cardiovascular risk individuals receiving atorvastatin 10 mg daily for four weeks . Those with CRP≥2.0mg/L were r and omized to another four-week treatment period with atorvastatin 40 mg , ezetimibe 10 mg or the combination of atorvastatin 40 mg / ezetimibe 10 mg . Lipids , markers of cholesterol absorption ( campesterol and β-sitosterol ) , and synthesis ( desmosterol ) , as well as CRP were quantified at baseline and end of study . KEY FINDINGS One hundred and twenty two individuals were included . Atorvastatin alone or combined with ezetimibe reduced both LDL-cholesterol and CRP ( P ezetimibe did not modify CRP . Ezetimibe-based therapies reduced absorption markers and their ratios to cholesterol ( P increased campesterol/cholesterol and β-sitosterol/cholesterol ratios ( P , ezetimibe also increased desmosterol and desmosterol/cholesterol ratio ( P a potent statin and ezetimibe decreasing inflammation , and preventing increase in cholesterol bio synthesis , an effect not observed with ezetimibe alone", "Objectives To assess the efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolaemia and coronary artery disease ( CAD ) . Design and setting Prospect i ve , multicentre , r and omized , double-blind , placebo-controlled trial conducted in three Middle Eastern countries . Patients Patients with known CAD , who were being treated with simvastatin 20 mg and had low-density lipoprotein cholesterol ( LDL-C ) concentrations of 2.6 to 4.1 mmol/l , were r and omized to receive daily coadministration of ezetimibe 10 mg or placebo . Main outcome measures The primary outcome was percentage reduction of LDL-C after 6 weeks of r and omization . Secondary endpoints included number of patients who achieved National Cholesterol Education Program Adult Treatment Panel III ( NCEP ATP III ) LDL-C level and safety and tolerability . Results We enrolled 144 patients of whom 120 had blood available for final analysis . The coadministration of ezetimibe with ongoing simvastatin therapy result ed in a statistically significant additional reduction in LDL-C concentration as compared with simvastatin monotherapy ( −26.7 versus −9.1 % , respectively ; total additional reduction of 17.6 % , P the ezetimibe and simvastatin group achieved NCEP ATP III LDL-C target levels than in the simvastatin monotherapy group ( 70 versus 33 % , respectively ; P = 0.0001 ) . The coadministration of ezetimibe with simvastatin was well tolerated with a safety profile similar to that of simvastatin monotherapy . Conclusion When coadministered with simvastatin therapy , ezetimibe result ed in significant additional reduction in LDL-C and enabled more patients to achieve NCEP ATP III LDL-C target levels . This was achieved safely and with excellent tolerability" ]

[ "Summary Aim : To evaluate the effect of ezetimibe on insulin sensitivity and lipid profile in obese and dyslipidaemic patients . Methods : A r and omized , double-blind , placebo-controlled clinical trial was carried out in 12 obese , dyslipidaemic patients , independently of their basal insulin sensitivity . At the beginning of the study , a metabolic profile was measured , and insulin sensitivity estimated using the euglycaemic-hyperinsulinaemic clamp technique . The volunteers were r and omly assigned to receive ezetimibe ( 10 mg/day in the morning ) or placebo for a period of 90 days . After intervention , a similar metabolic profile was measured and a second clamp study was performed . Results : Ezetimibe administration for 90 days decreased total ( 6.0 ± 0.5 vs. 4.2 ± 0.9 mmol/L , p = 0.011 ) and low-density lipoprotein ( 4.0 ± 0.7 vs. 2.2 ± 0.8 mmol/L , p=0.003 ) cholesterol concentrations without modification of insulin sensitivity ( 3.0 ± 0.6 vs. 2.9 ± 0.7 mg/kg/min , p = 0.345 ) . Conclusions : Ezetimibe significantly decreased total cholesterol and low-density lipoprotein cholesterol concentrations without affecting insulin sensitivity in obese and dyslipidaemic patients", "Objective . To evaluate the effects of ezetimibe/simvastatin ( EZE/SIMV ) and rosuvastatin ( ROSUV ) on oxidative stress ( OS ) markers in patients with diabetic polyneuropathy ( DPN ) . Methods . We performed a r and omized , double-blind , placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus ( T2DM ) and DPN , as evaluated by composite scores and nerve conduction studies ( NCS ) . Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo , EZE/SIMV 10/20 mg , or ROSUV 20 mg for 16 weeks . All patients were assessed before and after treatment : primary outcomes were lipid peroxidation ( LPO ) , and nitric oxide ( NO ) surrogate levels in plasma ; secondary outcomes included NCS , neuropathic symptom scores , and metabolic parameters . Data were expressed as mean ± SD or SEM , frequencies , and percentages ; we used nonparametric analysis . Results . LPO levels were reduced in both statin arms after 16 weeks of treatment ( p the placebo group . NO levels were not significantly affected by statin treatment , although a trend towards significance concerning increased NO levels was noted in both statin arms . No significant changes were observed for the NCS or composite scores . Discussion . EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy . This trial is registered with NCT02129231", "AIM Ezetimibe selectively blocks intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1 ( NPC1L1 ) and reducing LDL cholesterol ( LDL-C ) . In animals , ezetimibe reversed diet-induced obesity , liver steatosis , and insulin resistance . In humans , its potential effects on liver steatosis and insulin resistance have been suggested . We investigated the effects of ezetimibe on postpr and ial hyperlipidaemia and hyperglycaemia in obese subjects with dyslipidaemia in a double-blind r and omized crossover trial . METHODS Twenty obese men with hypertriglyceridaemia were assigned r and omly to an ezetimibe- or a placebo-precedence-treated group . Subjects in the ezetimibe group were treated with ezetimibe ( 10 mg/day ) for the first 4 weeks , followed by a 4-week interval and then treated with placebo for another 4 weeks . The placebo group received these treatments in reverse order . Subjects were requested to fast for at least 12 hours and then received a st and ard meal . Blood sample s were collected at 0 , 30 , 60 , 120 , 240 , 360 and 480 minutes after the meal on Days 0 , 28 , 56 and 84 and were used to measure the lipid and glucose metabolism markers . RESULTS Ezetimibe significantly decreased the postpr and ial serum triglyceride excursion ( p=0.01 ) and fasting serum LDL-C , remnant-like particles(RLP ) and ApoB48 levels ( p Postpr and ial glucose excursion , serum insulin levels , serum glucose-dependent insulinotropic polypeptide ( GIP ) and active glucagon-like peptide-1 ( GLP-1 ) were not significantly affected by ezetimibe treatment . CONCLUSION Ezetimibe restored the postpr and ial dysregulation of lipid but did not affect glucose metabolism in a double-blind r and omized crossover trial", "OBJECTIVE To assess the effects of inhibited gastrointestinal cholesterol absorption in statin-treated dyslipidemic patients . RESEARCH DESIGN AND METHODS In a multicenter prospect i ve r and omized double-blind placebo-controlled trial , we primarily compared by ANCOVA the effect of 2-month ezetimibe ( 10 mg/day ) or placebo therapy on LDL cholesterol serum levels in 108 type 2 diabetic patients with albuminuria 135 mg/dl despite simvastatin treatment ( 40 mg/day ) . RESULTS Unlike placebo , ezetimibe decreased LDL cholesterol from 99 ± 31 to 66 ± 22 mg/dl , total cholesterol from 162 ± 36 to 124 ± 30 mg/dl , and apolipoprotein B from 83 ± 22 to 64 ± 18 mg/dl ( P on ezetimibe or placebo achieved LDL levels Adding ezetimibe to simvastatin therapy helps to improve the pro-atherogenic lipoprotein profile in type 2 diabetic patients who fail to reach recommended lipid targets with statin therapy alone", "Background It has been demonstrated that statins can increase intestinal sterol absorption . Augments in phytosterolemia seems related to cardiovascular disease . Objective We examined the role of soluble fiber intake in endogenous cholesterol synthesis and in sterol absorption among subjects under highly effective lipid-lowering therapy . Design In an open label , r and omized , parallel- design study with blinded endpoints , subjects with primary hypercholesterolemia ( n = 116 ) were assigned to receive during 12 weeks , a daily dose of 25 g of fiber ( corresponding to 6 g of soluble fibers ) plus rosuvastatin 40 mg ( n = 28 ) , rosuvastatin 40 mg alone ( n = 30 ) , sinvastatin 40 mg plus ezetimibe 10 mg plus 25 g of fiber ( n = 28 ) , or sinvastatin 40 mg plus ezetimibe 10 mg ( n = 30 ) alone . Results The four assigned therapies produced similar changes in total cholesterol , LDL-cholesterol , and triglycerides ( p change HDL-cholesterol . Fiber intake decreased plasma campesterol ( p ezetimibe ( p receiving fiber plus ezetimibe ( p = 0.07 ) . Treatment with rosuvastatin alone or combined with soluble fiber was associated with decreased levels of desmosterol ( p = 0.003 vs. other groups ) . Compared to non-fiber supplemented individuals , those treated with fibers had weight loss ( p = 0.04 ) , reduced body mass index ( p = 0.002 ) and blood glucose ( p = 0.047 ) . Conclusion Among subjects treated with highly effective lipid-lowering therapy , the intake of 25 g of fibers added favorable effects , mainly by reducing phytosterolemia . Additional benefits include improvement in blood glucose and anthropometric parameters ", "Background Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus , but many of these patients fail to achieve the target LDL-C level . Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin . However , in patients with type 2 diabetes who are already being treated with satins , it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose . Therefore , this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins . Methods The subjects were type 2 diabetic patients under treatment with rosuvastatin ( 2.5 mg daily ) , who had LDL-C levels ≥80 mg/dL. They were r and omly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day ( combination group , n = 40 ) or an increase of the rosuvastatin dose to 5 mg/day ( dose escalation group , n = 39 ) . These two groups were compared at baseline and after 12 weeks of treatment . Results The percent change of LDL-C was −31 % in the combination group and −12 % in the dose escalation group . Both groups showed a significant decrease , but the decrease was greater in the combination group . In both groups , there was a significant decrease in the levels of small dense LDL-C , oxidized LDL and remnant-like lipoprotein cholesterol . For all of these parameters , the percent changes were greater in the combination group . Only the combination group showed a significant decrease of triglycerides . Multivariate analysis was performed to identify factors associated with reaching an LDL-C level with ezetimibe was extracted as a factor related to improvement of LDL-C. Conclusions Compared with increasing the dose of rosuvastatin , the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients , suggesting that this combination could suppress the progression of atherosclerosis . Trial registration", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Summary Aim We aim ed to compare the effects of fixed‐dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia , including a subgroup analysis of patients with diabetes mellitus ( DM ) or metabolic syndrome ( MetS ) . Method This multicenter eight‐week r and omized double‐blind phase III study evaluated the safety and efficacy of fixed‐dose combinations of ezetimibe 10 mg plus rosuvastatin , compared with rosuvastatin alone in patients with primary hypercholesterolemia . Four hundred and seven patients with primary hypercholesterolemia who required lipid‐lowering treatment according to the ATP III guideline were r and omized to one of the following six treatments for 8 weeks : fixed‐dose combinations with ezetimibe 10 mg daily plus rosuvastatin ( 5 , 10 , or 20 mg daily ) or rosuvastatin alone ( 5 , 10 , or 20 mg daily ) . Results Fixed‐dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol , total cholesterol , and triglyceride levels compared with rosuvastatin alone . Depending on the rosuvastatin dose , these fixed‐dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol , total cholesterol , and triglyceride reductions of 56%–63 % , 37%–43 % , and 19%–24 % , respectively . Moreover , the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non‐DM or non‐MetS patients , respectively , whereas the effect of rosuvastatin alone did not differ between DM vs non‐DM or MetS vs non‐MetS patients . Conclusion Fixed‐dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol , total cholesterol , and triglyceride levels . Moreover , the reduction rate was greater in patients with DM or", "Objective . To investigate the effect of ezetimibe on the insulin secretion in db/db mice . Methods . The db/db diabetic mice aged 8 weeks were r and omly assigned into 2 groups and intragastrically treated with ezetimibe or placebo for 6 weeks . The age matched db/m mice served as controls . At the end of experiment , glucose tolerance test was performed and then the pancreas was collected for immunohistochemistry . In addition , in vitro perfusion of pancreatic islets was employed for the detection of insulin secretion in the first phase . Results . In the ezetimibe group , the fasting blood glucose was markedly reduced , and the total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) were significantly lowered when compared with those in the control group ( P area under curve in the ezetimibe group was significantly smaller than that in the control group ( P first phase insulin secretion was improved . In addition , the insulin expression in the pancreas in the ezetimibe group was significantly increased as compared to the control group . Conclusion . Ezetimibe can improve glucose tolerance , recover the first phase insulin secretion , and protect the function of β cells in mice", "AIM To demonstrate the clinical benefit of inhibiting intestinal cholesterol absorption , we evaluated the effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis , lipid and glucose metabolism , and markers of obesity and inflammation . METHODS A total of 120 patients with dyslipidemia ( 46 men ; mean age 66.5 years ) , who had not achieved the low density lipoprotein cholesterol ( LDL-C ) goal recommended by the Japan Atherosclerosis Society Guideline despite diet and exercise or any statin therapy , were enrolled and additionally treated with ezetimibe ( 10 mg/day ) for 12 weeks . RESULTS Compared to the baseline , LDL-C was reduced by 19.2 % ( p ezetimibe monotherapy and by 24.7 % ( p ezetimibe and any statin . Ezetimibe therapy decreased cholesterol absorption markers and increased a cholesterol synthesis marker . Treatment with ezetimibe reduced the fasting serum insulin level ( p HbA1c ( p serum adiponectin ( p high-sensitive C-reactive protein ( hsCRP , p adverse events occurred during the study . CONCLUSION Thus , cholesterol absorption inhibition by ezetimibe is an important therapeutic strategy since LDL-C and cholesterol absorption markers had a positive correlation . Ezetimibe not only reduced the serum LDL-C level but also improved glucose metabolism as well as obesity and inflammation markers . These findings support the benefit of ezetimibe as a new option for the treatment of dyslipidemia", "Ezetimibe selectively inhibits dietary and biliary cholesterol absorption and reduces serum cholesterol levels when administered alone ( monotherapy ) and along with common lipid-regulating agents ( combination therapy ) . To evaluate the effect of ezetimibe therapy on the lipid profile , glucose metabolism , and levels of cholesterol absorption and synthesis markers , we administered 10 mg ezetimibe to 50 hypercholesterolemic patients with or without diabetes . The serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly reduced at 4 and 12 weeks of ezetimibe therapy in diabetic patients of both the monotherapy and combination-therapy groups and in nondiabetic patients of the combination-therapy group . The serum levels of the cholesterol absorption markers were significantly reduced , while those of the cholesterol synthesis markers were significantly increased at 12 weeks of ezetimibe therapy . No significant differences were noted in the values of the parameters of glucose metabolism in all patients . We also investigated the clinical characteristics of patients who exhibited a good response to ezetimibe ( ezetimibe responders ) ; however , multivariate regression analysis did not reveal a correlation between ezetimibe efficacy and patient characteristics such as gender , age , BMI , diabetic condition , method of ezetimibe administration , and the initial absolute values of cholesterol absorption/ synthesis markers levels . In conclusion , ezetimibe therapy significantly improved the lipid profile without disturbing glucose metabolism . We were unable to identify the specific characteristics of ezetimibe responders among our subjects . However , we may interpret this result as suggesting that ezetimibe can be used in any population to lower low-density lipoprotein cholesterol levels", "Background There exists a sub population of T2DM in whom first-line doses of statin are insufficient for optimally reducing LDL-C , representing a major risk of CVD . The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks . Methods Lipid changes were assessed in a r and omized , multicenter , 12-week , open-label study comparing a high-potency statin ( 10 mg of atorvastatin or 1 mg of pitavastatin ) plus ezetimibe ( EAT : n = 53 ) with a double dose of statin ( 20 mg of atorvastatin or 2 mg of pitavastatin ) ( DST : n = 56 ) in DM subjects who had failed to achieve the optimal LDL-C targets . Lipid variables were compared with a primary focus on LDL-C and with secondary focuses on the percentage of patients who reached the LDL-C targets and changes in the levels of RLP-C ( remnant like particle cholesterol ) and sd-LDL-C , two characteristic atherogenic risks of DM . Results The reduction of LDL-C ( % ) , the primary endpoint , differed significantly between the two groups ( -24.6 in EAT vs. -10.9 in DST ) . In the analyses of the secondary endpoints , EAT treatment brought about significantly larger reductions in sd-LDL-C ( -20.5 vs. -3.7 ) and RLP-C ( -19.7 vs. + 5.5 ) . In total , 89.4 % of the patients receiving EAT reached the optimized treatment goal compared to 51.0 % of the patients receiving DST . The changes in TC ( -16.3 vs. -6.3 ) and non-HDL-C ( -20.7 vs. -8.3 ) differed significantly between the two groups . Conclusion Ezetimibe added to high-potency statin ( 10 mg of atorvastatin or 1 mg of pitavastatin ) was more effective than the intensified-dose statin ( 20 mg of atorvastatin or 2 mg of pitavastatin ) treatment not only in helping T2DM patients attain more LDL-C reduction , but also in improving their atherogenic lipid profiles , including their levels of sd-LDL-C and RLP-C. We thus recommend the addition of ezetimibe to high-potency statin as a first line strategy for T2DM patients with insufficient statin response . Trial Registration The UMIN Clinical Trials Registry", "INTRODUCTION Type 2 diabetes is associated with atherogenic abnormalities of postpr and ial triglyceride-rich lipoproteins . This study evaluated whether ezetimibe , by inhibiting intestinal cholesterol absorption , influences chylomicrons and VLDL particles at fasting and after a st and ard meal . METHODS By a double blind cross-over design 15 subjects with type 2 diabetes and hypercholesterolaemia followed in r and om order a 6-week treatment with ezetimibe 10mg+simvastatin 20 mg ( EZE+S ) or placebo+simvastatin 20 mg ( P+S ) and , after a 6-week wash-out period , crossed over to the other treatment ( NCT00699023 ) . At the end of each period lipids , apoB-48 , and apoB-100 concentrations in plasma and lipoprotein fractions ( separated by discontinuous density gradient ultracentrifugation ) were determined before and over 6h following a high-fat test meal . RESULTS Compared with P+S , EZE+S induced , ( a ) beside a greater decrease in LDL cholesterol , ( b ) a significant decrease in chylomicron lipid content both at fasting and postpr and ially ( 4.4 ± 2.7 vs. 8.3 ± 8.7 mg/dl × 6 h total AUC for cholesterol , p mg/dl triglyceride concentrations at 6h , p decrease in chylomicron postpr and ial apoB-48 ( 0.03 ± 0.03 vs. 0.09 ± 0.08 mg/l at 4 h , p decreases in the cholesterol content of VLDL , IDL , and LDL , as shown by the significant reduction of the cholesterol/triglyceride ratio in these lipoproteins . CONCLUSIONS A 6-week treatment with ezetimibe and simvastatin , compared to simvastatin alone , positively influences lipoprotein profile both at fasting and postpr and ially in type 2 diabetic patients by favouring the production of cholesterol-poor chylomicrons and VLDL particles that have less atherogenic potential ", "BACKGROUND AND PURPOSE It remains undetermined whether the addition of ezetimibe to ongoing statin therapy is more effective than increasing the dose of statin for reducing remnant lipoprotein levels in patients with remnant lipoproteinemia on previous statin treatment . This study examined whether combined ezetimibe and statin therapy result ed in a greater improvement in remnant lipoprotein levels and endothelial function than with the dose of statin in patients with remnant lipoproteinemia on previous statin treatment . METHODS AND RESULTS A total of 63 patients with stable coronary artery disease and high levels of remnant-like lipoprotein particle cholesterol ( RLP-C ) ( ≥5.0 mg/dL ) on statin treatment were assigned r and omly to two groups and treated with either addition of ezetimibe ( 10mg/day , n=32 ) or doubling of statin dose ( n=31 ) . The lipid profiles and flow-mediated dilation ( FMD ) of the brachial artery were measured at enrollment and after 6 months of treatment . Statin and ezetimibe combined therapy reduced RLP-C and improved FMD to a greater extent than doubling the statin dose ( % reduction in RLP-C , 48 ± 18 % vs. 33 ± 24 % , respectively , p=0.01 ; % improvement in FMD , 47 ± 48 % vs. 24 ± 23 % , respectively , p=0.02 ) . CONCLUSIONS The addition of ezetimibe to ongoing statin treatment reduced RLP-C levels and improved endothelial dysfunction to a greater extent than doubling the statin dose in patients with high RLP-C levels on previous statin treatment . The present results are preliminary and should be confirmed by further studies on a larger number of study patients", "OBJECTIVE The effectiveness of the cholesterol absorption inhibitor ezetimibe on LDL subfractions and ultimately on the atherosclerotic risk profile remains controversial . We thus determined the concentration of atherogenic small , dense LDL ( sdLDL ) in patients with type 2 diabetes and an elevated cardiovascular risk profile . RESEARCH DESIGN AND METHODS Multicenter , r and omized , open-label 6-week study investigating the effect of ezetimibe 10 mg ( E ) , simvastatin 20 mg ( S ) and the combination of ezetimibe-/simvastatin 10/20 mg ( C ) on the concentration of sdLDL separated from fresh plasma by gradient ultracentrifugation in patients with type 2 diabetes ( NCT01384058 ) . RESULTS Fifty-six patients were screened for sdLDL , 41 were r and omized , and 40 patients ( 12 E , 14 S and 14 C ) completed the study . Total and LDL cholesterol fell by 14 % ( p=0.004 ) and 15 % ( p=0.006 ) with E , 22 % ( p reduced the concentration of sdLDL by 20 % ( p=0.043 ) whereas S and C reduced sdLDL by 24 % ( p=0.020 ) and 33 % ( p=0.003 ) , respectively , and non-sdLDL by 28 % ( p=0.004 ) and 42 % ( p drop in sdLDL by adding E to S was not significant . CONCLUSION Ezetimibe alone and in combination with simvastatin reduced the concentration of atherogenic sdLDL in patients with type 2 diabetes", "In addition to their expected effects on lipid profile , lipid-lowering agents may reduce cardiovascular events because of effects on nonclassic risk factors such as insulin resistance and inflammation . Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol as well as plant sterols . Although it is known that an additional reduction of low-density lipoprotein cholesterol ( LDL-C ) levels can be induced by the combination of ezetimibe with statins , it is not known if this can enhance some pleiotropic effects , which may be useful in slowing the atherosclerotic process . This study assessed the effects of simvastatin and ezetimibe , in monotherapy or in combination , on markers of endothelial function and insulin sensitivity . Fifty prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia were r and omly allocated to 2 groups receiving either ezetimibe ( 10 mg/d ) or simvastatin ( 20 mg/d ) for 12 weeks , after which the drugs were combined for both groups for an additional 12-week period . Clinical and laboratory parameters were measured at baseline and after 12 and 24 weeks of therapy . Homeostasis model assessment of insulin resistance index and the area under the curve of insulin were calculated . As expected , both groups receiving drugs in isolation significantly reduced total cholesterol , LDL-C , apolipoprotein B , and triglyceride levels ; and additional reductions were found after the combination period ( P plasminogen activator inhibitor-1 levels and urinary albumin excretion were lower in the simvastatin than in the ezetimibe group . No change in homeostasis model assessment of insulin resistance index , area under the curve of insulin , and adiponectin levels was observed after either the monotherapies or the combined therapy . However , simvastatin combined with ezetimibe provoked significant reductions in E-selectin and intravascular cellular adhesion molecule-1 levels that were independent of LDL-C changes . Our findings support cl aims that simvastatin may be beneficial in preserving endothelial function in prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia . Alternatively , a deleterious effect of ezetimibe on the endothelial function is suggested , considering the increase in intravascular cellular adhesion molecule-1 and E-selectin levels . Simvastatin and ezetimibe , in isolation or in combination , do not interfere with insulin sensitivity", "BACKGROUND Statin treatment may be associated with adverse effects on glucose metabolism . Whether this is a class effect is not known . In contrast , ezetimibe monotherapy may beneficially affect insulin sensitivity . OBJECTIVE The aim of this study was to compare the effects of three different regimens of equivalent low-density lipoprotein cholesterol ( LDL-C ) lowering capacity on glucose metabolism . METHODS A total of 153 patients ( 56 men ) , who had not achieved the LDL-C goal recommended by the National Cholesterol Education Program Adult Treatment Panel III ( NCEP-ATP III ) despite a 3-month dietary and lifestyle intervention , were r and omly allocated to receive open-label simvastatin 40 mg or rosuvastatin 10 mg or simvastatin/ezetimibe 10/10 mg for 12 weeks . The primary end point was changes in homeostasis model assessment of insulin resistance ( HOMA-IR ) . Secondary endpoints consisted of changes in fasting insulin levels , fasting plasma glucose ( FPG ) , glycosylated haemoglobin ( HbA(1c ) ) , the HOMA of β-cell function ( HOMA-B ) ( a marker of basal insulin secretion by pancreatic β-cells ) , LDL-C and high sensitivity C reactive protein ( hsCRP ) . RESULTS At week 12 , all three treatment regimens were associated with significant increases in HOMA-IR and fasting insulin levels ( p in FPG , HbA(1c ) and HOMA-B levels compared with baseline were noted in any of the three treatment groups . Changes in serum lipids and hsCRP were similar across groups . CONCLUSION To the extent that simvastatin 40 mg , rosuvastatin 10 mg and simvastatin/ezetimibe 10/10 mg are associated with adverse effects on insulin resistance , they appear to be of the same magnitude" ]

[ "UNLABELLED Among factors that affect diet-induced thermogenesis ( DIT ) are the sensory characteristics of food . The aim of this study was to test whether the sweet flavour obtained with a low-energy sweetener ( aspartame ) or with sucrose have a different effect on DIT . Following a st and ardized breakfast , 24 healthy male subjects were served three test lunches in a r and omized fashion . Lunch contained soft white cheese added with maltodextrins and aspartame , or sucrose , or maltodextrins only ( non-sweetened control ) ( each 900 kcal ) . Energy expenditure ( indirect calorimetry ) was monitored during the five postpr and ial hours . For the first two periods of measurement ( 30 - 60 and 90 - 120 min after meal ingestion ) , postpr and ial energy expenditure was significantly increased with sucrose compared to maltodextrins and maltodextrins plus aspartame , whereas no significant difference was found between maltodextrins and maltodextrins plus aspartame . No significant difference between lunches was observed for DIT expressed as incremental area above premeal baseline energy expenditure . Plasma glucose area under the curve was significantly lower for sucrose compared to maltodextrins plus aspartame . Plasma insulin area under the curve was significantly lower for sucrose compared to the other tests foods . IN CONCLUSION ( 1 ) variation in sweet-taste induced by aspartame or by sucrose does not seem to have a major effect on DIT in healthy humans ; ( 2 ) differences in energy expenditure observed in the early postpr and ial period suggest a substrate effect", "The long-term physiological effects of refined carbohydrates on appetite and mood remain unclear . Reported effects when subjects are not blind may be due to expectations and have rarely been studied for more than 24 h. The present study compared the effects of supplementary soft drinks added to the diet over 4 weeks on dietary intake , mood and BMI in normal-weight women ( n 133 ) . Subjects were categorised as ' watchers ' or ' non-watchers ' of what they ate then received sucrose or artificially sweetened drinks ( 4 x 250 ml per d ) . Expectancies were varied by labelling drinks ' sugar ' or ' diet ' in a counter-balanced design . Sucrose supplements provided 1800 kJ per d and sweetener supplements provided 67 kJ per d. Food intake was measured with a 7 d diary and mood with ten single Likert scales . By 4 weeks , sucrose supplements significantly reduced total carbohydrate intake ( F(1,129 ) = 53.81 ; P fat ( F(2,250 ) = 33.33 ; P protein intake ( F(2,250 ) = 28.04 ; P sweetener supplements . Mean daily energy intake increased by just under 1000 kJ compared with baseline ( t ( 67 df ) = 3.82 ; P sucrose to gain weight . There were no effects on appetite or mood . Neither dietary restraint status as measured by the Dutch Eating Behaviour Question naire nor the expectancy procedure had effects . Expectancies influenced mood only during baseline week . It is concluded that sucrose satiates , rather than stimulates , appetite or negative mood in normal-weight subjects", "Objective This r and omized , double-blind , crossover study was design ed to assess the effects of trehalose , a non-reducing disaccharide , alone and in combination with fructose , on postpr and ial serum insulin and glucose levels in obese men compared with a glucose control . Methods Participants ( n=21 ) ingested one of three study beverages , providing 75 g total carbohydrate , at each test visit , and venous blood sample s were collected immediately prior to consumption ( 0 min ) and at 30 min , 45 min , 60 min , 90 min , and 120 min post-consumption for assessment of serum insulin and plasma glucose levels . Results Consumption of beverages containing trehalose and the trehalose/fructose combination blunted glycemic and insulinemic incremental areas under the curve by 20–35 % , as compared with the glucose control . Conclusions Trehalose , alone or in combination with fructose , elicited lower glycemic and insulinemic responses in obese men as compared with glucose alone , and may have advantages in the development of food products", "BACKGROUND Evidence exists that beverages do not trigger appropriate anticipatory physiologic responses , such as cephalic phase insulin release . Therefore , it is of interest to eluci date the food properties necessary for triggering adaptive responses . Previously , we found a prolonged dose-dependent decrease in the hypothalamic functional magnetic resonance imaging signal after ingestion of a glucose solution . OBJECTIVES The aims of the present study were to measure the effects of sweet taste and energy content on the hypothalamic response to glucose ingestion and to measure the concomitant changes in blood glucose and insulin concentrations . DESIGN Five healthy , normal-weight men participated in a r and omized crossover design trial . The subjects were scanned 4 times for 37 min on separate days with functional magnetic resonance imaging . After 7 min , they ingested 1 of the following 4 stimuli ( 300 mL of each ) : water ( control ) , a glucose solution , an aspartame ( sweet taste ) solution , or a maltodextrin ( nonsweet carbohydrate ) solution . RESULTS Glucose ingestion result ed in a prolonged and significant signal decrease in the upper hypothalamus ( P maltodextrin ingestions result ed in similar increases in blood glucose and insulin concentrations . However , only glucose triggered an early rise in insulin concentrations . Aspartame did not trigger any insulin response . CONCLUSIONS Our findings suggest that both sweet taste and energy content are required for a hypothalamic response . The combination of sweet taste and energy content could be crucial in triggering adaptive responses to sweetened beverages", "BACKGROUND Fructooligosaccharides have been cl aim ed to lower fasting glycemia and serum total cholesterol concentrations , possibly via effects of short-chain fatty acids produced during fermentation . OBJECTIVE We studied the effects of fructooligosaccharides on blood glucose , serum lipids , and serum acetate in 20 patients with type 2 diabetes . DESIGN In a r and omized , single-blind , crossover design , patients consumed either glucose as a placebo ( 4 g/d ) or fructooligosaccharides ( 15 g/d ) for 20 d each . Average daily intakes of energy , macronutrients , and dietary fiber were similar with both treatments . RESULTS Compliance , expressed as the proportion of supplements not returned , was near 100 % during both treatments . Fructooligosaccharides did not significantly affect fasting concentrations ( mmol/L ) of serum total cholesterol ( 95 % CI : -0.07 , 0.48 ) , HDL cholesterol ( -0.04 , 0.04 ) , LDL cholesterol ( -0.06 , 0.34 ) , serum triacylglycerols ( -0.21 , 0.44 ) , serum free fatty acids ( -0.08 , 0.04 ) , serum acetate ( -0.01 , 0.01 ) , or blood glucose ( -0.37 , 0.40 ) . CONCLUSIONS We conclude that 20 d of dietary supplementation with fructooligosaccharides had no major effect on blood glucose , serum lipids , or serum acetate in patients with type 2 diabetes . This lack of effect was not due to changes in dietary intake , insufficient statistical power , or noncompliance of the patients", "BACKGROUND A high fructose intake can lead to postpr and ial hypertriacylglycerolemia . The underlying mechanism is unclear . OBJECTIVE The objective of the study was to investigate the mechanisms involved in fructose-induced hypertriacylglycerolemia and the contribution of de novo lipogenesis in an acute setting . DESIGN In a r and omized , crossover study , 14 subjects were given a fructose or glucose test meal after an overnight fast . [(2)H2]Palmitate and [U(13)C]d-fructose or [U(13)C]d-glucose were added to trace the h and ling of dietary fats and the fate of dietary sugars in the body . Blood sample s were taken before and after the meal . Respiratory exchange ratio was measured by using indirect calorimetry , and breath sample s were collected . RESULTS Plasma triacylglycerol and VLDL-triacylglycerol concentrations were significantly higher ( P = 0.001 for both ) , whereas the concentrations of insulin and [(2)H2]palmitate in nonesterified fatty acids were significantly lower after fructose than after glucose ( P = 0.002 and 0.03 , respectively ) . The respiratory exchange ratio was higher after fructose ( P = 0.04 ) ; significantly ( P = 0.003 ) more carbon from sugars was recovered in breath carbon dioxide over 6 h after fructose ( 30.5 % ) than after glucose ( 24.5 % ) . At 240 min , newly synthesized fatty acids from fructose made up approximately 0.4 % of circulating VLDL-triacylglycerol , whereas newly synthesized triacylglycerol-glycerol made up 38 % . Newly synthesized fatty acids and triacylglycerol-glycerol from glucose contributed almost none of VLDL-triacylglycerol ( P = 0.002 and 0.007 for glucose and fructose , respectively ) . CONCLUSIONS The lower insulin excursion after fructose may result in less activation of adipose tissue lipoprotein lipase , which led to impaired triacylglycerol clearance . The contribution of de novo lipogenesis to fructose-induced hypertriacylglycerolemia is small , but its effect on altering the partitioning of fatty acids toward esterification may be considerable", "BACKGROUND About 9 % of average dietary energy intake in the United States comes from fructose . Such a high consumption raises concern about the metabolic effects of this sugar . OBJECTIVE The objective of this study was to determine the effect of dietary fructose on plasma lipids . DESIGN The study was conducted in the General Clinical Research Center at Fairview-University of Minnesota Medical Center . The participants were 24 healthy adult volunteers ( 12 men and 12 women ; 6 of each sex were aged /=40 y ) . All subjects received 2 isoenergetic study diets assigned by using a r and omized , balanced crossover design . One diet provided 17 % of energy as fructose . The other diet was sweetened with glucose and was nearly devoid of fructose . Each diet was fed for 6 wk . Both diets were composed of common foods and contained nearly identical amounts of carbohydrate , protein , fat , fiber , cholesterol , and saturated , monounsaturated , and polyunsaturated fatty acids . All meals were prepared in the metabolic kitchen of the General Clinical Research Center . RESULTS The responses to the study diets differed by sex . In men , the fructose diet produced significantly higher fasting , postpr and ial , and daylong plasma triacylglycerol concentrations than did the glucose diet . The daylong plasma triacylglycerol concentration after 6 wk of the fructose diet was 32 % greater in men than the corresponding concentration during the glucose diet ( P : fructose diet had no significant effect on fasting or postpr and ial plasma triacylglycerol concentrations in women . The fructose diet also had no persistent effect on fasting plasma cholesterol , HDL cholesterol , or LDL cholesterol in either men or women . CONCLUSIONS Dietary fructose was associated with increased fasting and postpr and ial plasma triacylglycerol concentrations in men . Diets high in added fructose may be undesirable , particularly for men . Glucose may be a suitable replacement sugar", "Short-chain fructooligosaccharides ( FOS ) are prebiotics , which escape digestion in the small intestine and are fermented by the colonic microflora into short-chain fatty acids . Recently , we found that the daily consumption of 20 g FOS decreased basal hepatic glucose production in healthy subjects without any effect on insulin-stimulated glucose metabolism . In this study , we evaluated the effects of the chronic ingestion of FOS on plasma lipid and glucose concentrations , hepatic glucose production and insulin resistance in type 2 diabetics . Type 2 diabetic volunteers ( n = 10 ; 6 men , 4 women ) received either 20 g/d FOS or sucrose for 4 wk in a double-blind crossover design . FOS did not modify fasting plasma glucose and insulin concentrations or basal hepatic glucose production . The plasma glucose response to a fixed exogenous insulin bolus did not differ at the end of the two periods . Erythrocyte insulin binding also did not differ . Serum triacylglycerol , total and HDL cholesterol , free fatty acid , apolipoproteins A1 and B and lipoprotein ( a ) concentrations were not modified by the chronic ingestion of FOS . We conclude that 4 wk of 20 g/d of FOS had no effect on glucose and lipid metabolism in type 2 diabetics", "The impact of slow digestible sources of dietary carbohydrate in reducing the risk of developing obesity and related metabolic disorders is unclear . The aim of the present study was to compare the postpr and ial metabolic response to the ingestion of sucrose v. isomaltulose . We hypothesised that the reduced digestion and absorption rate of isomaltulose would result in lower glycaemic and insulinaemic responses when compared with the ingestion of sucrose , leading to greater postpr and ial fat oxidation rates . In a r and omised , single-blind , cross-over study , ten overweight subjects ingested two different carbohydrate drinks ( sucrose and isomaltulose , 75 g carbohydrate equivalents ) following an overnight fast ( 08.40 hours ) and with a st and ardised meal ( 12.30 hours , 25 % of total energy content was provided as either a sucrose or isomaltulose drink ) . Blood sample s were taken before ingestion and every 30 min thereafter for a period of 3 h , substrate use was assessed by indirect calorimetry and breath sample s were collected . Ingestion of carbohydrates with a mixed meal result ed in a lower peak glucose and insulin response and a lower change in area under the curve ( DeltaAUC ) following isomaltulose when compared with sucrose . Together with the lower glucose and insulin responses , postpr and ial fat oxidation rates were higher ( 14 % ) with isomaltulose when compared with sucrose when ingested with a mixed meal ( P = 0.02 ) . The attenuated rise in glucose and insulin concentrations following isomaltulose results in reduced inhibition of postpr and ial fat oxidation . The metabolic response to isomaltulose co-ingestion suggests that this may represent an effective nutritional strategy to counteract overweight-induced metabolic disturbances", "It has been found that honey ameliorates cardiovascular risk factors in healthy individuals and in patients with elevated risk factors . The present study investigated the effect of natural honey on total cholesterol , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , triacylglycerole , C-reactive protein ( CRP ) , fasting blood glucose ( FBG ) , and body weight in overweight individuals . There were 55 patients , overweight or obese , who were r and omly recruited into the study and assigned into two groups : control group ( 17 subjects ) and experimental group ( 38 subjects ) . Patients in the control group received 70 g of sucrose daily for a maximum of 30 days and patients in the experimental group received 70 g of natural honey for the same period . In the control and experimental groups , body weight , body mass index , body fat weight , total cholesterol , LDL-C , HDL-C , triacylglycerole , FBG , and CRP were measured before treatment and at day 31 after the commencement of treatment . Results showed that honey caused a mild reduction in body weight ( 1.3 % ) and body fat ( 1.1 % ) . Honey reduced total cholesterol ( 3 % ) , LDL-C ( 5.8 ) , triacylglycerole ( 11 % ) , FBG ( 4.2 % ) , and CRP ( 3.2 % ) , and increased HDL-C ( 3.3 % ) in subjects with normal values , while in patients with elevated variables , honey caused reduction in total cholesterol by 3.3 % , LDL-C by 4.3 % , triacylglycerole by 19 % , and CRP by 3.3 % ( p natural honey reduces cardiovascular risk factors , particularly in subjects with elevated risk factors , and it does not increase body weight in overweight or obese subjects", "Objective : To investigate appetite responses over 4 h to fructose beverages in obese men , relative to glucose and whey protein . Second , to investigate the effect of combining whey and fructose on postpr and ial appetite hormones . Design : R and omized , double-blind crossover study of four beverages ( 1.1 MJ ) containing 50 g of whey , fructose , glucose or 25 g whey+25 g fructose . Blood sample s and appetite ratings were collected for 4 h then a buffet meal was offered . Subjects : Twenty-eight obese men ( age : 57.0±1.6 years , body mass index : 32.5±0.6 kg/m2 ) Measurements : Plasma ghrelin ( total ) , glucagon-like peptide-1 ( GLP-1 7–36 ) , cholecystokinin-8 , glucose , insulin and appetite ratings were assessed at baseline and 30 , 45 , 60 , 90 , 120 , 180 , 240 min after beverages , followed by measurement of ad libitum energy intake . Results : Fructose produced lower glycaemia and insulinaemia compared to the glucose treatment ( P whereas postpr and ial ghrelin , GLP-1 and cholecystokinin responses were similar after both treatments . Whey protein produced a prolonged ( 2–4 h ) suppression of ghrelin ( P=0.001 ) and elevation of GLP-1 ( P=0.002 ) and cholecystokinin ( P=0.003 ) that were reduced when combined with fructose , while glucose and insulin responses were similar . Energy intake after 4 h was independent of beverage type ( glucose 4.7±0.2 MJ ; fructose 4.9±0.3 MJ ; whey 4.6±0.3 MJ ; whey/fructose 4.8±0.3 MJ ; P>0.05 ) . Conclusion : In obese men , fructose- and glucose-based beverages had similar effects on appetite and associated regulatory hormones , independent of the differing glycaemic and insulinaemic responses . The contrasting profile of plasma ghrelin , GLP-1 and cholecystokinin after whey protein consumption did not impact on ad libitum intake 4 h later and was attenuated when 50 % of whey was replaced with fructose ", "Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed", "AIM To compare the effect of 2 liquid nutritional supplements ( Enterex Diabetic and Glucerna SR ) design ed for the patient with diabetes mellitus on postpr and ial glucose , insulin secretion , and insulin sensitivity in healthy individuals . PATIENTS AND METHODS A r and omized , double-blind , crossover clinical trial was carried out in 14 healthy , young ( average age 21.7+/-2.8 years ) volunteers . Each individual received a single administration of 232 kcal in 232 mL of Enterex Diabetic or in 237 mL of Glucerna SR . Three days later , the intervention was crossed using the opposite supplement . At the beginning of each administration and later at 30 , 60 , 90 , and 120 minutes , glucose and insulin concentrations were measured . Triglyceride concentrations were measured at the beginning and at 120 minutes . Area under the curve of glucose and insulin was calculated . First-phase and total insulin secretion , as well as insulin sensitivity , were assessed . RESULTS Glucose concentration at 120 minutes was significantly lower after the administration of Enterex Diabetic in comparison with Glucerna SR ( 4.3+/-0.6 vs 4.7+/-0.4 mmol/L ; P=.012 ) . Enterex Diabetic compared with Glucerna SR showed a greater change of the glucose concentration from 0 to 120 minutes ( -0.7+/-0.6 vs -0.0+/-0.4 mmol/L ; P=.002 ) . Administration of Enterex Diabetic decreased insulin concentrations at 120 minutes ( 60+/-18 vs 48+/-19 pmol/L ; P=.013 ) . Administration of Glucerna SR increased triglyceride concentration at 120 minutes ( 1.0+/-0.3 vs 1.1+/-0.4 mmol/L ; P=.026 ) . CONCLUSION A single administration of Enterex Diabetic in healthy individuals decreased glucose and insulin concentrations at 120 minutes without any modification in triglyceride levels", "Previous studies indicate that leptin secretion is regulated by insulin-mediated glucose metabolism . Because fructose , unlike glucose , does not stimulate insulin secretion , we hypothesized that meals high in fructose would result in lower leptin concentrations than meals containing the same amount of glucose . Blood sample s were collected every 30 - 60 min for 24 h from 12 normal-weight women on 2 r and omized days during which the subjects consumed three meals containing 55 , 30 , and 15 % of total kilocalories as carbohydrate , fat , and protein , respectively , with 30 % of kilocalories as either a fructose-sweetened [ high fructose ( HFr ) ] or glucose-sweetened [ high glucose ( HGl ) ] beverage . Meals were isocaloric in the two treatments . Postpr and ial glycemic excursions were reduced by 66 + /- 12 % , and insulin responses were 65 + /- 5 % lower ( both P area under the curve for leptin during the first 12 h ( -33 + /- 7 % ; P diurnal amplitude ( peak - nadir ) ( 24 + /- 6 % ; P levels of the orexigenic gastroenteric hormone , ghrelin , were suppressed by approximately 30 % 1 - 2 h after ingestion of each HGl meal ( P suppression of ghrelin was significantly less pronounced after HFr meals ( P elevation of plasma triglycerides compared with the HGl day ( P circulating insulin and leptin and increased ghrelin concentrations , as demonstrated in this study , could lead to increased caloric intake and ultimately contribute to weight gain and obesity during chronic consumption of diets high in fructose", "Backgroud/ Objective : To compare postpr and ial responses elicited by sucromalt , a nutritive sweetener produced by treating a blend of sucrose and corn syrup with an enzyme from Leuconostoc mesenteroides , with those after 42 % of high-fructose corn syrup ( HFCS ) , and to see if the reduced responses after sucromalt could be accounted for by carbohydrate malabsorption . Subject and Methods : Three experiments were performed in separate groups of normal subjects studied after overnight fasts using double-blind , r and omized , cross-over design s. HFCS was used as the control because it contained a similar amount of fructose as sucromalt . Experiment 1 ( n=10 ) : plasma glucose and insulin were measured after 50 g sucromalt and 50 g HFCS . Experiment 2 ( n=10 ) : metabolic profiles were measured after 80 g HFCS , 80 g sucromalt or 56 g fructose/glucose blend plus 24 g inulin . Experiment 3 ( n=20 ) : the glycaemic indices of sucromalt and HFCS were determined . Results : Mean glucose and insulin responses after sucromalt were 66 and 62 % , respectively , of those after HFCS ( P inulin treatment , used to mimic the effects of carbohydrate malabsorption , elicited higher breath hydrogen ( H2 ) , lower glucose and insulin responses , and a significantly earlier rise in serum free fatty acids ( FFA ) than those of HFCS ( all P Sucromalt elicited no rise in breath H2 , and delayed falls in glucose and insulin , and a delayed rebound of FFA compared to HFCS ( all P glucose and insulin responses elicited by sucromalt are not explained by malabsorption and are more likely related to differences in either rate of digestion and absorption or postabsorptive h and ling by body", "It has been cl aim ed that sucrose intake induces a rise in beta-endorphins . In an attempt to discriminate between the sensorial and metabolic effects of sucrose intake in this process , the effects of two chocolate drinks were compared : one sweetened with 50 g of sucrose , the other with 80 mg of aspartame . Plasma beta-endorphin concentrations were more elevated after the aspartame drink than after sucrose or fasting , while insulin increased after drinking as much with aspartame as with sucrose . We suggest that the increase in beta-endorphin after aspartame edulcorated chocolate is related with insulin secretion in the absence of marked changes in blood glucose or with a direct effect of aspartame itself on beta-endorphin liberation", "Abstract Background : We investigated the effects of daily palatinose intake on the risk factors of metabolic syndrome in sedentary non-obese Japanese adults . Methods : Japanese adults ( 40 females and 10 males , age : 53 ± 9 years , range : 31–72 years old ) were r and omized into two groups for a double-blind , placebo-controlled intervention study and given either 40 g/day palatinose-blended sugar ( PS group ) or 40 g/day sucrose ( S group ) in their diet for 12 weeks . Results : After the intervention , the insulin resistance index ( HOMA-IR ) had significantly decreased only in the PS group ; the inter-group difference was significant at P = 0.006 . Although the S group showed a significant increase in the leptin concentration and the systolic blood pressure , the PS group showed no significant changes ; the inter-group differences were significant at P = 0.018 and P = 0.037 , respectively . Conclusion : Palatinose intake possibly improves insulin sensitivity when compared with sucrose intake", "BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects", "Twelve normal subjects and 10 subjects with non-insulin-dependent diabetes mellitus were given , in r and om order at intervals of ≥ 1 wk , three drinks of the same beverage : one unsweetened , one sweetened with 400 mg aspartame , and one sweetened with 135 mg saccharin . The amount of sweetener approximated that in 1 L of sugar-free soft drink . Plasma glucose , insulin , and glucagon were measured for 3 h after ingestion of the test beverage . Plasma glucose declined slightly throughout the test period , probably due to fasting , with no differences between the three treatments . Neither sweetener affected peak insulin levels in subjects with or without diabetes . Analysis of area under the curve showed that mean insulin levels were statistically significantly higher after aspartame than after saccharin or unsweetened beverage in normal subjects only , but the magnitude of the difference was small and unlikely to be of physiological importance in the absence of differences in glucose levels . Furthermore , the differences could largely be accounted for by a decrease in insulin values after both unsweetened beverage and saccharin , with no change from baseline after aspartame . Glucagon levels showed time-to-time variation but no overall differences . We conclude that ingestion of aspartame- or saccharin-sweetened beverages by fasting subjects , with or without diabetes , did not affect blood glucose homeostasis ", "Despite some reports that aspartame (APM)-sweetened beverages may increase subjective appetite , previously we demonstrated that drinking 280 ml of an APM-sweetened soft drink ( 170 mg APM ) had no effect on appetite , and 560 ml of the same soft drink ( 340 mg APM ) reduced appetite . The present study examined this appetite reduction to determine its cause . Eighteen normal weight young adult males received five treatments ( beverage preloads ) at 1100 h in a r and omized order , one per week : 280 ml of carbonated mineral water ( CMW ) ( control ) , 560 ml of CMW , 280 ml of CMW with 340 mg of encapsulated APM , 280 ml of CMW sweetened with 340 mg APM , 560 ml of an APM-sweetened soft drink ( 340 mg APM ) . Subjective hunger and food appeal were measured from 0930 a.m. to 1230 h , and food intake from a buffet lunch offered at 1205 h was measured . Treatment had no effect on food intake or macronutrient selection . Both 560 ml of CMW or soft drink suppressed appetite , although 280 ml of APM-sweetened mineral water significantly increased subjective appetite relative to the control . Encapsulated APM had no effect on appetite . Therefore , appetite reduction following consumption of an APM-sweetened drink is likely due to drink volume and not the APM content . In addition , consuming APM-sweetened CMW produces a short-term increase in subjective appetite", "For physicians , pharmacists , pharmacologists , and others , the medical literature is a key source of information about prescription drugs [ 1 , 2 ] . The medical literature on drugs includes articles from peer- review ed journals , non-peer- review ed ( controlled circulation or throwaway ) journals , and the published proceedings of symposia [ 3 , 4 ] . Symposia are a rapidly growing and potentially major means of disseminating information about drugs . In the clinical journals with the highest circulation rates , the number of symposia published increased from 83 during 1972 - 1977 to 307 during 1984 - 1989 . Approximately half of these symposia were on pharmaceutical topics [ 4 ] . Symposia can be valuable sources of information about drugs , but evidence suggests that they can also be used to market drugs and other interventions , especially if they are industry sponsored . Approximately 70 % of symposia on pharmaceutical topics are sponsored by drug companies [ 3 , 4 ] . Among symposia , sponsorship by a single drug company is associated with promotional characteristics that include a focus on a single drug , misleading titles , use of br and names , and lack of peer review [ 4 ] . Other studies indicate that clinical trials , including those published in symposia , are more likely to favor a new drug therapy if they are funded by the pharmaceutical industry than if they are not [ 5 , 6 ] . Although physicians often report that the peer- review ed literature is one of their main sources of drug information , industry sources of information can sometimes have a stronger influence on prescribing behavior [ 2 ] . Thus , if symposia sponsored by drug companies are a growing source of information about drugs for pharmacists and physicians , assessing the quality of the articles in these symposia is important . We compared the method ologic quality and relevance of drug studies published in symposia sponsored by single drug companies with those of studies that were published in symposia that had other sponsors or in the peer- review ed parent journals . We also assessed whether a methods section was present , because such a section is necessary for evaluating quality . Finally , we tested whether drug industry support of research was associated with study outcome . Methods A symposium is a collection of papers published as a separate issue or as a special section in a regular issue of a medical journal [ 4 ] . We defined original clinical drug articles as articles that 1 ) appeared to present original data from studies done in humans [ that is , articles that had at least one table or figure that was not acknowledged to have been reprinted from another source ] and 2 ) did not specifically state that they were review s [ 4 ] . Selection of Articles We identified original clinical drug articles that had a section describing the study methods , because such a section is needed to assess the quality of an article . Using a computer-generated list of r and om numbers from 1 to 625 , we r and omly selected symposia from 625 symposia that had been identified for a previous study [ 4 ] . We had data on the type of sponsorship of publication for each symposium . From each selected symposium , we r and omly selected one original clinical drug article that had a methods section . We continued selecting symposia until we had enough articles ( n = 127 ) according to the sample size estimates described below . We also calculated the proportion of articles in the selected symposia , overall and by type of sponsorship , that had methods sections . Quality Assessment We compared the quality of original clinical drug articles published in symposia sponsored by single drug companies with that of similar articles published in symposia that had other sponsors and in the peer- review ed parent journals . Sample Size Estimates We estimated the sample size needed to test the association between the independent variable type of sponsorship of publication and the main outcome measure , method ologic quality score . For a three-group comparison , a minimum sample of 108 symposium articles was needed to detect a minimum effect size of 0.10 ( on a scale of 0 to 1 ) , with an value of 0.05 and a value of 0.80 , and st and ard deviation of quality scores of 0.18 based on previous results [ 7 ] . To compare articles from symposia sponsored by single pharmaceutical companies with articles from the peer- review ed parent journals , we estimated that we would need 45 symposia articles and 45 journal articles ; this estimate was the result of sample size calculations done using the variables described above . Because date of publication , journal , and therapeutic class of drug could have confounded the association between source of publication and quality [ 8 - 10 ] , we matched each symposium article to an article from the parent journal by using these characteristics , as described previously [ 7 ] . Our sample of symposium articles contained 50 articles sponsored by single drug companies , but 5 articles published in Transplantation Proceedings were excluded from this analysis because no parent journal is associated with that publication . Instruments We used previously developed instruments to measure the method ologic quality of articles ( defined as the minimization of systematic bias and the consistency of conclusions with results ) and non method ologic indices of quality , such as clinical relevance and generalizability . Both instruments were valid and reliable and have been published elsewhere [ 7 ] . Four review ers independently assessed each article : Two used the method ologic quality instrument , and two used the clinical relevance instrument . We derived method ologic quality and clinical relevance scores for each article by using a previously described scoring system [ 7 ] . Each score was between 0 ( lowest quality ) and 1 ( highest quality ) and was the average of the scores of the two review ers . Two clinical pharmacologists with extensive research experience in the health sciences did the method ologic quality assessment . For the clinical relevance instrument , three pairs of review ers with clinical experience in general internal medicine and research experience in the health sciences each assessed one third of the articles . Each pair of review ers review ed the articles in the same r and omized order . For both instruments , review ers were trained as described previously [ 7 ] . For the quality assessment s , each review er worked independently , was blinded as to whether an article had been published in a symposium , and was given photocopies of articles from which author names , institution names , journal names , date s , and all other reference information had been obliterated . Review ers were unaware of our hypotheses and the purpose of their review ing , and they were paid for their work . None of the review ers were known to us or knew of our previous work before the study . We assessed the inter-rater reliability of quality scores by using the Kendall coefficient of concordance ( W ) with adjustment for tied ranks [ 11 ] and the intraclass correlation ( R ; treating both review ers and articles as r and om effects [ 12 ] ) . Inter-rater reliability of quality scores was high ( for method ologic quality scores : W equals 0.85 , R equals 0.74 [ 95 % CI , 0.67 to 0.80 ] ; for clinical relevance scores : W equals 0.77 , R equals 0.56 [ CI , 0.44 to 0.65 ] ) . Drug Company Support and Study Outcome For each article , one of us determined whether a drug company had supported the research and whether the article 1 ) reported an outcome favorable to the drug of interest , 2 ) did not report an outcome favorable to the drug of interest , or 3 ) did not test a hypothesis . The drug of interest ( as defined from the perspective of the authors , according to Gotzsche [ 13 ] ) was the newest drug if two or more drugs were studied . We defined research as having had drug company support if the article that reported the research acknowledged either that a drug company had provided funding or drugs or that any of the authors were employed by a drug company . We determined drug company support solely on the basis of information in the paper . If an article did not test a hypothesis , it was excluded from this analysis . We classified the remaining articles as favorable or unfavorable using Gotzsche 's definitions [ 13 ] . An article was favorable if the drug that seemed to be of primary interest to the authors had the same effect as the comparison drug or drugs but with less pronounced side effects , had a better effect without more pronounced side effects , or was preferred more often by patients when the effect and side-effect evaluations were combined . All other articles were considered not favorable . The conclusions of the authors were taken at face value , even if they conflicted with the study results . To test inter-rater reliability , the other author independently assessed a subset of the articles ( n = 90 ) . Agreement in classifying articles as favorable or not favorable was 85 % . Statistical Analyses Because method ologic quality and relevance scores were distributed normally ( Shapiro-Wilk test ) , we analyzed differences between groups ( type of sponsorship of publication ) by using parametric one-way analysis of variance followed by the Tukey test for multiple comparisons or two-way analysis of variance ( total error rate , 0.05 ) . We compared matched groups ( symposium articles and peer- review ed parent journal articles ) by using the paired t-test ( two-tailed equals 0.05 ) . To analyze categorical data on the outcome of studies , we tested for differences in proportions between groups by using the chi-square statistic . For tests of significance , we used an value of 0.05 . All hypothesis tests were two-sided . Results Presence of a Method Section To obtain 127 original clinical drug articles for quality assessment , we had to select 213 symposia containing a total of 5041 articles . The proportions of articles that reported original data but contained no methods sections were 4 % overall ( 195 of 5041 ) , 10 % ( 108 of 1064 ) in the symposia sponsored by single drug companies", "Studies suggest that honey has less influence on serum glucose concentrations than monosaccharides and disaccharides . This study aim ed to confirm these findings conclusively by comparing directly the effects of honey , an identical sugar solution , and oral glucose tolerance ( OGT ) test solution on serum glucose , insulin , and C-peptide values in healthy subjects . Twelve healthy men with a mean age of 27.7 years , a mean body mass index of 23.2 kg/m(2 ) , and no history of metabolic disorders participated in the study . Subjects underwent OGT testing to establish values and exclude pre clinical diabetes . One week later they were r and omly assigned to basswood honey or a glucose-fructose solution ( honey-comparable glucose-fructose solution ) . The following week subjects were given the other solution . All solutions contained 75 g of glucose . Serum glucose was measured before drinking test solutions and every 10 minutes for 120 minutes afterwards . C-peptide and insulin were measured at 60 and 120 minutes . Serum insulin and C-peptide values at 60 minutes were significantly lower for honey . The mean serum glucose concentration was also lower for honey , but direct comparisons at the various times showed no statistically significant differences between solutions . However , the area under the concentration-time profile for glucose response was lower for the honey than the honey-comparable glucose-fructose solution . Honey had less effect on serum glucose , C-peptide , and insulin values than the honey-comparable glucose-fructose solution . Further study to eluci date underlying mechanisms may be worthwhile , as may investigation of the implication s of these findings for diabetic patients", "BACKGROUND Industrialists are search ing for a sugar replacement in confectioneries such as hard c and ies , gum and chocolate . Lycasin HBC is a suitable c and i date . Nevertheless , no information on its plasma glucose and insulin responses exists . Therefore , we aim ed to evaluate the glycaemic and insulinaemic indices of Lycasin HBC in healthy subjects and in subjects with type 2 diabetes mellitus . METHODS Six healthy and six type 2 diabetic men participated in the study . Each subject absorbed , after an overnight fast , a challenge of either 50 g of glucose or 50 g of Lycasin HBC using a r and omised double-blind crossover design . Blood sample s for measuring plasma glucose and insulin concentrations were collected during a 3 hour period . RESULTS The calculated glycaemic index of Lycasin HBC was 47 + /- 10 % in healthy subjects and 25 + /- 6 % in patients with type 2 diabetes mellitus . The insulinaemic index of Lycasin HBC was 23 + /- 4 % and 39 + /- 14 % , respectively . As glucose levels oscillate in a very limited range in normal healthy subjects , the insulinaemic index must be considered here . On the other h and , it is the glycaemic rather than the insulinaemic index that must be assessed in diabetic subjects due to impairment of insulin secretion . CONCLUSIONS The tested Lycasin HBC showed a low insulinaemic index in healthy subjects ( 23 + /- 4 % ) and a low glycaemic index ( 25 + /- 6 % ) in type 2 diabetic patients . Thus , it might be considered as an interesting sucrose substitute in confectionery for individuals with or without diabetes", "St and ard toxicity tests with high levels of D-tagatose showed a reversible enlargement of the liver in Sprague-Dawley rats without increase of liver enzymes . The present study tests the hypotheses that partial substitution of dietary sucrose by D-tagatose for 28 days increases the volume of human liver and the concentration of liver glycogen . Twelve healthy , male volunteers were studied in a double-blind crossover study with ingestion of D-tagatose ( 3x15 g daily ) and placebo ( sucrose , 3x15 g daily ) for periods of 28 days each . Liver volume and glycogen concentration have been determined by magnetic resonance ( MR ) imaging and spectroscopy , which were accompanied by routine medical examinations . MR examinations before and after the treatments revealed no effects ( P>0.05 ) of treatment , period , or subject for changes in liver volume or glycogen concentration . A steady increase of liver volumes , independent of the D-tagatose or placebo intake , has been observed over the study in parallel with a slight increase in body weight . The treatment with D-tagatose was not associated with clinical ly relevant changes of the examined clinico-chemical and hematological parameters , including liver enzymes and uric acid", "BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin", "OBJECTIVE Fructose has been implicated in obesity , partly due to lack of insulin-mediated leptin stimulation and ghrelin suppression . Most work has examined effects of pure fructose , rather than high-fructose corn syrup ( HFCS ) , the most commonly consumed form of fructose . This study examined effects of beverages sweetened with HFCS or sucrose ( Suc ) , when consumed with mixed meals , on blood glucose , insulin , leptin , ghrelin , and appetite . METHODS Thirty lean women were studied on two r and omized 2-d visits during which HFCS- and Suc-sweetened beverages were consumed as 30 % of energy on isocaloric diets during day 1 while blood was sample d. On day 2 , food was eaten ad libitum . Subjects rated appetite at design ated times throughout visits . RESULTS No significant differences between the two sweeteners were seen in fasting plasma glucose , insulin , leptin , and ghrelin ( P > 0.05 ) . The within-day variation in all four items was not different between the two visits ( P > 0.05 ) . Net areas under the curve were similar for glucose , insulin , and leptin ( P > 0.05 ) . There were no differences in energy or macronutrient intake on day 2 . The only appetite variable that differed between sweeteners was desire to eat , which had a higher area under the curve the day after Suc compared with HFCS . CONCLUSION These short-term results suggest that , when fructose is consumed in the form of HFCS , the measured metabolic responses do not differ from Suc in lean women . Further research is required to examine appetite responses and to determine if these findings hold true for obese individuals , males , or longer periods", "The objective of the research was to determine the blood pressure ( BP ) lowering effects in older people of 50 g carbohydrate drinks with varying carbohydrate content using a r and omised , cross-over study with ten ( six females ) healthy older subjects ( mean age 72.20 ( sem 1.50 ) years ) . BP , heart rate and glucometer-derived blood glucose levels were determined at baseline and following the ingestion of equal volumes ( 300 ml ) of water and carbohydrate drinks with varying nutrient content ( glucose , sucrose and fructose ) . A significant decline in BP over the first 60 min was seen following glucose ( systolic BP ( SBP ) P diastolic BP ( DBP ) P mean arterial BP ( MAP ) P=0.03 ) and sucrose ( SBP P glucose than sucrose ingestion ( SBP 7.33 ( sem 2.19 ) v. 21.00 ( sem 4.30 ) min ( P=0.03 ) and MAP 11.22 ( sem 3.10 ) v. 17.00 ( sem 3.78 ) min ( P=0.03 ) ) . BP increased after water ingestion ( SBP P=0.04 , DBP P=0.18 , MAP P=0.02 ) but did not change after fructose ingestion ( SBP P=0.36 , DBP P=0.81 , MAP P=0.34 ) . Post hoc analyses revealed that the BP ( SBP , DBP and MAP ) decrease following glucose and sucrose ingestion were similar but significantly greater than following fructose or water ingestion . Sucrose , which is used widely ( table sugar ) , reduces BP as much as glucose . In contrast to this , fructose ingestion causes no change in BP . Further studies are required to determine if the substitution of glucose or sucrose with fructose may be beneficial in the medical management of older people with severe symptomatic postpr and ial hypotension", "Aging is associated with a decline in energy expenditure ( EE ) , glucose intolerance , and a reduction in body nitrogen content . In addition , a reduction in the thermic response to glucose but not to fructose or protein has been reported in the elderly . The present study was conducted to further examine nutrient-induced thermogenesis and the effects of specific sugars on amino acid metabolism in relation to age . After 3 days on a weight-maintaining , 250-g carbohydrate diet , 16 healthy non-obese men and women in two age groups ( 18 to 29 and 66 to 80 years ) consumed on 4 different days 500 mL of either a 75-g fructose or 75-g glucose solution , with or without 300 mg caffeine or vitamin C as a placebo . Blood substrate and hormone levels and EE , using indirect calorimetry , were measured at timed intervals for 3 hours after consumption of the drinks . There was no difference in the carbohydrate-induced increase in EE in either young or old even after adjustments for body weight and fat-free mass ( FFM ) . An approximately 20-fold increase in serum caffeine levels increased EE in both groups ( P plasma alanine from combined basal levels of 301 + /- 24 to approximately 500 + /- 18 mumol/L ( mean + /- SEM ) in both groups ( P < .001 ) . However , both fructose and glucose ingestion result ed in a similar decline in branched-chain and aromatic amino acids . ( ABSTRACT TRUNCATED AT 250 WORDS", "Fructose is known to elicit a lower glycemic response than sucrose , and high-fructose desserts have been recommended for a diabetic diet . We compared a cholesterol-free tofu-based frozen dessert ( TFD ) containing high-fructose corn syrups with a dairy-based sucrose-sweetened ice cream ( IC ) . Six male and six female non-insulin-dependent diabetic patients ( mean age 51 yr , mean ideal body weight 143 % , fasting blood glucose were studied . Subjects underwent three trials . In the first trial they ingested 50 g glucose , and in the next two trials they ingested 50-g carbohydrate equivalents of either TFD or IC in r and om sequence . Venous blood was drawn at intervals during the 3-h trials for glucose and insulin determinations . Fasting plasma glucose was not statistically different between IC and TFD trials ( 130 vs. 121 mg/dl ) . Peak glucose responses were at 120 min in both trials ( 190 mg/dl for IC and 222 mg/dl for TFD ) , with those for TFD being significantly higher ( P Mean glucose area and glycemic index for TFD were significantly greater than for IC ( P no significant difference between mean insulin areas . In summary , the TFD , which contains soybean curd and high-fructose corn syrup , might have been expected to produce more satisfactory postpr and ial blood glucose levels than IC , which contains sucrose , yet a higher glycemic response was elicited . This is related to the substantial amount of total glucose in this “ fructose ” dessert . The study highlights the error of using individual components of a commercially prepared food to recommend a product for diabetic patients", "To investigate the relative effects of fructose and glucose on blood glucose , plasma insulin and incretin ( glucagon-like peptide-1 [ GLP-1 ] and gastric inhibitory peptide [ GIP ] ) concentrations , and acute food intake , 10 ( 6 men , 4 women ) patients with diet-controlled type 2 diabetes ( diabetic ) ( 44 to 71 years ) and 10 age and body mass index ( BMI ) -matched ( 6 men , 4 women ) nondiabetic , control subjects with varying degrees of glucose tolerance ( nondiabetic ) , were studied on 3 days . In r and om order , they drank equienergetic preloads of glucose ( 75 g ) ( GLUC ) , fructose ( 75 g ) ( FRUCT ) or vehicle ( 300 mL water with noncaloric flavoring [ VEH ] ) 3 hours before an ad libitum buffet lunch . Mean glucose concentrations were lower after FRUCT than GLUC in both type 2 diabetics ( FRUCT v GLUC : 7.5 + /- 0.3 v 10.8 + /- 0.4 mmol/L , P Mean insulin concentrations were approximately 50 % higher after FRUCT in type 2 diabetics than in nondiabetics ( diabetics v nondiabetics : 23.1 + /- 0.7 v 15.1 + /- 1.3 microU/mL ; P Plasma GLP-1 concentrations after fructose were not different between type 2 diabetics and nondiabetics ( P > .05 ) . Glucose , but not FRUC , increased GIP concentrations , which were not different between type 2 diabetics and nondiabetics ( P > .05 ) . Food intake was suppressed 14 % by GLUC ( P .05 ) . We have confirmed that oral fructose ingestion produces a lower postpr and ial blood glucose response than equienergetic glucose and demonstrated that ( 1 ) fructose produces greater increases in plasma insulin concentration in type 2 diabetics than nondiabetics , not apparently due to greater plasma incretin concentrations and ( 2 ) fructose and glucose have equivalent short-term satiating efficiency in both type 2 diabetics and nondiabetics . We conclude that on the basis of improved glycemic control , but not satiating efficiency , fructose may be useful as a replacement for glucose in the diet of obese patients with type 2 diabetes" ]

[ "BACKGROUND In total knee replacement , sound early fixation of the prosthesis is crucial for achieving a good long-term result and for minimising the risk of loosening . Various types of prosthetic material , different surface textures and shapes and the incorporation of screws or pegs have been used to achieve good fixation , particularly in the uncemented knee . Hydroxyapatite ( HA ) coating of prosthetic joint components is another technique used to enhance early stability and so to improve the longevity of the prosthesis-bone fixation . HA ceramic coatings are mostly plasma sprayed onto the fixation surface of the implant . Plasma spraying is largely a ' line of sight ' technique and as such there are difficulties involved when covering three-dimensional planes , such as porous beaded fixation surfaces typically found on several knee prostheses . The objective of this study was to assess the clinical performance of the solution-deposited HA coating , Peri-Apatite , with regard to its ability to stimulate an endurable and stable implant fixation . PATIENTS AND METHODS We r and omised 60 patients into two groups ; one group received the porous coated prosthesis with solution-deposited HA , and the other group received a prosthesis without HA . Radiostereometric examination was used as the primary tool for measuring migration in the prosthetic components . RESULTS There was a lower incidence of early subsidence in the Peri-Apatite group . At 24 months there were no differences in clinical scorings or maximal total point motion . CONCLUSION Addition of solution-deposited HA coating appears to provide better early stable fixation in a porous coated knee prosthesis", "Background We have previously reported that 6 months of oral treatment with clodronate reduced the migration of the NexGen total knee prosthesis during the first postoperative year , as measured by radiostereometry ( RSA ) . We now report the 4-year results . Methods This was a double-blind r and omized study , using RSA with maximal total point motion ( MTPM ) . Results With analysis according to the “ intention to treat ” principle , the only remaining difference between the groups at 4 years was reduced rotation around the transverse axis ( a secondary variable ) in the clodronate group . However , 3 patients ( all clodronate ) did not take any tablet after surgery . If they are excluded , there was an almost statistically significant difference between the groups at 4 years regarding MTPM from baseline , with the clodronate group showing 25 % less migration . From 1 to 4 years , there was no difference in migration rate by MTPM , but there was a continuous increase in rotation around the transverse axis in the controls , which differed from the clodronate group . There were no cases of aseptic loosening . 2 patients had migration of more than 1.3 mm from baseline to 4 years ; neither of them had taken clodronate . The others had migration of less than 0.9 mm . Interpretation Because migration was clearly reduced by clodronate during the first postoperative year , and there was still a difference at 4 years when analyzed per protocol , it appears likely that this treatment can diminish the risk of loosening . The difference in the number of outliers also points in this direction , and may be more relevant than mean migration values", "BACKGROUND The mobile-bearing variant of a single-radius design is assumed to provide more freedom of motion compared to the fixed-bearing variant because the insert does not restrict the natural movements of the femoral component . This would reduce the contact stresses and wear which in turn may have a positive effect on the fixation of the prosthesis to the bone and thereby decreases the risk for loosening . The aim of this study was to evaluate early migration of the tibial component and kinematics of a mobile-bearing and fixed-bearing total knee prosthesis of the same single-radius design . METHODS Twenty Triathlon single-radius posterior-stabilized knee prostheses were implanted ( 9 mobile-bearing and 11 fixed-bearing ) . Fluoroscopy and roentgen stereophotogrammetric analysis ( RSA ) were performed 6 and 12 months post-operatively . FINDINGS The 1 year post-operative RSA results showed considerable early migrations in 3 out of 9 mobile-bearing patients and 1 out of 11 fixed-bearing patients . The range of knee flexion was the same for the mobile-bearing and fixed-bearing group . The mobile insert was following the femoral component during motion . INTERPRETATION Despite the mobile insert following the femoral component during motion , and therefore performing as intended , no kinematic advantages of the mobile-bearing total knee prosthesis were seen . The fixed-bearing knee performed as good as the mobile-bearing knee and maybe even slightly better based on less irregular kinematics and less early migrations", "The effect of bone cement viscosity and cement mantle thickness on the migration of the Exeter total hip prosthesis was studied in a prospect i ve , r and omized , double-blind clinical Roentgen Stereophotogrammetric Analysis study . Forty-one cemented total hip arthroplasty in 39 patients were included and r and omized into a low/medium Simplex P cement group and a high-viscosity Simplex AF cement group . At time of stem introduction , 5 minutes after mixing , the Simplex AF was more viscous than Simplex P. No statistical difference existed between the 2 cement groups , for neither translation nor rotation migration data . Subsidence of the stem at 2-year follow-up was 1.1 + /- 0.56 mm for Simplex AF cement and 1.5 + /- 1.00 mm for Simplex P cement . The mean rotation of the acetabular components about the sagittal axis was 1.7 degrees + /- 3.8 degrees in the Simplex AF group and 0.7 degrees + /- 2.1 degrees for the Simplex P group . No effect of cement mantle thickness on migration of neither the acetabular cups nor the femoral stems was found . Although there were no differences in migration data for the cups and the stems , 2 acetabular cups in the Simplex AF group ( almost 10 % ) were revised because of mechanical loosening . Because of these findings , we suggest caution before using this new high-viscosity bone cement for fixation of acetabular components", "Background and purpose There is no consensus on the best rehabilitation regime after uncemented total hip arthroplasty . Theoretically , bone ingrowth into the implant should benefit from initial partial weight bearing . We investigated whether the degree of postoperative weight bearing influences the periprosthetic bone mineral density ( BMD ) and /or the stability of the CLS stem . Patients and methods 38 patients received an uncemented CLS stem and were r and omized to either unrestricted postoperative weight bearing or to partial weight bearing for 3 months . Periprosthetic BMD was measured in the 7 Gruen zones with DXA and the stability of the femoral stem was assessed by radiostereometric analysis ( RSA ) after surgery and at 3 , 12 , 24 , and 60 months . Results Periprosthetic BMD was not influenced by the type of postoperative weight bearing . BMD was reduced by 8–15 % in all Gruen zones at 3 months . Restoration toward initial BMD was observed in all zones except in zone 7 ( calcar region ) , where BMD was reduced by 22 % at 5 years . Immediate weight bearing after surgery had no influence on the stability of the CLS stem , as assessed by RSA . Interpretation Immediate full weight bearing after uncemented total hip arthroplasty is safe . There is no difference in the periprosthetic BMD or in stability of the stem as measured by RSA compared to partial weight bearing for 3 months . BMD is reduced by more than 20 % in the calcar region around a CLS stem after 5 years", "Abstract Objective : Migration of the tibial component in total knee arthroplasty ( TKA ) is subject of many studies using roentgen stereophotogrammetric analysis ( RSA ) . In previous studies of cemented and uncemented tibial components , high migration values were found . Improvements in cementing technique , prosthetic design and pre-coating techniques reduced these values as shown in more recent studies . Material and subjects : A total of 35 patients were initially included in the study and operated on between 12/1999 and 10/2000 . All patients received a NexGen ® TKA cemented into the proximal tibia using Palamed ® G bone cement . The implants and the tibial metaphysis were marked with st and ard tantalum markers . Radiostereometric analysis was performed post-operatively and after 3 , 6 and 12 months using a st and ard digital radiostereometric analysis . Functional parameters were assessed using the Knee Society Score ( KSS ) clinical rating system . Results : There were no complications and failures within the first year . After 1 year radiostereometric measurements of the translational parameters along and the rotational parameters around the x- , y- and z-axis revealed : X-Trans –0.19 mm , Y-Trans + 0.02 mm , Z-Trans + 0.08 mm , X-Rot + 0.26 ° , Y-Rot –0.35 ° , Z-Rot + 0.09 ° . The maximum total point motion was + 0.96 mm and the mean maximum subsidence was –0.23 mm . Except for anterior-posterior , medio-lateral stability and extension leg all endpoints of the KSS clinical rating system showed a significant improvement . Conclusions : After 12 months , the use of Palamed ® G bone cement in total knee arthroplasty was demonstrated to be safe . Both the clinical and radiostereometric results were good and comparable to the results reported in other RSA studies in cemented total knee arthroplasty", "The influence of articulating surface design of AMK total knee prosthesis ( DePuy , Johnson & Johnson ) on migration and radiographic outcome at 5 years was evaluated . The knees were r and omly allocated to receive a flat or a concave insert with retention of the posterior cruciate ligament when preoperative deformity was less severe and either a concave or a posterior-stabilized insert with resection of the posterior cruciate ligament when deformity was more pronounced . In 64 knees , migration was measured with radiostereometry . The posterior-stabilized component displayed more varus-valgus tilting than the concave insert . Other statistically significant differences in migration were not seen . Radiolucent lines were frequently seen without differences between prosthesis groups", "We followed prospect ively 27 patients with severe acetabular bone-stock deficiencies due to developmental dysplasia of the hip . Mean preoperative patient age was 56 ( 34–78 ) years , mean Harris hip score was 31 ( 16–66 ) points and pre-operative mean acetabular angle of Sharp was 47 ° ( 34 ° –61 ° ) . Operative acetabular reconstruction was performed in 28 hips using reinforcement ring with a hook placed in the true acetabulum and autologous bone grafting . A 2-year clinical and radiological follow-up was available in 27 hips . Mean Harris hip score improved to 91 ( 70–100 ) points . There were no clinical or radiological signs of aseptic loosening in 25 hips , and the bone graft was radiologically incorporated in all hips . In 24 hips , a radiostereometric analysis showed low rates of non-progressive translation and rotation in 21 reinforcement rings . Three rings showed progressive translation and /or rotation at the 2-year follow-up and were rated probably loose . RésuméNous avons suivi 27 malades avec des déficiences acétabulaires sévères dû à une dysplasie de développement de la hanche . L’âge moyen préopératoire des malades était de 56 ans ( 34–78 ) , le score moyen de Harris était de 31 points ( 16–66 ) et l’angle moyen de Sharp préopératoire était de 47 ° ( 34 ° –61 ° ) . La reconstruction acétabulaire a été exécutée dans 28 hanches en utilisent un anneau de renforcement avec crochet , placé dans le paléo-cotyle , avec greffe osseuse autologue . Un suivi clinique et radiologique de 2 années était disponible pour 27 hanches . Le score moyen de Harris a été amélioré à 91 points ( 70–100 ) . Il n’y avait pas de signe clinique ou radiologique de descellement aseptique dans 25 hanches et la greffe osseuse était incorporée dans toutes les hanches . Dans 24 hanches une analyse radiostéréométrique a montré un faible taux de translation et de rotation , non progressive , de 21 anneaux de renforcement . Trois anneaux ont montré une translation et/ou une rotation progressive au cours du suivi de 2 années et ont été considérés comme descellés", "Background In uncemented total hip arthroplasty with hydroxyapatite coating , early weight bearing is frequently practice d but there is still not much evidence to support this recommendation . Method In a prospect i ve r and omized study we evaluated the effect of partial and full weight bearing after cementless total hip arthroplasty ( ABG ; Stryker-Howmedica ) using radiostereometric analysis ( RSA ) . Between February 1996 and February 2000 , 43 consecutive patients ( mean age 53 ( 41–63 ) years , 23 women ) with hip osteoarthrosis received an uncemented and hydroxyapatite-coated prosthesis with an anteverted stem . All patients were operated in a st and ardized way by three experienced surgeons and they were r and omized to partial ( P ) or full ( F ) weight bearing during the first 6 weeks after surgery . The patients in the partial weight bearing group were equipped with a pressuresensitive insole signaling when their load exceeded the prescribed weight limit . Results At 3-month follow-up , the mean proximal (+)/ distal ( - ) migration of the stem was -0.14 mm ( -1.93– 0.11 ) in group P and -0.31 mm ( -4.30–0.16 ) in group F ( p = 0.6 ) . At 1-year follow-up , the mean migration was –0.17 mm ( -2.18–0.21 ) and -0.28 mm ( -4.31–0.11 ) , respectively ( p = 0.9 ) . There was no significant difference in stem rotations either ( p ) . The cup translations , rotations , and femoral head penetration were similar in the two groups ( p adverse effect of full weight bearing immediately after operation , which justifies use of this regimen after uncemented total hip arthroplasty of the ABG type", "Background The question whether the tibial component of a total knee arthroplasty should be fixed to bone with or without bone cement has not yet been definitely answered . We studied movements between the tibial component and bone by radiostereometry ( RSA ) in total knee replacement ( TKR ) for 3 different types of fixation : cemented fixation ( C-F ) , uncemented porous fixation ( UC-F ) and uncemented porous hydroxyapatite fixation ( UCHA-F ) . Patients 116 patients with osteoarthrosis , who had 146 TKRs , were included in 2 r and omized series . The first series included 86 unilateral TKRs stratified into 1 of the 3 types of fixation . The second series included 30 patients who had simultaneous bilateral TKR surgery , and who were stratified into 3 subgroups of pairwise comparisons of the 3 types of fixation . Results After 5 years 2 knees had been revised , neither of which were due to loosening . 1 UCHA-F knee in the unilateral series showed a large and continuous migration and a poor clinical result , and is a pending failure . The C-F knees rotated and migrated less than UC-F and UCHA-F knees over 5 years . UCHA-F migrated less than UC-F after 1 year . Interpretation Cementing of the tibial component offers more stable bone-implant contact for 5 years compared to uncemented fixation . When using uncemented components , however , there is evidence that augmenting a porous surface with hydroxyapatite may mean less motion between implant and bone after the initial postoperative year", "Highly cross-linked polyethylene ( PE ) has been introduced as an alternative bearing material in total hip arthroplasty ( THA ) because of high wear resistance in laboratory tests but the clinical experience of this material is limited . We evaluated a highly cross-linked PE ( warm irradiated adiabatic melting , absorbed dose , 95 kGy ) in a r and omized study of cemented THAs . Cups of the same design but made of conventionally gamma irradiated PE ( absorbed dose , 25–40 kGy ) constituted the control group . Sixty-one hips ( 30 women , 30 men ) with a median age of 55 years ( range , 35–70 years ) were included . All patients received a Spectron stem with 28-mm CoCr head . Radiostereometric examinations with the patient supine or st and ing were done at regular intervals . Wear was measured with the patient in the supine position from the first postoperative week , whereas examinations done with the patient st and ing were initiated 3 months after the operation . Dual xray absorptiometry and conventional radiography were used to evaluate the bone mineral density and the radiolucencies around the acetabular component . Fifty-two patients ( 53 hips ; 25 highly cross-linked , 28 control ) have been followed up for 2 years . At the 2-year followup , the highly cross-linked cups showed 50 % reduction of proximal wear compared with the control group , when the patients were studied st and ing . When evaluated supine , the difference in proximal wear did not reach significance . The migration of the socket , the relative changes of periprosthetic bone mineral density , and the progression of radiolucencies between the immediately postoperative followup and 2-year followup did not differ . Highly cross-linked PE showed increase resistance to wear . Different mechanical properties of the two types of PE studied did not alter the performance of the cup in terms of fixation , periprosthetic bone loss , and radiographic appearance . However , the followup is short and these results are preliminary", "A prospect i ve radiostereometric analysis ( RSA ) study of 18 patients with cemented revision hip surgery and impaction grafting with an Exeter stem was done with a follow-up of 2 years for all patients . All factors that could influence migration ( ie , micromotion ) of the stem were analyzed with a repeated measurements analysis of variance . Two groups could be identified : a stable group and a continuous migrating group . Two factors significantly influenced micromotion during the follow-up measurements . The first factor was the Paprosky classification ( the bigger the defect , the higher the micromotion ) . The second factor was cement mantle defects in > or = 1 Gruen zones . The migrating hip stems had more Gruen zones with cement mantle defects ( 45 % ) compared with the stable prostheses ( 21 % ) . The effect of the first factor on micromotion was limited and probably clinical ly less relevant . Because the cement mantle defects found in this study were caused by poor instrumentation , the second factor stresses the importance of good instrumentation , which is essential to make this technically dem and ing technique effective in creating a stable stem-allograft construct in the defective femoral canal", "A few studies have shown that cementing the stem enhances fixation of the tibial baseplate in total knee replacement ( TKR ) . Even the horizontal technique has been shown to provide good fixation . We used radiostereometry to study migration of the tibial component in 30 knees operated with Profix TKR . The knees were r and omised for either complete ( both under the baseplate and around the stem ) or horizontal ( only under the baseplate ) cementing of the tibial component . At two years the tibial baseplate rotated externally a median of 0.18 ° in the uncemented stem group and internally a median of 0.23 ° in the cemented stem group . The tibial baseplate subsided 0.14 mm in the cemented stem group , and no translation was seen in the uncemented stem group . The differences in migration were small and probably without clinical significance . The findings do not favour either of the cementing techniques in TKR.RésuméPeu d’études ont démontré que la fixation cimentée de la queue améliorait la fixation du plateau tibial dans les prothèses totales du genou . Par ailleurs , les fixations horizontales ont également montré une bonne fixation . Nous avons utilisé la radiostéréométrie pour étudier la migration du composant tibial dans 30 genoux de type Profix . Les genoux ont été r and omisés cimentation sous le plateau et autour de la queue ou cimentation horizontale uniquement sous le plateau . À 2 ans le plateau tibial présente une rotation externe de 0,18 ° dans les PTG avec une queue non cimentée et une rotation interne moyenne de 0,23 ° dans le groupe des queues cimentées . La base du plateau tibial s’enfonce de 0,14 mm dans le groupe des queues cimentées et il n’y a pas de translation dans le groupe des queues non cimentées . En conclusion , la différence au niveau de la migration est minime et sans signification clinique . Cette étude ne permet pas de choisir dans les prothèses totales du genou l’une des deux techniques de cimentation", "Prosthesis migration in bone inevitably occurs in cemented and uncemented total knee arthroplasty tibial components . Cemented design s as the gold st and ard give immediate fixation whereas cementless design s need a period of bone ingrowth onto the surface irregularities of the implants . The addition of bioactive coatings may enhance this process of ingrowth . A controlled r and omized prospect i ve RSA study was carried out on 26 Duracon implants in a rheumatoid arthritis patient group to evaluate the effect of a periapatite coating on the fixation of the tibial tray . The coated and the noncoated groups were matched for sex , age , body mass index , and HSS Knee Score . Stage of preoperative joint destruction and preoperative and postoperative mechanical leg axis showed no differences . We saw no differences in migration between the two groups , but a trend for lesser translations along and rotations about all three axes in the periapatite group . The periapatite-coated components showed a lower variance in subsidence than did the uncoated components . Both groups also showed a high variance in anterior tilting of the components . The cementless PA-coated Duracon prosthesis used in patients with RA may provide improved fixation of tibial components although we could not demonstrate improvement in this small controlled series . Level of Evidence : Therapeutic Level II . See the Guidelines for Authors for a complete description of levels of evidence", "Background and purpose There is no st and ard for patient triage in total knee arthroplasty ( TKA ) based on joint functional characteristics . This is largely due to the lack of objective postoperative measurement of success in TKA in terms of function and longevity , and the lack of knowledge of preoperative metrics that influence outcome . We examined the association between the preoperative mechanical environment of the patients knee joint during gait and the post-TKA stability of the tibial component as measured with radiostereometric analysis ( RSA ) . Methods 37 subjects were recruited out of a larger r and omized RSA trial . 3-dimensional gait analysis was performed in the preoperative week . Longitudinal RSA data were gathered postoperatively at 6 months and 1 year . Results We found a statistically significant association between the pattern of the knee adduction moment during gait preoperatively and the total migration of the implant at 6 months postoperatively . A substantial proportion of the variability in the total postoperative tibial component migration ( R2 = 0.45 ) was explained by a combination of implant type , preoperative knee joint loading patterns during gait , and body mass index at 6 months postoperatively . The relationships did not remain statistically significant at 1 year postoperatively . Interpretation Our findings support the hypothesis that preoperative functional characteristics of patients , and particularly joint loading patterns during activities of daily living , are important for outcome in TKA . This represents a first step in the development of predictive models of objective TKA outcome based on preoperative patient characteristics , which may lead to better treatment strategies . Clinical Trials.gov ( NCT00405379", "Background On theoretical grounds mobile bearing total knees should reduce the micromotion of the tibial component relative to the bone . Patients and methods We used radiostereometric analysis to measure the three-dimensional micromotion in 42 tibial components during 2 years of follow-up . The patients had been r and omized as to whether they would receive a mobile bearing ( MB ) or posterior stabilized ( PS ) design . We expected that the MB knee would facilitate dissipation of forces from the prosthesis-bone interface by the motion of the bearing and by load sharing with the soft tissues , leading to less micromotion . In the PS design s , limited free rotation caused by the campost articulation might cause additional stress at the bone-prosthesis interface . Results We found no significant differences between the MB and PS group at the 2-year follow-up evaluation with respect to Knee Society scores and radiographic results . The PS group had a higher variability in subsidence and anterior-posterior tilting of the component than the MB group . Interpretation The low variability of the data in the MB knee prosthesis group suggests that this design is more predictable and forgiving with respect to micromotion of the tibial component", "Background and purpose After joint replacement , a repair process starts at the interface between bone and cement . If this process is disturbed , the prosthesis may never become rigidly fixed to the bone , leading to migration— and with time , loosening . Cox-2 inhibitors are widely used as postoperative analgesics , and have adverse effects on bone healing . This could tamper prosthesis fixation . We investigated whether celecoxib , a selective Cox-2 inhibitor , increases prosthesis migration in total knee replacement ( TKR ) . Methods 50 patients were r and omized to either placebo or celecoxib treatment , 200 mg twice daily , for 3 weeks after TKR ( NexGen ; Zimmer ) . Maximum total point motion ( MTPM ) of the tibial component was measured after 2 years using radiostereometric analysis ( RSA ) . In addition , range of motion , pain , and , subjective outcome were evaluated . Results No differences in prosthesis migration , pain scores , range of motion , and subjective outcome were found after 2 years . Confidence intervals were narrow . Interpretation It is unlikely that Celecoxib increases the risk of loosening , and it may be used safely in conjunction with TKR", "Introduction Whether biochemical markers of bone metabolism can be used in assessing the conditions of implant fixation is unknown . In this study , the serum levels of three bone markers were measured prospect ively in patients undergoing total knee arthroplasty ( TKA ) to determine if patients with different fixation conditions of the tibial component showed any differences in the levels of the markers . Material s and methods The fixation of the tibial component in 40 knees ( 40 patients , 14 male and 26 female , average age 71 years ) was assessed by radiostereometric analysis ( RSA ) , and based upon the pattern of migration , implants with stable fixation ( n=25 ) and potentially unstable fixation ( n=15 ) were identified . Serum levels of carboxyterminal propeptide of type I procollagen ( PICP ) , osteocalcin ( OC ) and cross-linked carboxyterminal telopeptide of type I collagen ( ICTP ) were assessed and compared between the two fixation groups . Blood sample s were obtained preoperatively ( baseline ) and repeated postoperatively at 1 week , 3 , 6 , 12 , and 24 months . Results The baseline levels of the markers were statistically the same ( p>0.05 ) between the two fixation groups . Postoperatively , ICTP levels in the unstable group were significantly higher than in the stable group from 6 to 24 months ( p=0.02 ) . Levels of OC in the unstable group were higher at 12 and 24 months compared with the stable group , reaching statistical significance only at 12 months ( p=0.03 ) . No difference in the levels of PICP was found between the two groups . Conclusion The findings indicate a more active bone turnover probably at the bone-cement/implant interface in knees with potentially unstable fixation . It reveals the potential value for biochemical markers in monitoring implant fixation and aseptic loosening and suggests a possibility for improving implant fixation by drugs which inhibit osteolysis", "We evaluated the influence of CT-free or CT-based computer assisted orthopaedic surgery ( CAOS ) on the alignment of total knee prostheses ( TK ) and micromotion of tibial components . This r and omised study compared 19 CT-free , 17 CT-based CAOS TK , and a matched control group of 21 conventionally placed TK . Using Roentgen stereophotogrammetric analysis ( RSA ) the migration was measured . The alignment and component positions were measured on radiographs . No significant difference in leg and tibial component alignment was present between the three groups . A significant difference was found for micromotion in subsidence , with the conventional group having a mean of 0.16 mm , compared to the CT-free group at 0.01 mm and the CT-based group at −0.05 mm . No clinical significant difference in alignment was found between CAOS and conventionally operated TK . More subsidence of the tibial component was seen in the conventional group compared to both CAOS groups at two year follow-up . RésuméBut de l'étude : Evaluer l'influence de la navigation avec ou sans scanner sur l'alignement des prothèses totales du genou et sur la micromobilité du composant tibial . Matériel et méthode : nous avons réalisé une étude r and omisée comparant 19 prothèses naviguées sans scanner , 17 prothèses naviguées avec scanner , croisées avec un groupe contrôle de 21 patients avec mise en place d'une prothèse par voie conventionnelle . Nous avons utilisé la méthode RSA pour mesurer la migration . L'alignement et les composants étaient mesurés sur les radiographies . Résultats : il n'y a pas de différence significative au niveau de l'alignement des composants pour les trois groupes , par contre il existe une différence significative en ce qui concerne la migration . Dans le groupe conventionnel celle-ci est d'environ 0,16 mm , 0,01 mm dans le groupe navigation sans scanner et 0,05 mm dans le groupe navigation avec scanner . Conclusion : il n'y a pas de différence significative dans l'alignement des prothèses totales du genou lors de la mise en place d'une prothèse totale avec ou sans navigation par contre , il existe une micromobilité avec petite migration du composant tibial si l'on compare le groupe conventionnel avec les groupes navigués", "The optimal mode of femoral fixation in total knee arthroplasty ( TKA ) remains controversial , especially for the young patient . In a prospect i ve r and omised study we compared the magnitude and pattern of the fixation of cemented versus uncemented femoral components during 2 years in patients younger than 60 years . Forty-one knees in 41 patients were r and omised to receive a NexGen ( Zimmer , Warsaw , USA ) cruciate-retaining TKA with either a cemented or an uncemented non HA-coated femoral component . The patients were examined by radiostereometric analysis ( RSA ) , as well as clinical and radiological evaluation . The magnitude and pattern of migration as measured by RSA did not differ significantly between the cemented and uncemented fixation during the 2-year follow-up , nor were there any differences between the groups in clinical parameters . These findings suggest that an uncemented and non HA-coated femoral component may behave equally as well as a cemented one in the long-term", "We performed this investigation to determine the possible migration starting immediately after surgery and the effect of different weightbearing regimens on the migration pattern of an uncemented hip stem ( CLS ) . Stem migration was determined with radiostereometry analysis with baseline when the patients still were anesthetized . Subsequent examinations were done up to 1 year . Twenty-nine patients ( mean age , 55 years ; range , 26 - 63 years ) were r and omized to either unrestricted weightbearing combined with intensive physiotherapy from the first day after surgery or to partial weightbearing and a conservative training regimen for the first 3 months after surgery . At 1 week , subsidence was −0.03 mm in the unrestricted weightbearing group and 0.01 mm in the partial weightbearing group . At 1 year , subsidence was 1.01 mm in the unrestricted weightbearing group and 0.51 mm in the partial weightbearing group . One patient in the unrestricted weightbearing group had revision surgery because of aseptic loosening at 1.5 years after surgery . The CLS stem did not have any migration from the end the surgery until 1 week , but there was small migration from 1 week to 3 months after which the stem remained stable . The degree of early weightbearing did not affect the migration pattern . Level of Evidence : Level I , therapeutic study ( r and omized study ) . See the Guidelines for Authors for a complete description of levels of evidence", "Background and purpose We performed a r and omized study to determine the migration patterns of the Spectron EF femoral stem and to compare them with those of the Charnley stem , which is regarded by many as the gold st and ard for comparison of implants due to its extensive documentation . Patients and methods 150 patients with a mean age of 70 years were r and omized , single-blinded , to receive either a cemented Charnley flanged 40 monoblock , stainless steel , vaquasheen surface femoral stem with a 22.2-mm head ( n = 30 ) or a cemented Spectron EF modular , matte , straight , collared , cobalt-chrome femoral stem with a 28-mm femoral head and a roughened proximal third of the stem ( n = 120 ) . The patients were followed with repeated radiostereometric analysis for 2 years to assess migration . Results At 2 years , stem retroversion was 2.3 ° and 0.7 ° ( p posterior translation was 0.44 mm and 0.17 mm ( p = 0.002 ) for the Charnley group ( n = 26 ) and the Spectron EF group ( n = 74 ) , respectively . Subsidence was 0.26 mm for the Charnley and 0.20 mm for the Spectron EF ( p = 0.5 ) . Interpretation The Spectron EF femoral stem was more stable than the Charnley flanged 40 stem in our study when evaluated at 2 years . In a report from the Norwegian arthroplasty register , the Spectron EF stem had a higher revision rate due to aseptic loosening beyond 5 years than the Charnley . Initial stability is not invariably related to good long-term results . Our results emphasize the importance of prospect i ve long-term follow-up of prosthetic implants in clinical trials and national registries and a stepwise introduction of implants", "Ceramic-on-ceramic hip replacements might stress the bone interface more than a metal-polyethylene because of material stiffness , microseparation , and sensitivity to impingement . To ascertain whether this potentially increased stress caused an increased cup migration we compared a ceramic-on-ceramic with a metal-on-polyethylene implant for cup migration . Sixty one patients ( 61 hips ) undergoing THA for osteoarthritis were r and omized to ceramic on ceramic ( Ce/Ce ) or cobalt-chromium on cross-linked polyethylene bearings ( PE ) in the same uncemented cup shell . Migration was followed with RSA . At 2 years we observed similar mean cup translations in the 3 directions ( 0.07 - 0.40 mm vs. 0.05 - 0.31 mm , Ce/Ce vs. PE ) , as well as similar rotations around the 3 axes ( 0.31 - 0.92 ° vs. 0.57 - 1.40 ° ) . WOMAC and SF-36 scores were also similar and no radiolucent lines or osteolysis found . The large migration seen in some cups in both implant groups will require close monitoring to ascertain the reasons . Mean proximal wear of the polyethylene liners measured 0.016 mm between 2 and 24 months . Our data suggest there is no increased cup migration in the ceramic-on-ceramic implant compared with the metal-on-polyethylene , and they seem an equally safe choice . However , the low wear measured with the more versatile and less expensive cross-linked polyethylene makes it a strong contender . Levels of Evidence : Therapeutic Level I. See the Guidelines for Authors for a complete description of levels of evidence", "New prostheses should be evaluated for stability and clinical performance . In a prospect i ve r and omized clinical trial , we implanted 22 titanium ( Ti ) and 20 hydroxyapatite-coated ( HA ) ProxiLock femoral hip prostheses during total hip arthroplasty in 42 patients . The patients were followed for 24 months with clinical , radiographic and radiostereometric analysis . Full weightbearing was allowed immediately postoperatively . One patient with a titanium stem was lost to followup . During the first two months , 34 of the 41 stems subsided and /or rotated towards retroversion , regardless of stem type . At the 24-month followup 35 of the 41 prostheses were either fully stabilized ( 16 HA and 11 Ti stems ) or had clinical irrelevant migration ( four HA and four Ti stems ) . Six Ti prostheses showed continuous migrations with maximums of 4.7 mm translation and 12.2 ° retroversion ; four of these were revised , the other two had no clinical complaints . Clinical relevance : The migration pattern we found indicates insufficient primary fixation of the ProxiLock stem in an immediate full weightbearing protocol . The HA coating improves the secondary stability of the prosthesis compared to the uncoated stem . Early migration is associated with an increased risk of possible future loosening and revision , and therefore we discontinued the use of this prosthesis . Level of Evidence : Therapeutic Level I. See Guidelines for Authors for a complete description of levels of evidence", "The clinical results of using different cemented stems in total hip arthroplasty may vary because of shape , surface finish , and choice of metal alloy . Less is known about the influence of size and offset using one and the same design . Data from 140 patients ( 140 hips ) of a cohort constituting 197 patients ( 231 hips ) implanted with cemented Spectron Primary stems were extracted from patients studied in four r and omized studies primarily design ed for other purpose s. Stem size ( 1 , 2 , 3 , or larger ) , normal/extra offset , neck length and true offset ( horizontal length between the stem and head center of the inserted modular implant ) were recorded in millimeters . The radiographic appearance of the cementing was grade d on the immediate postoperative radiograph according to Barrack . The patients were examined with radiostereometric analysis of stem migration for a 2-year followup period . Stem Size 1 ( the smallest ) showed an insignificant increase in subsidence compared with the bigger sizes . Using stepwise linear regression analysis , the quality of the cementing ( Barrack C2 ) was the only parameter that had any certain influence of the subsidence at 2 years . Stem size 2 tended to show minimum valgus alignment and sizes 1 and 3 and bigger showed minimum varus tilting . Our findings suggest that placement of the stem with the tip against the posterior cortex ( C2 ) and stem size influence the primary fixation in different ways . This effect is small , however , indicating that further confirmation with longer followup is necessary . Level of Evidence : Therapeutic Level II-1 ( prospect i ve cohort study ) . See the Guidelines for Authors for a complete description of levels of evidence", "Fixation of the tibial component in total knee arthroplasty in younger patients remains controversial . We evaluate the results of three different types of fixation of the Profix total knee arthroplasty in a r and omized controlled trial of 97 consecutive knees ( 85 patients ) with osteoarthrosis or inflammatory arthritis with 2-year followup of all patients . We r and omized patients to three different types of fixation of the tibial component : cemented , uncemented ( HA coated ) with screws , or uncemented ( HA coated ) without screws . We performed clinical evaluations and radiostereometric analysis at 6 weeks , and 3 , 6 , 12 and 24 months postoperatively . The knees in the uncemented groups migrated more than those in the cemented group during the first 3 months , but at 2 years we observed no differences . The uncemented implants displayed all migration within the first 3 months . The cemented implants did not stabilize but had continuously increasing migration during the followup . Cementless implants without screws did not migrate more than implants with screws and displayed similar pattern of migration , indicating screws do not improve fixation . Uncemented fixation using hydroxyapatite-coated implants without screws seems to be the best solution for the younger patient . Level of Evidence : Therapeutic Level I. See the Guidelines for Authors for a complete description of levels of evidence", "Background Bioactive coating of uncemented total knee arthroplasty ( TKA ) is believed to increase bone ingrowth and enhance early fixation of the TKA . In a prospect i ve r and omized study using radiostereometric analysis ( RSA ) we examined migrations of the tibial implant , in an uncemented TKA with and without bioactive coating . The study was performed according to new RSA guidelines , and focus was put on some important method ological issues . Material s and methods Twenty-three patients with osteoarthrosis of the knee received an uncemented Duracon TKA either with bioactive ( hydroxyapatite or periapatite ) coating ( + HA ) or without bioactive coating ( −HA ) . Patients had RSA examinations postoperatively and at 3 , 6 and 12 months . Nine patients were excluded during the study result ing in 14 knees for final analysis . Results At 12 months follow-up we found no significant differences in migrations between the two groups . However , in general the −HA group migrated more than the + HA group , and we found a significant larger variation in migration pattern in the −HA group . In the + HA group the tibia component stabilized after 6 months , whereas the −HA group showed continuous migration . Subsidence and posterior tilt were the main migration patterns in both groups . Conclusions Bioactive coating of TKA seems to enhance early stabilization of the tibia component . Similar results are found in previous studies", "Background The surface texture , localization , and magnitude of the surface material applied to the femoral stem can facilitate bone ingrowth and influence the survival of total hip arthroplasties . Clinical and radiographic studies have shown superior bone ingrowth in proximally porous-coated stems with a diaphyseal grit-blasted surface in comparison to a smooth diaphyseal surface . Surface textures — especially porous surface material —have been suggested to have a sealing effect against migration of polyethylene debris along the implant-bone interface and to reduce the inflammatory response , leading to a prolonged implant survival . Patients and methods Between 2004 and 2006 , we conducted a r and omized , controlled trial ( RCT ) involving 50 patients with non-inflammatory arthritis . They received either a distally tapered , extended coated stem or a straight , proximally coated stem . During surgery , tantalum markers were inserted into the greater and lesser trochanter . Implant migration was evaluated at 3 , 12 , and 24 months postoperatively by radiostereometric analysis . The primary endpoint was stem migration 2 years after surgery . Results All femoral components in both groups showed pronounced distal translation , with the highest rate of translation occurring between 0 and 3 months . After 2 years , the mean distal translation was 2.67 ( 95 % CI : –3.93 to –1.42 ) mm for the tapered , extended coated stem and 1.80 ( –2.45 to –1.15 ) mm for the straight , proximally coated stem . Half of the tapered , extended coated stems and two-thirds of the straight , proximally coated stems had migrated more than 1 mm . No difference between the 2 stems could be seen with regard to translation or rotation at any time point . After 2 years , 2 hips have been reoperated due to mechanical loosening of the stem . Interpretation An excessive amount of migration of both stem types was seen 2 years postoperatively . It is of vital importance to follow this patient cohort since radiostereometric analysis is known to be predictive of late implant failure , especially in this study where pronounced early migration was observed . We recommend longer follow-up of both stem types", "Purpose There is little evidence to support immediate weight bearing after uncemented total hip arthroplasty ( THA ) . Methods Thirty-seven patients with unilateral osteoarthritis of the hip received a press-fit cup . Cup stability was assessed with radiostereometry ( RSA ) over five years . Patients were r and omised to immediate full weight bearing , or partial weight bearing for three months . Results At five years , we found no difference in micromotion as assessed with radiostereometry . Numerically , there was more proximal translation and increased inclination with immediate weight bearing , but these values barely exceeded the precision limit for the method . Pooled data for the two groups revealed translations of 0.1 - 0.3 mm and rotations of 0.2 - 0.3 ° over the five year follow-up period . Conclusions We found no adverse effects of immediate weight bearing after THA in relation to stability of these press-fit cups . Early mobilisation might have other advantages", "The CFP stem represents a short collared neck-retaining stem with very proximal metaphyseal anchoring along the calcar combined with up-to- date metallurgy . Despite theoretical advantages , the stability and clinical outcome are unknown . We prospect ively measured the migration pattern of this new stem and cup . Twenty-six patients ( 26 hips ) with a mean age of 54 years ( range , 40 - 66 years ) underwent THA and were followed for 2 years with radiostereometry , radiographs , and clinical scores . The stem showed some early retroversion ( mean , SEM 0.6 ° , 0.3 ) , but stabilized before 1 year . Subsidence ( 0.05 mm , 0.06 ) and varus-valgus tilting ( 0.03 ° , 0.01 ) were low . We observed no bone loss in the calcar region . Factors related to patients , implant design , and implantation did not predict migration patterns . The two-dimensional wear of the ceramic/conventional articulation was 0.09 mm at 2 - 24 months . The low migration of this short neck preserving stem suggests a favorable long-term outcome but longer followup is needed to substantiate this prediction . This design might become an alternative to st and ard stems and hip resurfacing . Level of Evidence : Therapeutic Level IV . See The Guidelines for Authors for a complete description of levels of evidence", "BACKGROUND The use of highly cross-linked polyethylene is now commonplace in total hip arthroplasty . Hip simulator studies and short-term in vivo measurements have suggested that the wear rate of highly cross-linked polyethylene is significantly less than that of conventional ultra-high molecular weight polyethylene . However , long-term data to support its use are limited . The aim of this study was to compare the intermediate-term steady-state wear of highly cross-linked polyethylene compared with that of conventional ultra-high molecular weight polyethylene acetabular liners in a prospect i ve , double-blind , r and omized controlled trial with use of radiostereometric analysis . METHODS Fifty-four patients were r and omized to receive hip replacements with either conventional ultra-high molecular weight polyethylene acetabular liners ( Zimmer ) or highly cross-linked polyethylene liners ( Longevity ; Zimmer ) . All patients received a cemented , collarless , polished , tapered femoral component ( CPT ; Zimmer ) and an uncemented acetabular component ( Trilogy ; Zimmer ) . Clinical outcomes were assessed and the three-dimensional penetration of the head into the socket was determined for a minimum of seven years . Linear regression was used to calculate the steady-state wear rate following the creep-dominated penetration seen during the first year . RESULTS At a minimum of seven years postoperatively , the mean total femoral head penetration was significantly lower in the highly cross-linked polyethylene group ( 0.33 mm ; 95 % confidence interval [ CI ] , ±0.10 mm ) than it was in the ultra-high molecular weight polyethylene group ( 0.55 mm ; 95 % CI , ±0.10 mm ) ( p = 0.005 ) . The mean steady-state wear rate of highly cross-linked polyethylene was 0.005 mm/yr ( 95 % CI , ±0.015 mm/yr ) , compared with 0.037 mm/yr ( 95 % CI , ±0.019 mm/yr ) for conventional ultra-high molecular weight polyethylene ( p = 0.007 ) . No patient in the highly cross-linked polyethylene group had a wear rate above the osteolysis threshold of 0.1 mm/yr , compared with 9 % of patients in the ultra-high molecular weight polyethylene group . CONCLUSIONS This study demonstrates that highly cross-linked polyethylene has a significantly lower steady-state wear rate compared with that of conventional ultra-high molecular weight polyethylene . Longer-term follow-up is required to determine if this will translate into improved clinical performance and longevity of these implants", "This was a safety study where the hypothesis was that the newer- design CPCS femoral stem would demonstrate similar early clinical results and micromovement to the well-established Exeter stem . Both are collarless , tapered , polished cemented stems , the only difference being a slight lateral to medial taper with the CPCS stem . A total of 34 patients were enrolled in a single-blinded r and omised controlled trial in which 17 patients received a dedicated radiostereometric CPCS stem and 17 a radiostereometric Exeter stem . No difference was found in any of the outcome measures pre-operatively or post-operatively between groups . At two years , the mean subsidence for the CPCS stem was nearly half that seen for the Exeter stem ( 0.77 mm ( -0.943 to 1.77 ) and 1.25 mm ( 0.719 to 1.625 ) , respectively ; p = 0.032 ) . In contrast , the mean internal rotation of the CPCS stem was approximately twice that of the Exeter ( 1.61 degrees ( -1.07 degrees to 4.33 degrees ) and 0.59 degrees ( 0.97 degrees to 1.64 degrees ) , respectively ; p = 0.048 ) . Other migration patterns were not significantly different between the stems . The subtle differences in design s may explain the different patterns of migration . Comparable migration with the Exeter stem suggests that the CPCS design will perform well in the long term", "Background Postoperative migration of a joint prosthesis is related to the risk of late loosening . We have previously reported that oral treatment with clodronate reduced migration of the cemented NexGen total knee prosthesis during the first postoperative year , as measured by radiostereometry ( RSA ) . Oral bisphosphonate treatment is sometimes unpleasant , and local treatment will enable higher local concentrations . We now report the results of local peroperative treatment with another bisphosphonate , ib and ronate , with the same prosthesis . Methods This is a double-blind , r and omized study of 50 patients using RSA with maximal total point motion ( MTPM ) as primary effect variable . 1 mg ib and ronate ( 1 mL ) or 1 mL saline was applied to the tibial bone surface 1 min before cementation . RSA examination was done on the first postoperative day , and at 6 , 12 , and 24 months . Results One ib and ronate-treated patient died of unrelated causes , and 1 control patient refused to come for follow-up , leaving 24 patients in each group for analysis . There were no cases of aseptic loosening . By repeated measures ANOVA , migration ( MTPM ) was reduced by local application of ib and ronate ( p = 0.006 ) . The effect was most pronounced at 6 months , with a reduction from 0.45 to 0.32 mm ( 95 % CI for reduction : 0.04–0.21 mm ) . At 12 months , the migration from the postoperative examination was reduced from 0.47 to 0.36 mm ( 95 % CI for reduction : 0.02–0.20 mm ) . At 24 months , the reduction was from 0.47 to 0.40 mm ( 95 % CI : -0.01–0.16 mm ) . Interpretation This is the first study to show improvement of prosthesis fixation by local pharmacological treatment in humans . The treatment appears to be safe , cheap , and easy to perform . However , the improvement in postoperative stability was not greater than with systemic clodronate treatment", "Forty-two patients ( younger than 65 years ) with osteoarthritis were operated on with an uncemented CLS stem and r and omized to early unrestricted weight bearing combined with intensive physiotherapy or to partial weight bearing combined with self-training . Radiostereometric analysis showed 1.2 ( + 0.11 to -6.76 ) mm subsidence of the stem at 24 months in both groups . There was no significant difference in the migration pattern between the unrestricted and partial weight bearing groups . Actual loading on the operated leg , measured with the F-scan system , did not influence the migration of the stem . There was a strong correlation between the average subsidence at 3 and 24 months ( r = 0.96 ) . Early full weight bearing and active rehabilitation can be used for the uncemented CLS stem without increased risk of early loosening", "Measurement of early stem subsidence can be used to predict the likelihood of long-term femoral component loosening and clinical failure . Data that examines the early migration pattern of clinical ly proven stems will provide clinicians with useful baseline data with which to compare new stem design s. This study was performed to evaluate the early migration pattern of a hydroxyapatite-coated press-fit femoral component that has been in use for over ten years . We enrolled 30 patients who underwent THA for osteoarthritis . The median age was 70 years ( range , 55–80 years ) . Patients were clinical ly assessed using the Harris hip score . Radiostereometric analysis was used to evaluate stem migration at three to four days , six months , one year and two years . We observed a mean subsidence of 0.73 mm at six months , 0.62 mm at one year and 0.58 mm at two years and a mean retroversion of 1.82 ° at six months , 1.90 ° at one year and 1.59 ° at two years . This data suggests that subsidence is confined to the first six months after which there was no further subsidence . The results from this study can be compared with those from novel cementless stem design s to help predict the long-term outcome one may expect from new cementless stem design", "The quality of the subchondral bone in total knee arthroplasty ( TKA ) may be important for the outcome . We correlated a histomorphologic analysis of the prosthetic bone bed to micromotion as analyzed by roentgen stereophotogrammetric analysis ( RSA ) . Twenty-three knees , both osteo- and rheumatoid arthritic were studied . The mean migration after 1 year was 1 mm ( 0.21 - 2.68 ) , with no correlation to the bone variables or diagnosis . One patient underwent revision after 3 years because of pain . One patient underwent revision after 15 years because of aseptic loosening . This patient appeared stable according to changes in maximum total point motion ( MTPM ) , but the prosthesis migrated continuously according to segment motion . Prosthetic migration increased after 10 years , zones started to evolve , and the patient became symptomatic after 13 years . A biopsy of the bone bed was taken in all patients . A larger percentage of trabecular bone and a larger relative area of unmineralized osteoid surface were found in patients with rheumatoid arthritis compared with those with osteoarthritis . The latter finding is probably a result of increased bone turnover . In conclusion , no support currently exists for the idea that preoperative bone quality , evaluated as bone histomorphometry , has any impact on prosthetic micromotion in knee prostheses", "40 patients with non-inflammatory arthrosis and minor preoperative deformity ( / 5 ° ) were operated on with an AMK type ( DePuy , Johnson & Johnson ) total knee arthroplasty ( TKA ) . The posterior cruciate ligament was retained . The patients were divided into those with a flat ( terminology of the manufacturer : st and ard ) or a concave ( terminology of the manufacturer : constrained ) polyethylene insert ( 20 in each group ) . Radiostereometric ( RSA ) examinations were done postoperatively and after 3 , 12 and 24 months . The median absolute rotations of the tibial inserts varied between 0.12 and 0.24 ( range 0.00 - 1.54 ) degrees , with no differences between the 2 groups . The median maximum totalpoint motions ( flat/concave = 0.41/0.42 mm ) , the maximum subsidence or lift-off did not differ . The Hospital for Special Surgery knee score and the patients ' opinion about the operation , based on their preoperative expectations , showed little , if any , differences . At 2 years , 10 of 20 patients with flat and 13 of 19 with concave inserts regarded their knee function as normal or almost so", "Background Cementing technique is a crucial factor in prosthesis fixation . No r and omized studies have been published , however , comparing the outcome of conventional fingerpacking with the outcome of pressurization of the cement prior to cup insertion . Patients and methods We r and omized 50 THAs to either fingerpacking or sequential pressurization ( including individual pressurization of each anchorage hole ) and followed the patients with RSA for 5 years . The penetration of cement into the anchorage holes was measured on digital radiographs . Postoperative radiolucent lines around the cup were correlated to later RSA results . For clinical evaluation , we used SF-36 and HHS . Results The pressurized group of THAs was more stable regarding changes in inclination . We found no other difference in the migratory behavior . The cement penetration into the anchorage holes was deeper with the pressurization technique than with fingerpacking . For the whole group taken together , there was a strong relation between the presence of radiolucent lines as measured on the postoperative radiograph and later migration observed by RSA at 2 and 5 years . Interpretation Pressurization of the cement produced better cement penetration and increased the cup stability in terms of changes in inclination . Early findings of radiolucent lines can predict later unfavorable cup migration", "There has been renewed interest for metal-on-metal hip resurfacing due to improved design and manufacturing of implants , better material s , and enhanced implant fixation . In contrast to conventional total hip replacements , only a few clinical hip resurfacing trials using radiostereometry ( RSA ) have been reported , and solely for the Birmingham hip resurfacing arthroplasty . The purpose of this RSA trial was to describe the migration pattern of a new hip resurfacing system ( ReCap ) within the first two years after primary surgery . Twenty-six patients underwent total hip replacement . The patients were followed-up for up to 24 months and were evaluated with the use of radiostereometric measurements . The prosthesis showed mean translations and rotation close to zero . Maximum translation was seen along the transverse axis in the medial direction ( 0.13 mm ) . No statistically significant translation or rotation was seen at two-years follow-up , ( t-test , p translation or rotation )", "Improved fixation to bone is vital for improving the long term success of cemented implants . Addition of fluoride to acrylic bone cement may be one way to improve the quality of the bone cement interface and thereby reduce the risk of loosening . Ninety patients ( 97 hips ) with a median age of 70 years ( range , 31 - 81 years ) scheduled for total hip arthroplasty were r and omized to receive a stem fixed with fluoride-containing acrylic bone cement or conventional acrylic bone cement . Fixation and bone remodeling around the femoral component was studied with radiostereometry and dual-energy xray absorptiometry up to 5 years after the operation in 73 patients ( 77 hips ) . Radiostereometric evaluation at 5 years revealed no differences in stem migration ( subsidence/lift-off ) or rotations . The stem subsidence inside the mantle was similar in the two groups . At 5 years the study group had lost more bone mineral in Gruen regions 5 and 7 than the controls . The Harris hip and pain score did not differ . Use of fluoride containing bone cement did not improve the stem fixation compared with a conventional cement used up to 5 years , but result ed in more pronounced loss of bone mineral density in the medial cortex . Level of Evidence : Therapeutic Level I. See Guidelines for Authors for a complete description of levels of evidence", "We have carried out a radiostereometric study of 50 patients ( 54 knees ) with osteoarthritis of the knee who were r and omly allocated to receive a cemented or a hydroxyapatite-coated femoral component for total knee replacement . The patients were also stratified to receive one of three types of articulating surface ( st and ard , rotating platform , Freeman-Samuelson (FS)1000 ) all based on the Freeman-Samuelson design . The tibial components were cemented in all cases . Radiostereometry was performed post-operatively and at 3 , 12 and 24 months . The analysis was restricted to rotation of the femoral component over time . After two years , rotation of the femoral components in the transverse , longitudinal and sagittal planes did not differ between the cemented and the hydroxyapatite-coated implants ( p = 0.2 to 0.9 ) . In total knee replacements with a rotating platform , the femoral component tended to tilt more posteriorly than in the other two design s , regardless of the choice of fixation ( cemented or hydroxyapatite-coated , p = 0.04 ) . The st and ard version of the femoral component , whether cemented or hydroxyapatite-coated , rotated more into valgus than was observed with the rotating-platform and FS1000 design s ( p = 0.005 ) . The increased constraint provided by the FS1000 component did not appear to have any adverse effect on fixation of the femoral component", "Background We developed a total hip system using osseointegration guidelines , a metaphyseal-loading proximal femoral replacement in the retained neck and a dual-geometry titanium shell in the acetabulum . Patients and methods A r and omized controlled clinical trial was undertaken in 52 patients ( 53 hips ) , using the cemented Spectron stem and cementless Harris-Galante II cup as control implants ( 24 patients in experimental group , 29 control patients ) . Clinical measures of Harris Hip Score ( HHS ) , pain score and radiostereometric analysis ( RSA ) at regular intervals for up to three years were used to monitor progress . Results No statistically significant differences were found in HHS and pain score ; the stability of the cementless experimental implant was also comparable to that of the cemented controls by RSA . 3 revisions were required for migration in the experimental group and 1 was required for component dislocation in the control group . Interpretation Our findings indicate the practicality of osseointegration of titanium implants , but suggest that current performance is inadequate for clinical introduction . However , the stable fixation achieved in the retained neck in the majority of patients is indicative of osseointegration . This finding will encourage technical and design improvements for enhancement of clinical osseointegration and should also encourage further study . Periprosthetic osteolysis might be avoided by the establishment and maintenance of direct implant-bone connection : “ osseointegration ”", "We examined the in vivo displacement of mobile-bearing polyethylene and its effect on prosthesis-bone fixation . Thirty-five patients with the Interax ® ISA mobile platform total knee arthroplasties were examined by roentgen stereophotogrammetric analysis . Our protocol included weightbearing to measure the range of motion of the mobile platform in relation to the tibial component . We also studied the micromotions of the tibial component in relation to the tibia during a 2-year followup . The analysis of micromotion ( maximum total motion mean , 0.5 mm ; subsidence mean , 0.15 mm ) showed this mobile platform design is stable and improves fixation at the prosthesis-bone interface . Longitudinal rotations of the mobile platform occurred in all patients and followed a homogeneous pattern of motion , depending on the examination . However , anteroposterior translations did not show any patterns with specific examination . This suggests the meniscal movement adapts itself to different weightbearing conditions . We measured the in vivo mobile-bearing displacement under static loading conditions . We also observed improved fixation at the bone-prosthesis interface ", "Background First-generation highly cross-linked polyethylene liners have reduced the incidence of wear particle-induced osteolysis . However , failed acetabular liners have shown evidence of surface cracking , mechanical failure , and oxidative damage . This has led to the development of second-generation highly cross-linked polyethylene , which has improved wear and mechanical properties and resistance to oxidation in vitro . Owing to its recent introduction , there are no publications describing its clinical performance . Questions / purpose sWe assessed early clinical wear of a second-generation highly cross-linked polyethylene liner and compared its clinical performance with the published results of hip simulator tests and with first-generation highly cross-linked polyethylene annealed liners . Patients and Methods Twenty-one patients were enrolled in a prospect i ve cohort study . Clinical outcome and femoral head penetration were measured for 19 patients at 6 months and 1 and 2 years postoperatively . Results The median proximal head penetration was 0.009 mm and 0.024 mm at 1 and 2 years , respectively . The median two-dimensional ( 2-D ) head penetration was 0.083 mm and 0.060 mm at 1 and 2 years , respectively . The median proximal wear rate between 1 and 2 years was 0.015 mm/year . Conclusions The wear rate calculated was similar to the in vitro wear rate reported for this material ; however , it was less than the detection threshold for this technique . Although longer followup is required for wear to reach a clinical ly quantifiable level , this low level of wear is encouraging for the future clinical performance of this material .Level of Evidence Level IV , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence", "The R3 Acetabular component represents the next generation of acetabular shell with an enhanced porous ingrowth surface ( StikTite , Smith & Nephew , Memphis , Tenn ) to meet the needs of both primary and revision hip arthroplasty ; an optimized locking mechanism ; and the ability to accomo date polyethylene , metal , or ceramic liners . This prospect i ve clinical study reports on the safety and efficacy of the new StikTite porous ingrowth surface using radiostereometric analysis ( RSA ) . StikTite provides a superior \" sctratch-fit \" due to its greater coefficient of friction and less micromotion using RSA measurements", "This r and omized study was performed to compare wear and migration of five different cemented total hip joint articulations in 150 patients . The patients received either a Charnley femoral stem with a 22.2 mm head or a Spectron EF femoral stem with a 28 mm head . The Charnley articulated with a γ-sterilized Charnley Ogee acetabular cup . The Spectron EF was used with either EtO-sterilized non-cross-linked polyethylene ( Reflection All-Poly ) or highly cross-linked ( Reflection All-Poly XLPE ) cups , combined with either cobalt chrome ( CoCr ) or Oxinium femoral heads . The patients were followed with repeated RSA measurements for 2 years . After 2 years , the EtO-sterilized non-cross-linked Reflection All-Poly cups had more than four times higher proximal penetration than its highly cross-linked counterpart . Use of Oxinium femoral heads did not affect penetration at 2 years compared to heads made of CoCr . Further follow-up is needed to evaluate the benefits , if any , of Oxinium femoral heads in the clinical setting . The Charnley Ogee was not outperformed by the more recently introduced implants in our study . We conclude that this prostheses still represents a st and ard against which new implants can be measured", "We evaluated polyethylene wear by measuring femoral head penetration in 201 THA ( median age 62 ( 31 - 81 ) years , 117 women ) extracted from 5 r and omized studies aim ed to assess various fixation principles . There were 30 cemented all-polyethylene Lubinus cups sterilized by gamma irradiation in a reduced oxygen environment , 65 porous-coated Trilogy cups with liners gamma-sterilized in inert gas . Moreover , 37 cemented cups were sterilized with ethylene oxide ( Reflection all-poly ) and 69 porous-coated cups had liners sterilized in ethylene oxide ( Reflection ) . 28 mm femoral heads were used in all cups . The patients were followed with repeated radiostereometric measurements ( RSA ) up to 2 years . The activity level of the patients was evaluated by a question naire . After 2 years , cups with polyethylene sterilized in EtO had almost twice the proximal and 3D penetration rates , as compared with gamma-sterilized polyethylene . The penetration did not differ between the gamma-irradiated design s. Using stepwise linear regression analysis , we found that the type of sterilization , age and weight were the most important predictors and that they determined the direction of the proximal penetration rate . Activity score , male gender and proximal migration of the cup had little effect . The accelerated wear observed with the EtO-sterilized polyethylene causes concerns about long-term problems and especially in younger patients", "BACKGROUND Radiostereometry is a well documented method to measure the polyethylene wear after total hip replacements . Wear is measured according to the point motion of the head center in relation to the polyethylene as the reference segment . Increasing head sizes and new cup material s may diminish visibility of markers deteriorating the segment and leading to study drop outs . Alternatively markers in the periacetabular bone may be easier to detect rendering this segment more stable . Our aim was to compare wear measurements against the cup , the acetabuluar bone and a calculated wear estimation including cup migration . METHODS A prospect i ve r and omized controlled trial comparing reverse hybrid with cemented total hip replacement was conducted . 31 patients had tantalum markers in the polyethylene and in the periacetabular bone making it possible to measure wear using both as reference segments . We used a uniplanar radiostereometric technique . FINDINGS Wear in the y-axis was overestimated by 53 % when markers in the periacetabular bone were used ( P Proximal wear was 0.34 mm ( 95 % CI of mean : 0.29 - 0.38 ) when using the polyethylene as the reference and 0.52 mm ( 95 % CI of mean : 0.38 - 0.65 ) using the acetabular bone . Migration of the cup seemed to influence the wear calculations , overestimating wear when markers in the periacetabular bone were used as the reference segment . INTERPRETATION Wear measured with periacatebular bone markers is influenced by cup migration , overestimating wear measurements . We therefore recommend not using the acetabular bone as the reference segment", "The creep and wear behaviour of highly cross-linked polyethylene and st and ard polyethylene liners were examined in a prospect i ve , double-blind r and omised , controlled trial using radiostereometric analysis . We r and omised 54 patients to receive hip replacements with either highly cross-linked polyethylene or st and ard liners and determined the three-dimensional penetration of the liners over three years . After three years the mean total penetration was 0.35 mm ( SD 0.14 ) for the highly cross-linked polyethylene group and 0.45 mm ( SD 0.19 ) for the st and ard group . The difference was statistically significant ( p = 0.0184 ) . From the pattern of penetration it was possible to discriminate creep from wear . Most ( 95 % ) of the creep occurred within six months of implantation and nearly all within the first year . There was no difference in the mean degree of creep between the two types of polyethylene ( highly cross-linked polyethylene 0.26 mm , SD 0.17 ; st and ard 0.27 mm , SD 0.2 ; p = 0.83 ) . There was , however , a significant difference ( p = 0.012 ) in the mean wear rate ( highly cross-linked polyethylene 0.03 mm/yr , SD 0.06 ; st and ard 0.07 mm/yr , SD 0.05 ) . Creep and wear occurred in significantly different directions ( p = 0.01 ) ; creep was predominantly proximal whereas wear was anterior , proximal and medial . We conclude that penetration in the first six months is creep-dominated , but after one year virtually all penetration is due to wear . Highly cross-linked polyethylene has a 60 % lower rate of wear than st and ard polyethylene and therefore will probably perform better in the long term", "We performed a r and omised , radiostereometric study comparing two different bone cements , one of which has been sparsely clinical ly documented . R and omisation of 60 total hip replacements ( 57 patients ) into two groups of 30 was undertaken . All the patients were operated on using a cemented Charnley total hip replacement , the only difference between groups being the bone cement used to secure the femoral component . The two cements used were Palamed G and Palacos R with gentamicin . The patients were followed up with repeated clinical and radiostereometric examinations for two years to assess the micromovement of the femoral component and the clinical outcome . The mean subsidence was 0.18 mm and 0.21 mm , and the mean internal rotation was 1.7 degrees and 2.0 degrees at two years for the Palamed G and Palacos R with gentamicin bone cements , respectively . We found no statistically significant differences between the groups . Micromovement occurred between the femoral component and the cement , while the cement mantle was stable inside the bone . The Harris hip score improved from a mean of 38 points ( 14 to 54 ) and 36 ( 10 to 57 ) pre-operatively to a mean of 92 ( 77 to 100 ) and 91 ( 63 to 100 ) at two years in the Palamed G and Palacos R groups , respectively . No differences were found between the groups . Both bone cements provided good initial fixation of the femoral component and good clinical results at two years", "The quality of technique used at the time of socket cementation is crucial in ensuring a durable long-term result of the implant . We asked whether a new instrument , an aspirator retractor introduced into the wing of the ilium before socket preparation and cementation , would enhance cement fixation as defined by RSA and radiographic examination . We r and omized 38 patients into two groups . The surgical technique was identical between the groups with the exception of the use of the aspirator retractor . Patients were followed clinical ly and with radiostereometry at a minimum of 2 years . We compared gross radiographic appearances , including the depth of penetration of cement and the incidence of postoperative and 2-year radiolucent lines . There was no difference in proximal migration between the two groups . No improvement of fixation was proven from the measured translations and rotations of the socket in the suction group . We found no difference in the number or extent of radiolucent lines or the depth of cement penetration when the iliac suction device was used in conjunction with contemporary cementing techniques . Although the data suggest no short-term advantage in this small study , we will continue to follow these patients presuming there will be improved outcomes in the longer term and since the device provides an easier method of obtaining adequate fixation , especially if technical difficulties are encountered during the pressurization procedure", "Ninety patients ( 96 hips ) scheduled for THA were stratified to fixation of the acetabular component in three main groups of about equal size . Fluoride cement , porous coated press-fit cup with ceramic coating or Palacos cum Gentamicin cement were used . All patients received Spectron EF stem . The migration of the cups and the femoral head penetration into the socket were measured with radiostereometric analysis . At 2 years the choice of fixation did not influence the migration or rotation of the cup . Patients with compromised bone quality showed increased three-dimensional ( 3D or total ) migration . Proximal and 3D penetration rates were increased in cemented compared with the uncemented cups ( p Appearance of radiolucent lines was almost equal in the two cemented groups . Uncemented cups had less radiolucent lines at 2 years . Fluoride containing cement or uncemented fixation did not improve the early postoperative stability of the socket", "Our aim in this pilot study was to evaluate the fixation of , the bone remodelling around , and the clinical outcome after surgery of a new , uncemented , fully hydroxyapatite-coated , collared and tapered femoral component , design ed specifically for elderly patients with a fracture of the femoral neck . We enrolled 50 patients , of at least 70 years of age , with an acute displaced fracture of the femoral neck in this prospect i ve single-series study . They received a total hip replacement using the new component and were followed up regularly for two years . Fixation was evaluated by radiostereometric analysis and bone remodelling by dual-energy x-ray absorptiometry . Hip function and the health-related quality of life were assessed using the Harris hip score and the EuroQol-5D . Up to six weeks post-operatively there was a mean subsidence of 0.2 mm ( -2.1 to + 0.5 ) and a retroversion of a mean of 1.2 ° ( -8.2 ° to + 1.5 ° ) . No component migrated after three months . The patients had a continuous loss of peri-prosthetic bone which amounted to a mean of 16 % ( -49 % to + 10 % ) at two years . The mean Harris hip score was 82 ( 51 to 100 ) after two years . The two-year results from this pilot study indicate that this new , uncemented femoral component can be used for elderly patients with osteoporotic fractures of the femoral neck", " 52 knees scheduled for a total knee arthroplasty were r and omised to either a fixed or a mobile polyethylene bearing . The design was identical in all parts . The knee systems used were the Rotaglide Total Knee System ( RTK ) and the Nuffield Total Knee System ( NTK ) , both from the same manufacturer ( Corin Medical Ltd. , UK ) . All knees implanted were uncemented . The patients were followed for 2 years clinical ly and with radiostereometric analyses to assess migration over time and inducible displacement of the tibial component . Separate analysis of the mobility of the tibial insert in the knees with a mobile bearing was also made . The migration measured with RSA between the 1st and 2nd year expressed as maximum total point motion ( MTPM ) might predict the risk of loosening of the implant . There were no differences between the groups regarding clinical outcome ( HSS Knee score ) , migration or inducible displacement during the 2 years follow-up . The movement between the tibial tray and the mobile meniscal insert expressed as maximum total point motion ( MTPM ) was 6.8+/-3.3 mm at the 1st year follow-up", "We report the initial results of an ongoing r and omised , prospect i ve study on migration of the Exeter and Elite Plus femoral stems after impaction allografting , as measured by radiostereometry . Clinical ly , the impaction technique gave good results for both stems . The mean subsidence in the first year was 1.30 mm and 0.20 mm for the Exeter and the Elite Plus stems , respectively . In the second year , the Exeter stem continued to subside further by a mean of 0.42 mm , while the Elite Plus stem did not do so . Subsidence of the Exeter stem correlated with deficiency of bone stock as grade d on the Gustilo and Pasternak scale . This correlation was not found for the Elite Plus stem . None of the other parameters which were studied predisposed to subsidence . There was no significant association between the amount of subsidence and the radiological appearance of the graft for either stem . Our findings do not support the theory that radial compression , due to subsidence of the Exeter stem , is the essential stimulus for remodelling in impaction allografting", "Purpose Wear is a major contributor to osteolysis and aseptic loosening of total hip replacements ( THR ) . Both alumina ( Al2O3 ) and cobalt-chrome ( CoCr ) femoral heads are commonly used . We investigated wear comparing alumina heads to cobalt-chrome heads against conventional cemented polyethylene ( PE ) cups for up to ten years . Methods Linear wear was measured with radiostereometry ( RSA ) . Our material was derived from two prospect i ve r and omised trials that investigated fixation of femoral stems , not wear , and was evaluated retrospectively ( Level III ) . Results The mean ( 95 % CI ) proximal head penetration was 0.96 mm ( 0.68–1.23 ) in the cobalt-chrome group and 0.42 mm ( 0.30–0.53 ) in the alumina group at ten years ( P = 0.001 ) . The mean ( 95 % CI ) 3D penetration was 1.07 mm ( 0.79–1.35 ) and 0.53 mm ( 0.38–0.63 ) , respectively , at ten years ( P = 0.001 ) . Conclusion Alumina heads performed better than cobalt-chrome heads in this study after ten-year follow-up", "Background There is no consensus as to whether uncemented or cemented femoral stems should be used in younger patients . We compared the uncemented Cone stem to the cemented Bimetric stem in young patients with osteoarthritis . Patients and methods We r and omized 45 relatively young patients ( to either an uncemented Cone stem or a cemented Bimetric stem . All patients were followed for 2 years . Outcome was assessed by the Merle d’Aubigné score , conventional radiography and repeated radio-stereometric analysis ( RSA ) . We also followed 81 Cone stems for 8 ( 7–12 ) years with revision as endpoint . Results The clinical outcome was excellent . No patient had postoperative thigh pain . The migration was small . The Bimetric stem was stable during the whole observation period , while the Cone stem subsided and rotated to retroversion during the first 3 months post-operatively , and then remained stable . In the follow-up study of 81 Cone stems , 1 stem was revised . Interpretation We conclude that both the cemented Bimetric stem and the uncemented Cone stem are stable and give excellent clinical results after 2 years in relatively young patients with osteoarthritis . Although design ed for CDH hips , the Cone stem appears to be suitable also for patients with osteoarthitis .", "Sixty-two patients ( 64 hips ) were provided with porous press-fit cups ( Trilogy ) , plasma-sprayed with a coating consisting of 70 % hydroxyapatite and 30 % tricalcium phosphate . The patients were r and omized to a cup with cluster holes for adjunctive screw fixation ( n = 30 ) or to a cup without holes ( n = 34 ) . Radiostereometry was used to study migration and wear . Up to 2 years median translations and rotations median annual proximal wear ( 0.11 and 0.12 mm ) was within the expected range despite the use of a ceramic coating , and it did not differ between the 2 design s. Radiolucent lines were frequently seen postoperatively but diminished during the follow-up without any sign of migration into the gaps . At 2 years , the median Harris scores were 99 points ( range , 51 - 100 points ) in the group with and 98 points ( range , 69 - 100 points ) in the group without screws . The results indicate that early fixation can be achieved for ceramic-coated press-fit cups without using additional screw fixation", "A total of 51 knees ( 45 patients ) with osteoarthrosis were stratified in a r and omized study to receive a hydroxyapatite-coated Freeman-Samuelson ( FS HA ) or a porous-coated Miller-Galante II ( MG II ) uncemented total knee arthroplasty . Repeated clinical , radiographic , and radiostereometric analysis ( RSA ) evaluations of the tibial components were done for 5 years . The clinical outcome was equal at the 5-year follow-up ( mean Hospital for Special Surgery score , 93 ) . St and ard radiographs displayed more zones around the tibial stem in the MG II group . RSA revealed that the FS HA components migrated less ( smaller maximum total point motion and maximum subsidence ) after 5 years and showed less inducible displacements at the 1-year follow-up . The stability of the implants obtained is equal to or better than cemented implants after 5 years . Key words : knee prosthesis , cementless , hydroxyapatite , radiostereometry , inducible displacement", "To evaluate different modes of cementless fixation of hemispherical cups , we operated on 87 hips in 81 patients using 4 different means of cup fixation . The hips were r and omly assigned to fixation with press-fit technique only ( PF ) , or with augmentation with screws ( S ) , pegs ( P ) , or hydroxyapatite ( HA ) coating . The patients were evaluated with radiostereometric analysis ( RSA ) for cup migration and wear , conventional radiography for osteolysis , and Harris Hip Score for clinical outcome over 5 years . The fixation of the cups did not differ between the groups , but HA showed a tendency to decrease proximal migration . HA-coated cups displayed the best interface with hardly any signs of radiolucent lines , indicating a superior sealing effect of the HA coating . Cups with screws or pegs had more radiolucent lines and osteolytic lesions than the other groups . Radiolucent lines were correlated to higher proximal migration , young age , and female gender ( r2=.2 ) . The wear rate of the ethylene oxide-sterilized polyethylene liner was high ( 0.2 mm/y ) but did not differ between the groups . Two cups with a perioperative fracture of the acetabular rim showed large initial migration but stabilized thereafter", "Forty-one patients were r and omized to a cemented Miller-Galante unicompartmental ( Zimmer , Warsaw , Ind ) knee arthroplasty inserted with either minimally invasive surgery or with a st and ard exposure . Clinical data and conventional radiographs were recorded and patients were followed with radiostereometric analysis to measure migration rate of the tibial component . The rehabilitation of patients operated through a small incision was faster , and there was a significant difference in days of hospitalization ( P = .03 ) . No statistical significant difference was found between the 2 groups regarding clinical or radiographic data . The Hospital for Special Surgery score was 96 and 92 , respectively , for the minimally invasive surgery and conventional group at 2 years . The limb alignment was equal in both groups with a mean femorotibial axis of 182 degrees after surgery . The rate of migration for tibial components was very small , with a maximal total point motion of 0.8 mm for both groups after 2 years follow-up", " Forty-seven knees in 43 patients with severe deformities r and omly received AMK total knee arthroplasty with concave ( C , n = 25 ) or posterior-stabilized ( PS , n = 22 ) polyethylene insert and with resection of the posterior cruciate ligament . Radiostereometric examinations were done postoperatively and after 3 , 12 , and 24 months . Two patients ( 1 C , 1 PS ) underwent revision surgery . At the 2-year follow-up , the median absolute rotations of the tibial inserts ranged from 0.13 degrees to 0.26 degrees ( C vs PS ; P = .1-.7 ) . The maximum total point motion was almost identical in the 2 groups ( C , 0.38 ; PS , 0.39 ; P = .9 ) . Maximum subsidence , lift-off , and Hospital for Special Surgery scores did not differ ( P = .1-.6 ) . Recipients of 20 of 24 knees with concave design and 14 of 19 knees with posterior-stabilized design reported that their knee could be regarded as normal or almost normal . Variations of the configuration of the polyethylene insert did not alter the outcome in the short term", " Bone cement with reduced amount of monomer and low curing temperature may improve implant fixation due to reduced toxicity . We analyzed the mechanical , chemical and thermal properties of such a cement ( Cemex Rx ) using Palacos R as control . The in vivo performance of the 2 cements was also evaluated in a prospect i ve r and omized study of 47 hips , where either of the cement types was used to fixate Lubinus SP2 prostheses with the stem made of titanium alloy . Cemex Rx had a reduced tensile strength , probably because this cement was manually mixed , as recommended by the manufacturer . A st and ardized laboratory test showed lower curing temperature for Cemex , but measurements at 37 ° and with prechilled Palacos R and Cemex Rx , as in clinical work , showed no difference . In the clinical study radiostereometric measurements of cup and stem migration showed similar values in the 2 groups up to 5 years after the operation . The cement mantle was stable in both groups , but the stems migrated similarly inside the cement mantle regardless of the type of cement used . Proximal wear was low ( 0.04 - 0.05 mm/year ) and tended to be lower in the Cemex group ( p = 0.02 ) . Aluminum and vanadium levels in serum increased 5 years after the operation , but no difference was noted between the 2 groups . Collagen markers ( PICP , ICTP ) showed similar increases in bone turnover 6 weeks and 6 months after operation in both groups", "We studied CMW-1 bone cement with gentamicin in the laboratory and in a r and omized clinical study . Palacos bone cement containing gentamicin was used as the control . In the pre clinical evaluation , the CMW cement had slightly less mechanical strength . In the clinical study , 51 patients ( 51 knees ) operated on with total knee arthroplasty were studied for 2 years . We used radiostereometric analysis to measure migration of the tibial components , r and omized to fixation with either of the two types of cement . The extent and pattern of migration were similar in both groups , and we found no differences in the number , size and extent of radiolucent lines or clinical outcome . No complications occurred . Our findings suggest a need for more studies of CMW-1 bone cement containing gentamicin in a larger cohort of patients", "Mobile bearings were introduced to improve wear and knee kinematics . By uncoupling the forces generated at the articulation from the implant-bone interface this would , theoretically , also improve the fixation of the implant to bone . We did this study to evaluate whether mobile bearings improve the fixation of the tibial component to bone . Fifty-two consecutive knees in 47 patients ( average age , 72 years ; range , 62 - 84 years ) with primary osteoarthrosis were r and omized into two groups to receive a cemented total knee arthroplasty with either a fixed-bearing or mobile-bearing tibial component . The quality of fixation was analyzed with radiostereometric analysis for up to 2 years . Mobile bearings did not improve fixation . Both magnitudes and directions of component rotations were similar , and the number of implants with continuous migration was almost identical . Both implant types had a combination of subsidence and lift-off , but where the mobile bearing implants displayed more of subsidence , the fixed bearing knees showed more lift-off . It might be that the somewhat stiffer cobalt-chromium baseplate or the different joint conformity used in the mobile-bearing knees counteracts any potential effects of the mobile bearing . Level of Evidence : Therapeutic Level I. See the Guidelines for Authors for a complete description of levels of evidence", "Background We have developed a bone-conserving commercially pure titanium hip replacement system using osseointegration principles : a metaphyseal loading proximal femoral component affixing into the retained neck and metaphysis only , leaving the femoral canal untouched . The acetabular cup closely fits a dual-geometry cavity , avoiding stress protection at the dome . Patients and methods After extensive laboratory and clinical pilot trial investigations , the surface-engineered implants were su bmi tted to a prospect i ve r and omized controlled clinical trial involving 40 patients ( 40 hips ) , in which they were compared to the cemented Spectron femoral component and cementless Trilogy cup as control implant . The following clinical measures were used to monitor progress at regular intervals for the first 2 postoperative years : radiostereometric analysis ( RSA ) , Harris Hip Score , pain score , WOMAC , and SF-36 . Results After 2 years of follow-up , no statistically significant differences were seen between the groups concerning rotation or translation along the cardinal axes . The patients receiving the Gothenburg osseointegrated titanium ( GOT ) system had significantly higher Harris Hip Score at 6 months , suggesting more rapid recovery . WOMAC , SF-36 and pain analysis were similar for the first 2 postoperative years . Interpretation Our RSA data suggest that osseointegration was achieved for all patients receiving the GOT hip system . This bone-conserving prosthesis may provide a good alternative , especially for young and active patients", "There is uncertainty regarding whether and how the subchondral bone plate should be treated during acetabular preparation for cemented cup fixation in a total hip arthroplasty . We hypothesized that removing the bone plate would improve the cement-bone interface without jeopardizing the initial cup stability , and therefore , be advantageous to long-term cup survival . We r and omized 50 patients with primary osteoarthritis into two groups , one for removal and one for retention of the subchondral bone plate . The patients were evaluated during 2 years followup using repeated radiostereometric examinations , analyses of radiolucent lines , and clinical followups . Patient scoring was done using the Western Ontario and McMaster Universities Osteoarthritis Index , the Short Form-12 , and the Harris hip score . Removal of the subchondral bone plate result ed in a superior cement-bone interface with less development of radiolucent lines . The radiostereometry results showed small migrations in both groups . We found no differences in cup stability between groups , although a difference was observed in rotational behavior with the removal group stabilizing in a slightly vertical position whereas the retention group showed slight but progressive rotation into a more horizontal position . No differences were found during clinical followups . Removing the subchondral bone plate , where possible , improves the cement-bone interface without jeopardizing the stability , implying better long-term cup survival . However , it is a more dem and ing surgical technique . Level of Evidence : Therapeutic study , Level I ( high quality r and omized controlled trial with statistically significant difference or no statistically significant difference but narrow confidence intervals ) . See the Guidelines for Authors for a complete description of levels of evidence", "Background Minor design changes may cause major changes in implant performance . Thus , as part of a stepwise introduction of a new low-profile cup , we performed a r and omized trial comparing it to a well-docu-mented st and ard cup . Patients and methods 60 patients , stratified according to sex , weight , and age , underwent cemented total hip arthroplasty using a Lubinus SP2 stem with ceramic head and were r and omized to either the new low-profile Lubinus Flanged Anti-Luxation cup ( FAL ) or the Lubinus St and ard Eccentric cup ( St and ard ) . 7 patients were excluded and 53 ( 28 FAL ) were evaluated at 3 , 6 , 12 , and 36 months postoperatively . Primary outcome variables , cup migration ( MTPM ) , and wear ( total 3-dimensional femoral head penetration ) were measured with radiostereometry ( RSA ) . Clinical outcome was evaluated with the western Ontario and McMaster osteoarthritis index ( Womac ) and the visual analog pain score ( VAS ) . Results We found no difference in migration between the FAL and St and ard cups . There was no difference in wear between the two cups and there was no correlation between wear and migration . 3 cups ( 2 FAL and 1 St and ard ) showed continuous migration of a magnitude that indicated an increased risk of early loosening . Clinical outcome was excellent , without any difference between the 2 groups", "This prospect i ve , r and omized protocol evaluated femoral head penetration after total hip arthroplasty in a young population . Forty-five patients r and omly received either a cross-linked or conventional ultrahigh-molecular-weight polyethylene ( UHMWPE ) liner in a noncemented hemispheric cup ( Trilogy , Zimmer , Warsaw , Ind ) with a 28-mm femoral head . Radiostereometric analysis film pairs , Harris hip , UCLA , SF-12 , and Western Ontario and McMaster Universities scores were obtained through 2 years . Median femoral head penetration was less among cross-linked compared to conventional liners as follows : 0.06 mm ( 0.04 - 0.08 mm ) vs 0.08 mm ( 0.02 - 0.19 mm ) at 6 months , 0.07 mm ( -0.14 to 0.16 mm ) vs 0.11 mm ( 0.01 - 0.27 mm ) at 1 year , and 0.065 mm ( -0.04 to 0.193 mm ) vs 0.169 mm ( 0.09 - 0.22 mm ) at 2 years . Clinical outcomes were similar between the groups . Highly cross-linked UHMWPE demonstrated 55 % less femoral head penetration compared to conventional polyethylene at 2 years . Despite improvements in the manufacturing process and sterilization of conventional UHMWPE , the femoral head penetration rate is unchanged from historical st and ards", "Background : Femoral stems with reduced stiffness were introduced in total hip arthroplasty to facilitate proximal load transfer and thereby reduce periprosthetic bone loss . Poor fixation and unacceptably high revision rates turned out to be a major problem with these prostheses . The purpose of the present study was to evaluate the early performance of a low-modulus stem ( one that is less stiff ) with the potential to address the problem of fixation by the use of a surface coating . The coating consisted of a titanium porous mesh proximally covered with a mixture of hydroxyapatite and tricalcium phosphate . Methods : Thirty-nine men and twenty-six women ( sixty-eight hips ) with noninflammatory arthritis were studied . The patients were r and omized to receive either a porous-coated composite stem with reduced stiffness ( Epoch ) or a stiff stem with a porous coating ( Anatomic ) . Both stems were inserted without cement , had a ceramic coating on the proximal two-thirds , and were supplied with tantalum beads . At the time of the operation , tantalum markers were also placed into the proximal part of the femur . The patients were followed for up to two years after the operation and were evaluated with use of repeated radiostereometric measurements , measurements of bone-mineral density , conventional radiography , and Harris hip scores . Results : Both stems showed optimum fixation with median subsidence and stem rotations that were close to zero . Repeated measurements of bone-mineral density revealed early loss of bone mineral in all Gruen regions in both treatment groups . The loss of bone mineral around the Epoch stems was significantly reduced at two years in Gruen regions 1 , 2 , 6 , and 7 ( p the Epoch stems had significantly more endocortical contact on both the anteroposterior ( p the Epoch stems had fewer sclerotic lines surrounding the stem ( p £ 0.002 ) and less sclerosis at the tip of the prosthesis ( p = 0.001 ) compared with the Anatomic stems . The clinical results in terms of the Harris hip score , which was determined in all hips , and pain or discomfort , which was evaluated in thirty-seven hips treated at the same hospital , were not found to be different , with the numbers available . Conclusions : Contrary to previous studies of other design s with reduced stiffness , the Epoch stem achieved excellent primary fixation . Despite this rigid fixation , the proximal loss of bone-mineral density was less than that associated with the stem with a stiffer design . These results should encourage additional long-term studies with a larger patient population", " One hundred twenty-eight consecutive knees were operated on with the Duracon unicompartmental knee arthroplasty . Of 111 knees , followed 3 years ( range , 1 - 6 years ) , 109 knees were satisfactory . Two knees were revised because of progression of osteoarthritis and inexplicable pain . Radiostereometric analysis in 49 knees showed a migration of 0.6 mm after 2 years . The magnitude of migration was lower in comparison with published series . In a multicenter study comprising 4 other hospitals , there were 8 revisions in 123 operated knees . The reasons were loosening , subsidence , or fracture . These revisions were within 1 year and mostly related to operative technique . Unicompartmental knee arthroplasty is a dem and ing procedure that needs special experience and includes a risk of early failures during the introduction of a system", "We have evaluated the difference in the migration patterns over two years of two cementless stems in a r and omised , controlled trial using radiostereophotogrammetric analysis ( RSA ) . The implants studied were the Furlong HAC stem , which has good long-term results and the Furlong Active stem , which is a modified version of the former design ed to minimise stress concentrations between the implant and bone , and thus to improve fixation . A total of 23 Furlong HAC and 20 Furlong Active stems were implanted in 43 patients . RSA examinations were carried out immediately post-operatively and at six , 12 and 24 months post-operatively . The subsidence during the first year in the Furlong HAC stem , was approximately one-third that of the Furlong Active stem , the measured mean subsidence of the femoral head at six months being 0.27 mm ( 95 % confidence interval ( CI ) 0.03 to 0.51 ) and 0.99 mm ( 95 % CI 0.38 to 1.60 ) , respectively ( p = 0.03 ) . One Active stem continued to subside during the second year . All hips , regardless of the type of stem were clinical ly successful as judged by the Oxford hip score and a derived pain score without any distinction between the two types of stem . The initial stability of the Furlong Active stem was not as good as the established stem which might compromise osseo-integration to the detriment of long-term success . The changes in the geometry of the stem , to minimise stress have affected the attainment of initial stability", "In a double-blind study , we r and omized 50 patients to receive peroral clodronate medication or placebo from 3 weeks before until 6 months after a total knee replacement with a cemented NexGen implant . Migration of the tibial components was measured by radiostereometry at 1 year . Clodronate reduced prosthetic migration , as measured by maximum total point motion , from 0.40 mm to 0.29 mm ( p = 0.01 ) . This confirms that the early postoperative migration is related to bone resorption and thus the biology of the bone bed . Since early migration is related to late loosening , 6 months of clodronate medication might reduce the risk of loosening", "Eighty patients ( 84 hips ) r and omly received an anteverted cobalt-chromium stem ( Lubinus SP2 ; Waldemar Link , Hamburg , Germany ) with matte , polymethyl methacrylate-coated , or polished surface ( uncollared ) . Radiostereometry was used to study migration and wear ; and the bone mineral density was studied with dual-energy x-ray absorptiometry at 6 months , 1 year , 2 years , and 5 years . The polished stems had subsided 0.1 to 0.2 mm more at 6 months and 0.3 to 0.4 mm more at 5 years than the matte and precoated versions ( P rotations of the stem and the migration and wear of the cemented cup did not differ between the 3 groups . After 1 and 2 years , the polished stems had lost significantly less bone mineral in Gruen zones 1 , 2 , 6 , and 7 ( P = .004 to .03 ) ; but this difference had disappeared after 5 years . The period of improved bone remodeling around the polished version coincided with the early period of increased subsidence , suggesting that stem motions inside the mantle result ed in a favorable loading of the proximal femur . Our observations suggest that alternative shapes could be possible on future polished femoral stem design ", "The custom made Unique stem is design ed to fit closely to the metaphyseal region of the femur in order to obtain maximum mechanical stability and optimal load transfer . Thirty-seven patients ( 38 hips ) with non-inflammatory arthritis were r and omized to the uncemented custom made Unique stem or the Elite Plus stem inserted with cement . The patients have been followed clinical ly as well as with radiostereometry ( RSA ) and Dual-energy X-ray Absorptiometry ( DXA ) for 2 years . After 2 years the RSA result showed minimal translation and rotation for the Unique stem while the Elite Plus rotated slightly ( mean 1.05 degrees ) into retroversion . Compared to previous studies the Elite Plus was as stable as the Charnley prosthesis . The DXA results showed a significantly higher proximal and total ( 10 % for the Unique versus 5 % for Elite ) bone loss for the Unique stem compared to the Elite Plus . Thus the optimal proximal press-fit of the custom made stem did secure a stable fixation , but did not decrease the proximal bone loss", "A prospect i ve double-blind , r and omized , and controlled trial was conducted using roentgen stereophotogrammetric analysis ; 54 total hip arthroplasty patients were r and omized to receive either highly cross-linked polyethylene ( HXLPE ) or st and ard ultra-high-molecular-weight polyethylene ( UHMWPE ) liners . The 3-dimensional penetration of the liner was determined over 2 years . For the first 3 months , both polyethylene types had a rapid penetration rate ( HXLPE : 0.22 mm , SD = 0.17 mm ; UHMWPE : 0.21 mm , SD = 0.15 mm ; P = .78 ) . After 3 months , the HXLPE penetration rate ( 0.06 mm/y , SD = 0.06 mm/y ) was significantly lower than the UHMWPE penetration rate ( 0.10 mm/y , SD = 0.07 mm/y ; P = .04 ) . The penetration in the first 3 months was probably caused by creep or bedding in ; from 3 months onward , much of the penetration was probably caused by wear . We conclude that HXLPE has a 40 % lower wear rate as compared with UHMWPE , suggesting that it will perform better in the long term", "We evaluated the mechanical , chemical and clinical properties of Boneloc cement using radiostereometry and a series of laboratory tests . Compared to a st and ard cement ( Palacos ) the new cement displayed reduced tensile strength , elastic modulus , curing and glass transition temperatures . The amount of MMA extracted during 3 weeks in methanol was smaller for the Boneloc , but the total amount of released monomers was larger . The adhesion to stainless steel and bone did not differ . Radiostereometric analysis during the first postoperative year in 30 patients r and omized to fixation of hip prostheses using either of the 2 cements displayed increased proximal migration of the cup and increased stem subsidence when Boneloc had been used . Part of the stem subsidence occurred inside the cement mantle . On the basis of these findings , we conclude that the inferior fixation in the Boneloc group is mainly caused by its mechanical properties . Other mechanisms , such as increased release of monomers , may also be important", "VersaBond is a newly developed bone cement . To investigate its clinical performance , VersaBond was compared to Palacos R in a prospect i ve r and omized study in total knee replacement . Fifty-nine patients ( 61 knees ) undergoing total knee replacement were r and omized to either VersaBond or Palacos R bone cement and followed for 24 months using radiostereometric analysis ( RSA ) . Up to 2 years there were no significant differences in clinical performance between the two cements . The mean/median values for implant migration were very similar for the two bone cements , as were the dispersion , and distribution of outliers . Also the proportion \" stable \" and \" continuously migrating \" implants was similar between the two cements . The result of this study indicates that VersaBond bone cement will perform at least equally as well as Palacos R in total knee replacement as regards as aseptic loosening" ]

[ "Objectives To vali date muscle endurance estimation and to examine relationships with dependency and inflammation in elderly persons . Design Cross sectional validation and explorative study . Setting Hospitalized geriatric patients and community-dwelling controls . Participants 91 elderly patients ( aged 83±5 years ) , 100 elderly controls ( aged 74±5 years ) and 100 young controls ( aged 23±3 years ) . Measurements Grip strength ( GS ) was recorded continuously during sustained maximal contraction until exhaustion . Fatigue resistance ( FR ) was expressed as the time during which GS drops to 50 % of its maximum . Grip work ( GW ) was estimated as GW = GS*0.75*FR , and compared to the measured GW . In the elderly participants , relationships ( controlling for age and physical activity ) of GS , FR , GW and GW corrected for body weight ( GW/BW ) with dependency ( Katz-scale ) and inflammation ( circulating IL-6 and TNF-alpha ) were analyzed . Results Excellent correlation between estimated and measured GW was found ( r=0.98 , p Better GS , FR , GW and GW/BW was significantly related with less dependency ( all p Higher IL-6 was significantly related to worse dependency ( p with TNF-alpha were found . Conclusion GW estimation is a valid parameter reflecting muscle endurance in elderly persons presenting diverse clinical conditions . GW is significantly related to both dependency and circulating IL-6 , and is a promising outcome parameter in comprehensive geriatric assessment", "BACKGROUND Our aim was to determine the association between physical activity and physical performance , and inflammatory biomarkers in elderly persons . METHODS One thous and four persons aged 65 years or more , participants in a cross-sectional population -based study , were included . Interviewers collected information on self-reported physical activity during the previous year . Moreover , 841 participants performed a 400-meter walking test to assess physical performance . Plasma concentrations of inflammatory biomarkers were determined . RESULTS Compared to sedentary men , men practicing light and moderate-high physical activity had a significantly lower erythrocyte sedimentation rate ( -0.33 and -0.40 mm/h ; p = .023 and p = .006 , respectively ) , fibrinogen level ( -43 and -39 mg/dL ; p = .001 and p = .004 , respectively ) , and logarithm of C-reactive protein ( CRP ) ( -0.43 and -0.73 mg/L ; p = .025 and p moderate-high physical activity had a significantly lower uric acid level ( -0.57 mg/dL ; p = .023 ) , log(interleukin 6 ) levels ( -0.33 pg/mL ; p = .014 ) , and log(tumor necrosis factor-alpha ) ( -0.31 pg/mL ; p = .030 ) . In women , those practicing light and moderate-high physical activity had significantly lower uric acid ( -0.45 and -0.34 mg/dL ; p = .001 and p = .039 , respectively ) and log(interleukin 6 ) levels ( -0.18 and -0.30 pg/mL ; p = .043 and p = .004 , respectively ) ; only those women practicing moderate-high physical activity had significantly lower log(CRP ) ( -0.31 mg/L ; p = .020 ) . In women , when the analysis was adjusted for body mass index , the association between physical activity and CRP was no longer significant . Similar findings were observed when we carried these analyses according to physical performance . CONCLUSIONS Current physical activity practice and performance are associated with inflammatory biomarkers . A significant beneficial association is already observed with light physical activity practice and intermediate performance", "Background : Inflammatory markers are increased in chronic obstructive pulmonary disease ( COPD ) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance . Methods : The Health Aging and Body Composition ( Health ABC ) study is a prospect i ve observational cohort of well functioning individuals aged 70–79 years . A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation , muscle strength , and exercise capacity . These associations were compared in participants with and without obstructive lung disease ( OLD ) . Results : Of the 3075 participants enrolled in the Health ABC cohort , OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results . Of the participants with OLD , 35 % , 38 % , and 27 % participants had mild , moderate , and severe OLD , respectively . Participants with OLD had lower quadriceps strength ( 102.5 Nm v 108.9 Nm , p = 0.02 ) , lower maximum inspiratory pressure ( 64.7 cm H2O v 74.2 cm H2O , p higher systemic interleukin (IL)-6 levels ( 2.6 pg/ml v 2.2 pg/ml , p higher C-reactive protein ( CRP ) levels ( 3.5 mg/l v 2.5 mg/l , p expiratory volume in 1 second ( FEV1 ) was associated with IL-6 ( adjusted regression coefficients ( β ) = −5.3 ( 95 % CI −9.1 to−1.5 ) and −3.1 ( 95 % CI −4.3 to −1.9 ) , respectively ) . IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry ( β = −6.4 ( 95 % CI −12.8 to −0.03 ) and −3.4 ( 95 % CI −5.4 to −1.3 ) , respectively , for IL-6 and β = −10.1 ( 95 % CI −18.7 to −1.5 ) and −3.8 ( 95 % CI −7 to −0.6 ) , respectively , for TNF ) . IL-6 , quadriceps strength , and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups . Conclusions : In well functioning elderly subjects with or without OLD , IL-6 is associated with reduced FEV1 , quadriceps strength , and exercise capacity", "PURPOSE To study the effect of carbohydrate compared to placebo ingestion on plasma cytokines and muscle cytokine mRNA following 2.5 h of intensive cycling in 15 trained cyclists . METHODS Fifteen trained cyclists cycled for 2.5 h at 60 % Wmax on two occasions while receiving 4 mL.kg.15 min carbohydrate ( 6 % ) ( CHO ) or placebo ( PLA ) beverages in a r and omized , counterbalanced design . Blood and vastus lateralis muscle biopsy sample s were collected before and after exercise and 12 h postexercise and compared to sample s taken from five cyclists who rested in the lab during the exercise sessions . Blood cell counts were determined , and plasma was analyzed for interleukin (IL)-6 , IL-10 , IL-1 receptor antagonist ( ra ) , IL-8 , cortisol , epinephrine , glucose , and insulin . Muscle was analyzed for glycogen content and relative gene expression of four cytokines , IL-6 , IL-8 , tumor necrosis factor ( TNF ) alpha , and IL-1beta , using real-time quantitative reverse transcriptase polymerase chain reaction . RESULTS Plasma glucose and insulin were higher , and epinephrine , cortisol , IL-6 , IL-10 , and IL-1ra , but not IL-8 , were significantly lower postexercise in CHO versus PLA . Muscle glycogen content decreased 68 % immediately postexercise and the pattern of change did not differ between CHO and PLA . Muscle IL-6 , IL-8 , TNF-alpha , but not IL-1beta mRNA increased immediately postexercise compared to controls , with no differences between CHO and PLA . CONCLUSION CHO compared to PLA beverage ingestion attenuated the increase in plasma cortisol , epinephrine , IL-6 , IL-10 , and IL-1ra , but not muscle IL-6 , IL-8 , and TNF-alpha mRNA in athletes cycling 2.5 h at 60 % Wmax", "BACKGROUND The serum concentration of interleukin 6 ( IL-6 ) , a cytokine that plays a central role in inflammation , increases with age . Because inflammation is a component of many age-associated chronic diseases , which often cause disability , high circulating levels of IL-6 may contribute to functional decline in old age . We tested the hypothesis that high levels of IL-6 predict future disability in older persons who are not disabled . METHODS Participants at the sixth annual follow-up of the Iowa site of the Established Population s for Epidemiologic Studies of the Elderly aged 71 years or older were considered eligible for this study if they had no disability in regard to mobility or in selected activities of daily living ( ADL ) , and they were re-interviewed 4 years later . Incident cases of mobility-disability and of ADL-disability were identified based on responses at the follow-up interview . Measures of IL-6 were obtained from specimens collected at baseline from the 283 participants who developed any disability and from 350 participants selected r and omly ( 46.9 % ) from those who continued to be non-disabled . FINDINGS Participants in the highest IL-6 tertile were 1.76 ( 95 % CI , 1.17 - 2.64 ) times more likely to develop at least mobility-disability and 1.62 ( 95 % CI , 1.02 - 2.60 ) times more likely to develop mobility plus ADL-disability compared with to the lowest IL-6 tertile . The strength of this association was almost unchanged after adjusting for multiple confounders . The increased risk of mobility-disability over the full spectrum of IL-6 concentration was nonlinear , with the risk rising rapidly beyond plasma levels of 2.5 pg/mL. INTERPRETATION Higher circulating levels of IL-6 predict disability onset in older persons . This may be attributable to a direct effect of IL-6 on muscle atrophy and /or to the pathophysiologic role played by IL-6 in specific diseases", "OBJECTIVES To test whether accelerated sarcopenia in older persons with high interleukin (IL)-6 serum levels plays a role in the prospect i ve association between inflammation and disability found in many studies . DESIGN Cohort study of older women with moderate to severe disability . PARTICIPANTS Six hundred twenty older women from the Women 's Health and Aging Study in whom information on baseline IL-6 serum level was available . MEASUREMENTS Self-report of functional status , objective measures of walking performance , and knee extensor strength were assessed at baseline and over six semiannual follow-up visits . Potential confounders were baseline age , race , body mass index , smoking , depression , and medical conditions . RESULTS At baseline , women with high IL-6 were more often disabled and had lower walking speed . After adjusting for confounders , women in the highest IL-6 tertile ( IL-6>3.10 pg/mL ) were at higher risk of developing incident mobility disability ( risk ratio ( RR ) = 1.50 , 95 % confidence interval ( CI ) = 1.01 - 2.27 ) , disability in activities of daily living ( RR = 1.41 , 95 % CI = 1.01 - 1.98 ) , and severe limitation in walking ( RR = 1.61 , 95 % CI = 1.09 - 2.38 ) and experienced steeper declines in walking speed ( P in knee extensor strength was also steeper , but differences across IL-6 tertiles were not significant . After adjusting for change over time in knee extensor strength , the association between high IL-6 and accelerated decline of physical function was no longer statistically significant . CONCLUSIONS Older women with high IL-6 serum levels have a higher risk of developing physical disability and experience a steeper decline in walking ability than those with lower levels , which are partially explained by a parallel decline in muscle strength", "BACKGROUND Some studies have proposed chronic inflammation as an underlying biological mechanism responsible for physical function decline in elderly people . The aim of this study is to evaluate the relationship between several inflammatory markers and physical performance in an older population . METHODS This study is part of the \" Invecchiare in Chianti \" ( InCHIANTI ) study , a prospect i ve population -based study of older people , aim ed at identifying risk factors for late-life disability . The study sample consisted of 1020 participants aged 65 years and older living in the Chianti area of Italy . Physical performance was assessed using walking speed , the chair-st and test , and the st and ing balance test . H and -grip strength was assessed using a h and -held dynamometer . Serum levels of C-reactive protein ( CRP ) , interleukin (IL)-6 , tumor necrosis factor-alpha ( TNF-alpha ) , IL-10 , IL-1beta , IL-6sR , and IL-1RA were determined . Linear regression analyses were used to assess the multivariate relationship of inflammatory marker levels with physical performance , scored as a continuous variable from 0 to 3 , and h and -grip strength after adjustment for demographics , chronic conditions , medication use , and other biological variables . RESULTS CRP , IL-6 , and IL1RA were significantly correlated with physical performance ( r=-0.162 , r=-0.251 , and r=-0.127 , respectively ) . Significant correlations with h and -grip strength were found for CRP and IL-6 ( r=-0.081 and r=-0.089 , respectively ) . After adjustment for covariates , high levels of IL-6 and IL-1RA continued to be strongly associated with worse physical performance ( p of CRP ( p IL-6 ( p low h and -grip strength . Mean adjusted physical performance scores ranged from 2.21 in the CRP0.60 mg/dl group ( p for trend=.004 ) , and from 2.25 in the lowest IL-6 quartile to 2.08 in the highest IL-6 quartile ( p for trend adjusted h and -grip strength , with a range from 28.8 kg for the CRP0.60 mg/dl group ( p for trend=.001 ) , and from 27.4 kg for the lowest IL-6 quartile to 25.1 kg for the highest IL-6 quartile ( p for trend=.001 ) . CONCLUSIONS Inflammation , measured as high levels of IL-6 , CRP , and IL-1RA , is significantly associated with poor physical performance and muscle strength in older persons . These data also support the biological face validity of physical performance measures . The assessment of inflammatory markers may represent a useful screening test and perhaps a potential target of intervention", "This study examines the effects of 32 weeks of exercise training on balance , lower-extremity muscle strength , bone mineral density ( BMD ) and serum levels of bone metabolism and inflammatory markers in older adults . Forty-seven healthy older adults ( women=24 , men=23 ; mean age 68.2 years ) participated in a exercise intervention ( 60min/session ) that included resistance exercise training ( 2 days/week ) at 75 - 80 % of maximum plus a multicomponent weight-bearing impact exercise training ( 1 day/week ) . Outcome measures included lumbar spine and proximal femoral BMD , dynamic balance , muscle strength , serum levels of bone metabolism markers [ osteocalcin ( OC ) , C-terminal telopeptide of Type I collagen ( CTX ) , osteoprotegerin ( OPG ) and receptor activator of nuclear factor kappa B lig and ( RANKL ) ] and serum levels of inflammatory markers [ high sensitive (hs)-C-reactive protein ( CRP ) , interleukin (IL)-6 , tumor necrosis factor (TNF)-α , and interferon (IFN)-γ ] . Potential confounding variables included body composition , dietary intake ( using 4-day diet records ) , and accelerometer-based physical activity . After 32 weeks , both men and women increased dynamic balance ( 6.4 % ) , muscle strength ( 11.0 % ) and trochanter ( 0.7 % ) , intertrochanter ( 0.7 % ) , total hip ( 0.6 % ) , and lumbar spine BMD ( 1.7 % ) , while OC , CTX , OPG and RANKL levels remained unchanged . In addition , hs-CRP and IFN-γ levels were decreased , while TNF-α levels were unchanged , and a decrease in IL-6 levels was only observed in men . These findings suggest that our combined impact protocol reduces inflammation and increases BMD , balance , and lower-extremity muscle strength , despite having little effect on bone metabolism markers . This reinforces the role of exercise to counteract the age-related inflammation , and the muscle strength , balance and BMD reduction" ]

[ "Background In southern and eastern Mediterranean countries , changes in lifestyle and the increasing prevalence of excess weight in childhood are risk factors for high blood pressure ( BP ) during adolescence and adulthood . The aim of this study was to evaluate the BP status of Tunisian adolescents and to identify associated factors . Methods A cross-sectional study in 2005 , based on a national , stratified , r and om cluster sample of 1294 boys and 1576 girls aged 15 - 19 surveyed in home visits . The socio-economic and behavioral characteristics of the adolescents were recorded . Overweight/obesity were assessed by Body Mass Index ( BMI ) from measured height and weight ( WHO , 2007 ) , abdominal obesity by waist circumference ( WC ) . BP was measured twice during the same visit . Elevated BP was systolic ( SBP ) or diastolic blood pressure ( DBP ) ≥ 90th of the international reference or ≥ 120/80 mm Hg for 15 - 17 y. , and SBP/DBP ≥ 120/80 mm Hg for 18 - 19 y. ; hypertension was SBP/DBP ≥ 95th for 15 - 17 y. and ≥ 140/90 mm Hg for 18 - 19 y. Adjusted associations were assessed by logistic regression . Results The prevalence of elevated BP was 35.1%[32.9 - 37.4 ] : higher among boys ( 46.1 % vs. 33.3 % ; P : - obesity vs. no excess weight increased elevated BP ( boys OR = 2.1[1.0 - 4.2 ] , girls OR = 2.3[1.3 - 3.9 ] ) and hypertension ( boys OR = 3.5[1.4 - 8.9 ] , girls OR = 5.4[2.2 - 13.4 ] ) , - abdominal obesity ( WC ) was also associated with elevated BP in both genders ( for boys : 2nd vs. 1st tertile OR = 1.7[1.3 - 2.3 ] , 3rd vs.1st tertile OR = 2.8[1.9 - 4.2 ] ; for girls : 2nd vs. 1st tertile OR = 1.6[1.2 - 2.1 ] , 3rd vs.1st tertile OR = 2.1[1.5 - 3.0 ] ) but only among boys for hypertension . Associations with other covariates were weaker : for boys , hypertension increased somewhat with sedentary lifestyle , while elevated BP was slightly more prevalent among urban girls and those not attending school . Conclusion Within the limits of BP measurement on one visit only , these results suggest that Tunisian adolescents of both genders are likely not spared from early elevated BP . Though further assessment is likely needed , the strong association with overweight/obesity observed suggests that interventions aim ed at changing lifestyles to reduce this main risk factor may also be appropriate for the prevention of elevated BP", "OBJECTIVE To investigate the occurrence and association of arterial hypertension with several lifestyle variables . METHODS Transversal population -based study with a r and om sample of students ( 7 to 14 years of age ) of public and private schools . Variables investigated were nutritional status , blood pressure , and lifestyle ( tobacco use , alcohol intake , physical activity and eating habits ) . RESULTS Out of the 3,169 schoolchildren assessed , 5.0 % had arterial hypertension and 6.2 % had normal-high blood pressure . Classification by gender shows boys 6.4 % and girls 6.0 % with normal-high blood pressure , and boys 4.3 % and girls 5.7 % with arterial hypertension . Body mass index ( BMI ) measurements identified 16.0 % excess weight students , 4.9 % of whom were obese . A significant association ( p = 0.01 ) between arterial hypertension and excess weight was observed . Among the students participating in the study , 11.6 % did not attend physical education classes and 37.8 % had sedentary leisure habits . Twenty students ( 0.6 % ) were smokers and 32.7 % had already experimented with alcohol . None of these variables showed statistical significance as to blood pressure values and nutritional status . CONCLUSION In light of the findings in this study which show schoolchildren with a higher than expected frequency of mean blood pressure and BMI values , associated with a lifestyle that tends to favour the development of cardiovascular diseases , we felt led to propose interventional measures focused on the school as an agent of change and capable of conveying information to family units . This possibility encourages us to propose that schools be partners in promoting health", "OBJECTIVE The study aims are investigating the effect of body fat and fat localization on blood pressure . DESIGN Case-control study . SETTING The study was carried out in the school health primary care . SUBJECTS The case-control study included 220 obese and 220 non-obese children aged 7 - 18 years from Al Ain city , United Arab Emirates between September 1992 to May 1993 inclusive . Each group consisted of 120 males and 100 females . Two schools were r and omly selected from each of the three educational stages : primary , junior and secondary . The inclusion criterion for cases comprised children with body mass index ( BMI ; Quetelet index ) , > 90th percentile of age and sex-specific reference data of the French population . Non-obese healthy controls were r and omly selected from the same classes from where obese children were identified in order to ascertain that cases and controls were matched by age and sex . MEASUREMENTS Anthropometric measures ( weight , height , waist and hip circumferences ) , systolic and diastolic blood pressure were measured . To minimize inter-observer error , blood pressure was measured by one physician . We also collected information about other confounding social variables ( family history of obesity and mother 's education ) and behavioural variables ( preferred diet and physical activity ) . RESULTS There was significant difference of systolic and diastolic blood pressure means between obese and non-obese children ( P fatness index , BMI , was significantly related to systolic ( P diastolic ( P waist-to-hip circumference ratio ( WHR ) was not significant ( P = 0.803 in systolic and P = 0.648 in diastolic blood pressure respectively ) . CONCLUSIONS Systolic and diastolic blood pressure showed a positive relationship with the fatness index BMI , but not with WHR , in both boys and girls . This is an evidence that WHR may not be a reliable indicator of body fat distribution in children", "OBJECTIVE To assess the prevalence of high blood pressure ( BP ) and the association of overweight and obesity with high BP among adolescents in Aracaju , Brazil . DESIGN Cross-sectional study . The main outcome measure was the proportion of adolescents with high BP ( sex- , age- and height-specific ≥ 95th percentile ) . The main predictor variables were overweight and obesity defined according to the criteria of the International Obesity Task Force . Other covariates included age , socio-economic status and leisure-time physical activity . SETTING Aracaju , Brazil , capital city of Sergipe State , north-eastern Brazil . SUBJECTS A r and om sample of 1002 adolescents ( 442 boys and 560 girls ) aged 12 - 17 years selected from twenty public schools and ten private schools were studied . RESULTS The prevalence of high BP was 16.9 % ( 95 % CI 13.1 , 21.7 ) in boys and 12.9 % ( 95 % CI 9.0 , 18.0 ) in girls . After adjusting for age , socio-economic status and leisure-time physical activity in both boys and girls , overweight ( prevalence ratio ( PR ) = 1.93 , 95 % CI 1.08 , 3.48 ; PR = 4.34 , 95 % CI 2.58 , 7.30 , respectively ) and obesity ( PR = 4.87 , 95 % CI 2.35 , 10.11 ; PR = 5.18 , 95 % CI 2.67 , 10.06 , respectively ) were found to be associated with high BP . CONCLUSIONS These findings indicate a high prevalence of high BP in both boys and girls in Aracaju , Brazil . Overweight and obesity were strongly associated with high BP . These findings underscore the urgent need for public health measures to prevent increasing high BP in adolescents in Brazil . Targeting intervention in adolescence may be a critical method for preventing high BP in later life", "This study aims to identify risk factors for cardiovascular disorders in schoolchildren living in Ouro Preto City , Brazil . A cross-sectional study was carried out in a population -based sampling of schoolchildren ( 6–14 years old ) , r and omly selected and stratified by the proportion of students according to age and gender in each schools of the city . Biochemical , clinical and anthropometric variables as well as physical activity and family history were used in a logistic regression model for obesity or arterial hypertension . Out of 780 schoolchildren sample d , the risk of obesity was greater in subjects presenting high triglyceride and low high density lipoprotein-cholesterol levels , and those whose parents were obese , whilst the risk of hypertension was high in obese subjects and those who presented low birth weight . It was observed that 44.4 % of the schoolchildren were exposed to two or three cardiovascular disease ( CVD ) risk factors and 8.2 % were exposed to four or six factors . These findings should be considered in preventive measures to reduce the future risk for CVD among schoolchildren in Brazil", "Body mass index ( BMI , calculated as kg/m 2 ) is increased by high amounts of both lean and fat tissue . Therefore , a very muscular individual with low body fat could be classified as overweight by BMI . To evaluate this problem , the relationship between BMI , body fat as indicated by the sum of triceps and subscapular skinfolds , and muscle mass as indicated by upper arm muscle area ( UAMA ) was studied in 107 male and 106 female National Collegiate Athletic Association Division III athletes . Sex , the sum of triceps and subscapular skinfolds , and UAMA were significantly related to BMI ( overall P Thirty-eight athletes had a BMI of 25 or higher , indicating overweight or obesity . Of these , only four had excess body fat , as indicated by a sum of triceps and subscapular skinfolds greater than the 85th percentile , but 27 had high muscle mass , indicated by a UAMA greater than the 85th percentile . In the nonr and om sample of athletes we studied , BMI frequently classified muscular individuals who did not have high skinfold measurements as overweight", "To find out the factors responsible for variations of adolescent blood pressure , a community-based cross-sectional study was undertaken among 1081 adolescents , aged 10 - 19 years , selected by simple r and om sampling in an urban slum of Kolkata , Chetla in 2003 - 04 . Age , educational status , additional ghee/butter intake with diet , family history of hypertension , weight , height and body mass index were found to be associated with blood pressure in unifactorial analysis , hence these variables were considered for multifactorial analysis . All these independent variables were correlated with both systolic and diastolic blood pressure except additional ghee/butter intake with food . In stepwise multiple regression analysis , age , education , family history of hypertension , weight , height and body mass index contributed 64.6 % of the total variation of systolic blood pressure , where weight alone contributed to 62.6 % while 35.4 % of variations remained unexplained . In case of diastolic blood pressure , 56.8 % of the total variations were due to age , education , family history of hypertension , weight , height and body mass index , out of which weight alone contributed 56 % while remaining 43.2 % of total variations remained unexplained . Since single most important predictor of blood pressure was weight , regular aerobic physical activity , dietary modification , behavioral changes and health education are recommended for weight reduction and prevention of obesity", "OBJECTIVES The aims of this study were to provide data on blood pressure ( BP ) levels , to measure prevalence of high-normal or high BP and to identify a set of conditions that may predict high BP ( HBP ) in a population of children and adolescents in Italy . METHODS A r and om sample of students 6 - 18 years old attending r and omly selected schools in Catanzaro , Italy , was recruited . All students completed a question naire on their health and on health behaviours , such as physical activity , diet , drinking and smoking . Blood pressure , heart rate , height , weight and body mass index ( BMI ) were recorded . RESULTS Of the 603 subjects examined , 12.8 % had high-normal BP , 3.5 % hypertension ( HTN ) and 11.1 % were obese . High-normal or high diastolic BP ( DBP ) was significantly more likely in older subjects with a higher BMI , in those with a smoker mother and in preterm children , whereas high-normal or high systolic BP ( SBP ) was significantly more likely to be found in older subjects with a higher BMI and in those who had at least one parent with HTN . High-normal or high DBP or SBP were significantly predicted by BMI and age . CONCLUSIONS Interventions should focus at reducing obesity and encouraging proper dietary habits , sufficient exercise and cessation of smoking habit in parents too , especially in children with a family history of HTN", "PURPOSE An obesity paradox , a \" paradoxical \" decrease in morbidity and mortality with increasing body mass index ( BMI ) , has been shown in patients with heart failure and those undergoing percutaneous coronary intervention . However , whether this phenomenon exists in patients with hypertension and coronary artery disease is not known . METHODS A total of 22,576 hypertensive patients with coronary artery disease ( follow-up 61,835 patient years , mean age 66+/-9.8 years ) were r and omized to a verapamil-SR or atenolol strategy . Dose titration and additional drugs ( tr and olapril and /or hydrochlorothiazide ) were added to achieve target blood pressure control according to the Sixth Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure targets . Patients were classified into 5 groups according to baseline BMI : less than 20 kg/m2 ( thin ) , 20 to 25 kg/m2 ( normal weight ) , 25 to 30 kg/m2 ( overweight ) , 30 to 35 kg/m2 ( class I obesity ) , and 35 kg/m2 or more ( class II-III obesity ) . The primary outcome was first occurrence of death , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS With patients of normal weight ( BMI 20 to rate of primary outcome and death despite having smaller blood pressure reduction compared with patients of normal weight at 24 months ( -17.5+/-21.9 mm Hg/-9.8+/-12.4 mm Hg vs -20.7+/-23.1 mm Hg /-10.6+/-12.5 mm Hg , P population with hypertension and coronary artery disease , overweight and obese patients had a decreased risk of primary outcome compared with patients of normal weight , which was driven primarily by a decreased risk of all-cause mortality . Our results further suggest a protective effect of obesity in patients with known cardiovascular disease in concordance with data in patients with heart failure and those undergoing percutaneous coronary intervention " ]

[ "We have measured the psychological effects of acebutolol and atenolol in sixteen patients with essential hypertension . The drugs were administered in a r and omized , placebo-controlled , double-blind manner , in single daily doses of 100 mg atenolol , 400 mg acebutolol or placebo for periods of 6 weeks , each drug period being separated by a placebo period . At each 2 weekly clinic visit , a question naire design ed for assessment of state anxiety and state arousal was administered for self-completion . Arousal was significantly reduced by atenolol over the whole 6 weeks of administration . It was not affected by acebutolol . Anxiety was significantly reduced by acebutolol but only at the first of the three 2 weekly assessment s on treatment . It was not affected by atenolol . Differences in the psychological effects of these two beta-adrenoceptor blockers are discussed in terms of their lipid solubility and haemodynamic effects", "This study re-examines the proposal that beta-adrenoceptor blockers with intrinsic sympathomimetic activity decrease plasma noradrenaline levels . Thirteen patients ( aged 29 - 65 years ) with uncomplicated essential hypertension were r and omly allocated to a three period , double-blind cross-over trial . The treatment periods , each of 3 weeks duration , were composed of placebo , pindolol ( 5 mg twice daily ) and metoprolol ( 100 mg twice daily ) , dispensed in identical capsules . At the end of each treatment period , patients were exercised on a bicycle ergometer to a predetermined workload . Blood pressure and heart rate were measured before , immediately on completion of exercise and after 10 min post-exercise rest . Blood sample s for plasma noradrenaline and adrenaline determination were also collected at these times . Blood pressures were similar during treatment with pindolol and metoprolol . As expected , heart rate was consistently lower during metoprolol treatment . Basal , pre-exercise plasma noradrenaline and adrenaline were similar at the end of each treatment period . However , the increase following exercise was significantly greater during metoprolol treatment . The post-exercise increase during pindolol treatment was indistinguishable from that in the placebo period . These findings , in a r and omised placebo-controlled study , therefore demonstrate that pindolol does not influence basal or exercise-stimulated plasma noradrenaline and adrenaline concentrations . This is best explained by a lack of effect of pindolol on the plasma clearance of catecholamines , which is impaired by beta-adrenoceptor blockers devoid of intrinsic sympathomimetic activity", "Summary In a multicentre , double-blind , between-patient study the hypotensive effect of oxprenolol was investigated in 329 patients with mild to moderate hypertension . A factorial experimental design with three factors was chosen : oxprenolol — none or daily doses of 20 , 40 , 60 and 80 mg ; dihydralazine and hydrochlorothiazide , respectively , none or 30 mg daily . Each treatment was given for 4 weeks after an adequate period of withdrawal from any other possible hypotensive therapy and one week of placebo wash-out . Irrespective of the association with dihydralazine and /or hydrochlorothiazide , oxprenolol had a hypotensive effect linearly related to dose for st and ing systolic ( P diastolic ( P pressure , and for lying diastolic ( P pressure . The addition of dihydralazine enhanced the time-course of the hypotensive effect of oxprenolol , particularly the 80 mg dose level . In general , the combination of oxprenolol with dihydralazine and hydrochlorothiazide caused larger reductions in blood pressure , particularly with oxprenolol 80 mg . In the latter group , the eventual falls in blood pressure were 30.5 and 14.4 mmHg for lying systolic and diastolic , respectively ; and 32.1 and 20.0 mmHg for the st and ing systolic and diastolic pressures . The drug was well tolerated ; major side effects ( heart failure and bronchospasm ) occurred in three patients", "Summary Sixteen patients with essential hypertension completed a double blind factorial trial comparing the effects of indapamide ( 2.5 mg daily ) and pindolol ( 10 mg daily ) on blood pressure , heart rate , plasma renin activity and plasma aldosterone concentration . There were four r and omised test phases of eight weeks each during which patients received indapamide alone , pindolol alone , indapamide plus pindolol and no active treatment ( placebo ) . Blood pressure and heart rate were measured every two weeks . Supine mean arterial pressure fell from 117 mm Hg in the placebo phase to 111 mm Hg in the indapamide phase , 106 mm Hg in the pindolol phase and 103 mm Hg in the combined indapamide plus pindolol phase . Factorial analysis confirmed that the hypotensive effects of the two drugs were additive , without evidence of potentiation or antagonism . Indapamide caused significant reductions in plasma potassium and chloride , and increases in plasma bicarbonate and urate concentrations ; it also caused increases in plasma renin activity and aldosterone concentration . These changes are similar to those observed with thiazide diuretics", "1 Thirteen hypertensive patients completed a double-blind comparison of placebo , acebutolol 200 mg twice daily and acebutolol 400 mg once daily , administered for 4 weeks in r and om order . 2 Blood pressure and heart rate were significantly reduced by both acebutolol treatments . The mean reduction of resting pressure 12 h after 200 mg twice daily ( 12/7 mmHg ) was similar to that 24 hr after 400 mg once daily ( 13/9 mmHg ) . 3 Compared to placebo , reductions in exercise heart rate and systolic pressure at 12 h after 200 mg twice daily and 24 h after 400 mg once daily were significant and similar . 4 Beta-adrenoceptor antagonism was also assessed by inhibition of the heart rate response to sublingual glyceryl trinitrate taken in the st and ing position . Both acebutolol treatments reduced the response ; the reduction after twice daily treatment ( mean 25 beats/min ) was significantly greater than after once daily treatment ( mean 19 beats/min ) . 5 There was no difference in blood pressure control between acebutolol administered once and twice daily in a total daily dose of 400 mg", "Summary — To determine the optimal antihypertensive dose of bopindolol , we performed a r and omized double‐blind study in parallel groups . After 15 days of placebo single‐blind , 115 hypertensive patients received daily for 28 days one of 4 doses : 0 mg ( placebo ) , 0.5 mg , 1.0 mg , 2.0 mg . The reduction of supine diastolic blood pressure ( BP ) did not exhibit the pattern of a dose‐effect relationship . The effect of 0.5 mg belonged to the plateau of the dose‐effect curve ( P=0.1 , analysis of variance ) . The reduction of heart rate ( HR ) followed a typical dose‐effect curve , with a plateau beginning with 1 mg ( P = 0.02 ) . A trend toward an increase in the incidence of side‐effects with dosage was observed ( P=0.3 ) . Thus , the optimal antihypertensive dose may be 0.5 mg or less . Previous studies not using parallel r and omized groups suggested an antihypertensive dose ranging from 2 to 4 mg . This study confirms that the dose‐effect curves of beta blockers on HR and BP are dissociated . The dose‐effect curve of HR seems unsuitable for assessing the optimal antihypertensive dose of a beta blocker", "Summary Acebutolol , a new cardioselective beta-adrenoceptor blocking agent , has been evaluated for the treatment of hypertension . Thirty eight previously untreated male patients with essential hypertension received placebo treatment during a 4-week run-in period , and then they were r and omly ( double-blind ) allocated either to continued placebo treatment for three 4-week periods or to treatment with acebutolol 400 , 600 and 1200 mg daily , respectively , for three 4-week periods . Blood pressure and heart rate were recorded at the end of each 4-week period . Treatment with acebutolol produced statistically significant reductions in blood pressure and heart rate as compared to the placebo regimen", "Objectives . The most important risk factors for coronary heart disease are hypercholesterolemia , smoking and hypertension . To find out which one – lowering cholesterol concentration or using antihypertensive treatment-is more effective in modifying the total risk , we conducted a parallel group placebo-controlled study . The goal of the study was to assess the effect of two drugs on the calculated CHD Framingham risk score in subjects with both moderate hypertension and moderate hypercholesterolemia . Design . Celiprolol for hypertension and simvastatin for cholesterol-lowering were given as monotherapy or as combination treatment . The effects of the treatments on the CHD risk scores were calculated after 3 months . A total of 112 patients were r and omized . Results . The total CHD risk decreased in simvastatin and combination groups from 26 % to 19 % and from 26 % to 17 % , respectively . Celiprolol alone decreased the risk from 25 % to 21 % , which was not statistically different from placebo . Conclusions . It can be concluded that subjects with moderate hypercholesterolemia and hypertension benefit more from lipid-lowering treatment with simvastatin than from blood pressure-lowering with beta blocker celiprolol", "The antihypertensive actions of the beta-adrenergic blocking agent , prindolol , and of the diuretic , hydrochlorothiazide , were analysed in a double-blind r and omized 2 X 2 factorial trial in 16 patients . There were four eight-week phases in which patients received prindolol alone , hydrochlorothiazide alone , prindolol plus hydrochlorothiazide in combination , and no treatment . Both drugs were given in fixed doses : prindolol , 10 mg three times per day ; hydrochlorothiazide , 50 mg per day . Blood pressure was measured weekly , alternately at the outpatient clinic and at home . Supine mean arterial pressure ( MAP ) in resting patients fell from 127 mm Hg in the placebo phase to 117 mm Hg with hydrochlorothiazide alone , 116 mm Hg with prindolol alone , and 111 mm Hg with the combination of prindolol and hydrochlorothiazide . ( The st and ard error of difference between treatments was + /-3 - 58 ) . A mean factorial effect of -7 mm Hg for hydrochlorothiazide ( P less than 0 - 01 ) and -8 mm Hg for prindolol ( P less than 0 - 01 ) was obtained , and the two drugs acted in an additive manner . The effects on st and ing blood pressure in resting patients were similar . No serious side effects were noted", "A two-centre , double-blind , placebo controlled , r and omized 3-way crossover study was undertaken to assess the efficacy , tolerability and safety of celiprolol in mild to moderate essential hypertension . A 4-week single-blind placebo run-in/screening period , during which no antihypertensive medication was given , was followed by 3 consecutive 4-week treatment periods with placebo or celiprolol ( 200 mg or 400 mg daily ) . At the end of the 4-week placebo run-in/screening period , 26 hospital out- patients with a seated mean blood pressure ( systolic/diastolic ) of 161.4/101.7 mmHg and a mean pulse rate of 75 beats/min entered the double-blind crossover phase of the study . Results showed that there was no significant difference in seated mean systolic or diastolic blood pressure between 200 mg celiprolol daily ( 149.2/92.3 mmHg ) and 400 mg celiprolol daily ( 149.1/92.5 mmHg ) . However , mean seated systolic and diastolic blood pressures were significantly ( p less than 0.05 ) lower on celiprolol than on placebo ( 157.1/98.2 mmHg ) . Neither dose of celiprolol had a significant effect on seated pulse rate . No patient was withdrawn due to an adverse event and no laboratory assessment outside the normal range was reported to be of any clinical significance . It is concluded that oral celiprolol , 200 mg or 400 mg daily , is effective and well tolerated for controlling mild to moderate essential hypertension . Since both doses had very similar effects on blood pressure there is no advantage in this group of patients for the 400 mg daily dose of celiprolol", "BACKGROUND AND OBJECTIVE In patients with chronic glomerular nephropathy associated arterial hypertension and proteinuria are considered to be cardinal risk factors in the progressive deterioration of renal function . Treatment regimens which reduce proteinuria and hypertension improve prognosis . The effect of the new beta-receptor blockers compared to common ACE-Inhibitors is of special interest . PATIENTS AND METHODS The studied cohort consisted of 11 patients with CGN , hypertension and proteinuria > 400 mg/24 h. Four drugs were given for 4 weeks , doubly blinded and r and omized according to a \" Latin-square design \" : Celiprolol ( beta-1-antagonist , beta-2-agonist , 200 mg/d ) , Atenolol ( selective beta-1-antagonist , 50 mg/d ) , Ramipril ( ACE-inhibitor , 2.5 mg/d ) and placebo . There was a two-week wash-out phase between each of the four treatment phases . At the end of each treatment phase glomerular filtration rate ( GFR ) and effective renal plasma flow ( ERPF ) were measured by inulin and para-amino-hippuric acid ( PAH ) clearance . Proteinuria was determined in the course of a three-day collection period at the end of each treatment phase . During this period blood pressures were measured with a continuous 24-hour blood pressure monitor . RESULTS Mean arterial blood pressure ( MAP ) was significantly reduced , compared with placebo , by all three antihypertensives ( 108 + /- 9 mm Hg with placebo , 98 + /- 12 mg Hg with atenolol , 101 + /- 11 mm Hg with celiprolol and 98 + /- 8 mm Hg with ramipril ; P Celiprolol produced a significant rise In ERPF ( 322 + /- 109 ml/min with placebo , 391 + /- 110 ml/min with celiprolol : P GFR was slightly , but not significantly , reduced by celiprolol and atenolol . Filtration fraction remained unchanged with atenolol and celiprolol , while it was slightly , but not significantly , reduced with ramipril . Compared with the placebo , all three drugs significantly reduced proteinuria ( P atenolol , 1.2 + /- 1.1 g/24 h with celiprolol and 1.4 + /- 1.4 g/24 h with ramipril . CONCLUSION These data indicate that , in addition to ACE inhibitors , the new generation of beta-receptor blockers in particular , because of their vasodilator action , favourably influence proteinuria and renal blood flow in patients with CGN and arterial hypertension", "A double-blind , parallel group comparison study was carried out in 20 diabetic patients with mild to moderate hypertension to assess the effectiveness and tolerance of acebutolol compared with placebo . After a 4-week wash-out period on placebo , patients received either 400 mg acebutolol or placebo once daily for 12 weeks and then placebo for a further 4 weeks . The results showed that acebutolol was more effective than placebo in lowering raised blood pressure in these patients . No deterioration in diabetic control occurred during the study and no significant side-effects of the drug were observed compared with placebo . In particular , the previously described side-effects of beta-blocker therapy in diabetic patients were not observed as a clinical problem in this study", "A placebo-controlled , double-blind clinical trial of alprenolol was carried out in 20 hypertensive Africans . The active drug and placebo were each administered for 8 weeks using a crossover design . Alprenolol was given in the form of a slow-release tablet preparation at a dosage of 200 mg twice daily . Four patients were withdrawn from the study either because of side-effects ( 2 patients ) or non-compliance ( 2 patients ) . The mean reduction in blood pressure obtained in the 16 patients who completed the trial was less than that usually reported in Caucasians" ]

[ "Objective To compare the expression of the seven known P2X receptors in human bladder from male patients with detrusor instability caused by symptomatic bladder outlet obstruction with that from control bladders , using a quantitative reverse transcription‐polymerase chain reaction ( RT‐PCR ) method ", "PURPOSE We measured the membrane electrical characteristics as well as the response to adenosine triphosphate of cells isolated from the suburothelial layer of the bladder . MATERIAL S AND METHODS Suburothelial cells were isolated from biopsy sample s of human bladder by collagenase disruption . Electrophysiological measurements were done under current and voltage clamp to record membrane potential and ionic currents using patch pipettes with a K+ based filling solution . Intracellular [ Ca2 + ] was measured with Fura-2 . RESULTS Cells were different from epithelial cells by their spindle-shaped appearance with projections at either end . The cells stained for vimentin but epithelial and smooth muscle cells did not . The cells had small membrane capacitance ( 27 + /- 16 pF ) and a specific membrane resistance of 90 + /- 48 x 10(9 ) Omega cm2 . Average membrane potential was -63 + /- 14 mV but cells showed spontaneous spikes or r and om fluctuations of membrane potential . A small net inward current was superimposed by a larger outward current . Inward current was attenuated by the removal of extracellular Ca . Outward current showed large spontaneous fluctuations and was greatly decreased by 30 mM tetraethyl ammonium chloride . Adenosine triphosphate ( 30 to 100 microM ) elicited an inward current of about 50 pA and large intracellular Ca2 + transients . CONCLUSIONS These cells are electrically active which , in conjunction with the previous observation of connexin 43 labeling , suggests that they could act as an electrical network . A quantitative model of voltage distribution in such a network after the generation of inward current suggests that individual cells could not act as pacemakers , but rather a group of simultaneously activated cells could exert a peripheral excitatory effect that would amplify the magnitude of the original response . The implication s of this in terms of bladder sensation are discussed", "BACKGROUND An increasing body of evidence suggests a possible role of suburothelial myofibroblasts ( MFs ) in bladder mechanosensation and in the pathophysiology of detrusor overactivity ( DO ) . OBJECTIVE To determine whether markers of MFs , including gap junction protein connexin43 ( Cx43 ) and c-kit have altered immunohistochemical expression in the suburothelium of patients with neurogenic DO ( NDO ) or idiopathic DO ( IDO ) and whether this is affected by successful treatment of DO with botulinum neurotoxin type A ( BoNTA ) . DESIGN , SETTING , AND PARTICIPANTS Patients with NDO ( n=10 ) or IDO ( n=11 ) were treated in a single-centre , open-label study of intradetrusor BoNTA injections . Control tissue was obtained from 10 patients undergoing pelvic-floor repair procedures who had no overactive bladder ( OAB ) symptoms . This study is registered with Clinical Trials.gov , number NCT00662064 . INTERVENTIONS Bladder biopsies performed with flexible cystoscopes were obtained from control subjects and from NDO and IDO patients before BoNTA treatment and at 4 wk and 16 wk after treatment . They were studied with quantitative immunofluorescence using antibodies to connexin 43 ( Cx43 ) , vimentin , and c-kit . MEASUREMENTS Differences in Cx43 , vimentin , and c-kit immunoreactivity between control subjects and NDO or IDO patients ( primary outcomes ) . Changes in NDO or IDO , Cx43 immunoreactivity , and c-kit immunoreactivity after BoNTA treatment ( secondary outcomes ) . RESULTS AND LIMITATIONS Cx43 immunoreactivity was increased in both IDO and NDO patients compared to controls , but remained unchanged after BoNTA treatment . C-kit immunoreactivity was similar in NDO/IDO patients and controls and remained unchanged after BoNTA treatment . CONCLUSIONS Increased gap junction formation in the suburothelium has been demonstrated in biopsies from humans with DO . It is hypothesised that this change could have a significant role in the pathogenesis of the detrusor abnormality . Successful treatment of NDO or IDO does not appear to be associated with changes in the expression of Cx43 or c-kit on suburothelial MFs", "To compare PGP9.5 and transient receptor potential vanilloid receptor ( TRPV1 ) suburothelial immunoreactivity between controls and patients with spinal neurogenic detrusor overactivity ( NDO ) before and after treatment with intravesical resiniferatoxin , as suburothelial PGP9.5‐staining nerve fibres decrease in patients with spinal NDO who respond to intravesical capsaicin , and TRPV1 is present on these suburothelial nerve fibres in normal and overactive human urinary bladder " ]

[ "Background : CPP-ACP ( Phosphopeptide-Amorphous Calcium Phosphate ) has an important role in caries prevention in pediatric patients . This study was done , because of the great use of CPP-ACP and the need for restoration for teeth treated with CPP-ACP as well as the importance of shear bond strength of adhesives in the success of restorations . Objectives : This study aim ed to evaluate the effect of casein phosphopeptide-amorphous calcium phosphate ( CPP-ACP ) on shear bond strength of dental adhesives to enamel of primary teeth molars . Material s and Methods : This in vitro study was conducted on 180 extracted primary molars . They were r and omly divided into 6 groups and each group was divided into 2 subgroups ( treated with CPP-ACP and untreated ) . In subgroups with CPP-ACP , enamel was treated with CPP-ACP paste 1 h/d for 5 days . Types of adhesives that were evaluated in this study were Tetric N-Bond , AdheSE , AdheSE One F , single Bond 2 , SE Bond , and Adper Prompt L-Pop . Shear bond strength was tested with a universal testing machine and mode of failure was evaluated under stereomicroscope . Data were analyzed by T test , 2-way analysis of variance ( ANOVA ) , Tukey and Fisher exact test using SPSS18 . P Shear bond strengths of different adhesive systems to enamel of primary teeth treated and untreated with CPP-ACP showed no significant difference ( P > 0.05 ) . Mode of failure in all groups regardless of CPP-ACP administration was mainly adhesive type . Our results indicated that CPP-ACP did not affect shear bond strength of studied adhesives to primary teeth enamel . Conclusions : To have a successful and durable composite restoration , having a high strength bonding is essential . Considering the wide use of CPP-ACP in preventing tooth decay and the role of adhesive shear bond strength ( SBS ) in success of composite restoration , we conducted the present study to evaluate the effect of CPP-ACP on the SBS of adhesives to primary teeth enamel", "PURPOSE The aims of this in vitro study were to : ( 1 ) compare bond strength of different adhesive systems to primary and permanent dentin using microtensile test ; and ( 2 ) evaluate the interaction of these material s to primary and permanent dentin by means of scanning electron microscopy ( SEM ) . METHODS Middle-coronal dentin surfaces of 18 exfoliated primary and 18 extracted permanent molars were exposed and teeth were r and omly divided , according to their adhesive system , into 3 groups ( N=6 per group ) : ( 1 ) Clearfil SE Bond ( SE ) ; ( 2 ) One Up Bond F ( OU ) ; and ( 3 ) Single Bond ( SB ) . Then , 5-mm high composite blocks were constructed . After bonding procedures , the teeth were stored in distilled water at 37 degrees C for 24 hours prior to the specimens ' preparation . For the microtensile test , teeth ( N=5 per group ) were longitudinally sectioned into 2 axes rendering beam-specimens that were glued to special devices , which were mounted in a Universal Testing Machine to be loaded under a crosshead speed of 1 mm/min until fracture . One tooth of each group was prepared for SEM . RESULTS Microtensile bond strength mean values ( MPa ) to primary /permanent dentin were : ( 1 ) SE=60.0/61.4 ; ( 2 ) OU=54.5/53.3 ; and ( 3 ) SB=70.1/64.9 . Two-way analysis of variance ( ANOVA ) showed no significant differences ( P>.05 ) for the bond strength values among primary and permanent dentin groups , neither among groups SExSB and SExOU . SEM images of SE and SB showed a well-defined , uniform , and continuous hybrid layer . A continuous hybrid layer , however , was not found for OU . CONCLUSIONS Bond strength and micromorphologic characteristics of the adhesive systems evaluated were not influenced by the substrate . OU achieved worse results", "PURPOSE The purpose of this study was to evaluate the effect of the material s used for indirect pulp treatment ( IPT ) on the long-term outcome of primary molar teeth . METHODS Forty-eight teeth with deep carious lesions , but without signs and symptoms of irreversible pulpitis , were r and omly divided into 2 groups , according to the material placed on the demineralized dentin remain : ( 1 ) experimental group , adhesive system ( Scotchbond Multi purpose ) ; and ( 2 ) control group , calcium hydroxide liner ( Dycal ) . Both groups were followed by a resin restoration application . RESULTS After 4 to 5 years , the clinical and radiographic success rates between groups were similar ( group 1=14 of 15 ; group 2=8 of 10 ; P=0.350 ) . Subsequent to exfoliation , scanning electron microscopy revealed the presence of a hybrid layer at the resin-dentin interface and a microtensile bond strength of 9.63 MPa ( group 1 ) . Histological analysis showed that the pulp health status was similar in both groups . CONCLUSIONS Indirect pulp treatment has a high clinical and radiographic long-term success rate in primary teeth and is not material -dependent", "PURPOSE To investigate the bonding of a new universal adhesive applied using different etching strategies on sound and caries-affected dentin of primary teeth . MATERIAL S AND METHODS Flat dentin surfaces from 50 primary molars were r and omly assigned to 10 groups according to substrate ( sound dentin [ SD ] vs caries-affected dentin [ CAD ] pH cycled for 14 days ) and bonding approach ( Scotchbond Universal Adhesive : self-etching , vs dry or wet-bonding etch- and -rinse strategies ; Adper Single Bond Plus [ two-step etch- and -rinse adhesive ] and Clearfil SE Bond [ two-step self-etching system ] as controls ) . After 24 h of water storage , bonded sticks with cross-sectional areas of 0.8 mm2 were tested for microtensile bond strength ( μTBS ) . Two sticks from each tooth were immersed in silver nitrate solution in order to evaluate nanoleakage ( NL ) with SEM . The μTBS means were analyzed using two-way ANOVA and Tukey 's tests . For NL , the Kruskal-Wallis and Mann-Whitney tests were used ( α = 0.05 ) . RESULTS The influence of the etching strategy on the bonding performance of the universal adhesive was substrate dependent . The self-etching approach result ed in lower μTBS values and higher silver nitrate uptake into hybrid layers for Scotchbond Universal Adhesive on SD , while no difference among experimental groups was observed in CAD . CONCLUSION It is preferable to use the universal adhesive following either a dry- or wet-bonding etch- and -rinse approach on both sound and caries-affected primary dentin ", "The aims of this study were to evaluate the shear bond strength ( SBS ) off our adhesive systenms applied to primary dentin and enamel and verify , after SBS testing , the failure mode of the adhesive interface . Sixty extracted sound primary molars were selected and crowns were sectioned in a mesial-distal direction . Specimens were r and omly assigned into two groups ( adhesion to enamel and adhesion to dentin ) and then subdivided into four subgroups according to the adhesive system ( n=15 ) . Scotchbond Multi- Purpose (SMP)--Single Bond (SB)--Clearfil SE Bond ( and Adper Prompt L-Pop (APL)--SBS tests were performed and the obtained values were statistically analyzed using ANOVA and Tukey tests ( p failure mode analysis was performed with a Scanning Electron Microscope ( XL-30 , Philips ) . SBS mean values on enamel were [ MPa ( SD ) ] : SMP--2789 ( 749 ) ; SB--23.92 ( 8.8 ) ; CSB--24.36 ( 6.69 ) , APL--25.96 ( 4.08 ) ; and on dentin : SMP--17.29 ( 4.25 ) SB--18.2 ( 8.74 ) ; CSB--16.13 ( 714 ) ; APL--6 . 04 ( 3.35 ) . The predominant failure mode was cohesive ( primarily of the bonding agent ) . On enamel SBS was statistically similar for all four adhesives . On dentin SBS ofAPL was lower than the other tested adhesives", "PURPOSE The objective of this study was to assess in vitro the tensile bond strength of a self-etching and 2 total-etch , single-bottle adhesive systems to primary dentin . METHODS Thirty-six sound primary canine buccal surfaces were r and omly assigned to 3 groups ( N = 12 ) , corresponding to the tested adhesive systems : ( 1 ) group I = Excite ( EX ) ; ( 2 ) group II = Single Bond ( SB ) ; and ( 3 ) group III = Prompt L-Pop ( PLP ) . After 24-hour storage in distilled water , tensile bond strength was tested for failure at a crosshead speed of 0.5 mm/min . RESULTS Means ( MPa ) and st and ard deviation ( + /- ) were : ( 1 ) EX = 12.72 ( + /- .89 ) ; ( 2 ) SB = 10.86 ( + /- 2.09 ) ; ( 3 ) PLP = 8.66 ( + /- 2.23 ) . Single Bond and Excite showed statistically similar results ( P > .05 ) and provided the highest means . Prompt L-Pop was statistically different from the other groups ( P bond strength to primary dentin . CONCLUSIONS Total-etch agents provided the best overall bonding performance , whereas the all-in-one , self-etching , self-priming adhesive system yielded remarkably lower bond strength to primary teeth dentin", "BACKGROUND The objec tives of this study were to determine microtensile bond strengths of two dentin adhesives and to compare the micromorphological structure of the resin/dentin interface in caries-affected dentin with that of intact dentin . METHODS The authors r and omly divided 40 proximal dentinal carious primary teeth and 40 noncarious anterior primary teeth into two groups ( self-etching and total-etching ) . They used a caries-detecting dye as an indicator of the need to remove the outer carious dentin . The authors restored the teeth with a hybrid resin-based composite . After 24 hours ' storage in 37 C water , specimens were sectioned and shaped to form a curved section with a cross-sectional area of 1 square millimeter , then tension was applied until they fractured . The authors prepared the resin/dentin interfaces for the two bonding systems and examined them in 10 occlusal carious and 10 noncarious teeth . STATISTICAL ANALYSIS The bond strengths for intact and caries-affected dentin within the same group were analyzed via a t test . The authors compared the remaining dentin thickness ( RDT ) and dentin hardness using analysis of variance and the least significant difference test at the .05 level of significance . RESULTS The self-etching adhesive demonstrated no statistical difference in bond strength between intact and caries-affected dentin . However , the total-etching adhesive demonstrated different bond strengths for intact and caries-affected dentin . Moreover , the RDT of specimens with intact and caries-affected dentin was not significantly different , whereas the dentin hardness of caries-affected dentin was significantly lower than that of intact dentin . The authors found a thicker hybrid layer in intact and caries-affected dentin of specimens in the total-etching group . CONCLUSION The adhesives exhibited significantly different bond strengths in intact dentin of primary teeth . However , they exhibited similar bond strengths in caries-affected dentin", "PURPOSE To evaluate the bonding of simplified adhesive systems to sound and caries-affected dentin of primary teeth with microtensile ( µTBS ) and nanoleakage ( NL ) tests . MATERIAL S AND METHODS Occlusal cavities were prepared in 36 sound second primary molars . Half of the specimens were su bmi tted to pH cycling to simulate caries-affected dentin . Teeth were r and omly restored with one of three material s : the etch- and -rinse adhesive system Adper Single Bond 2 ( SB ) , the two-step self-etching adhesive system Adper SE Plus ( SE ) , and the one-step self-etching adhesive system Adper Easy One ( EASY ) . After storage for 24 h , specimens with cross-sectional areas of 0.8 mm2 were prepared for microtensile testing ( 1 mm/min ) . One stick from each tooth was immersed in silver nitrate solution ( 24 h ) and allowed to develop for 8 h in order to score the nano leakage with SEM . The fracture pattern was evaluated using a stereomicroscope ( 400X ) . The µTBS means were analyzed by two-way ANOVA and Tukey 's post-hoc test . For NL , the Kruskal- Wallis and Mann-Whitney tests were used ( α highest µTBS value to sound dentin , followed by EASY ( 26.3 ± 1.9 ) and SE ( 18.2 ± 6.5 ) ( p caries-affected dentin ( SB : 17.8 ± 4.2 ; SE : 13.9 ± 3.2 ; EASY : 14.4 ± 4.2 , p > 0.05 ) . For all groups , adhesive/mixed fracture prevailed . Caries affected dentin promoted silver nitrate uptake into the adhesive interface ; however , with SE , the nano leakage was more pronounced than in the other adhesive systems , even in sound dentin . CONCLUSION Caries-affected dentin negatively influences the bond strength and nano leakage of the two-step etch- and -rinse and one-step self-etching adhesive systems tested in primary teeth", "OBJECTIVES To evaluate the effect of shortening the etching time on roughness , microhardness and bond strength of three adhesive systems to primary tooth dentin . METHODS Flat dentin surfaces from primary molars were r and omly assigned to six experimental groups . Three different adhesive systems were used : an etch- and -rinse adhesive ( Single Bond ) , a two-step self-etching ( Clearfil SE Bond ) , and a one-step self-etching ( One-Up Bond F ) adhesive . In half of the specimens , the recommended etching time was used , in the other half the etching time was 50 % reduced . After applying the adhesive , resin composite build-ups were constructed and stored in a humid environment for 24h at 37 degrees C. Specimens were sectioned into 1mm(2 ) beams and tested for microtensile bond strength ( MTBS ) . Debonded surfaces were analyzed by scanning electron microscopy ( SEM ) . Additional surfaces were conditioned for microhardness measurements ( KHN ) and for atomic force microscopy ( AFM ) analysis . Intertubular and total surface roughness ( Ra ) were recorded . Results were analyzed with ANOVA and Student-Newman-Keuls tests ( P MTBS than One-Up Bond F. Bond strength and intertubular roughness increased when Single Bond and One-Up Bond F were used with a reduced etching time . For Clearfil SE Bond no differences in MTBS were detected when reducing the etching time . The application of phosphoric acid , Clearfil SE Bond primer and One-Up Bond F decreases dentin microhardness . CONCLUSIONS Shortening One-Up Bond F application time and reducing the etching time of phosphoric acid to one-half of the manufacturer 's recommended etching time when using Single Bond are recommended when bonding to primary dentin", "PURPOSE The purpose of this study was to assess in vitro the shear bond strength of self-etching and total-etch adhesive systems to Er : YAG laser-irradiated primary dentin . METHODS Forty crowns of primary canines were embedded in acrylic resin and mechanically ground to expose a flat dentin surface . The specimens were r and omly assigned to 2 groups ( N=20 ) , according to the adhesive system : ( A ) Single Bond ( SB ) ; and ( B ) Adper Prompt ( AP ) . Each group was divided into 2 subgroups ( N=10 ) , depending on the surface treatment : ( 1 ) conventional bonding protocol , as recommended by the manufacturers ; and ( 2 ) irradiation of the dentin site with a 2.94-microm wavelength Er : YAG laser , with a 300-mJ pulse energy and a 2-Hz repetition rate followed by the bonding protocol . In both groups , a 3-mm diameter dentin bonding site was demarcated , the adhesive systems were applied , and resin composite cylinders were bonded . After 24 hours in distilled water , shear bond strength was tested at a crosshead speed of 0.5 mm/minute . RESULTS Means ( in MPa ) were : group A1=14.14(+/-1.7 ) ; group A2=8.41(+/-1.04 ) ; group B1=6.88(+/-1.12 ) ; and group B2=4.19(+/-0.7 ) . Data were su bmi tted to statistical analysis using 2-way analysis of variance and t test at 5 % significance level . CONCLUSION Irradiation of primary dentin with the Er : YAG laser decreased the bond strength of total-etch and self-etching adhesive systems", "PURPOSE The aim of this study was to evaluate the effect of sodium hypochlorite ( NaOCl ) on the shear bond strength ( SBS ) using three bonding systems in primary dentin . MATERIAL S AND METHODS Forty-five sound extracted primary molars were selected . The crowns were longitudinally sectioned , embedded in polystyrene resin , and flattened until a dentin surface was reached . The sample s were assigned to 6 groups ( n = 15 ) : G1 , Single Bond ( SB ) ; G2 , NaOCl + SB ; G3 , Prime & Bond 2.1 ( PB ) ; G4 , NaOCl + PB ; G5 , Clearfil SE Bond ( CSE ) ; G6 , NaOCl + CSE . All the adhesive systems were applied according to the manufacturers ' instructions , except for the application of 10 % NaOCl solution for 60 s in groups 2 , 4 ( after acid etching ) , and 6 ( before applying adhesive system ) . The composite resin was placed in increments in a mold and light cured for 20 s. The sample s were stored in distilled water at 37 degrees C for 24 h and su bmi tted to SBS testing with a crosshead speed of 0.5 mm/min . The failure sites were observed with SEM . The data were treated with ANOVA and Tukey 's tests ( p statistically significant difference between the groups with or without treatment of the substrate with NaOCl , regardless the material used . The SBS averages in MPa ( + /-SD ) were : G1 : 15.8(1.9)a ; G2 : 14.6(1.3)a ; G3 : 10.2(0.7)a ; G4 : 9.9(0.2)a ; G5 : 13.3(1.2)a ; and G6 : 10.7(1.0)a . There was a statistically significant difference between the material s ( SB > or = CSE > or = PB ) . Mixed failure was the failure type most frequently observed for all groups . CONCLUSION Dentin surface treatment with NaOCl did not affect the resin-dentin bonding strength in primary teeth", "OBJECTIVE The aim of this study was to evaluate the shear bond strength to dentin of primary molars of a new self-adhering flowable resin composite with two ionomer-based cements and one flowable resin composite in combination with two different adhesive systems . STUDY DESIGN Fifty primary molars were grinded on the occlusal surface to obtain flat dentin substrate and r and omly divided into 5 groups ( n = 10 ) : OFL : Phosphoric Acid/Optibond FL/Premise Flow ; OAO : Optibond All-In-One/Premise Flowable ; II : Polyacrylic Acid/Fuji II ; IX : Polyacrylic Acid/Fuji IX ; V : Vertise Flow . Cylinders ( 3 mm diameter - 5 mm height ) of restorative material were built-up in three increments over the dentin surfaces . A shear load was applied until failure . Bond strength values were statistically analysed with Kruskall-Wallis ANOVA followed by Dunn 's test ( P failure mode distribution were assessed with Chi-square ( P bond strengths than the other groups . Adhesive failures were evident in all groups except OFL and OAO , in which also cohesive failures in dentin were observed . CONCLUSIONS Vertise Flow established on primary dentin bond strengths values similar to those of glass ionomer cements routinely used for restorations of primary teeth . The combination of flowable resin with etch- and -rinse or all-in-one adhesives obtained higher bond strength values , thus involving a more complex h and ling", "OBJECTIVE This r and omised clinical trial evaluated the survival rate of resin-based restorations in Class I and Class II beveled preparations in primary molars , over 48 months . METHODS Forty-eight children received 141 restorations in beveled cavosurface margin preparations in primary molars r and omly assigned by a lottery method : 46 received treatment with Vitremer Tri-Cure Glass Ionomer System ( 33 Class I and 13 Class II restorations ) ; 51 received treatment with Freedom ( 36 Class I and 15 Class II restorations ) ; 44 received treatment with TPH Spectrum ( 30 Class I and 14 Class II restorations ) . Two calibrated examiners ( weight kappa > or = 0.85 ) evaluated the restorations using the modified USPHS criteria and visible plaque index score at baseline and after 12 , 24 , 36 and 48 months . Cox regression with survival analysis and logistic regression evaluated the clinical performance of restorations . RESULTS After 48 months , 11 teeth had exfoliated , 16 restorations were dropouts , 83 restorations were clinical ly successful of which 26 had used Vitremer , 32 had used Freedom and 25 had used TPH Spectrum . Thirty-one restorations failed because of secondary caries , fractures and loss of retention . The cumulative survival was 73.9 % , 83.4 % and 79.6 % , respectively for Vitremer , Freedom and THP Spectrum with no differences among material s ( Log Rank Mantel-Cox , p>0.05 ) . However , the Class II cavity preparation reduced the survival of the restorations ( OR=5.1 ) for all material s evaluated ( p>0.05 ) . CONCLUSIONS The life expectancy of Vitremer , Freedom and THP Spectrum in Class I and Class II restorations could be comparable after 48 months", "PURPOSE To evaluate the effect of cariogenic challenge on the bond strength of adhesive systems to sound and artificially demineralized enamel of primary and permanent teeth . MATERIAL S AND METHODS Eighty molars ( 40 primary , 40 permanent ) were r and omly assigned to 16 groups ( n = 5 ) according to the type of tooth ( primary [ PRIM ] or permanent [ PERM ] ) , enamel condition ( sound [ S ] or demineralized [ DEM ] ) , treatment after the restorative procedure ( control [ C ] or cariogenic challenge [ pH ] ) , and adhesive system ( Adper Single Bond [ SB ] or Clearfil SE Bond [ SE ] ) . Teeth from the DEM group were subjected to cariogenic challenge by pH cycling prior to restorative procedures and pH group specimens were subjected to cariogenic challenge before the microshear test . One of two adhesive systems was applied to the flat enamel surfaces and composite cylinders ( 0.45 mm2 ) were built . The microshear bond test was performed . The data ( MPa ) were subjected to ANOVA and Tukey 's test ( α = 0.05 ) . RESULTS No statistically significant differences were detected between the adhesive systems . The S groups exhibited higher bond strength values than the DEM groups , as did C groups compared to pH groups . PERM groups also had higher bond strength values than PRIM groups , excluding PRIM S and PERM S , which had similar values . CONCLUSION The bond strength to demineralized enamel of primary teeth was lower than to the demineralized enamel of permanent teeth . Cariogenic challenge negatively influenced enamel bond strength , regardless of the type of tooth and adhesive system", "The bonding performance of current adhesive systems to primary enamel has not been thoroughly research ed . This study compared the micro-shear bond strength of two adhesive systems to primary and permanent tooth enamel . Two commercially available resin adhesives , a self-etching primer system ( Clearfil SE Bond ) and a single-bottle adhesive system ( Single Bond ) used with a total-etch wet bonding technique were tested . A micro-shear bond test was used to examine the adhesive systems on mid-coronal buccal enamel of extracted primary or permanent teeth . In addition , etched enamel surfaces and etched-bonded enamel interfaces were examined using scanning electron microscopy ( SEM ) . No statistically significant differences of shear bond strength values were found between the primary and permanent enamel or the adhesive systems used ( p>0.01 ) . The SEM observations showed that both adhesive systems etched the primary enamel deeper than the permanent enamel , suggesting that the action of acid etch seemed to be more intense on primary enamel than on permanent enamel . Bonding of the adhesive systems to primary enamel was almost identical to permanent enamel", "PURPOSE To evaluate the effect of chemical and microbiological methods of caries induction on microtensile bond strength ( μTBS ) of current adhesive systems to primary dentin . MATERIAL S AND METHODS Flat dentin surfaces from 36 primary molars were assigned to 3 groups according to the method of inducing caries-affected dentin : ( 1 ) control ( sound dentin ) ; ( 2 ) pH cycling ; and ( 3 ) microbiological . In both methods , teeth were su bmi tted to caries induction for 14 days , and the sound dentin was stored in distilled water for the same period . Specimens were then r and omly reassigned according to adhesive system : a two-step etch- and -rinse adhesive ( Adper Single Bond 2 ) or a two-step self-etching system ( Clearfil SE Bond ) . Composite buildups were constructed and the teeth were sectioned to obtain bonded sticks ( 0.8 mm2 ) to be tested for microtensile bond strength . The μTBS means were analyzed by two-way ANOVA and Tukey 's tests ( α = 0.05 ) . Failure mode was evaluated using a stereomicroscope ( 400X ) . RESULTS Both methods of caries induction result ed in lower μTBS values ( with no significant difference between them ) than those obtained for sound dentin . Adhesive systems showed similar bond strength values . The percentage of premature failure was higher in the microbiological group , regardless of adhesive system . CONCLUSION Microbiological and pH-cycling methods are both suitable for simulating caries-affected dentin for bonding evaluations in primary teeth", "PURPOSE To investigate the influence of etching time on the degradation of resin-dentin bonds produced in primary teeth . METHODS 40 primary molars were r and omly divided into four groups according to the adhesive system , Single Bond ( SB ) and Clearfil SE Bond ( CSEB ) , and acid etching time . SB was applied to dentin after phosphoric acid etching for 15 or 7 seconds , whereas CSEB was applied after the application of SE Primer for 20 or 10 seconds . Resin composite crowns were built-up followed by the production of specimens with a cross-sectional area of 0.49 mm2 , which were further divided according to the storage condition , 24 hours , 6 and 12 months in water . Data were su bmi tted to ANOVA and Tukey tests ( alpha=0.05 ) . RESULTS After 24 hours there was no significant difference between bond strengths produced by the adhesive systems , irrespective of the acid etching time . Water storage for 6 and 12 months significantly reduced bond strengths of SB , especially when the dentin was acid etched for 15 seconds . For CSEB , no significant alteration in bond strength was seen up to the storage period of 12 months for both etching times", "OBJECTIVES To verify whether substrate , shape , or thickness of microtensile specimens have a significant influence on their measured bond strength . METHODS Sixty-four extracted molars provided microtensile specimens , which were prepared on enamel and dentin , in different shapes and thicknesses . The teeth were r and omly divided into 16 groups ( n = 4 ) . Groups 1 - 8 included hourglass-shaped specimens . In Groups 1 - 4 specimens were prepared from enamel and in a thickness at the bonding interface of 0.5 mm x 0.5 mm , 1 mm x 1 mm , 1.5 mm x 1.5 mm , and 2 mm x 2 mm , respectively . In these same thicknesses , hourglasses were trimmed in Groups 5 - 8 , but the specimens were prepared from dentin . Groups 9 - 16 included specimens obtained following the non-trimming technique . Groups 9 - 12 provided enamel sticks in the four evaluated thicknesses . In these same thicknesses and shape but from dentin were cut the specimens of Groups 13 - 16 . Two specimens from each group were viewed using a scanning electron microscope . On the other ones , microtensile bond strength was measured and the values were statistically analyzed . RESULTS Substrate , shape , and thickness of the specimens had a significant effect on their recorded bond strength ( p bond strength values were recorded by dentin versus enamel specimens and by sticks versus hourglasses . Also , bond strength decreased as specimen thickness increased . SEM analysis revealed that the trimmed specimens , especially if from enamel , often exhibited lines of fracture in the area of action of the bur . SIGNIFICANCE It seems advisable to avoid the trimming action particularly on enamel specimens . If the hourglass shape is preferred , the cross-sectional area should not exceed 1 mm x 1 mm", "AIM The aim of this in vitro study is to evaluate the effects of three different caries removal techniques on the microtensile bond strength of adhesive material s to caries-affected dentin . MATERIAL S AND METHODS Thirty primary molar teeth were used . The teeth were r and omly divided into three groups according to the caries removal technique employed : conventional steel bur ( group 1 ) ; Er : YAG laser ( group 2 ) ; chemomechanical method ( group 3 ) . Each group was divided into two subgroups according to bonding agents : one-step self-etch adhesive and etch- and -rinse adhesive . The teeth were restored with composite resin . Vertical sticks were obtained and subjected to tensile stress . Data were analyzed by two-way analysis of variance ( ANOVA ) , Tukey 's test and an independent sample s t-test . RESULTS The values for the laser groups were significantly lower than those of the bur groups for both bonding agents ( p chemomechanical groups ( p > 0.05 ) . CONCLUSION Bur and chemomechanical techniques in primary teeth were found more successful . Similar results were found according to the adhesives used for each caries removal techniques", "OBJECTIVE The aim of this study was to investigate the influence of shortening the etching time on the bond strength of a conventional and a self-etching primer adhesive system used in primary tooth dentin . METHODS Flat dentin surfaces were obtained from 24 primary molars , r and omly assigned to 4 experimental groups . The adhesive systems Single Bond and Clearfil SE Bond were applied in two groups according to the manufacturers ' recommendations . In the other two groups , the adhesives were applied after half-time of acid etching , 7 s for Single Bond and 10 s for Clearfil SE Primer . Resin crowns were built up and after 24 h storage in water at 37 degrees C , the teeth were sectioned to produce beams with cross-sectional area of approximately 0.49 mm2 . Specimens were tested in tension at 0.5 mm/min until failure . Fractured specimens were analyzed to determine the failure mode . RESULTS Tensile bond strengths for Single Bond in primary dentin were higher than for Clearfil SE Bond . Shortening of acid etching time improved bond strength only for Single Bond , while no statistically significant difference was observed for Clearfil SE Bond when both etching times were compared . SIGNIFICANCE No detrimental effect on bond strength was observed when the time of acid etching was shortened in 50 % . Shortening the time for a procedure in a small child without compromising the quality of the work is a very important finding for the practicing pediatric dentist", "PURPOSE To evaluate the clinical performance of adhesive restorations of resin composite and resin-modified glass-ionomer cements in primary molars . METHODS This r and omized clinical trial included subjects ( 5 - 9 year-old children ) selected at two university centers ( UFRGS and UNIFRA ) . The sample consisted of 132 primary molars presenting active cavitated carious lesions ( with radiographic involvement of the inner half of the dentin ) , located on the occlusal and occlusal-proximal surface . The sample was r and omly divided into three groups , according to the restorative material : ( G1 ) universal restorative system ( Adper Single Bond 2 system and Filtek Z350 ) ; ( G2 ) : Resin-modified glass-ionomer cement ( Vitremer ) ; and ( G3 ) : Low shrink restorative system ( Filtek P90 ) . The restorations were clinical ly and radiographically followed every 6 months for up to 18 months using the USPHS modified criteria for clinical evaluation . Survival estimates for restoration longevity were evaluated using the Kaplan-Meier method . Log-rank test ( P success rate according to the type of the restorative material . RESULTS The type of restorative material used did not influence the longevity of the restorations . After clinical follow-up , there was no statistical difference in the rates of success for the three material s used to restore active cavitated carious lesions in primary molars . The survival rates for the follow-up were similar regarding the number of restored surfaces and the caries removal technique ( partial or complete ) . Mean estimated time of survival was 17.2 months ( 95 % CI : 16.7 - 17.7 ) . Estimated survival rates of the restorations were 100 % , 98 % , 88 % and 65 % at 1 , 6 , 12 and 18 months of clinical evaluations , respectively", "OBJECTIVES To verify the influence of cutting speed during microtensile specimen preparation , on bond strength values and on the sample microscopic integrity of a single-bottle adhesive system to enamel and dentin . METHODS Thirty sound human third molars were restored with light-cured Excite and Tetric Ceram according to manufacturers ' instructions , being half in ground enamel [ E ] , and half in flat dentin [ D ] . After 24 h storage in distilled water at 37 degrees C , the restored teeth were sectioned in x and y-axes under different cutting speed : 100 , 200 or 400 RPM , obtaining stick shaped specimens with cross-sectional area of 1.0 mm(2 ) . Five specimens from each experimental group were r and omly selected before being loaded for SEM analysis , while the remaining sample s were subjected to the microtensile bond strength test . Because the variance of dentin specimens was significantly higher than the variance of enamel sample s , analysis of the influence of the cutting speed was performed separately , by substrate . RESULTS The mean values in MPa were calculated including/excluding premature failures : E1 : 24.67/27.31(a ) ; E2 : 24.03/25.81(a ) ; E4 : 19.06/21.52(b ) ; D1 : 35.80/36.33(A ) ; D2 : 35.84/36.65(A ) ; D4 : 37.78/38.50(A ) . In the SEM analysis , better integrity of the dentin specimens was observed when compared to the enamel sample s , for which the integrity was greater in the lower cutting speed groups . SIGNIFICANCE It can be concluded that the cutting speed is an important factor that should be considered , mainly when enamel is involved , since it may affect the bond strength results and the integrity of the specimens" ]

[ "In practice the secondary prevention of work-related upper extremity ( WRUE ) symptoms generally targets biomechanical risk factors . Psychosocial risk factors have also been shown to play an important role in the development of WRUE symptom severity and future disability . The addition of a stress management component to biomechanically focused interventions may result in greater improvements in WRUE symptoms and functional limitations than intervening in the biomechanical risk factors alone . Seventy office workers with WRUE symptoms were r and omly assigned to an ergonomics intervention group ( assessment and modification of work station and stretching exercises ) or a combined ergonomic and job stress intervention group ( ergonomic intervention plus two 1-h workshops on the identification and management of workplace stress ) . Baseline , 3- and 12-month follow-up measures of observed ergonomic risks and self-reported ergonomic risks , job stress , pain , symptoms , functional limitation , and general physical and mental health were obtained from all participants . While both groups experienced significant decreases in pain , symptoms , and functional limitation from baseline to three months with improvements continuing to 12 months post baseline , no significant differences between groups were observed for any outcome measures . Findings indicate that the additional two-session job stress management component did not significantly enhance the short- or long-term improvements brought about by the ergonomic intervention alone", "BACKGROUND A prospect i ve study of computer users was performed to determine the occurrence of and evaluate risk factors for neck or shoulder ( N/S ) and h and or arm ( H/A ) musculoskeletal symptoms ( MSS ) and disorders ( MSD ) . METHODS Individuals ( n = 632 ) newly hired into jobs requiring > or = 15 hr/week of computer use were followed for up to 3 years . At study entry , workstation dimensions and worker postures were measured and medical and psychosocial risk factors were assessed . Daily diaries were used to document work practice s and incident MSS . Those reporting MSS were examined for specific MSD . Incidence rates of MSS and MSD were estimated with survival analysis . Cox regression models were used to evaluate associations between participant characteristics at entry and MSS and MSD . RESULTS The annual incidence of N/S MSS was 58 cases/100 person-years and of N/S MSD was 35 cases/100 person-years . The most common N/S MSD was somatic pain syndrome . The annual incidence of H/A MSS was 39 cases/100 person-years and of H/A MSD was 21 cases/100 person-years . The most common H/A disorder was deQuervain 's tendonitis . Forty-six percent of N/S and 32 % of H/A MSS occurred during the first month of follow-up . Gender , age , ethnicity , and prior history of N/S pain were associated with N/S MSS and MSD . Gender , prior history of H/A pain , prior computer use , and children at home were associated with either H/A MSS or MSD . CONCLUSIONS H/A and N/S MSS and MSD were common among computer users . More than 50 % of computer users reported MSS during the first year after starting a new job", "This study examined the effects of supplementary rest breaks on musculoskeletal discomfort , eyestrain , mood , and performance in data -entry workers . Two rest break schedules were compared in a within-subjects design . Workers alternated between a ‘ conventional ’ and a ‘ supplementary ’ schedule in 4-week intervals . The conventional schedule contained a 15-min break during the first half of the work shift and a 15-min break during the second half of the shift . The supplementary schedule contained the same two 15-min breaks , and a 5-min break during each hour which otherwise did not contain a break , for a total of 20 extra minutes of break time . Results are based on data from 42 workers . They indicated that discomfort in several areas of the body , and eyestrain , were significantly lower under the supplementary than under the conventional schedule . While symptoms increased from pre- to post-work periods under both schedules , the magnitude of the increases was significantly less under the supplementary schedule . In addition , increases in discomfort of the right forearm , wrist and h and over the course of the work week under the conventional schedule were eliminated under the supplementary schedule . These beneficial effects were obtained without reductions in data -entry performance", "This r and omized clinical trial evaluated the effects of keyboard keyswitch design on computer users with h and paresthesias . Twenty computer users were matched and r and omly assigned to keyboard A ( n = 10 ) or B ( n = 10 ) . The keyboards were of conventional layout and differed in keyswitch design . Various outcome measures were assessed during the 12 weeks of use . Subjects assigned keyboard A experienced a decrease in h and pain between weeks 6 and 12 when compared with keyboard B subjects ( P = 0.05 ) and demonstrated an improvement in the Phalen test time ( right h and , P = 0.006 ; left h and , P = 0.06 ) . Keyboard assignment had no significant effect on change in h and function or median nerve latency . We conclude that use of keyboard A for 12 weeks led to a reduction in h and pain and an improved physical examination finding when compared with keyboard B. There was no corresponding improvement in h and function or median nerve latency", "OBJECTIVES This study evaluated the effects on work-related neck and upper-limb disorders among computer workers stimulated ( by a software program ) to take regular breaks and perform physical exercises . Possible effects on sick leave and productivity were studied as well . A r and omized controlled design was used with cluster r and omization . Altogether 268 computer workers with complaints in the neck or an upper limb from 22 office locations were r and omized into a control group , one intervention group stimulated to take extra breaks and one intervention group stimulated to perform exercises during the extra breaks during an 8-weekperiod . Question naires were administered before and after the intervention , and questions were generated by the software during the intervention period . Computer usage was recorded online . RESULTS The data on self-reported recovery suggested a favorable effect ; more subjects in the intervention groups than in the control group reported recovery ( 55 % versus 34 % ) from their complaints and fewer reported deterioration ( 4 % versus 20 % ) . However , a comparison between the reported pre- and postintervention scores on the severity and frequency of the complaints showed no significant differences in the change among the three groups . No effects on sick leave were observed . The subjects in the intervention groups showed higher productivity . CONCLUSIONS The use of a software program stimulating workers to take regular breaks contributes to perceived recovery from neck or upper-limb complaints . There seems to be no additional effects from performing physical exercises during these breaks", "A prospect i ve epidemiological field study covering a 2 years period has earlier been published . The study has a parallel group design with two intervention groups ( T and S ) and one control group ( C ) of Visual Display Unit ( VDU ) operators . The present paper covers the period from 2 to 6 years of the study . After 3.5 years , the C group got the same intervention in terms of new lighting system , new workplaces and at last an optometric examination and corrections if needed . The C group reported a significant reduction in visual discomfort after interventions while the two groups ( T and S ) continued to report significant reduction of visual discomfort after 6 years . By supporting the forearm on the table top , the C group reported significant reduction of shoulder and neck pain while the T group reported significant reduction in shoulder and back pain after 6 years . Organizational and psychosocial factors at work and outside work did not show any significant changes during the study period", "Aims : To examine the effect of two workstation and postural interventions on the incidence of musculoskeletal symptoms among computer users . Methods : R and omised controlled trial of two distinct workstation and postural interventions ( an alternate intervention and a conventional intervention ) among 376 persons using computer keyboards for more than 15 hours per week . The incidence of neck/shoulder symptoms and h and /arm symptoms during six months of follow up among individuals in the intervention groups was compared to the incidence in computer users who did not receive an intervention ( comparison group ) . For individuals in the intervention groups , study staff adjusted workstations , where possible , and trained individuals to assume the intervention postures . Individuals reported musculoskeletal symptoms in a weekly diary . Participants who reported discomfort intensity of 6 or greater on a 0–10 visual analogue scale or who reported musculoskeletal symptoms requiring use of analgesic medication were considered symptomatic . Results : There were no significant differences in the incidence of musculoskeletal symptoms among the three intervention groups . Twenty two ( 18.5 % ) participants in the alternate intervention group , 25 ( 20.2 % ) in the conventional intervention group , and 25 ( 21.7 % ) in the comparison group developed incident arm or h and symptoms . Thirty eight ( 33.3 % ) participants in the alternate intervention group , 36 ( 31.0 % ) in the conventional intervention group , and 33 ( 30.3 % ) in the comparison group developed incident neck or shoulder symptoms . Compliance with all components of the intervention was attained for only 25–38 % of individuals , due mainly to the inflexibility of workstation configurations . Conclusions : This study provides evidence that two specific workplace postural interventions are unlikely to reduce the risk of upper extremity musculoskeletal symptoms among computer users", "BACKGROUND Despite widespread recommendations regarding posture during computer use , associations between specific postures and musculoskeletal health are not well characterized . METHODS Six hundred and thirty-two newly hired computer users were followed prospect ively to evaluate associations between posture and neck or shoulder ( N/S ) and h and or arm ( H/A ) musculoskeletal symptoms and musculoskeletal disorders . Participants ' postures were measured at entry and they reported symptoms on weekly diaries . Participants reporting symptoms were examined for specific disorders . Multivariate Cox regression models were used to estimate associations between postural variables and risk of symptoms and disorders , controlling for confounding variables . RESULTS Keying with an inner elbow angle > 121 degrees , greater downward head tilt , and presence of armrests on the participants chair were associated with lower risk of N/S symptoms or N/S disorders . Keying with elbow height below the height of the \" J \" key and the presence of a telephone shoulder rest were associated with a greater risk of N/S symptoms or N/S disorders . Horizontal location of the \" J \" key > 12 cm from the edge of the desk was associated with a lower risk of H/A symptoms and H/A disorders . Use of a keyboard with the \" J \" key > 3.5 cm above the table surface , key activation force > 48 g , and radial wrist deviation of > 5 degrees while using a mouse was associated with a greater risk of H/A symptoms or H/A disorders . The number of hours keying/week was associated with H/A symptoms and disorders . CONCLUSIONS The results suggest that the risk of musculoskeletal symptoms and musculoskeletal disorders may be reduced by encouraging specific seated postures", "This pilot study investigated whether group training , in which participants become role models and coaches , would reduce discomfort as compared to a nontreatment Control Group . Sixteen experimental participants participated in 6 weekly 2-hr group sessions of a Healthy Computing program whereas 12 control participants received no training . None of the participants reported symptoms to their supervisors nor were they receiving medical treatment for repetitive strain injury prior to the program . The program included training in ergonomic principles , psychophysiological awareness and control , sEMG practice at the workstation , and coaching coworkers . Using two-tailed t tests to analyze the data , the Experimental Group reported ( 1 ) a significant overall reduction in most body symptoms as compared to the Control Group and ( 2 ) a significant increase in positive work-style habits , such as taking breaks at the computer , as compared to the Control Group . This study suggests that employees could possibly improve health and work style patterns based on a holistic training program delivered in a group format followed by individual practice", "Using a computer keyboard with the forearms unsupported has been proposed as a causal factor for neck/shoulder and arm/h and diagnoses . Recent laboratory and field studies have demonstrated that forearm support might be preferable to working in the traditional \" floating \" posture . The aim of this study was to determine whether providing forearm support when using a normal computer workstation would decrease musculoskeletal discomfort in intensive computer users in a call centre . A r and omised controlled study ( n = 59 ) , of 6 weeks duration was conducted . Thirty participants ( Group 1 ) were allocated to forearm support using the desk surface with the remainder ( Group 2 ) acting as a control group . At 6 weeks , the control group was also set up with forearm support . Both groups were then monitored for another 6 weeks . Question naires were used at 1 , 6 and 12 weeks to obtain information about discomfort , workstation setup , working posture and comfort . Nine participants ( Group 1 n = 6 , Group 2 n = 3 ) withdrew within a week of commencing forearm support either due to discomfort or difficulty in maintaining the posture . At 6 weeks , the group using forearm support generated significantly fewer reports of discomfort in the neck and back , although the difference between the groups was not statistically significant . At 12 weeks , there were fewer reports of neck , back and wrist discomfort when preintervention discomfort was compared with post intervention discomfort . These findings indicate that for the majority of users , forearm support may be preferable to the \" floating \" posture implicit in current guidelines for computer workstation setup", "Purpose . Three types of progressive additions lenses ( PAL ) specially design ed for VDU-work and one single vision lens were compared in a prospect i ve field study . The aim was to investigate if these progressive lenses created a difference in the development of visual discomfort compared to single vision lenses when working on an optimized VDU-workstation . Methods . The study had a prospect i ve , parallel group design , with four groups of VDU-workers . Approximately 40 subjects in each group , selected after careful task analysis with special attention towards the visual angles and distances to the work tasks . The groups were followed over one year . A question naire concerning visual conditions , working conditions , discomfort in different body areas , the status of the subjects ’ optometric corrections , psychological factors both at work and at home , amount , frequency and duration of VDU-work etc . was filled in before the intervention , after six months and after one year . No other contact was made with the subjects . The VDU-lenses included were Interview ( Essilor ) , Gradal RD ( Zeiss ) and Technica ( American Optical ) . Pain intensity and duration were assessed on a 100 mm Visual Analogue Scale ( VAS ) before the intervention , and six and twelve months after the intervention . All subjects were given a complete optometric examination . Results . Only small changes in the development of headache and visual discomfort were registered . However , the subjective evaluation of area of clear vision and overall satisfaction was significantly improved for the Interview and Gradal RD lens ( p single vision lenses . Conclusion . Lens design s that cover viewing distances from near and out to approximately 2 meters work well compared to lens design s trying to cover greater range of clear vision . When tasks analysis shows that single vision correction may be used , this is still an acceptable solution", "Computer operators at two work sites ( n = 73 , n = 19 ) were prompted to take three 30-s and one 3-min break from computer work each hour in addition to conventional rest breaks . Some operators were asked to perform stretching exercises during the short breaks . Mood state and musculoskeletal discomfort were assessed at each work site over a 2- or 3-week baseline period and a 4- or 6-week treatment period , respectively . Operator productivity measures were obtained from company records . Operators complied with about half of the added breaks but favoured 3-min breaks over 30-s breaks . No improvement in productivity or well-being was found at the larger work site . At the smaller work site , productivity , eye , leg and foot comfort all improved when the short breaks included stretching exercises . These results provide evidence that frequent short breaks from continuous computer-mediated work can benefit worker productivity and well-being when the breaks integrate with task dem and", "Microbreaks are scheduled rest breaks taken to prevent the onset or progression of cumulative trauma disorders in the computerized workstation environment . The authors examined the benefit of microbreaks by investigating myoelectric signal ( MES ) behavior , perceived discomfort , and worker productivity while individuals performed their usual keying work . Participants were r and omly assigned to one of three experimental groups . Each participant provided data from working sessions where they took no breaks , and from working sessions where they took breaks according to their group assignment : microbreaks at their own discretion ( control ) , microbreaks at 20 min intervals , and microbreaks at 40 min intervals . Four main muscle areas were studied : the cervical extensors , the lumbar erector spinae , the upper trapezius/supraspinatus , and the wrist and finger extensors . The authors have previously shown that when computer workers remained seated at their workstation , the muscles performing sustained postural contractions displayed a cyclic trend in the mean frequency ( MNF ) of the MES ( McLean et al. , J. Electrophysiol . Kinesiol . 10 ( 1 ) ( 2000 ) 33 ) . The data provided evidence ( p microbreak protocol s were associated with a higher frequency of MNF cycling at the wrist extensors , at the neck when microbreaks were taken by the control and 40 min protocol groups , and at the back when breaks were taken by the 20 and 40 min protocol groups . No significant change in the frequency of MNF cycling was noted at the shoulder . It was determined ( p microbreaks had a positive effect on reducing discomfort in all areas studied during computer terminal work , particularly when breaks were taken at 20 min intervals . Finally , microbreaks showed no evidence of a detrimental effect on worker productivity . The underlying cause of MNF cycling , and its relationship to the development of discomfort or cumulative trauma disorders remains to be determined", "OBJECTIVES This study evaluated the effect of an ergonomic training program on workstation changes and on the prevalence of musculoskeletal disorders among video display unit ( VDU ) users at a large university . METHODS A pretest-posttest design with a reference group was used with r and om allocation of administrative and geographic units . In each group , the measurements involved direct observation of the workstations , a self-administered question naire , and a physical examination . The measurements were performed 2 weeks before and 6 months after the training in parallel in both groups . The study population was composed of 627 workers ( 81 % of those eligible ) . RESULTS The prevalence of all 3 of the postural stressors evaluated decreased in the experimental group after the training . In the reference group , 2 of the 3 stressors decreased in frequency but to a less extent . Some of these beneficial changes were more frequent in workers under 40 years of age . The prevalence of musculoskeletal disorders decreased among the workers under 40 years of age in the experimental group , from 29 % to 13 % determined by question naire and from 19 % to 3 % determined by physical examination . In other groups , there was no significant change in the prevalence of musculoskeletal disorders . CONCLUSIONS Improvements in postural stressors occurred more frequently in the experimental group , and these beneficial changes tended to be more frequent in workers under 40 years of age . Improvements in musculoskeletal disorders occurred in the experimental group among the workers under 40 years of age", "A comparative r and omised double masked multicentric clinical trial has been conducted to find out the efficacy and safety of a herbal eye drop preparation , itone eye drops with artificial tear and placebo in 120 patients with computer vision syndrome . Patients using computer for at least 2 hours continuosly per day having symptoms of irritation , foreign body sensation , watering , redness , headache , eyeache and signs of conjunctival congestion , mucous/debris , corneal filaments , corneal staining or lacrimal lake were included in this study . Every patient was instructed to put two drops of either herbal drugs or placebo or artificial tear in the eyes regularly four times for 6 weeks . Objective and subjective findings were recorded at bi-weekly intervals up to six weeks . Side-effects , if any , were also noted . In computer vision syndrome the herbal eye drop preparation was found significantly better than artificial tear ( p No side-effects were noted by any of the drugs . Both subjective and objective improvements were observed in itone treated cases . So , itone can be considered as a useful drug in computer vision syndrome", "The risk for the development of musculoskeletal disorders and associated conditions in clerical and office workers is well documented . The majority of work injury prevention programs for this population were single-faceted ( education , workstation re design , or task modification ) and yielded both positive and negative findings . This pilot study was conducted with 16 full-time clerical and office workers at a small private college . In a r and omized control trial , the intervention group received four hours of individualized training through a multi-faceted injury prevention program . Between group differences in musculoskeletal symptom frequency and intensity and perceived stress and energy levels existed , although were statistically insignificant . There was a statistically significant decrease in Lower Back ache/pain from pre to post measures for the intervention group", "Eighty computer users with musculoskeletal disorders participated in a six-month , r and omized , placebo-controlled trial evaluating the effects of four computer keyboards on clinical findings , pain severity , functional h and status , and comfort . The alternative geometry keyboards tested were : the Apple Adjustable Keyboard ™ [ kb1 ] , Comfort Keyboard System ™ [ kb2 ] , Microsoft Natural Keyboard ™ [ kb3 ] and placebo . Compared to placebo , kb3 and to a lesser extent kb1 groups demonstrated an improving trend in pain severity and h and function following six months of keyboard use . However , there was no corresponding consistent improvement in clinical findings in the alternative geometry keyboard groups compared to the placebo group . Overall , there was a significant correlation between improvement of pain severity and greater satisfaction with the keyboards . These results provide evidence that keyboard users may experience a reduction in h and pain after several months of use of some alternative geometry keyboards", "BACKGROUND Eye strain continues to be one of the chief complaints of people working at video display terminals . The increase in extorsion observed on elevation of gaze at near point may induce binocular disruption and strain . Binocular base-up and base-in prism might mitigate some of the visual complaints of computer users because they decrease the elevation and convergence required . A double blind study of 30 computer users indicates a significantly greater preference for a lens combining prism and plus power than for plus lenses having no prism", "BACKGROUND The aim of this project is to examine the potential connection between the astigmatic refractive corrections of subjects using computers and their productivity and comfort . We hypothesize that improving the visual status of subjects using computers results in greater productivity , as well as improved visual comfort . METHODS Inclusion criteria required subjects 19 to 30 years of age with complete vision examinations before being enrolled . Using a double-masked , placebo-controlled , r and omized design , subjects completed three experimental tasks calculated to assess the effects of refractive error on productivity ( time to completion and the number of errors ) at a computer . The tasks resembled those commonly undertaken by computer users and involved visual search tasks of : ( 1 ) counties and population s ; ( 2 ) nonsense word search ; and ( 3 ) a modified text-editing task . RESULTS Estimates of productivity for time to completion varied from a minimum of 2.5 % upwards to 28.7 % with 2 D cylinder miscorrection . Assuming a conservative estimate of an overall 2.5 % increase in productivity with appropriate astigmatic refractive correction , our data suggest a favorable cost-benefit ratio of at least 2.3 for the visual correction of an employee ( total cost 268 dollars ) with a salary of 25,000 dollars per year . CONCLUSIONS We conclude that astigmatic refractive error affected both productivity and visual comfort under the conditions of this experiment . These data also suggest a favorable cost-benefit ratio for employers who provide computer-specific eyewear to their employees ", "OBJECTIVE The purpose of this study was to evaluate the effectiveness of an active ergonomics training ( AET ) program in computer users . Two constructs from the social-cognitive theory were adopted to provide a more comprehensive assessment of the proximal markers of behavior change . METHOD Eighty-seven symptomatic and asymptomatic employees who worked at a computer for a minimum of 10 hours per week took part in a prospect i ve r and omized controlled study . Subjects participated in a six-hour training intervention at their workplace . Key elements of the AET intervention were skill development in workstation analysis , active participation , and implementation of multiple prevention strategies . RESULTS After receiving AET , risk factor exposure was significantly reduced for participants at higher risk [ F(1,82 ) = 6.42 , p knowledge [ F(1,74 ) = 8.39 , p self-efficacy [ F(1,73 ) = 6.95 , p outcome expectations [ F(1,75 ) = 8.75 , p AET intervention had significantly less upper back pain intensity ( z = -2.03 , p pain frequency ( z = -2.70 , p pain duration ( z = -3.25 , p work postures , work practice s , risk factor exposure , and pain", "OBJECTIVES This study evaluated the effect of an intensive ergonomic approach and education on workstation changes and musculoskeletal disorders among workers who used a video display unit ( VDU ) . METHODS A r and omized controlled design was used . The subjects ( N=124 ) were allocated into three groups ( intensive ergonomics , ergonomic education , reference ) using stratified r and om sampling . The evaluation involved question naires , a diary of discomfort , measurements of workload , and an ergonomic rating of the workstations . The assessment s were made 2 weeks before the intervention and after 2 and 10 months of follow-up . RESULTS The intensive and training groups showed less musculoskeletal discomfort than the reference group after 2 months of follow-up . Positive effects on discomfort were seen primarily for the shoulder , neck , and upper back areas . No significant differences were found for the strain levels or prevalence of pain . After the intervention the ergonomic level was distinctly higher in the intensive ergonomic group than in the education or reference group . CONCLUSIONS Both the intensive ergonomics approach and education in ergonomics help reduce discomfort in VDU work . In attempts to improve the physical ergonomics of VDU workstations , the best result will be achieved with cooperative planning in which both workers and practitioners are actively involved", "The study has a parallel group design with two intervention groups ( T and S ) and one control group ( C ) of VDU operators . Three serial interventions were carried out in the T and S groups , first a new lighting system , then new workplaces and last an optometric examination and corrections if needed . The new lighting gave significantly increased illuminance levels , increased luminances of the room surfaces and better luminance distribution . The two intervention groups reported significant improvement of the lighting conditions , as well as of the visual conditions and significantly reduced visual discomfort and glare . Significant reduction of headache was found in one of the intervention groups . Optometric corrections reduced the visual discomfort in both the intervention groups . When looking at those given new corrections , a significant reduction was found in the T group and a clear tendency was also found in the S group . The C group reported no improvements for any of these health outcomes . The workplace intervention gave the operator the possibility to support the whole forearm and h and on the table top . Before the intervention there were no significant differences between the three groups regarding shoulder pain and static trapezius electromyographic ( EMG ) load . Two years after the intervention , a significant reduction of shoulder pain was reported in the T and S groups in parallel with a significant reduction in static trapezius load , while no such reduction was found in the C group . At the same time , both static trapezius load and shoulder pain were significantly lower in the T and S groups compared with the C group . Pain in the forearm and h and showed no significant changes in any of the groups during the study period . However , there seem to be a relationship between pain in the forearm and h and and the time the operator used the mouse . The C group reported significantly higher intensity of pain and used the mouse significantly more than the S group", "The objective of this study was to examine the relationship between upper limb symptoms and keyboard use in a population survey . A question naire was mailed to 21,201 subjects aged 16 - 64 years , selected at r and om from the registers of 34 British general practice s. Information was collected on occupation and on regular use of keyboards ( for > 4 h in an average working day ) , pain in the upper limbs and neck , numbness or tingling in the upper limbs , headaches , and feelings of tiredness or stress . Associations were explored by logistic regression , with the result ant odds ratios converted into prevalence ratios ( PRs ) . Among 12,262 respondents , 4899 held non-manual occupations . These included 1871 regular users of keyboards ( e.g. computer operators , data processors , clerks , administrators , secretaries and typists ) . Pain in the neck or upper limbs and sensory symptoms were common in the non-manual workers overall ( with 1 week period prevalences of 30 and 15 % , respectively ) , and were associated with older age , smoking , headaches and tiredness or stress . After adjustment for these factors , regular keyboard use was significantly associated with pain in the past week in the shoulders ( PRs 1.2 - 1.4 ) and the wrists or h and s ( PR 1.4 ) , but not with elbow pain or sensory symptoms over the same period , or with neck or upper limb pain that prevented normal activities in the past year . Disabling symptoms were somewhat less prevalent among symptomatic keyboard users than among other symptomatic workers . We conclude that use of keyboards was associated with discomfort at the shoulder and wrist or h and , but risk estimates were lower than generally reported in workplace surveys . Previous estimates of risk in the occupational setting may have been biased by shared expectations , concerns , or other aspects of illness behaviour", "The effects of Ergorest ® arm supports on wrist angles and musculoskeletal strain in the neck-shoulder-arm region and electrical activity in the shoulder and arm muscles were studied during typing or the use of the mouse in work with a visual display unit ( VDU ) . Twenty-one women were r and omized into 3 groups ( 1 arm support , 2 arm supports , and control ) . Measurements were carried out before and after the 6-week intervention . The wrist extension of the mouse h and , the muscle activity of the trapezius muscle , and the subjective discomfort ratings indicated that 2 arm supports were better than 1 in work with a mouse . The Ergorest ® arm support alleviates muscle and joint strain in VDU work when used for both arms", "BACKGROUND An increasing number of people seek medical attention for symptoms of visual discomfort due to computer vision syndrome ( CVS ) . We compared the efficacy and adverse event rates of a new eye lubricant , OptiZen ( InnoZen , Inc. , polysorbate 80 0.5 % ) and Visine Original ( Pfizer Consumer Healthcare , tetrahydrozoline HCl 0.05 % ) . METHODS In this double-blind parallel arm trial , 50 healthy men and women , ages 18 to 65 years , with symptoms of CVS who use a video display terminal for a minimum of 4 hours per day were r and omized to OptiZen ( n = 25 ) or Visine Original ( n= 25 ) , 1 to 2 drops b.i.d . for 5 days . The primary end-points were ocular discomfort and adverse events . RESULTS OptiZen and Visine Original had similar efficacy in alleviating symptoms of ocular discomfort ( odds ratio of 1.23 [ 95 % confidence interval , 0.63 to 2.42 ] , P= 0.55 ) . OptiZen and Visine Original were very similar with respect to odds ratios and 95 % confidence interval ( CI ) for each of the measurement times ( P= 0.72 ) . Visine Original users reported a significantly higher incidence of temporary ocular stinging/burning immediately after drug instillation ( 28 % , 7/25 ) than did OptiZen users ( 4 % , 1/24 ) ( P= 0.05 ) . Patients using OptiZen were 89 % less likely to have stinging/burning effects than those patients using Visine Original ( 95 % CI : 0.01 to 0.95 ) . DISCUSSION OptiZen and Visine Original are effective at alleviating ocular discomfort associated with prolonged computer use . Adverse event findings suggest that OptiZen causes less ocular discomfort on instillation , potentially attributable to its milder ingredient profile", "The effect of \" neck school \" on neck and shoulder disorders was studied in medical secretaries . A neck school reinforced with compliance enhancing measures ( group B ) was compared with a traditional neck school ( group A ) and a control group ( group C ) . The results show that ergonomical knowledge was good even before the secretaries attended the neck schools and that compliance was significantly higher for group B. When comparisons were made within groups some improvements on neck and shoulder fatigue and pain were noted , particularly for group B. When workload was controlled no significant group differences were found . No differences were noted for range of neck motion , or sick leave in any group . Our conclusion is that neck schools , despite good compliance , appear to be of limited clinical value for prevention of neck and shoulder disorders" ]

[ "INTRODUCTION Resistance training has been well established as an effective treatment strategy to increase skeletal muscle mass and strength in the elderly . We assessed whether dietary protein supplementation can further augment the adaptive response to prolonged resistance-type exercise training in healthy elderly men and women . METHODS Healthy elderly men ( n = 31 , 70 ± 1 yr ) and women ( n = 29 , 70 ± 1 yr ) were r and omly assigned to a progressive , 24-wk resistance-type exercise training program with or without additional protein supplementation ( 15 g·d-1 ) . Muscle hypertrophy was assessed on a whole-body Dual-energy X-ray absorptiometry ( DXA ) , limb ( computed tomography ) , and muscle fiber ( biopsy ) level . Strength was assessed regularly by 1-repetition maximum ( RM ) strength testing . Functional capacity was assessed with a sit-to-st and and h and grip test . RESULTS One-RM strength increased by 45 % ± 6 % versus 40 % ± 3 % ( women ) and 41 % ± 4 % versus 44 % ± 3 % ( men ) in the placebo versus protein group , respectively ( P groups . Leg muscle mass ( women , 4 % ± 1 % vs 3 % ± 1 % ; men , 3 % ± 1 % vs 3 % ± 1 % ) and quadriceps cross-sectional area ( women , 9 % ± 1 % vs 9 % ± 1 % ; men , 9 % ± 1 % vs 10 % ± 1 % ) increased similarly in the placebo versus protein groups ( P ) . Type II muscle fiber size increased over time in both placebo and protein groups ( 25 % ± 13 % vs 30 % ± 9 % and 23 % ± 12 % vs 22 % ± 10 % in the women and men , respectively ) . Sit-to-st and improved by 18 % ± 2 % and 19 % ± 2 % in women and men , respectively ( P healthy elderly men and women . Additional protein supplementation ( 15 g·d-1 ) does not further increase muscle mass , strength , and /or functional capacity", "The aims of this r and omised controlled trial were to determine if a high-intensity functional exercise program improves balance , gait ability , and lower-limb strength in older persons dependent in activities of daily living and if an intake of protein-enriched energy supplement immediately after the exercises increases the effects of the training . One hundred and ninety-one older persons dependent in activities of daily living , living in residential care facilities , and with a Mini-Mental State Examination ( MMSE ) score of ? 10 participated . They were r and omised to a high-intensity functional exercise program or a control activity , which included 29 sessions over 3 months , as well as to protein-enriched energy supplement or placebo . Berg Balance Scale , self-paced and maximum gait speed , and one-repetition maximum in lower-limb strength were followed-up at three and six months and analysed by 2 x 2 factorial ANCOVA , using the intention-to-treat principle . At three months , the exercise group had improved significantly in self-paced gait speed compared with the control group ( mean difference 0.04 m/s , p = 0.02 ) . At six months , there were significant improvements favouring the exercise group for Berg Balance Scale ( 1.9 points , p = 0.05 ) , self-paced gait speed ( 0.05 m/s , p = 0.009 ) , and lower-limb strength ( 10.8 kg , p = 0.03 ) . No interaction effects were seen between the exercise and nutrition interventions . In conclusion , a high-intensity functional exercise program has positive long-term effects in balance , gait ability , and lower-limb strength for older persons dependent in activities of daily living . An intake of protein-enriched energy supplement immediately after the exercises does not appear to increase the effects of the training", "Objective To assess the effect of free leucine supplementation combined with resistance training versus resistance training only on muscle strength and functional status in older adults . Methods This was a r and omized , double-blind , placebo-controlled , parallel study with two intervention groups . Thirty older adults were r and omly assigned to receive either 10 g leucine/day ( leucine group [ LG ] , n=15 ) or a placebo ( control group [ CG ] , n=15 ) , plus resistance training over a 12-week period . Maximal overcoming isometric leg strength , functional status , nutritional status , body composition , health-related quality of life , depression , and dietary intake were assessed at 4 and 12 weeks . Missing data at 12 weeks were h and led using mixed models for repeated measurements for data imputation . Results Twenty-four subjects completed the 4-week assessment and eleven completed the 12-week intervention . Clinical ly significant gains were found in isometric leg strength at both assessment time points . Analysis of the effect size also showed how participants in LG outperformed those in CG for chair st and s and the timed up and go test . No significant changes were observed for the rest of the outcomes . Conclusion Our combined analysis showed moderate changes in isometric leg muscle strength and certain components of functional status . The magnitude of changes found on these outcomes should be qualified as a positive effect of the concomitant intervention", "Protein supplementation in combination with resistance training may increase muscle mass and muscle strength in elderly subjects . The objective of this study was to assess the influence of post-exercise protein supplementation with collagen peptides v. placebo on muscle mass and muscle function following resistance training in elderly subjects with sarcopenia . A total of fifty-three male subjects ( 72·2 ( sd 4·68 ) years ) with sarcopenia ( class I or II ) completed this r and omised double-blind placebo-controlled study . All the participants underwent a 12-week guided resistance training programme ( three sessions per week ) and were supplemented with either collagen peptides ( treatment group ( TG ) ) ( 15 g/d ) or silica as placebo ( placebo group ( PG ) ) . Fat-free mass ( FFM ) , fat mass ( FM ) and bone mass ( BM ) were measured before and after the intervention using dual-energy X-ray absorptiometry . Isokinetic quadriceps strength ( IQS ) of the right leg was determined and sensory motor control ( SMC ) was investigated by a st and ardised one-leg stabilisation test . Following the training programme , all the subjects showed significantly higher ( P . The effect was significantly more pronounced in subjects receiving collagen peptides : FFM ( TG + 4·2 ( sd 2·31 ) kg/PG + 2·9 ( sd 1·84 ) kg ; P ) ; IQS ( TG + 16·5 ( sd 12·9 ) Nm/PG + 7·3 ( sd 13·2 ) Nm ; P ) ; and FM ( TG –5·4 ( sd 3·17 ) kg/PG –3·5 ( sd 2·16 ) kg ; P compared with placebo , collagen peptide supplementation in combination with resistance training further improved body composition by increasing FFM , muscle strength and the loss in FM", "Studies in young adults have demonstrated that beta-hydroxy-beta-methylbutyrate ( HMB ) can increase gains in strength and fat-free mass during a progressive resistance-training program . The purpose of this study was to determine whether HMB would similarly benefit 70-y-old adults undergoing a 5 d/wk exercise program . Thirty-one men ( n = 15 ) and women ( n = 16 ) ( 70 + /- 1 y ) were r and omly assigned in a double-blind study to receive either capsules containing a placebo or Ca-HMB ( 3 g/d ) for the 8-wk study . Skin fold estimations of body composition as well as computerized tomography ( CT ) and dual X-ray absorptiometry ( DXA ) scans were measured before the study and immediately after the 8-wk training program . HMB supplementation tended to increase fat-free mass gain ( HMB , 0.8 + /- 0.4 kg ; placebo , -0.2 + /- 0.3 kg ; treatment x time , P = 0.08 ) . Furthermore , HMB supplementation increased the percentage of body fat loss ( skin fold : HMB , -0.66 + /- 0.23 % ; placebo , -0.03 + /- 0.21 % ; P = 0.05 ) compared with the placebo group . CT scans also indicated a greater decrease in the percentage of body fat with HMB supplementation ( P body composition can be accomplished in 70-y-old adults participating in a strength training program , as previously demonstrated in young adults , when HMB is supplemented daily", "Body composition changes and loss of functionality in the elderly are related to subst and ard diets and progressive sedentariness . The aim of this study was to assess the impact of an 18-mo nutritional supplementation and resistance training program on health functioning of elders . Healthy elders aged > or = 70 y were studied . Half of the subjects received a nutritional supplement . Half of the supplemented and nonsupplemented subjects were r and omly assigned to a resistance exercise training program . Every 6 mo , a full assessment was performed . A total of 149 subjects were considered eligible for the study and 98 ( 31 supplemented and trained , 26 supplemented , 16 trained and 25 without supplementation or training ) completed 18 mo of follow-up . Compliance with the supplement was 48 % , and trained subjects attended 56 % of programmed sessions . Activities of daily living remained constant in the supplemented subjects and decreased in the other groups . Body weight and fat-free mass did not change . Fat mass increased from 22.2 + /- 7.6 to 24.1 + /- 7.7 kg in all groups . Bone mineral density decreased less in both supplemented groups than in the nonsupplemented groups ( ANOVA , P Serum cholesterol remained constant in both supplemented groups and in the trained groups , but it increased in the control group ( ANOVA , P Upper and lower limb strength , walking capacity and maximal inspiratory pressure increased in trained subjects . In conclusion , patients who were receiving nutritional supplementation and resistance training maintained functionality , bone mineral density and serum cholesterol levels and improved their muscle strength", "Fighting against inactivity and inadequate nutritional intake are of utmost importance in the elderly . To our knowledge , the few studies which have been performed were conducted for only a short period and the results do not permit formal conclusions to be drawn . We therefore tried to fill this gap in our knowledge by determining whether an intervention combining an acceptable progressive exercise programme and nutritional supplements would be feasible for a long-term period in the very frail elderly , and would bring about concomitant benefits in body composition and muscle power . Accordingly , this exercise and nutritional combination was assessed in the frail elderly in a 9-month r and omised trial with a factorial design . Fifty-seven elderly volunteers over 72 years , from sixteen retirement homes in Lyon , France participated in the study . Dietary supplements were compared with placebo , and physical exercise was compared with memory training . Main outcome measures were fat-free mass ( FFM ) and muscle power . FFM was determined by labelled water , and muscle power was measured by a leg-extensor machine . At 9 months , the compliance was 63 % for exercise sessions , and 54 % for nutritional supplements . In patients with dietary supplements , muscle power increased by 57 % at 3 months ( P=0.03 ) , and showed only a tendency at 9 months ; although FFM increased by 2.7 % at 9 months , the difference was not significant ( P=0.10 ) . Exercise did not improve muscle power at 9 months , but improved functional tests ( five-time-chair rise , P=0.01 ) . BMI increased with supplements ( + 3.65 % ) , but decreased with placebo ( -0.5 % ) at 9 months ( P=0.007 ) . A long-term combined intervention is feasible in frail elderly individuals with a good rate of compliance . Nutritional supplements and exercise may improve muscle function . Despite no significant results on FFM , due to the limited number of volunteers , combined intervention should be suggested to counteract muscle weakness in the frail elderly", "BACKGROUND The benefit of protein supplementation on the adaptive response of muscle to exercise training in older people is controversial . OBJECTIVE To investigate the independent and combined effects of a multicomponent exercise program with and without a milk-based nutritional supplement on muscle strength and mass , lower-extremity fatigue , and metabolic markers . DESIGN A sample of 48 healthy sedentary men aged 60.8 ± 0.4 years were r and omly assigned to a 16-week multicomponent exercise training program with a milk-based supplement containing , besides proteins [ total milk proteins 4 or 10 g/day or soluble milk proteins rich in leucine ( PRO ) 10 g/day ] , carbohydrates and fat . Body composition , muscle mass and strength , and time to task failure , an index of muscle fatigue , were measured . Blood lipid , fibrinogen , creatine phosphokinase , glucose , insulin , C-reactive protein , interleukin-6 , tumor necrosis factor-α soluble receptors , and endothelial markers were assessed . RESULTS Body fat mass was reduced after the 4-month training program in groups receiving 10 g/day of protein supplementation ( P increase in dominant fat free mass ( + 5.4 % , P and in appendicular muscle mass ( + 4.5 % , P was decreased in the trained group receiving 10 g/day PRO . The index of insulin resistance ( homeostasis model assessment -insulin resistance ) and blood creatine phosphokinase were reduced in the groups receiving 10 g/day PRO , irrespective of exercise . The inflammatory and endothelial markers were not different between the groups . Training caused a significant improvement ( + 10.6 % to 19.4 % , P . Increased maximum voluntary contraction force was seen in the trained groups receiving 10 g/day of proteins ( about 3 % , P failure was improved in the trained participants receiving a 10 g/day supplementation with PRO ( P in skeletal muscle mass and strength after prolonged multicomponent exercise training in healthy older men", "Abstract Purpose The present study evaluated the effects of creatine monohydrate ( CrM ) consumption post-exercise on body composition and muscle strength in middle to older males following a 12-week resistance training program . Methods In a double-blind , r and omized trial , 20 males aged between 55 and 70 years were r and omly assigned to consume either CrM-carbohydrate ( CHO ) [ 20 g days−1 CrM + 5 g days−1 CHO × 7 days , then 0.1 g kg−1 CrM + 5 g CHO on training days ( average dosage of ~8.8 g ) ] or placebo CHO ( 20 g days−1 CHO × 7 days , then 5 g CHO on training days ) while participating in a high intensity resistance training program [ 3 sets × 10 repetitions at 75 % of 1 repetition maximum ( 1RM ) ] , 3 days weeks−1 for 12 weeks . Following the initial 7-day “ loading ” phase , participants were instructed to ingest their supplement within 60 min post-exercise . Body composition and muscle strength measurements , blood collection and vastus lateralis muscle biopsy were completed at 0 , 4 , 8 and 12 weeks of the supplement and resistance training program . Results A significant time effect was observed for 1RM bench press ( p = 0.016 ) , leg press ( p = 0.012 ) , body mass ( p = 0.03 ) , fat-free mass ( p = 0.005 ) and total myofibrillar protein ( p = 0.005 ) . A trend for larger muscle fiber cross-sectional area in the type II fibers compared to type I fibers was observed following the 12-week resistance training ( p = 0.08 ) . No supplement interaction effects were observed . Conclusion Post-exercise ingestion of creatine monohydrate does not provide greater enhancement of body composition and muscle strength compared to resistance training alone in middle to older males", "BACKGROUND Considerable discrepancy exists in the literature on the proposed benefits of protein supplementation on the adaptive response of skeletal muscle to resistance-type exercise training in the elderly . OBJECTIVE The objective was to assess the benefits of timed protein supplementation on the increase in muscle mass and strength during prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein . DESIGN Healthy elderly men ( n = 26 ) aged 72 + /- 2 y were r and omly assigned to a progressive , 12-wk resistance-type exercise training program with ( protein group ) or without ( placebo group ) protein provided before and immediately after each exercise session ( 3 sessions/wk , 20 g protein/session ) . One-repetition maximum ( 1RM ) tests were performed regularly to ensure a progressive workload during the intervention . Muscle hypertrophy was assessed at the whole-body ( dual-energy X-ray absorptiometry ) , limb ( computed tomography ) , and muscle fiber ( biopsy ) level . RESULTS The 1RM strength increased approximately 25 - 35 % in both groups ( P leg muscle mass ( 6 + /- 1 % in both groups ; P quadriceps ( 9 + /- 1 % in both groups ) , from 75.9 + /- 3.7 and 73.8 + /- 3.2 to 82.4 + /- 3.9 and 80.0 + /- 3.0 cm2 in the placebo and protein groups , respectively ( P Muscle fiber hypertrophy was greater in type II ( placebo : 28 + /- 6 % ; protein : 29 + /- 4 % ) than in type I ( placebo : 5 + /- 4 % ; protein : 13 + /- 6 % ) fibers , but the difference between groups was not significant . CONCLUSION Timed protein supplementation immediately before and after exercise does not further augment the increase in skeletal muscle mass and strength after prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein . This trial was registered at clinical trials.gov as NCT00744094", "Research indicates that lower extremity muscle weakness in the elderly is consistently related to impaired mobility and fall risk . Reversible components of the muscle weakness of aging include underuse syndromes and undernutrition , both of which are prevalent in nursing home population s. The Boston FICSIT study is a nursing home-based intervention to improve muscle strength through progressive resistance training of the lower extremities and /or multi-nutrient supplementation in chronically institutionalized subjects aged 70 - 100 . Baseline measurements of falls , medical status , psychological variables , functional status , nutritional intake and status , body composition , muscle mass and morphology , muscle function , and gait and balance are taken . The nursing home residents are then r and omly assigned to one of four treatment groups for 10 weeks : ( 1 ) high intensity progressive resistance training of the hip and knee extensors 3 days per week ; ( 2 ) multi-nutrient supplementation with a 360-kcal high carbohydrate , low fat liquid supplement every day ; ( 3 ) a combination of groups ( 1 ) and ( 2 ) ; and ( 4 ) a control group . Both non-supplemented groups receive a liquid placebo every day , and both non-exercising groups attend three sessions of \" leisure activities \" every week in order to control for the attentional aspects of the exercise and nutritional interventions . At the end of the 10-week period , all baseline measurements are re-assessed", "PURPOSE To assess the effects of a one year nutritional supplementation and resistance training program on muscle strength and walking capacity in the elderly . MATERIAL AND METHODS Elderly subjects from two outpatient clinics received a nutritional supplement , that provided 400 Kcal , 15 g/protein and 50 % of vitamin DRVs per day . Half the subjects receiving and not receiving the supplement were r and omly assigned to a resistance exercise training program with two sessions per week . Every six months , body composition using DEXA , limb muscle strength , maximal inspiratory and expiratory pressures and walking capacity were assessed . RESULTS One hundred forty nine subjects were considered eligible and 101 ( 31 supplemented and trained , 28 supplemented , 16 trained and 26 without supplementation nor training ) completed the year of follow up . Overall compliance with the supplement was 48 22 % and trained subjects attended 56 21 % of programmed sessions . No changes in fat free mass were observed in any of the groups , but fat mass increased from 22.5 7.3 to 23.2 7.3 kg in all groups ( p Upper and lower limb strength and walking capacity increased significantly in trained subjects whether supplemented or not . Maximal inspiratory pressure and right h and grip strength increased only in the supplemented and trained group . CONCLUSIONS Resistance training improved muscle strength and walking capacity", "The aim was to assess the effects of resistance training and vitamin D supplementation on physical performance of healthy elderly subjects . Ninety-six subjects , aged 70 years or more with 25 OH vitamin D levels of 16 ng/ml or less , were r and omized to a resistance training or control group . Trained and control groups were further r and omized to receive in a double blind fashion , vitamin D 400 IU plus 800 mg of calcium per day or calcium alone . Subjects were followed for nine months . Serum 25 OH vitamin D increased from 12.4+/-2.2 to 25.8+/-6.5 ng/ml among subjects supplemented with vitamin D. Trained subjects had significant improvements in quadriceps muscle strength , the short physical performance test and timed up and go . The latter improved more in trained subjects supplemented with vitamin D. At the end of the follow up , gait speed was higher among subjects supplemented with vitamin ( whether trained or not ) than in non-supplemented subjects ( 838+/-147 and 768+/-127 m/12 min , respectively , p=0.02 ) . Romberg ratio was lower among supplemented controls than non-supplemented trained subjects ( 128+/-40 % and 144+/-37 % , respectively , p=0.05 ) . In conclusion , vitamin D supplementation improved gait speed and body sway , and training improved muscle strength", "OBJECTIVE The aim of the Intervention by Nutrition and Exercise ( INE ) study was to investigate the effects of a mail-based intervention for sarcopenia prevention on muscle mass and anabolic hormones in community-dwelling older adults . DESIGN A cluster-r and omized controlled trial . SETTING AND PARTICIPANTS This trial recruited community-dwelling adults aged 65 years and older in Japan . The 227 participants were cluster r and omized into a walking and nutrition ( W/N ) group ( n = 79 ) , a walking ( W ) group ( n = 71 ) , and a control ( C ) group ( n = 77 ) . We analyzed the physical and biochemical measurements in this sub study . INTERVENTION Six months of mail-based intervention ( a pedometer-based walking program and nutritional supplementation ) . MEASUREMENTS The skeletal muscle mass index ( SMI ) using the bioelectrical impedance data acquisition system , biochemical measurements , such as those of insulinlike growth factor ( IGF-1 ) , dehydroepi and rosterone sulfate ( DHEA-S ) , and 25-hydroxy vitamin D ( 25[OH]D ) , as well as frailty , were assessed by the Cardiovascular Health Study criteria . RESULTS Participants in the W/N and W groups had significantly greater improvements in SMI , IGF-1 , and 25(OH)D ( P DHEA-S ( P frail , older adults . CONCLUSION These results suggest that the mail-based walking intervention of the remote monitoring type for sarcopenia prevention can increase anabolic hormone levels and SMI in community-dwelling older adults , particularly in those who are frail", "This study examined the effects of long-term creatine supplementation combined with resistance training ( RT ) on the one-repetition maximum ( 1RM ) strength , motor functional performance ( e.g. , 30-s chair st and , arm curl , and getting up from lying on the floor tests ) and body composition ( e.g. , fat-free mass , muscle mass , and % body fat using DEXA scans ) in older women . Eighteen healthy women ( 64.9 ± 5.0 years ) were r and omly assigned in a double-blind fashion to either a creatine ( CR , N = 9 ) or placebo ( PL , N = 9 ) group . Both groups underwent a 12-week RT program ( 3 days week−1 ) , consuming an equivalent amount of either creatine ( 5.0 g day−1 ) or placebo ( maltodextrin ) . After 12 week , the CR group experienced a greater ( P curl ( + 8.8 ) performance than the PL group . Furthermore , CR group gained significantly more fat-free mass ( + 3.2 ) and muscle mass ( + 2.8 ) and were more efficient in performing submaximal-strength functional tests than the PL group . No changes ( P > 0.05 ) in body mass or % body fat were observed from pre- to post-test in either group . These results indicate that long-term creatine supplementation combined with RT improves the ability to perform submaximal-strength functional tasks and promotes a greater increase in maximal strength , fat-free mass and muscle mass in older women", "Aging is associated with lower muscle mass and an increase in body fat . We examined whether creatine monohydrate ( CrM ) and conjugated linoleic acid ( CLA ) could enhance strength gains and improve body composition ( i.e. , increase fat-free mass ( FFM ) ; decrease body fat ) following resistance exercise training in older adults ( > 65 y ) . Men ( N = 19 ) and women ( N = 20 ) completed six months of resistance exercise training with CrM (5g/d)+CLA ( 6g/d ) or placebo with r and omized , double blind , allocation . Outcomes included : strength and muscular endurance , functional tasks , body composition ( DEXA scan ) , blood tests ( lipids , liver function , CK , glucose , systemic inflammation markers ( IL-6 , C-reactive protein ) ) , urinary markers of compliance ( creatine/creatinine ) , oxidative stress ( 8-OH-2dG , 8-isoP ) and bone resorption ( Ν-telopeptides ) . Exercise training improved all measurements of functional capacity ( P and strength ( P in most measurements of muscular endurance , isokinetic knee extension strength , FFM , and lower fat mass ( P ( P not creatinine clearance , increased for CrM+CLA , with no changes in serum CK activity or liver function tests . Together , this data confirms that supervised resistance exercise training is safe and effective for increasing strength in older adults and that a combination of CrM and CLA can enhance some of the beneficial effects of training over a six-month period . Trial Registration . Clinical Trials.gov", "Objective To investigate the combined and separate effects of exercise and milk fat globule membrane ( MFGM ) supplementation on frailty , physical function , physical activity level , and hematological parameters in community-dwelling elderly Japanese women . Methods A total of 131 frail , elderly women over 75 years were r and omly assigned to one of four groups : exercise and MFGM supplementation ( Ex+MFGM ) , exercise and placebo ( Ex+Plac ) , MFGM supplementation , or the placebo group . The exercise group attended a 60-minute training program twice a week for three months , and the MFGM group ingested 1 g of the MFGM supplement in pill form , daily for 3 months . The primary outcome measure was change in frailty status based on Fried ’s frailty phenotype . Secondary outcome measures included body composition , physical function and hematological parameters , and interview survey components assessing lifestyle factors . Participants were followed for 4 months post-intervention . Results Significant group × time interactions were observed for usual walking speed ( P = 0.005 ) , timed up & go ( P insulin-like growth factor-binding protein 3 / insulin-like growth factor 1 ratio ( P = 0.013 ) . The frailty components revealed that weight loss , exhaustion , low physical activity , and slow walking speed were reversed , but low muscle strength did not significantly changed . Frailty reversal rate was significantly higher in the Ex+MFGM ( 57.6 % ) than in the MFGM ( 28.1 % ) or placebo ( 30.3 % ) groups at post-intervention ( χ2 = 8.827 , P = 0.032 ) , and at the follow-up was also significantly greater in the Ex+MFGM ( 45.5 % ) and Ex+Plac ( 39.4 % ) groups compared with the placebo ( 15.2 % ) group ( χ2 = 8.607 , P = 0.035 ) . The exercise+MFGM group had the highest odds ratio ( OR ) for frailty reversal at post-intervention and follow-up ( OR = 3.12 , 95 % confidence interval ( CI ) = 1.13–8.60 ; and OR = 4.67 , 95 % CI = 1.45–15.08 , respectively ) . Conclusion This study suggests that interventions including exercise and nutrition can improve frailty status . Statistically significant additive effects of MFGM with exercise could not be confirmed in this population , and further investigation in larger sample s is necessary . Trial Registration The Japan Medical Association Clinical Trial Registry", "Purpose To examine the effects of 12 weeks of periodized resistance training ( RT ) with and without combined creatine and whey protein supplementation on changes in body composition , muscular strength , and functional performance . Methods Twenty-two male volunteers ( 68.1 ± 6.1 years ) were r and omly assigned to one of three groups : RT plus supplementation ( RTS , n = 7 ) ; RT only ( RT , n = 7 ) ; or control ( C , n = 8) . RTS consumed 0.3 g/kg/day of creatine for 5 days followed by 0.07 g/kg/day . RTS also consumed one 35 g liquid protein ready-to-drink daily . RT and RTS trained 3 days/week . Results Following 12 weeks of training , there were no significant differences in the main measured outcome variables between RT and RTS . RTS increased relative ( % change ) lean body mass ( LBM , 3.3 ± 3.1 % ) compared with C ( p = 0.01 ) . Compared to baseline , RT increased LBM at week 6 ( 60.2 ± 8.3 to 61.6 ± 9.4 kg ; p decreased fat mass ( 20.8 ± 4.2 to 19.0 ± 3.9 kg ; p = 0.05 ) and percentage body fat at week 12 ( 25.7 ± 3.8 to 23.8 ± 4.0 % ; p = 0.05 ) ; RTS increased LBM at week 6 ( p 0.01 ) , and decreased percentage body fat at week 12 ( 23.9 ± 4.4 to 22.0 ± 4.4 % ; p addition , compared to C , relative bench press 1-RM increased for RTS ( 72.4 ± 62.2 % ; p ) and RT ( 50.1 ± 21.5 % ; p = 0.05 ) ; relative leg press 1-RM increased for RTS ( 129.6 ± 39.4 % ; p RT ( 112.9 ± 22.7 % ; p power ( 38.3 ± 30.4 % ; p walk time decreased for RT ( −11 ± 9.2 % ; p RTS ( −9.6 ± 9.4 % ; p = 0.05 ) . RT increased estimated VO2Max at week 6 ( p baseline . Lastly , RTS increased estimated VO2Max at week 12 ( 36.3 ± 2.7 to 37.5 ± 3.3 ml/kg/min ; p = 0.05 ) compared to baseline . Conclusion Creatine and whey protein supplementation may not provide additional benefits in older adults performing periodized RT to augment muscular and functional performance", "Background / objectives : A few previous studies indicate that protein supplementation increases gains in muscle mass and strength during a resistance exercise program . The purpose of this study was to investigate whether whey protein supplementation results in greater increases in lean body mass , muscle strength and physical function in elderly individuals during 12 weeks of resistance exercise when compared to isocaloric carbohydrate supplementation . Subjects/ Methods : A total of 161 men and women , 65–91 years old , participated in a r and omized , controlled , double-blind intervention study , involving dietary supplementation and a 12-week resistance exercise program , design ed to increase muscle mass and strength of all major muscle groups . Participants exercised three times a week and received either 20 g of whey protein ( n=83 ) or isocaloric carbohydrate ( n=78 ) in liquid form immediately after each workout . Data were obtained at baseline and end point . Results : The primary outcomes , lean body mass , strength and physical function increased significantly during the course of the study . Type of dietary supplementation did not influence gains in lean body mass ( P=0.365 ) , quadriceps strength ( P=0.776 ) or performance during a 6-min walk ( P=0.726 ) or a timed up- and -go test ( P=0.151 ) . Twenty participants discontinued the intervention . Conclusions : Ingestion of 20 g of whey protein immediately after resistance exercise three times per week , does not lead to greater gains in lean body mass , strength and physical function in elderly people with sufficient energy and protein intakes when compared to isocaloric carbohydrate", "Objective Isoflavones and exercise have been shown to affect C-reactive protein ( CRP ) and body composition and to act synergistically on trunk and total fat mass ( FM ) , glucose metabolism , and lean body mass in postmenopausal women with a body mass index higher than 25 kg/m2 . We hypothesized that exercise and isoflavone supplementation ( Ex + ISO ) could reduce inflammation in the same sub population of women . The objective of this study was to investigate if 6 months of mixed exercise combined with isoflavones could have greater effects on specific inflammatory markers than exercise alone in overweight or obese postmenopausal women . Methods Thirty-four postmenopausal women aged 50 to 70 years were r and omly assigned to exercise and placebo ( Ex + PLA ; n = 15 ) or Ex + ISO ( n = 19 ) . At baseline and after 6 months , waist circumference , hip circumference , total FM , trunk FM , leg FM , and muscle mass index ( MMI ; = total fat free mass [ kg ] / height2 [ m ] ) were assessed ( dual-energy x-ray absorptiometry ) . Inflammatory markers ( CRP , tumor necrosis factor-&agr ; [ TNF-&agr ; ] , and interleukin-6 ) were obtained by enzyme-linked immunosorbent assay . T tests were used to compare groups at baseline . Results The Ex + PLA group showed significant changes in MMI ( + 0.33 kg/m2 , P ⩽ 0.009 ) and FM compartments ( waist circumference , −5.13 cm ; % FM , −1.31 % ; P ⩽ 0.001 ) , whereas inflammation remained unchanged . However , the Ex + ISO group showed significant changes in total FM ( −1.70 kg , P compartments ( hip circumference [ −2.51 cm , P = 0.019 ] , leg FM [ −1.16 kg , P = 0.037 ] , and trunk FM [ −0.72 kg , P = 0.006 ] ) , MMI ( + 0.39 kg , P = 0.011 ) , and inflammation ( CRP , −1.14 mg/L , P = 0.029 ; TNF-&agr ; , + 0.29 pg/mL , P = 0.010 ) . Conclusions Despite an increase in TNF-&agr ; , the use of isoflavones — when body weight remains stable — seems to enhance the beneficial effects of mixed-exercise training on body composition and CRP in overweight or obese postmenopausal women", "We examined whether post-exercise macronutrient supplementation during a 5-month home-based interval walking training ( IWT ) accelerated exercise-induced increases in skeletal muscle mass and strength in healthy middle-aged and older women . Thirty-five women ( 41 - 78 years ) were r and omly divided into two groups : IWT alone ( CNT , n = 18 ) or IWT plus post-exercise macronutrient ( 7.6 g protein , 32.5 g carbohydrate , and 4.4 g fat ) supplementation ( NUT , n = 17 ) . For IWT , all subjects were instructed to repeat five or more sets of 3-min low-intensity walking at 40 % peak aerobic capacity ( Vo2 peak ) , followed by a 3-min high-intensity walking above 70 % Vo2 peak per day for 4 or more days per week . We determined Vo2 peak , thigh muscle tissue area by computer tomography , and thigh muscle strength in all subjects before and after IWT . We found that an increase in hamstring muscle tissue area was 2.8 ± 1.2 % in NUT vs -1.0 ± 0.7 % in CNT and that in isometric knee flexion force was 16.3 ± 3.7 % in NUT vs 6.5 ± 3.0 % in CNT ; both were significantly higher in NUT than in CNT ( both , P , post-exercise macronutrient supplementation enhanced the increases in thigh muscle mass and strength , although partially , in home-based IWT in middle-aged and older women", "PURPOSE The intent of this investigation was to examine the effects of a daily oral provision consisting of amino acids ( L-lysine , L-leucine , L-valine , L-phenylalanine , L-threonine , L-histidine , L-isoleucine , and L-methionine ) in combination with carbohydrates ( dextrose , sucrose , and fructose ) on whole muscle strength and size characteristics during a 12-wk progressive knee extensor resistance training ( PRT ) program in older men ( > 65 yr ) . METHODS Seventeen older men were r and omly assigned to either the experimental ( EX ) or control ( CN ) groups . The EX ( N = 8) and CN ( N = 9 ) groups had the following characteristics-EX : 70.8 + /- 1.5 yr , 91.0 + /- 4.9 kg , and 177.0 + /- 3.9 cm ; CN : 72.1 + /- 1.9 yr , 75.4 + /- 4.7 kg , and 176.1 + /- 3.0 . Pre and post PRT maximal unilateral isometric torque ( N.m ) , isokinetic torque ( 1.05 , 1.57 , 2.09 , 3.14 , 4.19 , and 5.24 rad.s-1 ) , work capacity ( 30 consecutive reps at 3.14 rad.s-1 ) torque , one repetition maximum ( 1RM ) bilateral isotonic strength , and whole muscle cross-sectional area ( CSA ) of the mid-thigh were performed by computed tomography on each subject . RESULTS All variables showed an improvement with training ( P isometric strength by 21 % , and isokinetic torque by 24 % to 11 % with the varying velocities ( 1.05 - 5.24 rad.s-1 ) . Whole muscle 1RM strength and thigh CSA increased 50 % and 6.5 % , respectively . Additionally , voluntary torque/CSA increased 12 % in both the EX and CN groups ( P oral amino-acid complex during 12 wk of PRT in older men", "This study aim ed to examine the efficacy of creatine supplementation , associated or not with resistance training , in vulnerable older women . A 24-week , double-blind , r and omized , placebo-controlled trial was performed . Sixty subjects were assigned to compose the following groups : placebo ( PL ) , creatine supplementation ( CR ) , placebo with resistance training ( PL+RT ) , and creatine supplementation with resistance training ( CR+RT ) . The subjects were assessed at baseline and after 24weeks . The primary outcome was muscle strength , as assessed by one-repetition maximum ( 1-RM ) tests . Secondary outcomes included appendicular lean mass , bone mass , biochemical bone markers , and physical function tests . The changes in 1-RM leg press were significantly greater in the CR+RT group ( + 19.9 % ) than in the PL ( + 2.4 % ) and the CR groups ( + 3.7 % ) , but not than in the PL+RT group ( + 15 % ) ( p=0.002 , p=0.002 , and p=0.357 , respectively ) . The CR+RT group showed superior gains in 1-RM bench press ( + 10 % ) when compared with all the other groups ( p≤0.05 ) . The CR+RT group ( + 1.31 % ) showed greater appendicular lean mass accrual than the PL ( -1.2 % ) , the CR ( + 0.3 % ) , and the PL+RT groups ( -0.2 % ) ( p≤0.05 ) . The CR and the PL+RT groups experienced comparable gains in appendicular lean mass ( p=0.62 ) , but superior to those seen in the PL group . Changes in fat mass , bone mass and serum bone markers did not significantly differ between the groups ( p>0.05 ) . In conclusion , creatine supplementation combined with resistance training improved appendicular lean mass and muscle function , but not bone mass , in older vulnerable women . Clinical trials.gov : NCT01472393", "BACKGROUND Whey protein supplementation may augment resistance exercise-induced increases in muscle strength and mass . Further studies are required to determine whether this effect extends to mobility-limited older adults . The objectives of the study were to compare the effects of whey protein concentrate ( WPC ) supplementation to an isocaloric control on changes in whole-body lean mass , mid-thigh muscle cross-sectional area , muscle strength , and stair-climbing performance in older mobility-limited adults in response to 6 months of resistance training ( RT ) . METHODS Eighty mobility-limited adults aged 70 - 85 years were r and omized to receive WPC ( 40g/day ) or an isocaloric control for 6 months . All participants also completed a progressive high-intensity RT intervention . Sample sizes were calculated based on the primary outcome of change in whole-body lean mass to give 80 % power for a 0.05-level , two-sided test . RESULTS Lean mass increased 1.3 % and 0.6 % in the WPC and control groups , respectively . Muscle cross-sectional area was increased 4.6 % and 2.9 % in the WPC and control groups , respectively , and muscle strength increased 16%-50 % in WPC and control groups . Stair-climbing performance also improved in both groups . However , there were no statistically significant differences in the change in any of these variables between groups . CONCLUSIONS These data suggest that WPC supplementation at this dose does not offer additional benefit to the effects of RT in mobility-limited older adults", "OBJECTIVES To evaluate the effects of elastic b and resistance training in combination with nutrient supplementation on muscular strength and the ability to perform mobility-related activities of daily living in older adults living in retirement care facilities . DESIGN R and omized controlled trial , with a 6-month intervention period . SETTING A retirement care facility , Vienna , Austria . PARTICIPANTS One hundred and seventeen older adults ( 14 males ( 12 % ) and 103 females ( 88 % ) ) , aged 65 to 97 years ( mean age : 82.8 ± 6.0 ) , having a mini-mental state examination score ≥ 23 and no chronic diseases posing a medical contraindication to training therapy . INTERVENTION Participants were r and omly assigned , but stratified by sex , to one of three intervention groups : supervised resistance exercise training ( RT ) , RT in combination with nutrient supplementation ( RTS ) , or cognitive training group ( CT ) . All interventions were performed two times a week for 6 months . RT was design ed to train all major muscle groups using elastic b and s. The nutrient supplement ( rich in proteins , vitamin D , B2 , B12 ) was distributed every morning as well as after each RT session . MEASUREMENTS A battery of motor ability tests and functional test were performed prior to as well as following 3 months and finally after 6 months of intervention . These tests included isokinetic torque measurements of the knee extensors and flexors in concentric mode at 60 and 120 ° /s , isometric h and grip strength , senior arm-lifting test , chair st and test , maximum walking speed and a 6-minute walking test ( 6 MWT ) . RESULTS A repeated- measures ANOVA analysis revealed significant improvements in physical function of lower ( p=0.002 ) and upper extremities ( p=0.006 ) for RT and /or RTS in comparison to CT . For isokinetic measurements , 6 MWT , and gait speed time effects ( p showed lower performance in chair st and test ( p=0.012 ) , 6 MWT ( p=0.003 ) , and gait speed ( p=0.013 ) at baseline than that of the finishers of the study . CONCLUSION Six months of a low intensity resistance exercise using elastic b and s and own body weight is safe and beneficial in improving functional performance of institutionalised older people . Multinutrient supplementation did not offer additional benefits to the effects of RT in improving muscular performance", "Objective : To describe the independent and combined effects of oral nutrition supplementation and resistance training on health outcomes in nutritionally at risk older adults following lower limb fracture . Design : R and omized controlled trial with 12-week masked outcome assessment . Setting : Teaching hospital . Participants : One hundred nutritionally at risk older adults hospitalized following a fall-related lower limb fracture . Intervention : Commenced seven days after injury . Consisted of daily multinutrient energy-dense oral supplement ( 6.3 kJ/mL ) individually prescribed for six weeks ( n = 25 ) , tri-weekly resistance training for 12 weeks ( n = 25 ) , combined treatment ( n = 24 ) or attention control plus usual care and general nutrition and exercise advice ( n = 26 ) . Measurements : Weight change , quadriceps strength , gait speed , quality of life and health care utilization at completion of the 12-week intervention . Results : At 12 weeks , all groups lost weight : nutrition -6.2 % ( -8.4 , -4.0 ) ; resistance training -6.3 % ( -8.3 , -4.3 ) ; nutrition and resistance training -4.7 % ( -7.4 , -2.0 ) ; attention control -5.2 % ( -9.0 , -1.5 ) . Those receiving resistance training alone lost more weight than those receiving the combined treatment ( P = 0.029 ) . Significant weight loss was prevented if supplement was consumed for at least 35 days . Groups were no different at 12 weeks for any other outcome . Conclusion : Frail , undernourished older adults with a fall-related lower limb fracture experience clinical ly significant weight loss that is unable to be reversed with oral nutritional supplements . Those receiving a programme of resistance training without concurrent nutrition support are at increased risk of weight loss compared with those who receive a combined nutrition and resistance training intervention . In this high-risk patient group it is possible to prevent further decline in nutritional status using oral nutritional supplements if strategies are implemented to ensure prescription is adequate to meet energy requirements and levels of adherence are high", "OBJECTIVES This study determined the effect of enriched foods and all-around physical exercise on bone and body composition in frail elderly persons . METHODS A 17-week r and omized , controlled intervention trial , following a 2 x 2 factorial design --(1 ) enriched foods , ( 2 ) exercise , ( 3 ) both , or ( 4 ) neither -- was performed in 143 frail elderly persons ( aged 78.6 + /- 5.6 years ) . Foods were enriched with multiple micronutrients ; exercises focused on skill training , including strength , endurance , coordination , and flexibility . Main outcome parameters were bone and body composition . RESULTS Exercise preserved lean mass ( mean difference between exercisers and non-exercisers : 0.5 kg + /- 1.2 kg ; P bone mineral density ( + 0.4 % ) , bone mass ( + 0.6 % ) , and bone calcium ( + 0.6 % ) compared with groups receiving non-enriched foods , in whom small decreases of 0.1 % , 0.2 % , and 0.4 % , respectively , were found . These groups differed in bone mineral density ( 0.006 + /- 0.020 g/cm2 ; P = .08 ) , total bone mass ( 19 + /- g ; P = .04 ) , and bone calcium ( 8 + /- 21 g ; P = .03 ) . CONCLUSIONS Foods containing a physiologic dose of micronutrients slightly increased bone density , mass , and calcium , whereas moderately intense exercise preserved lean body mass in frail elderly persons", "BACKGROUND Magnesium deficiency is associated with poor physical performance , but no trials are available on how magnesium supplementation affects elderly people 's physical performance . OBJECTIVE The aim of our study was to investigate whether 12 wk of oral magnesium supplementation can improve physical performance in healthy elderly women . DESIGN In a parallel-group , r and omized controlled trial , 139 healthy women ( mean ± SD age : 71.5 ± 5.2 y ) attending a mild fitness program were r and omly allocated to a treatment group ( 300 mg Mg/d ; n = 62 ) or a control group ( no placebo or intervention ; n = 77 ) by using a computer-generated r and omization sequence , and research ers were blinded to their grouping . After assessment at baseline and again after 12 wk , the primary outcome was a change in the Short Physical Performance Battery ( SPPB ) ; secondary outcomes were changes in peak torque isometric and isokinetic strength of the lower limbs and h and grip strength . RESULTS A total of 124 participants allocated to the treatment ( n = 53 ) or control ( n = 71 ) group were considered in the final analysis . At baseline , the SPPB scores did not differ between the 2 groups . After 12 wk , the treated group had a significantly better total SPPB score ( Δ = 0.41 ± 0.24 points ; P = 0.03 ) , chair st and times ( Δ = -1.31 ± 0.33 s ; P and 4-m walking speeds ( Δ = 0.14 ± 0.03 m/s ; P = 0.006 ) than did the control group . These findings were more evident in participants with a magnesium dietary intake lower than the Recommended Dietary Allowance . No significant differences emerged for the secondary outcomes investigated , and no serious adverse effects were reported . CONCLUSIONS Daily magnesium oxide supplementation for 12 wk seems to improve physical performance in healthy elderly women . These findings suggest a role for magnesium supplementation in preventing or delaying the age-related decline in physical performance", "OBJECTIVES Protein supplementation has been proposed as an effective dietary strategy to augment the skeletal muscle adaptive response to prolonged resistance-type exercise training in elderly people . Our objective was to assess the impact of protein supplementation on muscle mass , strength , and physical performance during prolonged resistance-type exercise training in frail elderly men and women . DESIGN / SETTING / PARTICIPANTS A r and omized , double-blind , placebo-controlled trial with 2 arms in parallel among 62 frail elderly subjects ( 78 ± 1 year ) . These elderly subjects participated in a progressive resistance-type exercise training program ( 2 sessions per week for 24 weeks ) during which they were supplemented twice daily with either protein ( 2 * 15 g ) or a placebo . MEASUREMENTS Lean body mass ( DXA ) , strength ( 1-RM ) , and physical performance ( SPPB ) were assessed at baseline , and after 12 and 24 weeks of intervention . RESULTS Lean body mass increased from 47.2 kg ( 95 % CI , 43.5 - 50.9 ) to 48.5 kg ( 95 % CI , 44.8 - 52.1 ) in the protein group and did not change in the placebo group ( from 45.7 kg , 95 % CI , 42.1 - 49.2 to 45.4 kg , 95 % CI , 41.8 - 48.9 ) following the intervention ( P value for treatment × time interaction = .006 ) . Strength and physical performance improved significantly in both groups ( P = .000 ) with no interaction effect of dietary protein supplementation . CONCLUSIONS Prolonged resistance-type exercise training represents an effective strategy to improve strength and physical performance in frail elderly people . Dietary protein supplementation is required to allow muscle mass gain during exercise training in frail elderly people . TRIAL REGISTRATION clinical trials.gov identifier : NCT01110369", "BACKGROUND Physical inactivity , inadequate dietary protein , and low- grade systemic inflammation contribute to age-related muscle loss , impaired function , and disability . OBJECTIVE We assessed the effects of progressive resistance training ( PRT ) combined with a protein-enriched diet facilitated through lean red meat on lean tissue mass ( LTM ) , muscle size , strength and function , circulating inflammatory markers , blood pressure , and lipids in elderly women . DESIGN In a 4-mo cluster r and omized controlled trial , 100 women aged 60 - 90 y who were residing in 15 retirement villages were allocated to receive PRT with lean red meat ( ∼160 g cooked ) to be consumed 6 d/wk [ resistance training plus lean red meat ( RT+Meat ) group ; n = 53 ] or control PRT [ 1 serving pasta or rice/d ; control resistance training ( CRT ) group ; n = 47 ) ] . All women undertook PRT 2 times/wk and received 1000 IU vitamin D3/d . RESULTS The mean ( ± SD ) protein intake was greater in the RT+Meat group than in the CRT group throughout the study ( 1.3 ± 0.3 compared with 1.1 ± 0.3 g · kg⁻¹ · d⁻¹ , respectively ; P greater gains in total body LTM ( 0.45 kg ; 95 % CI : 0.07 , 0.84 kg ) , leg LTM ( 0.22 kg ; 95 % CI : 0.02 , 0.42 kg ) , and muscle strength ( 18 % ; 95 % CI : 0.03 , 0.34 ) than did the CRT group ( all P greater increase in serum insulin-like growth factor I ( P greater reduction in the proinflammatory marker interleukin-6 ( IL-6 ) ( P the change in blood lipids or blood pressure . CONCLUSION A protein-enriched diet equivalent to ∼1.3 g · kg⁻¹ · d⁻¹ achieved through lean red meat is safe and effective for enhancing the effects of PRT on LTM and muscle strength and reducing circulating IL-6 concentrations in elderly women . This trial was registered at the Australian Clinical Trials Registry as ACTRN12609000223235", "BACKGROUND Loss of muscle mass due to prolonged bed rest decreases functional capacity and increases hospital morbidity and mortality in older adults . OBJECTIVE To determine if HMB , a leucine metabolite , is capable of attenuating muscle decline in healthy older adults during complete bed rest . DESIGN A r and omized , controlled , double-blinded , parallel-group design study was carried out in 24 healthy ( SPPB ≥ 9 ) older adult subjects ( 20 women , 4 men ) , confined to complete bed rest for ten days , followed by resistance training rehabilitation for eight weeks . Subjects in the experimental group were treated with HMB ( calcium salt , 1.5 g twice daily - total 3 g/day ) . Control subjects were treated with an inactive placebo powder . Treatments were provided starting 5 days prior to bed rest till the end rehabilitation phase . DXA was used to measure body composition . RESULTS Nineteen eligible older adults ( BMI : 21 - 33 ; age : 60 - 76 year ) were evaluable at the end of the bed rest period ( Control n = 8 ; Ca-HMB n = 11 ) . Bed rest caused a significant decrease in total lean body mass ( LBM ) ( 2.05 ± 0.66 kg ; p = 0.02 , paired t-test ) in the Control group . With the exclusion of one subject , treatment with HMB prevented the decline in LBM over bed rest -0.17 ± 0.19 kg ; p = 0.23 , paired t-test ) . There was a statistically significant difference between treatment groups for change in LBM over bed rest ( p = 0.02 , ANOVA ) . Sub- analysis on female subjects ( Control = 7 , HMB = 8) also revealed a significant difference in change in LBM over bed rest between treatment groups ( p = 0.04 , ANOVA ) . However , differences in function parameters could not be observed , probably due to the sample size of the study . CONCLUSIONS In healthy older adults , HMB supplementation preserves muscle mass during 10 days of bed rest . These results need to be confirmed in a larger trial", "OBJECTIVES To evaluate the effectiveness of exercise and amino acid supplementation in enhancing muscle mass and strength in community-dwelling elderly sarcopenic women . DESIGN R and omized controlled trial . SETTING Urban community in Tokyo , Japan . PARTICIPANTS One hundred fifty-five women aged 75 and older were defined as sarcopenic and r and omly assigned to one of four groups : exercise and amino acid supplementation ( exercise + AAS ; n = 38 ) , exercise ( n = 39 ) , amino acid supplementation ( AAS ; n = 39 ) , or health education ( HE ; n = 39 ) . INTERVENTION The exercise group attended a 60-minute comprehensive training program twice a week , and the AAS group ingested 3 g of a leucine-rich essential amino acid mixture twice a day for 3 months . MEASUREMENTS Body composition was determined using bioelectrical impedance analysis . Data from interviews and functional fitness parameters such as muscle strength and walking ability were collected at baseline and after the 3-month intervention . RESULTS A significant group × time interaction was seen in leg muscle mass ( P = .007 ) , usual walking speed ( P = .007 ) , and knee extension strength ( P = .017 ) . The within-group analysis showed that walking speed significantly increased in all three intervention groups , leg muscle mass in the exercise + AAS and exercise groups , and knee extension strength only in the exercise + AAS group ( 9.3 % increase , P = .01 ) . The odds ratio for leg muscle mass and knee extension strength improvement was more than four times as great in the exercise + AAS group ( odds ratio = 4.89 , 95 % confidence interval = 1.89 - 11.27 ) as in the HE group . CONCLUSION The data suggest that exercise and AAS together may be effective in enhancing not only muscle strength , but also combined variables of muscle mass and walking speed and of muscle mass and strength in sarcopenic women", "We sought to determine whether creatine monohydrate ( CrM ) supplementation would enhance the increases in strength and fat-free mass that develop during resistance exercise training in older adults . Twenty-eight healthy men and women over the age of 65 years participated in a whole-body resistance exercise program 3 days per week for 14 weeks . The study participants were r and omly allocated , in a double-blind fashion , to receive either CrM ( 5 g/d + 2 g of dextrose ; n = 14 ) or placebo ( 7 g of dextrose ; n = 14 ) . The primary outcome measurements included the following : total body mass , fat-free mass , one-repetition maximum strength for each body part , isometric knee extension , h and grip , and dorsiflexion strength , chair st and performance , 30-m walk test , 14-stair climb performance , muscle fiber type and area , and intramuscular total creatine . Fourteen weeks of resistance exercise training result ed in significant increases in all measurements of strength and functional tasks and muscle fiber area for both groups ( p fat-free mass and total body mass , as compared with placebo ( p isometric knee extension strength in men and women , as compared with placebo ( p isometric dorsiflexion strength ( p intramuscular total creatine in the CrM group ( p side effects of treatment or exercise training . This study confirms that supervised heavy resistance exercise training can safely increase muscle strength and functional capacity in older adults . The addition of CrM supplementation to the exercise stimulus enhanced the increase in total and fat-free mass , and gains in several indices of isometric muscle strength", "AIM To investigate the effects of exercise and /or tea catechin supplementation on muscle mass , strength and walking ability in elderly Japanese women with sarcopenia . METHODS A total of 128 women aged over 75 years were defined as sarcopenic and r and omly assigned into four groups : exercise and tea catechin supplementation ( n = 32 ) , exercise ( n = 32 ) , tea catechin supplementation ( n = 32 ) or health education ( n = 32 ) . The exercise group attended a 60-min comprehensive training program twice a week and the tea catechin supplementation group ingested 350 mL of a tea beverage fortified with catechin daily for 3 months . Body composition was determined by bioelectrical impedance analysis . Interview data and functional fitness measurements , such as muscle strength , balance and walking ability , were collected at baseline and after the 3-month intervention . RESULTS There were significant group × time interactions observed in timed up & go ( P usual walking speed ( P = 0.007 ) and maximum walking speed ( P + catechin group showed a significant effect ( odds ratio 3.61 , 95 % confidence interval 1.05 - 13.66 ) for changes in the combined variables of leg muscle mass and usual walking speed compared with the health education group . CONCLUSIONS The combination of exercise and tea catechin supplementation had a beneficial effect on physical function measured by walking ability and muscle mass", "OBJECTIVE To examine the effects of an exercise program and an enriched food regimen on physical functioning of frail elderly persons . DESIGN A 17-week r and omized , placebo-controlled trial . SETTING Community . PARTICIPANTS One hundred fifty-seven independently living frail elderly ( mean age , 78.7 + /- 5.6yr ) . INTERVENTION Thirty-nine subjects participated in a twice weekly group exercise design ed to improve daily functioning ; 39 subjects daily ate foods enriched with vitamins and minerals ( at 25%-100 % of the recommended daily allowances ) ; 42 subjects exercised and ate enriched foods ; and 37 subjects served as controls . Nonexercising groups followed a social program ; nonsupplement groups received the same food products without the micronutrients . MAIN OUTCOME MEASURES Functional performance based on 6 performance tests , physical fitness based on 7 fitness tests , and disabilities based on the self-reported ability to perform 16 daily activities . RESULTS Performance sum scores were significantly enhanced in trained ( + 8 % ) compared with nontrained subjects ( -8 % ) ( difference in change : 1.9 points , p Fitness sum scores were significantly enhanced as well ( + 3 % in trained vs -2 % in nontrained ) ( difference in change : 0.9 points , p = .05 , adjusted for baseline scores ) . No exercise effects on the disability score were observed . Consumption of enriched products did not affect performance , fitness , or disability scores . CONCLUSION Our comprehensive exercise program , design ed for widespread applicability , enhanced physical performance and fitness in a population of frail elderly . Daily consumption of micronutrient enriched foods showed no functional benefits within 17 weeks", "BACKGROUND Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people , the efficacy of interventions targeted specifically at these deficits has not been carefully studied . METHODS We conducted a r and omized , placebo-controlled trial comparing progressive resistance exercise training , multinutrient supplementation , both interventions , and neither in 100 frail nursing home residents over a 10-week period . RESULTS The mean ( + /- SE ) age of the 63 women and 37 men enrolled in the study was 87.1 + /- 0.6 years ( range , 72 to 98 ) ; 94 percent of the subjects completed the study . Muscle strength increased by 113 + /- 8 percent in the subjects who underwent exercise training , as compared with 3 + /- 9 percent in the nonexercising subjects ( P Gait velocity increased by 11.8 + /- 3.8 percent in the exercisers but declined by 1.0 + /- 3.8 percent in the nonexercisers ( P = 0.02 ) . Stair-climbing power also improved in the exercisers as compared with the nonexercisers ( by 28.4 + /- 6.6 percent vs. 3.6 + /- 6.7 percent , P = 0.01 ) , as did the level of spontaneous physical activity . Cross-sectional thigh-muscle area increased by 2.7 + /- 1.8 percent in the exercisers but declined by 1.8 + /- 2.0 percent in the nonexercisers ( P = 0.11 ) . The nutritional supplement had no effect on any primary outcome measure . Total energy intake was significantly increased only in the exercising subjects who also received nutritional supplementation . CONCLUSIONS High-intensity resistance exercise training is a feasible and effective means of counteracting muscle weakness and physical frailty in very elderly people . In contrast , multi-nutrient supplementation without concomitant exercise does not reduce muscle weakness or physical frailty" ]

[ "Objectives To compare the Visual Analogue Scale ( VAS ) and the Verbal Numerical Rating Scale ( VNRS ) , in the assessment of acute pain in the emergency department ( ED ) . Furthermore , to determine the influence of demographics on this agreement and practical limitations of the scales . Setting St Vincent 's University Hospital , Dublin ; a 479-bed teaching hospital ; annual ED census 36 000 adult patients . Methods A prospect i ve observational study was conducted on ED patients with acute pain as a component of their presenting complaint . Eligible patients scored their pain on both VAS and VNRS within 1 hour of arrival . They rescored their pain every 30 minutes for 2 hours using both scales . The primary outcome measure was agreement between VAS and VNRS . Secondary outcomes were ease of pain scale use and effect of patient demographics on pain scores . Agreement between scores was evaluated using the Bl and -Altman method . Results 123 patients were included ( median age 35 ; 43.9 % male ) . There was a strong correlation between VAS and VNRS ( rs=0.93 ) . However , there was not perfect agreement between the two scales . Patient age ( older age , p VNRS . There was a preference for VNRS in those patients who expressed a preference for one pain scale over the other . Conclusions VAS and VNRS are not interchangeable in assessing an individual patient 's pain over time in the ED setting . VNRS has practical advantages over VAS in this setting", "Background : Pain intensity is commonly reported using a 0–10 Numeric Rating Scale in pain clinical trials . Analysis of the change on the Pain Intensity Numerical Rating Scale as a proportion has most consistently correlated with clinical ly important differences reported on the patient 's global impression of change . The correlation of data from patients with breakthrough pain with a Pain Relief Scale and a different global outcome measures will extend our underst and ing of these measures . Methods : Data were obtained from the open titration phase of a multiple crossover , r and omized , double-blind clinical trial comparing oral transmucosal fentanyl citrate with immediate-release oral morphine sulfate for the treatment of cancer-related breakthrough pain . Raw and percentage changes in the pain intensity scores from 1,307 episodes of pain in 134 oral transmucosal fentanyl citrate-naïve patients were correlated with the clinical ly relevant secondary outcomes of Pain Relief Verbal Response Scale and the global medication performance scale . The changes in raw and percentage change were assessed over time and compared with the ordinal Pain Relief Verbal Response Scale and Global Medication Performance Scale . Results : The P value of the interaction between the raw pain intensity difference was significant ( P = 0.034 ) for four 15-min time periods but not for the percentage pain intensity difference score ( P = 0.26 ) . We found similar results in comparison with the ordinal Pain Relief Verbal Response Scale ( P = 0.0048 and P = 0.36 respectively ) and global medication performance categories ( P = 0.048 and P = 0.45 , respectively ) . Conclusion : The change in pain intensity in breakthrough pain was more consistent over time and when compared with both the Pain Relief Verbal Response Scale and the Global Medication Performance Scale when the percentage change is used rather than raw pain intensity difference", "STUDY OBJECTIVE To identify the minimum clinical ly significant difference in pain in elderly emergency department ( ED ) patients . METHODS This was an observational , prospect i ve study of a convenience sample of patients aged 65 years or older with acute pain . Patients rated their pain on an 11-point numeric rating scale ( NRS ) on entering the study and every 30 minutes for 2 hours . The arithmetic minimum clinical ly significant difference was defined as the mean difference between current and preceding NRS scores when the subject described his or her pain as \" a little less pain \" or \" a little more pain . \" The proportional minimum clinical ly significant difference was change in NRS in a 30-minute interval divided by the NRS at the beginning of the interval . We used generalized estimating equations to adjust for nonindependence of pain scores and to test trend over time . RESULTS One hundred ninety-five patients were enrolled ( mean age 74 years ; 73 % women ; 51 % Hispanic ; 33 % black ) . The arithmetic minimum clinical ly significant difference averaged over all periods was 1.5 ( 95 % confidence interval 1.3 to 1.6 ) , the proportional minimum clinical ly significant difference was 25 % ( 95 % confidence interval 20 % to 29 % ) . The arithmetic minimum clinical ly significant difference unexpectedly decreased over time : 2.1 from baseline to 30 minutes , 1.4 from 30 to 60 minutes , 1.3 from 60 to 90 minutes , and 1.0 from 90 to 120 minutes ( P proportional differences were more stable : 27 % from baseline to 30 minutes , 22 % from 30 to 60 minutes , 22 % from 60 to 90 minutes , and 28 % from 90 to 120 minutes ( P=.89 ) . CONCLUSION The arithmetic minimum clinical ly significant difference in older ED patients was 1.5 NRS units and decreased over time , whereas the proportional change was 25 % and more stable", "In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials", "Study Design . Prospect i ve study of two sample s of patients with acute and chronic low back pain , respectively . Objectives . To compare the responsiveness of four functional status question naires , Rol and Morris Disability Question naire ( RMDQ ) , Oswestry Disability Index ( ODI ) , Disability Rating Index ( DRI ) , and Physical Functioning scale of the SF-36 ( PFSF-36 ) , and two pain scales , a Numerical Pain Rating Scale ( NRS ) and Visual Analogue Scale ( VAS ) . Summary of Background Data . Concurrent comparisons of different outcome measurements in back patients have been requested . Methods . Norwegian versions of the scales and question naires were completed by 54 patients with acute ( 3 months ) . Clinical change was estimated on a global change index . An alternative external criterion was the expected clinical course in the two cohorts . Mean changes , st and ardized response mean ( SRM ) , and area under the receiver operating characteristic ( ROC ) curves with cutoff point for highest sensitivity and specificity were calculated . Results . At the follow-up , 63 % of the acute and 41 % of the chronic sample reported improvement on the global change index . Large SRMs ( 1.3–2.0 ) and areas under the ROC curves ( 0.84–0.93 ) were found for the measurements in the acute sample . In the chronic sample , the SRMs ( 0.4–1.1 ) and areas under the ROC curves ( 0.65–0.83 ) were lower , in particular for the PFSF-36 and the VAS . There was no statistically significant difference between the responsiveness in the measurements , except for higher responsiveness in the NRS compared with the VAS when using expected clinical course as the external criterion for change . Conclusion . The results suggest that all the outcome measures were appropriate for measuring changes in functional status and pain in patients with acute low back pain , whereas among chronic patients the RMDQ , ODI , DRI , and NRS were most appropriate", "BACKGROUND : Self-reported pain scores are used widely in clinical and research setting s , yet little is known about their interpretability in children . In this prospect i ve , observational study we evaluated the relationship between 0 to 10 numerical rating scale ( NRS ) pain scores and other self-reported , clinical ly meaningful outcomes , including perceived need for medicine ( PNM ) , pain relief ( PR ) , and perceived satisfaction ( PS ) with treatment in children postoperatively . METHODS : This study included children ages 7 to 16 years undergoing surgery associated with postoperative pain . One to 4 observations were recorded in each child within the first 24 hours postoperatively . At each assessment , children rated their pain with the NRS , stated their PNM , and rated their satisfaction with pain management . Assessment s were repeated within 1 to 2 hours , and children additionally rated their PR as the same , better , or worse in comparison with the earlier assessment . Receiver operator characteristic curves were developed to examine potential NRS cut-points for PNM and PS , and the minimum clinical ly significant difference ( MCSD ) in pain score associated with PR was calculated . RESULTS : Three hundred ninety-seven observations ( including 189 pairs ) were recorded in 113 children . NRS scores associated with PNM were significantly higher than “ no need ” ( median 6 vs. 3 ; P NRS scores > 4 had good sensitivity ( 0.81 ) and specificity ( 0.70 ) to discriminate PNM , but with a large number of false positives and negatives ( e.g. , 42 % of children with scores > 4 did not need analgesia ) . The MCSD in NRS scores was −1 ( 95 % confidence interval [ CI ] −0.5 to 1 ) or + 1 ( CI 0.5 to 2.7 ) in relation to feel “ a little better ” or “ worse , ” respectively ( P NRS scores > 6 had a sensitivity of 0.82 and specificity of 0.76 in discriminating dissatisfaction with treatment , yet 46 % and 24 % of children with scores > 6 , respectively , were somewhat to very satisfied with their analgesia . CONCLUSIONS : This study provides important information regarding the clinical interpretation of NRS pain scores in children . Data further support the NRS as a valid measure of pain intensity in relation to the child 's PNM , PR , and PS in the acute postoperative setting . However , the variability in scores in relation to other clinical ly meaningful outcomes suggests that application of cut-points for individual treatment decisions is inappropriate", "OBJECTIVE The purpose of this study is to quantify , using the Color Analog Scale ( CAS ) , the degree of change in pain severity required to achieve a clinical ly significant improvement in pain . METHODS A prospect i ve descriptive study , using convenience sampling of children aged 5 and 12 years presenting to a pediatric emergency department ( ED ) with acute pain , was done . Children were asked to mark their pain severity on a previously vali date d CAS . After a pain intervention , the child was again asked to mark their pain intensity on the CAS and asked to describe the relative change in their pain . The main outcome measure was to quantify the smallest change required for the child to state that their pain was improved . RESULTS One hundred twenty-six children with a mean age of 8.6 years ( SD , 2.8 years ) were enrolled . Males accounted for 56 % . Pain was traumatic in 47.6 % and nontraumatic in 52.4 % . Of the 126 pain comparisons made , 28 children described their pain as \" the same \" and had a mean change in score of -0.10 cm ( 95 % confidence interval [ CI ] , -2.27 to 2.07 cm ) . Pain was judged to be a \" little less \" in 58 children , and the CAS score changed by a mean of -2.4 cm ( 95 % CI , -3.15 to -1.72 cm ) . In the 29 children who judged their pain to be \" much less , \" the CAS score decreased by a mean of -5.4 cm ( 95 % CI , -6.50 to -4.40 ) . CONCLUSION A decrease on the CAS pain scale of 2.4 cm ( 95 % CI , 2.95 - 1.92 ) is a clinical ly significant change in pain for children aged 5 to 12 years with acute pain . The CAS is a valuable tool in assessing responses to pain interventions", "To test the relative merits of administering question naires with previous responses available ( the informed condition ) or unavailable ( the blind condition ) , we administered blind and informed versions of a quality of life question naire ( the Chronic Respiratory Disease Question naire , or CRQ ) in a r and omized , double-blind trial of bronchodilators in chronic airflow limitation . The responsiveness of the two methods , as reflected in the p-values associated with salbutamol and theophylline effects were comparable for three of the four dimensions of the CRQ . The data suggested possible increased responsiveness of the informed method for the emotional function dimension of the question naire . Changes in the informed CRQ dyspnea and fatigue dimensions showed stronger correlations with changes in spirometry , 6 minute walk distance , and rating of dyspnea after the walk test than did blind administration . Further , changes in all four CRQ dimensions showed stronger correlations with corresponding global ratings using the informed question naire . These results suggest that by letting study subjects see their previous responses the validity of subjective measures of health status in clinical trials can be improved", "BACKGROUND In a l and mark hypothesis-generating study , Todd et al found that a difference of approximately 13 mm ( 95 % confidence interval [ CI ] 10 to 17 mm ) on a visual analog scale ( VAS ) represented the minimum change in acute pain that was clinical ly significant in a cohort of trauma patients . STUDY OBJECTIVE We test the hypothesis that the minimum clinical ly significant change in pain as measured by the VAS in an independent , more heterogeneous validation cohort is approximately 13 mm . METHODS This was a prospect i ve , observational cohort study of adults presenting to 2 urban emergency departments with pain . At 30-minute intervals during a 2-hour period , patients marked a VAS and were asked if their pain was \" much less , \" \" a little less , \" \" about the same , \" \" a little more , \" or \" much more . \" All data were obtained without reference to prior VAS scores . The minimum clinical ly significant change in pain was defined a priori as the difference in millimeters between the current and immediately preceding VAS scores when \" a little more \" or \" a little less pain \" was reported . RESULTS Ninety-six patients enrolled in the study , providing 332 paired pain measurements . There were 141 paired measurements design ated by patients as \" a little less \" or \" a little more \" pain . The mean clinical ly significant difference between consecutive ratings of pain in the combined \" little less \" or \" little more \" groups was 13 mm ( 95 % CI 10 to 16 mm ) . The difference between this finding and that of Todd et al was 0 mm ( 95 % CI -4 to 4 mm ) . CONCLUSION These data are virtually identical to previous findings indicating that a difference of 13 mm on a VAS represents , on average , the minimum change in acute pain that is clinical ly significant", "OBJECTIVES To evaluate the validity of change in visual analog Scale ( VAS ) as a measure of pain relief using a verbal descriptor Scale ( VDS ) of change in pain . METHODS A prospect i ve observational study of emergency department patients measured pain with VAS and recorded verbal report of change in pain . RESULTS One thous and four hundred ninety patients yielded 1999 comparisons between change in VAS and VDS . Correlation of change in VAS and VDS of change in pain was rho = 0.667 ( P in VAS , large st and ard deviations for the mean change in VAS , and discordance in the direction of change in VAS were present within each verbal descriptor category . CONCLUSIONS Change in VAS is moderately correlated with a VDS of change in pain . Wide variability in change in VAS and discordance with a VDS demonstrate that change in VAS is not a valid indicator of pain relief for individual patients", "OBJECTIVES To determine the minimum clinical ly significant difference in visual analog scale ( VAS ) pain scores for acute pain in the ED setting and to determine whether this difference varies with gender , age , or cause of pain . METHODS A prospect i ve , descriptive study of 152 adult patients presenting to the ED with acute pain . At presentation and at 20-minute intervals to a maximum of three measurements , patients marked the level of their pain on a 100-mm , nonhatched VAS . At each follow-up they also gave a verbal rating of their pain as \" a lot better , \" \" much the same , \" \" a little worse , \" or \" much worse . \" The minimum clinical ly significant difference in VAS pain scores was defined as the mean difference between current and preceding scores when pain was reported as a little worse or a little better . Data were compared based on gender , age more than or less than 50 years , and traumatic vs nontraumatic causes of pain . RESULTS The minimum clinical ly significant difference in VAS pain scores is 9 mm ( 95 % CI , 6 to 13 mm ) . There is no statistically significant difference between the minimum clinical ly significant differences in VAS pain scores based on gender ( p=0.172 ) , age ( p=0.782 ) , or cause of pain ( p=0.84 ) . CONCLUSIONS The minimum clinical ly significant difference in VAS pain scores was found to be 9 mm . Differences of less than this amount , even if statistically significant , are unlikely to be of clinical significance . No significant difference in minimum significant VAS scores was found between gender , age , and cause-of-pain groups", "OBJECTIVE The aim of this study was to define the degree of change on a visual analogue scale that corresponded to a clinical ly meaningful reduction in the level of pain reported by patients experiencing acute pain . METHOD Secondary analysis of data was performed from prospect i ve , descriptive studies of 152 adults and 73 children presenting to emergency departments with acute pain . At presentation and at 20 min intervals to a maximum of three measurements , patients marked the level of their pain on a 100 mm , non-hatched visual analogue scale . At each follow up , they also gave a verbal rating of their pain as ' a lot better ' , ' a little better ' , ' much the same ' , ' a little worse ' or ' much worse ' . Data from the groups reporting that pain was ' a lot better ' and ' about the same ' were analysed for mean and median absolute change in visual analogue scale and compared . RESULTS Of 559 pain comparisons , 60 were rated as ' a lot better ' and 257 as ' about the same ' . The mean absolute change in visual analogue scale for the group reporting that pain was ' a lot better ' was 24 mm ( median = 19 mm , 95 % confidence interval = 17 - 31 mm ) . For the group reporting that pain was ' about the same ' , the mean visual analogue scale change was 0 mm ( median = 0 mm , 95 % confidence interval = -1 to 1 mm ) . CONCLUSION When evaluating treatments for acute pain , a difference in visual analogue scale pain score of less than about 20 mm is unlikely to be clinical ly meaningful . Studies should be design ed and reported relative to this benchmark rather than the minimum clinical ly significant difference in visual analogue scale pain score", "Objective —To determine whether minimum clinical ly significant difference in visual analogue scale ( VAS ) pain score varies according to the severity of pain reported . Method — Prospect i ve descriptive study of adult patients in an urban emergency department ( ED ) . On presentation to the ED , patients marked the level of their pain on a 100 mm , non-hatched VAS scale . At 20 minute intervals thereafter they were asked to give a verbal categorical rating of their pain as “ a lot better ” , “ a little better ” , “ much the same ” , “ a little worse ” or “ much worse ” and to mark the level of pain on a VAS scale of the same type as used previously . It was pre-defined that patients with VAS pain scores of 30 mm or less would be categorised as having mild pain , those with scores of 70 mm or more were categorised as having severe pain and those from 31 mm to 69 mm , moderate pain . The minimal clinical ly significant difference ( MCSD ) in VAS pain score was defined as the mean difference between current and preceding scores when the subject reported “ a little worse ” or “ a little better ” pain . Results —156 patients were enrolled in the study , yielding 88 evaluable comparisons where pain was rated as “ a little better ” or “ a little worse ” . The MCSD in VAS score in the group overall was 12 mm ( 95%CI 9 mm to 15 mm ) . MCSD in VAS score for the “ mild pain ” group was 11 mm ( 95%CI 4 mm to 18 mm ) , for the “ moderate pain ” group 14 mm ( 95%CI 10 mm to 18 mm ) and for the severe pain group , 10 mm ( 95%CI 6 mm to 14 mm ) . There is no statistical difference between the MCSD in VAS score between the severity groups . Conclusions —The MCSD in VAS pain score does not differ with the severity of pain being experienced", "OBJECTIVES The objective was to determine the minimum and ideal clinical ly significant differences ( MCSD , ICSD ) in pain intensity in children for the Faces Pain Scale-Revised ( FPS-R ) and the Color Analog Scale ( CAS ) and to identify any differences in these estimates based on patient characteristics . METHODS This was a prospect i ve study of children aged 4 to 17 years with acute pain presenting to two urban pediatric emergency departments . Participants self-reported their pain intensity using the FPS-R and CAS and qualitatively described their changes in pain . Changes in pain score reported using the FPS-R and CAS that were associated with \" a little less \" and \" much less \" pain ( MCSD and ICSD , respectively ) were identified using a receiver operating characteristic-based method and expressed as raw change score and percent reductions . Estimates of MCSD and ICSD were determined for each category of initial pain intensity ( mild , moderate , and severe ) and patient characteristics ( age , sex , and ethnicity ) . Post hoc exploratory analyses evaluated categories of race , primary language , and etiology of pain . RESULTS A total of 314 children with acute pain were enrolled ; mean ( ±SD ) age was 9.8 ( ±3.8 ) years . The FPS-R raw change score and percent reduction MCSD estimates were 2/10 and 25 % , with ICSD estimates of 3/10 and 60 % . For the CAS , raw change score and percent reduction MCSD estimates were 1/10 and 15 % , with ICSD estimates of 2.75/10 and 52 % . For both scales , raw change score and percent reduction estimates of the MCSD remained unchanged in children with either moderate or severe pain . For both scales , estimates of ICSD were not stable across categories of initial pain intensity . There was no difference in MCSD or ICSD based on age , sex , ethnicity , race , primary language , or etiology of pain . CONCLUSIONS The MCSD estimates can be expressed as raw change score and percent reductions for the FPS-R and CAS . These estimates appear stable for children with moderate to severe pain , irrespective of age , sex , and ethnicity . Estimates of ICSD were not stable across different categories of initial pain intensity , therefore limiting their potential generalizability", "BACKGROUND Limited underst and ing of the interpretability of patient-reported pain scores may impact pain management . The current study assessed the minimal clinical ly significant improvement in pain and pain scores signifying patient-reported need for medication and treatment satisfaction in patients with sickle cell disease ( SCD ) . PROCEDURE Patients , 8 - 18-years-old , with SCD were recruited while receiving treatment for pain . Patients completed initial pain severity ratings using the Visual Analog Scale ( VAS ) and the Numeric Rating Scale ( NRS ) . Serial assessment s of pain severity , pain relief , perceived need for medication , and treatment satisfaction were completed in the emergency department and the hospitalization . Data were used to calculate the minimal clinical ly significant improvement in pain and pain scores associated with perceived need for pain medication and treatment satisfaction . RESULTS Twenty-eight patients completed 305 assessment s during 37 total visits . A decrease in pain severity score of 0.97 cm for the VAS and 0.9 for the NRS was found to be the minimum clinical ly significant improvement in pain . Pain scores > 7.45 cm on the VAS or 7.5 on the NRS were suggestive of patient-reported need for pain medication . Pain scores pain relief , need for pain medication , and treatment satisfaction . Collectively , this study provides data to improve our underst and ing of pain ratings of pediatric patients with SCD", "Background : Subacromial impingement syndrome ( SAIS ) is a painful condition result ing from the entrapment of anatomical structures between the anteroinferior corner of the acromion and the greater tuberosity of the humerus . Objective : The aim of this study was to evaluate the short-term effectiveness of high-intensity laser therapy ( HILT ) versus ultrasound ( US ) therapy in the treatment of SAIS . Design : The study was design ed as a r and omized clinical trial . Setting : The study was conducted in a university hospital . Patients : Seventy patients with SAIS were r and omly assigned to a HILT group or a US therapy group . Intervention : Study participants received 10 treatment sessions of HILT or US therapy over a period of 2 consecutive weeks . Measurements : Outcome measures were the Constant-Murley Scale ( CMS ) , a visual analog scale ( VAS ) , and the Simple Shoulder Test ( SST ) . Results : For the 70 study participants ( 42 women and 28 men ; mean [ SD ] age=54.1 years [ 9.0 ] ; mean [ SD ] VAS score at baseline=6.4 [ 1.7 ] ) , there were no between-group differences at baseline in VAS , CMS , and SST scores . At the end of the 2-week intervention , participants in the HILT group showed a significantly greater decrease in pain than participants in the US therapy group . Statistically significant differences in change in pain , articular movement , functionality , and muscle strength ( force-generating capacity ) ( VAS , CMS , and SST scores ) were observed after 10 treatment sessions from the baseline for participants in the HILT group compared with participants in the US therapy group . In particular , only the difference in change of VAS score between groups ( 1.65 points ) surpassed the accepted minimal clinical ly important difference for this tool . Limitations : This study was limited by sample size , lack of a control or placebo group , and follow-up period . Conclusions : Participants diagnosed with SAIS showed greater reduction in pain and improvement in articular movement functionality and muscle strength of the affected shoulder after 10 treatment sessions of HILT than did participants receiving US therapy over a period of 2 consecutive weeks", "OBJECTIVES A st and ard value for the minimum clinical ly significant difference ( MCSD ) in pain in nonelderly ED patients has been identified and has facilitated research in this age group . It is not clear that this value is similar in older patients . The st and ard method for calculating the MCSD in pain is to average scores on a numerical rating scale ( NRS ) over contiguous time periods . This method is based on the assumption that the MCSD remains constant over time . In an earlier hypothesis-generating study of elderly patients , this assumption was not met for the arithmetic MCSD , making it difficult to identify a single benchmark for measuring efficacy in analgesia trials in elders . The proportional MCSD was more stable , suggesting that it might constitute a better measure of analgesic efficacy in elderly patients . The objective of the study was to test the hypotheses that : 1 ) the arithmetic MCSD in adults 65 years and older declines over time and that 2 ) the proportional MCSD remains constant . METHODS This was an observational , prospect i ve , cohort study of emergency department ( ED ) patients ≥65 years with acute pain . Pain intensity was rated on a st and ard 11-point NRS upon study entry and every 30 minutes for 2 hours . The arithmetic MCSD was defined as the mean change in pain between contiguous 30-minute intervals when change in pain was described as \" a little less \" or \" a little more . \" The proportional MCSD was calculated as the arithmetic MCSD divided by pain intensity at the beginning of the interval . We used generalized estimating equations ( GEEs ) to test trend over time . RESULTS A total of 214 patients were enrolled : mean ( ± st and ard deviation [ SD ] ) age was 74 ( ±7.5 ) years , 66 % were female , 63 % were Hispanic , and 23 % were African American . The median initial NRS was 8 . The MCSD decreased 2.1 NRS units ( 95 % confidence interval [ CI ] = 1.7 to 2.4 ) between 0 and 30 minutes , 1.4 units ( 95 % CI = 1.0 to 1.7 ) between 30 and 60 minutes , 1.3 units ( 95 % CI = 1.0 to 1.5 ) between 60 and 90 minutes , and 0.8 units ( 95 % CI = 0.6 to 1.0 ) between 90 and 120 minutes ( p The proportional MCSD also varied from 27 % ( 95 % CI = 23 % to 32 % ) between 0 and 30 minutes , 19 % ( 95 % CI = 13 % to 24 % ) between 30 and 60 minutes , 22 % ( 95 % CI = 18 % to 27 % ) between 60 and 90 minutes , and 13 % ( 95 % CI = 9 % to 18 % ) between 90 and 120 minutes ( p in elderly patients in acute pain declined over time . Because both measures were numerically unstable , there does not appear to be a single value for the MCSD that can be used to identify the MCSD in pain for use in analgesic efficacy trials in elderly patients . A different metric may be needed to study pain and assess comparative analgesic efficacy in elderly patients", "OBJECTIVE : The goal of this study was to compare the analgesic effect of sucrose with that of the combination of sucrose and the local anesthetic cream EMLA during venipuncture in preterm neonates . METHODS : This r and omized , double-blind prospect i ve study included infants younger than 37 weeks ' gestational age during 1 routine venipuncture for blood sampling . Each child r and omly received either sucrose plus application of a placebo cream ( S group ) or sucrose plus EMLA cream ( S+E group ) before venipuncture . Venipuncture-induced pain was assessed through videotapes of the procedures by using the Douleur Aiguë Nouveau-né ( DAN ) behavioral scale . Pain was assessed at 2 phases : during venipuncture ( from needle introduction to its removal ) and during the recovery period ( 30 seconds after needle removal ) . Pain scores over time and between treatments were compared by using repeated- measures analysis of variance . RESULTS : The study included 76 children ( 37 in the S group , 39 in the S+E group ) . Mean ( SD ) DAN pain scores for the S group and the S+E group were 7.7 ( 2.1 ) and 6.4 ( 2.5 ) , respectively , during venipuncture and 7.1 ( 2.8 ) and 5.7 ( 3.3 ) during the postinjection period . A significant time and treatment effect in favor of the S+E group was observed . CONCLUSION : The combination of sucrose and EMLA cream revealed a higher analgesic effect than sucrose alone during venipuncture in these preterm infants", "OBJECTIVES Verbally administered numerical rating scales ( NRSs ) from 0 to 10 are often used to measure pain , but they have not been vali date d in the emergency department ( ED ) setting . The authors wished to assess the comparability of the NRS and visual analog scale ( VAS ) as measures of acute pain , and to identify the minimum clinical ly significant difference in pain that could be detected on the NRS . METHODS This was a prospect i ve cohort study of a convenience sample of adults presenting with acute pain to an urban ED . Patients verbally rated pain intensity as an integer from 0 to 10 ( 0 = no pain , 10 = worst possible pain ) , and marked a 10-cm horizontal VAS bounded by these descriptors . VAS and NRS data were obtained at presentation , 30 minutes later , and 60 minutes later . At 30 and 60 minutes , patients were asked whether their pain was \" much less , \" \" a little less , \" \" about the same , \" \" a little more , \" or \" much more . \" Differences between consecutive pairs of measurements on the VAS and NRS obtained at 30-minute intervals were calculated for each of the five categories of pain descriptor . The association between VAS and NRS scores was expressed as a correlation coefficient . The VAS scores were regressed on the NRS scores in order to assess the equivalence of the measures . The mean changes associated with descriptors \" a little less \" or \" a little more \" were combined to define the minimum clinical ly significant difference in pain measured on the VAS and NRS . RESULTS Of 108 patients entered , 103 provided data at 30 minutes and 86 at 60 minutes . NRS scores were strongly correlated to VAS scores at all time periods ( r = 0.94 , 95 % CI = 0.93 to 0.95 ) . The slope of the regression line was 1.01 ( 95 % CI = 0.97 to 1.06 ) and the y-intercept was -0.34 ( 95 % CI = -0.67 to -0.01 ) . The minimum clinical ly significant difference in pain was 1.3 ( 95 % CI = 1.0 to 1.5 ) on the NRS and 1.4 ( 95 % CI = 1.1 to 1.7 ) on the VAS . CONCLUSIONS The findings suggest that the verbally administered NRS can be substituted for the VAS in acute pain measurement", "& NA ; Reliable and valid measures of pain are essential for conducting clinical trials of pain treatments . Perhaps the most important aspect of a pain measure 's validity is its sensitivity , or ability to detect changes in pain over time and due to treatment . Several factors may affect a measure 's sensitivity , including the complexity of the rating task for the measure , the number of pain intensity levels assessed by the measure , the dimension of pain assessed ( e.g. pain intensity vs. pain relief ) , and the number of individual ratings ( e.g. single rating vs. composite score ) used to create the measure . The purpose of this study was to compare the relative sensitivity of three measures of outcome and a composite made up of all three measures for detecting analgesic effects in two sample s of persons participating in a r and omized controlled trial . One hundred and twenty‐three patients who had undergone knee surgery and 124 women who had undergone a laparotomy were given one of three medications in the day after their surgery : morphine , ketorolac , or placebo . Two measures of pain intensity ( a visual analog scale ( VAS ) and a 4‐point verbal rating scale ( VRS ) ) were administered at baseline , and these measures plus a 5‐point VRS of pain relief were administered at 16 additional time points up to 24 h following surgery . As predicted , we found variability in the sensitivity of the outcome measures used in these studies , with the 4‐point VRS showing less sensitivity than the VAS or relief ratings . However , contrary to our prediction , a composite measure of outcome made up of all three measures was not consistently superior to the individual measures for detecting treatment effects . Finally , we found that pain relief ratings were related to , but also distinct from , change in pain intensity as measured by changes in pain intensity ratings from baseline to each postmedication assessment point . These findings have important implication s for the assessment of pain in clinical trials", "& NA ; Although the verbal numeric scale ( VNS ) is used frequently at patients ’ bedsides , it has never been formally vali date d in children with acute pain . In order to vali date this scale , a prospect i ve cohort study was performed in children between 8 and 17 years presenting to a pediatric emergency department ( ED ) with acute pain . Pain was grade d using the VNS , the visual analogue scale ( VAS ) , and the verbal rating scale ( VRS ) . A second assessment was done before discharge . We determined a priori that in order to be valid , the VNS would need to : correlate with the VAS ( concurrent validity ) ; decrease after intervention to reduce pain ( construct validity ) ; and be associated with the VRS categories ( content validity ) . The VNS interchangeability with the VAS , its minimal clinical ly significant difference , and test – retest reliability were also determined . A total of 202 patients ( mean age : 12.2 ± 2.6 years ) were enrolled . The VNS correlated with the VAS : ric = 0.93 , p VNS before versus after interventions ( p VNS/VAS were outside the a priori set limit of ±2.0 : −1.8 , 2.5 . The VNS minimal clinical ly significant difference was 1 . The VNS had good test – retest reliability with 95 % limits of agreement of −0.9 and 1.2 . In conclusion , the VNS provides a valid and reliable scale to evaluate acute pain in children aged 8–17 years but is not interchangeable with the VAS ", "OBJECTIVE To quantify , using two pain assessment scales , the amount of change in pain severity required to achieve a clinical ly significant improvement in pain in children presenting to a pediatric emergency department ( ED ) with pain . METHODS Prospect i ve , descriptive study involving all children presenting to a pediatric ED between 5 and 16 years of age inclusive with acute pain . Children were excluded if they 1 ) were intoxicated or had altered sensorium , 2 ) were clinical ly unstable , 3 ) were non-English-speaking , or 4 ) were developmentally delayed . Written informed consent was obtained . Children were asked to mark their current pain severity on the st and ardized Color Analogue Scale ( CAS ) and Faces Pain Scale ( FPS ) . After each pain control intervention the child was asked to repeat these measurements and to describe whether his or her pain was \" much less , \" \" a little less , \" \" about the same , \" \" a little worse , \" or \" much worse \" compared with before . This process was repeated until the child was discharged from the ED or had a score of zero . The main outcome measure was the smallest change on the CAS or FPS necessary to cause the child to describe his or her pain as a \" little less . \" This was defined as the clinical ly significant change in pain . The \" ideal \" change in pain was defined as the amount of change necessary for the child to describe the pain as \" much less \" or at which point the child thought he or she no longer required any medicine to help the pain go away . RESULTS One hundred twenty-one children were enrolled with a mean age of 9.8 years ( SD + /- 3.15 ) . Males accounted for 56 % . Pain was traumatic in 65 % and nontraumatic in 35 % . A total of 153 pain comparisons were made using the CAS and 154 using the FPS . Only three children complained that their pain got worse ( two a little worse and one much worse ) . Pain was described as \" the same \" in 20 . Of the 60 pain comparisons judged to be a \" little less , \" the CAS score changed by a median of 2.0 cm [ interquartile ratio ( IQR ) 1 - 3 ] , and the FPS by 1.0 face ( IQR 1 - 2 ) . In the 71 children who judged their pain to be \" much less , \" the CAS decreased by a median of 4.0 cm ( IQR 2 - 5 ) and the FPS by 2.0 faces ( IQR 2 - 3 ) . CONCLUSIONS The assessment and treatment of pain in children are an important component of pediatric practice , especially in the ED . This study provides health care professionals and clinical investigators the information necessary to assess whether their method of pain control in children is clinical ly relevant", "BACKGROUND Vali date d health-related quality -of-life measures have become important st and ards in the evaluation of the outcomes of lumbar spine surgery . However , there are few well-defined criteria for clinical success based on these measures . The minimum clinical ly important difference is an important demarcation , but it could be considered a floor value rather than a goal in defining clinical success . Therefore , we sought to define thresholds of substantial clinical benefit for commonly used health-related quality -of-life measures following lumbar spine arthrodesis . METHODS Prospect ively collected preoperative and one-year postoperative health-related quality -of-life measures from 357 patients who were managed with lumbar spine arthrodesis for the treatment of degenerative conditions were identified . C and i date substantial clinical benefit thresholds for the Short Form-36 physical component score , Oswestry Disability Index , and back and leg pain numeric rating scales were identified with use of receiver operating characteristic curve analysis . Receiver operating characteristic curves were used to discriminate between patients who reported being \" much better \" or \" about the same \" with use of the vali date d Short Form-36 health transition item and between those who reported being \" mostly satisfied \" or \" unsure \" with use of a nonvali date d but more surgery-specific satisfaction-with- results survey . For each health-related quality -of-life measure , three response parameters were used : net change , percent change , and raw score at the time of the one-year follow-up . RESULTS Substantial clinical benefit thresholds for the Short Form-36 physical component score were a 6.2-point net improvement , a 19.4 % improvement , or a final raw score of > or = 35.1 points . Substantial clinical benefit thresholds for the Oswestry Disability Index were an 18.8-point net improvement , a 36.8 % improvement , or a final raw score of back pain and leg pain numeric rating scales were a 2.5-point net improvement or a final raw score of back pain numeric rating scale and 38.8 % for the leg pain numeric rating scale . CONCLUSIONS We believe that thresholds of substantial clinical benefit for commonly used health-related quality -of-life measures following lumbar spine arthrodesis are important as they describe a magnitude of change that the patient recognizes as a major improvement", "STUDY OBJECTIVE We sought to determine the minimum clinical ly significant difference in visual analog scale ( VAS ) pain score for children . METHODS We performed a prospect i ve , single-group , repeated- measures study of children between 8 and 15 years presenting to an urban pediatric emergency department with acute pain . On presentation to the ED , patients marked the level of their pain on a 100-mm nonhatched VAS scale . At 20-minute intervals thereafter , they were asked to give a verbal categoric rating of their pain as \" heaps better , \" \" a bit better , \" \" much the same , \" \" a bit worse , \" or \" heaps worse \" and to mark the level of pain on a VAS scale of the same type as used previously . A maximum of 3 comparisons was recorded for each child . The minimum clinical ly significant difference in VAS pain score was defined as the mean difference between current and preceding scores when the subject reported \" a bit worse \" or \" a bit better \" pain . RESULTS Seventy-three children were enrolled in the study , yielding 103 evaluable comparisons in which pain was rated as \" a bit better \" or \" a bit worse . \" The minimum clinical ly significant difference in VAS score was 10 mm ( 95 % confidence interval 7 to 12 mm ) . CONCLUSION This study found the minimum clinical ly significant difference in VAS pain score for children aged 8 to 15 years ( on a 100-mm VAS scale ) to be 10 mm ( 95 % confidence interval 7 to 12 mm ) . In studies of population s , differences of less than this amount , even if statistically significant , are unlikely to be of clinical significance", "BACKGROUND The patient acceptable symptom state ( PASS ) is the value beyond which patients can consider themselves well . This concept can help in interpreting results of clinical trials . OBJECTIVE To determine the PASS estimate for patients with knee and hip osteoarthritis ( OA ) by assessing pain , patient 's global assessment of disease activity , and functional impairment . METHODS A 4 week prospect i ve multicentre cohort study of 1362 out patients with knee or hip OA was carried out . Data on assessment of pain and patient 's global assessment of disease , measured on visual analogue scales , and functional impairment , measured on the Western Ontario McMaster Universities Osteoarthritis Index ( WOMAC ) function subscale , were collected at baseline and final visits . The patients assessed their satisfaction with their current state at the final visit . An anchoring method based on the patient 's opinion was used . RESULTS For patients with knee and hip OA , the estimates of PASS were , respectively , 32.3 and 35.0 mm for pain , 32.0 and 34.6 mm for patient global assessment of disease activity , and 31.0 and 34.4 points for WOMAC function score . The PASS varied moderately across the tertiles of baseline scores but not across age , disease duration , or sex . CONCLUSION The use of PASS in clinical trials would provide more meaningful results expressed as a proportion of patients in an acceptable symptom state", "OBJECTIVE To test whether a single-category improvement on a Likert pain relief scale equals the minimum clinical ly significant difference of 1.3 units in pain intensity reduction on a 10-unit numerical rating scale ( NRS ) . METHODS Prospect i ve cohort of adults with acute severe pain receiving st and ardized analgesia . Patients rated pain intensity via NRS before receiving morphine and 30 minutes later . Patients described pain relief as \" none , \" \" a little , \" \" moderate , \" \" a lot , \" or \" complete . \" The primary outcome was the difference in NRS scores between each contiguous pair of pain relief categories over 30 minutes . RESULTS One hundred thirty-one patients , age range 21 to 65 years , median baseline NRS pain score 10 ( interquartile range , 9 - 10 ) . Patients whose relief was \" complete , \" \" a lot , \" \" moderate , \" \" mild , \" and \" none \" had the following NRS unit reductions in pain , respectively : 9 , 5.7 , 3.9 , 2.1 , and -0.1 . The difference between each pair of relief categories was 3.3 , 1.8 , 1.8 , and 2.2 units . CONCLUSION Each single-category improvement on a pain relief scale exceeds the minimum clinical ly significant difference in pain intensity as measured on an NRS", "OBJECTIVE Intravenous morphine has been used as a common method of pain control in emergency care . Nebulized fentanyl is also an effective temporary substitute . This study was design ed to compare the effectiveness of nebulized fentanyl with intravenous ( IV ) morphine on management of acute limb pain . METHODS This was a placebo-controlled , double-blind r and omized clinical trial . Ninety emergency department patients with moderate to severe pain aged 15 to 50 years were blocked r and omized and enrolled in this study . Forty-seven patients in the experimental group received nebulized fentanyl ( 4 μg/kg ) and IV normal saline as placebo , and the remaining 43 patients in the control group received IV morphine ( 0.1 mg/kg ) and nebulized normal saline as placebo . All participants ' pain scores were assessed by Numerical Rating Scale before and after intervention at 5- , 10- , 15- , 30- , 45- , and 60-minute intervals . Patients ' vital sign and possible adverse effects were recorded respectively . Finally , all participants were assessed for their satisfaction . RESULTS The mean initial pain score in the experimental group was 8.7 and 8.4 in the control group ( P = .1 ) . Pain relief in both groups after 5 and 10 minutes were similar ( P = .72 ) . Although the pain relief was significantly greater with fentanyl at 15 minutes , this difference is not clinical ly significant . Pain management in both groups was successful and was more than 3 scores reduction in Numerical Rating Scale . Patient satisfaction in both groups was similar . No adverse effects were reported in the experimental group . CONCLUSION This study suggests that nebulized fentanyl is a rapid , safe , and effective method for temporary control of acute limb pain in emergency department patients", "Abstract Objectives : To assess the level of pain intensity at which patients feel the impetus to ask for a breakthrough cancer pain ( BTcP ) medication , and level of pain intensity at which patients consider they have achieved acceptable pain control after receiving a BTcP medication . Methods : A consecutive sample of patients who were receiving oral morphine equivalents equal to or more than 60 mg daily , and were prescribed rapid onset opioids for the management of episodes of BTcP , were included in the study . Focused educational activities regarding BTcP and numerical scales were established during hospital admission . At discharge patients were interviewed to find out what was the pain intensity level which gave the impetus to take the BTcP medication , what was the pain intensity for acceptable pain control after a BTcP medication had been given , and which factors prevented the patient calling for BTcP medication . A brief COPE ( coping orientation to problems experienced ) question naire was also administered . Results : Fifty-two patients were recruited for this study . The meaningful pain intensity for asking for a BTcP medication was 7.1 ; 77 % of patients had a pain intensity of 7–8 on a numerical scale of 0–10 . The meaningful pain intensity for adequate analgesia after a BTcP medication was 3.5 . Similarly , 77 % of patients had a pain intensity of 3–4 . There was no relationship with the variables examined . Concerns by patients about the use of BTcP medications were minimal . Conclusion : The meaningful BTcP intensity and pain intensity expected after BTcP medication can be useful in selecting patients in studies of BTcP. The principal limitation of this study was the specific setting of an acute unit with specific features and the relatively low number of patients . This observation should be followed up by further surveys with a larger number of patients and different setting", "BACKGROUND AND METHODS From the time that Sinatra et al. ( Anesthesiology . 2005;102:822 ) was published to FDA apaproval of intravenous ( IV ) acetaminophen , an exp and ed analysis of the original raw study data became necessary for the regulatory su bmi ssion . The following analyses were conducted : ( 1 ) sum of pain intensity differences over 24 hours ( SPID24 ) using currently accepted imputation methods to account for both missing data and the effects of rescue ; ( 2 ) efficacy results after the first 6 hours ; ( 3 ) effects of gender , race/ethnicity , age , weight , surgical site , ASA Class , and serotonin antagonists ; and ( 4 ) a stepwise regression analysis of why adverse events of nausea and vomiting were numerically ( although not statistically ) higher in the IV acetaminophen group compared with placebo . RESULTS Sum of pain intensity differences over 24 hours using a 0- to 100-mm visual analog scale was statistically significantly ( P IV acetaminophen ( n = 49 ) compared with placebo ( n = 52 ) . Time to rescue was found to be 3.9 and 2.1 hours , respectively , for total hip and knee arthroplasty compared with 0.8 hours for the placebo group . Rescue medication consumption , requests , and actual administration were all significantly lower in the IV acetaminophen group compared with placebo for each dosing interval , except in the 6- to 12-hours interval where a numerical trend was observed . Analysis of various subset variables demonstrated similar efficacy for each variable . A stepwise regression analysis demonstrated that AE reports of nausea and vomiting were most likely due to prer and omization events , particularly opioid consumption and presence of nausea prior to r and omization . CONCLUSION Repeated-dose 24-hours end points were found to be as robust as previously published results . IV acetaminophen efficacy and safety appeared to be unaffected by specific subset variables .", "BACKGROUND For patients with surgical third molar removal , it is unknown what constitutes a clinical ly important change in patients ' visual analogue scale ( VAS ) reports of pain intensity . OBJECTIVES To determine what constitutes a clinical ly important change in pain intensity on a VAS following surgical removal of the third molar . METHODS The study population consisted of patients participating in three r and omized trials . Patients were asked to rate their pain three times per day over a period of seven days on a 100 mm VAS after surgical removal of the third molar . Global Perceived Effect was measured on day 1 and day 7 and was used as the external criterion for assessing clinical ly important pain reduction . Global Perceived Effect scores of 6 ( ' much improved ' ) or higher were classified as clinical ly ' successful ' , and scores of 5 ( ' slightly improved ' ) or below were classified as clinical ly ' unsuccessful ' . For each trial , the mean absolute and relative changes in VAS scores were calculated for both ' successful ' and ' unsuccessful ' treatments . Sensitivity and specificity analyses were performed . RESULTS The patients who reported ' successful ' pain reduction showed a relative pain reduction of ≥69 % and an absolute pain reduction > 2.5 cm on the VAS , whereas patients who classified their pain reduction as ' unsuccessful ' had a relative pain reduction of ≤18.5 % and an absolute pain reduction relative pain reduction exhibited the best balance of sensitivity and specificity . CONCLUSION Relative pain reduction of ≥50 % and an absolute pain reduction of ≥2.5 cm on the VAS were most accurate in predicting a successful pain reduction after a given treatment", "OBJECTIVE To determine the most appropriate means to assess the response to treatment in terms of pain and functional impairment in a chronic rheumatic condition ( knee osteoarthritis [ OA ] ) and an acute rheumatic condition ( rotator cuff syndrome [ RCS ] ) . METHODS Two prospect i ve studies were conducted consisting of 1,019 out patients with knee OA and 271 patients with acute RCS . The minimal clinical ly important improvement and the patient acceptable symptom state were determined for knee OA pain using a visual analog scale , and for knee OA function using the Western Ontario and McMaster Universities Osteoarthritis Index function subscale ; for acute RCS pain , a numeral rating scale was used , and the Neer function subscale was used for RCS function . RESULTS The minimal clinical ly important improvement was shown to be the change required to achieve the patient acceptable symptom state , whatever the baseline level of symptom , the outcome ( pain or function ) , or type of condition ( chronic or acute ) . This acceptable state for pain was higher for chronic ( 27.0 - 36.4 across the baseline score ) than acute ( 16.7 - 24.1 ) conditions . The level of functional impairment considered satisfactory by patients with knee OA was higher for more disabled patients ( 43.1 ) than for less disabled patients ( 20.4 ) . CONCLUSION Patients consider that they experienced an important improvement only if this improvement allowed them to achieve a state they consider satisfactory . The most appropriate means to assess the response to therapy seems to be to assess whether patients feel good ( i.e. , achieve the patient acceptable symptom state )", "PURPOSE To determine whether adding regular acetaminophen ( paracetamol ) could improve pain and well-being in people with advanced cancer and pain despite strong opioids . PATIENTS AND METHODS Participants took acetaminophen for 48 hours and placebo for 48 hours . The order ( acetaminophen or placebo first ) was r and omly allocated . Pain was the primary outcome . Preferences , number of opioid breakthrough doses , overall well-being , nausea and vomiting , drowsiness , constipation , and cold sweats were secondary outcomes . Patients rated themselves daily with visual analog scales ( VAS ) and a verbal numeric scale ( VNS ) for pain , all scaled from 0 to 10 . RESULTS Thirty patients completed the trial . The oral opioid was morphine in 23 patients and hydromorphone in seven patients . The median daily opioid dose in oral morphine equivalents was 200 mg ( range , 20 to 2,100 mg ) . Nonsteroidal anti-inflammatory drugs , corticosteroids , or both were used by 16 patients . Pain and overall well-being were better for patients receiving acetaminophen than for those receiving placebo . The mean difference was 0.4 ( 95 % CI , 0.1 to 0.8 ; P = .03 ) in VNS for pain , 0.6 ( 95 % CI , -0.1 to 1.3 ; P = .09 ) in VAS for pain , and 0.7 ( 95 % CI , 0.0 to 1.4 ; P = .05 ) in VAS for overall well-being . More patients preferred the period they took acetaminophen ( n = 14 ) than the period they took placebo ( n = 8) , but many had no preference ( n = 8) . There were no differences in the other outcomes . CONCLUSION Acetaminophen improved pain and well-being without major side effects in patients with cancer and persistent pain despite a strong opioid regimen . Its addition is worth considering in all such patients", "BACKGROUND CONTEXT Various method ologies have been used in attempting to eluci date a st and ard method for calculating minimal clinical ly important difference ( MCID ) . A consensus-based decision ( Initiative on Methods , Measurement , and Pain Assessment in Clinical Trials [ IMMPACT ] group ) suggested a 30 % reduction from baseline as a means to define the MCID of self-report back pain measures . Additionally , important psychometric issues need to be addressed regarding use of an independent measure of the same construct as an external criterion , instead of simply using another self-report measure , when using an anchor-based approach to MCID . PURPOSE The purpose was to test the validity of recently published guidelines regarding MCID using self-report back pain measures and objective socioeconomic outcomes . STUDY DESIGN / SETTING This is a prospect i ve study assessing change scores on commonly used spinal pain assessment measures in patients with chronic disabling occupational spinal disorders ( CDOSDs ) treated in a regional referral rehabilitation center performing interdisciplinary functional restoration . PATIENT SAMPLE The study consisted of consecutive cohort of patients ( N=1,180 ) with CDOSDs completing a functional restoration program . OUTCOMES MEASURES Self-report measures including the Oswestry Disability Index ( ODI ) and the physical component summary ( PCS ) and mental component summary ( MCS ) of the Short Form-36 ( SF-36 ) obtained before and after treatment , were compared with objective socioeconomically relevant outcomes obtained 1 year after treatment ( ie , work status and additional health-care utilization ) , that were the external criteria for evaluating MCID . METHODS Pre- to posttreatment improvement was calculated separately for each measure , and subjects were divided into two groups based on the change in scores relative to baseline : 30 % or greater versus less than 30 % improvement . One-year posttreatment objective socioeconomic outcomes were used as independent external criteria relevant to the CDOSD population . This population is often studied as the most costly and problematic cohort in spine care . RESULTS The ODI and SF-36 MCS were not associated with any of the objective 1-year outcomes used as external criteria . Reduced post-rehabilitation health-care utilization ( based on the percentage of patients pursuing health care from a new provider ) was weakly associated with 30 % or greater improvement on the SF-36 PCS , relative to patients whose scores changed by less than 30 % relative to baseline ( 17.0 % vs. 21.1 % ) . The same was true for the ODI and return-to-work . CONCLUSIONS When objective and independent criteria are used ( socioeconomic outcomes ) in a CDOSD cohort , the 30 % improvement in the ODI and SF-36 may not be a valid MCID index . This replicates similar conclusions made by an independent research group using a distribution-based approach to MCID . The validity of the MCID concept rests on future research using objective external criteria . Moreover , there remains a question whether the term \" important \" in MCID can be unequivocally and operationally defined as a reliable construct", "OBJECTIVE To correlate measured pain intensity ( PI ) changes with pain relief and satisfaction with pain management . METHODS A prospect i ve single-group repeated- measures design study . A heterogeneous group of patients were asked to record their levels of PI at initial presentation and at ED release using a numerical descriptor scale ( NDS ) and a visual analog scale ( VAS ) . At release , a 5-point pain relief scale and a pain management satisfaction survey were also completed . RESULTS A convenience sample of 81 patients were enrolled over the study period . The average reduction in PI for all patients was 33 % . A 5 % , 30 % , and 57 % reduction in PI correlated with \" no , \" \" some/partial , \" and \" significant/complete \" relief , respectively ( p 5 ) required a reduction of 35 % and 84 % in PI to achieve \" some/partial \" and \" significant/complete \" relief , respectively . Patients in less pain ( NDS satisfied with their pain management . There was a positive association between pain relief and satisfaction with pain management . CONCLUSION There is a significant association between changes in PI and pain relief . Greater reductions in PI are required for patients presenting with more severe initial pain to achieve relief compared with those who have lesser initial PI . While there is a linear relationship between increasing pain relief and satisfaction , relief of pain appears to only partially contribute to overall satisfaction with pain management", "Aim : To quantify and compare the responsiveness within the meaning of clinical relevance of efficacy endpoints in a clinical trial with over the counter ( OTC ) analgesics for headache . Efficacy endpoints and observed differences in clinical trials need to be clinical ly meaningful and mirror the change in the clinical status of a patient . This must be demonstrated for the specific disease indication and the particular patient population based on the application of treatments with proven efficacy . Methods : Patient ’s global efficacy assessment during two study phases ( pre-phase and treatment phase ) was used to classify patients as satisfied or non-satisfied with the efficacy of their medication . The analysis is based on 1734 patients included in the efficacy analysis of a r and omized , placebo-controlled , double-blind , multi-centre parallel group trial with six treatment arms . Based on this classification and the pain intensity recorded by the patients on a 100 mm visual analogue scale , group differences by assessment categories and receiver operating characteristic ( ROC ) curve methods were used to quantify responsiveness of the efficacy endpoints ‘ time to 50 % pain relief ’ , ‘ time until reduction of pain intensity to 10 mm ’ , ‘ weighted sum of pain intensity difference ’ ( % SPIDweighted ) , ‘ pain intensity difference ( PID ) relative to baseline at 2 hours ’ , and ‘ pain-free at 2 hours ’ . Results : Clinical ly relevant differences between patients satisfied and non-satisfied with the treatment were observed for all efficacy endpoints . Patients with the highest rating of efficacy had the fastest and strongest pain relief . In comparison , patients assessing efficacy as ‘ less good ’ reached a 50 % pain relief on average nearly an hour later than those scoring efficacy as at least ‘ good ’ . Simultaneously , their extent of pain relief was only half as great 2 hours after medication intake . Patients scoring efficacy as ‘ poor ’ experienced practically no pain relief within the 4 hour observation interval . ROC curve calculations confirmed an adequate responsiveness for all continuous endpoints . The following cut-off points for differentiating between satisfied and non-satisfied patients were deduced from the data in the pre- and treatment phase , respectively : ‘ time to 50 % pain relief ’ 1:10 and 1:31 h : min , ‘ time until reduction of pain intensity to 10 mm ’ 2:40 and 3:00 h : min , ‘ % SPIDweighted ’ 68 and 64 % , ‘ PID at 2 hours ’ 35 and 35 mm . The sensitivity and specificity based on these cut-off points ranged from 70 to 79 % . The binary endpoint ‘ pain-free at 2 hours ’ showed a clearly higher specificity ( 80 and 87 % ) than sensitivity ( 65 and 61 % ) in the pre- and treatment phase , respectively . Conclusions : When global assessment of efficacy by the patient was used as external criterion , ROC curve calculations confirmed a high responsiveness for all efficacy endpoints included in this study . Clinical ly relevant differences between patients satisfied and non-satisfied with the treatment were observed . The endpoint ‘ % SPIDweighted ’ proved slightly but consistently superior to the other endpoints . SPID and % SPIDweighted are not easy to interpret and the time course of pain reduction is of high importance for the patients in the treatment of acute pain , including headache . The endpoint ‘ pain-free at 2 hours ’ showed the expected high specificity , but at the cost of a concurrently low sensitivity and clearly makes less use of the available information than the endpoint ‘ time to 50 % pain reduction ’ , which combines the highly relevant aspects of time course and extent of pain reduction . Responsiveness , the ability of an outcome measure to detect clinical ly important changes in a specific condition of a patient , should be added in future revisions of IHS guidelines for clinical trials in headache disorders", "The objective of the study was to assess the validity and reliability of the visual analog scale ( VAS ) in the measurement of acute abdominal pain , and to identify the minimum clinical ly significant difference in VAS scores among patients with acute abdominal pain . The study was undertaken in preparation for a r and omized clinical trial of opioid use in acute abdominal pain . A prospect i ve , observational cohort study of a convenience sample of patients presenting to 2 urban EDs with the chief complaint of acute abdominal pain was conducted . At time 0 and 1 minute later each subject indicated pain severity on a 100 mm VAS . This was repeated every 30 minutes for 2 hours . Patients were also asked to contrast their current pain severity with their pain in the preceding 30 minutes using one of 5 grade d verbal descriptors : \" much less pain , \" \" little less pain , \" \" the same pain , \" \" little more pain , \" and \" much more pain . \" Validity was assessed by performing an analysis of variance for linear trend on the association between the 5 categorical pain descriptors and change in VAS scores . Reliability was assessed using the intra-class correlation coefficient ( ICC ) between VAS scores taken 1 minute apart , supplemented by a Bl and -Altman analysis . The minimum clinical ly significant difference in pain was defined as the mean difference between sequential VAS scores obtained 30 minutes apart when the patient noted a \" little less \" or \" little more \" pain . Differences in VAS scores increased linearly as pain descriptors escalated from \" much less \" to \" much more \" pain ( P Reliability was high , ICC = 0.99 [ 95%CI 0.989 to 0.992 ] for 0 and 1 minute VAS scores . The minimum clinical ly significant difference in acute abdominal pain was 16 mm ( 95 % CI 13 , 18 mm ) . VAS measures of acute abdominal pain are valid and reliable . The 95 % CI surrounding the minimum clinical ly significant difference of approximately 16 mm overlaps with the 95 % CI of minimum clinical ly significant difference of approximately 13 mm reported previously in traumatic and other types of acute pain . We conclude that the VAS is a method ologically sound instrument for quantitative assessment of acute abdominal pain and for detecting clinical ly important changes in such pain", "STUDY OBJECTIVE To compare acetaminophen extended release 1,300 mg 3 times daily and ibuprofen 400 mg 3 times daily for treatment of signs and symptoms of grade I or II lateral ankle sprains . METHODS Patients ( N=260 ) 18 years or older and with grade I or II lateral ankle sprains were r and omized to receive acetaminophen extended release 1,300 mg 3 times daily or ibuprofen 400 mg 3 times daily for 9 days . Primary endpoint was change from baseline at day 4 in pain on walking . Other endpoints included change from baseline at day 9 in pain on walking ; change from baseline at days 4 and 9 in ability to walk and ankle swelling , bruising , and range of motion ; satisfaction with treatment on days 4 and 9 ; percentage of patients with positive anterior drawer test on day 4 ; and time to resume normal activity . Safety assessment s consisted of reported adverse events . This study had a noninferiority design in which the hypothesis was that acetaminophen extended release was not inferior to ibuprofen for treatment of signs and symptoms of grade I or II lateral ankle sprains . RESULTS The difference in least squares means ( acetaminophen extended release , ibuprofen ) with respect to the primary endpoint within the per- protocol population was -0.88 ; acetaminophen extended release was comparable to ibuprofen for the primary endpoint because the upper limit ( 3.26 ) of the 1-sided 95 % confidence interval ( CI ) for the difference in least squares means did not exceed the noninferiority limit of 6.90 . The intention-to-treat population was used to test the second step of the 2-step testing process because the None hypothesis was rejected in the noninferiority test . For this analysis , the difference between acetaminophen extended release and ibuprofen in the least squares mean change from baseline for the primary endpoint was -1.63 ( not significant ) . Results showed that acetaminophen extended release was noninferior to ibuprofen with respect to the secondary endpoints . No serious drug-related adverse events were reported . The most common adverse events , reported by 6.5 % of patients , were in the gastrointestinal system ( mainly nausea and upper abdominal pain ) . CONCLUSION Acetaminophen extended release 3,900 mg daily was comparable to ibuprofen 1,200 mg daily for treatment of grade I or II lateral ankle sprains . Both treatments were well tolerated", "IMPORTANCE Low back pain ( LBP ) is responsible for more than 2.5 million visits to US emergency departments ( EDs ) annually . These patients are usually treated with nonsteroidal anti-inflammatory drugs , acetaminophen , opioids , or skeletal muscle relaxants , often in combination . OBJECTIVE To compare functional outcomes and pain at 1 week and 3 months after an ED visit for acute LBP among patients r and omized to a 10-day course of ( 1 ) naproxen + placebo ; ( 2 ) naproxen + cyclobenzaprine ; or ( 3 ) naproxen + oxycodone/acetaminophen . DESIGN , SETTING , AND PARTICIPANTS This r and omized , double-blind , 3-group study was conducted at one urban ED in the Bronx , New York City . Patients who presented with nontraumatic , nonradicular LBP of 2 weeks ' duration or less were eligible for enrollment upon ED discharge if they had a score greater than 5 on the Rol and -Morris Disability Question naire ( RMDQ ) . The RMDQ is a 24-item question naire commonly used to measure LBP and related functional impairment on which 0 indicates no functional impairment and 24 indicates maximum impairment . Beginning in April 2012 , a total of 2588 patients were approached for enrollment . Of the 323 deemed eligible for participation , 107 were r and omized to receive placebo and 108 each to cyclobenzaprine and to oxycodone/acetaminophen . Follow-up was completed in December 2014 . INTERVENTIONS All participants were given 20 tablets of naproxen , 500 mg , to be taken twice a day . They were r and omized to receive either 60 tablets of placebo ; cyclobenzaprine , 5 mg ; or oxycodone , 5 mg/acetaminophen , 325 mg . Participants were instructed to take 1 or 2 of these tablets every 8 hours , as needed for LBP . They also received a st and ardized 10-minute LBP educational session prior to discharge . MAIN OUTCOMES AND MEASURES The primary outcome was improvement in RMDQ between ED discharge and 1 week later . RESULTS Demographic characteristics were comparable among the 3 groups . At baseline , median RMDQ score in the placebo group was 20 ( interquartile range [IQR],17 - 21 ) , in the cyclobenzaprine group 19 ( IQR,17 - 21 ) , and in the oxycodone/acetaminophen group 20 ( IQR,17 - 22 ) . At 1-week follow-up , the mean RMDQ improvement was 9.8 in the placebo group , 10.1 in the cyclobenzaprine group , and 11.1 in the oxycodone/acetaminophen group . Between-group difference in mean RMDQ improvement for cyclobenzaprine vs placebo was 0.3 ( 98.3 % CI , -2.6 to 3.2 ; P = .77 ) , for oxycodone/acetaminophen vs placebo , 1.3 ( 98.3 % CI , -1.5 to 4.1 ; P = .28 ) , and for oxycodone/acetaminophen vs cyclobenzaprine , 0.9 ( 98.3 % CI , -2.1 to 3.9 ; P = .45 ) . CONCLUSIONS AND RELEVANCE Among patients with acute , nontraumatic , nonradicular LBP presenting to the ED , adding cyclobenzaprine or oxycodone/acetaminophen to naproxen alone did not improve functional outcomes or pain at 1-week follow-up . These findings do not support use of these additional medications in this setting . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01587274", "OBJECTIVES /HYPOTHESIS Sore throat is a common , benign emergency department ( ED ) presentation ; however , peritonsillar abscess ( PTA ) is a complication that requires aggressive management . Use of systemic corticosteroids ( SCSs ) in PTA is occurring without clear evidence of benefit . This study examined the efficacy and safety of SCS treatment for patients with PTA . STUDY DESIGN R and omized , double-blind , placebo-controlled trial . METHODS A controlled trial with concealed allocation and double-blinding was conducted at two Canadian EDs . Following written informed consent , eligible patients received 48 hours of intravenous clindamycin and a single dose of the study drug ( dexamethasone [ DEX ] or placebo [ PLAC ] , intravenously [ IV ] ) . Follow-up occurred at 24 hours , 48 hours , and 7 days . The primary outcome was pain ; other outcomes were side effects and return to normal activities/diet . RESULTS A total of 182 patients were screened for eligibility ; 41 patients were enrolled ( 21 DEX ; 20 PLAC ) . At 24 hours , those receiving DEX reported lower pain scores ( 1.4 vs. 5.1 ; P = .009 ) ; however , these differences disappeared by 48 hours ( P = .22 ) and 7 days ( P = .4 ) . At 24 hours , more patients receiving DEX returned to normal activities ( 33 % vs. 11 % ) and dietary intake ( 38 % vs 25 % ) ; however , these differences were not significant and disappeared by 48 hours and 7 days . Side effects were rare and did not differ between groups ( P > .05 ) . CONCLUSIONS Combined with PTA drainage and IV antibiotics , 10 mg IV DEX result ed in less pain at 24 hours when compared to PLAC , without any serious side effects . This effect is short-lived , and further research is required on factors associated with PTA treatment success" ]

[ "Regression of hypertensive left ventricular hypertrophy ( LVH ) is associated with improved prognosis . The aim of this trial was to compare the effects of irbesartan versus atenolol on LVH in subjects with essential hypertension . Because electrocardiographic and echocardiographic parameters of LVH carry disparate prognostic information , both methods were applied in this trial . In the r and omized , double-blind , multicenter trial CardioVascular Irbesartan Project , 240 patients with essential hypertension were treated with irbesartan or atenolol for 18 months . Voltage criteria used for LVH were Sokolow index , Cornell index , Cornell voltage × QRS duration product and Lewis index . In parallel , left ventricular mass ( LVM ) was determined by 2-dimensional guided M-mode echocardiography . After 6 and 18 months , reductions of LVM and voltage criteria for LVH were only found in subjects treated with irbesartan . However , a reduction of LVM was only detectable in subjects within the highest quartile of baseline LVM but not overall . In contrast , reductions of voltage criteria for LVH were detectable after 6 and 18 months even within commonly used normal limits . In conclusion , treatment of hypertension with irbesartan result ed in a significant reduction in the voltage criteria for LVH , although an effect on LVM was only seen in subjects with high baseline LVM . In contrast , atenolol did not lead to reductions in electrocardiographic or echocardiographic parameters of LVH . Because voltage criteria for LVH have been shown to predict cardiovascular outcome independently from LVM , we suggest that both methods should be used to accurately assess the benefits of antihypertensive treatment", "Background — Heart failure ( HF ) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction ( PEF [ ≥50 % ] or REF [ , 42 418 high-risk hypertensive patients were r and omized to chlorthalidone , amlodipine , lisinopril , or doxazosin , providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF . Methods and Results — HF diagnostic criteria were prespecified in the ALLHAT protocol . EF estimated by contrast ventriculography , echocardiography , or radionuclide study was available in 910 of 1367 patients ( 66.6 % ) with hospitalized events meeting ALLHAT criteria . Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF ( overall and by PEF and REF ) . HF case fatality rates were examined . Of those with EF data , 44.4 % had HFPEF and 55.6 % had HFREF . Chlorthalidone reduced the risk of HFPEF compared with amlodipine , lisinopril , or doxazosin ; the hazard ratios were 0.69 ( 95 % confidence interval [ CI ] , 0.53 to 0.91 ; P=0.009 ) , 0.74 ( 95 % CI , 0.56 to 0.97 ; P=0.032 ) , and 0.53 ( 95 % CI , 0.38 to 0.73 ; P Chlorthalidone reduced the risk of HFREF compared with amlodipine or doxazosin ; the hazard ratios were 0.74 ( 95 % CI , 0.59 to 0.94 ; P=0.013 ) and 0.61 ( 95 % CI , 0.47 to 0.79 ; P Chlorthalidone was similar to lisinopril with regard to incidence of HFREF ( hazard ratio , 1.07 ; 95 % CI , 0.82 to 1.40 ; P=0.596 ) . After HF onset , death occurred in 29.2 % of participants ( chlorthalidone/amlodipine/lisinopril ) with new-onset HFPEF versus 41.9 % in those with HFREF ( P chlorthalidone/doxazosin comparison that was terminated early , 20.0 % of HFPEF and 26.0 % of HFREF patients died ( P=0.185 ; median follow-up , 1.55 years ) . Conclusions — In ALLHAT , with adjudicated outcomes , chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin . Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril . Among high-risk hypertensive men and women , HFPEF has a better prognosis than HFREF", "BACKGROUND The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear . In prespecified analyses , we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients . METHODS As part of the LIFE study , in a double-masked , r and omised , parallel-group trial , we assigned a group of 1195 patients with diabetes , hypertension , and signs of left-ventricular hypertrophy ( LVH ) on electrocardiograms losartan-based or atenolol-based treatment . Mean age of patients was 67 years ( SD 7 ) and mean blood pressure 177/96 mm Hg ( 14/10 ) after placebo run-in . We followed up patients for at least 4 years ( mean 4.7 years [ 1.1 ] ) . We used Cox regression analysis with baseline Framingham risk score and electrocardiogram-LVH as covariates to compare the effects of the drugs on the primary composite endpoint of cardiovascular morbidity and mortality ( cardiovascular death , stroke , or myocardial infa rct ion ) . FINDINGS Mean blood pressure fell to 146/79 mm Hg ( 17/11 ) in losartan patients and 148/79 mm Hg ( 19/11 ) in atenolol patients . The primary endpoint occurred in 103 patients assigned losartan ( n=586 ) and 139 assigned atenolol ( n=609 ) ; relative risk 0.76 ( 95 % CI 0.58-.98 ) , p=0.031 . 38 and 61 patients in the losartan and atenolol groups , respectively , died from cardiovascular disease ; 0.63 ( 0.42 - 0.95 ) , p=0.028 . Mortality from all causes was 63 and 104 in losartan and atenolol groups , respectively ; 0.61 ( 0.45 - 0.84 ) , p=0.002 . INTERPRETATION Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension , diabetes , and LVH . Losartan seems to have benefits beyond blood pressure reduction", "In the main Valsartan Antihypertensive Long-Term Use Evaluation ( VALUE ) report , we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens . In this report , we analyzed outcomes in 7080 patients ( 46.4 % ) who , at the end of the initial drug adjustment period ( 6 months ) , remained on monotherapy . Baseline characteristics were similar in the valsartan ( N=3263 ) and amlodipine ( N=3817 ) groups . Time on monotherapy was 3.2 years ( 78 % of treatment exposure time ) . The average in-trial blood pressure was similar in both groups . Event rates in the monotherapy group were 16 % to 39 % lower than in the main VALUE trial . In the first analysis , we censored patients when they discontinued monotherapy ( “ censored ” ) ; in the second , we counted events regardless of subsequent therapy ( intention-to-treat principle ) . We also assessed the impact of duration of monotherapy on outcomes . No difference was found in primary composite cardiac end points , strokes , myocardial infa rct ions , and all-cause deaths with both analyses . Heart failure in the valsartan group was lower both in the censored and intention-to-treat analyses ( hazard ratios : 0.63 , P=0.004 and 0.78 , P=0.045 , respectively ) . Longer duration of monotherapy amplified between-group differences in heart failure . New-onset diabetes was lower in the valsartan group with both analyses ( odds ratios : 0.78 , P=0.012 and 0.82 , P=0.034 ) . Thus , despite lower absolute event rates in monotherapy patients , the relative risks of heart failure and new-onset diabetes favored valsartan . Moreover , these findings support the feasibility of comparative prospect i ve trials in lower-risk hypertensive patients", "Hypertension is associated with reduced coronary vasodilatory capacity , possibly caused by structural changes in the coronary resistance vessels . Because vasodilatory treatment may correct abnormal structure better than nonvasodilating treatment , we compared whether long-term angiotensin-converting enzyme ( ACE ) inhibition has a greater effect on coronary reserve and cardiovascular structure than & bgr;-blockade in patients with essential hypertension . Thirty previously untreated hypertensive patients were r and omized in a double-blind design to treatment for 1 year with either perindopril ( 4 to 8 mg per day , n=15 ) or atenolol ( 50 to 100 mg per day , n=15 ) and furthermore compared with normotensive controls . Cardiac output and left ventricular mass were measured with echocardiography and resistance artery structure was determined in vitro . Using positron emission tomography , myocardial perfusion ( MP ) was determined at rest and during dipyridamole-induced hyperemia while still on medication . Perindopril reduced left ventricular mass by 14±4 % ( P peripheral vascular resistance by 12±6 % ( P and media thickness-to-lumen diameter ratio of resistance arteries by 16±4 % ( P whereas atenolol had no effect . Resting MP was decreased both by perindopril ( −11±4 % , P by atenolol ( −25±4 % , P reduction in rate pressure product . Hyperemic MP was unaltered by perindopril ( + 2±6 % , P = NS ) , but reduced by atenolol ( −32±5 % , P Compared with atenolol , perindopril treatment result ed in higher coronary reserve ( P regression of hypertensive resistance artery structure and left ventricular hypertrophy . Vasodilating may thus be superior to nonvasodilating treatment in repairing the hypertensive myocardial microcirculation", "The Losartan Intervention For Endpoint reduction in hypertension ( LIFE ) study showed that treatment with the angiotensin II type-1 receptor antagonist losartan reduces overall stroke risk compared with conventional therapy with the & bgr;-blocker atenolol . We conducted secondary analyses in LIFE to determine the extent to which the cerebrovascular benefits of losartan apply to different clinical subgroups and stroke subtypes and to assess the dependence of these benefits on baseline and time-varying covariates . Among 9193 hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy , r and om allocation to losartan-based treatment lowered the risk of fatal ( hazard ratio [ HR ] , 0.65 ; 95 % confidence interval [ CI ] , 0.43 to 0.96 ; P=0.032 ) and atherothrombotic stroke ( HR , 0.72 ; 95 % CI , 0.59 to 0.88 ; P=0.001 ) compared with atenolol-based therapy . Although comparable risk reductions occurred for hemorrhagic and embolic stroke , these were not statistically significant . The number of neurological deficits per stroke was similar , but there were fewer strokes in the losartan group for nearly every level of stroke severity . Effects were consistent in all clinical subgroups except for those defined by age and ethnicity . The benefits of losartan on all strokes were independent of baseline and time-varying risk factors , including blood pressure . The number needed to treat for 5 years to prevent 1 stroke was 54 for the average participant , declining to 25 , 24 , and 9 for patients with cerebrovascular disease , isolated systolic hypertension , and atrial fibrillation , respectively . In conclusion , substantial cerebrovascular benefit could be realized with the institution of losartan-based therapy over conventional therapy among hypertensive patients with left ventricular hypertrophy across the spectrum of cardiovascular risk", "BACKGROUND Treatment of hypertension with diuretics , beta-blockers , or both leads to improved outcomes . It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone . We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme ( ACE ) inhibitors with the outcomes in those treated with diuretic agents . METHODS We conducted a prospect i ve , r and omized , open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practice s. Subjects were followed for a median of 4.1 years , and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models . RESULTS At base line , the treatment groups were well matched in terms of age , sex , and blood pressure . By the end of the study , blood pressure had decreased to a similar extent in both groups ( a decrease of 26/12 mm Hg ) . There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group ( 56.1 per 1000 patient-years ) and 736 cardiovascular events or deaths from any cause in the diuretic group ( 59.8 per 1000 patient-years ; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [ 95 percent confidence interval , 0.79 to 1.00 ] ; P=0.05 ) . Among male subjects , the hazard ratio was 0.83 ( 95 percent confidence interval , 0.71 to 0.97 ; P=0.02 ) ; among female subjects , the hazard ratio was 1.00 ( 95 percent confidence interval , 0.83 to 1.21 ; P=0.98 ) ; the P value for the interaction between sex and treatment-group assignment was 0.15 . The rates of nonfatal cardiovascular events and myocardial infa rct ions decreased with ACE-inhibitor treatment , whereas a similar number of strokes occurred in each group ( although there were more fatal strokes in the ACE-inhibitor group ) . CONCLUSIONS Initiation of antihypertensive treatment involving ACE inhibitors in older subjects , particularly men , appears to lead to better outcomes than treatment with diuretic agents , despite similar reductions of blood pressure", "BACKGROUND Cardiac effects of hypertension include increased left ventricular ( LV ) mass and LV hypertrophy , as well as increased left atrial size , a predictor of stroke and atrial fibrillation . Although literature on reduction of LV mass with antihypertensive therapy is extensive , little information is available on effects of treatment on left atrial size . METHODS AND RESULTS Patients with mild to moderate hypertension ( diastolic blood pressure 95 to 109 mm Hg ) were r and omly allocated to treatment with atenolol , captopril , clonidine , diltiazem , hydrochlorothiazide , or prazosin in a double-masked trial . Two-dimensional targeted M-mode echocardiography was used to assess left atrial size and LV mass at baseline , 8 weeks , and 1 and 2 years . Longitudinal analysis examined changes in left atrial size from the baseline study , statistically adjusting for age , race , pretreatment left atrial size and LV mass , and serial measurements of systolic blood pressure , body weight , urinary sodium excretion , and physical activity score . Without adjustment for covariates , only hydrochlorothiazide was associated with decreases in left atrial size from baseline at 8 weeks ( -1.0 + /- 5.2 mm ; P=0.052 ) , 1 year ( -2.0 + /- 5.1 mm ; P=0.02 ) , and 2 years ( 4.6+/-7.2 mm ; P=0.002 ) . After adjustment for effects of covariates , patients with normal left atrial size had greater reduction ( -3.3 mm ) in left atrial size at 2 years with hydrochlorothiazide than with any other drug . For patients with left atrial enlargement , left atrial size decreased significantly with hydrochlorothiazide , atenolol , clonidine , and diltiazem at 1 year and with all treatments at 2 years . However , reduction at 2 years was greater with hydrochlorothiazide than with captopril or prazosin . CONCLUSIONS Antihypertensive drugs differ in their effects on left atrial size . Hydrochlorothiazide was associated with greater overall reduction of left atrial size than other drugs effective for the treatment of hypertension . Reduction of left atrial size with therapy is in part independent of factors known to influence left atrial size , including LV mass and reduction of LV mass with treatment . The clinical benefit of reducing left atrial size with antihypertensive treatment remains to be determined", "Background —The Prospect i ve R and omized Enalapril Study Evaluating Regression of Ventricular Enlargement ( PRESERVE ) study was design ed to test whether enalapril achieves greater left ventricular ( LV ) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis ( 10 g/m2 ) . Methods and Results —An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month r and omized therapy . Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure ( −22/12 versus −21/13 mm Hg ) and LV mass index ( −15 versus −17g/m2 , both P > 0.20 ) . No significant between-treatment difference was detected in population subsets defined by monotherapy treatment , sex , age , race , or severity of baseline hypertrophy . Similarly , there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow . More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide ( 59 % versus 34 % , P atenolol ( 27 % versus 22 % , NS ) . Conclusions —Once-daily antihypertensive treatment with enalapril or long-acting nifedipine , plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure , both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy", "BACKGROUND Diabetes mellitus is a strong risk factor for cardiovascular and renal disease . We investigated whether the angiotensin-converting-enzyme ( ACE ) inhibitor ramipril can lower these risks in patients with diabetes . METHODS 3577 people with diabetes included in the Heart Outcomes Prevention Evaluation study , aged 55 years or older , who had a previous cardiovascular event or at least one other cardiovascular risk factor , no clinical proteinuria , heart failure , or low ejection fraction , and who were not taking ACE inhibitors , were r and omly assigned ramipril ( 10 mg/day ) or placebo , and vitamin E or placebo , according to a two-by-two factorial design . The combined primary outcome was myocardial infa rct ion , stroke , or cardiovascular death . Overt nephropathy was a main outcome in a sub study . FINDINGS The study was stopped 6 months early ( after 4.5 years ) by the independent data safety and monitoring board because of a consistent benefit of ramipril compared with placebo . Ramipril lowered the risk of the combined primary outcome by 25 % ( 95 % CI 12 - 36 , p=0.0004 ) , myocardial infa rct ion by 22 % ( 6 - 36 ) , stroke by 33 % ( 10 - 50 ) , cardiovascular death by 37 % ( 21 - 51 ) , total mortality by 24 % ( 8 - 37 ) , revascularisation by 17 % ( 2 - 30 ) , and overt nephropathy by 24 % ( 3 - 40 , p=0.027 ) . After adjustment for the changes in systolic ( 2.4 mm Hg ) and diastolic ( 1.0 mm Hg ) blood pressures , ramipril still lowered the risk of the combined primary outcome by 25 % ( 12 - 36 , p=0.0004 ) . INTERPRETATION Ramipril was beneficial for cardiovascular events and overt nephropathy in people with diabetes . The cardiovascular benefit was greater than that attributable to the decrease in blood pressure . This treatment represents a vasculoprotective and renoprotective effect for people with diabetes", "OBJECTIVES We report on a sub analysis of the effects of losartan and atenolol on cardiovascular events in black patients in the Losartan Intervention For Endpoint reduction in hypertension ( LIFE ) study . BACKGROUND The LIFE study compared losartan-based to atenolol-based therapy in 9,193 hypertensive patients with left ventricular hypertrophy ( LVH ) . Overall , the risk of the primary composite end point ( cardiovascular death , stroke , myocardial infa rct ion ) was reduced by 13 % ( p = 0.021 ) with losartan , with similar blood pressure ( BP ) reduction in both treatment groups . There was a suggestion of interaction between ethnic background and treatment ( p = 0.057 ) . METHODS Exploratory analyses were performed that placed LIFE study patients into black ( n = 533 ) and non-black ( n = 8,660 ) categories , overall , and in the U.S. ( African American [ n = 523 ] ; non-black [ n = 1,184 ] ) . RESULTS A significant interaction existed between the dichotomized groups ( black/non-black ) and treatment ( p = 0.005 ) ; a test for qualitative interaction was also significant ( p = 0.016 ) . The hazard ratio ( losartan relative to atenolol ) for the primary end point favored atenolol in black patients ( 1.666 [ 95 % confidence interval ( CI ) 1.043 to 2.661 ] ; p = 0.033 ) and favored losartan in non-blacks ( 0.829 [ 95 % CI 0.733 to 0.938 ] ; p = 0.003 ) . In black patients , BP reduction was similar in both groups , and regression of electrocardiographic-LVH was greater with losartan . CONCLUSIONS Results of the sub analysis are sufficient to generate the hypothesis that black patients with hypertension and LVH might not respond as favorably to losartan-based treatment as non-black patients with respect to cardiovascular outcomes , and do not support a recommendation for losartan as a first-line treatment for this purpose . The sub analysis is limited by the relatively small number of events", "BACKGROUND We sought to determine the incidence of newly diagnosed diabetes in treated elderly hypertensive patients and the prognostic impact of diabetes on long-term survival . METHODS The Second Australian National Blood Pressure ( ANBP2 ) study r and omized 6,083 hypertensive patients aged 65 - 84 years to angiotensin-converting enzyme inhibitor ( ACEI ) or thiazide diuretic-based therapy and followed them for a median of 4.1 years . Long-term survival was determined in 5,678 patients over an additional median of 6.9 years after ANBP2 ( post-trial ) . RESULTS After ANBP2 , the cohort was classified into preexisting ( 7.2 % ) , newly diagnosed ( 5.6 % ) , and no diabetes ( 87.2 % ) groups . A 44 % higher incidence of newly diagnosed diabetes was observed in patients r and omized to thiazide diuretic compared with ACEI-based treatment . The other predictors of newly diagnosed diabetes were having a higher body mass index , having a higher r and om blood glucose , and living in a regional location compared to major cities ( a geographical classification based on accessibility ) at study entry . After completion of ANBP2 , compared with those with no diabetes , the preexisting diabetes group experienced higher cardiovascular ( hazards ratio ( HR ) = 1.65 ; 95 % confidence interval ( CI ) = 1.03 - 2.65 ) and all-cause mortality ( HR = 1.40 ; 95 % CI = 1.02 - 1.92 ) when adjusted for age , sex , and treatment . A similar pattern was observed after including the post-trial period for cardiovascular ( HR = 1.52 ; 95 % CI = 1.20 - 1.93 ) and all-cause mortality ( HR = 1.50 ; 95 % CI = 1.29 - 1.73 ) . However , when the newly diagnosed group was compared with the no diabetes group , no significant difference was observed in cardiovascular ( HR = 0.33 ; 95 % CI = 0.11 - 1.05 ) or all-cause mortality ( HR = 0.76 ; 95 % CI = 0.47 - 1.23 ) either during the ANBP2 trial or including post-trial follow-up ( cardiovascular : HR = 0.82 ; 95 % CI = 0.58 - 1.17 ; all-cause mortality : HR = 1.04 ; 95 % CI = 0.85 - 1.27 ) . CONCLUSIONS Long-term presence of diabetes reduces survival . Compared with thiazide diuretics , ACEI-based antihypertensives may delay the development of diabetes in those at risk and thus potentially improve cardiovascular outcome in the elderly", "Background — Diuretics are recommended as first-line agents for the treatment of hypertension . This r and omized , double-blind , multicenter study assessed the long-term efficacy and safety of the direct renin inhibitor aliskiren in comparison with the diuretic hydrochlorothiazide in patients with essential hypertension . Methods and Results — After a 2- to 4-week placebo run-in , 1124 patients ( mean sitting diastolic blood pressure [ BP ] 95 to 109 mm Hg ) were r and omized to aliskiren 150 mg ( n=459 ) , hydrochlorothiazide 12.5 mg ( n=444 ) , or placebo ( n=221 ) once daily . Forced titration ( to aliskiren 300 mg or hydrochlorothiazide 25 mg ) occurred at week 3 ; at week 6 , patients receiving placebo were reassigned ( 1:1 ratio ) to aliskiren 300 mg or hydrochlorothiazide 25 mg . From week 12 , amlodipine 5 mg was added and titrated to 10 mg from week 18 for patients whose BP remained uncontrolled . Efficacy variables were analyzed for the intent-to-treat population with the use of the last observation carried forward method . BP reductions ( mean sitting systolic BP/mean sitting diastolic BP ) were significantly greater with aliskiren- versus hydrochlorothiazide-based treatment at week 26 ( −20.3/−14.2 versus −18.6/−13.0 mm Hg ; P for mean sitting diastolic BP ) . At the end of the monotherapy period ( week 12 ) , aliskiren 300 mg was superior to hydrochlorothiazide 25 mg in reducing BP ( −17.4/−12.2 versus −14.7/−10.3 mm H ; P rates were similar with aliskiren- ( 65.2 % ) and hydrochlorothiazide-based therapy ( 61.5 % ) . Hypokalemia was more frequent with hydrochlorothiazide-based therapy than aliskiren-based therapy ( 17.9 % versus 0.9 % ; P Aliskiren treatment , both as monotherapy and with optional addition of amlodipine , provided significantly greater BP reductions than the respective hydrochlorothiazide regimens . Aliskiren-based therapy was well tolerated . Direct renin inhibition with aliskiren therefore represents an effective option for the long-term treatment of essential hypertension", "Diuretic-based therapy is less effective in reducing the cardiac complications of hypertension than the risk of stroke and may be less effective in reducing left ventricular ( LV ) mass than is therapy with angiotensin converting enzyme ( ACE ) inhibition . In view of the strong association of LV hypertrophy with cardiovascular risk , this study was design ed to compare the impact of therapy with a diuretic and ACE inhibition on cardiac and vascular structure . Fifty essential hypertensives ( 74 % male , 88 % nonwhite ) participated in a double-blind study for 6 months and were r and omized to either ramipril or hydrochlorothiazide ( HCTZ ) . Echocardiography , carotid ultrasonography , and ambulatory blood pressure ( BP ) monitoring were performed at baseline and 3 and 6 months after initiation of therapy . The 22 ramipril patients were comparable to the 28 HCTZ patients at baseline in age , race , and 24-h BP . Although HCTZ result ed in a greater reduction in 24-h BP , only treatment with ramipril result ed in a decrease in LV mass ( 193 to 179 g , P wall thicknesses but not in chamber diameter . In multivariate analysis , both change in BP and treatment group were independent predictors of change in LV mass . Importantly , although neither drug reduced carotid artery cross-sectional area , relative wall thickness increased due to a tendency for vessel diameter to decrease and wall thickness to increase , particularly in the diuretic group . Ramipril caused a sustained fall in plasma angiotensin II , whereas HCTZ increased angiotensin II levels . Although diuretic therapy was more effective in lowering ambulatory BP in this predominantly nonwhite population , only therapy with ACE inhibition was associated with regression of LV mass . Vascular geometry was altered consistent with the reduction in distending pressure result ing in vascular remodelling", "Background and Purpose — Angiotensin receptor blocker (ARB)–based treatment reduces cardiovascular events and stroke more than does β-blocker – based treatment despite similar blood pressure ( BP ) reduction . We investigated whether these treatments have different effects on cardiac and large-artery remodelling and evaluated the relation of arterial remodelling to hemodynamic changes in subjects with hypertension . Methods — We compared the treatment effects of an ARB ( c and esartan cilexetil)-based regimen and a β-blocker (atenolol)–based regimen for 52 weeks on common carotid artery ( CCA ) and left ventricular structure in hypertensive patients in a r and omized , double-blind study . Clinic brachial BP and 24-hour ambulatory BP , carotid BP , left ventricular mass index , CCA intima-media thickness , lumen diameter , intima-media area , and carotid blood flow were measured . Distensibility , circumferential tensile stress , Young ’s elastic modulus ( Em ) , and shear stress ( & tgr ; ) in the CCA were also calculated . Results — Both c and esartan and atenolol reduced intima-media thickness and intima-media area and increased distensibility to similar extents after 52 weeks of treatment . Despite similar reductions in BP , treatment with atenolol result ed in a lesser reduction in left ventricular mass index , a decrease in lumen diameter , and a reduction in carotid blood flow compared with c and esartan . Conclusions — BP-independent effects of ARB on cardiac and arterial structure may contribute to the beneficial effects of these agents on cardiovascular disease", "Background —Elevated urine albumin excretion ( UAER ) is a modifiable risk factor for renal and cardiovascular disease in type 2 diabetes . Blockade of the renin-angiotensin system lowers UAER , but whether this effect is independent of blood pressure ( BP ) reduction remains controversial . The MicroAlbuminuria Reduction With VALsartan ( MARVAL ) study was design ed to evaluate the BP-independent effect of valsartan on UAER in type 2 diabetic patients with microalbuminuria . Methods and Results —Three hundred thirty-two patients with type 2 diabetes and microalbuminuria , with or without hypertension , were r and omly assigned to 80 mg/d valsartan or 5 mg/d amlodipine for 24 weeks . A target BP of 135/85 mm Hg was aim ed for by dose-doubling followed by addition of bendrofluazide and doxazosin whenever needed . The primary end point was the percent change in UAER from baseline to 24 weeks . The UAER at 24 weeks was 56 % ( 95 % CI , 49.6 to 63.0 ) of baseline with valsartan and 92 % ( 95 % CI , 81.7 to 103.7 ) of baseline with amlodipine , a highly significant between-group effect ( P Valsartan lowered UAER similarly in both the hypertensive and normotensive subgroups . More patients reversed to normoalbuminuria with valsartan ( 29.9 % versus 14.5%;P = 0.001 ) . Over the study period , BP reductions were similar between the two treatments ( systolic/diastolic 11.2/6.6 mm Hg for valsartan , 11.6/6.5 mm Hg for amlodipine ) and at no time point was there a between-group significant difference in BP values in either the hypertensive or the normotensive subgroup . Conclusions —For the same level of attained BP and the same degree of BP reduction , valsartan lowered UAER more effectively than amlodipine in patients with type 2 diabetes and microalbuminuria , including the subgroup with baseline normotension . This indicates a BP-independent antiproteinuric effect of valsartan", "OBJECTIVE The Captopril Prevention Project ( CAPPP ) evaluated the effects of an ACE inhibitor-based therapeutic regimen on cardiovascular mortality and morbidity in hypertension . One planned sub analysis of the CAPPP was to evaluate the outcome in the diabetic patient group . RESEARCH DESIGN AND METHODS In the CAPPP , 572 ( 4.9 % of 10,985 hypertensive patients ) had diabetes at baseline and were studied according to a prospect i ve , r and omized , open , blinded , end point trial design . Patients aged 25 - 66 years with diastolic blood pressure > or = 100 mmHg were included and r and omized to receive either captopril or conventional antihypertensive treatment ( diuretics and /or beta-blockers ) . RESULTS The primary end point , fatal and nonfatal myocardial infa rct ion and stroke as well as other cardiovascular deaths , was markedly lower in the captopril than in the conventional therapy group ( relative risk [ RR ] = 0.59 ; P = 0.018 ) . Specifically , cardiovascular mortality , defined as fatal stroke and myocardial infa rct ion , sudden death , and other cardiovascular death , tended to be lower in the captopril group ( RR = 0.48 ; P = 0.084 ) , and no difference was observed between the study groups for stroke ( RR = 1.02 ; P = 0.96 ) . Myocardial infa rct ions were less frequent in the captopril group than in the conventional therapy group ( RR = 0.34 ; P = 0.002 ) . Furthermore , total mortality was lower in the captopril as compared with the conventional therapy group ( RR = 0.54 ; P = 0.034 ) . Patients with impaired metabolic control seemed to benefit the most from ACE inhibitor-based therapy . CONCLUSIONS Captopril is superior to a diuretic/beta-blocker antihypertensive treatment regimen in preventing cardiovascular events in hypertensive diabetic patients , especially in those with metabolic decompensation", "Abstract Objective : This study compared the antihypertensive effect and acceptability of a perindopril-based group with that of an atenolol-based group in Indian hypertensive type 2 ( non-insulin-dependent ) diabetic patients . Design and Setting : 100 ambulant patients aged between 35 and 69 years were recruited into this monocentric , r and omised , double-blind study in two parallel groups for 1 year after a 1-month washout period on placebo . The setting was a tertiary care institution . Patients : All patients had stable , essential hypertension between 95 mm Hg and 115 mm Hg , type 2 diabetes with glycosylated haemoglobin ( HbA1c ) There were 50 patients per treatment group and two patient population groups were studied , intention-to-treat ( ITT ) and per- protocol ( PP ) . The former constituted all patients , whilst the latter included those without major protocol deviation and who completed the 12-month study . Interventions : The study drugs were perindopril 4 to 8 mg once daily or atenolol 50 to 100 mg once daily . In each group therapeutic adjustment was planned by doubling the dose and then by the addition of hydrochlorothiazide 25 mg daily . Nifedipine 30 to 60 mg daily was subsequently added if the desired drop in blood pressure was not obtained . The ITT group was analysed by Student ’s t-test , and a 2-way analysis of variance was performed for the PP population . Main Outcome Measures : A comparison of the control of hypertension , biochemical abnormalities , blood sugar and adverse effects was performed in the atenolol group versus the perindopril group . Results : On single-dose therapy after 1 month 17 patients ( 60 % ) had normal blood pressure [ diastolic blood pressure ( DBP ) ≤90 mm Hg ] on atenolol 50 mg daily , while 13 % ( 30.23 % ) had normal blood pressure ( DBP ≤90 mm Hg ) on perindopril 4 mg daily ( p = 0.013 ) . In the ITT group the sitting systolic blood pressure ( SBP ) decreased by 14.4 ± 22.3 mm Hg at the end of the treatment period on atenolol from 174.4 ± 17.9 mm Hg at the initial period , and the sitting SBP decreased by 21.6 ± 20.3 mm Hg at the end of perindopril treatment from an initial value of 172.1 ± 20.3 mm Hg ( probability 0.091 ) . The sitting DBP decreased by 18.6 ± 8.7 mm Hg on atenolol from 100.5 ± 4.8 mm Hg at the initial period and by 15.8 ± 9.1 mm Hg on perindopril from 100.6 ± 5.2 mm Hg ( probability 0.112 ) . Glycaemic control was similar for HbA1c fasting and postpr and ial glucose in the ITT population , while fasting glucose increased over time from 10.7 ± 4.1 to 12.0 ± 3.4 mmol/L ; p more additional antihypertensive drugs compared with atenolol monotherapy . There was a significant increase in fasting blood sugar in the atenolol-based group ( p < 0.001 )", "The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial ( ALLHAT ) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker – initiated therapy in older hypertensive individuals . Patients were r and omized to amlodipine ( n=9048 ) or lisinopril ( n=9054 ) . The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infa rct ion , analyzed by intention-to-treat . Secondary outcomes included all-cause mortality , stroke , combined cardiovascular disease ( CVD ) , end-stage renal disease ( ESRD ) , cancer , and gastrointestinal bleeding . Mean follow-up was 4.9 years . Blood pressure control was similar in nonblacks , but not in blacks . No significant differences were found between treatment groups for the primary outcome , all-cause mortality , ESRD , or cancer . Stroke rates were higher on lisinopril in blacks ( RR=1.51 , 95 % CI 1.22 to 1.86 ) but not in nonblacks ( RR=1.07 , 95 % CI 0.89 to 1.28 ) , and in women ( RR=1.45 , 95 % CI 1.17 to 1.79 ) , but not in men ( RR=1.10 , 95 % CI 0.92 to 1.31 ) . Rates of combined CVD were higher ( RR=1.06 , 95 % CI 1.00 to 1.12 ) because of higher rates for strokes , peripheral arterial disease , and angina , which were partly offset by lower rates for heart failure ( RR=0.87 , 95 % CI 0.78 to 0.96 ) on lisinopril compared with amlodipine . Gastrointestinal bleeds and angioedema were higher on lisinopril . Patients with and without baseline coronary heart disease showed similar outcome patterns . We conclude that in hypertensive patients , the risks for coronary events are similar , but for stroke , combined CVD , gastrointestinal bleeding , and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy . Some , but not all , of these differences may be explained by less effective blood pressure control in the lisinopril arm", "Objective To compare the effects of the calcium channel blocker amlodipine and the angiotensin-converting enzyme inhibitor lisinopril on intima – media thickness ( IMT ) in elderly , previously untreated hypertensive individuals . Design A double-blind r and omized parallel-group trial ( the ELVERA trial ) . Patients The study population comprised 166 newly diagnosed hypertensive individuals ( aged 60–75 years ) with diastolic blood pressure between 95 and 115 mmHg or systolic blood pressure between 160 and 220 mmHg , or both . Intervention Patients were allocated r and omly to groups to receive amlodipine 5–10 mg or lisinopril 10–20 mg for 2 years . Main outcome measures Before and after 1 and 2 years of treatment , IMT was measured in three carotid and two femoral arterial sites by B-mode ultrasound . The primary endpoint was the change from baseline of the combined mean maximum far wall IMT of carotid and femoral arteries , evaluated by repeated measurement analysis of the treatment effect in an intention-to-treat analysis . Results After 2 years of treatment , amlodipine decreased IMT by 0.089 mm [ 95 % confidence interval ( CI ) 0.144 to 0.037 ] . Lisinopril decreased IMT by 0.065 mm ( 95 % CI 0.124 to 0.010 ) . No differences between the two drugs were found ( P = 0.18 ) . Both treatment regimens achieved the greatest reduction of IMT after 1 year , with a slight increase after the second year , whereas the reduction in blood pressure was maintained . Comparing the carotid and femoral arteries , a significant treatment difference in the change from baseline in favour of amlodipine was observed in the IMT of the elastic common carotid artery ( P amlodipine and lisinopril reduce IMT to a similar extent in newly diagnosed elderly hypertensive patients . It is suggested that the two drugs have different effects on arteries that are not prone to atherosclerosis", "Background — Hypertension is a major cause of heart failure ( HF ) and is antecedent in 91 % of cases . The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) stipulated assessment of the relative effect of chlorthalidone , lisinopril , and amlodipine in preventing HF . Methods and Results — ALLHAT was a double-blind , r and omized , clinical trial in 33 357 high-risk hypertensive patients aged ≥55 years . Hospitalized/fatal HF outcomes were examined with proportional-hazards models . Relative risks ( 95 % confidence intervals ; P values ) of amlodipine or lisinopril versus chlorthalidone were 1.35 ( 1.21 to 1.50 ; amlodipine or lisinopril versus chlorthalidone during year 1 were 2.22 ( 1.69 to 2.91 ; . Baseline blood pressures were equivalent ( 146/84 mm Hg ) and at year 1 were 137/79 , 139/79 , and 140/80 mm Hg in those given chlorthalidone , amlodipine , and lisinopril . At 1 year , use of added open-label atenolol , diuretics , angiotensin-converting enzyme inhibitors , and calcium channel blockers in the treatment groups was similar . Conclusions — HF risk decreased with chlorthalidone versus amlodipine or lisinopril use during year 1 . Subsequently , risk for those individuals taking chlorthalidone versus amlodipine remained decreased but less so , whereas it was equivalent to those given lisinopril . Prior medication use , follow-up blood pressures , and concomitant medications are unlikely to explain most of the HF differences . Diuretics are superior to calcium channel blockers and , at least in the short term , angiotensin-converting enzyme inhibitors in preventing HF in hypertensive individuals", "1 . Our objective was to compare the effect of a long-acting calcium antagonist ( nisoldipine ) compared with an angiotensin-converting enzyme inhibitor ( lisinopril ) on the non-neurogenic regulation of the microvascular blood flow in hypertensive Type I diabetes patients with diabetic nephropathy.2 . We performed a 1-year double-blind , double-dummy r and omized controlled study comparing nisoldipine ( 20 - 40 mg once daily ) with lisinopril ( 10 - 20 mg once daily ) in 48 hypertensive Type I diabetes patients with diabetic nephropathy . For comparison , 22 age-matched normotensive healthy control subjects were included . Measurements were performed at baseline and after 1 year of antihypertensive treatment . The minimal vascular resistance and distensibility ( stiffness ) of resistance vessels in skin and skeletal muscle were measured using the local isotope washout method .3 . Mean arterial pressure was reduced to the same extent in both groups : nisoldipine , 113+/-2.1 to 105+/-1.6 mmHg ( P lisinopril , 110+/-2.7 to 101+/-2.1 mmHg ( P Nisoldipine improved the skin vascular distensibility from 28+/-3.3 to 43+/-3.8 % ( P skin minimal vascular resistance from 16.9+/-1.0 to 13.6+/-0.8 mmHg.ml-1.min.100 g ( P Lisinopril had no significant effect on skin vascular distensibility ( 40+/-4.0 % and 41+/-4.4 % ) , but minimal vascular resistance tended to diminish ( 18.1+/-0.9 to 15.8+/-1.3 mmHg.ml-1 . min.100 g ( P=0.09 ) . Nisoldipine significantly increased the skin distensibility ( P=0.05 ) after 1 year of antihypertensive treatment compared with lisinopril.4 . The control group had a skin vascular distensibility of 54+/-3.2 % and a minimal vascular resistance of 10 . 8+/-0.7 mmHg.ml-1.min.100 g , both significantly different from the values in the diabetic groups ( P Skeletal muscle vascular distensibility was unaltered after 1 year of treatment with both nisoldipine ( 22+/-3.3 % and 19+/-2.7 % ) and lisinopril ( 19+/-2.1 % and 24+/-2.5 % ) , but was reduced compared with a control value of 43+/-3.7 % ( P nisoldipine nor lisinopril had any effect on the increased minimal vascular resistance or the reduced skeletal muscle distensibility.5 . Enhanced thickening of the basement membranes of the terminal arteriolar wall was found in skin biopsy specimens in 91 % of diabetic patients and 38 % only in control subjects ( P arteriolar hyalinosis.6 . The reduction in systemic blood pressure was identical during 1 year of treatment with nisoldipine or lisinopril . The abnormal arteriolar stiffness was more pronounced in the group treated with nisoldipine than with lisinopril and only nisoldipine compared with lisinopril improved the abnormal arteriolar stiffness and minimal vascular resistance in the skin . This suggests that nisoldipine can reverse the peripheral skin perfusion and thereby improve the local protection against development of ischaemic skin lesions in Type I diabetes patients with clinical diabetic nephropathy", "OBJECTIVE To compare the effects of the calcium channel blocker , nisoldipine , and the ACE inhibitor , lisinopril , on left ventricular mass ( LVM ) and systolic function in type 1 diabetic patients with diabetic nephropathy . RESEARCH DESIGN AND METHODS M-mode echocardiography was performed in 50 hypertensive type 1 diabetic patients with diabetic nephropathy enrolled in a 1-year , r and omized , double-blind , parallel study of antihypertensive treatment with nisoldipine CC ( 20 - 40 mg/day ) or lisinopril ( 10 - 20 mg/day ) . Ambulatory 24-h blood pressure was measured with the Takeda TM 2420 device ( A & D , Tokyo , Japan ) every 3 months . Three patients dropped out and seven patients were excluded due to technical difficulties . RESULTS The 24-h diastolic blood pressure was reduced from 83 to 80 mmHg in the nisoldipine group ( P = 0.06 ) and from 85 to 80 mmHg in the lisinopril group ( P = 0.02 ) . The decline in systolic blood pressure was not significant with any of the two treatments , and no difference in reduction of blood pressure was seen between groups . LVM corrected for body surface area ( LVMI ) was comparable between groups at baseline and increased from 96 + /- 5 to 107 + /- 6 g/m2 ( mean + /- SEM ; P = 0.007 ) in the nisoldipine group and from 95 + /- 4 to 103 + /- 5 g/m2 ( P = 0.03 ) in the lisinopril group . The mean difference between the change in LVMI in the two groups was 2.9 ( 95 % CI 6.8 to 12.7 ) g/m2 . The prevalence of left ventricular hypertrophy rose from 18 ( 95 % CI 6 - 30 ) to 30 % ( 16 - 44 ) during the study period . A multiple linear regression analysis revealed that after 1 year of treatment , LVMI increased with higher systolic blood pressure level and declining glomerular filtration rate ( R2 = 0.25 ) . Fractional shortening was within normal range at baseline , 42 + /- 1 vs. 41 + /- 1 % with nisoldipine and lisinopril , respectively , and did not change during follow-up . CONCLUSIONS Antihypertensive treatment with nisoldipine or lisinopril to bring diastolic blood pressure level within the normal target range does not hinder a rise in LVMI in type 1 diabetic patients with diabetic nephropathy", "BACKGROUND It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure . METHODS We r and omly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan ( 300 mg daily ) , amlodipine ( 10 mg daily ) , or placebo . The target blood pressure was 135/85 mm Hg or less in all groups . We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration , the development of end-stage renal disease , or death from any cause . We also compared them with regard to the time to a secondary , cardiovascular composite end point . RESULTS The mean duration of follow-up was 2.6 years . Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group ( P=0.02 ) and 23 percent lower than that in the amlodipine group ( P=0.006 ) . The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group ( P=0.003 ) and 37 percent lower in the irbesartan group than in the amlodipine group ( P irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups ( P=0.07 for both comparisons ) . These differences were not explained by differences in the blood pressures that were achieved . The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group ( P=0.008 ) and 21 percent more slowly than in the amlodipine group ( P=0.02 ) . There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point . CONCLUSIONS The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes . This protection is independent of the reduction in blood pressure it causes", "Seventeen male untreated mild essential hypertensive patients aged 41 + /- 2 years agreed to participate in a double-blind r and omized trial to test the effects of antihypertensive treatment on the structure and function of subcutaneous resistance arteries . Patients were treated with either 50 to 100 mg/d atenolol or 2.5 to 5 mg/d cilazapril . Blood pressure before treatment was 148 + /- 6/99 + /- 1 and 147 + /- 2/99 + /- 1 mm Hg , respectively . At 1 year of treatment blood pressure was 131 + /- 4/85 + /- 2 and 132 + /- 2/87 + /- 1 mm Hg , respectively . Resistance arteries ( 200 to 400 microns lumen diameter ) dissected from subcutaneous gluteal biopsies obtained before treatment and at 1 year showed that the media-lumen ratio of arteries from patients treated with cilazapril was reduced to 6.31 + /- 0.21 % from 7.54 + /- 0.31 % before treatment ( P media-lumen ratio of resistance arteries of normotensive control subjects ( 5.15 + /- 0.30 % ) . In contrast , in arteries from patients treated with atenolol there was no significant change with treatment ( 7.97 + /- 0.60 % before and 8.07 + /- 0.45 % after 1 year of treatment ) . Active wall tension responses to endothelin-1 were blunted in hypertensive patients and normalized in the cilazapril-treated patients . Depressed active media stress responses to norepinephrine , arginine vasopressin , and endothelin-1 were accordingly normalized in the patients receiving cilazapril as the media width became thinner but were unchanged in those taking atenolol . ( ABSTRACT TRUNCATED AT 250 WORDS", "A r and omized , double-blind , active-controlled , multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and ≥ 1 other coronary heart disease risk factors to receive chlorthalidone ( n=15,002 ) , amlodipine ( n=8898 ) , or lisinopril ( n=8904 ) for 4 to 8 years , when double-blinded therapy was discontinued . Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative data bases to ascertain deaths and hospitalizations . During the post-trial period , fatal outcomes and nonfatal outcomes were available for 98 % and 65 % of participants , respectively , due to lack of access to administrative data bases for the remainder . This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up . Primary outcome was cardiovascular mortality and secondary outcomes were mortality , stroke , coronary heart disease , heart failure , cardiovascular disease , and end-stage renal disease . For the post-trial period , data are not available on medications or blood pressure levels . No significant differences ( P in cardiovascular mortality for amlodipine ( hazard ratio [ HR ] , 1.00 ; 95 % confidence interval [ CI ] , 0.93 - 1.06 ) or lisinopril ( HR , 0.97 ; CI , 0.90 - 1.03 ) , each compared with chlorthalidone . The only significant differences in secondary outcomes were for heart failure , which was higher with amlodipine ( HR , 1.12 ; CI , 1.02 - 1.22 ) , and stroke mortality , which was higher with lisinopril ( HR , 1.20 ; CI , 1.01 - 1.41 ) , each compared with chlorthalidone . Similar to the previously reported in-trial result , there was a significant treatment-by-race interaction for cardiovascular disease for lisinopril vs chlorthalidone . Black participants had higher risk than non-black participants taking lisinopril compared with chlorthalidone . After accounting for multiple comparisons , none of these results were significant . These findings suggest that neither calcium channel blockers nor angiotensin-converting enzyme inhibitors are superior to diuretics for the long-term prevention of major cardiovascular complications of hypertension ", "BACKGROUND The multicenter double-blind , r and omized Bergamo Nephrologic Diabetes Complications Trial ( BENEDICT ) was design ed to assess whether angiotensin-converting-enzyme inhibitors and non-dihydropyridine calcium-channel blockers , alone or in combination , prevent microalbuminuria in subjects with hypertension , type 2 diabetes mellitus , and normal urinary albumin excretion . METHODS We studied 1204 subjects , who were r and omly assigned to receive at least three years of treatment with tr and olapril ( at a dose of 2 mg per day ) plus verapamil ( sustained-release formulation , 180 mg per day ) , tr and olapril alone ( 2 mg per day ) , verapamil alone ( sustained-release formulation , 240 mg per day ) , or placebo . The target blood pressure was 120/80 mm Hg . The primary end point was the development of persistent microalbuminuria ( overnight albumin excretion , > or = 20 microg per minute at two consecutive visits ) . RESULTS The primary outcome was reached in 5.7 percent of the subjects receiving tr and olapril plus verapamil , 6.0 percent of the subjects receiving tr and olapril , 11.9 percent of the subjects receiving verapamil , and 10.0 percent of control subjects receiving placebo . The estimated acceleration factor ( which quantifies the effect of one treatment relative to another in accelerating or slowing disease progression ) adjusted for predefined baseline characteristics was 0.39 for the comparison between verapamil plus tr and olapril and placebo ( P=0.01 ) , 0.47 for the comparison between tr and olapril and placebo ( P=0.01 ) , and 0.83 for the comparison between verapamil and placebo ( P=0.54 ) . Tr and olapril plus verapamil and tr and olapril alone delayed the onset of microalbuminuria by factors of 2.6 and 2.1 , respectively . Serious adverse events were similar in all treatment groups . CONCLUSIONS In subjects with type 2 diabetes and hypertension but with normoalbuminuria , the use of tr and olapril plus verapamil and tr and olapril alone decreased the incidence of microalbuminuria to a similar extent . The effect of verapamil alone was similar to that of placebo", "Background —Prevalent atrial fibrillation ( AF ) is associated with a higher sudden cardiac death ( SCD ) rate in some population s , and incident AF predicts increased mortality risk in the general population and after myocardial infa rct ion . However , the relationship of SCD to new-onset AF is unclear . Methods and Results —The relationship of SCD to new-onset AF was evaluated in 8831 hypertensive patients with electrocardiographic left ventricular hypertrophy with no history of AF , in sinus rhythm on their baseline electrocardiogram , r and omly assigned to losartan- or atenolol-based treatment . During 4.7±1.1 years mean follow-up , new-onset AF occurred in 701 patients ( 7.9 % ) and SCD in 151 patients ( 1.7 % ) . In univariate Cox analyses , new-onset AF was associated with a > 4-fold higher risk of SCD ( hazard ratio , 4.69 ; 95 % CI interval , 2.96–7.45 ; P myocardial infa rct ion , in-treatment use of digoxin , systolic and diastolic pressure , heart rate , QRS duration , Cornell voltage- duration product , and Sokolow-Lyon voltage left ventricular hypertrophy treated as time-varying covariates , new-onset AF remained associated with a > 3-fold increased risk of SCD ( hazard ratio , 3.13 ; 95 % confidence interval , 1.87–5.24 ; P hypertensive patients at increased risk of SCD . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00338260", "OBJECTIVES To compare the effects of three antihypertensive medications on cerebral hemodynamic and cognitive function in hypertensive individuals with executive dysfunction . DESIGN Double-blind r and omized clinical trial . SETTING Community . PARTICIPANTS Fifty-three individuals aged 60 and older with hypertension and executive dysfunction . INTERVENTION Lisinopril , c and esartan , or hydrochlorothiazide for 1 year . MEASUREMENTS Cerebral blood flow velocity ( BFV ; transcranial Doppler ultrasonography during rest , sitting , st and ing , hypercapnia , and hypocapnia ) , cognition , and blood pressure were measured at baseline and after 6 and 12 months . Linear mixed models were used to compare the three groups . RESULTS Of the 53 participants , 47 had successful insonation ( mean age 72 ; 70 % white ; 57 % women ) . There was a tendency toward an increase in BFV in the c and esartan group and a decrease in the lisinopril and hydrochlorothiazide groups ( between-group P = .57 ) that was significant in those with low BFV at baseline ( executive function ( Trail Making Test Part B improved by 17.1 seconds , vs hydrochlorothiazide improved by 4.2 seconds and lisinopril worsened by 14.4 seconds , P = .008 ) . Carbon dioxide vasoreactivity and vasomotor range declined significantly in the lisinopril ( within-group P = .001 for vasoreactivity and .02 for vasomotor range ) and hydrochlorothiazide groups ( within-group P = .10 and .009 , respectively ) but not in the c and esartan group ( within-group P = .25 and .38 , respectively ; between-group P = .30 and .46 , respectively ) . CONCLUSION Angiotensin receptor blockers may preferentially preserve cerebral hemodynamics and executive function in individuals with executive dysfunction . These findings warrant further investigation in a larger trial", "Hypertension has been associated with changes in endothelial function in both large muscular arteries and small resistance arteries . We evaluated the relationship between blood flow velocity and dilatation of the brachial artery following transient forearm ischemia and acetylcholine‐induced relaxation in subcutaneous small arteries and the influence of antihypertensive therapy on both in patients with essential hypertension . Thirty‐one previously untreated hypertensive patients were r and omized in a double‐blind fashion to treatment with either the angiotensin‐converting enzyme ( ACE ) inhibitor perindopril or the beta‐blocker atenolol and compared with 17 healthy normotensive controls . Before and after 1 year of treatment , while still on active medication , flow‐mediated dilatation ( FMD ) was measured in the brachial artery using ultrasound while relaxation to acetylcholine in small arteries was tested in vitro in a myograph . FMD correlated inversely to resting brachial artery diameter ( r = −0.38 , p ) . FMD corrected for resting diameter ( FMDcorr ) was lower in patients ( 3.0±0.2 % ) compared with controls ( 4.2±0.3 % , p controls , FMDcorr was related to flow velocity in a non‐linear way with FMDcorr reaching a maximum despite increasing flow velocities , and in the patients , FMDcorr was only reduced at high flow velocities . Furthermore , patients had a reduced acetylcholine‐induced relaxation in small arteries ( p = 0.04 ) . Perindopril and atenolol reduced blood pressure to similar levels and both drugs improved FMDcorr to a similar degree without any effects on relaxation to acetylcholine in small arteries . The present study demonstrates the role of correcting for differences in baseline diameter during measurements of FMD and a non‐linear relationship between flow velocity and FMD in the brachial artery . Furthermore , the results suggest different effects of antihypertensive treatment on endothelial function in large and small arteries", "Objective The FGB gene codes for fibrinogen-&bgr ; , a polypeptide of the coagulation factor fibrinogen , which is positively associated with cardiovascular diseases . Studies show that angiotensin-converting enzyme ( ACE ) inhibitors lower plasma fibrinogen concentrations , whereas diuretics and calcium-channel blockers do not . As carriers of the FGB-455 minor ‘ A ’ allele have higher levels of fibrinogen while ACE inhibitors lower it , we hypothesize that ‘ A ’ allele carriers benefit more from antihypertensive treatment with ACE inhibitors than calcium-channel blockers or diuretics , relative to ‘ GG ’ genotype individuals . Methods The Genetics of Hypertension Associated Treatment ( GenHAT ) study [ ancillary to Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) ] genotyped hypertensive participants for several hypertension-related c and i date genes , making this a post-hoc analysis of a r and omized trial . In total , 90.1 % of the ALLHAT population was successfully genotyped for FGB-455 . We included participants ( n=30 076 ) r and omized to one of three antihypertensive medications ( lisinopril , amlodipine , chlorthalidone ) , with two treatment comparisons : lisinopril versus chlorthalidone and lisinopril versus amlodipine . The primary outcome of ALLHAT/GenHAT was coronary heart disease , defined as fatal coronary heart disease or non-fatal myocardial infa rct ion , and secondary outcomes included stroke , heart failure , all-cause mortality , and end-stage renal disease ( ESRD ) with mean follow-up time of 4.9 years . Genotype-by-treatment interactions ( pharmacogenetic effects ) were tested with the Cox regression . Results Stroke : common ‘ GG ’ homozygotes had higher risk on lisinopril versus amlodipine [ hazard ratio (HR)=1.38 , P Mortality : ‘ GG ’ homozygotes had higher risk on lisinopril versus amlodipine ( HR=1.12 , P=0.02 ) or chlorthalidone ( 1.05 , P=0.23 ) , whereas ‘ A ’ allele carriers had slightly lower risk ( HR=0.92 , P=0.33 for lisinopril versus amlodipine ; HR=0.88 , P=0.08 for lisinopril versus chlorthalidone ; P value for interactions 0.04 and 0.03 , respectively ) . ESRD : ‘ GG ’ homozygotes had higher risk on lisinopril versus chlorthalidone ( HR=1.27 , P=0.08 ) , whereas ‘ A ’ allele carriers had lower risk ( HR=0.64 , P=0.12 ; P value for interaction=0.03 ) . Conclusion There was evidence of pharmacogenetic effects of FGB-455 on stroke , ESRD , and mortality , suggesting that relative to those homozygous for the common allele , variant allele carriers of the FGB gene at position −455 have a better outcome if r and omized to lisinopril than chlorthalidone ( for mortality and ESRD ) or amlodipine ( for mortality and stroke ) . For the models in which a pharmacogenetic effect was observed , the outcome rates among ‘ GG ’ homozygotes were higher in those r and omized to lisinopril versus amlodipine or chlorthalidone , whereas minor ‘ A ’ allele carriers had lower event rates when r and omized to lisinopril versus the other medications", "OBJECTIVE The Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial is a prospect i ve r and omized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications . The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy , retinopathy , and neuropathy . RESEARCH DESIGN AND METHODS The 470 hypertensive subjects , defined as having a baseline diastolic blood pressure of > or = 90 mmHg , were r and omized to intensive blood pressure control ( diastolic blood pressure goal of 75 mmHg ) versus moderate blood pressure control ( diastolic blood pressure goal of 80 - 89 mmHg ) . RESULTS The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group . During the 5-year follow-up period , no difference was observed between intensive versus moderate blood pressure control and those r and omized to nisoldipine versus enalapril with regard to the change in creatinine clearance . After the first year of antihypertensive treatment , creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria . In contrast , patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5 - 6 ml.min-1.1.73 m-2 per year throughout the follow-up period whether they were on intensive or moderate therapy . There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria ( 25 % intensive therapy vs. 18 % moderate therapy , P = 0.20 ) or microalbuminuria to overt albuminuria ( 16 % intensive therapy vs. 23 % moderate therapy , P = 0.28 ) . Intensive therapy demonstrated a lower overall incidence of deaths , 5.5 vs. 10.7 % , P = 0.037 . Over a 5-year follow-up period , there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neuropathy . In addition , the use of nisoldipine versus enalapril had no differential effect on diabetic retinopathy and neuropathy . CONCLUSIONS Blood pressure control of 138/86 or 132/78 mmHg with either nisoldipine or enalapril as the initial antihypertensive medication appeared to stabilize renal function in hypertensive type 2 diabetic patients without overt albuminuria over a 5-year period . The more intensive blood pressure control decreased all-cause mortality", "OBJECTIVE Hypertension ( HTN ) is a major risk factor for cardiovascular disease ( CVD ) in the setting of diabetes . There is no consensus on how best to treat hypertension among those with diabetes . Here we describe the characteristics of a cohort of hypertensive adults with diabetes who are part of a large prospect i ve blood pressure study . This study will help clarify the treatment of HTN in the setting of diabetes . RESEARCH DESIGN AND METHODS The Antihypertensive and Lipid-Lowering high-risk hypertensive participants , ages > or = 55 years , design ed to determine whether the incidence of fatal and nonfatal coronary heart disease ( CHD ) and combined cardiovascular events ( fatal and nonfatal CHD , revascularization surgery , angina pectoris , congestive heart failure , and stroke ) differs between diuretic ( chlorthalidone ) treatment and three alternative antihypertensive therapies : a calcium channel blocker ( amlodipine ) , an ACE inhibitor ( lisinopril ) , and an alpha-adrenergic blocker ( doxazosin ) . The planned follow-up is an average of 6 years , to be completed March 2002 . RESULTS There are 15,297 diabetic individuals in the ALLHAT study ( 36.0 % of the entire cohort ) . Of these individuals , 50.2 % are male , 39.4 % are African-American , and 17.7 % are Hispanic . Demographic and laboratory characteristics of the cohort are similar to those of other studies of the U.S. elderly population with HTN . The sample size has 42 and 93 % confidence , treatments for the two study outcomes . CONCLUSIONS The diabetic cohort in ALLHAT wil be able to provide valuable information about the treatment of hypertension in older diabetic patients at risk for incident CVD", "BACKGROUND Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension . Left ventricular hypertrophy ( LVH ) is a strong independent indicator of risk of cardiovascular morbidity and death . We aim ed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and , consequently , reduces cardiovascular morbidity and death . METHODS We did a double-masked , r and omised , parallel-group trial in 9193 participants aged 55 - 80 years with essential hypertension ( sitting blood pressure 160 - 200/95 - 115 mm Hg ) and LVH ascertained by electrocardiography ( ECG ) . We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event ( death , myocardial infa rct ion , or stroke ) . We used Cox regression analysis to compare regimens . FINDINGS Blood pressure fell by 30.2/16.6 ( SD 18.5/10.1 ) and 29.1/16.8 mm Hg ( 19.2/10.1 ) in the losartan and atenolol groups , respectively . The primary composite endpoint occurred in 508 losartan ( 23.8 per 1000 patient-years ) and 588 atenolol patients ( 27.9 per 1000 patient-years ; relative risk 0.87 , 95 % CI 0.77 - 0.98 , p=0.021 ) . 204 losartan and 234 atenolol patients died from cardiovascular disease ( 0.89 , 0.73 - 1.07 , p=0.206 ) ; 232 and 309 , respectively , had fatal or non-fatal stroke ( 0.75 , 0.63 - 0.89 , p=0.001 ) ; and myocardial infa rct ion ( non-fatal and fatal ) occurred in 198 and 188 , respectively ( 1.07 , 0.88 - 1.31 , p=0.491 ) . New-onset diabetes was less frequent with losartan . Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated . Losartan seems to confer benefits beyond reduction in blood pressure", "Objective To compare the effects of the angiotensin II antagonist , losartan , with those of atenolol on left ventricular hypertrophy ( LVH ) , blood pressure and neurohormone concentrations in hypertensive patients with LVH . Design A multinational , r and omized , double-blind trial . Setting Hospital . Patients Hypertensive patients with an echocardiographically documented left ventricular mass index ( LVMI ) > 120 g/m2 ( men ) or > 105 g/m2 ( women ) . Interventions Patients allocated r and omly to groups received either losartan or atenolol 50 mg/day for 36 weeks , with possible titration to 100 mg/day , and addition of hydrochlorothiazide 12.5 or 25 mg/day . Main outcome measures Changes in LVMI and sitting systolic ( SBP ) and diastolic ( DBP ) blood pressures after 36 weeks of treatment ( study powered for non-inferiority hypothesis ) . All echocardiographic data were read in a central laboratory by staff blinded to the treatments and sequence of echocardiographic tapes . Results The estimated treatment difference between the losartan and atenolol regimens ( mean change from baseline at week 36 ) in LVMI was −2.5 g/m2 [ 95 % confidence interval ( CI ) −7.36 to 2.37 g/m2 ] in favor of losartan , indicating that losartan was significantly non-inferior ( P atenolol in reducing LVMI . The losartan-based regimen significantly reduced LVMI after 36 weeks compared with baseline ( −6.56 g/m2 , 95 % CI −10.24 to −2.88 g/m2 , P atenolol-based regimen had no significant effect ( −3.71 g/m2 , 95 % CI −7.75 to 0.32 g/m2 , P = NS ) . In a subset of 82 patients , significant changes in serum concentrations of atrial natriuretic peptide , brain natriuretic peptide and immunoreactive amino-terminal pro-brain natriuretic peptide were recorded in losartan-treated ( P atenolol-treated patients . Losartan and atenolol significantly decreased SBP and DBP from baseline after 6 , 12 , 24 and 36 weeks . The changes from baseline in DBP were greater in the atenolol group at weeks 6 and 36 [ difference −2.6 mmHg ( P = 0.016 ) at week 36 ] . However , both treatment regimens achieved similar SBP/DBP values at week 36 ( 141.1 ± 12.8/86.8 ± 8.2 mmHg for losartan and 141.4 ± 17.2/85.0 ± 10.1 mmHg for atenolol , respectively ) . Overall , losartan treatment was associated with significantly fewer drug-related clinical adverse events , compared with atenolol ( 10 and 22 % , respectively , P = 0.028 ) . Conclusions Both losartan- and atenolol-based regimens effectively decreased blood pressure . Losartan was non-inferior and numerically superior to atenolol in regression of LVH . The reduction in hypertrophy with losartan treatment was accompanied by reductions in circulating concentrations of cardiac natriuretic peptides . Losartan , by specifically blocking angiotensin II , may therefore have effects on the heart beyond those expected from the decrease in blood pressure alone . Losartan was better tolerated than atenolol ", "Nitric oxide synthase 3 ( NOS3 ) catalyzes production of NO in the endothelium and may play a role in cardiovascular disease ( CVD ) . We assessed the pharmacogenetic associations of three NOS3 polymorphisms and three antihypertensive drugs with CVD outcomes . Hypertensive subjects ( n = 30,280 ) from a multi-center , double-blind clinical trial were r and omized to chlorthalidone , amlodipine , or lisinopril treatment ( mean follow up , 4.9 years ) . Outcomes included coronary heart disease ( CHD : fatal CHD and nonfatal myocardial infa rct ion ) ; stroke ; heart failure ( fatal , requiring hospitalization , or outpatient treatment ) ; all-cause mortality ; and end-stage renal disease ( ESRD ) . Main effects of NOS3 variants on outcome and genotype-treatment interactions were tested . For NOS3 −690 C > T ( rs3918226 ) , a higher hazard ratio ( HR ) was found in minor allele carriers for CHD ( CC = 1.00 , CT+TT = 1.12 ( 95 % confidence interval ( CI ) = 1.00–1.26 ) , P = 0.048 ) . For NOS3 −922 A > G ( rs1800779 ) , a higher HR was found in minor allele carriers for heart failure ( AA = 1.00 , AG+GG = 1.10 ( CI = 1.00–1.21 ) , P = 0.046 ) . Significant pharmacogenetic findings were observed for stroke and all-cause mortality . For −690 C > T , a lower HR was observed for stroke in minor allele carriers when treated with amlodipine versus lisinopril ( CC = 0.85 ( CI = 0.73–0.99 ) , CT+TT = 0.49 ( CI = 0.31–0.80 ) , P = 0.04 ) . For glu298asp G > T ( rs1799983 ) , a lower HR was observed for all-cause mortality in minor allele carriers when treated with amlodipine versus lisinopril ( GG = 1.01 ( CI = 0.91–1.13 ) , GT+TT = 0.85 ( CI = 0.75–0.97 ) , P = 0.04 ) . We observed significant associations with NOS3 variants and CHD and heart failure and significant pharmacogenetic effects for stroke and all cause mortality . This suggests that NOS3 variants may potentially provide useful clinical information with respect to treatment decisions in the future", "CONTEXT Hypertension is a leading cause of end-stage renal disease ( ESRD ) in the United States , with no known treatment to prevent progressive declines leading to ESRD . OBJECTIVE To compare the effects of 2 levels of blood pressure ( BP ) control and 3 antihypertensive drug classes on glomerular filtration rate ( GFR ) decline in hypertension . DESIGN R and omized 3 x 2 factorial trial with enrollment from February 1995 to September 1998 . SETTING AND PARTICIPANTS A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease ( GFR , 20 - 65 mL/min per 1.73 m(2 ) ) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years . INTERVENTIONS Participants were r and omly assigned to 1 of 2 mean arterial pressure goals , 102 to 107 mm Hg ( usual ; n = 554 ) or 92 mm Hg or less ( lower ; n = 540 ) , and to initial treatment with either a beta-blocker ( metoprolol 50 - 200 mg/d ; n = 441 ) , an angiotensin-converting enzyme inhibitor ( ramipril 2.5 - 10 mg/d ; n = 436 ) or a dihydropyridine calcium channel blocker , ( amlodipine 5 - 10 mg/d ; n = 217 ) . Open-label agents were added to achieve the assigned BP goals . MAIN OUTCOME MEASURES Rate of change in GFR ( GFR slope ) ; clinical composite outcome of reduction in GFR by 50 % or more ( or > or = 25 mL/min per 1.73 m2 ) from baseline , ESRD , or death . Three primary treatment comparisons were specified : lower vs usual BP goal ; ramipril vs metoprolol ; and amlodipine vs metoprolol . RESULTS Achieved BP averaged ( SD ) 128/78 ( 12/8 ) mm Hg in the lower BP group and 141/85 ( 12/7 ) mm Hg in the usual BP group . The mean ( SE ) GFR slope from baseline through 4 years did not differ significantly between the lower BP group ( -2.21 [ 0.17 ] mL/min per 1.73 m2 per year ) and the usual BP group ( -1.95 [ 0.17 ] mL/min per 1.73 m2 per year ; P = .24 ) , and the lower BP goal did not significantly reduce the rate of the clinical composite outcome ( risk reduction for lower BP group = 2 % ; 95 % confidence interval [ CI ] , -22 % to 21 % ; P = .85 ) . None of the drug group comparisons showed consistent significant differences in the GFR slope . However , compared with the metoprolol and amlodipine groups , the ramipril group manifested risk reductions in the clinical composite outcome of 22 % ( 95 % CI , 1%-38 % ; P = .04 ) and 38 % ( 95 % CI , 14%-56 % ; P = .004 ) , respectively . There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups . CONCLUSIONS No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal . Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline", "Background In the Valsartan Antihypertensive Long-term Use Evaluation ( VALUE ) trial the primary outcome ( cardiac morbidity and mortality ) did not differ between valsartan and amlodipine-based treatment groups , although systolic blood pressure ( SBP ) and diastolic blood pressure reductions were significantly more pronounced with amlodipine . Stroke incidence was non-significantly , and myocardial infa rct ion was significantly lower in the amlodipine-based regimen , whereas cardiac failure was non-significantly lower on valsartan . Objectives The study protocol specified additional analyses of the primary endpoint according to : sex ; age ; race ; geographical region ; smoking status ; type 2 diabetes ; total cholesterol ; left ventricular hypertrophy ; proteinuria ; serum creatinine ; a history of coronary heart disease ; a history of stroke or transient ischemic attack ; and a history of peripheral artery disease . Additional subgroups were isolated systolic hypertension and classes of antihypertensive agents used immediately before r and omization . Methods The 15 245 hypertensive patients participating in VALUE were divided into subgroups according to baseline characteristics . Treatment by subgroup interaction analyses were carried out by a Cox proportional hazard model . Within each subgroup , treatment effects were assessed by hazard ratios and 95 % confidence intervals . Results For cardiac mortality and morbidity , the only significant subgroup by treatment interaction was of sex ( P = 0.016 ) , with the hazard ratio indicating a relative excess of cardiac events with valsartan treatment in women but not in men , but SBP differences in favour of amlodipine were distinctly greater in women . No other subgroup showed a significant difference in the composite cardiac outcome between valsartan and amlodipine-based treatments . For secondary endpoints , a sex-related significant interaction was found for heart failure ( P heart failure with valsartan . Conclusion As in the whole VALUE cohort , in no subgroup of patients were there differences in the incidence of the composite cardiac endpoint with valsartan and amlodipine-based treatments , despite a greater blood pressure decrease in the amlodipine group . The only exception was sex , in which the amlodipine-based regimen was more effective than valsartan in women , but not in men , whereas the valsartan regimen was more effective in preventing cardiac failure in men than in women", "BACKGROUND The Valsartan Antihypertensive Long-term Use Evaluation ( VALUE ) trial was design ed to test the hypothesis that for the same blood-pressure control , valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk . METHODS 15?245 patients , aged 50 years or older with treated or untreated hypertension and high risk of cardiac events participated in a r and omised , double-blind , parallel-group comparison of therapy based on valsartan or amlodipine . Duration of treatment was event-driven and the trial lasted until at least 1450 patients had reached a primary endpoint , defined as a composite of cardiac mortality and morbidity . Patients from 31 countries were followed up for a mean of 4.2 years . FINDINGS Blood pressure was reduced by both treatments , but the effects of the amlodipine-based regimen were more pronounced , especially in the early period ( blood pressure 4.0/2.1 mm Hg lower in amlodipine than valsartan group after 1 month ; 1.5/1.3 mm Hg after 1 year ; p valsartan group ( 10.6 % , 25.5 per 1000 patient-years ) and 789 in the amlodipine group ( 10.4 % , 24.7 per 1000 patient-years ; hazard ratio 1.04 , 95 % CI 0.94 - 1.15 , p=0.49 ) . INTERPRETATION The main outcome of cardiac disease did not differ between the treatment groups . Unequal reductions in blood pressure might account for differences between the groups in cause-specific outcomes . The findings emphasise the importance of prompt blood-pressure control in hypertensive patients at high cardiovascular risk", "We investigated the effects of aggressive antihypertensive therapy based on hydrochlorothiazide , c and esartan or lisinopril on urinary albumin excretion , endothelial function and inflammatory activity in hypertensive type II diabetic individuals . A total of 70 hypertensive type II diabetic individuals were treated with three antihypertensive strategies in a r and omized , double-blind , double-dummy design . Blood pressure was titrated to levels below 130/85 mmHg or a decrease in systolic pressure of 10 % with a diastolic pressure below 85 mmHg . After titration , patients were treated for 12 months . Mean blood pressures changed from 157/93 , 151/94 and 149/93 at baseline to 135/80 , 135/82 and 131/80 mmHg after titration in the hydrochlorothiazide ( n=24 ) , c and esartan ( n=24 ) and lisinopril ( n=22 ) groups . About 70 % reached target blood pressures . However , only 45 % had blood pressures 130/85 mmHg . Urinary albumin excretion and levels of soluble vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 decreased ( GEE regression coefficients , −2.40 mg/24 h ( P but brachial artery endothelium-dependent and -independent vasodilation and levels of von Willebr and factor and C-reactive protein did not change ( GEE regression coefficients , 0.21 mm ( P=0.07 ) , 0.04 mm ( P=0.43 ) , 0.04 IU/ml ( P=0.33 ) and −1.15 mg/l ( P=0.64 ) ) . No differences in outcome variables between treatment groups were observed . These data show that achievement of target blood pressures below 130/85 mmHg in hypertensive type II diabetes is difficult . Aggressive antihypertensive therapy can improve urinary albumin excretion , endothelial function and inflammatory activity in hypertensive type II diabetic individuals , regardless of the type of antihypertensive therapy used", "BACKGROUND Treatment of hypertensive patients with a losartan-based regimen was associated with greater regression of electrocardiographic ( ECG ) left ventricular hypertrophy ( LVH ) than atenolol-based therapy in the Losartan Intervention for Endpoint Reduction in Hypertension ( LIFE ) study , independent of blood pressure ( BP ) changes . However , whether concomitant hydrochlorothiazide ( HCTZ ) therapy in > 70 % of LIFE patients was associated with greater regression of LVH independent of BP changes and whether this effect differed between treatment arms has not been examined . METHODS Changes in Cornell product and Sokolow-Lyon voltage LVH were assessed in 9,193 hypertensive patients r and omly assigned to treatment with losartan or atenolol , with additional HCTZ therapy added as necessary to achieve target BP goal per study protocol . RESULTS After controlling for baseline and change in systolic and diastolic pressure , age , sex , race , prior antihypertensive treatment , baseline and year-4 body mass index and baseline LVH by either Cornell product or Sokolow-Lyon voltage , at year-4 follow-up HCTZ therapy was associated with greater regression of Cornell product LVH ( -244 + /- 788 vs. -172 + /- 771 mm.msec , P Sokolow-Lyon voltage ( -4.2 + /- 6.7 vs. -3.0 + /- 7.0 mm , P patients on losartan ( -341 + /- 743 vs. -189 + /- 775 mm.msec and -5.2 + /- 6.6 vs. -3.3 + /- 6.6 mm ) than in patients on atenolol ( -142 + /- 822 vs. -158 + /- 765 mm.msec and -3.1 + /- 6.6 vs. -2.7 + /- 7.4 mm ; both P HCTZ with losartan vs. atenolol therapy ) . CONCLUSIONS HCTZ use was associated with greater regression of ECG LVH and this effect was greater in patients on losartan- than atenolol-based therapy , independent of baseline severity of ECG LVH and hypertension and changes in BP", "BACKGROUND AND PURPOSE Angiotensin II promotes cell growth and has been implicated in the development and maintenance of left ventricular ( LV ) hypertrophy and of structural vascular changes . We wished to examine whether an angiotensin receptor blocker ( ARB ) would influence structural vascular changes beyond the effects of blood pressure reduction . METHODS Hypertensive patients with LV hypertrophy ( age 55 + /- 9 years , blood pressure 162 + /- 19/104 + /- 8 mmHg , LV mass index 148 + /- 31 g m(-2 ) ; mean + /- SD ) were r and omized double-blind to the ARB irbesartan ( n=52 ) or the beta(1 ) receptor blocker atenolol ( n=56 ) for 48 weeks . Ultrasonography of the left and right common carotid artery ( CCA ) and echocardiography were performed at week 0 and 48 . RESULTS With similar reductions in blood pressure , CCA intima-media thickness ( IMT ) was reduced by irbesartan ( from 0.92 + /- 0.14 by 0.01 + /- 0.10 mm , NS ) , whereas it was increased by atenolol ( from 0.94 + /- 0.21 by 0.03 + /- 0.12 mm , P=0.018 ; P=0.002 between groups ) . CCA lumen diameter was less reduced by irbesartan than by atenolol . Thus , CCA intima-media area was reduced by irbesartan ( from 21.3 + /- 5.0 by 0.90 + /- 2.45 mm(2 ) , P=0.034 ) but not by atenolol ( from 21.3 + /- 6.1 by 0.18 + /- 2.71 mm(2 ) , NS ; P=0.037 between groups ) . Changes in CCA IMT or area did not relate to changes in LV mass . CONCLUSIONS The favourable effects by irbesartan on CCA IMT with an outward vascular remodelling suggest that angiotensin II mediates structural vascular changes , beyond the effects of blood pressure . This may be important in the prevention of cerebrovascular events", "Objectives To test whether microalbuminuria in patients with type 2 diabetes and hypertension is primarily dependent on the severity of hypertension , and to compare the effectiveness of two antihypertensive drugs with opposite effects on the renin – angiotensin system [ the diuretic , indapamide sustained release ( SR ) , and an angiotensin-converting enzyme inhibitor , enalapril ] in reducing microalbuminuria . Design A multinational , multicentre , controlled , double-blind , double-dummy , r and omized , two-parallel-groups study over 1 year . Methods After a 4-week placebo run-in period , 570 patients ( ages 60.0 ± 9.9 years , 64 % men ) with type 2 diabetes , essential hypertension [ systolic blood pressure ( SBP ) 140–180 mmHg , and diastolic blood pressure ( DBP ) were allocated r and omly to groups to receive indapamide SR 1.5 mg ( n = 284 ) or enalapril 10 mg ( n = 286 ) once a day . Amlodipine , atenolol , or both were added , if necessary , to achieve the target blood pressure of 140/85 mmHg . Results There was a significant reduction in the urinary albumin : creatinine ratio . Mean reductions were 35 % [ 95 % confidence interval ( CI ) 24 to 43 ] and 39 % ( 95 % CI 30 to 47 % ) in the indapamide SR and enalapril groups , respectively . Equivalence was demonstrated between the two groups [ 1.08 ( 95 % CI 0.89 to 1.31 % ) ; P = 0.01 ] . The reductions in mean arterial pressure ( MAP ) were 16.6 ± 9.0 mmHg for the indapamide SR group and 15.0 ± 9.1 mmHg for the enalapril group ( NS ) ; the reduction in SBP was significantly greater ( P = 0.0245 ) with indapamide SR . More than 50 % of patients in each group required additional antihypertensive therapy , with no differences between groups . Both treatments were well tolerated . Conclusions Indapamide-SR-based therapy is equivalent to enalapril-based therapy in reducing microalbuminuria with effective blood pressure reduction in patients with hypertension and type 2 diabetes", "We examined long-term influence of the angiotensin II type 1-receptor blocker irbesartan and the beta1-adrenergic receptor blocker atenolol on some neurohormonal systems implicated in the pathophysiology of cardiac hypertrophy . Thus , 115 hypertensive patients with left ventricular hypertrophy were r and omized to receive double-blind irbesartan or atenolol , with additional therapy if needed . Neurohormone measurements and echocardiography were performed at weeks 0 , 12 , 24 , and 48 . Left ventricular mass was reduced more by irbesartan than by atenolol ( −26 g/m2 versus −14 g/m2 , P = 0.024 ) , despite similar reductions in blood pressure . Plasma renin activity and angiotensin II increased ( P irbesartan ( 0.9 ± 0.7 to 3.4 ± 4.2 ng/mL × h , and 3.0 ± 1.6 to 13.0 ± 17.7 pmol/L ) , but decreased ( P atenolol ( 1.0 ± 0.6 to 0.7 ± 0.6 ng/mL × h , and 3.4 ± 1.6 to 3.2 ± 2.2 pmol/L ) . Serum aldosterone decreased ( P atenolol ( 315 ± 115 to 283 ± 77 pmol/L ) . Changes in left ventricular mass by irbesartan related inversely to changes in plasma renin activity , angiotensin II , and aldosterone ( all P remained largely unchanged in both groups . Thus , the renin-angiotensin aldosterone system appears to be an important non-hemodynamic factor in the regulation of left ventricular mass", "The objective of this study was to observe the antihypertensive effect of losartan and levamlodipine besylate on insulin resistance in patients with essential hypertension ( EH ) combined with isolated impaired fasting glucose ( i-IFG ) . Patients ( n=244 ) were r and omly assigned to losartan potassium tablets ( 50–100 mg per day ) or levamlodipine besylate tablets ( 2.5–5.0 mg per day ) for intensive antihypertensive treatment with no lifestyle interventions for 3 years . The changes in fasting plasma glucose , fasting insulin ( FINS ) and insulin sensitivity index ( ISI ) from before to after treatment were observed . Blood pressure ( BP ) in each group was significantly reduced by treatment ( P the FINS level in the losartan potassium group was significantly decreased and ISI was significantly increased compared with before treatment ( P levamlodipine besylate group ( P , FINS was significantly decreased and ISI was significantly improved in both groups compared with baseline ( P0.05 ) . The incidence of new-onset diabetes mellitus was not significantly different between two groups . The antihypertensive effect of losartan and levamlodipine besylate could amoliorate insulin resistance in patients with EH combined with i-IFG . The improvement of insulin resistance by losartan potassium at 12 months might be better than that by levamlodipine besylate ; however , after 24 and 36 months of follow-up , both agents significantly alleviated insulin resistance . These results suggest that the effects of these two drugs on insulin resistance are not significantly different", "The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity , largely due to a decreased incidence of stroke , whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies . Furthermore , treated hypertensive patients still have a higher cardiovascular complication rate , compared with matched normotensives . This is particularly evident in patients with left ventricular hypertrophy ( LVH ) , a major independent risk indicator for cardiovascular disease . In addition to elevating blood pressure , angiotensin II ( A-II ) exerts an important influence on cardiac structure and function , stimulating cell proliferation and growth . Thus , to further reduce morbidity and mortality when treating hypertensive patients , it may be important to effectively block the effects of A-II . This can be achieved directly at the A-II receptor level by losartan , the first of a new class of antihypertensive agents . It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy , and thus improves prognosis . The Losartan Intervention For Endpoint reduction ( LIFE ) in Hypertension study is a double-blind , prospect i ve , parallel group study design ed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients ( initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg ) with electrocardiographically documented LVH . The study , which will continue for at least 4 years and until 1,040 patients experience one primary endpoint , has been design ed with a statistical power that will detect a difference of at least 15 % between groups in the incidence of combined cardiovascular morbidity and mortality . It is also the first prospect i ve study with adequate power to link reversal of LVH to reduction in major cardiovascular events . The rationale of the study , which will involve more than 800 clinical centers in Sc and inavia , the United Kingdom , and the United States , is discussed , and the major features of its design and general organization are described . On April 30 , 1997 , when inclusion was stopped , 9,218 patients had been r and omized", "Essential hypertension is a major Public Health issue . Although the number of treated hypertensive patients has increased , only 25 % of treated patients have their blood pressure levels under control . The benefit of treating hypertension has been proven , but cardiovascular morbidity and mortality rates remain high . The ideal antihypertensive drug should not only normalize blood pressure levels , but also reduce the associated cardiovascular morbidity and mortality rates . The role of angiotensin II in systemic hypertension and its complications has been recently redefined . The potent trophic effects of angiotensin II on blood vessels and on cardiac cells have been well demonstrated , especially the role of angiotensin II in left ventricular hypertrophy , vascular hypertrophy , endothelial dysfunction , and congestive heart failure . Of all ongoing mortality and morbidity trials in systemic hypertension , VALUE ( Valsartan Antihypertensive Long-term Use Evaluation ) is the only one comparing an angiotensin II antagonist ( valsartan ) with a third-generation calcium channel blocker ( amlodipine ) . The main hypothesis of the VALUE trial is that , for an equivalent decrease in blood pressure , valsartan will be more effective than amlodipine in decreasing cardiac mortality and morbidity . VALUE is a prospect i ve , multinational , multicentre , double-blind , r and omized , active-controlled , 2-arm parallel group comparison with a response-dependent dose titration scheme . VALUE involves 14,400 patients in over 30 countries , who will be followed for 4 years or until 1450 patients experience a primary endpoint . The population to be included in VALUE consists of hypertensive men and women , aged 50 years or older , and at a relatively high risk of sustaining a cardiovascular event . The high risk profile is defined taking into account age , gender , and a list of cardiovascular risk factors and disease factors . Risk factors are cigarette smoking , hypercholesterolaemia , diabetes mellitus , uncomplicated left ventricular hypertrophy , proteinuria , and high serum creatinine . Disease factors include documented history of myocardial infa rct ion , peripheral vascular disease , stroke or transient ischaemic attack , or the presence of left ventricular hypertrophy with strain on the ECG . A unique feature of VALUE is the assessment of the predictive power of this cardiovascular risk factor scale in a large population of treated hypertensive patients . The trial started on 10 September 1997", "OBJECTIVE To compare the long-term effects of the angiotensin-converting enzyme (ACE)-inhibitor quinapril and the cardioselective beta-adrenergic blocking agent metoprolol on glycaemic control , with glycosylated haemoglobin ( HbA1c ) as the principal variable , in non-insulin-dependent diabetes mellitus ( NIDDM ) patients with hypertension . DESIGN A r and omized , double-blind , double-dummy , multicentre study during 6 months preceded by a 4 week wash-out and a 3 week run-in placebo period . Quinapril ( 20 mg ) and metoprolol ( 100 mg , conventional tablets ) were given once daily . No change was made in the treatment of diabetes ( diet and hypoglycaemic agents ) . SUBJECTS Seventy-two patients fulfilling the criteria were r and omized and entered the double-blind period . Twelve patients did not complete the study . Sixty patients , 26 on quinapril and 34 on metoprolol , were available for the final analysis . MAIN OUTCOME MEASURES The effect was assessed by changes in HbA1c , the fasting serum glucose and the post-load serum glucose , C-peptide and insulin levels during the oral glucose tolerance test . RESULTS In the quinapril group , the fasting serum glucose , oral glucose tolerance and the C-peptide and insulin responses , determined as the incremental area under the curves ( AUC ) , showed no change , but the mean HbA1c level increased from 6.2 + /- 1.1 % to 6.5 + /- 1.3 % ( P mean level of HbA1c , from 6.3 + /- 1.0 % to 6.8 + /- 1.3 % ( P quinapril , although there was no significant difference between the increments . The mean fasting serum glucose showed an increase from 9.1 + /- 1.9 mM to 10.1 + /- 2.8 mM ( P duration of diabetes ( P fasting serum triglycerides ( P oral glucose tolerance as well as C-peptide and insulin responses to the glucose load . CONCLUSIONS Treatment with quinapril for 6 months appears to have advantages over metoprolol in NIDDM patients with hypertension . Although treatment with quinapril or metoprolol over 6 months was concomitant with a rise in the HbA1c , increased fasting blood glucose , decreased oral glucose tolerance and decreased C-peptide and insulin responses to a glucose challenge were observed only in patients treated with metoprolol ", "As the population ages , the incidence of type 2 diabetes will increase as will the incidence of concomitant vascular complications . Hypertension substantially increases the risk of cardiovascular disease in patients with diabetes . Results from the recent Appropriate Blood Pressure Control in Diabetes ( ABCD ) trial demonstrated an advantage of an angiotensin-converting enzyme ( ACE ) inhibitor ( enalapril ) over a long-acting calcium antagonist ( nisoldipine ) with regard to the incidence of cardiovascular events over a 5-year follow-up period in hypertensive persons with type 2 diabetes . This trial was a prospect i ve , r and omized , blinded study comparing the effects of moderate blood pressure control ( target diastolic pressure 80 - 89 mm Hg ) with those of intensive control ( target diastolic pressure 75 mm Hg ) on the incidence and progression of diabetic vascular complications . The study also compared nisoldipine with enalapril as first-line antihypertensive therapy in terms of prevention and progression of complications of diabetes . In 470 hypertensive patients , the incidence of fatal and nonfatal myocardial infa rct ions was significantly ( p = 0.001 ) higher among those receiving nisoldipine ( n = 25 ) compared with those receiving enalapril ( n = 5 ) . Comparison with previous studies suggests that the difference observed between nisoldipine and enalapril result ed from a beneficial effect of enalapril rather than a deleterious effect from nisoldipine . Since these findings in the ABCD trial are based on a secondary endpoint , they require confirmation . Nevertheless , they suggest that ACE inhibitors should be the initial antihypertensive medication used in patients with type 2 diabetes and hypertension", "Objective Beta-blockers and angiotensin II receptor blockers have different effects on lipids . Methods We examined lipid levels in the Losartan Intervention For Endpoint reduction in hypertension study and their impact on the primary composite endpoint of cardiovascular death , myocardial infa rct ion , or stroke . We measured total and high-density lipoprotein cholesterol at baseline and annually during 4.8 years of losartan-based compared with atenolol-based treatment in 8611 patients with hypertension and left ventricular hypertrophy . Results Patients r and omized to losartan-based or atenolol-based treatment had similar baseline total ( 6.04 ± 1.12 vs. 6.05 ± 1.13 mmol/l , NS ) and high-density lipoprotein ( HDL ) cholesterol ( 1.50 ± 0.44 vs. 1.49 ± 0.44 mmol/l , NS ) . Total cholesterol decreased significantly but equally ( −0.37 ± 1.05 vs. −0.34 ± 1.09 mmol/l , NS ) , whereas HDL cholesterol decreased less during the first 2 years in patients r and omized to losartan compared with atenolol ( −0.13 ± 0.24 vs. −0.19 ± 0.25 mmol/l ) and remained higher each year ( 1.38 , 1.37 , 1.42 , 1.47 , and 1.48 mmol/l vs. 1.32 , 1.30 , 1.36 , 1.40 , and 1.42 mmol/l , all P , baseline total cholesterol [ hazard ratio ( HR ) = 1.08 ( 1.02–1.14 ) per mmol/l , P HDL cholesterol [ HR = 0.56 ( 0.48–0.66 ) per mmol/l , P the predictive strength of HDL cholesterol was increased [ HR = 0.36 ( 0.30–0.44 ) per mmol/l , P that of total cholesterol [ HR = 1.03 ( 0.97–1.09 ) per mmol/l , NS ] and treatment allocation [ HR = 0.91 ( 0.80–1.03 ) , NS ] were reduced . Conclusion Losartan blunted the decrease in HDL cholesterol during antihypertensive treatment in the LIFE study . Higher intreatment HDL cholesterol was associated with fewer composite endpoints and may partly explain the better outcome of losartan-based treatment", "BACKGROUND It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications . Because this issue remains controversial , we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were r and omly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study . METHODS The Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial is a prospect i ve , r and omized , blinded trial comparing the effects of moderate control of blood pressure ( target diastolic pressure , 80 to 89 mm Hg ) with those of intensive control of blood pressure ( diastolic pressure , 75 mm Hg ) on the incidence and progression of complications of diabetes . The study also compared nisoldipine with enalapril as a first-line antihypertensive agent in terms of the prevention and progression of complications of diabetes . In the current study , we analyzed data on a secondary end point ( the incidence of myocardial infa rct ion ) in the subgroup of patients in the ABCD Trial who had hypertension . RESULTS Analysis of the 470 patients in the trial who had hypertension ( base-line diastolic blood pressure , > or = 90 mm Hg ) showed similar control of blood pressure , blood glucose and lipid concentrations , and smoking behavior in the nisoldipine group ( 237 patients ) and the enalapril group ( 233 patients ) throughout five years of follow-up . Using a multiple logistic-regression model with adjustment for cardiac risk factors , we found that nisoldipine was associated with a higher incidence of fatal and nonfatal myocardial infa rct ions ( a total of 24 ) than enalapril ( total , 4 ) ( risk ratio , 9.5 ; 95 percent confidence interval , 2.7 to 33.8 ) . CONCLUSIONS In this population of patients with diabetes and hypertension , we found a significantly higher incidence of fatal and nonfatal myocardial infa rct ion among those assigned to therapy with the calcium-channel blocker nisoldipine than among those assigned to receive enalapril . Since our findings are based on a secondary end point , they will require confirmation", "Context Previously published results of this r and omized , double-blind trial showed that high-risk patients with type 2 diabetic nephropathy had better renal protection if they were treated with irbesartan rather than amlodipine in addition to conventional antihypertensive therapy . Contribution These detailed analyses showed no differences in overall cardiovascular outcomes between patients given irbesartan or amlodipine . Fewer patients given irbesartan had heart failure and fewer patients given amlodipine had heart attacks . Caution s The trial had limited power to detect important differences between groups in mortality or strokes , and most patients received several antihypertensive agents . The Editors Patients with diabetes have an increased risk for cardiovascular complications and death ( 1 ) . Studies that analyzed the effects of inhibition of the reninangiotensin system on the risk for cardiovascular complications included a substantial number of patients with diabetes ( 2 - 5 ) or were done exclusively in patients with diabetes ( 6 - 8 ) . The meta- analysis of these studies ( 9 ) , the analysis of the diabetic cohorts in the Heart Outcomes Prevention Evaluation ( HOPE ) study ( 2 ) , and the Losartan Intervention for Endpoint Reduction in Hypertension ( LIFE ) trial ( 5 ) demonstrated that angiotensin-converting enzyme ( ACE ) inhibitors ( 2 , 9 ) and angiotensin-receptor blockers ( 5 ) had a statistically significant advantage over placebo or alternative agents in decreasing the risk for several cardiovascular events . These studies r and omly assigned few patients with renal involvement and overt proteinuria . Overt proteinuria occurred in fewer than 20 % of the 470 patients in the Appropriate Blood Pressure Control in Diabetes ( ABCD ) trial ( 6 ) , and only 11 % of the 1195 patients in the LIFE trial ( 5 ) . The Captopril Prevention Project ( CAPP ) ( 3 ) and the Swedish Trial in Old Patients with Hypertension-2 ( STOP Hypertension-2 ) ( 4 ) did not state the number of patients with diabetes and overt proteinuria . There were no such patients in the Fosinopril versus Amlodipine Cardiovascular Events Trial ( FACET ) ( 7 ) , and patients with dipstick-positive albuminuria were excluded from the HOPE trial ( 2 ) . Since proteinuria is an independent risk factor for cardiovascular disease ( 10 , 11 ) , the data obtained in the aforementioned trials can not be extrapolated to patients with type 2 diabetes and overt nephropathy . Trials performed in such patients have reported a blood pressureindependent effect of two different angiotensin-receptor blocker agents to protect against nephropathy ( 12 , 13 ) without a change in all-cause mortality . Apart from studies in heart failure , few cardiovascular data exist for receptor blockers compared with either placebo or calcium-channel blockers . We report on the analysis of the cardiovascular end points that were monitored as secondary end points in the Irbesartan Diabetic Nephropathy Trial ( IDNT ) ( 12 ) and assess whether an angiotensin II receptor blocker or a calcium-channel blocker alters the risk for cardiovascular events beyond those observed by blood pressure reduction alone without such agents . Methods Patients The IDNT was a r and omized , double-blind study on the effect of treatment with irbesartan or amlodipine compared with placebo in patients with type 2 diabetic nephropathy . The protocol of this study has been published ( 12 , 14 ) . Entry criteria required that patients be between 30 and 70 years of age and have type 2 diabetes mellitus and overt nephropathy , as evidence d by current treatment for hypertension or by a protein excretion rate of 900 mg/d or greater , serum creatinine level of 89 mol/L ( 1.0 mg/dL ) to 266 mol/L ( 3.0 mg/dL ) in women or of 106 mol/L ( 1.2 mg/dL ) to 266 mol/L ( 3.0 mg/dL ) in men , and baseline seated blood pressure greater than 135/85 mm Hg . The institutional review boards of each center approved the protocol . All patients gave written informed consent . Treatment and R and omization Patients were r and omly assigned central ly by computer to receive treatment with irbesartan , 300 mg/d ( Avapro , Bristol-Myers Squibb , Princeton , New Jersey ) ; amlodipine , 10 mg/d ( Norvasc , Pfizer , New York ) ; or matched placebo . To minimize any center effect , r and omization was blocked by center . All patients had blood pressure controlled to the same blood pressure goal of less than 135/85 mm Hg by using antihypertensive agents other than ACE inhibitors , angiotensin II receptor blocking agents , or calcium-channel blockers . For the analysis of cardiovascular end points , patients were followed to initiation of treatment for end-stage renal failure ( dialysis or renal transplantation ) , reaching a serum creatinine level of 530.4 mol/L ( 6.0 mg/dL ) or higher , death , or administrative censoring in December 2000 . Outcomes We prospect ively established cardiovascular outcomes , defined in the Appendix Table . Appendix Table . Classification for Fatal and Nonfatal Cardiovascular Events Ascertainment of Cardiovascular Events Information about hospitalizations and adverse events were screened at Bristol-Myers Squibb , Princeton , New Jersey , by trained , blinded clinical research associates to identify potential cardiovascular events . Investigators used study forms to report and characterize all cardiovascular outcomes . For all potential events , records , including laboratory values , electrocardiograms , and radiographic reports were obtained for clarification . Since myocardial infa rct ions may go unrecognized , a central electrocardiogram reading center was established at Brigham and Women 's Hospital , Boston , Massachusetts , where two cardiologists review ed every electrocardiogram . Electrocardiography was performed at baseline , 6 months , 12 months , and annually thereafter . A total of 5698 electrocardiograms were review ed at the center . When a new Q-wave infa rct ion was found , the cardiologists asked whether a clinical myocardial infa rct ion was reported . Even when myocardial infa rct ions were not clinical ly reported , these Q-wave infa rct ions were adjudicated as myocardial infa rct ions . Adjudication of Cardiovascular Events Investigators at each center reported cardiovascular events , defined in the Appendix Table . The information on all potential events was referred to one member of the Outcomes Confirmation and Classification Committee ( Appendix ) . If the committee member agreed with the judgment of the center investigator , their combined judgment was accepted . If the center investigator and the committee member differed , the case material was review ed by the membership of the committee , whose decision was accepted . Deaths were adjudicated by a Mortality Committee ( Appendix ) . Each death was review ed by two members of the committee and presented to the membership , whose decision was accepted as final . Statistical Analysis For graphical presentation ( Figure ) and overall testing for statistically significant differences among the three treatment groups , time to the first occurrence of either a specific cardiovascular outcome or one of the composite outcomes was analyzed by product-limit survival curves and the log-rank test ( 15 ) . We used proportional hazards modeling to determine hazard ratios . For the cardiovascular death outcome , which could occur only once , we used the st and ard proportional hazards model ( 16 ) , with treatment assignment as the only independent covariate . For other cardiovascular outcomes , which could occur more than once , we used the And ersonGill formulation of the proportional hazards model ( 17 ) , in which patients are considered at risk for the first event from r and omization to the first event , at risk for the second event from the day following the first event to the second event , and so forth , permitting use of all the data . In accordance with the method of Lee and colleagues ( 18 ) , we used a robust variance estimate that accounts for the possibility of correlation of risk for several events within a patient . We believed that occurrence of a first event of a given type increases the likelihood of a subsequent similar event . Therefore , both treatment assignment and a time-dependent covariate indicating whether the event was the first of its type or a subsequent event were included in these analyses . The time-dependent covariate was statistically significant in each case , confirming the above assumption . There was no statistically significant interaction between treatment and the time-dependent covariatethe effects of treatment assignment were similar for first and subsequent events and inclusion of the time-dependent covariate did not change either the estimates of the treatment effect or their statistical significance s. Figure . Time to first cardiovascular composite event as a function of treatment assignment . P Data management and computations were done by using SAS software for Windows , version 8 ( SAS Institute , Inc. , Cary , North Carolina ) , or S-Plus for Windows , version 6.0 ( Insightful Corp. , Seattle , Washington ) . Statistical tests were two sided . A P value of 0.05 or less , unadjusted for the multiple comparisons , was considered statistically significant . Role of the Funding Sources The funding sources were involved in the data collection but not in the analysis or interpretation or the decision to su bmi t the manuscript for publication . Results The baseline characteristics of the three groups are shown in Table 1 . A flow diagram of the study is shown in the Appendix Figure . Table 1 . Baseline Characteristics Appendix Figure . Flow diagram for the Irbesartan Diabetic Nephropathy Trial . Clinical Management During the study , the blood pressure decreased from the baseline values to 140/77 mm Hg in the irbesartan group , 141/77 mm Hg in the amlodipine group , and 144/80 mm Hg in the placebo group . Blood pressure in the two active treatment groups did not differ ; values in both groups were statistically significantly lower than in the placebo group ( P = 0.001 ) . The distribution of non study drugs used to achieve the target blood pressure was similar", "Postmenopausal women are at greater risk for hypertension-related cardiovascular disease . Antihypertensive therapy may help alleviate arterial stiffness that represents a potential modifiable risk factor of hypertension . This r and omized controlled study investigated the difference between an angiotensin receptor blocker and a calcium channel blocker in reducing arterial stiffness . Overall , 125 postmenopausal hypertensive women ( age , 61.4 ± 6 years ; systolic blood pressure/diastolic blood pressure [ SBP/DBP ] , 158 ± 11/92 ± 9 mm Hg ) were r and omized to valsartan 320 mg ± hydrochlorothiazide ( HCTZ ) ( n = 63 ) or amlodipine 10 mg ± HCTZ ( n = 62 ) . The primary outcome was carotid-to-femoral pulse wave velocity ( PWV ) changes after 38 weeks of treatment . Both treatments lowered peripheral blood pressure ( BP ) ( -22.9/-10.9 mm Hg for valsartan and -25.2/-11.7 mm Hg for amlodipine , P = not significant ) and central BP ( -15.7/-7.6 mm Hg for valsartan and -19.2/-10.3 mm Hg for amlodipine , P reduced the carotid-femoral PWV ( -1.9 vs -1.7 m/s ; P = not significant ) . Amlodipine was associated with a higher incidence of peripheral edema compared with the valsartan group ( 77 % vs 14 % , P postmenopausal women led to a reduction in arterial stiffness as assessed by PWV measurement . Both regimens reduced PWV to a similar degree after 38 weeks of treatment despite differences in central BP lowering , suggesting that the effect of valsartan on PWV is mediated through nonhemodynamic effects", "AIMS Treatment of hypertension in patients with chronic renal failure has been shown to postpone the decline in renal function . Treatment with an ACE inhibitor has been shown to be superior to conventional antihypertensive treatment , but it is not known how an ACE inhibitor compares to treatment with a calcium channel blocker or to treatment with a combination of these drugs . The aim of the study was to evaluate the rate of decline in GFR in patients with chronic renal failure and hypertension treated with isradipine and spirapril as monotherapy and in combination . METHODS Sixty patients with chronic renal failure and hypertension were enrolled in the study . After enrollment , patients were followed prospect ively for 6 months in the outpatient clinic on their usual antihypertensive medication , and then r and omized to a double-blinded comparison of either spirapril 6 mg daily , isradipine 5 mg daily or spirapril 3 mg and isradipine 2.5 mg daily . After r and omization , patients were followed for 21 months or until the need for dialysis . Every 3 months before and 3.5 months after r and omization the glomerular filtration rate was measured by 51Cr-EDTA clearance and the effective renal plasma flow evaluated using the renal clearance of paraaminohippuric acid . RESULTS Blood pressure and the decline in glomerular filtration rate did not differ between the groups before r and omization . After r and omization , the mean decline in the glomerular filtration rate was -0.32 ml/(min x month x 1.73 m2 ) in the spirapril group , -0.58 ml/(min x month x 1.73 m2 ) in the isradipine group and -0.14 ml/(min x month x 1.73 m2 ) in the combination group ( p = 0.38 ) . Twelve patients , 4 in each group , reached end-stage renal failure . No significant difference was found with respect to diastolic ( p = 0.10 ) or systolic blood pressure ( p = 0.08 ) during the treatment period , but a trend towards a better blood pressure control in the combination group was present . During treatment , the rate of decline in renal plasma flow did not differ significantly between the groups ( p = 0.09 ) , neither did the changes in filtration fraction ( FF ) ( p = 0.58 ) nor the mean FF ( p = 0.22 ) during the treatment . CONCLUSIONS Our study indicated differences between the 3 treatment modalities in favor of combined therapy with respect to both the rate of decline in GFR and blood pressure control , but the differences where insignificant . Thus , the treatments might differ , but we were unable to confirm this because of large variation in GFR and small sample size", "Abstract Background and objectives : Hypertension is a significant cause of chronic renal injury and its effective treatment is capable of reducing the rate of renal failure . β-Adrenoceptor antagonists ( β-blockers ) have been reported to induce a deterioration in renal function , while several data have indicated a renoprotective effect of treatment with the angiotensin II type 1 receptor antagonist losartan . Previous studies of the interaction between the selective β1-blocker bisoprolol and kidney function were performed only for short- and medium-term periods . The aim of this study was to compare the antihypertensive efficacy and renal and cardiac haemodynamic effects of bisoprolol with those of losartan over a 1-year time period in patients with essential hypertension . Methods : Seventy-two patients ( 40 males ) with recently diagnosed uncomplicated ( European Society of Hypertension [ ESH ] criteria stage 1–2 ) hypertension ( mean ± SD age 52 ± 12 years ) were enrolled in the study . After a run-in period of 14 days on placebo , the patients were r and omized in a double-blind , prospect i ve study to receive either bisoprolol 5 mg or losartan 50 mg , administered once daily for 1 year . At recruitment and 12 months after treatment , cardiac output and renal haemodynamics and function were evaluated by echocardiography and radionuclide studies , respectively . Results : There were no significant differences in baseline clinical data , including glomerular filtration rate and blood pressure , between the two treatment groups . At 1 year , blood pressure had decreased significantly ( p , and heart rate was reduced only in the group taking bisoprolol . The long-term effects on renal haemodynamics and cardiac function were similar with both drugs , the only change being a significant reduction in the filtration fraction for each group . Conclusions : These data suggest that both bisoprolol and losartan are effective agents for the treatment of patients with recently diagnosed ESH stage 1–2 hypertension . Over a 1-year period , both agents maintained good renal and cardiac performance and haemodynamics ", "OBJECTIVES We conducted a subgroup analysis in the Losartan Intervention For Endpoint reduction in hypertension ( LIFE ) study to determine whether aspirin interacted with the properties of losartan , an angiotensin-II receptor antagonist . BACKGROUND Negative interactions between angiotensin-converting enzyme inhibitors and aspirin have been reported . There are no data reported from clinical trials about possible interactions between angiotensin-II receptor antagonists and aspirin . METHODS The LIFE study assigned 9,193 patients with hypertension and left ventricular hypertrophy ( LVH ) to losartan- or atenolol-based therapy for a mean of 4.7 years , with 1,970 ( 21.4 % ) taking aspirin at baseline . The primary composite end point ( CEP ) included cardiovascular death , stroke , and myocardial infa rct ion ( MI ) . The present cohort was stratified by aspirin use at baseline . RESULTS Blood pressures were reduced similarly in the losartan with aspirin ( n = 1,004 ) and atenolol with aspirin ( n = 966 ) groups . The CEP was reduced by 32 % ( 95 % confidence interval 0.55 to 0.86 , p = 0.001 ) with losartan with aspirin compared to atenolol with aspirin , adjusted for Framingham risk score and LVH . The test for treatment versus aspirin interaction , excluding other covariates , was significant for the CEP ( p = 0.016 ) and MI ( p = 0.037 ) . CONCLUSIONS There was a statistical interaction between treatment and aspirin in the LIFE study , with significantly greater reductions for the CEP and MI with losartan in patients using aspirin than in patients not using aspirin at baseline . Further studies are needed to clarify whether this represents a pharmacologic interaction or a selection by aspirin use of patients more likely to respond to losartan treatment", "Background . Low serum potassium ( K ) is associated with increased blood pressure , impaired cardiac function and renal dysfunction . Although lower serum K is associated with cardiac hypertrophy in animal models , the relationship of low serum K to the presence and severity of electrocardiographic left ventricular hypertrophy ( LVH ) is unclear . Methods . Baseline and yearly Cornell product LVH levels were examined in relation to low serum K ( serum K ≤ 3.90 mEq/l , the lowest quartile of baseline K levels ) in 8586 patients with baseline K levels . Patients were r and omized to losartan-vs atenolol-based treatment and additional hydrochlorothiazide ( HCTZ ) therapy as needed . Results . After adjusting for age , sex , race , prior antihypertensive treatment , losartan vs atenolol therapy , HCTZ use , baseline diastolic and systolic pressure , body mass index , serum creatinine and urine albumin/creatinine ratio , baseline serum K ≤ 3.90 was associated with significantly higher mean baseline Cornell product LVH ( 2898 vs 2801 mm•ms , p = 0.001 ) and a 24 % higher risk of Cornell product LVH > 2440 mm•ms at baseline ( OR 1.24 , 95 % CI 1.11–1.38 , p baseline Cornell product and changes in diastolic and systolic pressure between baseline and each year of measurement , in-treatment serum K ≤ 3.90 determined yearly was associated with significantly higher mean Cornell product LVH at years 1–3 and with statistically significant 16–32 % increased risks of LVH by Cornell product at years 1–4 . Conclusions . A low serum K is independently associated with a greater likelihood and severity of Cornell product LVH during antihypertensive therapy", "OBJECTIVE To compare six antihypertensive interventions for the treatment of mild hypertension . DESIGN R and omized , double-blind , placebo-controlled clinical trial . SETTING Four hypertension screening and treatment centers in the United States . PARTICIPANTS Hypertensive men and women , aged 45 to 69 years , with diastolic blood pressure less than 100 mm Hg . INTERVENTION Sustained nutritional-hygienic advice to all participants to reduce weight , dietary sodium intake , and alcohol intake , and increase physical activity . Participants were r and omly allocated to take ( 1 ) placebo ( n = 234 ) ; ( 2 ) chlorthalidone ( n = 136 ) ; ( 3 ) acebutolol ( n = 132 ) ; ( 4 ) doxazosin mesylate ( n = 134 ) ; ( 5 ) amlodipine maleate ( n = 131 ) ; or ( 6 ) enalapril maleate ( n = 135 ) . MAIN OUTCOME MEASURES Blood pressure , quality of life , side effects , blood lipid levels and analysis of other serum components , echocardiographic and electrocardiographic changes , and incidence of cardiovascular events over an average of 4.4 years of follow-up . RESULTS Blood pressure reductions were sizable in all six groups , and were significantly greater for participants assigned to drug treatment than placebo ( -15.9 vs -9.1 mm Hg for systolic blood pressure and -12.3 vs -8.6 mm Hg for diastolic blood pressure ; P died or experienced a major nonfatal cardiovascular event than those assigned to the placebo group ( 5.1 % vs 7.3 % ; P = .21 ) . After including other clinical events , the percentage of participants affected was 11.1 % for those in the drug-treatment groups and 16.2 % for those in the placebo group ( P = .03 ) . Incidence rates of most resting electrocardiographic abnormalities were lower and quality of life was improved more for those assigned to drug-treatment groups rather than the placebo group . Differences among the five drug treatments did not consistently favor one group in terms of regression of left ventricular mass , blood lipid levels , and other outcome measures . CONCLUSIONS As an initial regimen , drug treatment in combination with nutritional-hygienic intervention was more effective in preventing cardiovascular and other clinical events than was nutritional-hygienic treatment alone . Drug-treatment group differences were minimal . Pending results from large-scale clinical trials to evaluate drug treatments for their effect on cardiovascular clinical events , these findings support the recommendations of the new fifth Joint National Committee report regarding treatment choices for people with stage 1 ( \" mild \" ) hypertension", "Background The Swedish irbesartan left ventricular hypertrophy investigation versus atenolol ( SILVHIA ) . Objective Angiotensin II induces myocardial hypertrophy . We hypothesized that blockade of angiotensin II subtype 1 ( AT1 ) receptors by the AT1-receptor antagonist irbesartan would reduce left ventricular mass ( as measured by echocardiography ) more than conventional treatment with a beta blocker . Design and methods This double-blind study r and omized 115 hypertensive men and women with left ventricular hypertrophy to receive either irbesartan 150 mg q.d . or atenolol 50 mg q.d . for 48 weeks . If diastolic blood pressure remained above 90 mmHg , doses were doubled , and additional medications ( hydrochlorothiazide and felodipine ) were prescribed as needed . Echocardiography was performed at weeks 0 , 12 , 24 and 48 . Results Baseline mean blood pressure was 162/104 mmHg , and mean left ventricular mass index was 157 g/m2 for men and 133 g/m2 for women . Systolic and diastolic blood pressure reductions were similar in both treatment groups . Both irbesartan ( P and atenolol ( P reduced left ventricular mass index , e.g. by 26 and 14 g/m2 ( 16 and 9 % ) , respectively , at week 48 , with a greater reduction in the irbesartan group ( P = 0.024 ) . The proportion of patients who attained a normalized left ventricular mass ( i.e. ⩽ 131 g/m2 for men and ⩽ 100 g/m2 for women ) tended to be greater with irbesartan ( 47 versus 32 % , P = 0.108 ) . Conclusions Left ventricular mass was reduced more in the irbesartan group than in the atenolol group . These results suggest that blocking the action of angiotensin II at AT1-receptors may be an important mechanism , beyond that of lowering blood pressure , in the regulation of left ventricular mass and geometry in patients with hypertension", "Summary We have studied 250 patients with mild to moderate essential hypertension ( diastolic blood pressure 95 – 114 mmHg ) and dyslipidaemia ( high-density lipoprotein cholesterol ( HDL-C ) below 1.03 mmol·l−1 , total cholesterol 5.17–9.05 mmol·l−1 , and triglycerides 2.26–5.64 mmol·l−1 ) in a controlled double-blind , multicentre , parallel group trial . The patients took a fat-modified diet . After a 4-week placebo period , patients who continued to fulfil the selection criteria were r and omly allocated to treatment with either carvedilol ( a vasodilating β-blocker ) 25–50 mg o.d . ( n=116 ) or captopril ( an ACE inhibitor ) 25–50 mg o.d . ( n=117 ) for 6 months . In both groups there were favourable effects on the serum lipids . The relative changes ( medians ) in the carvedilol and captopril group were respectively : increase in HDL-C by 11 % and 8 % , decrease in total cholesterol by 11 % and 10 % , in low-density lipoprotein cholesterol by 16 % and 12 % , and in triglycerides by 13 % and 14 % . Equivalence of the two treatments was confirmed for the target variable change in HDL-C at a significance level of 5%.Reductions in supine systolic/diastolic blood pressures were comparable in the two groups ( carvedilol : 23/19 mmHg , captopril : 20/18 mmHg).The improvement in lipid metabolism in patients treated with carvedilol is probably due to its α1-blocking properties", "We examined long-term changes in cognitive function and quality of life ( QL ) in hypertensive patients by comparing the antihypertensive effect of hydrochlorothiazide ( HCTZ ) and losartan . We studied 69 patients ( age range , 30 to 73 years ) with mild-to-moderate hypertension . All patients , in a double-blind study , were r and omly allocated to either treatment with 50 mg losartan once daily or 25 mg HCTZ once daily . The sample in each treatment group was divided by age ( younger than 60 years or 60 years or older ) . At baseline and after 26 months , a QL question naire appropriate for the hypertensive patients was given . Cognitive function was evaluated , at baseline and after 26 months , by psychometric tests consisting of items from the Mini-Mental State Examination ( MMSE ) and the S and oz Clinical Assessment Geriatric ( SCAG ) . A score of less than 24 on the MMSE and more than 40 on the SCAG was predictive of cognitive impairment . The losartan group had a significant improvement in SCAG ( P MMSE ( P Sixty-five percent of the elderly had a MMSE score less than 24 and 70 % had a SCAG score greater than 40 , v. 35 % and 48 % , respectively , in younger patients . The health state index of QL improved significantly in both groups ( losartan group , P improvement in QL scores in patients using HCTZ was significant only in subjects aged 60 years and older ( P blood pressure but also on impaired cognitive function , reversing even minimal cognitive deficits induced by hypertension . The elderly patients in our sample had worse scores and cognitive performance was lower than in younger patients , even if in the losartan group the score improvement was the same at all ages . The same could not be said for HCTZ", "OBJECTIVES To assess the peripheral and central haemodynamics , in particular the effect on minimal resistance in the h and , with an ACE inhibitor in comparison with a diuretic . DESIGN Double-blind r and omized parallel group study . SUBJECTS Twenty-eight previously untreated men with essential hypertension ( supine diastolic blood pressure > 95 mmHg repeatedly on placebo ) . METHODS /INTERVENTION : Causal and intra-arterial blood pressure , dye-dilution technique , water plethysmography at rest and at ischaemia , enalapril ( n = 14 ) , hydrochlorothiazide ( n = 14 ) . RESULTS After 6 months the mean arterial pressure was reduced from 112.7 to 96.9 mmHg ( change -15.9 mmHg ; 95 % confidence interval ( CI ) -21.9 , -9.8 ) on enalapril and from 110.1 to 101.5 mmHg ( change -8.6 mmHg ; CI -14.4 , -2.8 ) . Heart rate did not change on any of the therapies . Enalapril reduced blood pressure mainly through a reduction in total peripheral resistance ( delta -3.0 PRU100 ; CI -5.6 , -0.4 ) while hydrochlorothiazide reduced blood pressure mainly through a reduction in cardiac output ( delta -0.8 l/min-1 ; CI -1.5 , -0.07 ) . Minimal vascular resistance ( mean of right and left h and ) displayed a significant time x treatment interaction indicating a different trend with enalapril than hydrochlorothiazide with a change of -0.12 PRU100 ( CI -0.33 , 0.05 ) on enalapril and a change of 0.14 ( CI -0.29 , 0.56 ) on hydrochlorothiazide . The resistance level after 6 months was significantly higher on hydrochlorothiazide than on enalapril ( P = 0.0105 ) . CONCLUSION Enalapril reduced blood pressure through vasodilatation and hydrochlorothiazide through decreased cardiac output . The two therapies also affected minimal vascular resistance ( an indirect measure of vascular wall thickness ) differently ; with enalapril showing a favourable response in contrast to hydrochlorothiazide ", "The Losartan Intervention For Endpoint reduction in hypertension ( LIFE ) study reported that a losartan-based antihypertensive regimen reduced cardiovascular morbidity and mortality ( composite of cardiovascular death , stroke , and myocardial infa rct ion ) more than therapy based on atenolol in patients with left ventricular hypertrophy and isolated systolic hypertension ( ISH ) . Patients aged 55 - 80 years with blood pressures 160 - 200/ Blood pressure was similarly reduced in the losartan ( n=660 ) and atenolol ( n=666 ) ISH groups . There were 88 ( 6.6 % ) patients who experienced a stroke , 18 of which were fatal . Of patients experiencing strokes , 72.7 % had an ischemic stroke . ISH patients in LIFE compared to the non-ISH group had a higher incidence of any stroke and embolic stroke , and similar incidences of fatal , atherosclerotic , and hemorrhagic/other strokes . The incidence of any stroke ( 40 % risk reduction [ RR ] , p=0.02 ) , fatal stroke ( 70 % RR , p=0.035 ) , and atherothrombotic stroke ( 45 % RR , p=0.022 ) was significantly lower in losartan-treated compared to the atenolol-treated patients . The 36 % RR for embolic strokes in the losartan group was not statistically significantly ( p=0.33 ) different from the atenolol group . These data suggest that losartan-based treatment is more effective than an atenolol-based treatment for patients with ISH and a high risk for stroke", "CONTEXT Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality , but the optimal first-step therapy is unknown . OBJECTIVE To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease ( CHD ) or other cardiovascular disease ( CVD ) events vs treatment with a diuretic . DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , active-controlled clinical trial conducted from February 1994 through March 2002 . SETTING AND PARTICIPANTS A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers . INTERVENTIONS Participants were r and omly assigned to receive chlorthalidone , 12.5 to 25 mg/d ( n = 15 255 ) ; amlodipine , 2.5 to 10 mg/d ( n = 9048 ) ; or lisinopril , 10 to 40 mg/d ( n = 9054 ) for planned follow-up of approximately 4 to 8 years . MAIN OUTCOME MEASURES The primary outcome was combined fatal CHD or nonfatal myocardial infa rct ion , analyzed by intent-to-treat . Secondary outcomes were all-cause mortality , stroke , combined CHD ( primary outcome , coronary revascularization , or angina with hospitalization ) , and combined CVD ( combined CHD , stroke , treated angina without hospitalization , heart failure [ HF ] , and peripheral arterial disease ) . RESULTS Mean follow-up was 4.9 years . The primary outcome occurred in 2956 participants , with no difference between treatments . Compared with chlorthalidone ( 6-year rate , 11.5 % ) , the relative risks ( RRs ) were 0.98 ( 95 % CI , 0.90 - 1.07 ) for amlodipine ( 6-year rate , 11.3 % ) and 0.99 ( 95 % CI , 0.91 - 1.08 ) for lisinopril ( 6-year rate , 11.4 % ) . Likewise , all-cause mortality did not differ between groups . Five-year systolic blood pressures were significantly higher in the amlodipine ( 0.8 mm Hg , P = .03 ) and lisinopril ( 2 mm Hg , P chlorthalidone , and 5-year diastolic blood pressure was significantly lower with amlodipine ( 0.8 mm Hg , P amlodipine vs chlorthalidone , secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine ( 10.2 % vs 7.7 % ; RR , 1.38 ; 95 % CI , 1.25 - 1.52 ) . For lisinopril vs chlorthalidone , lisinopril had higher 6-year rates of combined CVD ( 33.3 % vs 30.9 % ; RR , 1.10 ; 95 % CI , 1.05 - 1.16 ) ; stroke ( 6.3 % vs 5.6 % ; RR , 1.15 ; 95 % CI , 1.02 - 1.30 ) ; and HF ( 8.7 % vs 7.7 % ; RR , 1.19 ; 95 % CI , 1.07 - 1.31 ) . CONCLUSION Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive . They should be preferred for first-step antihypertensive therapy", "Microalbuminuria and hypertension are risk factors for diabetic nephropathy in Type 2 diabetic patients . Recent data suggest that blockade of the renin-angiotensin system slows the progression of diabetic nephropathy ; in contrast , the results on the renoprotective effect of calcium channel antagonists are conflicting . We evaluated the effectiveness of lercanidipine , in comparison with ramipril , on the reduction in albumin excretion rate ( AER ) and blood pressure in mild-to-moderate hypertensive patients with Type 2 diabetes and persistent microalbuminuria . A total of 277 patients were enrolled in a multicentric , r and omized , double-blind , active-controlled , parallel-group trial ; 180 were r and omized to receive 10 - 20 mg/day of lercanidipine or 5 - 10 mg/day of ramipril and followed up for 9 - 12 months . The primary outcome was the change in AER from baseline . After 9 - 12 months of follow-up , a reduction in AER of -17.4+/-65 microg/min ( p lercanidipine and ramipril group , respectively , was observed , without differences between the groups . A significant reduction in systolic and diastolic blood pressure was observed in both the lercanidipine and ramipril-based treatment groups ( p lercanidipine 10 - 20 mg/day does not worsen albuminuria in microalbuminuric Type 2 diabetic patients with hypertension . Indeed , both lercanidipine and ramipril treatments result ed in a significant reduction in AER without a statistically significant difference between the two groups", "CONTEXT Renin profiling and age-race subgroup may help select single-drug therapy for stage 1 and stage 2 hypertension . OBJECTIVE To compare the plasma renin profiling and age-race subgroup methods as predictors of response to single-drug therapy in men with stage 1 and 2 hypertension as defined by the Joint National Committee on Prevention , Detection , Evaluation and Treatment of High Blood Pressure . DESIGN The Veterans Affairs Cooperative Study on Single-Drug Therapy of Hypertension , a r and omized controlled trial . SETTING Fifteen Veterans Affairs hypertension centers . PATIENTS A total of 1105 ambulatory men with entry diastolic blood pressure ( DBP ) of 95 to 109 mm Hg , of whom 1031 had valid plasma and urine sample s for renin profiling . INTERVENTIONS R and omization to 1 of 6 antihypertensive drugs : hydrochlorothiazide , atenolol , captopril , clonidine , diltiazem ( sustained release ) , or prazosin . MAIN OUTCOME MEASURE Treatment response as assessed by percentage achieving goal DBP ( response rates regardless of renin profile ( 76 % , 67 % , and 80 % for low , medium , and high renin , respectively , for clonidine and 83 % , 82 % , and 83 % , respectively , for diltiazem for patients with baseline DBP of 95 - 99 mm Hg ) . Hydrochlorothiazide and prazosin were best in low- and medium-renin profiles ; captopril was best in medium- and high-renin profiles ( low- , medium- , and high-renin response rates were 82 % , 78 % , and 14 % , respectively , for hydrochlorothiazide ; 88 % , 67 % , and 40 % , respectively , for prazosin ; and 51 % , 83 % , and 100 % , respectively , for captopril for patients with baseline DBP of 95 - 99 mm Hg ) . Response rates for patients with baseline DBP of 95 to 99 mm Hg by age-race subgroup ranged from 70 % for clonidine to 90 % for prazosin for younger black men , from 50 % for captopril to 97 % for diltiazem for older black men , from 70 % for hydrochlorothiazide to 92 % for atenolol for younger white men , and from 84 % for hydrochlorothiazide to 95 % for diltiazem for older white men . Patients with a correct treatment for their renin profile but incorrect for age-race subgroup had a response rate of 58.7 % ; patients with an incorrect treatment for their renin profile but correct for age-race subgroup had a response rate of 63.1 % ( P = .30 ) . After controlling for DBP and interactions with treatment group , age-race subgroup ( P single-drug therapy , whereas renin profile was of borderline significance ( P= .05 ) . CONCLUSIONS In these men with stage 1 and stage 2 hypertension , therapeutic responses were consistent with baseline renin profile , but age-race subgroup was a better predictor of response", "-Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension . The Losartan Intervention For Endpoint ( LIFE ) Reduction in Hypertension Study is a double-blind , prospect i ve , parallel group study design ed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality . Patients with essential hypertension , aged between 55 and 80 years , and ECG-documented left ventricular hypertrophy ( LVH ) were included . Altogether , 9223 patients in Sc and inavia , the United Kingdom , and the United States were r and omized from June 1995 through April 1997 , and 9194 remain after exclusion of a study center at which irregularities were discovered . This population of hypertensives ( mean systolic/diastolic blood pressure , 174.4/97.8 mm Hg ) with LVH comprises women ( 54.1 % ) and men , mostly retired from active work ( mean age , 66.9 years ) , with a high prevalence of overweight ( mean body mass index , 28.0 kg/m2 ) , diabetes mellitus ( 12.3 % ) , lipid disorders ( 18.0 % ) , and symptoms or signs of coronary heart disease ( 15.1 % ) . There were fewer current smokers ( than in the general population , and approximately 7 % were nonwhite . Almost 30 % of participants had been untreated for at least 6 months when screened for the study . Only 1557 persons who entered the placebo run-in period of 14 days were excluded , predominantly because of sitting blood pressures above or below the predetermined range of 160 - 200/95 - 115 mm Hg and ECG-LVH criteria not met . By application of simple 12-lead ECG criteria for LVH ( Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory ) , hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3 % according to the Framingham score were identified . This population is now being treated ( goal , < 140/90 mm Hg ) in adherence with the protocol for at least 4 years after final enrollment ( ie , through April 2001 ) and until at least 1040 patients suffer myocardial infa rct ion , stroke , or cardiovascular death", "BACKGROUND Characteristics such as age and race are often cited as determinants of the response of blood pressure to specific antihypertensive agents , but this clinical ly important issue has not been examined in sufficiently large trials , involving all st and ard treatments , to determine the effect of such factors . METHODS In a r and omized , double-blind study at 15 clinics , we assigned 1292 men with diastolic blood pressures of 95 to 109 mm Hg , after a placebo washout period , to receive placebo or one of six drugs : hydrochlorothiazide ( 12.5 to 50 mg per day ) , atenolol ( 25 to 100 mg per day ) , captopril ( 25 to 100 mg per day ) , clonidine ( 0.2 to 0.6 mg per day ) , a sustained-release preparation of diltiazem ( 120 to 360 mg per day ) , or prazosin ( 4 to 20 mg per day ) . The drug doses were titrated to a goal of less than 90 mm Hg for maximal diastolic pressure , and the patients continued to receive therapy for at least one year . RESULTS The mean ( + /- SD ) age of the r and omized patients was 59 + /- 10 years , and 48 percent were black . The average blood pressure at base line was 152 + /- 14/99 + /- 3 mm Hg . Diltiazem therapy had the highest rate of success : 59 percent of the treated patients had reached the blood-pressure goal at the end of the titration phase and had a diastolic blood pressure of less than 95 mm Hg at one year . Atenolol was successful by this definition in 51 percent of the patients , clonidine in 50 percent , hydrochlorothiazide in 46 percent , captopril in 42 percent , and prazosin in 42 percent ; all these agents were superior to placebo ( success rate , 25 percent ) . Diltiazem ranked first for younger blacks ( ) and older blacks ( > or = 60 years ) , among whom the success rate was 64 percent , captopril for younger whites ( success rate , 55 percent ) , and atenolol for older whites ( 68 percent ) . Drug intolerance was more frequent with clonidine ( 14 percent ) and prazosin ( 12 percent ) than with the other drugs . CONCLUSIONS Among men , race and age have an important effect on the response to single-drug therapy for hypertension . In addition to cost and quality of life , these factors should be considered in the initial choice of a drug", "Left ventricular ( LV ) hypertrophy is associated with a substantial risk for malignant arrhythmias and sudden death . The effects of antihypertensive therapy on QT dispersion , which reflects cardiac repolarization heterogeneity , in relation to changes in LV mass has not been well studied . Repeat echocardiography and QT measurements ( st and ard 12-lead electrocardiograms ) were performed in hypertensive patients with LV hypertrophy , who were r and omized double-blind to receive the angiotensin II type 1-receptor blocker irbesartan ( n = 44 ) or the beta(1)-receptor blocker atenolol ( n = 48 ) for 48 weeks , and in 37 matched hypertensive control subjects without LV hypertrophy . LV mass index was related to QT dispersion ( r = 0.34 , p reduction in LV mass was greater using irbesartan than using atenolol ( -27 + /- 28 vs -15 + /- 21 g/m(2 ) at 48 weeks , p = 0.021 ) , with similar reductions in blood pressure . Irbesartan decreased QT dispersion ( from 56 + /- 24 ms to 45 + /- 20 ms at 48 weeks ; p QTc dispersion ( from 57 + /- 24 to 44 + /- 19 ms at 48 weeks ; p atenolol had minor effects . The decreases in QT and QTc dispersions were greater using irbesartan than using atenolol ( p = 0.001 and p = 0.011 , respectively ) ; the same results were found when changes in LV mass , blood pressure , and heart rate were also included in multivariate analyses . Thus , heterogeneity of ventricular repolarization is related to the degree of LV hypertrophy . Irbesartan , but not atenolol , reduces QT and QTc dispersions independent of changes in LV mass , blood pressure , or heart rate , and thus seems to induce structural and electrical remodeling in a direction that could decrease the risk of fatal events in hypertensive patients", "Context The Losartan Intervention for Endpoint reduction in hypertension ( LIFE ) trial showed that losartan-based treatment improved cardiovascular outcomes more than atenolol-based treatment in patients with hypertension and left ventricular hypertrophy . Because the study sample was heterogeneous , clinicians wondered about effects in the lower-risk participants . Contribution This analysis of lower-risk participants without known vascular disease showed that both losartan and atenolol reduced blood pressure similarly . Cardiovascular events , particularly strokes , and new-onset diabetes occurred less frequently with losartan than with atenolol . Implication s Patients with hypertension and left ventricular hypertrophy but no known vascular disease benefit more from losartan than atenolol . The Editors Benefits of lowering blood pressure by using antihypertensive treatment are well established , especially in high-risk individuals ( 1 ) . However , treated hypertensive patients still have more cardiovascular events than matched normotensive adults . Possible reasons are failure to normalize blood pressure ; adverse effects of reninangiotensin system overactivity ; and residual target organ damage , such as left ventricular hypertrophy ( LVH ) . Recent evidence has supported the hypothesis that reversal of LVH has prognostic benefit independent of blood pressure lowering ( 2 , 3 ) . Reducing cardiovascular event rates by reninangiotensin system inhibition was initially shown by a comparison of the angiotensin-converting enzyme inhibitor ramipril with placebo in patients with clinical ly evident vascular disease in the Heart Outcomes Prevention Evaluation ( HOPE ) trial ( 4 ) . Subsequently , the Losartan Intervention for Endpoint reduction in hypertension ( LIFE ) study ( 5 ) showed that the angiotensin II AT1-receptor antagonist losartan reduced cardiovascular morbidity and mortality compared with active antihypertensive therapy with the -blocker atenolol ( 6 - 8 ) . This study also linked this benefit to hypertrophy regression ( 9 ) . The LIFE trial enrolled hypertensive patients with electrocardiogram-defined LVH and included patients at especially high risk because of clinical ly evident vascular disease ( 5 , 10 ) . Thus , antagonism of potentially toxic angiotensin II effects has been shown to reduce cardiovascular events in trials conducted wholly or partly in patients with preexisting atherosclerotic disease , but whether this is also true in most hypertensive patients without clinical ly evident vascular disease has not been extensively analyzed . Accordingly , we performed a subgroup analysis in the LIFE study to determine whether angiotensin II AT1-receptor antagonism with losartan reduces cardiovascular morbidity and mortality , compared with active therapy with established -blockerbased therapy , in hypertensive participants with electrocardiogram-defined LVH who did not have clinical ly evident coronary , cerebral , or peripheral arterial disease at the time of enrollment . Methods Study Design The LIFE study is an investigator-initiated , multinational , multicenter , double-blind , double-dummy , r and omized , active-controlled , parallel-group study . The primary objective was to evaluate the long-term effects of once-daily losartan-based antihypertensive therapy compared with atenolol-based antihypertensive therapy in patients with hypertension and electrocardiogram-defined LVH on cardiovascular morbidity and mortality . The complete LIFE study protocol , with study design , organization , clinical measures , end point definitions , choice of comparative agent , statistical considerations , recruitment details , patient characteristics , and main outcomes , has been published ( 5 - 9 , 11 ) . Patients gave informed consent under protocol s approved by the concerned ethics committees ; an independent data and safety monitoring board oversaw the trial . Target Population , Treatment , and Measurement of LVH A total of 9193 patients 55 to 80 years of age with previously treated or untreated hypertension and electrocardiogram-defined LVH ( 5 ) were r and omly assigned after 1 to 2 weeks of placebo use to losartan or atenolol if trough sitting blood pressures were 160 to 200/95 to 115 mm Hg . The present analysis included all LIFE participants , with particular focus on the subgroup without previous diagnoses of coronary , cerebral , or peripheral vascular disease by either self-report or report of treating physicians . Patients in the present subgroup analysis were enrolled from 26 June 1995 through 2 May 1997 . A total of 6886 r and omly assigned patients from centers in Denmark ( 1030 ) , Finl and ( 1237 ) , Icel and ( 96 ) , Norway ( 1112 ) , Sweden ( 1634 ) , the United Kingdom660 , and the United States ( 1067 ) did not have clinical ly evident vascular disease . Patients were followed for 4 years or longer with regular visits and upward titration of the medication dose to reach the goal blood pressure of less than 140/90 mm Hg ( 5 , 10 ) . Electrocardiogram Coding and LVH Criteria All screening , baseline , annual , and end point electrocardiograms were evaluated at one core reading center . Patients were accepted into the study if a screening electrocardiogram fulfilled the LVH criteria ( 5 , 10 ) . On the basis of evidence that combined electrocardiogram assessment of QRS voltage and duration enhances sensitivity for LVH detection at acceptable levels of specificity ( 12 , 13 ) , the product of QRS duration multiplied by Cornell voltage ( with sex adjustment of 8 mm in women [ 14 ] and a partition value of > 2440 mm ms ) was chosen to recognize hypertrophy . Because of evidence that the sex adjustment was excessive and that patients with LVH by traditional electrocardiogram criteria were being missed , two changes were made for patients recruited after 30 April 1996 : Sex adjustment of Cornell voltage was reduced to 6 mm , and SokolowLyon voltage greater than 38 mm was accepted as an alternative criterion ( 10 ) . As previously described , it was estimated ( and later confirmed with electrocardiography in a sub study of 960 patients [ 15 ] ) that more than 70 % of patients who met LIFE electrocardiogram criteria from one screening electrocardiogram had anatomic LVH . Outcome Measures The primary end point of cardiovascular morbidity and death was a composite of the first occurrence of cardiovascular death , stroke , or clinical ly evident myocardial infa rct ion . Other prespecified outcomes were total mortality , angina pectoris or heart failure requiring hospitalization , coronary or peripheral revascularization procedures , resuscitated cardiac arrest , and new-onset diabetes . An end point committee , blinded to therapy , separately review ed clinical records for all events reported by clinical centers to determine whether they met protocol end point criteria . The Electrocardiogram Core Center evaluated regression of hypertrophy on the electrocardiogram . New-onset diabetes , defined according to 1985 World Health Organization criteria ( 16 ) , was reported by investigators on the basis of fasting hyperglycemia on two occasions or a positive result on a glucose tolerance test . Sitting blood pressure was measured at trough ( that is , 24 hours after dose ; range , 22 to 26 hours ) . Adverse experiences , classified as drug-related or nondrug-related , as well as serious or nonserious , according to International Conference on Harmonization guidelines for good clinical practice , were recorded by investigators using open-ended worksheets at every visit . The LIFE study ran its full course , and end point follow-up was stopped at midnight local time , 16 September 2001 , which was the time-point for the last end point to count . After the stopping date , patients had a follow-up clinic visit or at least a check of vital status within 6 weeks . Statistical Analysis Allocation numbers were associated with treatment groups by using a computer-generated allocation schedule ; patients were considered r and omly assigned when they received an allocation number . Blinding was maintained in a double-dummy fashion : All patients received both blinded losartan and blinded atenolol : One tablet consisted of active treatment and one tablet consisted of placebo . All cardiovascular end points were analyzed by using the intention-to-treat approach ; all r and omly assigned patients were included in their assigned treatment group , and all available follow-up information was included from r and omization through the end of the study . Only events confirmed by the end point committee were analyzed . Patients with several end points were counted as having had an event in all relevant end point analyses ; however , only the first event in a specific category counted in individual analyses . Safety analyses included all r and omly assigned patients from r and omization through 16 September 2001 or permanent discontinuation of therapy with blinded study medication , whichever came first . Differences between treatment groups in rates of clinical events were assessed by Cox regression models with degree of LVH ( using Cornell voltage duration product and SokolowLyon voltage as continuous variables ) and the Framingham risk score ( 17 ) defined by baseline characteristics as covariates . This adjusted analysis was chosen a priori as primary to account for differences in key risk predictors at baseline . Secondary unadjusted analyses were performed to vali date the adjusted results . Interaction between treatment and vascular disease status was tested by including indicators for these factors and the product of these indicators in a Cox regression model . Treatment effects were measured by hazard ratios ( relative risks ) , and their 95 % CIs were calculated from Cox regression models . The risk reduction for losartan versus atenolol was calculated as : 100 ( 1 relative risk ) . Event rates over time are presented as KaplanMeier curves . Adjustment for blood pressure was based on Cox regression models with blood pressure values throughout the trial as time-varying covariates . Differences between groups in changes in electrocardiogram", "Objective To compare the effects of a calcium antagonist ( nitrendipine ) and an angiotensin converting enzyme inhibitor ( enalapril ) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension . Design A double-blind r and omized , placebo-controlled trial . Setting General practitioners referred patients to the trial physician . Patients The study population comprised 121 patients with non-insulin-dependent diabetes mellitus . Inclusion criteria for blood pressure were diastolic blood pressure 90–115 mmHg and systolic blood pressure ⩽ 200 mmHg , while subjects were not being administered blood-pressure-lowering drugs for 3 weeks . Intervention Patients were r and omly allocated to receive nitrendipine ( n = 40 ) , enalapril ( n = 40 ) or placebo ( n = 41 ) . The treatment period was 48 weeks . Main outcome measures The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment . The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly . Left ventricular mass was measured by M-mode echocardiography . Results Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures . During 48 weeks left ventricular mass index decreased by 5 % for patients in the nitrendipine group ( decrease by 12 g/m2 , 95 % confidence interval 1–23 ) , remained about the same for patients in the enalapril group ( decrease by 1 g/m2 , 95 % confidence interval decrease by 10 to increase by 9 ) and increased by 9 % for patients in the placebo group ( increase by 9 g/m2 , 95 % confidence interval 2–16 ) . Conclusion These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension reduces left ventricular mass index . Enalapril appears not to induce regression , but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo . J Hypertens 16:689–696 © 1998 Lippincott-Raven Publishers", "BACKGROUND Elevated blood glucose levels are reported with thiazide-type diuretic treatment of hypertension . The significance of this finding is uncertain . Our objectives were to compare the effect of first-step antihypertensive drug therapy with thiazide-type diuretic , calcium-channel blocker , or angiotensin-converting enzyme inhibitor on fasting glucose ( FG ) levels and to determine cardiovascular and renal disease risks associated with elevated FG levels and incident diabetes mellitus ( DM ) in 3 treatment groups . METHODS We performed post hoc subgroup analyses from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) among nondiabetic participants who were r and omized to receive treatment with chlorthalidone ( n = 8419 ) , amlodipine ( n = 4958 ) , or lisinopril ( n = 5034 ) and observed for a mean of 4.9 years . RESULTS Mean FG levels increased during follow-up in all treatment groups . At year 2 , those r and omized to the chlorthalidone group had the greatest increase ( + 8.5 mg/dL [ 0.47 mmol/L ] vs + 5.5 mg/dL [ 0.31 mmol/L ] for amlodipine and + 3.5 mg/dL [ 0.19 mmol/L ] for lisinopril ) . The odds ratios for developing DM with lisinopril ( 0.55 [ 95 % confidence interval , 0.43 - 0.70 ] ) or amlodipine ( 0.73 [ 95 % confidence interval , 0.58 - 0.91 ] ) vs chlorthalidone at 2 years were significantly lower than 1.0 ( P FG level change at 2 years with subsequent coronary heart disease , stroke , cardiovascular disease , total mortality , or end-stage renal disease . There was no significant association of incident DM at 2 years with clinical outcomes , except for coronary heart disease ( risk ratio , 1.64 ; P = .006 ) , but the risk ratio was lower and nonsignificant in the chlorthalidone group ( risk ratio , 1.46 ; P = .14 ) . CONCLUSIONS Fasting glucose levels increase in older adults with hypertension regardless of treatment type . For those taking chlorthalidone vs other medications , the risk of developing FG levels higher than 125 mg/dL ( 6.9 mmol/L ) is modestly greater , but there is no conclusive or consistent evidence that this diuretic-associated increase in DM risk increases the risk of clinical events", "The antihypertensive effect of indapamide has never been clearly understood , particularly in hypertensive patients with diabetes mellitus . A total of 565 patients were r and omly selected to receive either indapamide 1.5 mg or enalapril 10 mg daily for 12 months . Brachial blood pressure ( BP ) and plasma and urinary electrolytes were measured at baseline and at the end of follow-up . Sodium and potassium levels and excretion rates were measured in overnight urine collection s. After 12 months ' treatment , similar significant reductions were observed in systolic and diastolic BP and pulse pressure levels in both treatment arms ( P body mass index , diabetes duration , and plasma sodium reductions were shown to be major , independent factors influencing BP reduction with indapamide , but not with enalapril . Regression coefficients were positive for age and plasma sodium reductions ( P ≤ .009 ) but negative for body mass index and diabetes duration ( P ≤ .008 ) . Similar findings were observed for pulse pressure . These results were more notable in elderly patients , did not differ regardless of whether BP reduction was measured in absolute or percent values , and were associated with increased sodium and potassium excretion rates . Indapamide is more effective than enalapril at reducing BP in elderly diabetic hypertensives with marked sodium retention", "Objective Hypertension causes arteriolar narrowing and rarefaction in the retinal circulation , but the extent to which these changes are reversible by antihypertensive treatment is not well studied . We compared the effect of antihypertensive treatment with a calcium-channel-blocker-based regimen and an angiotensin-converting-enzyme-inhibitor-based regimen on the retinal microvasculature . Methods Twenty-five patients ( 17 men , age range 24–71 years ) with untreated hypertension were r and omized to treatment with an amlodipine-based ( n = 12 ) or lisinopril-based ( n = 13 ) regimen in a double-blind , prospect i ve parallel limb trial for 52 weeks . Measurements of blood pressure and the retinal microvasculature were made at baseline and at the end of the study . Results Both the amlodipine-based and lisinopril-based treatments reduced blood pressure to similar extents . Blood pressure reduction was associated with a reduction in arteriolar narrowing , a widening of arteriolar branch angle and an increase in arteriolar density . There were no significant differences between the two treatment regimens . Conclusion Antihypertensive treatment is associated with improvement in arteriolar narrowing and rarefaction . Improved microvascular structure may contribute to the beneficial effects of antihypertensive treatment in hypertension", "The effects of an ACE-inhibitor ( ramipril ) , a calcium antagonist ( felodipine ) and placebo on glomerular filtration rate ( GFR ) , urinary albumin/creatinine ratio , blood pressure ( BP ) and vasoactive hormones were investigated in a r and omized , prospect i ve , double-blind , placebo-controlled study of patients with chronic glomerulonephritis and hypertension , with measurements at entrance and after 12 and 24 months . In total , 33 patients were included : 21 completed the study with 7 patients in each group . GFR was measured as 51Cr-EDTA clearance and the vasoactive hormones with radioimmunoassays . The reduction in GFR was significantly more pronounced in the felodipine group ( -7 ml/min ) than in the ramipril group ( 0 ml/min ) but the same as in the placebo group ( -6 ml/min ) . The urinary albumin/creatinine ratio was significantly more reduced in the ramipril group ( -74 mg/mmol ) than in the placebo group ( -11 mg/mmol ) , which did not deviate from the felodipine group ( -10 mg/mmol ) . BP was significantly reduced by ramipril and felodipine , but not by placebo . Angiotensin II and aldosterone in plasma increased or tended to increase in the felodipine and placebo groups , but were unchanged in the ramipril group . Endothelin increased only in the placebo group , and vasopressin , atrial natriuretic peptide , and brain natriuretic peptide were not significantly changed in any of the groups . It is concluded that ramipril seems to be superior to felodipine in chronic glomerulonephritis owing to better preservation of GFR", "BACKGROUND Hypertension is a common complication in autosomal dominant polycystic kidney disease ( ADPKD ) . This prospect i ve r and omized double-blind study was performed to compare the renal and cardiac effects of the ACE inhibitor ramipril and the beta-blocker metoprolol as first line therapy in ADPKD patients with hypertension . METHODS Forty-six hypertensive ADPKD patients were r and omized to either ramipril ( n = 23 ) or metoprolol ( n = 23 ) . Twenty-four hour ( 24-h ) ambulatory blood pressure ( BP ) , glomerular filtration rate ( GFR ) as calculated by the Cockcroft and Gault formula , urinary albumin excretion ( albumin/creatinine ratio ) , and left ventricular mass index ( LVMI ) were established at baseline and at yearly intervals . The total follow-up was 3 years . Baseline characteristics were similar in both groups . RESULTS Mean arterial pressure ( MAP ) decreased significantly in both the ramipril and the metoprolol group (-8 + /- 2 and -6 + /- 2 mmHg ; both P renal function during follow-up which was similar in patients treated with ramipril or metoprolol ( -2.5 + /- 0.7 vs -2.9 + /- 0.8 ml/min/year ; P = NS ) . After the 3 years follow-up , no differences in GFR , LVMI and urinary albumin excretion were observed between the ramipril and the metoprolol group ( 80.7 + /- 10.7 vs 78.0 + /- 7.6 ml/min , 102.6 + /- 6.8 vs 100.3 + /- 5.4 g/m(2 ) ; and 42.6 + /- 12.3 vs 70.3 + /- 32.5 mg/g , respectively ; all P = NS ) . A post-hoc analysis evaluating the effects of BP control , revealed that LVMI increased in patients with st and ard BP control while it remained stable in patients with rigorous BP control with a significant difference in LVMI between the groups after 3 years of follow-up ( 110.5 + /- 6.3 vs 90.9 + /- 4.7 g/m(2 ) ; P = 0.017 ) . Also , by the end of the study albuminuria was lower in patients with rigorous vs st and ard BP control ( 23.5 + /- 6.7 vs 94.8 + /- 35.4 mg/g ; P = 0.05 ) . CONCLUSIONS In our study population of hypertensive ADPKD patients , no differences in renal function , urinary albumin excretion and LVMI were detected between those treated with ramipril or metoprolol , respectively , during a 3 years follow-up . Rigorous BP control prevented an increase in LVMI and reduced urinary albumin excretion , suggesting a crucial role of BP control for slowing progression of cardiac and renal organ damage in ADPKD", "BACKGROUND Placebo-controlled trials have found that angiotensin-converting enzyme inhibitors ( ACEIs ) decrease proteinuria and slow the progression of nondiabetic nephropathies . However , head-to-head comparisons of ACEIs and calcium channel blockers ( CCBs ) have shown conflicting results . Indeed , a recent meta analysis concluded that there is still uncertainty about the greater renoprotection seen with ACEIs or angiotensin II receptor blockers in nondiabetic patients with renal disease , particularly when using true glomerular filtration rate ( GFR ) as the primary outcome . OBJECTIVE The objective of this 3-year , r and omized , multicenter , double-blind , placebo-controlled study was to compare true GFR decline ( measured by yearly 51Cr-EDTA blood clearance ) in nondiabetic , nonnephrotic adult hypertensive patients with estimated creatinine clearance of 20 to 60 mL/min.1.73 m(2 ) , when r and omized to a CCB ( amlodipine , 5 - 10 mg/d ) or an ACEI ( enalapril , 5 - 20 mg/d ) . METHODS Patients ( aged 18 - 80 years ) entered a 4-week placebo run-in washout period and previous antihypertensive drugs were tapered off over 2 weeks . Add-on treatments were atenolol ( 50 - 100 mg/d ) , loop diuretics ( furosemide , 20 - 500 mg/d or torsemide , 5 - 200 mg/d ) , alpha-blockers ( prazosin , 2.5 - 5 mg/d or doxazosin , 1 - 16 mg/d ) , and central ly acting drugs ( rilmenidine , 1 - 2 mg/d or methyldopa , 250 - 500 mg/d ) . The primary end point was true GFR measured by yearly (51)Cr-EDTA blood clearance . Secondary end points included a clinical composite of renal events and tolerability collected by a full clinical and laboratory evaluation at each study visit . Post hoc analyses for the change in GFR , proteinuria , and time to clinical events were also planned on baseline proteinuria subgroups ( or=1 g/d ) before unblinding the data base . RESULTS Three hundred eighteen patients entered the run-in period and 263 patients ( 156 men/107 women ; mean age , 58 years ) were r and omized to receive either amlodipine ( 5 mg/d , n=132 ) or enalapril ( 5 mg/d , n=131 ) . Blood pressure declined from 165/102 mm Hg to 138/84 mm Hg and 138/85 mm Hg with amlodipine and enalapril , respectively ( no between-group significance ) . Only 20.8 % of the patients r and omized to ACEI treatment received diuretics at the last observation . No statistically significant difference was found between amlodipine and enalapril in GFR decline ( -4.92 and -3.98 mL/min.1.73 m(2 ) , respectively , at last observation ) and composite secondary end point after a median follow-up of 2.9 years , including in the subgroup of patients with proteinuria > 1 g/d at baseline . Protein excretion rate decreased significantly from baseline in patients taking enalapril plus diuretics ( median -270 mg/d ; P amlodipine plus diuretics ( -25 mg/d at last observation ) . CONCLUSION In this cohort of nondiabetic , nonnephrotic hypertensive patients , no statistically significant difference in true GFR decline was found over 3 years between amlodipine-treated patients and enalapril-treated patients with main add-on treatment with ss-blockers , including in the subgroup of patients with proteinuria > 1 g/d", "Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient", "CONTEXT The NPPA gene codes for the precursor of atrial natriuretic polypeptide , suggesting that NPPA may modulate the efficacy of some antihypertensive drugs . OBJECTIVE To test whether participants with minor NPPA alleles in the T2238C or G664A variants had different rates of cardiovascular disease or blood pressure ( BP ) changes than common allele homozygotes when treated with a diuretic vs other antihypertensive medications . DESIGN , SETTING , AND PATIENTS Post hoc analysis of 38,462 participants with hypertension from ALLHAT , a multicenter r and omized clinical trial conducted in the United States and Canada . Genotyping was performed from February 2004 to January 2005 . INTERVENTION Participants were r and omly assigned to receive a diuretic ( chlorthalidone ; n = 13,860 ) , a calcium antagonist ( amlodipine ; n = 8174 ) , an angiotensin-converting enzyme inhibitor ( lisinopril ; n = 8233 ) , or an alpha-blocker ( doxazosin ; n = 8195 ) . MAIN OUTCOME MEASURE The primary outcome measure was coronary heart disease ( CHD ) , defined as fatal CHD or nonfatal myocardial infa rct ion ( mean follow-up , 4.9 years ) . Secondary outcomes were stroke , all-cause mortality , combined cardiovascular disease outcomes , and 6-month systolic and diastolic BP changes . Genotype x treatment interactions were tested where genotypes were modeled additively and dominantly . RESULTS Depending on genotype , the event rates per 1000 person-years were 15.3 to 19.7 for CHO , 9.6 to 15.4 for stroke , and 27.4 to 30.7 for all-cause mortality . For the NPPA T2238C variant , lower event rates were found for the C allele carriers than for the TT homozygous individuals when comparing chlorthalidone and amlodipine ( CHD : CC = 0.86 ; TC = 0.90 ; TT = 1.09 ; P = .03 [ dominant model ] ; stroke : CC = 1.18 ; TC = 0.82 ; TT = 1.26 ; P = .01 [ additive and dominant models ] ; all-cause mortality : CC = 0.87 ; TC = 0.98 ; TT = 1.12 ; P = .05 [ dominant model ] ) . Combined end points yielded similar results . Consistent with these clinical findings , 6-month changes in systolic BP for those with the CC genotype showed larger reductions with chlorthalidone ( -6.5 mm Hg ) than with amlodipine ( -3.8 mm Hg ) , lisinopril ( -2.4 mm Hg ) , or doxazosin ( -3.8 mm Hg ) . Among those with the TT genotype , systolic BP differences between drugs were less ( range , -5.4 to -7.5 mm Hg ; P value , diastolic BP showed similar results . We found no pharmacogenetic associations with the NPPA G664A variant . CONCLUSIONS The NPPA T2238C variant was associated with modification of antihypertensive medication effects on cardiovascular disease and BP . Minor C allele carriers experienced more favorable cardiovascular disease outcomes when r and omized to receive a diuretic , whereas TT allele carriers had more favorable outcomes when r and omized to receive a calcium channel blocker", "Abstract Background . Pulse pressure ( PP ) has been related to risk of cardiovascular events in hypertension . However , less is known about modification of this risk marker during antihypertensive treatment in patients with left ventricular ( LV ) hypertrophy . Methods . Associations of in-treatment PP with LV systolic function and cardiovascular events was assessed in 883 patients with electrocardiographic LV hypertrophy during 4.8 years of r and omized losartan- or atenolol-based treatment within the echocardiographic sub study of the Losartan Intervention For Endpoint reduction in hypertension ( LIFE ) study . Results . PP was similarly reduced by both treatments . In different multiple regression models , lower in-treatment PP was independently associated with lower in-treatment LV ejection fraction ( β=0.16 ) , stress-corrected midwall shortening ( β=0.20 ) , stroke volume ( β=0.11 ) and cardiac index ( β=0.07 , all p higher rate of cardiovascular events [ hazard ratio , HR = 1.28 ( 1.09 – 1.52 ) , p hypertensive patients with electrocardiographic LV hypertrophy , lower in-treatment PP was associated with lower in-treatment LV function and cardiac output as well as higher rate of cardiovascular events ", "WHAT IS KNOWN AND OBJECTIVE There is considerable interest in pharmacogenetic and molecular biomarkers . Our aim was to evaluate the effects of enalapril/lercanidipine combination on some emerging biomarkers for cardiovascular risk stratification of hypertensive patients , such as lipoprotein(a ) [ Lp(a ) ] , soluble advanced glycation end products ( sRAGE ) , soluble CD40 lig and ( sCD40L ) and serum myeloperoxidase ( MPO ) . RESEARCH DESIGN AND METHODS Three hundred and forty-five patients were enrolled in this r and omized , double-blind , clinical trial : 120 hypertensive patients were r and omized to enalapril 20 mg , 110 to lercanidipine 10 mg and 115 to enalapril/lercanidipine 20/10 mg fixed combination . We measures the following markers at baseline and after 6 , 12 , 18 and 24 months : blood pressure , fasting plasma glucose ( FPG ) , lipid profile , Lp(a ) , sRAGE , sCD40L and MPO . RESULTS There was a decrease in blood pressure in all groups compared with baseline , even if , as expected , enalapril/lercanidipine combination was more effective in reducing blood pressure compared with the monotherapies . No variations in lipid profile or FPG were recorded in any of the groups . Lercanidipine , but not enalapril , improved Lp(a ) levels compared with baseline . The combination enalapril/lercanidipine improved it more than the single therapies . All treatments increased sRAGE levels , and decreased sCD40L and MPO , with a better effect seen with the enalapril/lercanidipine combination compared with single monotherapies . WHAT IS NEW AND CONCLUSION The combination enalapril/lercanidipine seems to be better than the single monotherapies in reducing not only blood pressure , but also the levels of some emerging biomarkers , potentially useful for cardiovascular risk stratification of hypertensive patients" ]

[ "Probiotic supplementation has been part of the discussion on methods to enhance humoral immunity . Administration of Bifidobacterium bifidum OLB6378 ( OLB6378 ) reduced the incidence of late-onset sepsis in infants . In this non-r and omized study , we aim ed to determine the effect of administration of live OLB6378 on infants ’ humoral immunity . Secondly , we tried to eluci date whether similar effects would be observed with administration of non-live OLB6378 . Low birth weight ( LBW ) infants weighing 1500–2500 g were divided into three groups : Group N ( no intervention ) , Group L ( administered live OLB6378 concentrate ) , and Group H ( administered non-live OLB6378 concentrate ) . The interventions were started within 48 h after birth and continued until six months of age . Serum immunoglobulin G ( IgG ) levels ( IgG at one month/IgG at birth ) were significantly higher in Group L than in Group N ( p higher serum IgG levels ( p higher intestinal secretory immunoglobulin A ( SIgA ) levels ( p the mortality or morbidity between groups . Thus , OLB6378 administration in LBW infants enhanced humoral immunity , and non-live OLB6378 , which is more useful as a food ingredient , showed a more marked effect than the viable bacteria", "BACKGROUND Probiotics have strain specific effects and the effects of fungi in preventing diseases in preterm infants have been investigated poorly . Saccharomyces boulardii is a yeast which acts both as a probiotic and a polyamine producer . AIM The objective of this study was to investigate the efficacy of S. boulardii in preventing necrotizing enterocolitis ( NEC ) or sepsis in very low birth weight infants . STUDY DESIGN AND SUBJECTS A prospect i ve , double blind , placebo controlled trial was conducted in preterm infants ( ≤ 32 GWs , ≤ 1500 g birth weight ) . They were r and omized either to receive feeding supplementation with S. boulardii 50 mg/kg every 12 h or placebo , starting with the first feed until discharged . OUTCOME MEASURES Necrotizing enterocolitis ( NEC ) or sepsis and NEC or death . RESULTS Birth weight and gestational age of the study ( n = 104 ) and the control ( n = 104 ) groups were 1126 ± 232 vs 1162 ± 216 g and 28.8 ± 2.2 vs 28.7 ± 2.1 weeks , respectively . Neither the incidence of stage ≥ 2 NEC or death nor stage ≥ 2 NEC or late onset culture proven sepsis was significantly lower in the study group when compared with the control group ( 9.6 % vs 7.7 % , p = 0.62 ; 28.8 % vs 23 % , p = 0.34 ) . Time to reach 100 mL/kg/day of enteral feeding ( 11.9 ± 7 vs 12.6 ± 7 days , p = 0.37 ) was not different between the groups . CONCLUSIONS Saccharomyces boulardii did not decrease the incidence of NEC or sepsis", "BACKGROUND Probiotics may reduce necrotising enterocolitis and late-onset sepsis after preterm birth . However , there has been concern about the rigour and generalisability of some trials and there is no agreement about whether or not they should be used routinely . We aim ed to test the effectiveness of the probiotic Bifidobacterium breve BBG-001 to reduce necrotising enterocolitis , late-onset sepsis , and death in preterm infants . METHODS In this multicentre , r and omised controlled phase 3 study ( the PiPS trial ) , we recruited infants born between 23 and 30 weeks ' gestational age within 48 h of birth from 24 hospitals in southeast Engl and . Infants were r and omly assigned ( 1:1 ) to probiotic or placebo via a minimisation algorithm r and omisation programme . The probiotic intervention was B breve BBG-001 suspended in dilute elemental infant formula given enterally in a daily dose of 8·2 to 9·2 log10 CFU ; the placebo was dilute infant formula alone . Clinicians and families were masked to allocation . The primary outcomes were necrotising enterocolitis ( Bell stage 2 or 3 ) , blood culture positive sepsis more than 72 h after birth ; and death before discharge from hospital . All primary analyses were by intention to treat . This trial is registered with IS RCT N , number 05511098 and EudraCT , number 2006 - 003445 - 17 . FINDINGS Between July 1 , 2010 , and July 31 , 2013 , 1315 infants were recruited ; of whom 654 were allocated to probiotic and 661 to placebo . Five infants had consent withdrawn after r and omisation , thus 650 were analysed in the probiotic group and 660 in the placebo group . Rates of the primary outcomes did not differ significantly between the probiotic and placebo groups . 61 infants ( 9 % ) in the probiotic group had necrotising enterocolitis compared with 66 ( 10 % ) in the placebo group ( adjusted risk ratio 0·93 ( 95 % CI 0·68 - 1·27 ) ; 73 ( 11 % ) infants in the probiotics group had sepsis compared with 77 ( 12 % ) in the placebo group ( 0·97 ( 0·73 - 1·29 ) ; and 54 ( 8 % ) deaths occurred before discharge home in the probiotic group compared with 56 ( 9 % ) in the placebo group ( 0·93 [ 0·67 - 1·30 ] ) . No probiotic-associated adverse events were reported . INTERPRETATION There is no evidence of benefit for this intervention in this population ; this result does not support the routine use of B breve BBG-001 for prevention of necrotising enterocolitis and late-onset sepis in very preterm infants . FUNDING UK National Institute for Health Research Health Technology Assessment programme", "BACKGROUND AND OBJECTIVE : Late-onset sepsis frequently complicates prematurity , contributing to morbidity and mortality . Probiotics may reduce mortality and necrotizing enterocolitis ( NEC ) in preterm infants , with unclear effect on late-onset sepsis . This study aim ed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset sepsis . METHODS : A prospect i ve multicenter , double-blinded , placebo-controlled , r and omized trial compared daily administration of a probiotic combination ( Bifidobacterium infantis , Streptococcus thermophilus , and Bifidobacterium lactis , containing 1 × 109 total organisms ) with placebo ( maltodextrin ) in infants born before 32 completed weeks ’ gestation weighing The primary outcome was at least 1 episode of definite late-onset sepsis . RESULTS : Between October 2007 and November 2011 , 1099 very preterm infants from Australia and New Zeal and were r and omized . Rates of definite late-onset sepsis ( 16.2 % ) , NEC of Bell stage 2 or more ( 4.4 % ) , and mortality ( 5.1 % ) were low in controls , with high breast milk feeding rates ( 96.9 % ) . No significant difference in definite late-onset sepsis or all-cause mortality was found , but this probiotic combination reduced NEC of Bell stage 2 or more ( 2.0 % versus 4.4 % ; relative risk 0.46 , 95 % confidence interval 0.23 to 0.93 , P = .03 ; number needed to treat 43 , 95 % confidence interval 23 to 333 ) . CONCLUSIONS : The probiotics B infantis , S thermophilus , and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants , but not definite late-onset sepsis or mortality . Treatment with this combination of probiotics appears to be safe", "Background This study evaluated the benefit of Bifidobacterium bifidum OLB6378 ( B. bifidum ) in very low-birthweight ( VLBW ) infants ( birthweight for the acceleration of enteral feeding . Methods A cluster-r and omized , double-blind , placebo-controlled trial was conducted in 19 hospitals , divided into two groups : the B group ( n = 10 hospitals ; B. bifidum given to infants within 48 h of birth ) and the P group ( n = 9 hospitals ; infants received a placebo ) . The primary outcome was establishment of enteral feeding after birth , defined as the postnatal day at which enteral feeding exceeded 100 mL/(kg/day ) . Secondary outcomes were defined as incidence of morbidity and somatic growth before discharge . Results Overall , 283 VLBW infants were enrolled in the study : B group , n = 153 ; and P group , n = 130 . Enteral feeding was established within 21 days after birth in 233 infants , of whom 119 received B. bifidum and 114 received placebo until their bodyweight reached 2000 g. Enteral feeding was established significantly earlier in the B group , at 11.0 ± 3.6 days versus 12.1 ± 3.8days in P group ( P unit was not different between groups , but the incidence of late-onset sepsis among all enrolled infants was significantly lower in the B group ( 3.9 % , 6/153 ) than in the P group ( 10.0 % , 13/130 ; P in the incidence of other adverse outcomes including mortality . Conclusions B. bifidum in VLBW infants accelerated the establishment of enteral feeding after birth without increasing the incidence of adverse effects ", "Background The pathogenesis of bronchopulmonary dysplasia ( BPD ) is multifactorial . In addition to prenatal inflammation , postnatal malnutrition also affects lung development . Methods A retrospective study was performed to analyse during the first two weeks of life the total , enteral and parenteral nutrition of premature infants ( Results Ninety-five premature infants were analysed : 26 with BPD ( 27 ± 1 weeks ) and 69 without BPD ( 28 ± 1 weeks ) . There was no statistical significant difference in the total intake of fluids , calories , glucose or protein and weight gain per day in both groups . The risk of developing BPD was slightly increased in infants with cumulative caloric intake below the minimal requirement of 1230 kcal/kg and a cumulative protein intake below 43.5 g/kg . Furthermore , the risk of developing BPD was significantly higher when infants had a cumulative fluid intake above the recommended 1840 ml/kg . In infants who developed BPD , the enteral nutrition was significantly lower than in non-BPD infants [ 456 ml/kg ( IQR 744 , 235 ) vs. 685 ( IQR 987 , 511 ) ] . Infants who did not develop BPD reached 50 % of total enteral feeding significantly faster [ 9.6 days vs. 11.5 ] . Conclusions Preterm infants developing BPD received less enteral feeding , even though it was well compensated by the parenteral nutrient supply . Data suggest that a critical minimal amount of enteral feeding is required to prevent development of BPD ; however , a large prospect i ve clinical study is needed to prove this assumption", "BACKGROUND Preterm infants have increased intestinal permeability which can render them susceptible to infections from enterobacteriae . OBJECTIVES The primary objective was to investigate whether probiotic administration to preterm infants decreases intestinal permeability . Secondary outcomes studied were : somatic growth , tolerance , rates of sepsis and necrotizing enterocolitis . METHODS In a prospect i ve r and omized case-control study 41 stable preterm infants of 27 to 36 weeks gestation and 34 matched comparison infants consecutively admitted to the neonatal unit were studied . The study group received a preterm formula supplemented with Bifidobacter lactis ( 2 x 10(7 ) cfu/g of dry milk ) while the control group received the same formula but without supplementation . Intestinal permeability was measured within two days of birth and then seven and thirty days later using the sugar absorption test . Additionally anthropometric parameters were recorded throughout the study as well as acceptance and tolerance of the formula . RESULTS All infants tolerated the study formula well . Median counts of stool bifidobacteria and lactulose/mannitol ratios at baseline were comparable . After 7 days of supplementation median bifidobacteria counts were significantly higher in the study group than in the control group ( p=0.0356 ) and they remained higher to the end of the study ( p at day 30=0.075 ) . The L/M ratio in the study group was significantly lower at day 30 of the study as compared to the control group ( p=0.003 ) . Head growth was significantly higher in the study group ( p=0.001 ) . CONCLUSIONS The administration of a bifidobacter supplemented infant formula decreases intestinal permeability of preterm infants and leads to increased head growth", "Objective : The objective of this trial was to test whether probiotic-supplemented feeding to extremely low-birth-weight ( ELBW ) infants will improve growth as determined by decreasing the percentage of infants with weight below the 10th percentile at 34 weeks postmenstrual age ( PMA ) . Other important outcome measures , such as improving feeding tolerance determined by tolerating larger volume of feeding per day and reducing antimicrobial treatment days during the first 28 days from the initiation of feeding supplementation were also evaluated . Study Design : We conducted a multicenter r and omized controlled double-blinded clinical study . The probiotics-supplementation ( PS ) group received Lactobacillus rhamnosus GG and Bifidobacterium infantis added to the first enteral feeding and continued once daily with feedings thereafter until discharge or until 34 weeks ( PMA ) . The control ( C ) group received unsupplemented feedings . Infant weight and feeding volumes were recorded daily during the first 28 days of study period . Weights were also recorded at 34 weeks PMA . Result : A total of 101 infants were enrolled ( PS 50 versus C 51 ) . There was no difference between the two groups in the percentage of infants with weight below the 10th percentile at 34 weeks PMA ( PS group 58 % versus C group 60 % , ( P value 0.83 ) ) or in the average volume of feeding during 28 days after study entry ( PS group 59 ml kg−1 versus C group 71 ml kg−1 , ( P value 0.11 ) ) . Calculated growth velocity was higher in the PS group compared with the C group ( 14.9 versus 12.6 g per day , ( P value 0.05 ) ) . Incidences of necrotizing enterocolitis ( NEC ) , as well as mortality were similar between the two groups . Conclusion : Although probiotic-supplemented feedings improve growth velocity in ELBW infants , there was no improvement in the percentage of infants with growth delay at 34 weeks PMA . There were no probiotic-related adverse events reported", "OBJECTIVE To evaluate the growth and neurodevelopment outcomes of very low-birth-weight ( VLBW ) preterm infants supplemented with oral probiotics for the prevention of necrotizing enterocolitis ( NEC ) . STUDY DESIGN This prospect i ve follow-up study was conducted in a cohort of VLBW preterm infants enrolled in a r and omized controlled clinical trial to evaluate the efficacy of oral probiotics for the prevention of NEC . Growth outcomes included weight , length , and head circumference . Cognitive and neuromotor development were assessed by using the Bayley Scales of Infant Development II . Sensory and neurological performance was evaluated by st and ard techniques . The primary outcome was neurodevelopmental impairment at 18 to 22 months ' corrected age . RESULTS A total of 221 infants completed the trial protocol . Of the 208 infants eligible for follow-up , 174 infants ( 86 in the probiotics group and 88 in the control group ) were evaluated . There was no significant difference in growth and neurodevelopmental outcomes between the two groups . CONCLUSION Oral probiotic administered to VLBW infants to reduce the incidence and severity of NEC started with the first feed did not affect growth , neuromotor , neurosensory , and cognitive outcomes at 18 to 22 months ' corrected age", "OBJECTIVE To test the efficacy of probiotic and prebiotic , alone or combined ( synbiotic ) , on the prevention of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants . STUDY DESIGN A prospect i ve , r and omized , controlled trial was conducted at 5 neonatal intensive care units in Turkey . VLBW infants ( n = 400 ) were assigned to a control group and 3 study groups that were given probiotic ( Bifidobacterium lactis ) , prebiotic ( inulin ) , or synbiotic ( Bifidobacterium lactis plus inulin ) added to breastmilk or formula for a maximum of 8 weeks before discharge or death . The primary outcome was NEC ( Bell stage ≥2 ) . RESULTS The rate of NEC was lower in probiotic ( 2.0 % ) and synbiotic ( 4.0 % ) groups compared with prebiotic ( 12.0 % ) and placebo ( 18.0 % ) groups ( P The times to reach full enteral feeding were faster ( P the rates of clinical nosocomial sepsis were lower ( P = .004 ) , stays in the neonatal intensive care unit were shorter , ( P = .002 ) , and mortality rates were lower ( P = .003 ) for infants receiving probiotics , prebiotics , or synbiotic than controls . The use of antenatal steroid ( OR 0.5 , 95 % CI 0.3 - 0.9 ) and postnatal probiotic ( alone or in synbiotic ) ( OR 0.5 , 95 % CI 0.2 - 0.8 ) decreased the risk of NEC , and maternal antibiotic exposure increased this risk ( OR 1.9 , 95 % CI 1.1 - 3.6 ) . CONCLUSIONS In VLBW infants , probiotic ( Bifidobacterium lactis ) and synbiotic ( Bifidobacterium lactis plus inulin ) but not prebiotic ( inulin ) alone decrease NEC", "Abstract Objective : The aim of the study was to evaluate the neurodevelopment outcomes of very low birth weight ( VLBW ) preterm infants supplemented with oral probiotics for the prevention of necrotizing enterocolitis ( NEC ) . Methods : A prospect i ve follow-up study was performed in a cohort of VLBW preterm infants enrolled in a single center r and omized controlled clinical trial to evaluate the efficacy of oral probiotics for the prevention of NEC . Cognitive and neuromotor developments were assessed by using the Bayley scales of infant development II . Sensory and neurological performance was evaluated by st and ard techniques . The primary outcome was neurodevelopmental impairment at 18–24 months ’ corrected age . Results : A total of 400 infants completed the trial protocol . Of the 370 infants eligible for follow-up , 249 infants ( 124 in the probiotics group and 125 in the control group ) were evaluated . There was no significant difference in any of the neurodevelopmental and sensory outcomes between the two groups . Conclusion : Oral probiotic given to VLBW infants to reduce the incidense and severity of NEC started with the first feed did not affect neuromotor , neurosensory and cognitive outcomes at 18–24 months ’ corrected age", "We hypothesized that giving the probiotic strain Lactobacillus reuteri ( L. reuteri ) DSM 17938 to preterm , formula-fed infants would prevent an early traumatic intestinal inflammatory insult modulating intestinal cytokine profile and reducing the onset of feeding intolerance . Newborn were r and omly allocated during the first 48 h of life to receive either daily probiotic ( 108 colony forming units ( CFUs ) of L. reuteri DSM 17938 ) or placebo for one month . All the newborns underwent to gastric ultrasound for the measurement of gastric emptying time . Fecal sample s were collected for the evaluation of fecal cytokines . Clinical data on feeding intolerance and weight gain were collected . The costs of hospital stays were calculated . The results showed that the newborns receiving L. reuteri DSM 17938 had a significant decrease in the number of days needed to reach full enteral feeding ( p days of hospital stay ( p days of antibiotic treatment ( p fecal cytokine profiles . The anti-inflammatory cytokine interleukin (IL)-10 , was increased in newborns receiving L. reuteri DSM 17938 . Pro-inflammatory cytokines : IL-17 , IL-8 , and tumor necrosis factor (TNF)-alpha levels were increased in newborns given placebo . Differences in the gastric emptying and fasting antral area ( FAA ) were also observed . Our study demonstrates an effective role for L. reuteri DSM 17938 supplementation in preventing feeding intolerance and improving gut motor and immune function development in bottle-fed stable preterm newborns . Another benefit from the use of probiotics is the reducing cost for the Health Care service", "BACKGROUND Necrotizing enterocolitis ( NEC ) is the most serious gastrointestinal problem in very low birth weight preterm infants . Multiple risk factors activate the inflammatory cascade leading to high expressions of pro-inflammatory mediators causing bowel injury in NEC . The anti-inflammatory effect of probiotics is due to the inhibition and reduction of inflammatory signal in intestinal epithelium . OBJECTIVE To evaluate the efficacy of probiotics supplementation in the prevention of NEC among very low birth weight preterm infants . STUDY DESIGN A prospect i ve r and omized controlled trial . MATERIAL AND METHOD All preterm infants with gestational age less than or equal to 34 weeks and birth weight less than or equal to 1,500 grams admitted in neonatal care unit , Queen Sirikit National Institute of Child Health during June 1st , 2012 and January 31th , 2013 were enrolled in this study . They were r and omized into two groups , study and control group . Infants in the study group were fed Infloran ( Lactobacillus acidophilus 1 x 10(9 ) and Bifidobacterium bifidum 1 x 10(9 ) organisms ) dose 125 mg/kg/dose twice a day with breast milk or premature formula from the start of feeding until 6 weeks or discharge . Infants in the control group were fed with either breast milk or premature formula alone . The primary outcome was NEC stage ≥ 2 . RESULTS Sixty infants completed the study , 31 infants in the study group and 29 infants in the control group . The baseline characteristic data of infants were similar except for more males in the present study group . Incidence of NEC stage ≥ 2 were similar in both the groups , 3.2 vs. 3.4 % ( p = 0.74 ) . There were no deaths during the study period . Days to reach full feeding , 150 ml/kg/day , were no differences between the two groups , 12.03 ± 5.49 days vs. 13.76 ± 8.25 days ( p = 0.31 ) . No adverse effects such as sepsis , flatulence or diarrhea were noted . CONCLUSION In this study , there was no difference in incidence of NEC stage ≥ 2 between the two groups . No adverse effects of probiotics supplementation were observed", "A novel combination of culturing and DNA-based terminal restriction fragment length polymorphism ( TRFLP ) analysis was used to investigate the effect of probiotics on antibiotic-induced gut microbiota alterations to determine if a probiotic preparation containing bifidobacteria and lactobacilli , taken during and after antibiotic therapy , can minimize antibiotic disturbance of faecal microbiota . Healthy subjects administered amoxicillin/clavulanate were r and omized and concomitantly received a placebo or probiotic mixture . The primary end point was similarity of faecal microbiota as determined by culturing and TRFLP from subjects taking probiotics compared to those taking a placebo measured by comparing data from baseline to post-treatment for each subject . TRFLP analysis revealed a high subject to subject variation in the baseline faecal microbiota . The most common antibiotic-induced disturbance was a relative increase in Clostridium , Eubacterium , Bacteroides and Enterobacteraceae . The mean similarity to the baseline increased over time in both treatment groups , although the probiotic group was less disturbed according to both TRFLP and culture data . The culture method revealed that post-antibiotic faecal microbiota in probiotic-consuming subjects were more similar to the baseline microbiota than the control group ( P=0.046 ) . Changes in Enterobactereaceae ( P=0.006 ) and Bifidobacterium ( P=0.030 ) counts were significantly different between the groups . Analysis of TRFLP data reinforced the trend between groups but was not statistically significant ( P=0.066 ) . This study indicates this mixture of probiotics promotes a more rapid return to pre-antibiotic baseline faecal bacterial microbiota", "RATIONALE Bronchopulmonary dysplasia is the most common morbidity of prematurity , but the validity and utility of commonly used definitions have been question ed . OBJECTIVES To compare three commonly used definitions of bronchopulmonary dysplasia in a contemporary prospect i ve , multicenter observational cohort of extremely preterm infants . METHODS At 36 weeks postmenstrual age , the following definitions of bronchopulmonary dysplasia were applied to surviving infants with and without imputation : need for supplemental oxygen ( Shennan definition ) , National Institutes of Health Workshop definition , and \" physiologic \" definition after a room-air challenge . MEASUREMENTS AND MAIN RESULTS Of 765 survivors assessed at 36 weeks , bronchopulmonary dysplasia was diagnosed in 40.8 , 58.6 , and 32.0 % of infants , respectively , with the Shennan , workshop and physiologic definitions . The number of unclassified infants was lowest with the workshop definition ( 2.1 % ) and highest with the physiologic definition ( 16.1 % ) . After assigning infants discharged home in room air before 36 weeks as no bronchopulmonary dysplasia , the modified Shennan definition compared favorably to the workshop definition , with 2.9 % unclassified infants . Newer management strategies with nasal cannula flows up to 4 L/min or more and 0.21 FiO2 at 36 weeks obscured classification of bronchopulmonary dysplasia status in 12.4 % of infants . CONCLUSIONS Existing definitions of bronchopulmonary dysplasia differ with respect to ease of data collection and number of unclassifiable cases . Contemporary changes in management of infants , such as use of high-flow nasal cannula , limit application of existing definitions and may result in misclassification . A contemporary definition of bronchopulmonary dysplasia that correlates with respiratory morbidity in childhood is needed . Clinical trial registered with www . clinical trials.gov ( NCT01435187 )" ]

[ "OBJECTIVE To determine the role of ultrasound and magnetic resonance imaging ( MRI ) compared with conventional radiography in the detection of chronic and acute inflammatory manifestations of rheumatoid arthritis ( RA ) of the shoulder joint . METHODS Forty-three consecutive patients with known RA prospect ively underwent clinical examination , radiography , ultrasound , and MRI of the shoulder joints . Each patient was assigned a clinical /laboratory score consisting of 7 parameters , including measurements of shoulder mobility , the erythrocyte sedimentation rate , and C-reactive protein level . Conventional radiography was st and ardized and performed in 2 planes . Ultrasound was performed in 10 predefined planes using a 7.5-MHz linear transducer . MRI at 1.5 T comprised transverse and oblique coronal T1- and T2 * -weighted fast spin-echo , gradient-echo ( GRE ) , and inversion-recovery sequences with a matrix size of up to 512 pixels . A dynamic T1-weighted GRE sequence was acquired with intravenous administration of contrast medium . Erosions were assessed using all 3 imaging techniques on a 4-point scale . Soft-tissue involvement was evaluated according to the presence of synovitis , tenosynovitis , and bursitis on ultrasound and MRI . The results in the study group were compared with those obtained in a control group of 10 patients with shoulder pain . RESULTS In the study group , erosions of the humeroscapular joint were detected by conventional radiography in 26 patients , by ultrasound in 30 patients , and by MRI in 39 patients ; the differences were statistically significant for the comparisons of conventional radiography with MRI and for ultrasound versus MRI ( P Conventional radiography detected 12 erosions of the scapula and MRI detected 15 . Synovitis was demonstrated in 12 patients by ultrasound and in 27 patients by MRI ( P = 0.0003 ) . Tenosynovitis was observed in 15 patients by ultrasound and in 28 patients by MRI ( P = 0.0064 ) . Bursitis was detected in 13 patients by ultrasound and in 18 patients by MRI . The findings on dynamic contrast-enhanced MRI correlated significantly with the detection of synovitis by ultrasound and erosions by static MRI ( P Ultrasound and MRI supplement conventional radiography in assessing the shoulder joint . Although conventional radiography can be used as the sole method of following up known joint destruction in RA , ultrasound and , preferably , MRI are recommended as additional techniques in the initial diagnostic evaluation when radiography yields negative results", "OBJECTIVES To evaluate the role of magnetic resonance imaging ( MRI ) of the wrist in detecting early joint damage in patients with rheumatoid arthritis ( RA ) . METHODS MRI was performed on 42 patients with early RA ( median symptom duration of four months ) . Scans were scored separately by two musculoskeletal radiologists using a newly devised scoring system , which was vali date d. MRI findings were compared with plain radiography , clinical measures , and HLA-DRB*01/04 genotyping . RESULTS Interobserver reliability for the overall MRI score was high ( r = 0.81 ) as was intraobserver reliability ( r = 0.94 for observer 1 and 0.81 for observer 2 ) . There was more variation in scoring synovitis ( interobserver reliability : r = 0.74 ) . Erosions were detected in 45 % of scans ( 19 of 42 ) , compared with 15 % of plain radiographs . The most common site for erosions was the capitate ( 39 % ) , for synovitis the ulnar aspect of the radiocarpal joint , and for tendonitis , the extensor carpi ulnaris tendon . The total MRI score and MRI synovitis score correlated most significantly with C reactive protein ( r = 0.40 and 0.42 respectively , p MRI erosion score was highly correlated with MRI bone marrow oedema ( r = 0.83 ) as well as the Ritchie score and disease activity score ( r = 0.32 , p HLA-DRB1 * 04 or * 01 ( shared epitope + ve ) was found in 76 % of patients ; 84 % of those with MRI erosions and 69 % of those without ( NS , p = 0.3 ) . CONCLUSIONS A high proportion of RA patients develop MRI erosions very early in their disease , when plain radiography is frequently normal . MRI of the dominant wrist may identify those requiring early aggressive treatment", "Objective . To evaluate the sensitivity and specificity of magnetic resonance imaging ( MRI ) in detecting erosions , bone edema , and synovitis in the metacarpophalangeal and wrist joints for rheumatoid arthritis ( RA ) . Methods . MRI scans of bilateral h and s and wrists of 40 healthy subjects and 40 RA patients were performed using 0.2 T extremity-MRI and read blindly using a modified RA MRI ( RAMRIS ) system ( no contrast injection , imaging in 1 plane only ) . To determine interreader reliability , images of 10 r and omly selected subjects were read independently by a musculoskeletal radiologist . Results . A total of 3360 bones were evaluated . Patients with RA had significantly more erosions as well as higher scores for bone edema and synovitis than healthy subjects . Age had a significant effect on the number of erosions in both groups . However , when disease duration was factored in , age became insignificant in RA patients . Erosion number correlated with positive rheumatoid factor and higher C-reactive protein values . The intraclass correlation coefficient between the 2 readers was 0.76 for individual joints and 0.88 for total scores . When having a single erosion was used as a positive test for RA , the sensitivity of this test was 90 % , but the specificity was only 35 % . Presence of bone edema provided 65 % sensitivity and 82.5 % specificity . Eliminating the lunate from scoring for bone edema increased the specificity to 87.5 % while decreasing the sensitivity to 62.5 % . Conclusion . While MRI is a highly sensitive tool for identifying and tracking the progression of erosions , erosions detected by MRI with measures commonly used in a rheumatologist ’s office ( no contrast , imaging in 1 plane ) provide low specificity for RA . Bone marrow edema is the most specific MRI lesion for RA in this setting", "Objectives To determine the accuracy of ultrasonography ( US ) for bone erosion detection in different areas of rheumatoid arthritis ( RA ) metacarpophalangeal ( MCP ) joints with multislice CT as the reference method . Second , to establish the necessary bone volume loss on CT for US to reliably detect it as an erosion , and finally to compare two semiquantitative US-erosion scoring methods . Methods The 2nd–5th MCP joints of 49 patients with RA were examined by CT and US , and evaluated for the presence of bone erosion in each MCP joint quadrant . On CT , erosion volume was scored according to the OMERACT-RAMRIS score ( bone volume loss in 10 % increments of original bone volume ) . US erosions were scored 0–3 according to the Szkudlarek and Scoring by UltraSound Structural erosion ( ScUSSe ) systems , respectively . Results Seven hundred and eighty-four MCP joint quadrants were examined . Erosions were detected by CT in 259 quadrants and by US in 142 quadrants . Sensitivity/specificity/accuracy of US was overall 44%/95%/78 % compared with 71%/95%/90 % in areas with good US accessibility ( radial 2nd MCP , ulnar 5th MCP and all dorsal/palmar aspects ) . US detected 95 % of erosions with bone volume loss > 20 % . In US accessible areas , 63 % of erosions with 1–10 % bone volume loss and 94 % of erosions with > 10 % bone loss were detected . The two US scoring systems agreed well on large erosions , whereas the smallest erosions ( Szkudlarek grade 1 , of which 86 % were confirmed by CT ) were not scored by ScUSSe . Conclusion In accessible areas , US was highly accurate for detection and semiquantitative assessment of RA bone erosion . Even the smallest erosions , only detected in one plane , were generally confirmed by CT", "OBJECTIVE Magnetic resonance imaging ( MRI ) is capable of revealing synovitis and tendinitis in early rheumatoid arthritis ( RA ) , as well as bone edema and erosion . These features are visible before radiographic joint damage occurs . We sought to examine whether MRI of one body region ( the wrist ) can be used to predict whole-body radiography scores reflecting joint damage at 6 years . METHODS We conducted a 6-year prospect i ve study of a cohort of patients who fulfilled the criteria for RA at presentation , using clinical parameters , radiographs , and MRI scans of the dominant wrist . Of the 42 patients enrolled at baseline , full MRI , radiographic , and clinical data were available for 31 at 6-year followup . MRI scans were scored by 2 radiologists , using a vali date d scoring system . Radiographs of the h and s and feet were grade d using the modified Sharp scoring method . MRI and radiography scores obtained at baseline and 6 years were compared , and baseline MRI scores were examined for their ability to predict radiographic outcome at 6 years . RESULTS At 6 years , the total Sharp score correlated significantly with the total MRI score and the MRI erosion score ( r = 0.81 , P 6-year Sharp score also correlated with the baseline total MRI and MRI erosion scores ( r = 0.56 , P MRI synovitis and bone edema scores remained constant for the group as a whole over 6 years , but bone erosion scores progressed ( P = 0.0001 ) , consistent with radiographic deterioration . Erosions on 6-year MRI scans were frequently preceded by MRI bone edema at baseline ( odds ratio 6.5 , 95 % confidence interval 2.78 - 18.1 ) . Regression models indicated that the baseline MRI bone edema score was predictive of the 6-year total Sharp score ( P = 0.01 ) , as was the C-reactive protein ( CRP ) level ( P = 0.0002 ) . Neither shared epitope status nor swollen or tender joint counts predicted radiographic outcome in this cohort . A model incorporating baseline MRI scores for erosion , bone edema , synovitis , and tendinitis plus the CRP level and the erythrocyte sedimentation rate explained 59 % of the variance in the 6-year total Sharp score ( R(2 ) = 0.59 , adjusted R(2 ) = 0.44 ) . CONCLUSION MRI scans performed at the first presentation of RA can be used to help predict future radiographic damage , allowing disease-modifying therapy to be targeted to patients with aggressive disease", "OBJECTIVE To simultaneously image bone and synovium in the individual joints characteristically involved in early rheumatoid arthritis ( RA ) . METHODS Forty patients with early , untreated RA underwent gadolinium-enhanced magnetic resonance imaging ( MRI ) of the second through fifth metacarpophalangeal joints of the dominant h and at presentation , 3 months , and 12 months . In the first phase ( 0 - 3 months ) , patients were r and omized to receive either methotrexate alone ( MTX ) or MTX and intraarticular corticosteroids ( MTX + IAST ) into all joints with clinical ly active RA . The MTX-alone group received no further corticosteroids until the second phase ( 3 - 12 months ) , when both groups received st and ard therapy . RESULTS In the first phase , MTX + IAST reduced synovitis scores more than MTX alone . There were significantly fewer joints with new erosions on MRI in the former group compared with the latter . During the second phase , the synovitis scores were equivalent and a similar number of joints in each group showed new erosions on MRI . In both phases , there was a close correlation between the degree of synovitis and the number of new erosions , with the area under the curve for MRI synovitis the only significant predictor of bone damage progression . In individual joints , there was a threshold effect on new bone damage related to the level of synovitis ; no erosions occurred in joints without synovitis . CONCLUSION In early RA , synovitis appears to be the primary abnormality , and bone damage occurs in proportion to the level of synovitis but not in its absence . In the treatment of patients with RA , outcome measures and therapies should focus on synovitis", "We prospect ively evaluated the diagnostic value of sonography and magnetic resonance imaging ( MRI ) in 24 shoulders in 23 patients with suspected rotator cuff tears using arthrography as gold st and ard . Sonography demonstrated 14 of 15 , MRI 10 of 15 rotator cuff tears , respectively . Sonography diagnosed seven of nine intact rotator cuffs correctly , MRI eight of nine . In a retrospective study we review ed the diagnostic value of sonography and MRI in other pathologies of the shoulder including intra-articular pathology , humeral head and acromioclavicular joint pathology , and calcification . We conclude that with regard to cost and patient compliance , sonography should be the first radiologic examination in suspected rotator cuff tears if performed by an experienced sonographer . MRI is superior in depicting additional pathology and is less operator dependent . It may thus become the method of choice for the evaluation of the rotator cuff and related pathology in the future", "OBJECTIVES To determine the accuracy of ultrasound in early detection of bone erosions and monitoring disease activity in rheumatoid arthritis ( RA ) patients using magnetic resonance imaging ( MRI ) as a gold st and ard technique . MATERIAL AND METHODS This prospect i ve study was carried out on 50 patients with known RA and 15 healthy controls . Conventional radiography was st and ardized and performed in two planes . Ultrasound ( US ) and MRI was performed to evaluate the presence of synovitis , tenosynovitis , and bursitis as well as erosions on ultrasound and MRI . The results in the study group were compared with those obtained in a control group . RESULT In the study group , the most frequent US finding of shoulder joint was Tenosynovitis of the long head of the biceps tendon . Tenosynovitis was observed in the long head of biceps tendon in 20 joints ( 40 % ) . Erosions of the humeroscapular joint were detected by conventional radiography in 15 ( 30 % ) , by US in 41 ( 82 % ) , and by MRI in 46 ( 92 % ) of the shoulders examined , no statistically significant difference is noted between US and MRI in overall detection of erosion ( P = .333 ) . CONCLUSION US is a helpful imaging method and in comparison with MRI in assessing the shoulder joint and , preferably with MRI , are recommended as additional techniques in the initial diagnostic evaluation when radiography yields negative results", "PURPOSE To evaluate prospect ively the use of magnetic resonance ( MR ) imaging for differentiating true rheumatoid arthritis ( RA ) from systemic lupus erythematosus ( SLE ) or primary Sjögren syndrome in patients who have inflammatory polyarthralgia of the h and s but no radiographic evidence of RA . MATERIAL S AND METHODS This study had institutional review board approval , and patient informed consent was obtained . Twenty-eight patients ( 16 female and 12 male patients ; mean age , 42 years ) with early RA and 19 patients ( 18 female and one male patient ; mean age , 46 years ) with SLE ( n = 14 ) or primary Sjögren syndrome ( n = 5 ) underwent MR imaging of both h and s. All patients had inflammatory polyarthralgia of the h and s and no evidence of erosive changes on radiographs . Coronal T2-weighted short inversion time inversion-recovery , transverse T1-weighted spin-echo , transverse fat-suppressed gadolinium-enhanced T1-weighted spin-echo , and transverse gadolinium-enhanced three-dimensional gradient-echo MR images were obtained . The following MR imaging variables were assessed in the wrist and nonthumb metacarpophalangeal joints : synovitis , bone lesions ( erosion , defect , and edema ) , and tenosynovitis . Synovitis and bone lesions were scored with the OMERACT RA-MRI scoring system . Findings in patients with RA and those without RA were compared by means of Mann-Whitney , chi2 , and Fisher exact tests . RESULTS The only significant difference between the two groups in terms of individual scores for synovitis , bone lesions , and tenosynovitis was the more frequent presence of tenosynovitis of the right fourth extensor tendon in patients without RA ( P = .04 ) . There were no significant differences between patients with RA and those without RA in terms of global scores for synovitis , bone lesions , and tenosynovitis . However , bone marrow edema in the metacarpophalangeal joints was seen more frequently in patients with RA ( P patients with early RA and those without RA ( ie , those with SLE or primary Sjögren syndrome ) by means of MR imaging", "Objective To evaluate the diagnostic potential of susceptibility-weighted imaging ( SWI ) for the detection of erosions of the h and , compared to T1-weighted ( T1w ) magnetic resonance imaging ( MRI ) . Computed tomography ( CT ) was used as a reference st and ard . Material s and methods We prospect ively investigated 37 patients with suspected arthritic activity of the h and . All patients underwent T1w , SWI , and CT on the same day . Patients were r and omized to MRI or CT first . CT , T1w , SWI , and T1w/SWI were scored for erosions according to OMERACT RAMRIS guidelines . Specificity , sensitivity , and diagnostic accuracy were separately calculated for T1w , SWI , and T1w/SWI on a per-patient and per-bone basis using CT as reference . The one-tailed McNemar test was performed to test the number of erosion-positive patients in T1w , SWI , and T1w/SWI for non-inferiority . Measured erosion sizes were compared using Pearson ’s test . Results CT was positive for erosions in 16 patients and 55 bones . SWI and T1w/SWI had superior diagnostic accuracy ( 91.2 and 93.8 % ) compared to T1w ( 87.8 % ) driven by a higher specificity ( 93.8 and 96.5 % ) compared to T1w ( 88.8 % ) . On the patient level , SWI and T1w/SWI showed non-inferiority ( p = 0.11 and p = 0.38 ) but not T1w alone ( p lesion size on CT correlated better with SWI ( Pearson ’s r = 0.92 ) compared to T1w ( r = 0.69 ) . Conclusions Adding SWI to a st and ard MRI protocol has the potential to improve erosion detection in h and s by increasing specificity . SWI depicts bony erosions more accurately compared to st and ard MRI techniques", "Objective : To identify predictors of radiographic progression in a 2-year r and omised , double-blind , clinical study ( CIMESTRA ) of patients with early rheumatoid arthritis ( RA ) . Methods : Patients with early RA ( n = 130 ) were treated with methotrexate , intra-articular betamethasone and ciclosporin/placebo-ciclosporin . Baseline magnetic resonance imaging ( MRI ) of the wrist ( wrist-only group , n = 130 ) or MRI of wrist and metacarpophalangeal ( MCP ) joints ( wrist+MCP group , n = 89 ) ( OMERACT RAMRIS ) , x-ray examination of h and s , wrists and forefeet ( Sharp/van der Heijde Score ( TSS ) ) , Disease Activity Score ( DAS28 ) , anti-cyclic citrullinated peptide antibodies ( anti-CCP ) , HLA-DRB1-shared epitope ( SE ) and smoking status were assessed . Multiple regression analysis was performed with delta-TSS ( 0–2 years ) as dependent variable and baseline DAS28 , TSS , MRI bone oedema score , MRI synovitis score , MRI erosion score , anti-CCP , smoking , SE , age and gender as explanatory variables . Results : Baseline values : median DAS28 5.6 ( range 2.4–8.0 ) ; anti-CCP positive 61 % ; radiographic erosions 56 % . At 2 years : DAS28 2.0 ( 0.5–5.7 ) , in DAS remission : 56 % , radiographic progression 26 % ( wrist+MCP group , similar for wrist-only group ) . MRI bone oedema score was the only independent predictor of delta-TSS ( wrist+MCP group : coefficient = 0.75 ( 95 % CI 0.55 to 0.94 ) , p p score explained 41 % of the variation in the progression of TSS ( wrist+MCP group ) , 25 % in wrist-only group ( Pearson ’s r = 0.64 and r = 0.50 , respectively ) . Results were confirmed by sensitivity analyses . Conclusion : In a r and omised controlled trial aim ing at remission in patients with early RA , baseline RAMRIS MRI bone oedema score of MCP and wrist joints ( and of wrist only ) was the strongest independent predictor of radiographic progression in h and s , wrists and forefeet after 2 years . MRI synovitis score , MRI erosion score , DAS28 , anti-CCP , SE , smoking , age and gender were not independent risk factors . Trial registration number : NCT00209859", "Objective . In rheumatology , magnetic resonance imaging ( MRI ) is predominantly applied in the assessment and outcome measurement of rheumatoid arthritis ( RA ) in h and s and wrists , leading to the development of the RAMRIS ( RA-MRI-Scoring ) system . It was initiated by the Outcome Measures in Rheumatoid Arthritis Clinical Trials ( OMERACT ) . The RAMRIS system has not been applied widely in the measurement of feet . We investigated the interreader and intrareader agreement of the RAMRIS scoring system in the assessment of feet in RA . Methods . Twenty-nine patients with RA who had radiological damage and /or arthritis underwent MRI . Two experienced readers independently read both complete sets . One reader read 6 r and om sets after the initial session , in order to assess the intrareader agreement . For evaluation of the intrareader and interreader reliability , quadratic-weighted κ scores were calculated per joint and lesion . Results . For the forefeet , interreader scores were excellent , ranging from 0.77 ( bone edema ) to 0.95 ( bone erosion ) . Hindfoot interreader agreement scores were highest for erosion ( 0.90 ) and synovitis global score ( 0.88 ) , but edema and synovial thickness agreement were also acceptable ( 0.83 and 0.86 ) . Intrareader scores were on the whole slightly lower , but excellent . Conclusion . Reliability ( interreader and intrareader agreement ) in the assessment of the rheumatoid foot according to the RAMRIS method is excellent" ]

[ "The objective of this r and omized study was to determine if fiber-supplemented soy formula reduced regurgitation in young infants . We compared regurgitation in 179 infants r and omly assigned cow ’s milk-based ( CM , 90 ) formula or soy formula with fiber ( SF , 89 ) . Initial daily incidence was similar ( CM , 3.6 ; SF , 3.9 episodes ) , but significantly lower after 7 days on SF ( CM , 3.4 ; SF , 2.3 ; p = 0.001 ) . Less frequent regurgitation after 7 days on SF was sustained after 28 days ( CM , 48 % ; SF , 31 % of feedings ; p = 0.001 ) . Feeding SF effectively managed regurgitation while providing balanced nutrition without altering caloric distribution as occurs with adding rice cereal to formula", "Purpose The use of soy products is common in young children with cow milk allergy ( CMA ) . The aim was to examine prospect ively the association between infantile consumption of soy-based formula , growth parameters and early pubertal signs , in comparison to cow milk-based formula . Methods A nested case – control study was conducted , selected from a cohort of infants prospect ively followed from birth until the age of 3 years for eating habits and the development of IgE-mediated CMA . Infants who consumed only soy-based formula were included in the soy group . The control group was r and omly selected from those without IgE-CMA and not receiving soy formula . Study participants were reevaluated between ages 7.8 and 10.5 years by an interview , nutritional intake by 3 days diaries , and height , weight , and pubertal signs by physical examination . Results The soy-fed group included 29 participants ( 17 males ) , median age 8.92 years IQR ( 8.21 , 9.42 ) . The control group included 60 participants ( 27 males ) , median age 8.99 years IQR ( 8.35 , 9.42 ) . The groups had comparable height and BMI z scores ( − 0.17 ± 1.08 versus − 0.16 ± 1.01 , p = 0.96 , and 0.67 ± 1.01 versus 0.53 ± 1.02 , p = 0.56 , for soy and control groups , respectively ) . Four ( three males and one female ) from the soy-group ( 13.8 % ) and eight females from the control-group ( 13.3 % ) had early pubertal signs ( p = 0.95 ) . No association was detected between puberty and infantile nutrition , after controlling for BMI and family data . No association with puberty or differences between groups were found in current daily consumption of soy , micronutrients , energy , carbohydrates , fat , and protein . Conclusions This is the first prospect i ve , physical examination-based study , demonstrating no association between infantile soy-based formula consumption and growth and puberty parameters", "BACKGROUND Early feeding with cow 's milk ( CM ) may increase the risk of cow 's milk allergy ( CMA ) . OBJECTIVE We sought to examine prospect ively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared with feeding with pasteurized human milk or hydrolyzed formula . METHODS We studied 6209 unselected healthy , full-term infants , of whom 5385 ( 87 % ) required supplementary milk while in the hospital . The infants were r and omly assigned to receive CM formula ( 1789 infants ) , pasteurized human milk ( 1859 infants ) , or whey hydrolysate formula ( 1737 infants ) . The comparison group ( 824 infants ) was composed of infants who were exclusively breast-fed . The infants were followed for 18 to 34 months for symptoms suggestive of CMA . The primary endpoint was a challenge-proven adverse reaction to CM after a successful CM elimination diet . RESULTS The cumulative incidence of CMA in the infants fed CM was 2.4 % compared with 1.7 % in the pasteurized human milk group ( odds ratio [ OR ] , 0.70 ; 95 % confidence interval [ CI ] , 0 . 44 - 1.12 ) and 1.5 % in the whey hydrolysate group ( OR , 0.61 ; 95 % CI , 0 . 38 - 1.00 ) . In the comparison group , CMA developed in 2.1 % of the infants . Among the infants who required supplementary feeding at hospital , both exposure to CM while in the hospital ( OR , 1.54 ; 95 % CI , 1.04 - 2.30 ; P = .03 ) and obvious parental atopy ( OR , 2.32 ; 95 % CI , 1.53 - 3.52 ; P CMA . CONCLUSIONS Our data indicate that feeding of CM at maternity hospitals increases the risk of CMA when compared with feeding of other supplements , but exclusive breast-feeding does not eliminate the risk", "BACKGROUND Hydrolyzed formulas used to feed infants with cow 's milk-allergy can be classified as soy based , extensively hydrolyzed ( casein , whey and mixed ) , and amino-acid based . Their unsatisfactory taste is reported by parents and physicians . OBJECTIVE The aim of this study was to ascertain the palatability of these formulas in a double-blind taste test . MATERIAL S AND METHODS Fifty healthy volunteers performed a r and omized-order double-blind test with 12 different milks . The taste , smell , smell , and texture of each formula were evaluated o n scales ranging from 1 ( worst ) t o 5 ( best ) . The Pearson correlation coefficient between the peptide weight of each formula and the score obtained for each evaluated attribute was calculated . RESULTS The soy formulas and rice formula had the best taste scores , followed by the whey hydrolysates ; the mixed hydrolysates and the casein hydrolysates had the lowest taste scores . Individually the most palatable formula was mixed hydrolysate 1 , by total score . We found a statistically significant correlation between peptide weight , reflecting the degree of hydrolysis of each formula , and the scores obtained for taste , texture , and overall palatability . CONCLUSION The palatability of formulas is determined by the amount of bitter peptides obtained through hydrolysis . Flavorings and sweeteners may also contribute to palatability . Further studies are needed in order to determine how to modify the organoleptic properties of these products with the purpose of improving their palatability", "UNLABELLED B ACKGROUND : Feeding neonates with humanized milk formula in maternity hospitals may increase the prevalence of milk allergy in infants . However , prospect i ve studies of the possible allergenic effect of very early soy-based formula feeding are lacking . OBJECTIVES To assess the prevalence of soy allergy in infants fed soy-based formula in the first 3 days of life . METHODS The study group included 982 healthy full-term infants born within a 7 month period at a hospital that routinely uses soy-based formula to supplement breastfeeding . In-hospital feeding was recorded and the parents were interviewed once monthly over the next 6 months regarding feeding practice s and clinical symptoms suggesting soy allergy in the infant . RESULTS Ninety-nine percent of the infants received soy-based formula supplement in hospital , and 33%-42 % at home . No cases of immediate allergic reaction to soy or soy-induced enterocolitis were reported . CONCLUSIONS The use of soy-based formula in the early neonatal period does not apparently increase the prevalence of soy allergy in infants followed for the next 6 months", "Abstract Aim : To determine current treatment patterns for infants with cow milk allergy ( CMA ) and the associated re source implication s and budget impact , from the perspective of the UK 's National Health Service ( NHS ) . Methods : A computer-based model was constructed depicting current management of newly-diagnosed infants with CMA derived from patients suffering from this allergy in The Health Improvement Network ( THIN ) Data base . The model spanned a period of 12 months following initial presentation to a general practitioner ( GP ) and was used to estimate the 12-monthly healthcare cost ( at 2006/07 prices ) of treating an annual cohort of 18,350 infants from when they initially present to their GP . Results : Patients presenting with a combination of gastrointestinal and atopic symptoms accounted for 59 % of all patients . From the initial GP visit for CMA it took a mean 2.2 months to be put on diet , although treatment varied according to presenting symptoms . A total of 60 % of all infants were initially treated with soy , 18 % with an extensively hydrolysed formula and 3 % with an amino acid formula . A mean 9 % of patients remained symptomatic on soy and 29 % on an extensively hydrolysed formula . The total cost of managing CMA over the first 12 months following initial presentation to a GP was estimated to be £ 1,381 per patient and £ 25.6 million for an annual cohort of 18,350 infants . Limitations : Patients were not r and omised to treatment and re source use was not collected prospect ively . Nevertheless , 1,000 eligible patients have been included in the analysis , which should be a sufficiently large sample to accurately assess treatment patterns and healthcare re source use in actual clinical practice . The diagnosis of CMA may not be secure in all cases . Nevertheless , patients were diagnosed as having CMA by a clinician and have been managed by their GP as if they had CMA . Conclusion : CMA imposes a substantial burden on the NHS . Any strategy that improves healthcare delivery and thereby shortens time to treatment , time to diagnosis and time to symptom resolution should potentially decrease the burden this allergy imposes on the health service and release re sources for alternative use", "OBJECTIVES We conducted a prospect i ve , r and omized study to evaluate the cumulative incidence of allergy or other adverse reactions to soy formula and to extensively hydrolyzed formula up to the age of 2 years in infants with confirmed cow 's milk allergy . STUDY DESIGN Infants ( n = 170 ) with documented cow 's milk allergy were r and omly assigned to receive either a soy formula or an extensively hydrolyzed formula . If it was suspected that the formula caused symptoms , a double-blind , placebo-controlled challenge ( DBPCFC ) with the formula was performed . The children were followed to the age of 2 years , and soy-specific immunoglobulin E antibodies were measured at the time of diagnosis and at the ages of 1 and 2 years . RESULTS An adverse reaction to the formula was confirmed by challenge in 8 patients ( 10 % ; 95 % confidence interval , 4.4%-18.8 % ) r and omly assigned to soy formula and in 2 patients ( 2.2 % ; 95 % confidence interval , 0.3 % to 7.8 % ) r and omly assigned to extensively hydrolyzed formula . Adverse reactions to soy were similar in IgE-associated and non-IgE-associated cow 's milk allergy ( 11 % and 9 % , respectively ) . IgE to soy was detected in only 2 infants with an adverse reaction to soy . Adverse reactions to soy formula were more common in younger ( Soy formula was well tolerated by most infants with IgE-associated and non-IgE-associated cow 's milk allergy . Development of IgE-associated allergy to soy was rare . Soy formula can be recommended as a first-choice alternative for infants > or=6 months of age with cow 's milk allergy" ]

[ "Association between white rice intake and risk factors of cardiovascular diseases remained uncertain . Most of the previous published studies have been done in western countries with different lifestyles , and scant data are available from the Middle East region , including Iran . This cross-sectional study was conducted in the structure of Isfahan Healthy Heart Program ( IHHP ) to assess the association between white rice consumption and risk factors of cardiovascular diseases . In the present study , 3,006 men were included from three counties of Isfahan , Najafabad , and Arak by multistage cluster r and om-sampling method . Dietary intake was assessed with a 49-item food frequency question naire ( FFQ ) . Laboratory assessment was done in a st and ardized central laboratory . Outcome variables were fasting blood glucose , serum lipid levels , and anthropometric variables . Socioeconomic and demographic data , physical activity , and body mass index ( BMI ) were considered covariates and were adjusted in analysis . In this study , Student 's t-test , chi-square test , and logistic regression were used for statistical analyses . Means of BMI among those subjects who consumed white rice less than 7 times per week and people who consumed 7 - 14 times per week were almost similar—24.8±4.3 vs 24.5±4.7 kg/m2 . There was no significant association between white rice consumption and risk factors of cardiovascular diseases , such as fasting blood sugar and serum lipid profiles . Although whole grain consumption has undeniable effect on preventing cardiovascular disease risk , white rice consumption was not associated with cardiovascular risks among Iranian men in the present study . Further prospect i ve studies with a semi-quantitative FFQ or dietary record question naire , representing type and portion-size of rice intake as well as cooking methods and other foods consumed with rice that affect glycaemic index ( GI ) of rice , are required to support our finding and to illustrate the probable mechanism", "Objective To highlight the contribution of the gut microbiota to the modulation of host metabolism by dietary inulin-type fructans ( ITF prebiotics ) in obese women . Methods A double blind , placebo controlled , intervention study was performed with 30 obese women treated with ITF prebiotics ( inulin/oligofructose 50/50 mix ; n=15 ) or placebo ( maltodextrin ; n=15 ) for 3 months ( 16 g/day ) . Blood , faeces and urine sampling , oral glucose tolerance test , homeostasis model assessment and impedancemetry were performed before and after treatment . The gut microbial composition in faeces was analysed by phylogenetic microarray and qPCR analysis of 16S rDNA . Plasma and urine metabolic profiles were analysed by 1H-NMR spectroscopy . Results Treatment with ITF prebiotics , but not the placebo , led to an increase in Bifidobacterium and Faecalibacterium prausnitzii ; both bacteria negatively correlated with serum lipopolysaccharide levels . ITF prebiotics also decreased Bacteroides intestinalis , Bacteroides vulgatus and Propionibacterium , an effect associated with a slight decrease in fat mass and with plasma lactate and phosphatidylcholine levels . No clear treatment clustering could be detected for gut microbial analysis or plasma and urine metabolomic profile analyses . However , ITF prebiotics led to subtle changes in the gut microbiota that may importantly impact on several key metabolites implicated in obesity and /or diabetes . Conclusions ITF prebiotics selectively changed the gut microbiota composition in obese women , leading to modest changes in host metabolism , as suggested by the correlation between some bacterial species and metabolic endotoxaemia or metabolomic signatures", "Aims We aim ed to assess the effects of psyllium supplementation on insulin sensitivity and other parameters of the metabolic syndrome in an at risk adolescent population . Methods This study encompassed a participant-blinded , r and omized , placebo-controlled , crossover trial . Subjects were 47 healthy adolescent males aged 15–16 years , recruited from secondary schools in lower socio-economic areas with high rates of obesity . Participants received 6 g/day of psyllium or placebo for 6 weeks , with a two-week washout before crossing over . Fasting lipid profiles , ambulatory blood pressure , auxological data , body composition , activity levels , and three-day food records were collected at baseline and after each 6-week intervention . Insulin sensitivity was measured by the Matsuda method using glucose and insulin values from an oral glucose tolerance test . Results 45 subjects completed the study , and compliance was very high : 87 % of participants took > 80 % of prescribed capsules . At baseline , 44 % of subjects were overweight or obese . 28 % had decreased insulin sensitivity , but none had impaired glucose tolerance . Fibre supplementation led to a 4 % reduction in and roid fat to gynoid fat ratio ( p = 0.019 ) , as well as a 0.12 mmol/l ( 6 % ) reduction in LDL cholesterol ( p = 0.042 ) . No associated adverse events were recorded . Conclusions Dietary supplementation with 6 g/day of psyllium over 6 weeks improves fat distribution and lipid profile ( parameters of the metabolic syndrome ) in an at risk population of adolescent males . Trial Registration Australian New Zeal and Clinical Trials Registry", "Lupin kernel fiber beneficially modifies blood lipids because of its bile acid-binding capacity . The aim of this study was to evaluate the preventive effects of a lupin kernel fiber preparation on cardiovascular diseases and to clarify possible mechanisms . In a r and omized , double-blind , controlled crossover trial , 60 moderately hypercholesterolemic adults ( plasma total cholesterol : > 5.2 mmol/L ) passed 3 intervention periods in different orders with a 2-wk washout phase between each . Participants consumed either a high-fiber diet containing 25-g/d lupin kernel fiber ( LF ) or citrus fiber ( CF ) , or a low-fiber control diet ( CD ) for 4 wk each . Anthropometric , plasma , and fecal variables were assessed at baseline and after the interventions . Contrary to the CF period , total ( 9 % ) and LDL ( 12 % ) cholesterol as well as triacylglycerols ( 10 % ) were lower after the LF period when compared with the CD period [ P ≤ 0.02 , adjusted for baseline , age , gender , and body mass index ( BMI ) ] . HDL cholesterol remained unchanged . Moreover , the LF period reduced high-sensitivity C-reactive protein ( P = 0.02 ) and systolic blood pressure ( P = 0.01 ) when compared with baseline . Bile acid binding could not be shown because the excretion of total bile acids remained constant after the high-fiber diets . However , the LF period result ed in an enhanced formation of the main short-chain fatty acids in comparison with the CD period . During the CF period , only acetate increased significantly . Both high-fiber diets led to higher satiety and modified nutritional behavior , result ing in significantly lower body weight , BMI , and waist circumference compared with the CD period . The blood lipid-lowering effects of LF are apparently not a result of bile acid binding . Rather , we hypothesize for the first time , to our knowledge , that the blood lipid-lowering effects of LF may be mainly attributed to the formation of short-chain fatty acids , specifically propionate and acetate . This trial was registered at clinical trials.gov as NCT01035086", "Background Fat infiltration of the liver , muscle and pancreas is associated with insulin resistance and risk of diabetes . Weight loss reduces ectopic fat deposition and risk of diabetes , but is difficult to sustain to due to compensatory increases in appetite . Fermentable carbohydrates have been shown to decrease appetite and food intake , and promote weight loss in overweight subjects . In animal studies , fermentable carbohydrate reduces ectopic fat independent of weight loss . We aim ed to investigate the effect of the fermentable carbohydrate inulin on weight maintenance , appetite and ectopic fat in subjects with prediabetes . Methods Forty-four subjects with prediabetes were r and omized to 18 weeks ’ inulin or cellulose supplementation . During weeks 1–9 ( weight loss phase ) all subjects had four visits with a dietitian to guide them towards a 5 % weight loss . During weeks 10–18 ( weight maintenance phase ) subjects continued taking their assigned supplementation and were asked to maintain the weight they had lost but were offered no further support . All subjects attended study sessions at baseline , 9 and 18 weeks for measurement of weight ; assessment of adipose tissue and ectopic fat content by magnetic resonance imaging and magnetic resonance spectroscopy ; glucose , insulin and GLP-1 levels following a meal tolerance test ; and appetite by ad libitum meal test and visual analogue scales . Results Both groups lost approximately 5 % of their body weight by week nine ( −5.3 ± 0.1 % vs −4.3 ± 0.4 % , p = 0.13 , but the inulin group lost significantly more weight between 9 and 18 weeks ( −2.3 ± 0.5 % vs −0.6 ± 0.4 % , p = 0.012 ) . Subjects taking inulin had lower hepatic ( p = 0.02 ) and soleus muscle ( p fat content at 18 weeks compared to control even after controlling for weight loss and consumed less at the ad libitum meal test ( p = 0.027 ) . Fasting glucose significantly decreased at week nine only ( p = 0.005 ) , insulin concentrations did not change , and there was a significant increase in GLP-1 in the cellulose group at 9 and 18 weeks ( p Conclusion Inulin may have a two-pronged effect on the risk of diabetes by 1 ) promoting weight loss 2 ) reducing intrahepatocellular and intramyocellular lipid in people with prediabetes independent of weight loss . Trial registration Clinical trial number : NCT01841073", "Improvement of insulin resistance and inflammation is a basic strategy in the management of type 2 diabetes . There is limited evidence that prebiotics improve insulin resistance and inflammation . However , the ameliorating effect of resistant dextrin , as a prebiotic , on insulin resistance and inflammation in patients with type 2 diabetes has not been investigated so far . Therefore , the present study aim ed to examine the effects of resistant dextrin on insulin resistance and inflammation in type 2 diabetic patients . In a r and omised controlled clinical trial , fifty-five women with type 2 diabetes were assigned to two groups : the intervention group ( n 30 ) and the control group ( n 25 ) . The intervention group received a daily supplement of 10 g resistant dextrin and the control group received a similar amount of maltodextrin as placebo for 8 weeks . Fasting plasma glucose ( FPG ) , HbA1c , insulin , high-sensitivity C-reactive protein ( hs-CRP ) , IL-6 , TNF-α , malondialdehyde ( MDA ) and serum endotoxin concentrations were measured before and after the intervention . Data were analysed using SPSS ( version 13 ) . Paired and unpaired t tests and ANCOVA were used to compare quantitative variables after the intervention . Patients supplemented with resistant dextrin exhibited a significant decrease in fasting insulin ( 20.1 pmol/l , 22.8 % ) , homeostasis model assessment of insulin resistance ( 1.3 , 24.9 % ) , quantitative insulin sensitivity check index ( 0.2 , 7.2 % ) , IL-6 ( 1.4 pg/ml , 28.4 % ) , TNF-α ( 5.4 pg/ml , 18.8 % ) , MDA ( 1.2 nmol/ml , 25.6 % ) and endotoxin ( 6.2 endotoxin units/ml , 17.8 % ) concentrations than those supplemented with maltodextrin ( P in FPG ( 0.05 mmol/l , 0.6 % ) , HbA1c ( 0.5 % , 9.6 % ) and hs-CRP ( 2.7 ng/ml , 35.1 % ) concentrations in the resistant dextrin group were not significant when compared with the maltodextrin group . In conclusion , resistant dextrin supplementation can modulate inflammation and improve insulin resistance in women with type 2 diabetes", "BACKGROUND Acute studies with alginate-based preloads suggested that these strong gelling fibers may induce increased feelings of satiety and reduce energy intakes . However , the long-term efficacy and safety of alginate supplementation on body weight regulation are lacking . OBJECTIVE The primary aim of the study was to investigate the effects in subjects of alginate supplementation in conjunction with energy restriction ( -300 kcal/d ) on loss of body weight and fat and , second , on metabolic risk markers in comparison with in a placebo group . DESIGN In a parallel , double-blind , placebo-controlled study , we r and omly assigned 96 obese subjects to either an energy-restricted diet plus a placebo preload supplement or an energy-restricted diet plus an alginate-based preload supplement ( 15 g fiber ) . The preload was administered as a beverage 3 times/d before main meals for a period of 12 wk . RESULTS No differences in loss of body weight and fat between groups were shown in the intension-to-treat ( ITT ) analysis ( P > 0.1 ) . However , in the completer analysis ( n = 80 ) , we showed a greater weight loss with alginate ( 6.78 ± 3.67 kg ) than with the placebo ( 5.04 ± 3.40 kg ) ( P = 0.03 ) , which was mainly attributed to a reduction in the percentage of body fat ( P = 0.03 ) . In the ITT analysis , a larger decrease in systolic and diastolic blood pressure was shown in the placebo group than in the alginate group ( P ) . Plasma concentrations of glucose , insulin , C-reactive protein , and ghrelin , HOMA-IR , and lipid metabolism did not differ between treatment groups in the ITT analysis ( P > 0.1 ) . CONCLUSION These results suggest that alginate supplementation as an adjunct to energy restriction may improve weight loss in obese subjects who complete a 12-wk dietary intervention", "Background Gum Arabic ( acacia Senegal ) is a complex polysaccharide indigestible to both humans and animals . It has been considered as a safe dietary fiber by the United States , Food and Drug Administration ( FDA ) since the 1970s . Although its effects were extensively studied in animals , there is paucity of data regarding its quantified use in humans . This study was conducted to determine effects of regular Gum Arabic ( GA ) ingestion on body mass index and body fat percentage among healthy adult females . Methods A two-arm r and omized , placebo controlled , double-blind trial was conducted in the Department of Physiology at the Khartoum University . A total of 120 healthy females completed the study . They were divided to two groups : A test group of 60 volunteers receiving GA ( 30 gm /day ) for 6 weeks and a placebo group of 60 volunteers receiving pectin ( 1 gm/day ) for the same period of time . Weight and height were measured before and after intervention using st and ardized height and weight scales . Skin fold thickness was measured using Harpenden Skin fold caliper . Fat percentage was calculated using Jackson and Pollock 7 caliper method and Siri equation . Results Pre and post analysis among the study group showed significant reduction in BMI by 0.32 ( 95 % CI : 0.17 to 0.47 ; P body fat percentage by 2.18 % ( 95 % CI : 1.54 to 2.83 ; P Gum Arabic for six weeks . Side effects caused by GA ingestion were experienced only in the first week . They included unfavorable viscous sensation in the mouth , early morning nausea , mild diarrhea and bloating abdomen . Conclusions GA ingestion causes significant reduction in BMI and body fat percentage among healthy adult females . The effect could be exploited in the treatment of obesity", "The current study assesses the impact on appetite and food intake of a novel co-processed ingredient containing a viscous fibre and whole-grain high-amylose corn flour , a source of type 1 and type 2 resistant starch ( HAM-RS ) . Ninety adults completed a crossover , placebo-controlled study comparing two doses of the ingredient ( 20 and 30 g ) to a maltodextrin control in a fruit-based smoothie served with breakfast . Ad libitum food intake was measured over the day and visual analogue scales were used to assess subjective appetite sensations . Subjects consumed 7 % less energy intake at dinner following the 30 g dose ( p = 0.02 ) compared to control . In addition , a trend for lower lunch intake ( 5 % less weight of food ) was observed for the 20 g dose ( p = 0.10 ) . Reductions were also observed for the two meals combined , with 3 % lower energy intake for the 20 g dose ( p = 0.04 ) and 5 % less weight of food consumed for the 30 g dose ( p = 0.04 ) . Lower ratings of hunger were reported at 3 h after breakfast for both doses and also at 2 and 3 h after lunch for the 30 g dose . With ratings combined to compute an overall appetite score , a trend for lower appetite scores at 3 h after breakfast was found for both doses . Consistent with this , significant reductions in AUC hunger and prospect i ve consumption were identified in the 30 g condition . A similar pattern of results was observed for fullness and desire to eat . The results of this study show that a new composite satiety ingredient comprised of a viscous fibre and whole-grain corn flour can affect acute satiety responses in men and women", "Background . Few safe and effective dietary supplements are available to promote weight loss . We evaluated the safety and efficacy of glucomannan , a water-soluble fiber supplement , for achieving weight loss in overweight and moderately obese individuals consuming self-selected diets . Methods . Participants were r and omly assigned to take 1.33 grams of glucomannan or identically looking placebo capsules with 236.6 mL ( 8 ounces ) of water one hour before breakfast , lunch , and dinner for 8 weeks . The primary efficacy outcome was change in body weight after 8 weeks . Other efficacy outcomes were changes in body composition , hunger/fullness , and lipid and glucose concentrations . Safety outcomes included gastrointestinal symptoms/tolerance and serum liver enzymes and creatinine levels . Results . A total of 53 participants ( 18–65 years of age ; BMI 25–35 kg/m2 ) were enrolled and r and omized . The two groups did not differ with respect to baseline characteristics and compliance with the study supplement . At 8 weeks , there was no significant difference between the glucomannan and placebo groups in amount of weight loss ( −.40 ± .06 and −.43 ± .07 , resp . ) or other efficacy outcomes or in any of the safety outcomes . Conclusions . Glucomannan supplements administered over 8 weeks were well tolerated but did not promote weight loss or significantly alter body composition , hunger/fullness , or lipid and glucose parameters . This trial is registered with NCT00613600", "Background The purpose of this study was to evaluate the effects of high performance inulin supplementation on blood glycemic control and antioxidant status in women with type 2 diabetes . Methods In a r and omized , triple-blind controlled trial , 49 females ( fiber intake The participants were divided into one of two groups in which the participants either received 10 g/day of inulin ( intervention , n=24 ) or maltodextrin ( control , n=25 ) for 2 months . Fasting blood sample s were obtained and both glycemic control and antioxidant status were determined at baseline and at the end of the study . Results At the end of the study period , there were significant decreases in fasting plasma glucose ( 8.47 % ) , glycosylated hemoglobin ( 10.43 % ) , and malondialdehyde ( 37.21 % ) levels and significant increases in total antioxidant capacity ( 18.82 % ) and superoxide dismutase activity ( 4.36 % ) in the inulin group when compared to the maltodextrin group ( P in fasting insulin , homeostasis model assessment of insulin resistance , and catalase activity were not significant in the inulin group when compared with the maltodextrin group . Glutathione peroxidase activity remained unchanged in both groups . Conclusion Inulin supplementation may improve some glycemic and antioxidant indices and decrease malondialdehyde levels in women with type 2 diabetes . Further investigations are needed in order to confirm the positive effects that inulin may have on the glycemic and antioxidant indices of patients with type 2 diabetes", "Endothelial dysfunction and increased arterial stiffness occur early in the pathogenesis of the metabolic syndrome and they are both powerful independent predictors of cardiovascular risk . A high-fibre diet has been correlated with lower BMI and a lower incidence of hyperlipidaemia , CVD , hypertension and diabetes . The present r and omised , parallel- design study compared the effects of fibre intake from a healthy diet v. fibre supplement diets on blood pressure ( BP ) and vascular function over 12 weeks . Overweight and obese adults were r and omised to one of three groups : control ( with placebo ) , fibre supplement ( FIB ) or healthy eating group with placebo ( HLT ) . Systolic blood pressure ( SBP ) was lower in the FIB group compared with the control group at week 6 , but not at week 12 . However , SBP was lower in the HLT group compared with control group at week 12 . At week 6 , the FIB group presented lower diastolic blood pressure and augmentation index compared with the control group , but this result did not persist to the end of the study . The present study did not show any improvements in BP or vascular function in overweight and obese individuals with psyllium fibre supplementation over 12 weeks of intervention . However , a healthy diet provided the greatest improvements in BP in overweight and obese subjects . Further research with hypertensive individuals is necessary to eluci date whether increased fibre consumption in the form of psyllium supplementation may provide a safe and acceptable means to reduce BP , vascular function and the risk of developing CVD", "Limited evidence suggests that the dietary inclusion of oligofructose , an inulin-type fructan with prebiotic properties , may increase satiety and , thus , reduce energy intake and body weight in overweight and obese adults . The aim of the present study was to assess the effect of oligofructose supplementation for 12 weeks on the BMI of overweight and obese children . A total of ninety-seven children aged 7 - 18 years who were overweight and obese ( BMI > 85th percentile ) were r and omly assigned to receive placebo ( maltodextrin ) or oligofructose ( both at an age-dependent dose : 8 g/d for children aged 7 - 11 years and 15 g/d for children aged 12 - 18 years ) for 12 weeks . Before the intervention , all children received dietetic advice and they were encouraged to engage in physical activity . The primary outcome measure was the BMI -for-age z-score difference between the groups at the end of the intervention . Data from seventy-nine ( 81 % ) children were available for analysis . At 12 weeks , the BMI -for-age z-score difference did not differ between the experimental ( n 40 ) and control ( n 39 ) groups ( mean difference 0.002 , 95 % CI - 0.11 , 0.1 ) . There were also no significant differences between the groups with regard to any of the secondary outcomes , such as the mean BMI -for-age z-score , percentage of body weight reduction and the difference in total body fat . Adverse effects were similar in both groups . In conclusion , oligofructose supplementation for 12 weeks has no effect on body weight in overweight and obese children", "Aims : This trial aims to determine the effects of resistant starch ( RS ) subtype 2 ( RS2 ) on glycemic status , metabolic endotoxemia and markers of oxidative stress . Methods : A r and omized , controlled , parallel-group clinical trial group of 56 females with type 2 diabetes mellitus ( T2DM ) was divided to 2 groups . The intervention group ( n = 28 ) and control group ( n = 28 ) received 10 g/day RS2 or placebo for 8 weeks , respectively . Fasting blood sample s were taken to determine glycemic status , endotoxin , high sensitivity C-reactive protein ( hs-CRP ) , malondialdehyde ( MDA ) , total antioxidant capacity ( TAC ) , antioxidant enzymes concentrations as well as uric acid at baseline and after the intervention . Results : After 8 weeks , RS2 caused a significant decrease in the levels of MDA ( -34.10 % ) , glycosylated hemoglobin ( -9.40 % ) , insulin ( -29.36 % ) , homeostasis model of insulin resistance ( -32.85 % ) and endotoxin ( -25.00 % ) , a significant increase in TAC ( 18.10 % ) and glutathione peroxidase ( 11.60 % ) as compared with control . No significant changes were observed in fasting plasma glucose , quantitative insulin sensitivity check index , hs-CRP , superoxide dismutase , catalase and uric acid in the RS2 group as compared with the control group . Conclusion : Supplementation with RS2 may be improved glycemic status , endotoxemia and markers of oxidative stress in patients with T2DM", "Background : Viscous or gel-forming dietary fibers can increase satiety by a more firm texture and increased eating time . Effects of viscous or gel-forming fibers on satiety by post-ingestive mechanisms such as gastric emptying , hormonal signals , nutrient absorption or fermentation are unclear . Moreover , it is unclear whether the effects persist after repeated exposure . Objective : To investigate satiety and energy intake after single and repeated exposure to gelled fiber by post-ingestive mechanisms . Design : In a two-arm crossover design , 32 subjects ( 24 female subjects , 21±2 y , BMI 21.8±1.9 kg m−2 ) consumed test foods once daily for 15 consecutive days , with 2 weeks of washout . Test foods were isocaloric ( 0.5 MJ , 200 g ) with either 10 g gel-forming pectin or 3 g gelatin and 2 g starch , matched for texture and eating time . Hourly satiety ratings , ad libitum energy intake and body weight were measured on days 1 ( single exposure ) and 15 ( repeated exposure ) . In addition , hourly breath hydrogen , fasting glucose , insulin , leptin and short-chain fatty acids were measured . Results : Subjects rated hunger , desire to eat and prospect i ve intake about 2 % lower ( P0.64 ) . After receiving pectin , energy intake was lower ( −5.6 % , P=0.012 ) and breath hydrogen was elevated ( + 12.6 % , P=0.008 ) after single exposure , but not after repeated exposure . Fasting glucose concentrations were higher both after single and repeated exposure to pectin ( + 2.1 % , P=0.019 ) . Body weight and concentrations of insulin , leptin and short-chain fatty acids did not change during the study . Conclusions : Gelled pectin can increase satiety and reduce energy intake by post-ingestive mechanisms . Although the effects were small , the effects on satiety were consistent over time , whereas the effects on energy intake reduction were not", "Several regulatory bodies have approved a health cl aim on the cholesterol-lowering effects of oat β-glucan at levels of 3·0 g/d . The present study aim ed to test whether 1·5 g/d β-glucan provided as ready-to-eat oat flakes was as effective in lowering cholesterol as 3·0 g/d from oats porridge . A 6-week r and omised controlled trial was conducted in eighty-seven mildly hypercholesterolaemic ( ≥ 5 mmol/l and ( 25 % energy ( E% ) protein ; 45 E% carbohydrate ; 30 E% fat , at energy requirements for weight maintenance ) : ( 1 ) minimal β-glucan ( control ) ; ( 2 ) low-dose oat β-glucan ( 1·5 g β-glucan ; oats low - OL ) or ( 3 ) higher dose oat β-glucan ( 3·0 g β-glucan ; oats high - OH ) . Changes in total cholesterol and LDL-cholesterol ( LDL-C ) from baseline were assessed using a linear mixed model and repeated- measures ANOVA , adjusted for weight change . Total cholesterol reduced significantly in all groups ( - 7·8 ( sd 13·8 ) % , - 7·2 ( sd 12·4 ) % and - 5·5 ( sd 9·3 ) % in the OH , OL and control groups ) , as did LDL-C ( - 8·4 ( sd 18·5 ) % , - 8·5 ( sd 18·5 ) % and - 5·5 ( sd 12·4 ) % in the OH , OL and control groups ) , but between-group differences were not significant . In responders only ( n 60 ) , β-glucan groups had higher reductions in LDL-C ( - 18·3 ( sd 11·1 ) % and - 18·1 ( sd 9·2 ) % in the OH and OL groups ) compared with controls ( - 11·7 ( sd 7·9 ) % ; P = 0·044 ) . Intakes of oat β-glucan were as effective at doses of 1·5 g/d compared with 3 g/d when provided in different food formats that delivered similar amounts of soluble β-glucan", "Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists", "ABSTRACT Increased inflammation occurs with excessive adiposity and yeast β-glucan modulates immune responses . This study investigated the potential effect of yeast β-glucan on inflammatory cytokines in overweight/obese people . A r and omized , double blinded , placebo-controlled , clinical trial design enrolled 44 overweight/obese participants with body mass index ≥23 kg/m2 , r and omized to two groups receiving β – glucan 477 mg/capsule ( n = 22 ) or placebo ( n = 22 ) orally for six weeks . At weeks one to two , participants received 1 β – glucan or placebo capsule/day and at four weeks two tablets/day . Anthropometric changes , lipid profiles , liver and renal functions , and inflammatory cytokines were measured . β-glucan reduced waist circumference ( p = 0.037 ) and blood pressure ( p = 0.006 ) compared with controls after six weeks of intervention . No statistical significance between groups was observed for triglyceride , cholesterol , lipid profile , liver and renal function , or energy and nutrient intake compared with controls at week six . β-glucan increased interlukin-10 ( IL-10 ) , an anti-inflammatory cytokine , by 23.97 % from baseline at week two ( p ( p β-glucan reduced pro-inflammatory cytokines IL-6 at week six ( p = 0.005 ) and tumor necrosis factor-α at week two ( p = 0.037 ) compared with controls . Supplementation of yeast β-glucan for six weeks modulated pro-cytokines that accelerate overweight/obese comorbidities and reduced blood pressure as well as waist circumference , the strong risk factors for cardiovascular disease , in overweight/obese subjects . Thus , β-glucan might have the potential to decrease comorbid conditions associated with overweight/ obesity", "BACKGROUND High viscosity fibre is known to exert many beneficial effects on appetite and metabolism . It could potentially help in weight management , in dieting or nondieting individuals . The present study investigated the effects of the daily intake of a novel high viscosity polysaccharide ( HVP ) over 3 months in nondieting obese or overweight men and women . METHODS The study comprised a double-blind , r and omised controlled clinical trial . Participants ingested 5 - 15 g per day of either HVP ( n = 29 , experimental group ) or inulin ( n = 30 , control group ) for 15 weeks . Changes in anthropometry ( weight , waist and hip circumferences ) , blood lipids and glucose tolerance were studied from the beginning to the end of administration . Compliance and tolerance were examined . RESULTS Differences appeared between HVP and inulin supplementation in female participants only . Mean ( SD ) decreases in body weight [ 1.6 ( 3.2 ) kg ; approximately 2 % of initial weight ] and hip circumference [ 2.8 ( 3.6 ) cm ] occurred in women of the HVP group but not in controls ( Time × Group interactions , P ≤ 0.002 ) . Total , high-density lipoprotein and low-density lipoprotein-cholesterol were lower at the end of supplementation in the women of the HVP group compared to controls ( P ≤ 0.021 ) . No effect appeared in waist circumference and triacylglycerol . No difference was noted in the number or severity of the adverse effects reported in both groups . Adverse effects were mild and agreed with commonly reported reactions to intake of dietary fibre . CONCLUSIONS Beneficial although modest effects appeared after several weeks of daily HVP intake in nondieting obese or overweight women . The effects of HVP should be investigated in the context of a weight loss programme", "Strong evidence supports the ability of dietary fibers to improve satiety . However , large variations in the physical and chemical characteristics of dietary fiber modulate the physiologic responses . We hypothesized that a nonviscous soluble dietary fiber may influence satiety . This r and omized , double-blind , placebo-controlled clinical study in 100 overweight healthy adults in China investigated the effect of different dosages of dietary supplementation with a dextrin , NUTRIOSE ( ROQUETTE frères , Lestrem , France ) , on short-term satiety over time . Subjects were r and omized by body mass index and energy intake and then assigned to receive either placebo or 8 , 14 , 18 , or 24 g/d of NUTRIOSE mixed with orange juice ( n = 20 volunteers per group ) . On days -2 , 0 , 2 , 5 , 7 , 14 , and 21 , short-term satiety was evaluated with a visual analog scale , and hunger feeling status was assessed with Likert scale . NUTRIOSE exhibits a progressive and significant impact on short-term satiety , which is time and dosage correlated . Some statistical differences appear for the group 8 g/d from day 5 , and from day 0 for the groups 14 , 18 , and 24 g/d . The hunger feeling status decreases significantly from day 5 to the end of the evaluation for the group 24 g and from day 7 for the groups 14 and 18 g. By day 5 , the group 24 g showed significantly longer time to hunger between meals compared with placebo . These results suggest that dietary supplementation with a soluble fiber can decrease hunger feeling and increase short-term satiety over time when added to a beverage from 8 to 24 g/d with time- and dose-responses relationship", "OBJECTIVE To investigate the effect of nutrient stimulation of gut hormones by oligofructose supplementation on appetite , energy intake ( EI ) , body weight ( BW ) and adiposity in overweight and obese volunteers . METHODS In a parallel , single-blind and placebo-controlled study , 22 healthy overweight and obese volunteers were r and omly allocated to receive 30 g day(-1 ) oligofructose or cellulose for 6 weeks following a 2-week run-in . Subjective appetite and side effect scores , breath hydrogen , serum short chain fatty acids ( SCFAs ) , plasma gut hormones , glucose and insulin concentrations , EI , BW and adiposity were quantified at baseline and post-supplementation . RESULTS Oligofructose increased breath hydrogen ( P late acetate concentrations ( P = 0.024 ) , tended to increase total area under the curve (tAUC)420 mins peptide YY ( PYY ) ( P = 0.056 ) and reduced tAUC450 mins hunger ( P = 0.034 ) and motivation to eat ( P = 0.013 ) when compared with cellulose . However , there was no significant difference between the groups in other parameters although within group analyses showed an increase in glucagon-like peptide 1 ( GLP-1 ) ( P = 0.006 ) in the cellulose group and a decrease in EI during ad libitum meal in both groups . CONCLUSIONS Oligofructose increased plasma PYY concentrations and suppressed appetite , while cellulose increased GLP-1 concentrations . EI decreased in both groups . However , these positive effects did not translate into changes in BW or adiposity", "This study compared the effects of four types of fiber on satiety and energy intakes at the next meal using a st and ard double-blinded preload study design . Study participants ( 14 men and 22 women ) each took part in 6 study sessions . Study preloads were a combination of a solid snack and a liquid beverage ( energy range 0.78 - 0.83 MJ ) containing four different types of fiber : soluble fiber dextrin ( 12 g ) , soluble corn fiber ( 11.8 g ) , polydextrose ( 11.8 g ) , and resistant starch ( 11.2 g ) . All four fibers were compared to two control conditions of equal volume : an isoenergetic , low-fiber preload and a lower-energy , low-fiber preload . All preloads were presented twice for a total of 0.35 - 1.65 MJ and 1 - 24 g fiber . Satiety ratings were collected for 20 min intervals for 220 min during the morning testing session . A test meal was served at 1200 h and plate waste measured . The five higher-energy preloads led to higher fullness and lower hunger ratings compared to the low-energy control but were not significantly different from each other . Relative to the isoenergetic control , only soluble fiber dextrin significantly suppressed energy intakes ( p=0.023 ) . Supplementing beverages with soluble fiber dextrin affects short term energy intake and may have implication s for weight control", "Viscous dietary fibers such as sodium alginate extracted from brown seaweed have received much attention lately for their potential role in energy regulation through the inhibition of energy intake and increase of satiety feelings . The aim of our study was to investigate the effect on postpr and ial satiety feelings , energy intake , and gastric emptying rate ( GER ) , by the paracetamol method , of two different volumes of an alginate-based preload in normal-weight subjects . In a four-way placebo-controlled , double-blind , crossover trial , 20 subjects ( age : 25.9 ± 3.4 years ; BMI : 23.5 ± 1.7 kg/m(2 ) ) were r and omly assigned to receive a 3 % preload concentration of either low volume ( LV ; 9.9 g alginate in 330 ml ) or high volume ( HV ; 15.0 g alginate in 500 ml ) alginate-based beverage , or an iso-volume placebo beverage . The preloads were ingested 30 min before a fixed breakfast and again before an ad libitum lunch . Consumption of LV-alginate preload induced a significantly lower ( 8.0 % ) energy intake than the placebo beverage ( P = 0.040 ) at the following lunch meal , without differences in satiety feelings or paracetamol concentrations . The HV alginate significantly increased satiety feelings ( P = 0.038 ) , reduced hunger ( P = 0.042 ) and the feeling of prospect i ve food consumption ( P = 0.027 ) , and reduced area under the curve ( iAUC ) paracetamol concentrations compared to the placebo ( P = 0.05 ) . However , only a 5.5 % reduction in energy intake was observed for HV alginate ( P = 0.20 ) . Although they are somewhat contradictory , our results suggest that alginate consumption does affect satiety feelings and energy intake . However , further investigation on the volume of alginate administered is needed before inferring that this fiber has a possible role in short-term energy regulation", "This r and omized , controlled , 2-week intervention study in 24 obese subjects tested the effect on body weight loss and gastrointestinal tolerance of consuming low viscous alginate fibre-based preloads of 3 % concentration ( 500 ml volume ) three times a day as an adjuvant to a calorie-restricted diet . The pilot study showed that intake of the alginate preloads was moderately acceptable to the majority of subjects but did not produce additional body weight loss beyond calorie restriction ( -1.42 ± 0.38 kg ) ( n=12 ) compared to control group ( -1.56 ± 0.21 kg ) ( n=8 ) . These results do not support that alginate supplementation enhance the weight loss effects of a hypo-caloric diet , but a sufficiently powered long-term study is needed to explore whether alginate could be an aid for improving weight loss during caloric-restriction", "Objective : Refined grains consumption is positively associated with obesity . White rice is the most usual refined grain in Iran . However , few studies have assessed the association between rice intake and anthropometric measures among adolescents . Therefore , we aim ed to compare anthropometric measures as well as the diet quality indices across the tertiles of white rice consumption among Iranian adolescents . Methods : This cross-sectional study was conducted on 415 female adolescents who were chosen by using a systematic cluster r and om sampling . Dietary intake assessment was done using a vali date d semiquantitative food frequency question naire . Anthropometric measures were done according to the st and ard protocol s. Diet quality indices ( including dietary energy density [ DED ] , nutrient adequacy ratio [ NAR ] , and mean adequacy ratio [ MAR ] ) were calculated using st and ard definitions . Results : The prevalence of overweight across the tertiles of rice consumption was 11.6 , 17.8 , and 24.6 % , respectively ( p = 0.03 ) . Corresponding values for obesity were 2.1 , 5.7 , and 8.6 % , respectively ( p = 0.04 ) . A significant positive association was observed for the prevalence of central obesity across the tertile of rice intake ( 13.1 , 21.4 , and 28.1 % ; p = 0.02 ) . Dietary fiber and energy intake and diet quality indices were significantly different among different tertiles of white rice intake . Those in the highest tertiles of white rice intake had the lowest scores for MAR and NAR and highest scores for DED . Conclusion : There was significant association between rice consumption and obesity as well as diet quality indices among Iranian adolescents" ]

[ "The treatment of choice for Type II or non-insulin-dependent diabetes mellitus is a behavioral program for the management of weight . However , compliance with this lifelong dietary regimen is often poor . In the current investigation male and female adults with diagnosed Type II diabetes were r and omly assigned to either a behavior modification , a cognitive modification , a cognitive-behavior modification , or a control group . Patients were evaluated in terms of weight , percentage of body fat , and glycosylated hemoglobin measures . Men lost signficantly more weight than women and subjects in the behavior modification group lost more weight and demonstrated greater decreases in diabetes control than subjects in the cognitive-behavior modification , cognitive , and control groups . A significant interaction indicated that diabetic men may benefit more from behavioral weight reduction programs than diabetic women . Several explanations for these findings are considered", "BACKGROUND Previous findings are unclear regarding the possible glycemic benefits of applying behavioral relaxation training in non-insulin-dependent diabetes mellitus ( NIDDM ) . METHODS Subjects with NIDDM were r and omized to relaxation training ( 6 sessions of progressive muscle relaxation and imagery , n = 12 ) or control treatment ( routine medical care , n = 10 ) . Physiological measures were total glycosylated hemoglobin ( GHb ) and area under the 2-hour oral-glucose-tolerance curve ( AUC ) . Psychological measures of generalized distress , anxiety and daily stress were also administered . All subjects were assessed before and after the 8-week intervention , and again at 16 weeks of long-term follow-up . RESULTS There were no postintervention group differences in physiological variables . Highly distressed subjects and those who rated their glucose as more stress responsive tended to practice relaxation less between sessions . Within the treated group only , lower preintervention stress responsivity was associated with greater improvement in GHb , and lower anxiety and distress levels predicted long-term improvement in AUC . CONCLUSIONS It remains unclear whether relaxation training produces glycemic benefits in NIDDM . Perhaps the least anxious and stress-responsive patients only benefit from group-based relaxation training , whereas anxious individuals require intensive individually administered interventions", "OBJECTIVE There is conflicting evidence regarding the utility of stress management training in the treatment of diabetes . The few studies that have shown a therapeutic effect of stress management have used time-intensive individual therapy . Unfortunately , widespread use of such interventions is not practical . The aim of the present investigation is to determine whether a cost-effective , group-based stress management training program can improve glucose metabolism in patients with type 2 diabetes and to determine whether a particular subset of patients is more likely to get positive results . RESEARCH DESIGN AND METHODS Patients with type 2 diabetes were r and omized to undergo a five-session group diabetes education program with or without stress management training . Participants ( n = 108 ) were followed for 1 year , during which HbA(1c ) tests and question naires assessing perceived stress , anxiety , and psychological health were administered at regular intervals to evaluate treatment effects . RESULTS Stress management training was associated with a small ( 0.5 % ) but significant reduction in HbA(1c ) . Compliance with the treatment regimen decreased over time but was similar to that seen in patients receiving stress management for other reasons in the clinic . Trait anxiety ( a measure of stable individual differences in anxiety proneness ) did not predict response to treatment , showing that highly anxious patients did not derive more benefit from training . CONCLUSIONS The current results indicate that a cost-effective , group stress management program in a \" real-world \" setting can result in clinical ly significant benefits for patients with type 2 diabetes", "OBJECTIVE The aim of this r and omized pilot study was to examine whether the addition of motivational interviewing strategies to a behavioral obesity intervention enhances adherence and glucose control in older obese women with NIDDM . RESEARCH DESIGN AND METHODS Twenty-two older obese women ( 41 % black ) with NIDDM were r and omly assigned to 1 ) a st and ard 16-week group behavioral weight-control program that provided instruction in diet , exercise , and behavioral modification or 2 ) the same group behavioral program with three individualized motivational interviewing sessions added . RESULTS The motivational group attended significantly more group meetings ( 13.3 vs. 8.9 ) , completed significantly more food diaries ( 15.2 vs. 10.1 ) , and recorded blood glucose significantly more often ( 46.0 vs. 32.2 days ) than the st and ard group . Further , participants in the motivational group had significantly better glucose control post-treatment ( 9.8 vs. 10.8 % ) . Although both groups demonstrated significant weight loss , no differences were apparent between groups . CONCLUSIONS These results suggest that augmenting a st and ard behavioral treatment program for obese women with NIDDM with a motivational interviewing component may significantly enhance adherence to program recommendations and glycemic control . Preliminary data warrant further investigation with larger sample s and a longer follow-up", "The present study examined the effects of progressive relaxation training and EMG biofeedback on acute glucose disposal in diabetic subjects , as measured by glucose tolerance and three other measures of diabetic metabolic control . Twenty subjects with non-insulin-using Type II diabetes took part in progressive relaxation training and EMG biofeedback in a pre-post treatment versus wait-list experimental design . Treatment effects were assessed on glucose tolerance along with three measures of diabetic control : fasting blood glucose , two-hour postpr and ial blood glucose , and fructosamine . Stress reduction and relaxation was assessed with two physiological measures and two subjective question naires . The training program produced significant reductions in stress , as measured by State Anxiety , and significant changes in physiological measures of muscle activity and skin conductance compared to the control condition . However , no changes were found in glucose tolerance ( while practicing relaxation ) nor in any of the three measures of general diabetic metabolic control . The major implication of this study is that relaxation training does not appear to directly improve diabetic control in mildly stressed non-insulin-using Type II diabetic patients", "OBJECTIVES The aim of the present study was to develop , implement and evaluate a brief intervention to improve adherence to the recommended lifestyle changes for patients with Type 2 diabetes , in particular to help patients to reduce the total amount of fat consumed and to increase lifestyle physical activity levels . DESIGN AND METHOD A brief , tailored lifestyle self-management intervention for patients with Type 2 diabetes was evaluated in a r and omized controlled trial . One hundred participants ( aged 40 - 70 yrs ) completed assessment s at three time points- baseline , three months and one year . Participants were allocated to either an intervention group who received the brief tailored intervention including follow-up telephone calls , or a usual care control group . RESULTS Results indicate that the intervention was successful in helping patients to reduce fat intake and , to a lesser extent , increase lifestyle physical activity levels . These self-reported changes in behaviour were reflected in the objective data with weight maintenance in the intervention group compared to the control group , together with a significant reduction ( 2 cm ) in waist circumference . CONCLUSIONS These results provide further evidence of the effectiveness of tailored interventions for lifestyle change", "OBJECTIVE Because of other competing priorities , physical activity ( PA ) is seldom addressed in a consistent way in either primary care or diabetes education . This 8-week pilot study evaluated the short-term benefits of an Internet-based supplement to usual care that focused on providing support for sedentary patients with type 2 diabetes to increase their PA levels . RESEARCH DESIGN AND METHODS A total of 78 type 2 diabetic patients ( 53 % female , average age 52.3 years ) were r and omized to the Diabetes Network ( D-Net ) Active Lives PA Intervention or an Internet information-only condition . The intervention condition received goal - setting and personalized feedback , identified and developed strategies to overcome barriers , received and could post messages to an on-line \" personal coach , \" and were invited to participate in peer group support areas . Key outcomes included minutes of PA per week and depressive symptomatology . RESULTS There was an overall moderate improvement in PA levels within both intervention and control conditions , but there was no significant improvement in regard to condition effects . There was substantial variability in both site use and outcomes within the intervention and control conditions . Internal analyses revealed that among intervention participants , those who used the site more regularly derived significantly greater benefits , whereas those in the control condition derived no similar benefits with increased program use . CONCLUSIONS Internet-based self-management interventions for PA and other regimen areas have great potential to enhance the care of diabetes and other chronic conditions . We conclude that greater attention should be focused on methods to sustain involvement with Internet-based intervention health promotion programs over time", "The aim of this study was to compare the effects of an intensive educational approach incorporating longer time , greater simplicity , repetition , and cognitive motivational techniques with a conventional one in subjects with established non-insulin-dependent diabetes mellitus ( NIDDM ) whose weight , glycemic control , and diet were not optimal . Subjects were r and omly allocated to intensive or conventional education . Of 350 subjects , 70 met the study criteria , which included established NIDDM ( ≥3 mo ) , suboptimal recent glycemic control , dietary fat intake ≥35 % of total energy intake , and body massindex ≥25 kg/m2 . The intensive approach was associated with significantly greater improvements in dietary compliance , dietary intake ( complex carbohydrate , [ P = 0.013 ] , legumes [ P 0.0001 ] , fiber [ P 0.0001 ] , total fat [ P 0.004 ] , saturated fat [ P level ( P = 0.007 ) . The transient improvement in glycemic control was similar in both groups . An intensive education program can improve dietary compliance in established NIDDM subjects more than a conventional one . These recommended dietary improvements achieve better improvement in total cholesterol but do not necessarily improve glycemic control ", "The specificity and magnitude of the effects of cognitive behavior therapy in the treatment of bulimia nervosa were evaluated . Seventy-five patients who met strict diagnostic criteria were treated with either cognitive behavior therapy , a simplified behavioral version of this treatment , or interpersonal psychotherapy . Assessment was by interview and self-report question naire , and many aspects of functioning were evaluated . All three treatments result ed in an improvement in the measures of the psychopathology . Cognitive behavior therapy was more effective than interpersonal psychotherapy in modifying the disturbed attitudes to shape and weight , extreme attempts to diet , and self-induced vomiting . Cognitive behavior therapy was more effective than behavior therapy in modifying the disturbed attitudes to shape and weight and extreme dieting , but it was equivalent in other respects . The findings suggest that cognitive behavior therapy , when applied to patients with bulimia nervosa , operates through mechanisms specific to this treatment and is more effective than both interpersonal psychotherapy and a simplified behavioral version of cognitive behavior therapy", "In this r and omized trial patients with non-insulin-dependent diabetes were allocated to one of four programs : a minimal instruction program ( n=59 ) . an education program of individual visits ( n=57 ) , an education program incorporating a group education course ( n=66 ) , and a behavioral program ( n=59 ) . Individual and group education programs had higher attrition rates than the behavioral and minimal programs . The four programs , which involved different amounts of patient contact time , delivery format , and instructional strategies . all produced reductions in HbA atid BMI , with no significant differences between the programs . There were no differences between groups over three time periods in total cholesterol , HDL cholesterol , systolic blood pressure , or proportion of patients consulting an ophthalmologist . The behavioral program ploduced a greater reduction in diastolic blood pressure over 12 months that the education programs and a greater reduction in the cholesterol risk ratio over 3 months than the other programs . The behavioral program patients were more likely to have visited a podiatrist after 6 months and reported higher satisfaction", "BACKGROUND This study was done to determine the efficacy and ease of administration of education/behavior modification classes , provided by a nurse and a dietitian in a primary care clinic for improving control of type 2 diabetes mellitus . METHODS Patients were divided r and omly into two groups . Eighteen patients completed 6 months of structured , office-based classes , and 20 similar patients served as control subjects . All were patients of the same group practice and had their usual office visits . Glycemic control , lipid levels , body weight , knowledge about diabetes , medication requirements , and symptoms were monitored during the 6 months , with follow-up at 12 months . RESULTS At the end of 6 months , the intervention group had significant reductions in mean fasting blood glucose , glycosylated hemoglobin , total cholesterol , and low-density lipoprotein cholesterol ( LDL-C ) values . Their mean body weight was significantly reduced at 12 months , and their knowledge of diabetes was improved . Control patients had significant improvement only in glycosylated hemoglobin and body weight at 6 months . Minimal physician time was required . CONCLUSION The education/behavior modification program was clinical ly worthwhile , and it was easy to administer", "The course of depression in patients with comorbid medical illness is poorly understood . We report a 5-year follow-up study of 25 diabetic patients who had participated in an 8-week depression treatment trial . When a patient completed the trial , primary physicians were informed of patient outcomes and advised to monitor for relapse and treat those with ongoing depression . At the 5-year reevaluation depression was assessed using DSM-III-R criteria , and a depression severity scale was formed that reflected the presence , severity , frequency , and duration of depression episodes as well as a global assessment of functioning . Recurrence or persistence of depression occurred in 23 ( 92 % ) of the patients with an average of 4.8 depression episodes over the 5-year follow-up period . The duration of the longest episode averaged 16 + /- 4 months . Reversion to major depression occurred frequently and rapidly also in the subset that remitted during the treatment trial : 58.3 % were depressed again within the first year . At the time of the follow-up interview , major depression was evident in 16 ( 64 % ) of the subjects , and glycemic control was significantly worse in this group compared with those without depression ( gHb : 13.3 % + /- 2.6 % vs 11.1 % + /- 1.9 % , P = 0.03 ) . Severity of depression over follow-up was related to the presence of neuropathy at entry and to incomplete remission during the initial treatment trial . Nineteen patients ( 82.6 % of those who relapsed ) received additional courses of antidepressant therapy , but none was treated continuously for depression prophylaxis . In this diabetic sample , depression was a recurrent condition in the vast majority of cases , and initial treatment response did not confer lasting euthymia . Whether maintenance antidepressant medication would be useful in preventing depression recurrence and promoting better glycemic control in diabetes remains to be studied", "OBJECTIVE To examine the benefits of relaxation training for patients with NIDDM and to investigate individual differences that could predict a positive response to relaxation training . RESEARCH DESIGN AND METHODS Thirty-eight subjects with NIDDM were treated with intensive conventional diabetes therapy after an initial metabolic evaluation and psychological and pharmacological testing . Half were assigned to also receive biofeedback-assisted relaxation training . Treatment effects on GHb levels and glucose tolerance were evaluated after 8 wk . RESULTS Subjects demonstrated significant improvements in GHb level , but not in glucose tolerance , after 8 wk of intensive conventional treatment . These improvements persisted throughout the follow-up period . However , the group provided with relaxation training did not experience greater improvements on either measure than the group given conventional diabetes treatment only . Within the group that received relaxation training , correlations occurred between the improvements in glucose tolerance after treatment and individual differences in trait anxiety and in the effect of alprazolam on glucose tolerance . Differences in the effects of EPI on glucose tolerance and personality measures of neuroticism and perceived locus of control also appeared to be related to improvements in glucose tolerance after training . CONCLUSIONS Relaxation training did not confer added benefit over and above that provided by conventional diabetes treatment for patients with NIDDM . Additional research is needed to determine whether the administration of relaxation training to selected patients , especially those who are most responsive to stress , would provide benefits for glucose control that are not achieved by conventional treatment", "The implication s of behavioral analysis for practice and research have significant potential for nursing . This present study was conducted to determine the effectiveness of nurses and patients actively participating in behavioral analysis and the implementation of behavioral strategies in order to improve the patients ' self-management of their Type H diabetes . Patients ( N = 156 ) were r and omly assigned to one of four groups . The attention control group ( n = 41 ) received routine care . The compliance group ( n = 32 ) agreed to practice compliance behaviors related to the prescribed medical regimen . The behavioral strategies group ( n = 42 ) participated in behavioral analysis and agreed to practice behavioral strategies . The behavioral strategies with instruction group ( n = 41 ) participated in behavioral analysis , agreed to practice behavioral strategies , and received classes and programmed instruction about behavioral analysis and behavioral strategies . There were no outcome differences between groups relative to glycosylated hemoglobin ( GHb ) and weight loss . There were differences in the outcome measures in subgroups by age , gender , and employment , which have practice and research implication s for the individualization of interventions using behavioral strategies", "The purpose of our study was to compare the effect on diabetes control of group management with the advice-educational technique traditionally used in managing obese out patients with poorly controlled non-insulin-dependent diabetes mellitus ( NIDDM ) . Forty-one patients were r and omly assigned to these two treatment programs , and 32 patients completed the 6-mo study . Initially , patients were seen for 1-h sessions at 1- and 2-wk intervals and later at 1-mo intervals . Patients were asked to do home blood glucose monitoring , decrease caloric intake , increase exercise , and if they were taking insulin , to adjust the dose to attain approximate euglycemia and to stabilize food and exercise patterns . The combined groups reduced mean ± SD glycohemoglobin from 10.9 ± 3.1 to 9.4 ± 2.4 % ( P Scale was negatively and significantly correlated with initial and subsequent glycohemoglobin values ( the more internal , the lower the glycohemoglobin ) . At the end of the study the patients in the group management program had significantly lower blood glucose levels than those given advice and education , but no significant differences in glycohemoglobin values or percentage overweight were observed . One patient had a normal initial glycohemoglobin , and only 4 patients had values in the normal range of 4–6.8 % at the end of the study . Better management programs need to be developed for treating obese out patients with NIDDM", " Forty-nine obese diabetic patients with obese spouses ( diabetic or nondiabetic ) were r and omly assigned to an alone or together condition . Patients in the alone group participated by themselves in a 20-week behavioral weight control program ; their spouses attended assessment sessions only . Patients in the together group attended the program with their spouses ; both were targeted for weight loss and taught social support strategies . Weight losses of patients treated alone and together did not differ significantly at posttreatment ( 19.9 vs. 19.1 lb ) or 1-year follow-up ( 11.6 vs. 7.0 lb ) . However , there was a significant interaction of treatment and gender ; women did better when treated with their spouses , whereas men did better when treated alone . A \" family-based \" approach was not effective for these obese Type II diabetic patients as a whole but may be helpful for women", "To determine whether a group behavior modification approach might be preferable to individual counseling in the nutritional therapy of non-insulin-dependent diabetes mellitus , 40 adults younger than 65 yr of age with diabetes mellitus who were not receiving insulin were r and omized to either a program of individualized dietary review and recommendations or a program of group meetings aim ed at controlling the signals leading to overeating and noncompliance with a diabetic dietary regimen . Statistically significant ( P body weight , sum skin-fold thickness , fasting serum glucose , and serum triglycerides but not LDL-C or HDL-C were observed . The individual counseling group had a greater amount of weight loss than the behavior modification group . There were no significant ( P anxiety , internal versus external locus of control and perceived disease severity , and compliance with advice — were significantly associated with weight loss in the behavior modification group while only the latter index was of value in the individual counseling group . Thus , our use of these programs does not identify a clear advantage of either approach in the nutritional therapy of non-insulin-dependent diabetic patients", "Aims This preliminary study addresses three related issues . First , there is a need to test the effectiveness of cognitive behavioural therapy ( CBT ) for binge eating in population s with Type 2 diabetes . Second , the impact of a treatment for binge eating on diabetes management is unknown . Finally , whilst a number of treatment modalities have been shown to improve binge eating , there has not been a comparison between CBT and a non-specific therapy for binge eating . Methods Group CBT for binge eating was compared with a group non-prescriptive therapy ( NPT ) , a therapy for which there is no theoretical or empirical support in eating disorders , in a r and omized trial which included a post-treatment assessment and a 3-month follow-up . Results There were no differences between CBT and NPT at post-treatment , with both treatments being associated with significant changes in binge eating , mood and body mass index . However , there was a significant relapse in binge eating at the 3-month follow-up in the NPT condition . This was in contrast to the CBT condition , where treatment gains were maintained . Finally , across treatments , reduction in binge eating from pre- to post-treatment was associated with reduction in HbA(1c ) . Conclusions Binge eating in Type 2 diabetes is responsive to psychosocial treatment , and reduction in binge eating appears to improve glycaemic control . However , this is a small study with a short follow-up period . Future studies will need to extend the follow-up period to assess for long-term maintenance of the effects of CBT on binge eating and diabetic control in this population", "BACKGROUND Psychotherapy is the principal nonpharmacologic method for the management of depression , but its usefulness for depressed patients with diabetes remains unknown . OBJECTIVE To assess the efficacy of cognitive behavior therapy ( CBT ) for depression in patients with diabetes . DESIGN R and omized , controlled trial . SETTING Referral-based academic medical center . PATIENTS 51 patients with type 2 diabetes and major depression . INTERVENTION Patients were assigned either to a group that received 10 weeks of individual CBT or to a control group that received no specific antidepressant treatment . All patients participated in a diabetes education program to control for the effects of supportive attention and the possible influence of enhanced diabetes control on mood . MEASUREMENTS Degree of depression was measured by using the Beck Depression Inventory ; glycemic control was measured by using glycosylated hemoglobin levels . Outcomes were assessed immediately after treatment and 6 months after treatment . RESULTS The percentage of patients achieving remission of depression ( Beck Depression Inventory score remission ( difference , 57.7 percentage points [ 95 % CI , 33 to 82 percentage points ] ) ( P remission ( difference , 36.7 percentage points [ CI , 9 to 65 percentage points ] ) ( P = 0.03 ) . Post-treatment glycosylated hemoglobin levels were not different in the two groups , but follow-up mean glycosylated hemoglobin levels were significantly better in the CBT group than in the control group ( 9.5 % compared with 10.9 % ; P = 0.03 ) . CONCLUSIONS The combination of CBT and supportive diabetes education is an effective nonpharmacologic treatment for major depression in patients with type 2 diabetes . It may also be associated with improved glycemic control" ]

[ "Alemtuzumab , the monoclonal anti-CD52 antibody , has clinical activity in B-cell and T-cell malignancies at the dose of 30 mg three times weekly for 9 – 12 weeks . This st and ard regimen induced responses usually shorter than 6 months . To prolong time to progression , we initialized a phase II study with an identical initial scheme until partial response , followed by a maintenance therapy lasting at least 4 months . Eleven heavily pretreated patients ( 8 with B-chronic lymhocytic leukemia ( B-CLL ) and 3 with small lymphoctyic lymphoma ( SLL ) ) have been treated with this maintenance regimen ( MR patients ) and were retrospectively compared to 5 patients ( 3 B-CLL and 2 SLL ) treated with the st and ard regimen ( SR patients ) . Patients characteristics before treatment were identical in both groups . Objective response was reached by 9 ( 82 % ) MR patients and 3 ( 60 % ) SR patients ( p NS ) . After the treatment , 8 ( 73 % ) MR patients and all SR patients progressed with a median time at 12.2 months and 3 months respectively . Survival time from alemtuzumab was significatively different ( P died in the MR group with a median follow-up at 16 months . In the SR group , the median survival from alemtuzumab was 5.9 months . We did not observe any differences in terms of hematological toxicites and infections between the two groups . In conclusion , maintenance alemtuzumab therapy seems to increase the time to progression and the survival , without adding hematological toxicities and infectious complications . More patients are needed to confirm this observation", "One hundred seventy-four patients with progressive or advanced chronic lymphocytic leukemia ( CLL ) have received initial therapy with fludarabine as a single agent or fludarabine combined with prednisone . The overall response rate was 78 % and the median survival was 63 months . No difference in response rate or survival was noted in the 71 patients receiving fludarabine as a single agent compared with the 103 patients who received prednisone in addition . The median time to progression of responders was 31 months and the overall median survival was 74 months . Patients over the age of 70 years had shorter survivals . Patients with advanced stage disease ( Rai III and IV ) had a somewhat shorter survival than earlier stage patients . More than half the patients who relapsed after fludarabine therapy responded to salvage treatment , usually with fludarabine-based regimens . Second remissions were more common in patients who had achieved a complete remission on their initial treatment . The CD4 and CD8 T-lymphocyte sub population s decreased to levels in the range of 150 to 200/microL after the first 3 courses of treatment . Although recovery towards normal levels was slow , the incidence of infections was low in patients in remission ( 1 episode of infection for every 3.33 patient years at risk ) and decreased with time off treatment . There was no association of infections or febrile episodes with the use of corticosteroids or the CD4 count at the end of treatment and a poor correlation with the increase in CD4 counts during remission . Infectious episodes were less common in patients who had a complete response compared with partial responders . Richter 's transformation occurred in 9 patients and Hodgkin 's disease occurred in 4 patients . Five other patients died from other second malignancies . Fludarabine appears to be an effective initial induction therapy with a reasonable safety profile for patients with CLL", "Recent studies have suggested that rituximab has clinical activity and modulates antiapoptotic proteins associated with drug resistance in chronic lymphocytic leukemia ( CLL ) . We performed a r and omized phase 2 study to determine the efficacy , safety , and optimal administration schedule of rituximab with fludarabine in previously untreated CLL patients . Patients were r and omized to receive either 6 monthly courses of fludarabine concurrently with rituximab followed 2 months later by 4 weekly doses of rituximab for consolidation therapy or sequential fludarabine alone followed 2 months later by rituximab consolidation therapy . A total of 104 patients were r and omized to the concurrent ( n = 51 ) and sequential ( n = 53 ) regimens . During the induction portion of treatment , patients receiving the concurrent regimen experienced more grade 3 or 4 neutropenia ( 74 % versus 41 % ) and grade 3 or 4 infusion-related toxicity ( 20 % versus 0 % ) as compared with the sequential arm . The consolidation rituximab therapy was tolerated well in both arms . All other toxicities were similar in the 2 arms . The overall response rate with the concurrent regimen was 90 % ( 47 % complete response [ CR ] , 43 % partial response [ PR ] ; 95 % confidence interval [ CI ] , 0.82 - 0.98 ) compared with 77 % ( 28 % CR , 49 % PR ; 95 % CI , 0.66 - 0.99 ) with the sequential regimen . With a median follow-up time of 23 months , the median response duration and survival have not been reached for either regimen . Rituximab administered concurrently with fludarabine in previously untreated CLL patients demonstrates marked clinical efficacy and acceptable toxicity . Phase 3 studies using this combination approach for patients with CLL are warranted", " Patients with CLL responding to initial chemotherapy with fludarabine alone ( F ) or in combination with cyclophosphamide ( FC ) were r and omized for treatment with alemtuzumab ( 30 mg i.v . TIW , 12 weeks ) or observation . Of 21 evaluable patients , 11 were r and omized to alemtuzumab before the study was stopped due to severe infections in seven of 11 patients . These infections ( one life-threatening pulmonary aspergillosis IV ; four CMV reactivations III requiring i.v . ganciclovir ; one pulmonary tuberculosis III ; one herpes zoster III ) were successfully treated and not associated with cumulative dose of alemtuzumab . In the observation arm , one herpes zoster infection II and one sinusitis I were documented . At 6 months after r and omization , two patients in the alemtuzumab arm converted to CR , while three patients in the observation arm progressed . After alemtuzumab treatment , five of six patients achieved a molecular remission in peripheral blood while all patients in the observation arm remained MRD-positive ( P=0.048 ) . At 21.4 months median follow-up , patients receiving alemtuzumab showed a significant longer progression-free survival ( no progression vs mean 24.7 months ; P=0.036 ) . In conclusion , a consolidation therapy with alemtuzumab is able to achieve molecular remissions and longer survival in CLL , but a safe treatment regimen needs to be determined", "Summary . We evaluated the efficacy and toxicity of fludarabine combined with cyclophosphamide and mitoxantrone ( FCM ) in patients with relapsed or resistant chronic lymphocytic leukaemia ( CLL ) . In total , 37 patients with recurrent or resistant CLL received FCM : fludarabine 25 mg/m2 intravenously ( IV ) , d 1–3 ; cyclophosphamide 200 mg/m2 IV , d 1–3 ; and mitoxantrone 6 mg/m2 IV , d 1 , at 4‐week intervals for up to six courses . Moreover , 23 patients received FCM with cyclophosphamide 600 mg/m2 i.v . and mitoxantrone 8 mg/m2 i.v . on d 1 . In addition to clinical methods , response was assessed using cytofluorometric and molecular techniques . ‘ In vitro ’ sensitivity to the FCM regimen was also analysed in 20 sample s. The median number of courses given was 3 ( range : 1–6 ) . Overall , 30 patients ( 50 % ) achieved complete response ( CR ) , including 10 cases of negative minimal residual disease ( MRD(– ) ) ( 17 % ) , and 17 ( 28 % ) partial response ( PR ) . The median duration of response was 19 months . ‘ In vitro ’ sensitivity also correlated with CR achievement ( P = 0·04 ) . Main toxicity consisted of neutropenia , infections ( 8 % of courses ) , and nausea and vomiting . The treatment‐related mortality was 5 % . FCM did not hamper stem cell harvesting in patients who were c and i date s for autologous stem cell transplantation . FCM induced a high CR rate , including an important number of MRD(– ) , in patients with previously treated CLL", "This multicenter phase 2 trial investigated safety and efficacy of a new immunochemotherapeutic regimen combining rituximab ( R ) and fludarabine ( F ) in patients with fludarabine- and anthracycline-naive chronic lymphocytic leukemia ( CLL ) . The rationale for using R + F includes single-agent efficacy of both drugs , in vitro synergism of R and F , and no apparent overlapping toxicity . Of 31 eligible patients with B-CLL enrolled , 20 were previously untreated and 11 relapsed . Treatment consisted of fludarabine administered at st and ard doses ( 25 mg/m(2)/d ; days 1 - 5 , 29 - 33 , 57 - 61 , and 85 - 89 ) and rituximab ( 375 mg/m(2)/d ) given on days 57 , 85 , 113 , and 151 . Side effects such as fever , chills , and exanthema were generally mild ( National Cancer Institute Common Toxicity Criteria [ NCI-CTC ] grade 1/2 in 48 % and grade 3 and /or 4 in 3 % of patients ) . Fever and chills were mainly associated with the first rituximab infusion . Hematologic toxicity included neutropenia ( grade 1 and /or 2 in 26 % , grade 3 and /or 4 in 42 % ) and thrombocytopenia ( grade 1 and /or 2 in 19 % , grade 3 and /or 4 in 9 % ) . One patient died of cerebral bleeding during prolonged thrombocytopenia after the second cycle of fludarabine . There were a total of 32 infections in 16 patients , none of which was fatal . The overall response rate ( complete remission [ CR ] and partial remission [ PR ] ) was 87 % ( 27 of 31 evaluable patients ) . In 20 previously untreated patients , 17 ( 85 % ) responded . Ten of 31 patients achieved CR ( 5 of 20 untreated ; 5 of 11 pretreated ; 9 of 21 Binet stage B , 1 of 10 Binet stage C ) . The median duration of response was 75 weeks . We conclude that the combination of rituximab and fludarabine is feasible and effective in patients with B-CLL", "Fludarabine and rituximab combination therapies in chronic lymphocytic leukemia ( CLL ) have yielded promising early results , but no comparative efficacy data relative to st and ard fludarabine treatment regimens have been reported . To assess the effect of the addition of rituximab to fludarabine therapy , we retrospectively compared the treatment outcome of patients with similar clinical characteristics enrolled on 2 multicenter clinical trials performed by the Cancer and Leukemia Group B and the US Intergroup that used fludarabine and rituximab ( CALGB 9712 , n = 104 ) or fludarabine ( CALGB 9011 , n = 178 ) . In multivariate analyses controlling for pretreatment characteristics , the patients receiving fludarabine and rituximab had a significantly better progression-free survival ( PFS ; P overall survival ( OS ; P = .0006 ) than patients receiving fludarabine therapy . Two-year PFS probabilities were 0.67 versus 0.45 , and 2-year OS probabilities were 0.93 versus 0.81 . Infectious toxicity was similar between the 2 treatment approaches . These comparative data are retrospective and could be confounded by differences in supportive care or dissimilar enrollment of genetic subsets on each trial . Confirmation of these findings will require a prospect i ve r and omized trial comparing fludarabine and rituximab to fludarabine", "Alemtuzumab ( anti-CD52 ; Campath-1H ) is effective in fludarabine-refractory chronic lymphocytic leukemia ( CLL ) , but is associated with infection and early onset neutropenia . To reduce toxicity , filgrastim ( G-CSF ) was administered concurrently with alemtuzumab . In total , 14 CLL patients ( median age 59 ) with a median of 3.5 prior regimens ( range 1–12 ) received i.v . alemtuzumab , stepped up from 3 to 30 mg the first week , then 30 mg thrice weekly for 12 weeks . Filgrastim 5 μg/kg was administered daily 5 days before and throughout alemtuzumab therapy . Six patients developed cytomegalovirus ( CMV ) reactivation 3–6 weeks into treatment ; six patients developed fever , three neutropenia , and one pneumonia . The patient with CMV pneumonia died ; ganciclovir cleared CMV in the other patients . Five patients developed early neutropenia ( weeks 2–5 ) . Four patients developed delayed neutropenia ( weeks 10–13 ) unassociated with CMV reactivation . Nine patients ceased therapy because of infectious and hematologic toxicity . Five partial responses were noted , all in patients with lymph nodes > 5 cm , lasting a median of 6.5 months ( range 5–13 ) . Filgrastim and alemtuzumab were given concurrently with manageable infusion toxicity and clinical activity , but the efficacy of this regimen was limited by delayed neutropenia of unclear etiology and CMV reactivation . Filgrastrim should not be administered prophylactically during alemtuzumab therapy outside clinical trials", "Ninety-six patients with stage III and stage IV chronic lymphocytic leukemia ( CLL ) were r and omized into one of three treatment schedules . Prednisone was common to all three schedules and was given daily in an initial dosage of 0.8 mg/kg for the first 14 days , with successive halving of the daily dose on days 15 and 29 for a total 6-wk course . Prednisone was then given once a month at 0.8 mg/kg once a day for each of 7 consecutive days . Schedule I was prednisone plus chlorambucil ( CLB ) given as a once-a-month dose of 0.4 - 0.8 mg/kg ; schedule II was both drugs , but the CLB was given as a daily dose of 0.08 mg/kg ; schedule III was prednisone alone . Complete and partial remission ( CR + PR ) was 47 % for schedule I , 38 % for schedule II , and 11 % for schedule III . Patients who responded ( CR + PR ) in each of the treatment schedules survived longer than the nonresponders . Complete remission was obtained in both CLB treatment schedules , but not with the prednisone alone regimen . Although overall survival was best in the intermittent CLB arm , there was no significant difference in survival time between the three treatment schedules . Toxicity was minimal in all three regimens . Augmentation of the intermittent monthly CLB , even to 1.5 and 2.0 mg/kg , was tolerated without undue marrow toxicity . About 22 % of these patients either had diabetes mellitus at the time of entry on the study or manifested hyperglycemia during the course of treatment and observation ", "N 1988 , THE National Cancer Institute-sponsored Working Group ( NCI-WC ) on chronic lymphocytic leukemia ( CLL ) published guidelines for the design and conduct of clinical trials in CLL with two major objectives : first , to facilitate comparisons of results of clinical trials in CLL by providing st and ardized eligibility , response , and toxicity criteria ; and , second , to encourage a framework on which to evaluate new scientific studies related to our increasing underst and ing of the biology and immunology of this disease . ' These guidelines were rapidly adopted by the majority of the clinical trials community , and were also used by the Food and Drug Administration during its evaluation process for the approval of fludarabine . The differences between these guidelines and those subsequently published by the International Working Group on CLL ( IWCLL ) , which were general- practice recommendations ' are listed in Table 1 . For diagnosis , the NCI-WC requires a lymphocyte count of 5 X loy & which is lower than the 10 X 109/L required by the IWCLL , unless the lymphocytes are B cells and the bone marrow is involved . To be considered a complete remission ( CR ) , the NCI-WC criteria specify that less than 30 % lymphocytes must be present in the bone marrow , with a recommendation that the clinical significance of lymphoid nodules be assessed prospect ively ( Table 1 ) ; the IWCLL allows focal infiltrates or nodules in the bone marrow aspirate and biopsy for CR . The IWCLL uses a shift in clinical stage as the sole index of partial remission ( PR ) , whereas the NCI-WC provides more specific criteria and recommends validation of the relevance of stage shift . The major differences were the well-defined criteria in the NCI guidelines regarding when to initiate therapy , hematologic toxicity , and other important components for clinical trials design . The purpose of this report is to present those revisions as considered necessary in view of advances in the past 8 years . Many of these revisions evolved as the guidelines were used in a systematic fashion in large clinical trials and , also , with the experience following the use of newer , more effective agents , such as fludarabine . \" ' Although this report will focus on those changes recommended by the NCI-sponsored CLL Working Group , it will include sufficient details from the original guidelines so that the reader would find it a complete document by itself without having to refer to the older version", "The efficacy and toxicity of cladribine ( 2-CdA ) + prednisone ( P ) versus chlorambucil ( Chl ) + P were compared in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia ( CLL ) in a r and omized , multicenter prospect i ve trial . Eligible patients were assigned to either 2-CdA 0.12 mg/kg per day in 2-hour infusions and P 30 mg/m(2 ) per day for 5 consecutive days or Chl 12 mg/m(2 ) per day and P 30 mg/m(2 ) per day for 7 consecutive days . Three courses were administered at 28-day intervals or longer if myelosuppression developed . The therapy was finished if complete response ( CR ) was achieved . Of 229 available patients 126 received 2-CdA+P and 103 received Chl+P as a first-line treatment . CR and overall response rates were significantly higher in the patients treated with 2-CdA+P ( 47 % and 87 % , respectively ) than in the patients treated with Chl+P ( 12 % and 57 % , respectively ) ( P = .001 ) . Progression-free survival was significantly longer in the 2-CdA-treated group ( P = .01 ) , but event-free survival was not statistically different . Thirteen percent of patients were refractory to 2-CdA+P and 43 % to Chl+P ( P = .001 ) . Drug-induced neutropenia was more frequently observed during 2-CdA+P ( 23 % ) than Chl+P therapy ( 11 % ) ( P = .02 ) , but thrombocytopenia occurred with similar frequency in both groups ( 36 % and 27 % , respectively ) . Infections were seen more frequently in the 2-CdA+P-treated group ( 56 % ) than in the Chl+P-treated group ( 40 % ; P = .02 ) . Death rates have so far been similar in patients treated with 2-CdA ( 20 % ) and with Chl ( 17 % ) . The probability of overall survival calculated from Kaplan-Meier curves at 24 months was also similar for both groups ( 78 % and 82 % , respectively ) . ( Blood . 2000;96:2723 - 2729", "Recent studies have suggested that epoetin treatment of anaemia may influence the survival of patients with cancer . We conducted an analysis of long‐term survival in patients with lymphoproliferative malignancies treated with epoetin‐β or placebo in a large‐scale study . This was a r and omized , double‐blind trial in which patients with transfusion‐dependent anaemia and lymphoproliferative malignancy received epoetin‐β 150 IU/kg or placebo three times weekly for 16 weeks . Long‐term survival data were analysed by st and ard Kaplan – Meier methods and differences between groups were assessed using a log‐rank test . The intention‐to‐treat population consisted of 343 patients ( epoetin‐β , n = 170 ; placebo , n = 173 ) . There were no major differences between the two treatment groups in demographic or clinical characteristics/prognostic factors . A total of 110 ( 65 % ) patients died in the epoetin‐β group ( censored , n = 60 ) and 109 ( 63 % ) died in the placebo group ( censored , n = 64 ) up to the end of long‐term follow up . Kaplan – Meier curves for survival were similar in both groups . Median survival was 17 months with epoetin‐β and 18 months with placebo . A log‐rank test indicated no significant difference in survival ( P = 0·76 ) . This long‐term follow up indicated that epoetin‐β has no significant effect on survival compared to placebo in anaemic patients with lymphoproliferative malignancies", "We have assessed autologous stem cell transplantation after treatment with fludarabine in previously untreated patients with chronic lymphocytic leukemia ( CLL ) . This study is the first to enroll previously untreated patients and follow them prospect ively . The initial response rate to fludarabine was 82 % ( 94 of 115 patients ) . Stem cell mobilization was attempted in 88 patients and was successful in 59 ( 67 % ) . Overall 65 of 115 patients ( 56 % ) entered into the study proceeded to autologous transplantation . The early transplant-related mortality rate was 1.5 % ( 1 of 65 patients ) . The number of patients in complete remission after transplantation increased from 37 % ( 24 of 65 ) to 74 % ( 48 of 65 ) , and 26 of 41 patients ( 63 % ) who were not in complete remission at the time of their transplantation achieved a complete remission after transplantation . The 5-year overall and disease-free survival rates from transplantation were 77.5 % ( CI , 57.2%-97.8 % ) and 51.5 % ( CI , 33.2%-69.8 % ) , respectively . None of the variables examined at study entry were found to be predictors of either overall or disease-free survival . Sixteen of 20 evaluable patients achieved a molecular remission on a polymerase chain reaction ( PCR ) for immunoglobulin heavy-chain gene rearrangements in the first 6 months following transplantation . Detectable molecular disease by PCR was highly predictive of disease recurrence . It is of concern that 5 of 65 ( 8 % ) patients developed posttransplant acute myeloid leukemia/myelodysplastic syndrome", "OBJECTIVE To compare the efficacy of norfloxacin and ciprofloxacin in preventing bacterial infection in neutropenic patients . DESIGN A r and omized , controlled , multicenter trial . SETTING Twenty-one hematologic units in tertiary care or university hospitals . PATIENTS Eight hundred and one consecutive , afebrile , adult patients who had hematologic malignancies or who had bone marrow transplantation and chemotherapy-induced neutropenia ( neutrophil count , less than 1000/mm3 ) expected to last more than 10 days . INTERVENTION Patients were r and omly assigned to receive orally every 12 hours norfloxacin , 400 mg , or ciprofloxacin , 500 mg . MEASUREMENTS Efficacy analysis was done for 619 patients : 319 treated with norfloxacin and 300 treated with ciprofloxacin . MAIN RESULTS More patients receiving ciprofloxacin did not develop fever during neutropenia and did not receive antibiotics ( 34 % ) compared with those receiving norfloxacin ( 25 % ) ( P = 0.01 ) . Patients receiving ciprofloxacin had a lower rate of microbiologically documented infection ( 17 % compared with 24 % ; P = 0.058 ) , particularly of infection from gram-negative bacilli ( 4 % compared with 9 % ; P = 0.03 ) . The interval to the first febrile episode was also longer in patients receiving ciprofloxacin ( 8.3 compared with 7.2 days ; P = 0.055 ) . The rates of clinical ly documented infection , fever of unknown origin , and mortality as well as compliance and tolerability were similar in the two groups . Patients who had neutropenia for less than 15 days , who had severe neutropenia for less than 7 days , and who received antifungal prophylaxis benefited most from ciprofloxacin therapy . CONCLUSION Ciprofloxacin should be used to prevent the development of infection in neutropenic patients with hematologic malignancies", "Combination chemotherapy with fludarabine plus cyclophosphamide ( FC ) was compared with the st and ard regimen of fludarabine monotherapy in first-line treatment of younger patients with chronic lymphocytic leukemia ( CLL ) . Between 1999 and 2003 , a total of 375 patients younger than 66 years who predominantly had advanced CLL were r and omly assigned to receive either fludarabine ( 25 mg/m(2 ) for 5 days intravenously , repeated every 28 days ) or FC combination therapy ( fludarabine 30 mg/m(2 ) plus cyclophosphamide 250 mg/m(2 ) for 3 days intravenously , repeated every 28 days ) . Both regimens were administered to a maximum of 6 courses . FC combination chemotherapy result ed in significantly higher complete remission rate ( 24 % ) and overall response rate ( 94 % ) compared with fludarabine alone ( 7 % and 83 % ; P FC treatment also result ed in longer median progression-free survival ( 48 vs 20 months ; P = .001 ) and longer treatment-free survival ( 37 vs 25 months ; P median overall survival has been observed . FC caused significantly more thrombocytopenia and leukocytopenia but did not increase the number of severe infections . In summary , first-line treatment with FC increases the response rates and the treatment-free interval in younger patients with advanced CLL", "The Eastern Cooperative Oncology Group ( ECOG ) conducted a study in which patients with advanced chronic lymphocytic leukemia ( CLL ) were r and omized between a regimen consisting of chlorambucil ( 30 mg/m2 orally day 1 ) and prednisone ( 80 mg orally days 1 to 5 ) ( C + P ) administered every 2 weeks and a more intensive regimen of cyclosphosphamide ( 300 mg/m2 orally days 1 to 5 ) , vincristine ( 1.4 mg/m2 intravenously [ IV ] day 1 ) , and prednisone ( 100 mg/m2 orally days 1 to 5 ) ( CVP ) given every 3 weeks . Treatment was continued for up to 18 months to maximal response . Of the 122 eligible patients , 60 received C + P , while 62 received CVP . With a median follow-up of 7 years , there were no significant differences in survival ( 4.8 v 3.9 years , P = .12 ) , complete remission ( CR ) rate ( 25 % v 23 % ; P = .83 ) , or duration of response ( 2.0 v 1.9 years ; P = .78 ) between C + P and CVP . Toxicity was modest despite the prolonged treatment . The long median survival of 4.1 years for stage III and IV patients is superior to that usually reported . This could stem from continuing treatment to maximal response rather than an increase in intensity of therapy . These results are comparable to those reported with cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) therapy by other investigators . The data suggest that intermittent C + P administered to maximal response continues to be the st and ard treatment approach for advanced CLL", "The Medical Research Council ( MRC ) Working Party on Leukaemia in Adults has conducted two r and omised trials in CLL since 1978 . CLL 1 ran from 1978 to 1984 and recruited 660 eligible patients . The number of males was twice the number of females and the distribution of cases by stage was different in the sexes : 58 % of females were stage A , 25 % stage B and 17 % stage C ; in males the proportions for stages A , B and C were 40 % , 30 % and 30 % respectively . The most important prognostic factor was stage ( A , B , C ) , followed by age , sex and response to treatment , which were confirmed as independent variables by stratified log-rank and Cox multivariate analyses . Causes unrelated to CLL accounted for 28 % of all deaths and were more common in older patients and in stage A disease . No significant difference was observed between the CLL 1 treatment schedules : chlorambucil , penta Cop and splenic irradiation ( SI ) , although a somewhat better survival was seen for patients treated by SI . ( When CLL deaths only were considered SI appeared superior to chlorambucil ( p less than 0.05 ] . CLL 2 started in 1984 and is still accruing patients ; 556 had been entered by July 1988 . This trial compares early versus delayed therapy for stage A , chlorambucil with and without prednisolone for stages B and C in patients with a small or nonpalpable spleen , and SI vs chlorambucil with or without prednisolone for stages B and C in patients with a larger spleen ( greater than or equal to 5 cm ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "PURPOSE To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab ( FluCam ) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia ( B-CLL ) . PATIENTS AND METHODS A total of 36 patients were treated in this phase II study ( median age , 61.47 years ; mean number of prior chemotherapies , 2.6 ; Binet stage C , n = 28 ) . After an initial dose escalation of alemtuzumab over 3 days , alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days . Treatment was repeated after 28 days for up to six cycles . Restaging ( following National Cancer Institute criteria ) was carried out after cycles 2 and 4 and 1 month after the end of treatment . RESULTS The overall response rate was 83 % ( 11 complete responses , 19 partial responses , one stable disease , and five progressive diseases ) . Two patients with progressive disease developed fungal pneumonias , and one patient died as a result of Escherichia coli sepsis . Two sub clinical cytomegalovirus reactivations occurred . CONCLUSION The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL", "The objective of this study was to investigate the efficacy and safety of alemtuzumab , the humanized anti‐CD52 monoclonal antibody , in patients with B‐cell chronic lymphocytic leukemia and residual disease after chemotherapy", "In a double-blind study , we r and omly assigned 84 patients with chronic lymphocytic leukemia who were judged to be at increased risk of bacterial infection to receive intravenous immunoglobulin G ( 400 mg per kilogram of body weight ) or a placebo every three weeks for one year . Eligible patients had hypogammaglobulinemia , a history of infection , or both . The patients receiving immunoglobulin had significantly fewer bacterial infections during the study period than those receiving placebo ( 23 vs. 42 ; P = 0.01 ) . This reduction was most striking in the patients who completed a full year of treatment ( 14 vs. 36 ; P = 0.001 ) . The period from study entry to the first serious bacterial infection was significantly longer in the patients receiving immunoglobulin ( P = 0.026 ) . There was no significant difference between the two groups in the incidence of nonbacterial infection . Immunoglobulin therapy was tolerated well ; there were no serious adverse reactions , and the incidence of minor reactions was low . We conclude that selected patients with chronic lymphocytic leukemia who are at risk of bacterial infection can be substantially protected from this complication by the regular intravenous administration of immunoglobulin", "PURPOSE Fludarabine and cyclophosphamide ( FC ) , which are active in treatment of chronic lymphocytic leukemia ( CLL ) , are synergistic with the monoclonal antibody rituximab in vitro in lymphoma cell lines . A chemoimmunotherapy program consisting of fludarabine , cyclophosphamide , and rituximab ( FCR ) was developed with the goal of increasing the complete remission ( CR ) rate in previously untreated CLL patients to > /= 50 % . PATIENTS AND METHODS We conducted a single-arm study of FCR as initial therapy in 224 patients with progressive or advanced CLL . Flow cytometry was used to measure residual disease . Results and safety were compared with a previous regimen using FC . RESULTS The median age was 58 years ; 75 patients ( 33 % ) had Rai stage III to IV disease . The CR rate was 70 % ( 95 % CI , 63 % to 76 % ) , the nodular partial remission rate was 10 % , and the partial remission rate was 15 % , for an overall response rate of 95 % ( 95 % CI , 92 % to 98 % ) . Two thirds of patients evaluated with flow cytometry had less than 1 % CD5- and CD19-coexpressing cells in bone marrow after therapy . Grade 3 to 4 neutropenia occurred during 52 % of courses ; major and minor infections were seen in 2.6 % and 10 % of courses , respectively . One third of the 224 patients had > /= one episode of infection , and 10 % had a fever of unknown origin . CONCLUSION FCR produced a high CR rate in previously untreated CLL . Most patients had no detectable disease on flow cytometry at the end of therapy . Time to treatment failure analysis showed that 69 % of patients were projected to be failure free at 4 years ( 95 % CI , 57 % to 81 % )", "BACKGROUND Zeta-chain associated protein (ZAP)-70 has been proposed as a surrogate marker for immunoglobulin heavy-chain variable region ( IgVH ) mutation in chronic lymphocytic leukemia ( CLL ) , but it is still not clear whether it is an independent prognostic factor . METHODS The authors evaluated ZAP-70 expression by flow cytometry in 201 untreated patients and correlated ZAP-70 levels with CD38 expression , genetic abnormalities detected by fluorescence in situ hybridization ( FISH ) , and the time from diagnosis to first treatment . RESULTS Fifty-seven patients ( 28 % ) were positive for ZAP-70 ( > or = 20 % ) . Positive ZAP-70 status was associated with advanced disease stage , atypical morphology , CD38-positive status , trisomy 12 , del(6q ) , or no detectable abnormalities ; negative ZAP-70 status was correlated with del(13q ) as a sole abnormality . The treatment-free interval ( TFI ) was 17.7 months for ZAP-70-positive patients and 44.6 months for ZAP-70-negative patients ( P advanced stage , CD38 > or = 7 % , and the absence of del(13q ) as a sole abnormality as independent factors for short TFI . Excluding FISH , ZAP-70 status acquired independent prognostic value along with CD38 status . The authors proposed a risk model that combines ZAP-70 and CD38 to identify patients who are likely to progress . When both markers were positive , the TFI was 12 months ; when both were negative , the median TFI was 54 months ; a median TFI of 26 months was observed in patients who had discordant results ( P ZAP-70 and CD38 should be tested prospect ively in all patients with early-stage CLL", "Ninety‐six patients with advanced chronic lymphocytic leukemia ( CLL ) ( Stage C ; anemia and /or thrombocytopenia of nonimmune origin ) were r and omized to receive either chlorambucil ( CLR ) ( 0.4 mg/kg orally , day 6 ) plus prednisone ( PDN ) ( 60 mg/m2 orally , days 1–5 ) every 2 weeks or cyclophosphamide ( 600 mg/m2 intravenously , day 6 ) , vincristine ( 1 mg/m2 intravenously , day 6 ) , and prednisone ( 60 mg/m2 orally , days 1–5 ) ( COP ) each month for 5 months . Complete remission ( CR ) was defined as the total disappearance of signs and symptoms related to the disease . Partial remission ( PR ) was considered to be achieved when , after treatment , the clinical stage changed to a less advanced one . Thirty ( 59 % ) responses ( 8 % CR ) with CLR plus PDN and 14 ( 31 % , 2 % CR ) with COP were observed ( P 0.01 ) . The survival was not significantly different for the two groups . Patients previously treated had a lower number of responses ( 11/35 , 31 % ) than those with no previous treatment ( 33/61 , 54 % ) ( P a CR or a good PR had longer survivals ( median not reached ) than those with a poor PR ( median , 25.2 months ) or those who did not respond to treatment ( median , 11.5 months ) ( P < 0.005 )", "Survivals of two series of CLL patients ( 99 from a retrospective series and 196 from a prospect i ve series ) were studied separately . The three main staging systems ( Rai , Binet , Rundles ) agreed well , but as far as survival is concerned , too many stages are defined . The authors performed a Cox multivariate analysis of survival in order to isolate important prognostic factors at diagnosis and to use them to build a simple three‐stage classification . Thrombopenia and anemia appeared as the most important risk factors . Among the nonanemic and nonthrombopenic patients , the number of involved areas was clearly related to prognosis in the authors ' two series . This study allowed the authors to propose a new classification in three prognostic groups . Group C : anemia ( Hb and /or thrombopenia ( platelets Group B : no anemia , no thrombopenia , three or more involved areas ( counting as one each of the following : axillary , cervical , inguinal , lymph nodes , whether unilateral or bilateral , spleen and liver ) ; about 30 % of patients ; median of 7 years . Group A : no anemia , no thrombopenia , less than three involved areas ; about 55 % of patients ; the survival of this group does not seem different from that of the French population of the same age and sex distribution . This three‐stage classification only requires clinical examination and routine hemogram , has a good prognostic value which was confirmed on the series of Montserrat and Rozman ( 146 patients ) , and should therefore be helpful in planning new clinical trials", "PURPOSE Several new prognostic factors predicting rapid disease progression in chronic lymphocytic leukemia ( CLL ) have been identified , including unmutated Ig V(H ) mutational status , del(11)(q23 ) , del(17)(p13.1 ) , and p53 mutations . To date , the impact of these same prognostic factors have not been examined relative to treatment outcome with chemoimmunotherapy . METHODS We examined the impact of these new prognostic factors on predicting treatment outcome in symptomatic , untreated CLL patients who received chemoimmunotherapy with fludarabine and rituximab as part of a completed , r and omized phase II study , Cancer and Leukemia Group B ( CALGB ) 9712 . RESULTS Eighty-eight patients treated as part of CALGB 9712 had detailed prognostic factor assessment performed . Using Ig V(H ) mutational status to classify risk , there was no association between complete response rate with either unmutated Ig V(H ) mutational status or high-risk interphase cytogenetics . However , the median progression-free survival ( PFS ; P = .048 ) and overall survival ( OS ; P = .01 ) were shorter among the Ig V(H ) unmutated patients as compared with the Ig V(H ) mutated patients . Using the hierarchical classification of Döhner , PFS ( P = .005 ) and OS ( P = .004 ) were significantly longer as the classification moved from high risk [ del (11)(q22.3 ) or del (17)(p13.1 ) ] to low risk . CONCLUSION These data demonstrate that high-risk CLL patients characterized by Ig V(H ) unmutated ( > or = 98 % ) or high-risk interphase cytogenetics , including either del(17p ) or del(11q ) , appear to have a shorter PFS and OS with chemoimmunotherapy . Larger prospect i ve studies will be required to determine the independent influence of Ig V(H ) mutational status and interphase cytogenetics on treatment outcome", "PURPOSE To assess the efficacy and toxicity of first-line single-agent rituximab , followed by re-treatment with rituximab at 6-month intervals , in previously untreated patients with chronic lymphocytic leukemia ( CLL ) or small lymphocytic lymphoma ( SLL ) . PATIENTS AND METHODS Forty-four previously untreated patients with CLL/SLL received rituximab 375 mg/m2 weekly for 4 consecutive weeks . All patients were required to have one or more indications for treatment . Patients with objective response or stable disease continued to receive identical 4-week rituximab courses at 6-month intervals , for a total of four courses . RESULTS The objective response rate after the first course of rituximab was 51 % ( 4 % complete responses ) . Twenty-eight patients received one or more additional courses of rituximab . At present , the overall response rate is 58 % , with 9 % complete responses . After a median follow-up of 20 months , the median progression-free survival ( PFS ) time was 18.6 months , and the 1- and 2-year PFS rates were 62 % and 49 % , respectively . Treatment was well tolerated , with only two episodes of grade 3 to 4 infusion-related toxicity . No cumulative toxicity or opportunistic infections occurred . CONCLUSION Single-agent rituximab , used at a st and ard dose and schedule , is active in the first-line treatment of patients with CLL/SLL , producing substantially higher response rates than previously reported in relapsed or refractory patients ( 51 % v 13 % , respectively ) . Re-treatment with rituximab at 6-month intervals is well tolerated . The PFS time of 18.6 months in patients with CLL/SLL seems shorter than the 36- to 40-month median PFSs previously reported with first-line plus maintenance rituximab in patients with follicular lymphoma . Additional follow-up is required to fully assess the impact of this treatment strategy", "PURPOSE To test whether eradication of minimal residual disease ( MRD ) in B-cell chronic lymphocytic leukemia ( CLL ) by alemtuzumab is associated with a prolongation of treatment-free and overall survival . PATIENTS AND METHODS Ninety-one previously treated patients with CLL ( 74 men and 17 women ; median age , 58 years [ range , 32 to 75 years ] ; 44 were refractory to purine analogs ) received a median of 9 weeks of alemtuzumab treatment between 1996 and 2003 . Regular bone marrow assessment s by MRD flow cytometry were performed with the aim of eradicating detectable MRD ( alemtuzumab . Detectable CLL was eradicated from the blood and marrow in 18 patients ( 20 % ) . Median survival was significantly longer in MRD-negative patients compared with those achieving an MRD-positive CR , PR , or NR . Patients achieving an MRD-negative CR had a longer treatment-free survival than patients with MRD-positive CRs , PR , or NR : MRD-negative CRs , not reached ; MRD-positive CRs , 20 months ; PRs , 13 months ; NR , 6 months ( P Overall survival for the 18 patients with MRD-negative remissions was 84 % at 60 months . Eight ( 47 % ) of the MRD-negative patients converted to MRD positivity at a median of 28 months . CONCLUSION MRD-negative remission in CLL is achievable with alemtuzumab , leading to an improved overall and treatment-free survival", "Pilot studies showed that alemtuzumab is active in lymphoproliferative disorders . The authors conducted a Phase II trial to evaluate the efficacy and safety of alemtuzumab in advanced or refractory chronic lymphoproliferative disorders" ]

[ "OBJECTIVES : To assess if the implementation of guidelines for occupational rehabilitation of patients with low back pain by means of process variables -- a set of objective criteria for technical performance and continuity of care -- led to a better outcome in clinical and return to work variables . METHODS : The study group consisted of 59 patients with at least 10 days of sick leave because of low back pain . Univariate analyses as well as multiple logistic regression and Cox 's regression analyses were performed to assess the relation between quality of care and outcome . RESULTS : Process indicators for technical competence , continuity of care , and total performance were all significantly related to satisfaction of employees . Continuity of care and total performance were significantly related to working status at 3 months , and time to return to work . None of the process indicators was related to pain or disability after 3 months follow up . Satisfaction was not related to any of the other outcome variables . This indicates that if guidelines for occupational rehabilitation are met , outcome is better . CONCLUSION : Quality of the process of care was related to outcome . Interventions of occupational physicians need improvement in the areas of continuity of care and communication with treating physicians . The effectiveness of an improved intervention should be studied in a subsequent r and omised clinical trial", "This paper describes a participatory ergonomics program aim ed at early return to regular work of workers suffering from subacute occupational back pain and assesses the perceptions of the participants on the implementation of ergonomic solutions in the workplace . The participatory ergonomics program was used in the rehabilitation of workers suffering from subacute back pain for more than 6 weeks , a program that was associated with an increased rate of return to work . The perceptions of the participatory ergonomics participants were assessed 6 months after completion of the ergonomic intervention through a question naire sent to employer representatives , union representatives and injured workers of participating workplaces . About half of the ergonomic solutions were implemented according to the perception of the participants , with a substantial agreement between respondents", "Study Design . Population ‐based r and omized clinical trial . Objectives . To develop and test a model of management of subacute back pain , to prevent prolonged disability . Summary of Background Data . The present management of back pain seems inadequate , and development of innovative models has been urged . Methods . A model for the treatment of subacute work‐related back pain has been developed and evaluated in a population ‐based r and omized clinical trial . Workers ( n = 130 ) from eligible workplaces in the Sherbrooke area ( N = 31 ) , who had been absent from work for more than 4 weeks for back pain , were r and omized , based on their workplace , in one of four treatment groups : usual care , clinical intervention , occupational intervention , and full intervention ( a combination of the last two ) . The duration of absence from regular work and from any work was evaluated using survival analysis . Functional status and pain were compared at study entry and after 1 year of follow‐up . Results . The full intervention group returned to regular work 2.41 times faster than the usual care intervention group ( 95 % confidence interval 1.19‐4.89 ; P = 0.01 ) . The specific effect of the occupational intervention accounted for the most important part of this result , with a rate ratio of return to regular work of 1.91 ( 95 % confidence interval = 1.18‐3.10 ; P demonstrated either a statistically significant reduction or a trend toward reduction in the three intervention groups , compared with the trend in the usual care intervention group . Conclusions . Close association of occupational intervention with clinical care is of primary importance in impeding progression toward chronicity of low back pain", "OBJECTIVE To assess the efficacy of a back school program for patients with a first episode of acute work-related low back pain requiring compensation . DESIGN A r and omized single-blind controlled trial . SETTING A private physiatrics outpatient clinic . PATIENTS The mean duration of low back pain was 15 days . INTERVENTION Eligible patients were r and omized to a st and ard treatment program that included daily physiotherapy ( n = 86 ) or the same program with the addition of back school ( n = 82 ) . The back school program consisted of three 90-minute sessions given by a single trained instructor at 0 , 1 , and 8 weeks . MAIN OUTCOME MEASURES The primary outcomes were the time off work for the presenting episode of back pain and the number and duration of recurrences in the year following the study onset . Secondary outcomes included the level of pain , spinal mobility , active straight-leg raising , and functional disability assessed by the Oswestry and Rol and -Morris scales . RESULTS Those r and omized to the back school group gained significantly more knowledge , based on the multiple choice examination ( p = .0001 ) and performed the exercise program significantly better ( p = .0001 ) than the st and ard care group . There were no differences between the two treatment groups for either of the primary outcomes . The median time to return to work from r and omization was 33 days for both the back school and the st and ard care groups ( p = .48 ) . The number of compensated recurrences of low back pain over 1 year was similar ( back school = 14 , st and ard care = 10 , p = .16 ) , as was the median duration of these episodes ( back school = 25 days , st and ard care = 70 days , p = .21 ) . There were no significant differences favoring the back school group for any of the secondary outcomes at the posttreatment , 6-month , or 12-month assessment s. CONCLUSION A back school intervention in addition to st and ard care result ed in no reduction in the time to return to work or the number or duration of recurrences of low back pain requiring compensation over a period of one year", "Study Design An inception cohort design was used in which 421 patients were evaluated systematic ally with a st and ard battery of psychosocial assessment tests ( Structured Interview for DSM-III-R Diagnosis , Minnesota Multiphasic Personality Inventory , and Million Visual Pain Analog Scale ) within 6 weeks of acute back pain onset . Objectives The present study evaluated the predictive power of a comprehensive assessment of psychosocial and personality factors in identifying acute low back pain patients who subsequently develop chronic pain disability problems ( as measured by job-work status at 1-year follow-up evaluation ) . Summary of Background Data There has been a relative paucity of prospect i ve research in the United States comprehensively evaluating potential psychoscial risk factors that are associated with those injured workers who subsequently fail to return to work and productivity after 1 year because of low back pain disability . Such research has been quite limited because of the time and cost involved in conducting prospect i ve studies . Methods All study patients were symptomatic with lumbar pain syndrome for no more than 6 weeks , These acute patients were tracked every 3 months , culminating in a structured telephone interview being conducted 1 year after the initial evaluation to document return-to-work status . Results Logistic regression analyses , conducted to differentiate between patients who were back at work after 1 year versus patients who were not because of the original back injury , revealed the importance of three psychosocial measures : self-reported pain and disability , scores on Scale 3 of the Minnesota Multiphasic Personality Inventory , and workers ' compensation and personal injury insurance status . The model generated correctly classified 90.7 % of the cases . Results revealed that major psychopathology , such as depression and substance abuse , did not precede or cause the development of chronic pain disability . Conclusions These results show the presence of a robust “ psychosocial disability factor ” that is associated with those injured workers who are likely to develop chronic low back pain disability problems . Based on these data , a statistical algorithm has been generated that can identify those acute patients who will require early intervention to prevent the development of chronic disability . The second major result is that preinjury or concomitant psychopathology does not appear to predispose patients to chronic pain disability , although high rates of psychopathology have been shown in chronic low back pain . Future research should be directed at emotional vulnerability and psychosocial events in the period after the injury that may lead to chronicity", "Objectives Given the individual and economic burden of chronic work disability in low back pain patients , there is a need for effective preventive interventions . The aim of the present study was to investigate whether problem-solving therapy had a supplemental value when added to behavioral grade d activity , regarding days of sick leave and work status . Design R and omized controlled trial . Patients and Setting Employees who were recently on sick leave as a result of nonspecific low back pain were referred to the rehabilitation center by general practitioner , occupational physician , or rehabilitation physician . Forty-five employees had been r and omly assigned to the experimental treatment condition that included behavioral grade d activity and problem-solving therapy ( GAPS ) , and 39 employees had been r and omly assigned to behavioral grade d activity and group education ( GAGE ) . Outcome Measures Days of sick leave and work status . Data were retrieved from occupational health services . Results Data analyses showed that employees in the GAPS group had significantly fewer days of sick leave in the second half-year after the intervention . Moreover , work status was more favorable for employees in this condition , in that more employees had a 100 % return-to-work and fewer patients ended up receiving disability pensions one year after the intervention . Sensitivity analyses confirmed these results . Conclusions The addition of problem-solving therapy to behavioral grade d activity had supplemental value in employees with nonspecific low back pain", "Abstract Objectives : To quantify the relative contribution of premorbid and episode specific factors in determining the long term persistence of disabling symptoms of low back pain . Design : Prospect i ve cohort study . Setting : Two general practice s in the south Manchester area . Participants : 180 patients , who previously participated in a cross sectional population survey , who consulted because of low back pain during the study period . They were followed at 1 week and 3 and 12 months after consultation . Main outcome measure : Persistent disabling low back pain in the 12 months after the consultation . Results : Disabling low back pain persisted in one third of participants after consultation and was more common with increasing age , among those with a history of low back pain , and in women . Persistence of symptoms was associated with “ premorbid ” factors ( high levels of psychological distress ( odds ratio 3.3 ; 95 % confidence interval 1.5 to 7.2 ) , poor self rated health ( 3.6 ; 1.9 to 6.8 ) , low levels of physical activity ( 2.8 ; 1.4 to 5.6 ) , smoking ( 2.1 ; 1.0 to 4.3 ) , dissatisfaction with employment ( 2.4 ; 1.3 to 4.5 ) ) and factors related to the episode of low back pain ( duration of symptoms , pain radiating to the leg ( 2.6 ; 1.3 to 5.1 ) , widespread pain ( 6.4 ; 2.7 to 15 ) , and restriction in spinal mobility ) . A multivariate model based on six factors identified groups whose likelihood of persistent symptoms ranged from 6 % to 70 % . Conclusions : The presence of persistent low back pain is determined not only by clinical factors associated with pain but also by the premorbid", "BACKGROUND AND METHODS Bed rest is widely advocated for sciatica , but its effectiveness has not been established . To study the effectiveness of bed rest in patients with a lumbosacral radicular syndrome of sufficient severity to justify treatment with bed rest for two weeks , we r and omly assigned 183 subjects to either bed rest or watchful waiting for this period . The primary outcome measures were the investigator 's and patient 's global assessment s of improvement after 2 and 12 weeks , and the secondary outcome measures were changes in functional status and in pain scores ( after 2 , 3 , and 12 weeks ) , absenteeism from work , and the need for surgical intervention . Neither the investigators who assessed the outcomes nor those involved in data entry and analysis were aware of the patients ' treatment assignments . RESULTS After two weeks , 64 of the 92 patients in the bed-rest group ( 70 percent ) reported improvement , as compared with 59 of the 91 patients in the control ( watchful-waiting ) group ( 65 percent ) ( adjusted odds ratio for improvement in the bed-rest group , 1.2 ; 95 percent confidence interval , 0.6 to 2.3 ) . After 12 weeks , 87 percent of the patients in both groups reported improvement . The results of assessment s of the intensity of pain , the bothersomeness of symptoms , and functional status revealed no significant differences between the two groups . The extent of absenteeism from work and rates of surgical intervention were similar in the two groups . CONCLUSIONS Among patients with symptoms and signs of a lumbosacral radicular syndrome , bed rest is not a more effective therapy than watchful waiting", "In an attempt to prevent acute low-back pain from becoming a chronic disability problem , an earlier study developed a statistical algorithm which accurately identified those acute low-back pain patients who were at high risk for developing such chronicity . The major goal of the present study was to evaluate the clinical effectiveness of employing an early intervention program with these high-risk patients in order to prevent the development of chronic disability at a 1-year follow-up . Approximately 700 acute low-back pain patients were screened for their high-risk versus low-risk status . On the basis of this screening , high-risk patients were then r and omly assigned to one of two groups : a functional restoration early intervention group ( n = 22 ) , or a nonintervention group ( n = 48 ) . A group of low-risk subjects ( n = 54 ) who did not receive any early intervention was also evaluated . All these subjects were prospect ively tracked at 3-month intervals starting from the date of their initial evaluation , culminating in a 12-month follow-up . During these follow-up evaluations , pain disability and socioeconomic outcomes ( such as return-to-work and healthcare utilization ) were assessed . Results clearly indicated that the high-risk subjects who received early intervention displayed statistically significant fewer indices of chronic pain disability on a wide range of work , healthcare utilization , medication use , and self-report pain variables , relative to the high-risk subjects who do not receive such early intervention . In addition , the high-risk nonintervention group displayed significantly more symptoms of chronic pain disability on these variables relative to the initially low-risk subjects . Cost-comparison savings data were also evaluated . These data revealed that there were greater cost savings associated with the early intervention group versus the no early intervention group . The overall results of this study clearly demonstrate the treatment- and cost-effectiveness of an early intervention program for acute low-back pain patients", "Abstract We evaluated three different conservative treatment methods for acute low-back pain patients in groups following a manual therapy programme , an intensive training programme , or a general practitioner programme , the latter serving as the control group . Patients aged 19–64 years on sick leave for low-back pain with or without sciatica were included in a prospect i ve r and omised study evaluating outcomes such as impairment , pain , functional disability , socio-economic disability and satisfaction with the treatment or explanations . Evaluation by unbiased observers was performed at 1 , 3 and 12 months . The three treatment groups were comparable at baseline . With regard to satisfaction , the patients in the manual therapy programme and those in the intensive training programme were more satisfied with the treatment than those in the general practitioner programme at all follow-ups . With regard to the explanations of current low-back pain episodes , the patients in the manual therapy programme were more satisfied than those in the general practitioner programme at all follow-ups . The manual therapy programme group were also more satisfied with the explanations than those in the intensive training programme at the 1-month follow-up . However , no differences were revealed between the groups with respect to outcomes on measures of impairment , pain , functional disability or socio-economic disability . All three study groups showed rapid improvement . After 1 month a significant improvement was noted in all outcome values compared with the values on entry to the study . Within the limitations discussed in our study , it is concluded that ( 1 ) patients sick listed with acute low-back pain , with or without sciatica , will be significantly improved after 1 month regardless of conservative treatment programme ; ( 2 ) they will be more satisfied with the treatment if they are referred to a manual treatment programme or a training treatment programme ; ( 3 ) they will be more satisfied with the explanations of the acute low-back problem if they are referred to one of the above groups , especially the manual treatment group ; ( 4 ) they will not show any other differences with respect to subjective and objective variables , either at short-term or at long-term follow-ups", "Study Design . A controlled clinical trial . Objectives . To examine the long‐term effect of an informative approach to low back pain . Summary of Background Data . In management and prevention of low back pain , back school based on an ergonomic approach have played an important role . The effect of such informative interventions is not clear . Methods . A 5‐year follow‐up study was done on patients included in a previous study . The outcome was measured by return to work or still on sick leave . The patients were allocated to an intervention group ( n = 245 ) and a control group ( n = 244 ) . Only the intervention group was called in for examination and intervention and answered a battery of tests for psychological and health factors . The intervention apart from the clinical examination consisted of education in a \" mini back school . \" The program was based on a new medical model for low back pain . Results . Forty‐seven ( 19 % ) of the patients in the intervention group , compared with 84 patients ( 34 % ) in the control group , were still on sick leave after 5 years ( P fewer recurrences of sick leave ( P Based on Internal Health Locus of Control , number of children , and income , 75 % were correctly classified as nonreturners in the intervention group . Conclusions . This study indicates that subchronic low back pain may be managed successfully with an approach that includes clinical examination combined with information for patients about the nature of the problem , provided in a manner design ed to reduce fear and give them reason to resume light activity", "Study Design . A prospect i ve cohort study was conducted on workers cl aim ing earnings-related compensation for low back pain . Information obtained at the time of the initial cl aim was linked to compensation status ( still cl aim ing or not cl aim ing ) 3 months later . Objective . To identify individual , psychosocial , and workplace risk factors associated with the transition from acute to chronic occupational back pain . Summary of Background Data . Despite the magnitude of the economic and social costs associated with chronic occupational back pain , few prospect i ve studies have investigated risk factors identifiable in the acute stage . Methods . At the time of the initial compensation cl aim , a self-administered question naire was used to gather information on a wide range of risk factors . Then 3 months later , chronicity was determined from cl aim ants ’ computerized records . Results . The findings showed that 3 months after the initial assessment , 204 of the recruited 854 cl aim ants ( 23.9 % ) still were receiving compensation payments . A combined multiple regression model of individual , psychosocial , and workplace risk factors demonstrated that severe leg pain ( odds ratio [ OR ] , 1.9 ) , obesity ( OR , 1.7 ) , all three Oswestry Disability Index categories above minimal disability ( OR , 3.1–4 ) , a General Health Question naire score of at least 6 ( OR , 1.9 ) , unavailability of light duties on return to work ( OR , 1.7 ) , and a job requirement of lifting for three fourths of the day or more all were significant , independent determinants of chronicity ( P < 0.05 ) . Conclusions . Simple self-report measures of individual , psychosocial , and workplace factors administered when earnings-related compensation for back pain is cl aim ed initially can identify individuals with increased odds for development of chronic occupational disability", "The intensity of work recovery in LBP has been studied using the National Health Register . Nine hundred forty men , 40 - 47 years old , were selected r and omly from the census register of the city of Göteborg , Sweden . Sickness absence data were obtained from the Health Register , in which all sickness absence from age 16 is recorded . The rate of return to work decreases as expected with an increase in absence period . Different rates were found for different diagnoses , however , with low return intensities in patients with sciatica compared with those with back pain , ie , return to work was slower in patients with sciatica . Men with manual work had a significantly longer average sickness absence than white-collar workers . The intensity of work recovery was lower in blue-collar workers during the first 20 days of absence , while the reverse was true after 20 days of sickness absence , ie , the white-collar workers who were absent more than 20 days had a slower rate of recovery than blue-collar workers who had been absent for 20 days . Data as presented here can be used to study the effect of intervention ( for example , manual therapy ) on the natural course of work recovery . It also can be used , as above , to study differences in sickness absence patterns between different diagnoses and work groups ", "BACKGROUND Rigorous evidence on factors affecting the prognosis of work-related soft-tissue injuries remains limited . Although shown to be important for a wide variety of clinical conditions , recovery expectations have rarely been assessed as prognostic factors for workers with soft-tissue injuries . We examined the predictive role of various measures of recovery expectations among workers with injuries result ing in time off work . METHODS We identified a prospect i ve cohort of 1566 injured workers shortly after they filed a cl aim for their injury with the Ontario Workers ' Compensation Board ( OWCB ) . They had soft-tissue injuries to the back or upper or lower extremities , had new , lost-time cl aims from May to November 1993 and were still off work at the time of the first interview . We interviewed participants by telephone within 3 weeks after the injury and measured their recovery expectations ( perceptions regarding progress , expected change in condition , expected time until return to usual activities and expectations regarding return to usual job ) along with other , potentially important prognostic factors . The primary outcome was total time receiving 100 % wage-replacement benefits during the year following injury , obtained from OWCB administrative files . Self-reported measures of pain , health-related quality of life and functional status , obtained up to 4 times during the year following injury , were both independent predictors and secondary outcomes . RESULTS The 4 measures of recovery expectations together explained one-sixth of the variation in time receiving benefits . All but expectations regarding return to usual job were individually predictive of time receiving benefits . Judging one 's recovery as much better than expected result ed in a 30 % ( 95 % confidence interval [ CI ] 9%-46 % ) faster rate of stopping receiving benefits ( and likely returning to work ) compared with judging one 's recovery as much worse than expected . Similarly , participants who expected to return to usual activities within 3 weeks had a 37 % ( 95 % CI 26%-47 % ) faster rate of stopping receiving benefits than those who responded \" Do n't know \" to this question , and participants who stated that they were fully recovered or would get better soon had a 25 % ( CI 5%-40 % ) faster rate than those who thought they would never get or stay better . Positive recovery expectations were also associated with reductions in pain grade and improvement in functional status outcomes . INTERPRETATION Expectations regarding recovery may provide useful information on the complex process of recovering from work-related soft-tissue injuries . For clinicians , patients ' negative or uncertain expectations may indicate the need for further probing and intervention on psychosocial factors to facilitate recovery" ]

[ "Background There is limited knowledge about what happens to people after long-term sick leave . The aim of this report was to conduct a prospect i ve study of individuals who were on prolonged sick leave during a particular year , considering their activities and sources of income during subsequent years . To enable comparison of different time periods , we used three cohorts of individuals with different starting years . Methods Using data from national registers , three separate cohorts were constructed that included all people living in Sweden who were 20 - 64 years of age ( > 5 million ) in the years 1995 , 2000 and 2005 , respectively . The individual members of the cohorts were classified into the following groups based on their main source of income and activity in 1995 - 2008 : on long-term sick leave , employed , old-age pensioner , long-term unemployed , disability pensioner , on parental leave , social assistance recipient , student allowance recipient , deceased , or emigrated . Results Most individuals on long-term ( > 6 months ) sick leave in 1995 were not employed 13 years later . Only 11 % of the women and 13 % of the men were primarily in employment after 13 years . Instead , a wide range of alternatives existed , for example , many had been granted disability pension , and about 10 % of the women and 17 % of the men had died during the follow-up period . A larger proportion of those with long-term sick leave were back in employment when 2005 was the starting year for the follow-up . Conclusions The low future employment rates for people on long-term sick leave may seem surprising . There are several possible explanations for the finding : The disorders these people may have , might have entailed longst and ing difficulties on the labor market . Besides , long-term absence from work , no matter what its causes were , might have worsen the chances of further employment . The economic cycles may also have been of importance . The improving labor market during later years seems to have improved the chances for employment among those earlier on long-term sick leave", "OBJECTIVE : To examine the effects of weight loss on health-related quality of life ( HRQL ) in subjects with severe obesity . DESIGN : Controlled clinical trial of the outcomes of surgical vs conventional weight reduction treatment . SUBJECTS : The first 487 surgical cases and their conventionally treated , matched controls were followed for two years in the Swedish Obese Subjects ( SOS ) intervention study . MEASUREMENTS : A battery of generic and study -specific self- assessment instruments or subscales was used to characterize HRQL in the severely obese ( BMI ) ≥34 kg/m2 for males and BMI ≥38 kg/m2 for females ) . Measures of general health perceptions ( general health rating index ; current health ) , mental well-being ( mood adjective check list ; pleasantness , activation and calmness ) , mood disorders ( hospital anxiety and depression scale ; anxiety and depression ) and social interaction ( sickness impact profile ) , were supplemented by obesity-specific modules on obesity-related psychosocial problems and eating behavior ( three-factor eating question naire ; restrained eating , disinhibition and perceived hunger ) . Assessment s were conducted prior to treatment and repeated after 6 , 12 and 24 months . RESULTS : Poor HRQL before intervention was dramatically improved after gastric restriction surgery , while only minor fluctuations in HRQL scores were observed in the conventionally treated controls . Peak values were observed in the surgical group at 6 or 12 months after intervention with a slight to moderate decrease at the two-year follow-up . The positive changes in HRQL after two years were related to the magnitude of weight loss , that is , the greater the weight reduction , the greater the HRQL improvements . Eating behavior improved accordingly . CONCLUSION : Quality of life in the severely obese is improved by substantial weight loss . Most patients benefit from weight reduction surgery , while HRQL in surgical patients with minor reduction in overweight is less positive . Further research is needed to determine outcome predictors of the surgical management of severe obesity and to ensure that HRQL improvements are maintained", "BACKGROUND Few long-term reports with high rates of follow-up are available after gastric bypass . We report changes in weight , co-morbidity , cardiovascular risk , and health-related quality of life ( HRQoL ) 5 years after gastric bypass . METHODS Patients who had gastric bypass ( 2004 - 2006 ) were included . Prospect i ve data were review ed . Long-term complications , cardiovascular risk factors , and HRQoL were evaluated , and the 10-year risk for coronary heart disease was estimated ( Framingham risk score ) . Outcomes were compared in patients with body mass index ( BMI ) A total of 184 of 203 patients ( 91 % ) met to follow-up . The mean ± SD preoperative BMI was 46 ± 5 kg/m(2 ) , and the mean ± SD age was 38 ± 9 years ; 75 % were women . Thirty-two percent of the patients had a BMI ≥50 kg/m(2 ) , and 30 % had type 2 diabetes . Follow-up was 63 ± 5 months . After 5 years , total weight loss was 27 % ± 11 % . Remission of type 2 diabetes had occurred in 67 % . The prevalence of hypertension , dyslipidemia , sleep apnea , and metabolic syndrome had decreased . HRQoL was improved . The Framingham risk score was reduced ( 5.6 % versus 4.6 % ; P = .021 ) . Sixty-one patients ( 33 % ) had long-term complications , most commonly chronic abdominal pain ( 10 % ) . BMI was 33 ± 5 and 37 ± 7 kg/m(2 ) in patients with preoperative BMI but changes in metabolic , cardiovascular risk profile and HRQoL were broadly similar . CONCLUSIONS Beneficial effects on weight loss , cardiovascular risk , and HRQoL were documented 5 years after gastric bypass in morbidly and super-obese patients", "OBJECTIVE To evaluate the private third-party payer return on investment for bariatric surgery the United States . STUDY DESIGN Morbidly obese patients aged 18 years or older were identified in an employer cl aims data base of more than 5 million beneficiaries ( 1999 - 2005 ) using International Classification of Diseases , Ninth Revision , Clinical Modification code 278.01 . Each of 3651 patients who underwent bariatric surgery during this period was matched to a control subject who was morbidly obese and never underwent bariatric surgery . Bariatric surgery patients and controls were matched based on patient demographics , selected comorbidities , and costs . METHODS Total healthcare costs for bariatric surgery patients and their controls were recorded for 6 months before surgery through the end their continuous enrollment . To account for potential differences in patient characteristics , we calculated the cost differential by estimating a Tobit model . A return on investment was estimated from the result ing coefficients . Costs were inflation adjusted to 2005 US dollars using the Consumer Price Index for Medical Care , and the cost savings were discounted by 3.07 % , the month Treasury bill rate during the same period . RESULTS The mean bariatric surgery investment ranged from approximately $ 17,000 to $ 26,000 . After controlling for observable patient characteristics , we estimated all costs to have been recouped within 2 years for laparoscopic surgery patients and within 4 years for open surgery patients . CONCLUSIONS Downstream savings associated with bariatric surgery are estimated to offset the initial costs in 2 to 4 years . R and omized or quasiexperimental studies would be useful to confirm this conclusion , as unobserved characteristics may influence the decision to undergo surgery and can not be controlled for in this analysis", "BACKGROUND Physical , emotional , and social functioning are impaired in obesity . It is unknown whether and , if so , to what extent and in which domain obese subjects who lose weight may catch up to normal-weight levels . Our objective was to compare the health-related quality -of-life ( HRQL ) of obese subjects with that of a normal-weight reference group before and 1 year after a weight loss program that centered around laparoscopic and open gastric b and ing . METHODS An HRQL question naire consisting of a battery of both generic and specific measures was administered to 50 morbidly obese subjects on 2 occasions and to 100 healthy , normal-weight subjects , matched for age , gender , education , and vocational training . In addition to weight loss and health gain , the influences of achieved weight loss goals , satisfaction with outcome and operative approach ( laparoscopy/laparotomy ) were assessed . RESULTS Quality -of-life was significantly impaired in obese subjects . With a substantial weight loss of 35 kg and 42 % loss of excessive weight , and correction of disturbed metabolic parameters , they significantly improved in general well-being , health distress , and perceived attractiveness , approaching halfway the values of a normal-weight reference group . Improvement in values for depression and self-regard lagged behind . In physical activity , they bypassed the reference group . Days of sick leave decreased to the level of the reference group . Improvements in HRQL paralleled the rate of weight loss . Personal satisfaction and surgical approach were of minor influence . CONCLUSIONS The obese subjects ' impaired physical and social functioning improved considerably , catching up midway to normal-weight reference values after weight loss . Psychologic amelioration lagged behind . Whether the latter will catch up later and physical/social improvements will be maintained is the subject of further studies", "Background The purpose of this study was to determine the impact of bariatric surgery on employment status in underserved , unemployed patients with severe obesity . Methods A retrospective review of all unemployed severely obese patients seen in our urban safety-net bariatric surgery program was performed . Preoperative patient question naires and medical records were review ed to evaluate patient employment status at the time of initial evaluation by the multidisciplinary bariatric surgery team . Follow-up data was obtained on all available patients ( including those who did not undergo surgery ) , including weight and employment status . A st and ardized telephone question naire was administered to supplement details regarding employment . Changes in employment status and body weight were determined in both groups . Results Here , 193 unemployed severely obese patients were evaluated by the multidisciplinary obesity team . The vast majority of patients ( > 80 % ) were minorities ( primarily Hispanic ) and publicly insured . Seventy-two underwent bariatric surgery and 121 did not . Twenty-four percent of the surgical patients and 9 % of the non-surgical patients had acquired full-time employment at least one year postoperatively ( p = 0.043 ) . There was a 10-point body mass index reduction in the surgical group , compared to 1-point reduction in the non-surgical group after one year . Conclusions Bariatric surgery may improve employment status in an unemployed severely obese patient cohort . Future research in this area should collect detailed prospect i ve data on employment prior to surgery and assess changes longitudinally to provide a more complete picture of the impact of bariatric surgery on employment", "BACKGROUND Obesity is an increasing public health problem . A small number of studies have examined the relationship between obesity and sickness absence , with mixed results , particularly regarding short-term sickness absence . AIMS To determine if obesity is associated with short- and long-term sickness absence and to investigate the mechanisms that may underlie any association . METHODS Cross-sectional ( n = 1489 ) and prospect i ve ( n = 625 ) analyses were conducted on staff from London Underground Ltd. All participants underwent regular clinical examinations that involved their height and weight being measured , obesity-related medical problems being diagnosed and psychiatric disorders being identified . The number of days taken for short- ( long-term sickness absence were recorded by managers on an electronic data base . RESULTS There was a positive linear association between employees ' body mass index ( BMI ) and the number of days ' work missed due to sickness absence on both cross-sectional and prospect i ve analyses ( P short- and long-term sickness absence . Obese individuals typically took an extra 4 days sick leave every year . The majority of the increased risk for long-term sickness absence appeared to be mediated via co-morbid chronic medical conditions . The excess short-term sickness absence was not explained by obesity-related medical problems , psychiatric disorders or workplace factors . CONCLUSIONS Obese employees take significantly more short- and long-term sickness absence than workers of a healthy weight . There is growing evidence to support employers becoming more involved in tackling obesity", "BACKGROUND Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk , but whether these benefits persist over time is unknown . METHODS The prospect i ve , controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched , conventionally treated obese control subjects . We now report follow-up data for subjects ( mean age , 48 years ; mean body-mass index , 41 ) who had been enrolled for at least 2 years ( 4047 subjects ) or 10 years ( 1703 subjects ) before the analysis ( January 1 , 2004 ) . The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years . RESULTS After two years , the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group ( P weight had increased by 1.6 percent and decreased by 16.1 percent , respectively ( P Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period . Two- and 10-year rates of recovery from diabetes , hypertriglyceridemia , low levels of high-density lipoprotein cholesterol , hypertension , and hyperuricemia were more favorable in the surgery group than in the control group , whereas recovery from hypercholesterolemia did not differ between the groups . The surgery group had lower 2- and 10-year incidence rates of diabetes , hypertriglyceridemia , and hyperuricemia than the control group ; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable . CONCLUSIONS As compared with conventional therapy , bariatric surgery appears to be a viable option for the treatment of severe obesity , result ing in long-term weight loss , improved lifestyle , and , except for hypercholesterolemia , amelioration in risk factors that were elevated at baseline", "Abstract Purpose : To examine the associations between medical , work-related , organizational and sociodemographic factors and job loss during sick leave in a Dutch population of 4132 employees on sick leave . Methods : Data were assessed by occupational health physicians ( OHPs ) on sociodemographic , medical , work-related and organizational factors . Odds ratios for job loss were calculated in logistic regression models . Results : Job loss during sick leave is associated with mental disorder , a history of sick leave due to these disorders , lack of co-worker and supervisor support , job insecurity and working as a civil servant or a teacher . Associations vary for gender and for company size . Conclusions : Job loss during sick leave is associated with medical , work-related , organizational and socio-demographic factors . The findings of this study might help the OHP or other health professionals involved in the management of employees on sick leave to identify those employees who are at risk for job loss during sick leave , and might help policymakers to decide on priorities in prevention and treatment . Future studies should have a longitudinal , prospect i ve design and include information about the type of contract , possible causes for job loss , severity and treatment of the disorder causing the sick leave . Implication s for Rehabilitation The labor market moves to more and more flexible and temporary contracts . This leads to more precarious types of employment . The risk of job loss during sick leave is associated with medical , work-related , organizational and sociodemographic factors . Occupational health physicians and other professionals in the field of work rehabilitation should be aware of these associations to prevent job loss due to these factors", "Background Patients undergoing bariatric surgery generally report improved work performance after this procedure ; however , previous research has been limited by a lack of st and ardized employment measures and a failure to account for the impact of psychiatric illness on employment outcomes . To address these limitations , this study aims to assess changes in patients ’ employment impairment and productivity 12 months post-surgery and to identify psychosocial predictors of change in employment outcomes . Methods A total of 164 patients underwent bariatric surgery between February 2010 and November 2012 in this prospect i ve cohort study . The primary outcome was a change in employment impairment ( EI ) as measured by total Lam Employment Absence and Productivity Scale ( LEAPS ) scores and changes in participants ’ job status category . Multiple linear regression models assessed whether baseline demographic or clinical factors , including a history of psychiatric illness and changes in depressive , anxiety and quality of life ( QOL ) symptoms , were associated with a change in LEAPS scores . Results Participants reported a significant reduction in EI post-surgery ( p improvement in work productivity ( p in depression ( confidence interval ( CI ) 0.46 , 0.76 , p ) , anxiety ( CI 0.49 , 0.85 , p and mental QOL ( CI −0.30 , −0.17 , p in EI total scores . Logistic regression analysis did not identify significant predictors of change in participant job status . Conclusions Patients with pre-bariatric surgery psychiatric distress are more likely to report greater employment impairment and worse employment productivity pre-surgery . These patients also experience the greatest improvements in post-surgery employment functioning " ]

[ "The purpose of this prospect i ve , r and omised study was to evaluate the clinical and radiological results comparing the identical cemented or cementless NexGen total knee prostheses implanted bilaterally in the same patient . Sequential simultaneous bilateral total knee replacements were performed in 50 patients ( 100 knees ) . There were 39 women and 11 men with a mean age of 58.4 years ( 51 to 67 ) who received a cemented prosthesis in one knee and a cementless prosthesis in the other . The mean follow-up was 13.6 years ( 13 to 14 ) . At final review , the mean Knee Society scores ( 96.2 ( 82 to 100 ) versus 97.7 ( 90 to 100 ) ) , the mean Western Ontario and McMaster Universities osteoarthritis index ( 34.5 ( 4 to 59 ) versus 35.6 ( 5 to 51 ) ) , the mean ranges of knee movement ( 124 ° ( 100 ° to 140 ° ) versus 128 ° ( 110 ° to 140 ° ) ) , mean patient satisfaction ( 8.1 ( SD 1.9 ) versus 8.3 ( SD 1.7 ) ) , and radiological results were similar in both groups . The rate of survival of the femoral components was 100 % in both groups at 14 years . The rate of survival of the cemented tibial component was 100 % and 98 % in the cementless tibial component . No osteolysis was identified in either group . Our data have shown no advantage of cementless over cemented components in total knee replacement", "A significant increase in younger patients undergoing total knee arthroplasty raises the theoretical concern for revision secondary to micromotion and fixation failure with cemented components . We prospect ively studied 100 consecutive tantalum monoblock uncemented tibial components and 312 concurrent cemented controls . Patients younger than 55 years with adequate bone stock were enrolled . This cementless patient group was younger and had higher preoperative functional status . Prostheses were posterior-substituting uncemented femoral and tibial components with a cemented patellar button . Knee Society pain and function scores and radiographs were obtained , and a cost analysis was performed . Knee Society scores were excellent and equivalent beyond 6 months . There was no significant difference in perioperative blood loss , complication rates , or cost . There was a significant decrease in operative time in the uncemented group . Radiographs revealed no failures of ingrowth at last follow-up . There were 3 uncemented group failures , but none were due to failure of fixation . The use of a porous tantalum tibia at minimum 5 years has yielded promising clinical and radiographic results in a younger patient population", "We report the long-term survival of a prospect i ve r and omised consecutive series of 501 primary knee replacements using the press-fit condylar posterior cruciate ligament-retaining prosthesis . Patients received either cemented ( 219 patients , 277 implants ) or cementless ( 177 patients , 224 implants ) fixation . Altogether , 44 of 501 knees ( 8.8 % ) underwent revision surgery ( 24 cemented vs 20 cementless ) . For cemented knees the 15-year survival rate was 80.7 % ( 95 % confidence interval ( CI ) 71.5 to 87.4 ) and for cementless knees it was 75.3 % ( 95 % CI 63.5 to 84.3 ) . There was no significant difference between the two groups ( cemented vs cementless ; hazard ratio ( HR ) 0.83 , 95 % CI 0.45 to 1.52 , p = 0.55 ) . When comparing the covariates there was no significant difference in the rates of survival between the side of operation ( HR 0.58 , p = 0.07 ) , age ( HR 0.97 , p = 0.10 ) and diagnosis ( HR 1.25 p = 0.72 ) . However , there was a significant gender difference , with males having a higher failure rate with cemented fixation ( HR 2.48 , p = 0.004 ) . Females had a similar failure rate in both groups . This single-surgeon series , with no loss to follow-up , provides reliable data of the revision rates of one of the most commonly-used total knee replacements . The survival of the press-fit condylar total knee replacement remained good at 15 years , irrespective of the method of fixation", "We have carried out a long-term survival analysis of a prospect i ve , r and omised trial comparing cemented with cementless fixation of press-fit condylar primary total knee replacements . A consecutive series of 501 replacements received either cemented ( 219 patients , 277 implants ) or cementless ( 177 patients , 224 implants ) fixation . The patients were contacted at a mean follow-up of 7.4 years ( 2.7 to 13.0 ) to establish the rate of survival of the implant . The ten-year survival was compared using life-table and Cox 's proportional hazard analysis . No patient was lost to follow-up . The survival at ten years was 95.3 % ( 95 % CI 90.3 to 97.8 ) and 95.6 % ( 95 % CI 89.5 to 98.2 ) in the cemented and cementless groups , respectively . The hazard ratio for failure in cemented compared with cementless prostheses was 0.97 ( 95 % CI 0.36 to 2.6 ) . A comparison of the clinical outcome at ten years in 80 knees showed no difference between the two groups . The survival of the press-fit condylar total knee replacement at ten years is good irrespective of the method of fixation and brings into question the use of more expensive cementless implants", "Purpose : The objective of this prospect i ve study was to evaluate the medium-term clinical and radiological results after navigated cementless implantation , without patella resurfacing , of a total knee endoprosthesis with tibial and femoral press-fit components , with a focus on survival rate and clinical outcome . The innovation is the non-cemented fixation together with the use of a navigation system . Scope and Methods : Sixty patients with gonarthrosis were included consecutively in this study . In all cases , the cementless Columbus total knee endoprosthesis with a coating out of pure titanium was implanted , using a navigation system . The Knee Society Score showed a statistically significant increase from 75 ( ± 21.26 ) before surgery to 180 ( ± 16.15 ) after a mean follow-up of 5.6 ( ± 0.25 ) years . The last radiological examination revealed no osteolysis . No radiolucent lines were seen at any time in the area of the femoral prosthetic components . In the tibial area , radiolucent lines were seen in 24.4 % of the cases , mostly in the distal uncoated part of the stem . During follow-up , no prosthesis had to be replaced because of aseptic loosening while in 2 cases revision surgery was necessary due to septic loosening and in 1 case due to unexplainable pain . Results and Conclusions : Navigated cementless implantation of the Columbus total knee endoprosthesis yielded good clinical and radiological results in the medium term . The excellent radiological osteointegration of the prosthetic components , coated with a microporous pure titanium layer and implanted with a press-fit technique , should be emphasized", "We have carried out a prospect i ve study comparing the results at five years in patients older than 75 years of age undergoing hydroxyapatite-coated , cementless total knee replacement ( TKR ) with those who were younger . The Knee Society clinical rating scores were recorded before and after operation . Of 559 patients undergoing TKR , 135 were in the elderly age group . The knee scores at five years or more showed comparable results , with patients under 75 years of age reaching a score of 183 and those aged 75 years or over reaching 174 . These differences were predominantly due to the functional component of the score . We conclude that elderly patients do just as well as the younger group using this prosthesis", "We carried out a prospect i ve study of 118 hydroxyapatite-coated , cementless total knee replacements in patients who were The mean period of follow-up was 7.9 years ( 5 to 12.5 ) . The Knee Society clinical scores improved from a pre-operative mean of 98 ( 0 to 137 ) to a mean of 185 ( 135 to 200 ) at five years , and 173 ( 137 to 200 ) at ten years . There were two revisions of the tibial component because of aseptic loosening , and one case of polyethylene wear requiring further surgery . There was no osteolysis or progressive radiological loosening of any other component . At 12 years , the overall rate of implant survival was 97.5 % ( excluding exchange of spacer ) and 92.1 % ( including exchange of spacer ) . Cementless total knee replacement can achieve excellent long-term results in young , active patients with osteoarthritis . In contrast to total hip replacement , polyethylene wear , osteolysis and loosening of the prosthesis were not major problems for these patients , although it is possible that this observation could change with longer periods of follow-up", " A prospect ively studied group of 59 knees with cementless fixation were compared to a retrospectively studied but matched group of 59 knees with cement fixation using a Press Fit Condylar prosthesis . The only significant preoperative difference between the patient groups was mean age ; the cemented group was on average nine years older than the cementless group ( p knee scores between the two groups . Radiolucent lines adjacent to the tibial component were similar in both groups . The complication rate of 20 % in the cementless knees was higher than the 12 % rate in the cemented knees ; this was primarily related to polyethylene wear of metal-backed patellar components . Cement or cementless fixation of this prosthesis appears to provide equivalent early results", " This study examines the early clinical and radiographic results of the first 216 cases of a cementless fixed bearing tibial tray without screw holes in 191 patients . We hypothesize that stable fixation can be achieved without the use of screws . There were 16 cases lost to follow-up , leaving 200 cases with known outcome . The Hospital for Special Surgery knee scores improved from an average preoperative score of 54/100 to 82/100 postoperatively . Three patients had incomplete radiolucent lines involving the medial aspect of the tibial tray . All of the tibial components review ed radiographically were bone ingrown . We conclude that the tray provides excellent primary stability , allowing early bone ingrowth , free from osteolysis and with good clinical outcomes . All of the tibial components were bone ingrown by radiographic criteria", "The Miller-Galante I knee replacement was inserted in 25 women and three men ( 33 knees ) with osteoarthrosis . All patients received a TiAlV femoral component with a commercially pure titanium fiber-mesh undersurface . Cemented or cementless fixation was used based on a r and omization protocol . Micromotions of the femoral components were recorded with roentgen stereophotogrammetric analysis during the first 2 postoperative years . The magnitude of migration did not differ between cemented and uncemented fixation . The number of nonmigrating prostheses decreased from 21 ( 12 cemented and nine uncemented ) at 3 months to six ( three cemented and three uncemented ) at 24 months . In both groups , the magnitude of prosthetic tilting about the longitudinal axis ( internal-external rotation ) was as large as that about the transverse axis ( flexion-extension ) . Rotation into extension was as common as rotation into flexion . The largest translations were recorded at either of the posterior condyles . In 10 uncemented components , radiolucent lines were seen at the distal interface postoperatively . Proximal migration of the femoral component was recorded in these knees , and the width of the lines decreased or the lines disappeared totally at 24 months . After 2 years , lines were noted around four cemented and four uncemented replacements , mainly anteriorly or distally . All of these prostheses migrated . One prosthesis , revised because of malalignment , displayed pronounced migration after an initial period of stability . Bone ingrowth was observed anteriorly and anterodistally despite the presence of motions of 1 mm or more", "We performed a prospect i ve study of 54 patients ( 76 knees ) who underwent Osteonics series 3000 cruciate-retaining cementless total knee arthroplasty between December 1990 and June 1993 . Five patients ( seven knees ) were lost to follow-up ( 90.7 % completion ) . One patient required revision at 10.5 years after operation . The rate of survival was 100 % at ten years and 96.7 % at 13 years . The mean ten-year knee and function scores were 79 and 59 respectively . Both were significantly better than the pre-operative scores . The range of movement also improved . Although a radiolucent line around the tibial component enlarged in six knees ( 20.7 % ) at ten years , the clinical outcome was generally good . In a patient who died after 5.5 years , post-mortem examination of the knee showed no bony ingrowth into the tibial component . Despite poor bony ingrowth , press-fit fixation was satisfactory and good results can be obtained with this cementless , cruciate-retaining prosthesis", "We studied the effect of a layer of cement placed under the tibial component of Freeman-Samuelson total knee prostheses with a metal back and an 80 mm intramedullary stem , using roentgen stereophotogrammetry to measure the migration of the tibial component during one year in 13 uncemented and 16 cemented knees . The addition of cement produced a significant reduction in migration at one year , from a mean of 1.5 mm to one of 0.5 mm ( p less than 0.01 ) , including a significant reduction in pure subsidence . One year postoperatively the clinical results were similar between the groups , but , at three years , one uncemented knee had required revision", "Twenty-six women and three men ( 34 knees ) with osteoarthrosis were operated with the Miller-Galante I ( Zimmer , Warsaw , IN ) knee prosthesis . The patients were r and omized to either cemented or uncemented fixation of the tibial component . All patients received a TiVaAl alloy tibial plate with four pegs and titanium fiber-mesh undersurface . In the uncemented knees four screws were added . The fixation of the tibial component was determined by roentgen stereophotogrammetric analysis during the first 2 postoperative years . Rotations of the entire tibial component were recorded , as well as proximal or distal translation of various parts of the prosthetic edge corresponding to subsidence and lift-off . The uncemented components displayed almost all rotation and translation during the first 6 weeks , whereas the cemented ones displayed a more gradually increasing migration during the 2 years . Tibial component rotation about the sagittal axis was significantly increased in the uncemented knees throughout the investigation period . This corresponded to increased subsidence medially or laterally in the uncemented knees , whereas lift-off was equal in the two groups . Thin ( 8.5 mm ) uncemented tibial components displayed more subsidence than the thicker ones at the medial or lateral edge 3 months after surgery", " Fifty-five total knee arthroplasties ( TKAs ) in thirty-nine adult ( mean age , 62 years ) patients with rheumatoid arthritis were studied prospect ively for a period of 1 - 7 years . All of the procedures were performed using cementless fixation of the tibial and femoral components . The Knee Society clinical rating system mean knee scores increased 56 points after operation ( mean , 88 points ) , and the mean functional scores increased 28 points ( mean , 64 points ) . Two revisions ( 4 % ) have been required , one for secondary late infection and one for failure of a cementless metal-backed patellar component . Good bone stock was retained in both , allowing for uneventful cementless revision . Forty-two arthroplasties ( 76 % ) were completely pain-free , twelve ( 22 % ) had mild , occasional discomfort with weight-bearing , and one ( 2 % ) had moderate pain at last examination . In this older rheumatoid population , cementless TKA offers good or excellent early clinical results and excellent preservation of bone stock should revision become necessary", "We performed a 12-month prospect i ve study on 59 patients ( 92 knees ) who underwent NexGen ( Zimmer Inc , Warsaw , IN ) cruciate-retaining total knee arthroplasty . In the control group , uncoated components were fixed using screws , whereas the hydroxyapatite-tricalcium phosphate ( HA-TCP ) group underwent screwless fixation of coated components . At 12 months postoperatively , there was a radiographic clear zone around the femoral and tibial components of 56.5 % and 32.6 % of the knees in the control group . The HA-TCP group showed a clear zone at the medial aspect of the tibial component in only 1 knee . These results suggested that HA-TCP-coated articular components show good initial fixation without using screws . The NexGen coated knee arthroplasty may be useful for solving the problems of cementless fixation", "This study compared two groups of consecutive patients undergoing total knee arthroplasty ( TKA ) with an identical cementless tibial baseplate supplementally fixated with and without screws . In 58 TKAs , two 6.5-mm cancellous screws were used for fixation , and in 58 TKAs , screwless fixation was used . Clinical evaluation was performed using the Hospital for Special Surgery knee score , and fluoroscopically guided radiographs were evaluated for radiolucencies . In the screw fixation group , average follow-up was 82+/-6 months ( range , 59 - 89 months ) and average patient age at surgery was 63 years . For the screwless fixation group , average follow-up was 67+/-5 months ( range , 48 - 76 months ) and average patient age at surgery was 62 years . Average knee score was 97 for the screw fixation group and 98 for the screwless fixation group . This study demonstrated stability in cementless TKA both with and without screw fixation in the mid-term using the Natural-Knee II tibial component", "BACKGROUND The aim of this prospect i ve paper is to present the results of a cementless LCS rotating-platform artificial knee design without resurfacing of the patella in patients over 60 years of age . MATERIAL / METHODS In this prospect i ve series , 234 patients were included with 251 knees . The LCS rotating-platform uncemented design was used in all cases , without replacement of the patella . Thirty-four patients were men and 200 were women . Two hundred three patients were suffering from osteoarthrosis ( 10 bilateral ) and 31 patients ( 7 bilateral ) from rheumatoid arthritis . Seventeen patients had a bilateral procedure . Prophylactic antibiotics and anticoagulants were also instituted to all patients . RESULTS Forty-nine patients developed deep vein thrombosis and responded well to the applied conservative treatment . Overall results in the first 251 cementless cases at 2 to 9.8 years ' follow-up ( average : 5.7 years ) were good to excellent in 94.4 % , fair in 4.7 % , and poor in 0.7 % . Radiographs of the knees showed good bonding and no signs of radiolucency . The average clinical and functional Knee Society Ratings were 21.07 points and 30.95 points , respectively , preoperatively and 87.95 points and 78.56 points , respectively , at the final follow-up evaluation . CONCLUSIONS With an average follow-up of 5.7 years , uncemented LCS rotating-platform knee joint arthroplasty without replacing the patella in patients over 60 years old was found to perform well , with encouraging clinical and radiological results and a survival rate of 98.1 %", " A prospect ively studied group of 55 uncemented Press Fit Condylar total knee arthroplasties was compared retrospectively with a matched group of 51 cemented Press Fit Condylar total knee arthroplasties at a mean of 10 years after operation . For the cemented group , the pain and function scores improved from 32 and 45 preoperatively to 95 and 77 , respectively . For the uncemented group the scores improved from 33 and 50 preoperatively to 93 and 60 , respectively . There were 10 revisions in the uncemented group for femoral or tibial aseptic loosening or osteolysis compared with two revisions in the cemented group . Exclusive of problems related to patellar metal backing , survival to revision for aseptic failure or radiographic loosening was 72 % in the uncemented group and 94 % in the cemented group at 10 years . A significantly higher revision rate was found in the uncemented compared with cemented total knee arthroplasty of the Press Fit Condylar design", "Cementless posteriorly stabilized ( PS ) total knee arthroplasty has not been widely accepted primarily because of prior unpredictable results and concern about micromotion at the tibial fixation interface caused by the cam/post interaction . A prospect i ve consecutive series of 114 cementless , tricompartmental periapatite-coated single-radius PS implants in 110 patients with a mean age 62 years was performed to determine if initial stability and biologic fixation could be achieved . At a mean follow-up of 36 months , all implants demonstrated radiographic evidence of stable biologic fixation with no evidence of loosening , osteolysis , stress shielding , or progressive radiolucent lines . Based on these early results , cementless , periapatite-coated single-radius PS total knee arthroplasty offers marked promise" ]

[ "Objective To evaluate the potential clinical , metabolic , and economic advantages of enteral nutrition over total parenteral nutrition . Design Prospect i ve , r and omized clinical trial . Setting Department of surgery in a university hospital . Patients Two hundred and fifty-seven patients with cancer of the stomach ( n = 121 ) , pancreas ( n = 110 ) , or esophagus ( n = 26 ) were r and omized to receive postoperative total parenteral nutrition ( TPN group , n = 131 ) or early enteral nutrition ( EEN group , n = 126 ) . The nutritional goal was 25 kcal/kg/day . The two nutritional formulas were isocaloric and isonitrogenous , and they were continued until oral intake was at least 800 kcal/day . Measurements Morbidity , mortality , length of hospital stay , and treatment costs were evaluated in all patients . In 40 consecutive patients , selected nutritional , immunologic and inflammatory variables were studied . Moreover , intestinal oxygen tension was evaluated by micropolarographic implantable probes . Main Results The nutritional goal was reached in 100/126 ( 79.3 % ) patients in the EEN group and in 128/131 ( 97.7 % ) patients in the TPN group ( p EEN group , hyperglycemia ( serum glucose , > 200 mg/dL ) was observed in 4.7 % of the patients vs. 9.1 % in the TPN group ( p = NS ) . Alteration of serum electrolyte levels was 3.9 % in the EEN group vs. 13.7 % in the TPN group ( p in nutritional , immunologic , and inflammatory variables between the two groups . The overall complication rate was similar ( 40.4 % for TPN vs. 35.7 % , for EEN;p = .52 ) . No difference was detected for either infectious or noninfectious complications , length of hospital stay , and mortality . From postoperative day 5 , intestinal oxygen tension recovered faster in the EEN group than in the TPN group ( 43 ± 5 mm Hg vs. 31 ± 4 mm Hg at day 7;p ) . EEN was four-fold less expensive than TPN ( $ 25 vs. $ 90.60/day , respectively ) . Conclusion EEN represents a rational alternative to TPN in patients who undergo upper gastrointestinal tract surgery for cancer and who clinical ly require postoperative artificial nutrition", "In a double blind controlled study including 60 patients it was found that Metoclopramide has a negative effect upon the resolution of postoperative adynamic ileus . Metoclopramide causes a delay in the time from operation to the first passage of flatus", "AIM To evaluate the feasibility , safety , and tolerance of early removing gastrointestinal decompression and early oral feeding in the patients undergoing surgery for colorectal carcinoma . METHODS Three hundred and sixteen patients su bmi tted to operations associated with colorectostomy from January 2004 to September 2005 were r and omized to two groups : In experimental group ( n=161 ) , the nasogastric tube was removed after the operation from 12 to 24 h and was promised immediately oral feeding ; In control group ( n=155 ) , the nasogastric tube was maintained until the passage of flatus per rectum . Variables assessed included the time to first passage of flatus , the time to first passage of stool , the time elapsed postoperative stay , and postoperative complications such as anastomotic leakage , acute dilation of stomach , wound infection and dehiscense , fever , pulmonary infection and pharyngolaryngitis . RESULTS The median and average days to the first passage of flatus ( 3.0+/-0.9 vs 3.6+/-1.2 , P first passage of stool ( 4.1+/-1.1 vs 4.8+/-1.4 , P length of postoperative stay ( 8.4+/-3.4 vs 9.6+/-5.0 , P anastomotic leakage ( 1.24 % vs 2.58 % ) , acute dilation of stomach ( 1.86 % vs 0.06 % ) and wound complications ( 2.48 % vs 1.94 % ) were similar in the groups , but fever ( 3.73 % vs 9.68 % , P pulmonary infection ( 0.62 % vs 4.52 % , P pharyngolaryngitis ( 3.11 % vs 23.23 % , P gastrointestinal decompression after colorectostomy can not effectively reduce postoperative complications . On the contrary , it may increase the incidence rate of fever , pharyngolaryngitis and pulmonary infection . These strategies of early removing gastrointestinal decompression and early oral feeding in the patients undergoing colorectostomy are feasible and safe and associated with reduced postoperative discomfort and can accelerate the return of bowel function and improve rehabilitation", "We attempted to determine whether the administration of erythromycin shortens the period of postoperative ileus by a prospect i ve , double-blind , placebo-controlled study . Seventy-seven patients were r and omized and included in the statistical calculations . The patients were stratified according to the operation performed ( cholecystectomy , celiotomy , or other major abdominal operations ) . Forty-one patients ( group 1 ) received 250 mg erythromycin intravenously every 8 h for nine doses upon admission to the recovery room . Thirty-six patients ( group 2 ) received placebo . The time ( in hours ) to first passage of flatus , first liquid meal , first bowel movement , and total length of hospital stay was recorded . There was no significant difference between group 1 and group 2 in time to first flatus ( 54.9 + /- 29 vs. 53.9 + /- 27 h , respectively ) , first meal ( 70.4 + /- 44 vs. 71.7 + /- 65 ) , first bowel movement ( 81.8 + /- 32 vs. 80.1 + /- 28 ) , or length of hospital stay ( 185.2 + /- 183 vs. 182.1 + /- 163 ) . Erythromycin , in the dosage tested in this study , does not seem to alter clinical parameters of gastrointestinal motility after an abdominal operation . New prokinetic agents may deserve further studies", "Between August 1988 and September 1989 , 100 consecutive patients who underwent elective abdominal colorectal surgical procedures were prospect ively r and omized to receive or not to receive metoclopramide . Metoclopramide was intravenously administered every 8 hours from the completion of surgery until a solid food diet was able to be tolerated . Seven patients were not included in the final tabulations because of one death , one small bowel obstruction requiring laparotomy , one anastomotic leak requiring laparotomy , and four protocol violations . Ninety-three patients , 37 men and 56 women ( mean age , 59.5 ; range , 14–89 years ) underwent 40 segmental colectomies , 13 total abdominal colectomies , 8 abdominoperineal resections , 8 ileoanal pouch procedures , 7 small bowel resections , and 17 other colorectal procedures . The 40 patients who received postoperative metoclopramide were in Group 1 , and the 53 who did not were in Group 2 . The mean length of time between laparotomy and commencement of oral fluid and oral solid intake in Groups 1 and 2 were 3.5 and 4.8 days , and 3.5 and 5.0 days , respectively . These differences were not statistically significant ( P>0.05 ) . Prolonged ileus was seen in seven patients in Group 1 and in eight patients in Group 2 . These differences were also not statistically significant ( P>0.05 ) . Prolonged ileus was defined as the need for nasogastric tube reinsertion or discontinuation of oral intake . We conclude that metoclopramide does not significantly alter the course of postoperative ileus", "Purpose Our objective was to determine the effect of erythromycin ( EM ) in improving gastrointestinal motility in subtotal gastrectomized patients . We used radio-opaque Kolomarks as an objective method . We conducted a prospect i ve , controlled clinical trial study of 24 patients . Methods All patients underwent subtotal gastrectomy with 3 capsules containing Kolomarks ( 20 markers per 1 capsule ) in the remnant stomach before anastomosis . From the day of the operation to the 2nd postoperative day , patients in the EM group began receiving 200 mg of EM intravenously for 30 minutes continuously . We counted the number of Kolomarks in the stomach , passed by stomach , in rectum , and in stool with serial simple abdominal X-ray films on the first postoperative day up to the 7th postoperative day . Results The study population included 14 patients in the control group and 10 patients in the EM group . The two study groups were compared in terms of their characteristics including age , gender , past medical history , cancer stage , and operation type . No significant differences were found for the demographics between the two groups . We only found a significant difference for the number of Kolomarks passed by the stomach on the 3rd postoperative day ( P = 0.026 ) . Conclusion Our results demonstrated that 200 mg of EM intravenous infusion during the postoperative period induced rapid gastric emptying , although it did not improve gastrointestinal motility for the entire gastrointestinal tract in subtotal gastrectomized patients", "OBJECTIVE : This prospect i ve r and omized clinical study was conducted to evaluate the safety and tolerability of early oral feeding after colorectal operations . METHODS : A total of 199 patients underwent colorectal surgery and were r and omly assigned to early feeding ( n = 99 ) or a regular diet ( n = 100 ) . Patients ' characteristics , diagnoses , surgical procedures , comorbidity , bowel movements , defecation , nasogastric tube reinsertion , time of tolerance of solid diet , complications , and length of hospitalization were assessed . RESULTS : The two groups were similar in terms of gender , age , diagnosis , surgical procedures , and comorbidity . In the early feeding group , 85.9 % of patients tolerated the early feeding schedule . Bowel movements ( 1.7±0.89 vs. 3.27±1.3 ) , defecation ( 3.4±0.77 vs. 4.38±1.18 ) and time of tolerance of solid diet ( 2.48±0.85 vs. 4.77±1.81 ) were significantly earlier in the early feeding group . There was no change between the groups in terms of nasogastric tube reinsertion , overall complication or anastomotic leakage . Hospitalization ( 5.55±2.35 vs. 9.0±6.5 ) was shorter in the early feeding group . CONCLUSIONS : The present study indicated that early oral feeding after elective colorectal surgery was not only well tolerated by patients but also affected the postoperative outcomes positively . Early postoperative feeding is safe and leads to the early recovery of gastrointestinal functions", "Background : The current trend in postoperative nutrition is to promote a normal oral diet as early as possible . However , postoperative ileus is a frequent and common problem after major abdominal surgery . This study was design ed to investigate whether early enteral nutrition ( EEN ) , as a bridge to a normal diet , can reduce postoperative ileus . Methods : Patients undergoing major rectal surgery for locally advanced primary or recurrent rectal carcinoma ( after neoadjuvant (chemo)-radiation , with or without intraoperative radiotherapy ) were r and omly assigned to EEN ( n = 61 ) or early parenteral nutrition ( EPN , n = 62 ) in addition to an oral diet . Early nutrition was started 8 hours after surgery . Early parenteral nutrition was given as control nutrition to obtain caloric equivalence and minimize confounding . The primary endpoint was time to first defecation ; secondary outcomes were morbidity , other ileus symptoms , and length of hospital stay . Results : Baseline characteristics were similar for both groups . In intention-to-treat analysis , the time to first defecation was significantly shorter in the enteral nutrition arm than in the control arm ( P = 0.04 ) . Moreover , anastomotic leakage occurred significantly less frequently in the enteral group ( 1 patient ) compared with parenteral supplementation ( 9 patients , P = 0.009 ) . Mean length of stay in the enteral group was 13.4 ± 2.2 days versus 16.7 ± 2.3 days in the parenteral group ( P = 0.007 ) . Conclusions : Early enteral nutrition is safe and associated with significantly less ileus . Early enteral nutrition is associated with less anastomotic leakage in patients undergoing extensive rectal surgery", "BACKGROUND This study assesses the safety outcome of early oral feeding and reports on the factors affecting early postoperative feeding after colorectal procedures . PATIENTS AND METHODS Between June 2005 and April 2008 , 120 consecutive patients underwent elective colonic anastomosis and were then r and omized into two groups . The early feeding group began fluids on the first postoperative day while the regular feeding group was managed in the traditional way - nothing by mouth until the resolution of ileus . RESULTS The majority of patients ( 75 % ) tolerated the early feeding . The times to first passage of flatus ( 3.3+/-0.9 days vs 4.2+/-1.2 days ) and stool ( 4.1+/-1.2 days vs 4.9+/-1.2 days ) were significantly quicker in group 1 . Hospital stay was also significantly shorter in the early feeding group ( 6.2+/-0.2 days vs 6.9+/-0.5 days ) . Operative time and amount of blood loss had an impact on the tolerability of early feeding while age , gender , type of operation and previous abdominal operation had no such impact . CONCLUSION Early oral feeding after colorectal surgery is safe and tolerated by the majority of patients . Operative time and amount of blood loss do , however , have an impact on the tolerability of early feeding", "Background A r and omized controlled trial was performed to assess the outcome of early oral postoperative feeding ( EOF ) compared with traditional oral feeding ( TOF ) in gynecologic oncology patients undergoing a complex laparotomy , including upper abdominal surgery . Methods Patients aged 18–75 years , undergoing an elective laparotomy and with a preoperative suspicion of gynecologic malignancy , were eligible . Exclusion criteria included infectious conditions , intestinal obstruction , severe malnutrition , American Society of Anesthesiologists score ≥4 , intestinal resection , and postoperative stay in the intensive care unit lasting > 24 h. Patients allocated to EOF received liquid diet in the first postoperative day and then regular diet . Patients received traditional feeding scheme until resolution of postoperative ileus to start liquid diet . The primary end-point of the trial was length of hospital stay . Results Between January 1 , 2007 , and November 17 , 2007 , a total of 143 patients were r and omized to receive either EOF or TOF . Hospital stay for patients who received EOF ( n = 71 ) was 4.7 vs. 5.8 days for the TOF group ( n = 72 ) ( P = 0.006 ) . The mean level of postoperative satisfaction was significantly higher in the EOF group ( 82.8 vs. 71.7 mm , P ≤ 0.001 ) . Patients who received the TOF scheme had significantly higher overall postoperative complications ( 39 vs. 17 % in EOF group , P = 0.003 ) and infective complications ( 14 % in TOF group vs. 3 % in EOF group , P = 0.017 ) . Variables such as nausea and vomiting , analgesic and antiemetic requirement as well as level of pain and quality of life were not different between groups . Conclusions On the basis of these findings , the policy of EOF should be used after a complex gynecologic oncologic laparotomy", "STUDY OBJECTIVE To assess the efficacy of metoclopramide for treatment of postoperative ileus in patients who underwent exploratory laparatomy . DESIGN Prospect i ve observational study SETTING Surgical intensive care unit ( SICU ) . PATIENTS Thirty-two patients who underwent exploratory laparatomy INTERVENTION Sixteen patients received metoclopramide , and 16 did not . The primary outcome was time to first postoperative bowel movement . Secondary end points were length of stay ( LOS ) in the SICU and total hospital LOS . MEASUREMENTS AND MAIN RESULTS The mean number of days to first bowel movement was nearly identical for both the treatment group and control group ( 4.8 vs 4.7 days , respectively , p=0.93 ) . Length of stay in the SICU was 8.3 days for the treatment group and 8.6 days for the control group ( p=0.89 ) , and total LOS was 18.0 and 20.1 days , respectively ( p=0.63 ) . CONCLUSION The time to first bowel movement was not significantly different between the treatment and control groups . Also , metoclopramide did not decrease LOS . Metoclopramide does not have a role in the treatment of postoperative ileus", "Background : Nasogastric ( NG ) intubation is widely used following elective abdominal operations although it is associated with morbidity and discomfort . The present study is a r and omised controlled trial on the effect of early oral feeding without NG decompression following elective colorectal resection for cancer", "BACKGROUND / AIMS Due to the lack of interest in using early oral feeding and the need for a trial study in this regard , this study aim ed to compare the outcome of early oral feeding and traditional oral feeding in patients with upper gastrointestinal surgery . METHODS Fifty-two patients who underwent upper gastrointestinal surgery were r and omly assigned into two groups in a consecutive manner as either the early oral feeding group or traditional oral feeding group . Tolerance of oral feeding , ileus , nausea and vomiting , post-operative stay , and complications were recorded . RESULTS Tolerance of oral feeding for the two groups was 24 ( 92.3 % ) in the early oral feeding group and 21 ( 91.3 % ) in the traditional oral feeding group ( p=0.89 ) . The post-operative hospital stays were 5.62 and 8.04 days in the early oral feeding and traditional oral feeding groups , respectively ( p time of the first gas passing/defecation , the post-operative hospital stays , starting time of oral feeding , and satisfaction regarding early nasogastric tube removal . CONCLUSIONS The results of this study show that early oral feeding is a safer and more cost-effective procedure in upper gastrointestinal surgery", "PURPOSE : This prospect i ve , r and omized study was design ed to evaluate whether or not early postoperative feeding ( cl aim ed as a unique benefit of laparoscopic surgery ) is possible after laparotomy and colorectal resection . METHODS : The trial was performed between July 1 , 1992 and October 31 , 1992 and included all 64 consecutive patients who underwent laparotomy with either a colonic or an ileal resection . In all cases the nasogastric tube was removed immediately after the operation . Group 1 consisted of 32 patients ( age range , 15–81 years ; mean , 52 years ) who received a regular diet on the first postoperative morning . Group 2 consisted of 32 patients ( age range , 15–87 years ; mean , 52 years ) who were fed in a traditional manner . Regular food was permitted after resolution of ileus as defined by resumption of bowel movements in the absence of abdominal distention , nausea , or vomiting . RESULTS : The rate of nasogastric tube reinsertion for distention with persistent vomiting was 18.7 percent ( six patients ) in Group 1 and 12.5 percent ( four patients ) in Group 2 . Although vomiting was experienced more frequently by patients in Group 1 ( 44 percentvs.25 percent , respectively ) , there was no difference between the two groups with regard to the duration of postoperative ileus ( 3.6vs.3.4 days , respectively ) . In the 26 patients from Group 1 who did not require nasogastric tube reinsertion , there was a trend toward shorter hospitalization ( 6.7vs.8.0 days , respectively ) . CONCLUSION : Early oral intake is possible after laparotomy and colorectal resection . Thus , the laparoscopic surgeon 's cl aim of early tolerated oral intake may not be unique to laparoscopy", "Background A r and omized controlled trial was performed to assess the outcome of early oral postoperative feeding ( EOF ) compared with traditional oral feeding ( TOF ) in gynecologic oncology patients undergoing laparotomy with associated intestinal resection . Methods Patients aged 18–75 years , undergoing elective laparotomy , and with preoperative diagnosis of gynecologic malignancy , were eligible . Exclusion criteria included infectious conditions , intestinal obstruction , severe malnutrition , American Society of Anesthesiologists ( ASA ) score ≥4 , and postoperative stay in the intensive care unit lasting > 24 h. Patients allocated to EOF received liquid diet in the first postoperative day and then regular diet . Patients received traditional feeding scheme until resolution of postoperative ileus to start liquid diet . The primary end-point of the trial was length of hospital stay . Results Between January 1st , 2007 and March 15th , 2008 , 40 patients were r and omized to receive either EOF or TOF . Hospital stay in patients who received EOF ( n = 18 ) was 6.9 days versus 9.1 days in the TOF group ( n = 22 ) ( P = 0.022 ) . Requirements for analgesic and antiemetic drugs , intensity of pain , intestinal function recovery , mean levels of postoperative satisfaction , postoperative complications , and quality -of-life scores did not differ between the two groups . Conclusion Early resumption of oral intake is feasible and safe in gynecologic oncology patients undergoing intestinal resection as part of a planned surgical procedure . Moreover , significant reduction in length of hospital stay was demonstrated", "Objective To compare early feeding with traditional postoperative dietary management for development of postoperative gastrointestinal symptoms , including ileus after major gynecologic surgery for benign conditions . Methods Women who had major gynecologic surgery for benign conditions were r and omly allocated to early feeding of low residue diets 6 hours postoperatively or traditional dietary management of clear liquids with normal bowel sounds , and regular diet with passage of flatus . Demographic and perioperative data were collected , and patients answered question naires on their perception of bowel function and pain using the McGill Pain Scale . Power analysis found that 130 women were needed to find a twofold greater incidence of ileus in the early feeding group with 80 % power and & agr ; = .05 . Results Complete data were available for 139 women , 67 allocated to the early feeding group and 72 to the late feeding group . The incidence of postoperative ileus for the study population was 4.4 % and did not differ between groups ( early 3 % versus late 5.8 % , P = .68 ) . There were no differences in patient demographics , surgical procedures , anesthesia used , and intraoperative complications between groups . With the exception of more complaints of nausea in the late feeding group ( 23 % versus 13 % , P = .04 ) , there were no differences in other postoperative variables , including other perioperative complications , pain medicine requirements , fluid and caloric intake , median pain scores , and gastrointestinal function . The low incidence of perioperative complications made the power to detect differences between groups low . Conclusion Low residue diet 6 hours after major gynecologic surgery for benign indications was not associated with increased postoperative gastrointestinal complaints , including ileus", "Background We have proposed a simplified perioperative rehabilitation program for elective colonic surgery that is focused on early oral nutrition and that could reduce hospital stay and postoperative ileus time without raising complications and readmission rates . Patients and methods Fifty-four patients admitted for elective colonic surgery were prospect ively r and omized into two groups : ( 1 ) an early feeding group (EFG)—on the first postoperative day , patients initially received a oral liquid diet and were advanced to a regular diet within the next 24 h as tolerated and at their discretion ; ( 2 ) a traditional care group— patients were managed by nothing per orus until the elimination of the first flatus and then su bmi tted to an oral liquid diet , followed by a regular diet within the next 24 h as described for the EFG . All patients followed a well-defined , simplified rehabilitation program . Results Patients ' baseline characteristics were similar in the two groups . Hospital stay was significantly lower in the EFG ( 4.0 [ ±3.7 ] versus 7.6 [ ±8.1 ] days ; p = 0.000 ) . Diet tolerance and progression were similar between groups . Time to first flatus after surgery was significantly lower in the EFG ( 1.5 [ ±0.5 ] versus 2.0 [ ±0.7 ] days ; p = 0.019 ) . Complication and readmission rates were similar in both groups . Conclusions Early oral nutrition associated with a simplified perioperative rehabilitation program reduces postoperative length of hospital stay and ileus time after elective colonic resection without increasing rates of complications or readmissions ", "BACKGROUND The concept of early initiation of oral feeding after caesarean delivery is well tolerated by patients , yet not routinely practice d in Mulago Hospital . An effective postoperative dietary management schedule could have major implication s on the management of maternal post-caesarean section mothers . OBJECTIVES To compare the effect of time initiation of oral feeding on acceptability , benefits and gastrointestinal functions in women who had undergone caesarean section in Mulago Hospital . DESIGN A r and omised controlled study . SETTING Mulago Hospital . SUBJECTS One hundred and ninety two women admitted on the postnatal ward after emergency or elective caesarean section for various indications and who satisfied the eligibility criteria were recruited and r and omized into the study . Assignment to the early feeding group or routine feeding group was done r and omly using a computer generated numbers . The early feeding group were encouraged to take sips of water within six to eight hours followed by oral soup or milk at least 150 millilitres at a time within 8 to 12 hours post operative under supervision . The routine group were managed by restricting oral intake for twenty four hours and administration of orals sips of water 24 to 48 hours post operative . The outcome measures were rate of ileus symptoms , post operative presence of bowel sounds , maternal pyrexia and acceptability and benefits of early feeding . RESULTS The mean age , parity and gravidity were similar in the two groups . The study shows that women of the early feeding group had more rapid return of their bowel function with significant more shorter mean post operative time intervals to bowels sounds ( 24.2 hours versus 34.2 hours ) , passage of flatus ( 51.6 hours versus 62.1 hours ) and bowel movement ( 67.8 hours versus 75.8 hours ) . The women who fed early , made more rapid recovery and expressed their interest in earlier hospital discharge . The findings significantly indicated that women in the early feeding group got out of bed ( patient mobilisation ) earlier ( p = 0.001 ) than their control group ( 15.1 hours versus 17.8 hours ) . This could probably have been because of the adequate rehydration and improved early energy intake . In comparison those who were fed early required less number of bottles of intravenous fluids ( 5.0 bottles versus 7.0 bottles ) . The average hospital stay was similar and not statistically significant in both groups ( 5.5 days versus 6.0 days ) . CONCLUSION Early initiation of oral feeding after caesarean delivery is safe and well tolerated and can be implemented without an increase in gastrointestinal symptoms or paralytic ileus ", "Background : No conclusive data exists supporting the use of any prokinetic agent in the postoperative setting . The study was design ed to examine the effect of erythromycin on small bowel motility in a placebo-controlled trial of post gastric bypass patients utilizing a st and ardized nuclear medicine test . Methods : A consecutive series of 21 patients undergoing elective gastric bypass surgery for morbid obesity between September 1999 and March 2001 were enrolled in this prospect i ve double-blind r and omized controlled trial . St and ard open , divided gastric bypass was performed . Patients were r and omized to receive either erythromycin 250 mg I. V. ( 11 patients ) or placebo ( 10 patients ) every 8 hours . On postoperative day 2 , a hepatic iminodiacetic acid ( HIDA ) scan was obtained . Tracer movement through the biliary tree and proximal small bowel was quantified and compared . Results : Tracer clearance from the liver and biliary tree was no different between groups from time of injection through 1 hour . Tracer material clearance from the duodenum into the jejunum was no different between the erythromycin and control groups at 1 hour , 37 % ±13 % and 37 % ±22 % respectively ( P=0.95 ) . At 4 hours , clearance was greater in the erythromycin group , 77%±6 % , compared to control , 60%±20 % ( P = 0.036 ) . The rate of tracer change between hour 1 and 4 ( slope ) was steeper in the erythromycin group ( P=0.048 ) . Conclusions : Erythromycin increases intestinal transit in the postoperative setting", "BACKGROUND A period of starvation after colorectal resections to allow for resolution of the clinical evidence of ileus has been an unchallenged surgical doctrine until recent times . A prospect i ve r and omized trial comparing early feeding to traditional management in patients undergoing open elective colorectal resections is reported . METHODS Patients undergoing elective intraperitoneal colorectal resections without stoma formation were r and omized to either an early feeding or control group . The early feeding group were allowed free fluids from 4 h postoperatively progressing to a solid diet from the first postoperative day as they tolerated it . The control group remained nil orally until passage of flatus or bowel motion and were then commenced on fluids progressing to solids over 24 - 48 h. RESULTS There were 40 patients in each group well matched for age , sex , type and duration of operation , method of analgesia and mobilization . Thirty-two patients ( 80 % ) in the early feeding group tolerated a diet within 48 h. There was no significant difference in the rate of vomiting , nasogastric reinsertion or complications . The early feeding group tolerated a diet , passed flatus , used their bowels , and were discharged from hospital significantly earlier than the control group . CONCLUSION Early feeding after elective open colorectal resections is successfully tolerated by the majority of patients , leading to earlier resolution of ileus and hospital discharge", "BACKGROUND & AIMS The evidence in support of Early Enteral Nutrition ( EEN ) after upper gastrointestinal surgery is inconclusive . The aim of this study was to determine if EEN improved clinical outcomes and shortened length of hospital stay . METHODS Open , prospect i ve multicentre r and omised controlled trial within a regional UK Cancer Network . One hundred and twenty-one patients with suspected operable upper gastrointestinal cancer ( 54 oesophageal , 38 gastric , 29 pancreatic ) were studied . Patients were r and omised to receive EEN ( n = 64 ) or Control management postoperatively ( nil by mouth and IV fluid , n = 57 ) . Analysis was based on intention-to-treat and the primary outcome measure was length of hospital stay . RESULTS Operative morbidity was less common after EEN ( 32.8 % ) than Control management ( 50.9 % , p = 0.044 ) , due to fewer wound infections ( p = 0.017 ) , chest infections ( p = 0.036 ) and anastomotic leaks ( p = 0.055 ) . Median length of hospital stay was 16 days ( IQ = 9 ) after EEN compared with 19 ( IQ = 11 ) days after Control management ( p = 0.023 ) . CONCLUSIONS EEN was associated with significantly shortened length of hospital stay and improved clinical outcomes . These findings reinforce the potential benefit of early oral nutrition in principle and as championed within enhanced recovery after surgery programmes , and such strategies deserve further research in the arena of upper GI surgery", "Objective This prospect i ve r and omized controlled trial was conducted to compare the safety , tolerability and outcome of early oral feeding vs. traditional feeding in patients undergoing elective open bowel surgery . Methods A total of 120 consecutive patients who underwent elective open bowel surgeries were r and omized into either early feeding ( n = 60 ) or traditional feeding group ( n = 60 ) . Patients in the early feeding group were started on oral fluids on post-operative day 1 , while those in the traditional feeding group were started orals after the resolution of ileus . Patient characteristics , surgical procedures , co-morbidity , first flatus , first defecation , time of starting solid diet , complications and length of hospitalization were assessed between the two groups . Results The two groups were similar in demographic and baseline data . The number of days to first flatus ( p first defecation ( p length of post-operative stay ( p = 0.011 ) and time of starting solid diet ( p Anastomotic leak , wound infection , fever , vomiting , abdominal distention and other complications were similar . Multivariate analysis showed that patients in the early oral feeding group were discharged 3.4 days earlier ( p = 0.037 ) . Conclusion In patients undergoing elective open bowel surgeries , early post-operative feeding is safe , is well tolerated and reduces the length of hospitalization", "Although studies have shown that early oral feeding after abdominal surgery is feasible , many surgeons still advocate a careful , slow introduction of postoperative oral feeding . This study was conducted to investigate whether patient‐controlled postoperative feeding is possible in patients undergoing colonic or aortic surgery", "BACKGROUND AND AIMS The impact of early enteral nutrition in elective upper gastrointestinal surgery was the focus of this study , with particular reference to its feasibility and benefits . METHOD This prospect i ve study was carried out over 2 years . The study group included 30 patients and the control group had 31 patients . Twenty-two patients in each group underwent truncal vagotomy and gastrojejunostomy for chronic duodenal ulcer and gastric outlet obstruction . Eight patients in the study group and nine in the control group underwent gastrectomy for carcinoma stomach . A st and ard milk-based diet was initiated 12 hours after surgery through a nasojejunal tube . The patients were monitored for side effects of enteral feeding and postoperative infective complications . Nitrogen balance and nutritional parameters like the body weight , serum albumin , and serum transferrin were measured pre and postoperatively . RESULTS The groups were comparable with respect to age , sex , and preoperative nutritional factors like body weight , serum albumin , and serum transferrin . The return of bowel sounds and passage of flatus took place significantly earlier in the study group ( 1.43 vs. 2.81 days ) . Diarrhoea and abdominal cramps were the significant complications noted in the study group in relation to early enteral feeding . No patient required withdrawal of enteral feeds . They showed a positive nitrogen balance on the fourth postoperative day . The patients in the study group showed significant increase in the serum transferrin level compared with the preoperative level but the serum albumin level was not significantly altered . CONCLUSION Early enteral feeding through the nasojejunal tube following elective upper gastrointestinal surgery is feasible , safe and improves the nutritional status", "Background Early oral feeding ( EOF ) has been demonstrated to be safe and beneficial after abdominal elective surgery . The aim of this r and omized controlled trial is to assess the safety and benefits of EOF compared to traditional postoperative care ( TPC ) after abdominal emergency surgery . Methods Patients assigned to the EOF group commenced a soft diet within 24 h after surgery . In the TPC group , a liquid diet was commenced upon passage of flatus or stool and then advanced to soft food . The primary endpoint was the complication rate . Secondary endpoints were severity of complications , mortality , gastrointestinal leaks , surgical-site infection , reoperation , diet intolerance , time to first flatus and stool , amount of food intake , postoperative discomfort , hospital stay , weight loss at the 15th postoperative day and incisional hernias . Results A total of 295 patients assigned to EOF ( n = 148 ) or TPC ( n = 147 ) were analyzed . No significant differences were seen in the complications rates ( EOF 45.3 % vs. TPC 37.4 % ; p = 0.1 ) . There was a significantly higher rate of vomiting with EOF ( EOF 13.5 % vs. TPC 6.1 % ; p = 0.03 ) , with no differences in nasogastric tube reinsertion . EOF patients ’ food intake was proportionally lower for the first three meals than that of TPC patients ( p hunger in the TPC group ( p postoperative ileus or length of hospital stay . Conclusions EOF was safe after abdominal emergency surgery . EOF was associated with more vomiting ( treated easily and without patient discomfort ) and less hunger than with TPC . No other EOF-related benefits could be demonstrated during this trial", "OBJECTIVE To compare early versus delayed postoperative feeding in women undergoing major gynaecological surgery with regard to clinical outcomes , duration of postoperative stay , and patient satisfaction . METHODS We conducted a parallel-r and omized controlled trial at a tertiary care centre in Montreal , Quebec , between June 2000 and July 2001 . Patients undergoing major gynaecological surgery were r and omized following a 1:1 allocation ratio to receive either early postoperative feeding in which oral clear fluids were begun up to six hours after surgery followed by solid foods as tolerated , or delayed postoperative feeding , in which clear fluids were begun on the first postoperative day and solid foods on the second or third day as tolerated . The primary outcomes analyzed were duration of postoperative stay and patient satisfaction . Secondary outcomes included mean time to appetite , passage of flatus , and bowel movement , as well as the presence of symptoms of paralytic ileus . RESULTS A total of 119 patients were r and omized ; 61 patients were assigned to the early feeding group and 58 to the delayed feeding group . Demographic characteristics , including age , weight , smoking status , and prior surgical history were comparable between both groups . There was no difference in length of postoperative stay between the two groups ( 86.4 ± 21.0 hours in the early feeding group vs. 85.6 ± 26.2 hours in the delayed feeding group ; P > 0.05 ) . No significant difference was noted in patient satisfaction ( P > 0.05 ) . No difference was found in the frequency of postoperative ileus , mean time to appetite , passage of flatus , or first bowel movement . CONCLUSION The introduction of early postoperative feeding appears to be safe and well tolerated by patients undergoing major gynaecological surgery . The duration of postoperative stay , patient satisfaction , and gastrointestinal symptoms are comparable between patients undergoing early or delayed postoperative feeding", "AIM To assess the efficacy of metoclopramide ( Met ) for prevention of prolonged post-operative ileus in advanced gastric cancer patients undergoing D2 gastrectomy and intra-peritoneal chemotherapy ( IPC ) . METHODS Thirty-two advanced gastric cancer patients undergoing D2 gastrectomy and IPC were allocated to two groups . Sixteen patients received Met immediately after operation ( group A ) , and 16 did not ( group B ) . Another 16 patients who underwent D2 gastrectomy without IPC were enrolled as the control group ( group C ) . All patients had received epidural pain control . The primary endpoints were time to first post-operative flatus and time until oral feeding with a soft diet without discomfort . Secondary endpoints were early complications during hospitalization . RESULTS Gender , the type of resection , operating time , blood loss , tumor status and amount of narcotics were comparable in the three groups . However , the group C patients were older than those in groups A and B ( 67.5+/-17.7 vs 56.8+/-13.2 , 57.5+/-11.7 years , P = 0.048 ) . First bowel flatus occurred after 4.35+/-0.93 d in group A , 4.94+/-1.37 d in group B , and 4.71+/-1.22 d in group C ( P>0.05 ) . Oral feeding of a soft diet was tolerated 7.21+/-1.92 d after operation in group A , 10.15+/-2.17 d in group B , and 7.53+/-1.35 d in group C ( groups A and C vs group B , P first flatus among the three groups . However , the time of tolerating oral intake with soft food in groups A and C patients was significantly shorter than that in group B patients . Levels of C-reactive protein ( CRP ) were significantly lower in group C and there was a more prominent and prolonged response in CRP level in patients undergoing IPC . The incidence of post-operative complications was similar in the three groups except for prolonged post-operative ileus . There was no increased risk of anastomotic leakage in patients receiving Met . CONCLUSION The results suggest that a combination of intravenous Met and epidural pain control may be required to achieve a considerable decrease in time to resumption of oral soft diet in advanced gastric cancer patients who underwent gastrectomy and IPC . Furthermore , the administration of Met did not increase anastomotic leakage . Met has a role in the prevention of prolonged post-operative ileus", "Objective To evaluate the safety and efficacy of early oral feeding after intra-abdominal surgery in gynecologic oncology patients . Methods During a 1-year period , 200 gynecologic oncology patients undergoing intra-abdominal surgery were enrolled in a r and omized controlled trial of early compared with traditional oral postoperative feeding . Patients allocated to early postoperative oral feeding began a clear liquid diet on the first postoperative day and then advanced to a regular diet as tolerated . Patients allocated to traditional postoperative oral feeding received nothing by mouth until return of bowel function ( defined as the passage of flatus in the absence of vomiting or abdominal distention ) , then began a clear liquid diet , and advanced to a regular diet as tolerated . Results Age , case distribution , surgery length , blood loss , and first passage of flatus were similar in the early and traditional feeding groups . Significantly more patients in the early group developed nausea . Despite this , the incidence of vomiting , abdominal distention , incidence and duration of nasogastric tube use , and percentage of patients who tolerated clear liquid and regular diets on the first attempt were comparable in both groups . Time to development of bowel sounds , time to initiation of clear liquid and regular diets , and hospital stay were significantly longer in the traditional group . Major complications ( eg , pneumonia , atelectasis , and wound complications ) and febrile morbidity occurred equally in both groups . There were no known anastamotic complications or aspirations in either group . Postoperative changes in hematologic indices and electrolytes were com-parable in both groups . Conclusion Early postoperative feeding in gynecologic oncology patients undergoing intra-abdominal surgery is safe and well tolerated", "PURPOSE Prolonged nasogastric decompression increases pulmonary complications by inhibiting clearance of respiratory secretions . The literature supports early nasogastric tube removal following bowel resection . Metoclopramide stimulates bowel activity , promoting return of function . We examined combining early nasogastric tube removal with metoclopramide after radical cystectomy . MATERIAL S AND METHODS From 1994 to 1996 , 27 prospect i ve cystectomy patients received intravenous metoclopramide ( metoclopramide group ) combined with early nasogastric tube removal ( less than 24 hours ) . A total of 54 concurrent cystectomy controls received no metoclopramide and nasogastric tubes remained until return of normal bowel function . RESULTS Preoperative and perioperative factors were comparable between the 2 groups . Nasogastric tubes were removed from 78 % of the metoclopramide group in less than 24 hours , 11 % on day 2 and 11 % on day 3 compared to none on day 1 , 50 % on day 2 and 50 % on day 3 or greater in controls . The metoclopramide group had a more rapid return of normal bowel sounds ( 2.9 versus 4.0 days , p = 0.0002 ) and earlier tolerance of solid food ( 6.7 versus 7.9 days , p = 0.04 ) . Nasogastric tube replacement was required in 3 of 27 metoclopramide cases versus 5 of 54 controls . Atelectasis occurred more often in the control group ( 33 versus 15 % ) . There were no bowel related complications in the metoclopramide group but partial small bowel obstruction in 2 controls was treated conservatively . CONCLUSIONS This preliminary study suggests that combining intravenous metoclopramide with early nasogastric tube removal after cystectomy and urinary diversion may reduce postoperative atelectasis and speed return of bowel function while posing no danger to the small bowel anastomosis . This regimen may result in fewer complications and shorter hospitalizations , translating into lower costs without compromising quality of care", "BACKGROUND Several investigators have demonstrated that routine nasogastric decompression after abdominal surgery is unnecessary and can be safely eliminated , and 1 recent study demonstrated the safety of early oral feedings . OBJECTIVE To test the hypothesis that successful early feeding would lead to a shorter duration of hospitalization and , therefore , would be more cost-effective . PATIENTS Fifty-eight patients with elective colorectal surgery . METHODS Patients were prospect ively r and omized to 1 of 2 postoperative treatment arms : early feeding ( EF group , n = 29 ) and traditional feeding ( TF group , n = 29 ) . All patients in the EF group began a liquid diet on the first postoperative day and were advanced to a regular diet when they consumed 1000 mL in 24 hours . All patients in the TF group began a liquid diet after resolution of the postoperative ileus and were advanced to a regular diet after consuming 1000 mL in 24 hours . Patients were dismissed after tolerating two thirds of the regular diet . Both groups had intraoperative orogastric tubes that were removed at the end of surgery . Nasogastric tubes were inserted for persistent postoperative vomiting . RESULTS No significant differences were noted in age , types of procedures , or in prior abdominal surgery in either group . No significant differences were seen in rates of nausea ( 55 % in EF vs 50 % in TF group ) or vomiting ( 48 % in EF vs 33 % in TF group ) . One patient in the EF group had aspiration pneumonia , and anastomotic leak result ed in sepsis and eventual death of 1 patient in the TF group . No significant difference was observed in length of hospital stay between the 2 groups ( mean + /- SD , 7.2 + /- 3.3 days in EF vs 8.1 + /- 2.3 days in TF group ) . CONCLUSIONS Early oral feeding after elective colorectal surgery is safe . Most of the patients tolerated EF ; however , there was no significant difference in duration of hospitalization in these patients", "Abstract . In reports on earlier non- prospect ively r and omized trials the authors have cl aim ed that early oral postoperative feeding is a unique benefit of laparoscopic surgery . On the other h and , some authors have suggested that early feeding could be tolerated by the majority of patients after elective open surgery . Aim . This prospect i ve r and omized study was undertaken to assess the feasibility and safety of immediate oral feeding in patients subjected to elective open colorectal surgery . Methods . This trial included 190 patients who underwent an elective colon or rectal operation . Patients were r and omized after the operative procedure into one of two groups . Group I ( n = 95 ) : On the first evening after the operation , patients were allowed ab libitum intake of clear liquids ; this continued until the first postoperative day at which time they progressed to a regular diet as desired . Group II ( n = 95 ) : In this group the nasogastric tube was removed when the surgeon considered that postoperative ileus had been resolved . Results . Early oral intake was tolerated by 79.6 % of the patients in the first 4 days in group I ; there were no differences between the two groups from the 4th day on . The incidence of vomiting and nasogastric tube insertion ( 21.5 % ) was higher in patients in group I than in those in group II . The time until the first bowel movement was 4.3 days in group I and 4.7 days in group II . Complications appeared in 17.3 % of the patients in group I and in 19.3 % in group II . Conclusion : This study has objective ly demonstrated that early oral feeding is feasible and safe in patients who have elective colorectal surgery . Résumé . Des travaux r and omisés non prospect ifs ont affirmé que l'alimentation orale postopératoire précoce est un des gr and s bénéfices de la chirurgie laparoscopique . Les auteurs ont suggéré , d'autre part , une réalimentation précoce et bien tolérée par la plupart des patients après chirurgie élective ouverte . Le but de ce travail prospect if est d'établir la faisabilité et la sécurité d'une alimentation orale immédiate chez des patients ayant subi une chirurgie colo-rectale élective ouverte . Cette étude inclut 190 patients devant subir une opération colo-rectale élective . Le collectif a été r and omisé après l'intervention en deux groupes . Les patients du groupe 1 ( n = 95 ) ont été autorisés à ingurgiter des liquides ad libitum le soir de l'intervention ; au premier jour postopératoire , ils ont pus'alimenter progressivement avec un régime normal . Dans le groups 2 ( n = 95 ) la sonde naso-gastrique a été etirée lorsque le chirurgien a considéré que la phase d'iléus postopératoire s'était résolue . Résultats . La réalimentation précoce a été bien tolérée chez 79.6 % des patients au cours des 4 premiers jours du groupe 1 . Il n'y a pas de différence entre les deux groupes au 4e jour . L'incidence des vomissements et la nécessité de replacer une sonde nasogastrique ( 21,5 % ) est plus élevée dans le groupe 1 que dans le groupe 2 . La première exonération s'est produite au 4,3e jour dans le groupe 1 et au 4,7e jour dans le groupe 2 . Des complications sont apparues chez 17,3 % des patients du groupe 1 et 19,3 % des patients du groupe 2 . En conclusion , cette étude a démontré de manière objective que la réalimentation orale précoce est possible et sûre chez des patients soumis à une chirurgie colo-rectale élective", "PURPOSE : Nausea and vomiting three to seven days after an elective operation on the colon and rectum remain a persistent clinical problem . Erythromycin , a safe , inexpensive drug that stimulates intestinal motilin receptors , has previously been shown to accelerate gastric emptying significantly after upper gastrointestinal surgery . We aim ed to evaluate the effect of postoperative intravenous erythromycin on postoperative ileus in patients undergoing elective surgery for primary colorectal cancer . METHODS : Between May 1998 and April 1999 , 150 patients undergoing primary resection of colon or rectal cancer were enrolled in this prospect i ve , r and omized , placebo-controlled trial . One hundred thirty-four patients completed the study . Patients were excluded if they had extensive metastatic disease , were taking medications known to interact with erythromycin , or if they required an ileostomy . Patients received either 200 mg of intravenous erythromycin or placebo every six hours . Clinical endpoints were recorded and continuous endpoints are presented as mean ± st and ard deviation . RESULTS : There were no significant complications related to erythromycin . The erythromycin ( n=65 ) and placebo ( n=69 ) groups were comparable regarding demographic and operative factors . The erythromycin group had a slightly shorter length of time to passage of flatus ( 4.1 ± 1.3vs . 4.4 ± 1.1 days;P=0.03 ) . There was no significant difference between erythromycin and placebo in time to first solid food ( 5.6 ± 1.9vs . 5.4 ± 1.8 days ) , time to first bowel movement ( 5.2 ± 1.9vs . 5.4 ± 1.3 days ) , or time to discharge from hospital ( 7.5 ± 2.0vs . 7.6 ± 2.8 days ) . There was no difference in the rate of clinical ly significant nausea ( 26vs . 26 percent;P=0.99 ) , vomiting ( 17vs . 16 percent;P=0.88 ) , or nasogastric tube placement ( 9vs . 7 percent;P=0.68 ) . CONCLUSIONS : Erythromycin does not seem to alter clinical ly important outcomes related to postoperative ileus in patients undergoing resection for colorectal cancer", "Postoperative convalescence is mainly determined by the extent and duration of postoperative ileus . This r and omized clinical trial evaluated the effects of early oral feeding on functional gastrointestinal recovery and quality of life", "Objective . To evaluate the safety and efficacy of early oral feeding after cesarean delivery . Methods . Two hundred women who had cesarean section were r and omly assigned to early feeding or routine feeding . Women in the early feeding group were encouraged to take sips of water 8 h post-operatively , followed by oral tea of 100 mL at the time of supervision . Women in the routine feeding group were managed by restricting oral intake for the first 24 h and administration of sips of water 24–48 h post-operatively . The outcome measures include the rate of ileus symptoms , post-operative time interval to presence of bowel sounds , passage of flatus and bowel movement , time interval to return to regular diet , length of hospital stay , post-operative complications , acceptability and benefit of early oral feeding . Results . The early feeding group had a shorter mean post-operative time interval to bowel sounds 18.90 ± 4.17 h versus 36.21 ± 3.52 h ( p passage of flatus 44.81 ± 3.73 h versus 60.58 ± 4.40 h ( p and bowel movement 58.30 ± 5.91 h versus 72.76 ± 4.25 h ( p difference in paralytic ileus symptoms . Early feeding group had a shorter mean hospital stay 4.80 ± 0.59 days versus 6.69 ± 0.71 days ( p = 0.001 ) . Early feeding group required less intravenous fluid 7.14 ± 1.34 bottles versus 11.8 ± 1.32 bottles ( p Early feeding after cesarean section was well tolerated and safe and can be implemented without an increase in adverse outcome", "OBJECTIVES Treatment of postoperative ileus remains unsatisfactory . Erythromycin ( EM ) , a macrolide antibiotic , has prokinetic effects on the gut . We investigated whether intravenous erythromycin decreases the time to the return of normal bowel function after bowel surgery in patients with bladder cancer and interstitial cystitis who have undergone cystectomy and urinary diversion . METHODS We conducted a double-blind , r and omized , placebo-controlled study of 22 volunteers . On the first postoperative day , patients began receiving intravenous erythromycin ( 125 mg ) or placebo every 8 hours ( maximum of 21 doses ) . The patients ' ability to tolerate a general diet and return of bowel function was monitored . RESULTS A general diet was tolerated at a median of 9 days postoperatively for the EM arm and 8 for the placebo arm ( P = 0.60 ) . The first bowel sounds were detected at an average of 2 postoperative days for the EM arm and 3 for the placebo arm ( P = 0.88 ) . First flatus was present an average of 5 days postoperatively for both study arms ( P = 0.35 ) . The first bowel movement was present an average of 6 days postoperatively for the EM arm and 5 for the placebo arm ( P = 0.98 ) . CONCLUSIONS No significant difference was found between EM and placebo with regard to the onset of bowel sounds , passage of flatus , passage of the first bowel movement , and the time to tolerate a general diet . These data indicate that erythromycin is not useful in improving postoperative bowel function", "Abstract Objectives : To assess whether immediate postoperative enteral feeding in patients who have undergone gastrointestinal resection is safe and effective . Design : R and omised trial of immediate postoperative enteral feeding through a nasojejunal tube v conventional postoperative intravenous fluids until the re introduction of normal diet . Setting : Teaching hospitals in London . Subjects : 30 patients under the care of the participating consultant surgeon who were undergoing elective laparotomies with a view to gastrointestinal resection for quiescent , chronic gastrointestinal disease . Two patients did not proceed to resection . Main outcome measures : Nutritional state , nutritional intake and nitrogen balance , gut mucosal permeability measured by lactulose-mannitol differential sugar absorption test , complications , and outcome . Results : Successful immediate enteral feeding was established in all 14 patients , with a mean ( SD ) daily intake of 6.78 ( 1.57 ) MJ ( 1622 ( 375 ) kcal before re introduction of oral diet compared with 1.58 ( 0.14 ) MJ ( 377 ( 34 ) kcal ) for those on intravenous fluids ( P Urinary nitrogen balance on the first postoperative day was negative in those on intravenous fluids but positive in all 14 enterally fed patients ( mean ( SD ) -13.2 ( 11.6 ) g v 5.3 ( 2.7 ) g ; P gut mucosal permeability in the enterally fed group but a significant increase from the test ratios seen before the operation in those on intravenous fluids ( 0.11 ( 0.06 ) v 0.15 ( 0.12 ) ; P postoperative complications in the enterally fed group ( P Immediate postoperative enteral feeding in patients undergoing intestinal resection seems to be safe , prevents an increase in gut mucosal permeability , and produces a positive nitrogen balance . Key messages Key messages It is safe , with patients experiencing fewer complications There seems to be an improvement in nutritional state Patients may have an improved", "PURPOSE This study investigated the impact of early enteral nutrition ( EEN ) on the clinical outcomes of gastric cancer patients after radical gastrectomy . METHODS Four hundred gastric cancer patients undergoing radical gastrectomy of any extend with D2 nodal dissection were r and omly divided into an experimental and a control group with 200 cases in each group . Patients in the control group received postoperative parenteral nutrition ( PN ) , while patients in the experimental group received postoperative EEN . After treatment , the clinical outcomes , postoperative immune function , and nutritional status of the two groups were evaluated . RESULTS The postoperative fever time , intestinal function recovery time , anal exhaust time , and the length of hospital stay for patients in the experimental group were significantly shorter than those of the control group . We did not find significant differences in anastomotic leak , postoperative ileus and regurgitation between the two groups . The activities of multiple immune cell types , including CD3⁺ , CD4⁺ , CD4⁺/CD8⁺ , and natural killer ( NK ) cells , were significantly lower in both groups on postoperative day 1 when compared with the preoperative levels ( p The level of CD8⁺ was not significantly different between the two groups ( p>0.05 ) . After treatment , levels of CD3⁺ , CD4⁺ , CD4⁺/CD8⁺ , and NK cells in the experimental group patients were 35.6 ± 4.2 , 42.2 ± 3.0 , 1.7 ± 0.3 , and 27.3 ± 5.3 % , respectively , on postoperative day 7 , which were similar to the preoperative levels . The immune cell levels from the control group patients remained significantly lower when compared with preoperative values ; in addition , these values were also significantly lower when compared with the EEN patients ( p gastric cancer patients undergoing radical gastrectomy , the clinical outcome , immune function and nutritional status after EEN were significantly improved . These data suggest the widespread use of EEN in clinical practice", "Purpose Ileus is a common event following cesarean section . Early post-cesarean recovery is very important not only for the mother but also for the baby who is dependent on breastfeeding . This article aims to demonstrate the efficacy of metoclopramide for the prevention of ileus after cesarean . Methods In this r and omized controlled trial , 696 women scheduled for cesarean were r and omized in two groups . Three hundred fifty-three persons settled in control group and 343 were assigned in intervention group who received an injection of 10-mg intramuscular metoclopramide prior to operation . After cesarean , the participants recorded the first flatus , defecation , feeling of hunger , feeding and ambulation in a question naire , and also their sense of bloating in a visual analog scale under supervision of a research assistant . The data was analyzed by SPSS 17 , t test , and chi-square , while p interval between cesarean and the first flatus ( p 0.0001 ) , defecation ( p feeling of hunger ( p feeding ( p = 0.007 ) , and ambulation ( p metoclopramide group . In addition , polytomous logistic regression analysis showed the metoclopramide group had less bloating with significant difference ( OR = 2.83 and CI 1.91–4.21 ) . Conclusions Our study proved the functionality of metoclopramide in preventing ileus . As this drug is safe , tolerable , harmless , inexpensive and available , and also no definite method has been developed to prevent ileus after cesarean ; yet , metoclopramide could be considered as a suitable option . Certainly with regard to some limitations in our study , further comprehensive studies are still required to ensure validity of the obtained results", "BACKGROUND To date , early oral feeding after gastrectomy for gastric cancer has not been accepted universally . Therefore , we performed a r and omized clinical trial to determine whether early oral feeding after curative surgery for gastric cancer can be tolerated and whether it has an effect on recovery . METHODS From July 2008 to February 2009 , 58 patients were enrolled and 4 were excluded according to set criteria . The patients in the early feeding group began a liquid diet on the second postoperative day , and then were fed a soft diet from the third day until the day they were discharged . The patients in the control group began a liquid diet on the fourth day . The primary endpoint of this study was the duration of postoperative hospitalization . RESULTS No significant differences were found in the clinico-operative characteristics between the 2 groups . The duration of hospitalization ( P = .044 ) and time until flatus ( P = .036 ) in the early group were decreased significantly . With regard to the rates of morbidity , cost of hospitalization , postoperative symptoms , and pain scales , no significant differences were found . The quality of life scores were decreased significantly at the fatigue ( P = .007 ) and nausea and vomiting ( P = .048 ) immediately after operation in the early feeding group . CONCLUSION Early oral feeding after gastric cancer surgery is feasible and can result in shorter hospitalization and improvements in several aspects of quality of life in the early postoperative period" ]

[ "Objective We investigated the associations of both physical activity time ( PA ) and energy expenditure ( EE ) with weight and fat mass ( FM ) loss in patients following Roux-en-Y gastric bypass ( RYGB ) surgery . Methods Ninety-six non-diabetic patients were included in this analysis . Post RYGB patients were r and omized in one of two treatments : A 6-month exercise training program ( RYBG+EX ) or lifestyle educational classes ( RYGB ) . Body composition was assessed by dual-energy X-ray absorptiometry and computed tomography . We quantified components of PA and EE by a multisensory device . We explored dose-response relationships of both PA and EE with weight loss and body composition according to quartiles of change in steps/day . Results Patients in the highest quartile of steps/day change lost more fat mass ( FM ) ( 3rd = −19.5 kg and 4th=−22.7 kg , P ) and abdominal adipose tissue ( − 4th=−313cm2 , P maintained skeletal muscle mass ( 3rd = 3.1cm2 and −4th=−4.5cm2 , P reductions in resting metabolic rate . Decreases in sedentary EE , increases in Light EE and age were significant predictors of both Δweight and ΔFM ( R2 = 73.8 % and R2 = 70.6 % , respectively ) . Conclusion Non-diabetic patients who perform higher - yet still modest - amounts of PA following RYGB have greater energy deficits , lose more weight and body fat mass , while maintaining higher skeletal muscle mass", "Background : Bariatric surgery is effective for the treatment of stage II and III obesity and its related diseases , although increasing evidence is showing weight regain ~12–24 months postsurgery . Weight regain increases the risk of physical function decline , which negatively affects an individual 's ability to undertake activities of daily living . The study assessed the effects of a 12-week supervised exercise intervention on physical function and body composition in patients between 12 and 24 months post bariatric surgery . Methods : Twenty-four inactive adult bariatric surgery patients whose body mass index remained ⩾30 kg m2 12 to 24 months post surgery were r and omised to an exercise intervention ( n=12 ) or control group ( n=12 ) . Supervised exercise consisted of three 60-min gym sessions per week of moderate intensity aerobic and resistance training for 12 weeks . Control participants received usual care . The incremental shuttle walk test ( ISWT ) was used to assess functional walking performance after the 12-week exercise intervention , and at 24 weeks follow-up . Measures of anthropometric , physical activity , cardiovascular and psychological outcomes were also examined . Using an intention-to-treat protocol , independent t-tests were used to compare outcome measures between groups . Results : Significant improvements in the exercise group were observed for the ISWT , body composition , physical function , cardiovascular and self-efficacy measures from baseline to 12 weeks . A large baseline to 12-week change was observed for the ISWT ( exercise : 325.00±117.28 m ; control : 355.00±80.62 m , P exercise group at 24 weeks recorded an overall mean improvement of 143.3±86.6 m and the control group recorded a reduction of −32.50±75.93 m. Findings show a 5.6 kg difference between groups in body mass change from baseline to 24 weeks favouring the exercise group . Conclusions : A 12-week supervised exercise intervention led to significant improvements in body mass and functional walking ability post intervention , with further improvements at the 24-week follow-up", "ABSTRACT The purpose of this study was to examine the effect of a 12-week resistance training programme on fat-free mass ( FFM ) , muscle cross-sectional area , muscular strength and muscle quality in women who underwent Roux-en-Y gastric bypass surgery . Participants were 16 women ( mean age = 44.9 ± 10.2 years ) from bariatric surgical groups who were r and omly assigned into either a control or an intervention group . Air displacement plethysmography measured FFM and magnetic resonance imaging measured quadriceps muscle cross-sectional area and whole thigh muscle cross-sectional area . Muscular strength and quality was assessed using an estimated 1-Repetition Maximum assessment . All measurements were collected twice , at baseline and at a 12-week follow-up . There were significantly greater improvements in leg press strength ( mean differences = 55.4 % , P ) , leg extension strength ( mean differences = 18.0 % , P = 0.014 , Cohen ’s d = 0.86 ) and leg press muscle quality ( mean differences = 54.5 % , P the resistance training programme . The resistance training intervention significantly improved muscular strength and quality ; however , it did not illicit changes in FFM or muscle cross-sectional area in women who underwent Roux-en-Y gastric bypass surgery", "OBJECTIVE Bariatric surgery results in significant weight loss and reduces cardiovascular morbidity . However , a large variation in postsurgery weight loss is seen . Physical activity promotes weight loss in nonsurgically treated subjects with obesity . The aim of this study was to investigate the effects of 6 months of supervised physical training following Roux-en-Y gastric bypass surgery ( RYGB ) on body weight and cardiovascular risk markers . METHODS Sixty participants eligible for RYGB were included . Six months post surgery , the participants were r and omly assigned to either twice-weekly supervised physical training sessions in a fitness center ( INT ) or a control group ( CON ) for 26 weeks . Before surgery and 6 , 12 , and 24 months after surgery , the participants underwent an examination program that included anthropometric measurements , blood pressure , heart rate , blood sample s , and an abdominal computed tomography scan . RESULTS RYGB significantly reduced body weight and improved cardiovascular risk markers ( all P physical training intervention result ed in a 4.2-kg ( CI : -0.2 to -8.3 kg ) lower body weight in INT compared with CON at the study end ( P = 0.042 ) . The high-density lipoprotein concentration was significantly higher in INT than in CON at the termination of the intervention , but this was not maintained at the 24-months examination . CONCLUSIONS Physical training following RYGB improves weight loss and cardiovascular health", "BACKGROUND AND AIMS Obesity and physical inactivity are both associated with low- grade inflammation and endothelial dysfunction . Bariatric surgery improves markers of inflammation and endothelial function , but it is unknown if physical training after bariatric surgery can improve these markers even further . Therefore , we aim ed to investigate the effects of Roux-en-Y gastric bypass ( RYGB ) followed by physical training on markers of low- grade inflammation and endothelial function . METHODS Sixty patients approved for RYGB underwent examinations pre-surgery , 6 , 12 , and 24 months post-surgery . Six months post-surgery , they were r and omized 1:1 to an intervention group or a control group . The interventions consisted of two weekly sessions of supervised moderate intensity physical training for a period of 26 weeks . Fasting blood sample s were analyzed for concentrations of interleukin 6 ( IL-6 ) , C-reactive protein ( CRP ) , intercellular adhesion molecule 1 ( ICAM-1 ) , tissue-type plasminogen activator antigen ( t-PA : Ag ) and von Willebr and factor ( vWF ) . RESULTS RYGB markedly improved markers of inflammation ( IL-6 , CRP ) ( p endothelial function ( ICAM-1 , t-PA : Ag , vWF ) ( p changes in weight or BMI and the changes in markers of inflammation and endothelial function , except that the change in vWF was found to be inversely correlated with the changes in weight and BMI . We observed no effects of supervised physical training on markers on inflammation or endothelial function ( p>0.1 for all ) . CONCLUSIONS RYGB causes substantial and sustained favorable effects on markers of inflammation and endothelial function . Supervised physical training after RYGB did not cause additional improvements", "BACKGROUND The Bari-Active trial found that a physical activity ( PA ) intervention ( PAI ) , versus st and ard presurgical care control ( SC ) , produced significant increases in daily bout-related moderate-to-vigorous PA ( MVPA , in≥10-min bouts ) preoperatively . The present study examined whether PAI also produces superior improvements in psychological and /or motivational processes that may be important for PA adoption . OBJECTIVES Compare PAI and SC on baseline to postintervention changes in PA-related enjoyment , self-efficacy , and motivations , and examine whether greater bout-related MVPA changes are associated with greater improvements in these variables . SETTING University hospital , United States . METHODS Participants ( 87 % female ; body mass index = 45.0±6.5 kg/m(2 ) ) were r and omly assigned to 6 weeks of PAI ( n = 40 ) or SC ( n = 35 ) . PAI received weekly counseling sessions to increase daily walking exercise . At baseline and postintervention , both groups completed 7-day objective PA monitoring and question naires to evaluate changes in bout-related MVPA and PA enjoyment , self-efficacy , and motivation . RESULTS Retention was 84 % at postintervention . Intent-to-treat analyses showed that PAI on average reported more favorable changes than SC in PA enjoyment , self-efficacy , amotivation ( i.e. , lack of PA motivation ) , and identified and intrinsic regulations ( i.e. , more autonomous PA motivations ; P , changes in bout-related MVPA and psychological/motivational variables were unrelated . CONCLUSION PAI produced greater improvements in PA-related enjoyment , self-efficacy , and motivations than SC . The lack of association between objective ly measured PA changes and psychological/motivational processes highlights the need for future research to identify which processes are most important for PA adoption and maintenance in bariatric surgery patients , and to determine whether the method used to measure PA affects the pattern of association", "BACKGROUND Roux-en-Y gastric bypass ( RYGB ) surgery causes profound weight loss and improves insulin sensitivity ( S(I ) ) in obese patients . Regular exercise can also improve S(I ) in obese individuals ; however , it is unknown whether exercise and RYGB surgery-induced weight loss would additively improve S(I ) and other cardiometabolic factors . METHODS We conducted a single-blind , prospect i ve , r and omized trial with 128 men and women who recently underwent RYGB surgery ( within 1 - 3 months ) . Participants were r and omized to either a 6-month semi-supervised moderate exercise protocol ( EX , n = 66 ) or a health education control ( CON ; n = 62 ) intervention . Main outcomes measured included S(I ) and glucose effectiveness ( S(G ) ) , which were determined from an intravenous glucose tolerance test and minimal modeling . Secondary outcomes measured were cardiorespiratory fitness ( VO2 peak ) and body composition . Data were analyzed using an intention-to-treat ( ITT ) and per- protocol ( PP ) approach to assess the efficacy of the exercise intervention ( > 120 min of exercise/week ) . RESULTS 119 ( 93 % ) participants completed the interventions , 95 % for CON and 91 % for EX . There was a significant decrease in body weight and fat mass for both groups ( P S(I ) improved in both groups following the intervention ( ITT : CON vs. EX ; + 1.64 vs. + 2.24 min⁻¹/μU/ml , P = 0.18 for Δ , P additive S(I ) improvement ( PP : CON vs. EX ; + 1.57 vs. + 2.69 min⁻¹/μU/ml , P = 0.019 ) above that of surgery . Exercise also improved S(G ) ( ITT : CON vs. EX ; + 0.0023 vs. + 0.0063 min⁻¹ , P = 0.009 ) compared with the CON group . Exercise improved cardiorespiratory fitness ( VO2 peak ) compared with the CON group . CONCLUSION Moderate exercise following RYGB surgery provides additional improvements in S(I ) , S(G ) , and cardiorespiratory fitness compared with a sedentary lifestyle during similar weight loss . TRIAL REGISTRATION clinical trials.gov identifier : NCT00692367 . FUNDING This study was funded by the NIH/National Institute of Diabetes and Digestive and Kidney Diseases ( R01 DK078192 ) and an NIH/National Center for Research Re sources / Clinical and Translational Science Award ( UL1 RR024153 )", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "OBJECTIVE —The effectiveness of intentional weight loss in reducing cardiovascular disease ( CVD ) events in type 2 diabetes is unknown . This report describes 1-year changes in CVD risk factors in a trial design ed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events . RESEARCH DESIGN AND METHODS —This study consisted of a multicentered , r and omized , controlled trial of 5,145 individuals with type 2 diabetes , aged 45–74 years , with BMI > 25 kg/m2 ( > 27 kg/m2 if taking insulin ) . An intensive lifestyle intervention ( ILI ) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education ( DSE ) condition . RESULTS — Participants assigned to ILI lost an average 8.6 % of their initial weight vs. 0.7 % in DSE group ( P Mean fitness increased in ILI by 20.9 vs. 5.8 % in DSE ( P ILI participants had reductions in diabetes , hypertension , and lipid-lowering medicines . Mean A1C dropped from 7.3 to 6.6 % in ILI ( P DSE . Systolic and diastolic pressure , triglycerides , HDL cholesterol , and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants ( all P ILI result ed in clinical ly significant weight loss in people with type 2 diabetes . This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE . Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk ", "Summary Background The main associations of body-mass index ( BMI ) with overall and cause-specific mortality can best be assessed by long-term prospect i ve follow-up of large numbers of people . The Prospect i ve Studies Collaboration aim ed to investigate these associations by sharing data from many studies . Methods Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospect i ve studies with 894 576 participants , mostly in western Europe and North America ( 61 % [ n=541 452 ] male , mean recruitment age 46 [ SD 11 ] years , median recruitment year 1979 [ IQR 1975–85 ] , mean BMI 25 [ SD 4 ] kg/m2 ) . The analyses were adjusted for age , sex , smoking status , and study . To limit reverse causality , the first 5 years of follow-up were excluded , leaving 66 552 deaths of known cause during a mean of 8 ( SD 6 ) further years of follow-up ( mean age at death 67 [ SD 10 ] years ) : 30 416 vascular ; 2070 diabetic , renal or hepatic ; 22 592 neoplastic ; 3770 respiratory ; 7704 other . Findings In both sexes , mortality was lowest at about 22·5–25 kg/m2 . Above this range , positive associations were recorded for several specific causes and inverse associations for none , the absolute excess risks for higher BMI and smoking were roughly additive , and each 5 kg/m2 higher BMI was on average associated with about 30 % higher overall mortality ( hazard ratio per 5 kg/m2 [ HR ] 1·29 [ 95 % CI 1·27–1·32 ] ) : 40 % for vascular mortality ( HR 1·41 [ 1·37–1·45 ] ) ; 60–120 % for diabetic , renal , and hepatic mortality ( HRs 2·16 [ 1·89–2·46 ] , 1·59 [ 1·27–1·99 ] , and 1·82 [ 1·59–2·09 ] , respectively ) ; 10 % for neoplastic mortality ( HR 1·10 [ 1·06–1·15 ] ) ; and 20 % for respiratory and for all other mortality ( HRs 1·20 [ 1·07–1·34 ] and 1·20 [ 1·16–1·25 ] , respectively ) . Below the range 22·5–25 kg/m2 , BMI was associated inversely with overall mortality , mainly because of strong inverse associations with respiratory disease and lung cancer . These inverse associations were much stronger for smokers than for non-smokers , despite cigarette consumption per smoker varying little with BMI . Interpretation Although other anthropometric measures ( eg , waist circumference , waist-to-hip ratio ) could well add extra information to BMI , and BMI to them , BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22·5–25 kg/m2 . The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal . At 30–35 kg/m2 , median survival is reduced by 2–4 years ; at 40–45 kg/m2 , it is reduced by 8–10 years ( which is comparable with the effects of smoking ) . The definite excess mortality below 22·5 kg/m2 is due mainly to smoking-related diseases , and is not fully explained . Funding UK Medical Research Council , British Heart Foundation , Cancer Research UK , EU BIOMED programme , US National Institute on Aging , and Clinical Trial Service Unit ( Oxford , UK )", "Background Evidence suggests that exercise training improves CVD risk factors . However , it is unclear whether health benefits are limited to aerobic training or if other exercise modalities such as resistance training or a combination are as effective or more effective in the overweight and obese . The aim of this study is to investigate whether 12 weeks of moderate-intensity aerobic , resistance , or combined exercise training would induce and sustain improvements in cardiovascular risk profile , weight and fat loss in overweight and obese adults compared to no exercise . Methods Twelve-week r and omized parallel design examining the effects of different exercise regimes on fasting measures of lipids , glucose and insulin and changes in body weight , fat mass and dietary intake . Participants were r and omized to either : Group 1 ( Control , n = 16 ) ; Group 2 ( Aerobic , n = 15 ) ; Group 3 ( Resistance , n = 16 ) ; Group 4 ( Combination , n = 17 ) . Data was analysed using General Linear Model to assess the effects of the groups after adjusting for baseline values . Within-group data was analyzed with the paired t-test and between-group effects using post hoc comparisons . Results Significant improvements in body weight ( −1.6 % , p = 0.044 ) for the Combination group compared to Control and Resistance groups and total body fat compared to Control ( −4.4 % , p = 0.003 ) and Resistance ( −3 % , p = 0.041 ) . Significant improvements in body fat percentage ( −2.6 % , p = 0.008 ) , abdominal fat percentage ( −2.8 % , p = 0.034 ) and cardio-respiratory fitness ( 13.3 % , p = 0.006 ) were seen in the Combination group compared to Control . Levels of ApoB48 were 32 % lower in the Resistance group compared to Control ( p = 0.04 ) . Conclusion A 12-week training program comprising of resistance or combination exercise , at moderate-intensity for 30 min , five days/week result ed in improvements in the cardiovascular risk profile in overweight and obese participants compared to no exercise . From our observations , combination exercise gave greater benefits for weight loss , fat loss and cardio-respiratory fitness than aerobic and resistance training modalities . Therefore , combination exercise training should be recommended for overweight and obese adults in National Physical Activity Guidelines .This clinical trial was registered with the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) , registration number : ACTRN12609000684224", "Purpose The aim of this study is to conduct a pilot r and omized trial testing an exercise program specifically adapted for post-bariatric patients . Methods A total of 51 post-bariatric patients , 6–24 months post-surgery , were r and omly assigned to usual care control ( n = 25 ) or the exercise intervention ( n = 26 ) . The intervention included twice weekly 60-min group exercise classes with functional strength , flexibility , and aerobic activities ; at least 3 days per week of self-directed exercise ; daily pedometer ; recording of steps and activities ; and weekly telephone counseling . There was also a 6-month maintenance period . Results Patients were 49 ± 12 years old , 84 % female , 59 % non-Hispanic white , with a BMI of 32.9 ± 5.7 kg/m2 and percent excess BMI loss since surgery of 56 ± 35 % . Patients were 14 ± 5 months post-surgery . A total of 44 patients ( 86 % ) completed both phases of the program and all assessment s. The following measures improved significantly for intervention participants with no significant change in control participants : yards walked in 6 min , seconds for 8-foot up- and -go , number of arm curls , and distance in inches for chair sit- and -reach . Intervention changes remained after 6 months of maintenance . Conclusions When compared to patients in usual care , a specially adapted exercise program for post-bariatric patients result ed in significant improvements in objective ly monitored health outcomes . This program was delivered in a clinical setting and could be implemented in a variety of setting s to improve health outcomes for post-bariatric patients", "Both Roux-en-Y gastric bypass ( RYGB ) surgery and exercise can improve insulin sensitivity in individuals with severe obesity . However , the impact of RYGB with or without exercise on skeletal muscle mitochondria , intramyocellular lipids , and insulin sensitivity index ( SI ) is unknown . We conducted a r and omized exercise trial in patients ( n = 101 ) who underwent RYGB surgery and completed either a 6-month moderate exercise ( EX ) or a health education control ( CON ) intervention . SI was determined by intravenous glucose tolerance test . Mitochondrial respiration and intramyocellular triglyceride , sphingolipid , and diacylglycerol content were measured in vastus lateralis biopsy specimens . We found that EX provided additional improvements in SI and that only EX improved cardiorespiratory fitness , mitochondrial respiration and enzyme activities , and cardiolipin profile with no change in mitochondrial content . Muscle triglycerides were reduced in type I fibers in CON , and sphingolipids decreased in both groups , with EX showing a further reduction in a number of ceramide species . In conclusion , exercise superimposed on bariatric surgery – induced weight loss enhances mitochondrial respiration , induces cardiolipin remodeling , reduces specific sphingolipids , and provides additional improvements in insulin sensitivity", "Objective Roux-en-Y gastric bypass(RYGB ) can cause profound weight loss and improve overall cardiometabolic risk factors . Exercise ( EX ) training following RYGB can provide additional improvements in insulin sensitivity(SI ) and cardiorespiratory fitness . However , it remains unknown if a specific amount of EX post-RYGB is required to achieve additional benefits . Methods We performed a post-hoc analysis of participants who were r and omized into either a 6-month structured EX program or a health education control ( CON ) . EX(N=56 ) were divided into tertiles according to the amount of weekly exercise performed , compared to CON(N=42 ) : Low-EX=54±8 ; Middle-EX=129±4 ; High-EX=286±40 minutes per week . Results The High-EX lost a significantly greater amount of body weight , total fat mass and abdominal deep subcutaneous abdominal fat compared to CON(p ) . SI improved to a greater extent in both the Middle-EX and High-EX compared to CON(p ) . Physical fitness ( VO2max ) significantly improved in the High-EX(+9.3±4.2 % ) compared to CON(−6.0±2.4%)(p respiration was significantly higher in the High-EX compared to CON . Conclusion A modest volume of structured exercise provides additional improvements in insulin sensitivity following RYGB , but higher volumes of exercise are required to induce additional weight loss , changes in body composition and improvements in cardiorespiratory fitness and skeletal muscle mitochondrial capacity", "Background This study seeks to assess the effect of inspiratory muscle training ( IMT ) on pulmonary function , respiratory muscle strength , and endurance in morbidly obese patients su bmi tted to bariatric surgery . Methods Thirty patients were r and omly assigned to sham muscular training , or to IMT with a threshold device ( 40 % of maximum inspiratory pressure , MIP ) , for 30 min/day , from the 2nd until 30th postoperative ( PO ) day . All of them were su bmi tted to a st and ard respiratory kinesiotherapy and early deambulation protocol . Data on spirometry , maximum static respiratory pressures , and respiratory muscle endurance were collected on the PO days 2 , 7 , 14 , and 30 in a blinded matter . Results IMT enabled increases in PO MIP and endurance , and an earlier recovery of the spirometry parameters FEV1 , PEF , and FEF25–75 % . Comparing to preoperative values , MIP was increased by 13 % at the 30th PO day in the trained group , whereas control group had a reduction of 8 % , with higher values for the IMT group ( 30th PO , IMT—130.6 ± 22.9 cmH2O ; controls—112.9 ± 25.1 cmH2O ; p at the 30th PO day was increased in the trained group comparing to preoperative value ( 61.5 ± 39.6 s vs 114.9 ± 55.2 s ; p Conclusions IMT improves inspiratory muscle strength and endurance and accounts for an earlier recovery of pulmonary airflows in morbidly obese patients su bmi tted to bariatric surgery", "Summary Objectives Physical activity is important for weight management . However , it remains unclear what type of physical activity prescription/programme is optimal for increasing physical activity during a st and ard behavioural weight loss intervention . This study examined changes in physical activity after a 12‐week supervised programme prescribed in minutes per week ( SUP‐PA ) , an unsupervised programme prescribed in minutes per week ( UNSUP‐PA ) and an unsupervised programme prescribed in steps per day ( STEP ) . Methods Fifty‐two adults who were overweight or obese ( age : 43.5 ± 10.1 years , BMI : 31.5 ± 3.5 kg·m−2 ) were r and omized to STEP ( n = 18 ) , UNSUP‐PA ( n = 17 ) and SUP‐PA ( n = 17 ) . Subjects attended weekly in‐person group intervention sessions and were prescribed a calorie‐restricted diet ( 1,200–1,800 kcals·day−1 ) combined with increased physical activity ( 150 min·week−1 or 10,000 steps·day−1 with 2,500 brisk steps·day−1 ) . Results All three groups significantly increased moderate‐to‐vigorous physical activity ( STEP : 80.6 ± 218.5 min·week−1 , UNSUP‐PA : 112.9 ± 180.4 min·week−1 and SUP‐PA : 151.1 ± 174.0 min·week−1 , p differences in weight loss between the groups ( p = 0.81 ) . Conclusions In this short‐term study , all three physical activity programmes increased physical activity and elicited modest weight loss when combined with a st and ard behavioural weight loss intervention", "Weight regain is a problem among many bariatric surgery patients . Whether a high-volume exercise program ( HVEP ) , a strategy to limit weight regain , is feasible in these patients is unknown . The feasibility of an HVEP in obese post-bariatric-surgery patients was determined by r and omizing 33 Roux-en-Y gastric bypass ( RYGB ) and gastric b and ing ( GB ) surgery patients with a mean BMI of 41 ± 6 kg/m2 to an HVEP or control group for 12 weeks . The HVEP group was instructed to expend ≥ 2,000 kcal/week in moderate-intensity exercise . All patients were counseled to limit energy intake . Treatment effect was assessed by repeated measures analysis . During the last 4 weeks of the study , 53 % of the HVEP group expended ≥ 2,000 kcal/week and 82 % expended ≥ 1,500 kcal/week . Step count , reported time spent and energy expended during moderate physical activity , maximal oxygen consumption relative to weight , and incremental area under the postpr and ial blood glucose curve were significantly improved over 12 weeks in the HVEP group compared to controls ( group-by-week effect : P = 0.009 - 0.03 ) . Both groups reported significant improvement in some quality -of-life scales . Changes in weight , energy and macronutrient intake , resting energy expenditure ( REE ) , fasting lipids and glucose , and fasting and postpr and ial insulin concentrations were not different between the two groups . HVEP is feasible in about 50 % of the patients and enhances physical fitness and reduces postpr and ial blood glucose in bariatric surgery patients", "Background Obesity is a major public health concern on a global scale . Bariatric surgery is among the treatment options , result ing in significant and sustainable weight loss as well as amelioration of comorbidities . The purpose of this study was to evaluate whether a 12-week aerobic exercise program positively impacts heart rate variability ( HRV ) and functional capacity after gastric bypass surgery ( GBS ) in a female cohort . Methods Of the 52 patients initially recruited , 21 were r and omized to a training group ( TG ) or control group and successfully completed the study . Patients were tested on two occasions : 1 week before GBS and 4 months after GBS . Anthropometric variables , body composition , record of heart rate and R-R intervals , and 6-min walk test ( 6MWT ) were assessed at both time points . The TG underwent an aerobic exercise training program on a treadmill ( 1-h session , totaling 36 sessions over 12 weeks ) . Results The main findings from this study were : ( 1 ) only the TG demonstrated a significant increase ( p indexes of heart rate variability ( HRV ) after 12 weeks of aerobic exercise training and ( 2 ) only the TG demonstrated a significant increase ( p 6MWT distance and decrease in diastolic blood pressure after aerobic exercise training . Conclusions We conclude that 12 weeks of aerobic exercise training improves cardiac autonomic modulation and functional capacity 4 months after GBS", "BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application", "Background In recent years , the p and emic explosion of obesity has led to the definition of a pre-eminent therapeutic role for bariatric surgery , confining physical activity to a success parameter of surgery rather than a primary prevention measure . The aim of this study is to evaluate the role for aerobic physical activity ( road running ) in strengthening the metabolic and psychosocial effects of bariatric surgery . Methods Ten patients who underwent gastric bypass for morbid obesity were su bmi tted to an intensive program of road running training , aim ed at completing a 10.5-km competition in September 2013 . Inclusion criteria included age ( were enrolled as a control group . During the training period , patients were su bmi tted to biometrical , sport performance , cardiopulmonary , metabolic , and psychiatric evaluations . Results Protocol adherence was 70 % ; no physical injury was registered among participants . More than weight loss ( BMI 29.3 to 27.1 ) , the runners experienced a redistribution of body mass with significant differences in fat percentage and waist/hip ratio . Participants had a significant running performance improvement and , differently from the controls , a significant amelioration of echocardiographic and cardiopulmonary parameters , predicting a reduction in cardiovascular risk . Psychiatric evaluation underlined a tendency to a reduction in anxiety , depression , and general psychopathology symptoms . Conclusions Road running seems to have an important supporting role in boosting bariatric surgery results . The utilization of monitored and regulated training programs represents a fundamental prerequisite to achieving satisfactory results and patient compliance", "OBJECTIVE To test the effectiveness of two levels of physical activity interventions before and up to 6½ months after bariatric surgery . METHODS Before surgery , individuals completed submaximal exercise testing on a treadmill . After r and om assignment to st and ard care , pedometer use , or exercise counseling plus pedometer , participants wore an accelerometer for approximately 2 weeks and returned it to the bariatric center before surgery and 2 , 4 , and 6 months postoperatively . RESULTS Individuals in exercise counseling plus pedometer had higher steps per day and bout minutes of exercise per week than st and ard care and pedometer use over the course of the study . There were no group differences related to exercise tolerance ; however , all groups made significant improvement . There was no statistically significant change in sedentary or light activity nor was there a difference between groups . CONCLUSIONS Exercise counseling using pedometers increases physical activity from the perioperative period to 6½ months after surgery , but providing pedometers without professional feedback may not be more effective than st and ard bariatric surgery treatments . Rapid weight loss increases exercise tolerance and may mask the fitness improvements achieved through a modest physical activity intervention during the first 6 months after bariatric surgery", "Obesity and physical inactivity are major health problems . Roux‐en‐Y gastric bypass ( RYGB ) surgery results in significant weight loss and reduces obesity‐related morbidity and mortality . Physical activity lowers the risk of cardiovascular disease and premature death . The aims of this study were to eluci date the effects of RYGB followed by 6 months of supervised physical training on physical capacity . In a r and omized controlled trial , 60 participants eligible for RYGB were r and omized 6 months post‐surgery to either two weekly physical training sessions for 26 weeks ( INT ) or a control group ( CON ) . Aerobic capacity ( VO2max ) , muscle strength ( MS ) of the shoulder and hip and physical function were measured pre‐surgery and 6 , 12 and 24 months post‐surgery . RYGB per se decreased MS in all tested muscle groups , had no effects on VO2max but improved physical function . After the intervention , INT had a significant 0.33 L min−1 increase in VO2max compared to CON ( 95 % CI : 0.07–0.57 , P = 0.013 ) . Furthermore , MS in the hip adductor increased significantly with 13 N ( 95 % CI : 3.6–22.4 , P = 0.007 ) and a between‐group difference was found in the Stair Climb Test ( 0.46 repetitions [ 95 % CI : 0.02–0.91 , P = 0.042 ] ) . The effects were not maintained at follow‐up . Supervised physical training following RYGB improved VO2max , hip MS and physical function , but the positive effects were not maintained at follow‐up . While activities of daily life may become easier as a result of RYGB , the observed extensive post‐operative loss of MS requires more attention to increase the patient 's physical capacity prospect ively", "Background Obesity is associated with physical inactivity and impaired health-related quality of life ( HRQoL ) . We aim to test the hypothesis that Roux-en-Y gastric bypass ( RYGB ) followed by supervised physical training improves physical activity ( PA ) levels and HRQoL. Methods Sixty patients , qualified for RYGB , were at 6 months post-surgery r and omized to 26 weeks of a supervised physical training intervention ( INT ) or to a control ( CON ) group . PA was assessed by accelerometry and using the question naire RPAQ . HRQoL was measured by the SF-36 question naire . All assessment s were performed pre-surgery and 6 , 12 , and 24 months post-surgery . Results RYGB did not improve objective ly or self-reported PA , but improved all domains of SF-36 ( all p light PA , moderate to vigorous PA , and step counts tended to increase in INT compared to CON 12 months after RYGB ( 0.05 SF-36 domain “ general health ” increased in INT compared to CON 24 months after RYGB ( p = 0.041 ) . Conclusion RYGB improves HRQoL , but does not increase PA . Supervised physical training intervention improves general health 24 months after RYGB and tends to improve certain domains of PA right after the intervention period , but fails to increase the patients ’ overall PA level over time . Clinical Trial Registration Registered at Clinical Trials.gov — no . NCT01690728", "Background Respiratory physiotherapy plays an important role preventing complications in bariatric surgery . Aim To assess the effects of out-patient physiotherapy during post-operative period through respiratory pressures and functional capacity in individuals su bmi tted to bariatric surgery . Method A prospect i ve longitudinal and controlled study was done in adults with body mass index ( BMI ) equal or greater than 40 kg/m² , who have been su bmi tted to bariatric surgery . They were divided into two groups : intervention-group , who performed out-patient physiotherapy twice a week , from thirty to sixty days after surgery ; and the control-group , who only followed home instructions . Both groups were evaluated before surgery and sixty days after surgery through manovacuometry , six-minute walk test and the Borg Scale of perceived exertion . Results Twenty participants were included the intervention-group and twenty-three in the control-group . Both groups had significant and similar weight loss after surgery . The manovacuometry presented no differences comparing pre- and post-surgery and in the comparison between the groups . The result of the six-minute walk test for the intervention-group increased by 10.1 % in the post-operative period in relation to pre- . The Borg scale of perceived exertion in the intervention-group in pre-surgery decreased by 13.5 % in the post-surgery compared to pre-surgery . In the control-group there was no difference comparing pre- and post-operative values , as in the comparison with the intervention-group . Conclusion The low-intensity exercise program , carried out between the 30th and the 60th day after bariatric surgery provided better functional capacity ; did not change respiratory muscle strength ; and improved the perceived exertion rate" ]

[ "OBJECTIVE This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation ( AF ) . BACKGROUND Although intermittent AF is common , relatively little is known about the attendant risk of stroke . METHODS A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years . Independent risk factors for ischemic stroke were identified by multivariate analysis . RESULTS Patients with intermittent AF were , on average , younger ( 66 vs. 70 years , p women ( 37 % vs. 26 % p heart failure ( 11 % vs. 21 % , p annualized rate of ischemic stroke was similar for those with intermittent ( 3.2 % ) and sustained AF ( 3.3 % ) . In patients with intermittent AF , independent predictors of ischemic stroke were advancing age ( relative risk [ RR ] = 2.1 per decade , p hypertension ( RR = 3.4 , p = 0.003 ) and prior stroke ( RR = 4.1 , p = 0.01 ) . Of those with intermittent AF predicted to be high risk ( 24 % ) , the observed stroke rate was 7.8 % per year ( 95 % confidence interval 4.5 to 14 ) . CONCLUSIONS In this large cohort of AF patients given aspirin , those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors . Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation . High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF", "BACKGROUND AND PURPOSE Nonvalvular atrial fibrillation ( AF ) is a strong , independent risk factor for stroke , but the absolute rate of stroke varies widely among AF patients , importantly influencing the potential benefit of antithrombotic prophylaxis . We explore factors associated with ischemic stroke in AF patients taking aspirin . METHODS We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low , inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years , during which 130 ischemic strokes were observed . RESULTS Age ( relative risk [RR]=1.8 per decade , P hypertension ( RR=2.0 , P systolic blood pressure > 160 mm Hg ( RR=2.3 , P prior stroke or transient ischemic attack ( RR=2.9 , P stroke risk . Regular consumption of > /=14 alcohol-containing drinks per week was associated with reduced stroke risk ( adjusted RR=0.4 , P=0.04 ) . Among SPAF III participants , estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke ( adjusted RR=3.2 , P=0.007 ) . With the use of these variables , a risk stratification scheme for primary prevention separated participants into those with high ( 7.1%/y , 22 % of the cohort ) , moderate ( 2.6%/y , 37 % of the cohort ) , and low ( 0.9%/y , 41 % of the cohort ) rates of stroke . Ischemic strokes in low-risk participants were less often disabling ( P Patients with AF who have high and low rates of stroke during treatment with aspirin can be identified . However , validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management . Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF , but these findings require confirmation", "In a prospect i ve study of 312 older patients with chronic atrial fibrillation , at 36-month follow-up evaluation , new thromboembolic stroke developed in 162 of 312 patients ( 52 % ) . Significant independent risk factors for new thromboembolic stroke were prior stroke ( risk ratio = 1.6 ) , rheumatic mitral stenosis ( risk ratio = 2.0 ) , left ventricular ( LV ) hypertrophy ( risk ratio = 2.8 ) , abnormal LV ejection fraction ( risk ratio = 1.8 ) , serum total cholesterol ( risk ratio = 1.005 ) , and serum high-density lipoprotein cholesterol ( risk ratio = 0.96 )", "OBJECTIVE To identify echocardiographic predictors of arterial thromboembolism in patients with nonrheumatic atrial fibrillation and to determine whether these add to clinical variables for risk stratification . DESIGN Cohort study of patients assigned to placebo in a r and omized clinical trial . SETTING Five hundred sixty-eight in patients and out patients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study . Patients were followed for a mean of 1.3 years . MEASUREMENTS M-mode and two-dimensional ( 2-D ) echocardiograms performed at study entry and interpreted by local cardiologists . The predictive value of 14 echocardiographic variables for later ischemic stroke or systemic embolism was assessed by multivariate analysis . MAIN RESULTS Left ventricular dysfunction from 2-D echocardiograms ( P = 0.003 ) and the size of the left atrium from M-mode echocardiograms ( P = 0.02 ) were the strongest independent predictors of later thromboembolism . Multivariate analysis of these two independent echocardiographic predictors with the three independent clinical predictors of thromboembolism ( history of hypertension , recent congestive heart failure , previous thromboembolism ) identified 26 % of the cohort with a low risk for thromboembolism ( 1.0 % per year ; 95 % Cl , 0.2 % to 4.0 % ) . Compared with risk stratification using clinical variables alone , echocardiographic results altered thromboembolic risk stratification in 18 % of the entire cohort and in 38 % of those without clinical risk factors . CONCLUSIONS Both left ventricular and left atrial variables are significant predictors of thromboembolism in patients with nonvalvular atrial fibrillation . Our results challenge traditional views of the pathogenesis of ischemic stroke in patients with atrial fibrillation and suggest that st and ard echocardiography contributes to risk stratification , differentiating the one third of patients without clinical risk factors who are at increased risk for stroke from the remainder who may not need antithrombotic prophylaxis", "Abstract Chronic atrial fibrillation ( AF ) in the presence or absence of rheumatic valvular heart disease is associated with an increased incidence of stroke . 1,2 We reported in a prospect i ve study that at 27-month follow-up , echocardiographic left ventricular ( LV ) hypertrophy in elderly patients with systolic or diastolic hypertension was associated with an increased incidence of new atherothrombotic brain infa rct ion . 3 We also demonstrated in a prospect i ve study that at 3-year follow-up , risk factors for atherothrombotic brain infa rct ion were cigarette smoking , systolic or diastolic hypertension and diabetes mellitus in elderly men and systolic or diastolic hypertension , diabetes mellitus and obesity in elderly women . 4 This report correlates in elderly patients with chronic AF the prevalence of thromboembolic ( TE ) stroke with the presence or absence of rheumatic mitral stenosis , mitral anular calcium , valvular aortic stenosis , systolic or diastolic hypertension , prior myocardial infa rct ion , left atrial enlargement and LV hypertrophy", "BACKGROUND AND PURPOSE The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation ( NRAF ) varies from 2 % to 15 % in the first year and is approximately 5 % yearly thereafter . Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population . METHODS We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial . The mean follow-up was 1.6 years . RESULTS By means of multivariate modeling , six independent variables were identified : history of previous thromboembolism , ischemic heart disease , enlarged cardiothoracic ratio on chest roentgenogram , systolic blood pressure greater than 160 mm Hg at study entry , NRAF for more than 1 year , and presence of an ischemic lesion on CT scan . These variables could also be used to stratify patients in low- , medium- , and high-risk subgroups for the other two arms of the trial , those treated with anticoagulation and aspirin . Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment . CONCLUSIONS Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke", "CONTEXT Nonvalvular atrial fibrillation ( AF ) carries an increased risk for stroke , but absolute rates of stroke vary widely within the broad spectrum of AF patients . OBJECTIVE To prospect ively vali date a risk stratification scheme identifying patients with AF with low rates of stroke when given aspirin . DESIGN Prospect i ve cohort study with mean duration of follow-up of 2.0 years , conducted between 1993 and 1997 . SETTING Outpatient clinics affiliated with academic medical centers . PATIENTS Patients with AF categorized as \" low risk \" based on the absence of 4 prespecified thromboembolic risk factors : recent congestive heart failure or left ventricular fractional shortening of 25 % or less , previous thromboembolism , systolic blood pressure greater than 160 mm Hg , or female sex at age older than 75 years . INTERVENTION All participants given aspirin , 325 mg/d . MAIN OUTCOME MEASURES Ischemic stroke ( considered disabling when Rankin score was II or worse 1 - 3 months later ) and systemic embolism ( primary events ) . RESULTS Among 892 participants , the mean ( SD ) age was 67 ( 10 ) years , 78 % were men , and histories of hypertension , diabetes , and ischemic heart disease were present in 46 % , 13 % , and 16 % , respectively . The rate of primary events was 2.2 % per year ( 95 % confidence interval [ CI ] , 1.6%-3.0 % ) , of ischemic stroke was 2.0 % per year ( 95 % CI , 1.5%-2.8 % ) , and of disabling ischemic strokes was 0.8 % per year ( 95 % CI , 0.5%-1.3 % ) . Those with a history of hypertension had a higher rate of primary events ( 3.6 % per year ) than those with no history of hypertension ( 1.1 % per year ) ( P rate of disabling ischemic stroke was low in those with and without a history of hypertension ( 1.4 % per year and 0.5 % per year , respectively ) . The rate of major bleeding during aspirin therapy was 0.5 % per year . CONCLUSION Patients with AF who have relatively low rates of ischemic stroke , particularly disabling stroke , during treatment with aspirin can be reliably identified", "PURPOSE R and omized controlled trials have demonstrated that anticoagulant therapy is very effective at preventing stroke among patients with nonrheumatic atrial fibrillation . However , these trials have reported too few strokes for powerful risk factor analysis . Observational studies may provide additional information . The purpose of this study was to identify risk factors in a larger number of patients with stroke and nonrheumatic atrial fibrillation , using case-control methodology . PATIENTS AND METHODS We identified all patients discharged from one hospital over an 8-year period who met our case definition of nonrheumatic atrial fibrillation and ischemic stroke ( n = 134 ) , and compared them with contemporaneous control subjects who were discharged with nonrheumatic atrial fibrillation without stroke ( n = 131 ) . RESULTS Cases and controls were similar in terms of duration of atrial fibrillation ; proportion with paroxysmal atrial fibrillation ; percentage with a past medical history of angina , myocardial infa rct ion , congestive heart failure , diabetes , or smoking ; and mean left atrial size . In contrast , cases were significantly older than controls ( 78.5 versus 74.8 years , p = 0.002 ) and more likely to have a history of hypertension ( 55 % versus 38 % , p = 0.0093 ) . The relative odds for stroke was 1.91 for patients with hypertension , 1.73 for patients older than 75 years , and 3.26 for patients with both factors . CONCLUSIONS Our analysis suggests that age and hypertension should be considered when deciding upon long-term anticoagulant therapy to prevent stroke in patients with nonrheumatic atrial fibrillation", "OBJECTIVE To identify those patients with nonrheumatic atrial fibrillation who are at high risk and those at low risk for arterial thromboembolism . DESIGN Cohort study of patients assigned to placebo in a r and omized clinical trial . SETTING Five hundred sixty-eight in patients and out patients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study . Patients were followed for a mean of 1.3 years . MEASUREMENTS Clinical variables were assessed at study entry and correlated with subsequent ischemic stroke and systemic embolism by multivariate analysis . MAIN RESULTS Recent ( within 3 months ) congestive heart failure , a history of hypertension , and previous arterial thromboembolism were each significantly and independently associated with a substantial risk for thromboembolism ( greater than 7 % per year ; P less than or equal to 0.05 ) . The presence of these three independent clinical predictors ( recent congestive heart failure , history of hypertension , previous thromboembolism of 2.5 % per year ( no risk factors ) , 7.2 % per year ( one risk factor ) , and 17.6 % per year ( two or three risk factors ) . Nondiabetic patients without these risk factors , comprising 38 % of the cohort , had a low risk for thromboembolism ( 1.4 % per year ; 95 % Cl , 0.05 % to 3.7 % ) . Patients without clinical risk factors who were under 60 years of age had no thromboembolic events . CONCLUSION Patients with atrial fibrillation at high risk ( greater than 7 % per year ) and low risk ( less than 3 % per year ) for thromboembolism can be identified by readily available clinical variables", "BACKGROUND Anticoagulants are more effective than antiplatelet agents at reducing stroke risk in patients with atrial fibrillation , but whether this benefit outweighs the increased risk of bleeding in elderly patients is unknown . We assessed whether warfarin reduced risk of major stroke , arterial embolism , or other intracranial haemorrhage compared with aspirin in elderly patients . METHODS 973 patients aged 75 years or over ( mean age 81.5 years , SD 4.2 ) with atrial fibrillation were recruited from primary care and r and omly assigned to warfarin ( target international normalised ratio 2 - 3 ) or aspirin ( 75 mg per day ) . Follow-up was for a mean of 2.7 years ( SD 1.2 ) . The primary endpoint was fatal or disabling stroke ( ischaemic or haemorrhagic ) , intracranial haemorrhage , or clinical ly significant arterial embolism . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N89345269 . FINDINGS There were 24 primary events ( 21 strokes , two other intracranial haemorrhages , and one systemic embolus ) in people assigned to warfarin and 48 primary events ( 44 strokes , one other intracranial haemorrhage , and three systemic emboli ) in people assigned to aspirin ( yearly risk 1.8%vs 3.8 % , relative risk 0.48 , 95 % CI 0.28 - 0.80 , p=0.003 ; absolute yearly risk reduction 2 % , 95 % CI 0.7 - 3.2 ) . Yearly risk of extracranial haemorrhage was 1.4 % ( warfarin ) versus 1.6 % ( aspirin ) ( relative risk 0.87 , 0.43 - 1.73 ; absolute risk reduction 0.2 % , -0.7 to 1.2 ) . INTERPRETATION These data support the use of anticoagulation therapy for people aged over 75 who have atrial fibrillation , unless there are contraindications or the patient decides that the benefits are not worth the inconvenience", "OBJECTIVE To examine the cost-effectiveness of prescribing warfarin sodium in patients who have nonvalvular atrial fibrillation ( NVAF ) with or without additional stroke risk factors ( a prior stroke or transient ischemic attack , diabetes , hypertension , or heart disease ) . DESIGN Decision and cost-effectiveness analyses . The probabilities for stroke , hemorrhage , and death were obtained from published r and omized controlled trials . The quality -of-life estimates were obtained by interviewing 74 patients with atrial fibrillation . Costs were estimated from literature review , phone survey , and Medicare reimbursement . PATIENTS In the base case , the patients were 65 years of age and good c and i date s for warfarin therapy . INTERVENTIONS Treatment with warfarin , aspirin , or no therapy in the decision analytic model . MAIN OUTCOME MEASURES Quality -adjusted survival and marginal cost-effectiveness of warfarin as compared with aspirin or no therapy . RESULTS For patients with NVAF and additional risk factors for stroke , warfarin therapy led to a greater quality -adjusted survival and to cost savings . For patients with NVAF and one additional risk factor , warfarin therapy cost $ 8000 per quality -adjusted life-year saved . For 65-year-old patients with NVAF alone , warfarin cost about $ 370,000 per quality -adjusted life-year saved , as compared with aspirin therapy . However , for 75-year-old patients with NVAF alone , prescribing warfarin cost $ 110,000 per quality -adjusted life-year saved . For patients who were not prescribed warfarin , aspirin was preferred to no therapy on the basis of both quality -adjusted survival and cost in all patients , regardless of the number of risk factors present . CONCLUSIONS Treatment with warfarin is cost-effective in patients with NVAF and one or more additional risk factors for stroke . In 65-year-old patients with NVAF but no other risk factors for stroke , prescribing warfarin instead of aspirin would affect quality -adjusted survival minimally but increase costs significantly", "BACKGROUND Clinical features that consistently predict ischemic stroke in patients with nonvalvular atrial fibrillation have been identified , while echocardiographic risk factors are less well defined . OBJECTIVE To determine whether the results of transthoracic echocardiography add independent information to the clinical risk factors for stroke in patients with atrial fibrillation . METHODS Transthoracic echocardiographic findings and clinical features from 1066 patients with atrial fibrillation assigned to placebo or control in 3 r and omized trials ( Boston Area Anticoagulation Trial for Atrial Fibrillation , Stroke Prevention in Atrial Fibrillation I Study , and Veterans Affairs Prevention in Atrial Fibrillation Study ) were correlated with subsequent ischemic stroke by multivariate analysis . RESULTS The mean + SD age of patients was 67 + /- 10 years , 78 % were men , 55 % had a history of hypertension , 19 % had a history of diabetes , 7 % had a previous transient ischemic attack or stroke , and 27 % had a history of heart failure . During a mean follow-up of 1.6 years , 78 ischemic strokes occurred ( annual rate , 4.7 % ) . Moderate to severe left ventricular systolic dysfunction shown via 2-dimensional echocardiography was a strong independent predictor of stroke ( relative risk , 2.5 ; P stroke ( relative risk , 1.02/mm ; P = .10 ) . Of 163 patients categorized as low risk based on clinical features ( annual stroke rate , 0.8 % ; 95 % confidence interval , 0.2%-3.0 % ) , 10 had moderate to severe left ventricular dysfunction shown via 2-dimensional echocardiography and a 9.3 % per year risk of stroke ( 95 % confidence interval , 1.3%-66 % ) . Conversely , 728 of the 847 patients at high risk for stroke based on clinical criteria had normal or mildly abnormal left ventricular function ; their stroke rate was 4.4 % ( 95 % confidence interval , 3.4%-5.8 % ) . CONCLUSIONS Left ventricular systolic dysfunction shown via 2-dimensional transthoracic echocardiography independently predicts risk of stroke in patients with atrial fibrillation . Echocardiography may prove most useful in a small group of patients who have a low risk of stroke according to clinical factors", "CONTEXT Warfarin has been shown to be highly efficacious for preventing thromboembolism in atrial fibrillation in r and omized trials , but its effectiveness and safety in clinical practice is less clear . OBJECTIVE To evaluate the effect of warfarin on risk of thromboembolism , hemorrhage , and death in atrial fibrillation within a usual care setting . DESIGN Cohort study assembled between July 1 , 1996 , and December 31 , 1997 , and followed up through August 31 , 1999 . SETTING Large integrated health care system in Northern California . PATIENTS Of 13,559 adults with nonvalvular atrial fibrillation , 11,526 were studied , 43 % of whom were women , mean age 71 years , with no known contraindications to anticoagulation at baseline . MAIN OUTCOMES Ischemic stroke , peripheral embolism , hemorrhage , and death according to warfarin use and comorbidity status , as determined by automated data bases , review of medical records , and state mortality files . RESULTS Among 11,526 patients , 397 incident thromboembolic events ( 372 ischemic strokes , 25 peripheral embolism ) occurred during 25,341 person-years of follow-up , and warfarin therapy was associated with a 51 % ( 95 % confidence interval [ CI ] , 39%-60 % ) lower risk of thromboembolism compared with no warfarin therapy ( either no antithrombotic therapy or aspirin ) after adjusting for potential confounders and likelihood of receiving warfarin . Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke . A nested case-control analysis estimated a 64 % reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy . Warfarin was also associated with a reduced risk of all-cause mortality ( adjusted hazard ratio , 0.69 ; 95 % CI , 0.61 - 0.77 ) . Intracranial hemorrhage was uncommon , but the rate was moderately higher among those taking vs those not taking warfarin ( 0.46 vs 0.23 per 100 person-years , respectively ; P = .003 , adjusted hazard ratio , 1.97 ; 95 % CI , 1.24 - 3.13 ) . However , warfarin therapy was not associated with an increased adjusted risk of nonintracranial major hemorrhage . The effects of warfarin were similar when patients with contraindications at baseline were analyzed separately or combined with those without contraindications ( total cohort of 13,559 ) . CONCLUSIONS Warfarin is very effective for preventing ischemic stroke in patients with atrial fibrillation in clinical practice while the absolute increase in the risk of intracranial hemorrhage is small . Results of r and omized trials of anticoagulation translate well into clinical care for patients with atrial fibrillation", "BACKGROUND Atrial fibrillation ( AF ) may occur without symptoms . Little is known about demographic features and prognostic information in patients with asymptomatic AF . METHODS In the AFFIRM study , 4060 patients were r and omized to either rhythm or rate control . At baseline , patients were identified as asymptomatic if they answered \" no \" to a 15-item question naire related to cardiac symptoms during AF in the 6 months before study entry . RESULTS There were 481 ( 12 % ) asymptomatic patients at baseline . Compared with symptomatic patients , asymptomatic patients were more often men and had a lower incidence of coronary artery disease and congestive heart failure , but had more cerebrovascular events . Asymptomatic patients had a longer duration of AF , a lower maximum heart rate , and better left ventricular function . They received fewer cardiac medications and fewer therapies to maintain sinus rhythm . At 5 years , there was a trend for better survival in asymptomatic patients ( 81 % vs 77 % , P = .058 ) , and they were more likely to be free from disabling stroke or anoxic encephalopathy , major bleeding , and cardiac arrest ( 79 % vs 67 % , P = .024 ) . However , mortality and major events were similar after correction for baseline differences . CONCLUSIONS Patients with asymptomatic AF have less serious heart disease but more cerebrovascular disease . Asymptomatic patients receive different therapies than symptomatic patients . However , the absence of symptoms and the differences in treatment does not confer a more favorable prognosis when differences in baseline clinical parameters are considered . Anticoagulation should be considered in these patients", "As previously reported , 1007 patients with chronic atrial fibrillation participated in the Copenhagen AFASAK study . Before inclusion to trial , they all had a physical examination , chest roentgenogram , and echocardiogram with determination of left atrial size . This study evaluated the importance of cardiovascular risk factors for development of thromboembolic complications . To exclude any treatment effects on occurrence of thromboembolic complications , we included only the 336 patients from the placebo group . Using Cox 's regression model , previous myocardial infa rct ion was a significant risk factor for development of thromboembolic complications . Age , gender , heart failure , chest pain , hypertensive heart disease , diabetes , systolic and diastolic blood pressure , smoking , relative heart volume , and left atrial size were all without statistical importance", "PURPOSE The risk of ischemic stroke varies widely among patients with nonvalvular atrial fibrillation , influencing the choice of prophylactic antithrombotic therapy . We assessed three schemes for stroke risk stratification in these patients who were treated with aspirin and who did not have prior cerebral ischemia . SUBJECTS AND METHODS Criteria from three schemes of risk stratification were applied to a longitudinally observed cohort of patients with atrial fibrillation who did not have prior cerebral ischemia and who were treated with aspirin alone or aspirin combined with low , ineffective doses of warfarin in a multicenter clinical trial . The ability of the schemes to identify patients at high ( > /=6 % ) , low ( /=2 % ) , and intermediate annual risks of ischemic stroke was assessed . RESULTS During a mean follow-up of 1.8 years , 48 ischemic strokes occurred among 1,073 patients with atrial fibrillation who were taking aspirin ( rate = 2.5 per 100 person-years ) . Each of the three schemes predicted stroke and disabling stroke , and successfully identified patients at low risk ( observed stroke rates of 0.3 to 1.1 per 100 person-years ) , although the fractions of the cohort that were categorized as low risk varied from 14 % to 45 % . The observed rates of ischemic stroke among patients categorized as high risk ranged from 3.5 to 7.2 per 100 person-years among the stratification schemes . Two schemes considered all patients > 75 years old as high risk ( observed stroke rate 4.2 per 100 person-years ) , while the remaining scheme classified one third of patients in this age group as low risk ( observed stroke rate 0.6 per 100 person-years ) . CONCLUSIONS When tested in a large cohort of patients with atrial fibrillation who were treated with aspirin , available risk-stratification schemes successfully identified patients with low rates of ischemic stroke , but less consistently identified high-risk patients" ]

[ "Introduction The causes for revision of primary total hip arthroplasty ( THA ) are various and quite well known . The developing use of dual-mobility THA ( DM-THA ) seems a relevant option to decrease the risk of instability . Due to lack of long-term follow-up , this innovative retentive concept is suspected to increase the risk of polyethylene ( PE ) wear . the aim of the study was to analyse the causes for DM-THA revision and assess whether or not its occurrence is different from that of fixed-st and ard ( FS ) THA , particularly for aseptic loosening or wear and /or osteolysis . Material s and methods The SoFCOT group conducted an observational prospect i ve multicentre study from 1 January 2010 to 31 December 2011 . Inclusion criteria comprised an exhaustive collection of 2044 first-revision THAs with 251 DM-THAs and 1793 FS-THAs . After excluding complications linked to patient factors ( infection and periprosthetic fractures ) , we performed a matched case – control study ( matching ratio 1:1 ) comparing two groups of 133 THAs . Results Revisions for aseptic loosening or osteolysis/wear were as frequent in DM-THA ( 58.7 % ) as in FS-THA ( 57.1 % ) ( p 0.32 ) ; 7.5 % of DM-THA were revised for dislocation versus 19.5 % of FS-THA ( p 0.007 ) . Discussion Revision for osteolysis/wear and aseptic loosening were as frequent in DM-THA as in FS-THA ; revision for dislocation was less frequent in DM-THA . This confirms the efficiency of the DM concept regarding the risk of dislocation . Causes for revision were different between groups , and revisions for dislocation were less frequent in DM-THA . Only prospect i ve comparative studies could provide reliable information that may support broader use of the DM concept", "Background and purpose — Revision total hip arthroplasty ( THA ) is associated with higher dislocation rates than primary THA . We compared the risk of dislocation within 6 months and all-cause re-revision during the whole study period using either the dual-mobility cup or the unipolar cup . Methods — We used a prospect i ve hospital registry-based cohort including all total and cup-only revision THAs performed between 2003 and 2013 . The cups used were either dual-mobility or unipolar ; the choice was made according to the preference of the surgeon . 316 revision THAs were included . The mean age of the cohort was 69 ( 25–98 ) years and 160 THAs ( 51 % ) were performed in women . The dual-mobility group ( group 1 ) included 150 THAs ( 48 % ) and the mean length of follow-up was 31 ( 0–128 ) months . The unipolar group ( group 2 ) included 166 THAs ( 53 % ) and the mean length of follow-up was 52 ( 0–136 ) months . Results — The incidence of dislocation within 6 months was significantly lower with the dual-mobility cup than with the unipolar cup ( 2.7 % vs. 7.8 % ) . The unadjusted risk ratio ( RR ) was 0.34 ( 95 % CI : 0.11–1.02 ) and the adjusted RR was 0.28 ( 95 % CI : 0.09–0.87 ) . The number of patients needed to treat with a dual-mobility cup in order to prevent 1 case of dislocation was 19 . The unadjusted incidence rate ratio for all-cause re-revision in the dual-mobility group compared to the unipolar group was 0.6 ( 95 % CI : 0.3–1.4 ) . Interpretation — Use of a dual-mobility rather than a unipolar cup in revision THA reduced the risk of dislocation within 6 months", "Purpose To evaluate early performance of contemporary dual mobility acetabular systems with second generation annealed highly cross-linked polyethylene for primary hip arthroplasty of patients under 55 years of age . Methods A prospect i ve observational five years study across five centers in Europe and the USA of 321 patients with a mean age of 48.1 years was performed . Patients were assessed for causes of revision , hip instability , intra-prosthetic dissociation , Harris hip score and radiological signs of osteolysis . Results There were no dislocations and no intra-prosthetic dissociations . Kaplan Meier analysis demonstrated 97.51 % survivorship for all cause revision and 99.68 % survivorship for acetabular component revision at five years . Mean Harris hip score was 93.6 . Two acetabular shells were revised for neck-rim implant impingement without dislocation and ten femoral stems were revised for causes unrelated to dual mobility implants . Conclusion Contemporary highly cross-linked polyethylene dual mobility systems demonstrate excellent early clinical , radiological , and survivorship results in a cohort of patients that dem and high performance from their implants . It is envisaged that DM and second generation annealed HXLPE may reduce THA instability and wear , the two most common causes of THA revision in hip arthroplasty", "We evaluated all revisions performed from March 1996 to December 2008 and compared complications , mortality , and clinical outcomes between patients 80 years and older and patients younger than 80 years . Data were collected prospect ively . There were 325 revisions , 84 ( 25.8 % ) in patients 80 years and older and 241 in patients younger than 80 years ( 62 % revision for aseptic loosening in both groups ) . The mean follow-up was 4.3 years . The results , 80 years and older vs younger than 80 years , revealed the following : mortality , 5 % vs 0 % 3 months postoperatively ; medical complications in 23.8 % vs 6.2 % ; postoperative fractures , 9.5 % vs 2.5 % ; and improved Merle d'Aubigné scores from 9.6 to 13.0 vs 10.4 to 14.3 . Revision total hip arthroplasty in patients 80 years and older was associated with substantial clinical improvement and patient satisfaction . However , medical complications and 90-day mortality were higher , and postoperative fractures occurred more frequently", "BACKGROUND Constrained acetabular components have been used to treat hips with recurrent instability following total hip arthroplasty and hips that demonstrate instability during revision surgery . In such hips , when a secure cementless acetabular shell is present , the surgeon can cement a constrained liner into the existing shell . The purpose of this study was to evaluate the clinical and radiographic outcome of this technique with use of a tripolar constrained liner that was cemented into a well-fixed cementless acetabular shell . METHODS Between 1988 and 2000 , constrained liners were cemented into thirty-one well-fixed cementless acetabular shells at three centers . The average age of the patients at the time of the index surgery was 72.1 years , and the indications for the procedure were recurrent hip instability in sixteen hips and intraoperative instability in fifteen hips . The patients were evaluated with respect to the clinical outcome and radiographic evidence of shell loosening and osteolysis . RESULTS At an average duration of follow-up of 3.9 years , twenty-nine liners ( 94 % ) were securely fixed in the cementless shells and two constrained liners had failed . One liner failed because it separated from the cement , and one failed because of fracture of the capturing mechanism . Both hips were successfully revised with another cemented tripolar constrained liner . No acetabular component demonstrated radiographic evidence of progressive loosening or osteolysis . CONCLUSIONS A constrained tripolar liner cemented into a secure , well-positioned cementless acetabular shell provides stability and durability at short-term follow-up . Careful attention to the preparation of the liner , the sizing of the component , and the cementing technique are likely to reduce the failure of this construct , which can be used for difficult cases of total hip instability", "BACKGROUND Constrained liners are used as part of a salvage procedure to provide stability for patients at high risk for dislocation after a total hip arthroplasty . However , no recent studies exist highlighting their effectiveness and /or limitations . METHOD This prospect i ve review included 166 consecutive hip arthroplasties , either primary ( 27 % ) or revision ( 73 % ) , with a unique design of a constrained liner : Lefèvre retentive cup . There were 113 females ( 69 % ) , and the average age at index surgery was 75.9 years ( range , 35 - 94 ) . The mean follow-up was 6.2 years ( range , 0.3 - 11 ) . RESULTS Twenty patients had a reoperation ; 10 for infection ( 4 acute and 6 chronic joint infection ) and 10 for cup failure ( 5 fixation failure , 3 aseptic loosening , and 2 dislocation ) . Ten-year survivals for cup revision were 89 % ( CI , 83 - 94 ) and 92 % ( CI , 89 - 97 ) for all revision and revision for noninfectious reasons , respectively . When solely evaluating for dislocation , the survival at 10 years was 99 % ( CI , 97 - 100 ) . Considering primary and revision cases , 10-year survivals cup revision for aseptic reasons were 92.4 % ( CI , 84 - 100 ) and 92.5 % ( CI , 87 - 98 ) , respectively . CONCLUSIONS The Lefèvre retentive cup demonstrated excellent 10-year 's survivorship . With the rate of aseptic loosening around 2 % and a dislocation rate around 1 % , the cup is as effective as other available devices and is therefore a cost-effective tool to reduce the risk of dislocation in at-risk patients undergoing hip arthroplasty", "BACKGROUND Total hip arthroplasty ( THA ) using dual-mobility ( DM ) design permits larger hip range of motion . However , it is unclear how it benefits the patients during activities of daily living . The purpose was to compare kinematic variables of the operated limb between THA patients using either DM or single-bearing ( SB ) implants during a squat task . METHODS Twenty-four THA patients were r and omly assigned to either a DM or SB implant and matched to 12 healthy controls ( CTRLs ) . They underwent 3-dimensional squat motion analysis before and 9 months after surgery . Sagittal and frontal plane angles of the pelvis and the hip were analyzed using statistical parametric mapping . Paired analyses compared presurgery and postsurgery squat depth . RESULTS Peak sagittal pelvis angle of DM was closer to normal compared with that of SB . Both implant groups had similar hip angle patterns and magnitude but significantly lower than the CTRLs . SB reached a much large hip abduction compared with the other groups . Both surgical groups had significantly worst squat depth than the CTRLs . CONCLUSION Neither THA implant groups were able to return pelvis and hip kinematics to the level of CTRLs . The deficit of DM implants at the pelvis combined with the poorer functional scores should caution clinicians to use this implant design in active patients . SB design causes a larger hip abduction to reach their maximum squat depth . Post-THA rehabilitation should focus on improving joint range of motion and strength" ]

[ "Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries , which GH dosage to use and which age to start puberty induction are issues of debate . This study shows final height ( FH ) in 60 girls with Turner syndrome treated in a r and omized dose-response trial , combining GH treatment with low dose estrogens at a relatively young age . Girls were r and omly assigned to group A ( 4 IU/m(2).d ; approximately 0.045 mg/kg/d ) , group B ( first year , 4 IU/m(2).d ; thereafter 6 IU/m(2).d ) , or group C ( first year , 4 IU/m(2).d ; second year , 6 IU/m(2).d ; thereafter , 8 IU/m(2).d ) . After a minimum of 4 yr of GH treatment , at a mean age of 12.7 + /- 0.7 yr , low dose micronized 17beta-estradiol was given orally . After a mean duration of GH treatment of 8.6 + /- 1.9 yr , FH was reached at a mean age of 15.8 + /- 0.9 yr . FH , expressed in centimeters or SD score , was 157.6 + /- 6.5 or -1.6 + /- 1.0 in group A , 162.9 + /- 6.1 or -0.7 + /- 1.0 in group B , and 163.6 + /- 6.0 or -0.6 + /- 1.0 in group C. The difference in FH in centimeters , corrected for height SD score and age at start of treatment , was significant between groups A and B [ regression coefficient , 4.1 ; 95 % confidence interval ( CI ) , 1.4 , 6.9 ; P of the 60 girls ( 83 % ) had reached a normal FH ( FH SD score , more than -2 ) . After starting estrogen treatment , the decrease in height velocity ( HV ) changed significantly to a stable HV , without affecting bone maturation ( change in bone age/change in chronological age ) . The following variables contributed significantly to predicting FH SD score : GH dose , height SD score ( ref . normal girls ) , chronological age at start of treatment , and HV in the first year of GH treatment . GH treatment was well tolerated . In conclusion , GH treatment leads to a normalization of FH in most girls , even when puberty is induced at a normal pubertal age . The optimal GH dosage depends on height and age at the start of treatment and first year HV", "Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged", " Seventy girls with Turner syndrome , verified by karyotype , were r and omly assigned to observation or treatment with human growth hormone ( hGH ) , ox and rolone , or a combination of hGH plus ox and rolone for a period of 12 to 24 months , to assess the effect of treatment on growth velocity and adult height . Subsequently , all subjects received either hGH alone or hGH plus ox and rolone . Data are presented for 62 subjects treated for a period of 3 to 6 years . When compared with the anticipated growth rate in untreated patients , the growth rate after treatment with hGH , both alone and in combination with ox and rolone , showed a sustained increase for at least 6 years . Treatment is continuing in over half of the subjects ; at present , 14 ( 82 % ) of 17 girls receiving hGH alone and 41 ( 91 % ) of 45 girls receiving combination therapy exceeded their expected adult heights . Thirty girls have completed treatment ; mean height for these 30 patients is 151.9 cm , compared with their mean original projected adult height of 143.8 cm . We conclude that therapy with hGH , alone and in combination with ox and rolone , can result in a sustained increase in growth rate and a significant increase in adult height for most prepubertal girls with Turner syndrome", " Beginning in 1983 , 71 girls with Turner syndrome were enrolled in a prospect i ve , r and omized study of human growth hormone ( hGH ) , alone and in combination with ox and rolone ; 4 - 5 patient-year data are currently available on 66 subjects . While the annual growth rate of the untreated control group ( expressed as a Z score for untreated Turner girls ) was -0.1 SD , the annual Turner growth rate Z scores for girls receiving hGH alone were + 3.1 , + 2.0 , + 1.5 and + 2.9 SD for years 1 - 4 , respectively ( hGH was given daily in year 4 ) . mean annual Turner growth rate Z scores for subjects on combination therapy with ox and rolone were + 6.6 , + 4.3 , + 3.0 and + 2.7 SD for years 1 - 4 , respectively . The mean height for the 20 subjects greater than or equal to 16 years of age is 150 cm", "The aims of this comparative multicenter study of 67 girls with Turner syndrome ( TS ) on three different therapeutical regimens were , first , to evaluate the effect of either recombinant human growth hormone ( GH ) alone or in combination with the anabolic steroid ox and rolone ( Oxa ) on height velocity and on Turner-specific bone age ( BA'TS ) and , second , to estimate the gain in final height taking the age at the onset of treatment into account . The mean advancement of BA'TS in 2 years of treatment was 2.5 years/2 years in group 1 ( low dose GH : 16 IU/m2/week ) , 2.8 years/2 years in group 2 ( high dose GH : 28 IU/m2/week ) and 3.3 years/2 years in group 3 ( GH : 24 IU/m2/week + Oxa : 0.06 mg/kg/day ) instead of the expected 2 years/2 years advancement in untreated girls with TS . On all treatment regimens the advancement of BA'TS was more pronounced in the younger girls . In many girls with a BA'TS below 9 years at the onset of treatment the increase in height did not outweigh the advancement in BA'TS , suggesting that starting growth-promoting treatment before 9 years would not be the best way to improve final height . In our opinion , the optimal age for starting growth-promoting therapy is at 9 years . A start at a younger age might have no advantage in regard of an ultimate gain in final height . On the other h and , therapy should not be delayed much after the age of 9 years giving the girls with TS the possibility to catch up substantially before estrogen treatment is initiated", "PURPOSE We aim ed to assess the impact of spin ( ie , reporting to convince readers that the beneficial effect of the experimental treatment is greater than shown by the results ) on the interpretation of results of abstract s of r and omized controlled trials ( RCTs ) in the field of cancer . METHODS We performed a two-arm , parallel-group RCT . We selected a sample of published RCTs with statistically nonsignificant primary outcome and with spin in the abstract conclusion . Two versions of these abstract s were used-the original with spin and a rewritten version without spin . Participants were clinician corresponding authors of articles reporting RCTs , investigators of trials , and review ers of French national grants . The primary outcome was clinicians ' interpretation of the beneficial effect of the experimental treatment ( 0 to 10 scale ) . Participants were blinded to study hypothesis . RESULTS Three hundred clinicians were r and omly assigned using a Web-based system ; 150 clinicians assessed an abstract with spin and 150 assessed an abstract without spin . For abstract s with spin , the experimental treatment was rated as being more beneficial ( mean difference , 0.71 ; 95 % CI , 0.07 to 1.35 ; P = .030 ) , the trial was rated as being less rigorous ( mean difference , -0.59 ; 95 % CI , -1.13 to 0.05 ; P = .034 ) , and clinicians were more interested in reading the full-text article ( mean difference , 0.77 ; 95 % CI , 0.08 to 1.47 ; P = .029 ) . There was no statistically significant difference in the clinicians ' rating of the importance of the study or the need to run another trial . CONCLUSION Spin in abstract s can have an impact on clinicians ' interpretation of the trial results", "In systematic review s , meta‐analyses are routinely applied to summarize the results of the relevant studies for a specific research question . If one can assume that in all studies the same true effect is estimated , the application of a meta‐ analysis with common effect ( commonly referred to as fixed‐effect meta‐ analysis ) is adequate . If between‐ study heterogeneity is expected to be present , the method of choice is a meta‐ analysis with r and om effects . The widely used DerSimonian and Laird method for meta‐analyses with r and om effects has been criticized due to its unfavorable statistical properties , especially in the case of very few studies . A working group of the Cochrane Collaboration recommended the use of the Knapp‐Hartung method for meta‐analyses with r and om effects . However , as heterogeneity can not be reliably estimated if only very few studies are available , the Knapp‐Hartung method , while correctly accounting for the corresponding uncertainty , has very low power . Our aim is to summarize possible methods to perform meaningful evidence syntheses in the situation with only very few ( ie , 2‐4 ) studies . Some general recommendations are provided on which method should be used when . Our recommendations are based on the existing literature on methods for meta‐ analysis with very few studies and consensus of the authors . The recommendations are illustrated by 2 examples coming from dossier assessment s of the Institute for Quality and Efficiency in Health Care", "Background / Aims : Untreated girls with Turner syndrome ( TS ) have growth failure , and adult height is , on average , 20 cm less than predicted height . Treatment with growth hormone ( GH ) is now st and ard of care . The objective of this study was to investigate the benefit of adding ox and rolone ( Ox ) to GH in a long-term , r and omized , placebo (Pl)-controlled prospect i ve trial to near adult height in TS . Methods : Prospect i ve , r and omized , Pl-controlled study : 76 girls with TS ( ages 10–14.9 years ) were r and omized to receive Ox ( 0.06 mg/kg/day ) or Pl in combination with GH ( 0.35 mg/kg/week , daily ) over 2 years . Auxologic data , breast and pubic hair Tanner stages , and hormone and lipid levels were measured . Subjects who chose to continue were followed in a 2-year double-blind extension , also received estrogen therapy ( years 3 , 4 ) , and had dual-energy X-ray absorptiometry evaluation of bone density ( years 3 , 4 ) . Results : At year 4 , the change in absolute height and height SDS was greater in the GH/Ox versus GH/Pl group [ 26.2 ± 6.7 vs. 22.2 ± 5.1 cm , analysis of covariance ( ANCOVA ) p p 0.001 ] . Bone mineral density ( BMD ) of the wrist ( 0.51 ± 0.17 vs. 0.54 ± 0.05 g/cm2 ) and spine ( 0.91 ± 0.34 vs. 0.96 ± 0.13 g/cm2 ) in the GH/Ox versus GH/Pl groups was similar after 4 years . Breast development was slower in the GH/Ox versus GH/Pl group [ year 4 : Tanner stage 2.9 ±1.3 ( Ox ) vs. 4.1 ± 1.3 ( Pl ) , p = 0.003 ] , and menarche was approximately 1 year later . Conclusions : The addition of Ox to GH at mean age 12.0 ± 1.7 year augmented height gain after 4 years of treatment , slowed breast development and did not affect BMD in girls with TS . Whether initiation of Ox prior to initiation of pubertal development would optimize height gain without impeding breast development will require further study", "OBJECTIVE The study aims to provide information about variance components of psychosocial outcomes : within and between-participant variance , within-participant correlation and for cluster r and omised trials , the intra-cluster correlation ( ICC ) and , also , to demonstrate how estimates of these variance components and ICCs can be used to design r and omised trials and cluster r and omised trials . METHOD Data from 15 longitudinal multi-centre psycho-oncology studies were analysed , and variance components including ICCs were estimated . Studies with psychosocial outcomes that had at least one measurement post-baseline including individual r and omised controlled trials , cluster r and omised trials and observational studies were included . RESULTS Variance components and ICCs from 87 outcome measures were estimated . The unadjusted , single timepoint ( first post-baseline ) ICCs ranged from 0 to 0.16 , with a median value of 0.022 and inter-quartile range 0 to 0.0605 . The longitudinal ICCs ranged from 0 to 0.09 with a median value of 0.0007 and inter-quartile range 0 to 0.018 . CONCLUSIONS Although the magnitude of variance components and ICCs used for sample -size calculation can not be known in advance of the study , published estimates can help reduce the uncertainty in sample -size calculations . Psycho-oncology research ers should be conservative in their sample -size calculations and use approaches that improve efficiency in their design and analysis", "In 1983 , a multicenter , collaborative , prospect i ve study was begun to investigate the efficacy of human growth hormone ( hGH ) , alone and in combination with ox and rolone , in girls with Turner syndrome . While subjects in the control group grew 3.8 cm/yr ( -0.1 SD for untreated Turner patients ) , subjects receiving hGH alone grew 6.6 , 5.4 and 4.6 cm/yr in years 1 - 3 , respectively ( + 3.1 , + 2.0 , + 1.4 SD ) . Subjects in the combination therapy group grew 9.8 , 7.4 and 6.1 cm/yr ( + 6.6 , + 4.3 , + 3.0 SD ) . Turner subjects in both treatment groups showed increased in Bayley-Pinneau predicted adult heights and in Turner projected adult heights", "Background There are limited long-term r and omized controlled trials of growth hormone ( GH ) supplementation to adult height and few published reports of the health-related quality of life ( HRQOL ) following treatment . The present follow-up study of young adults from a long-term controlled trial of GH treatment in patients with Turner syndrome ( TS ) yielded data to examine whether GH supplementation result ed in a higher HRQOL ( either due to taller stature or from the knowledge that active treatment and not placebo had been received ) or alternatively a lower HRQOL ( due to medicalization from years of injections ) . Methods The original trial r and omized 154 Canadian girls with TS aged 7 - 13 years from 13 centres to receive either long-term GH injections at the pharmacologic dose of 0.3 mg/kg/week or to receive no injections ; estrogen prescription for induction of puberty was st and ardized . Patients were eligible for the follow-up study if they were at least 16 years old at the time of follow-up . The instrument used to study HRQOL was the SF-36 , summarized into physical and mental component scales ( PCS and MCS ) ; higher scores indicate better HRQOL . Results Thirty-four of the 48 eligible participants ( 71 % ) consented to participate ; data were missing for one patient . Both groups ( GH and no treatment ) had normal HRQOL at this post-treatment assessment . The GH group had a ( mean ± SD ) PCS score of 56 ± 5 ; the untreated group 58 ± 4 ; mean score for 16 - 24 year old females in the general population 53.5 ± 6.9 . The GH group had a mean MCS score of 52 ± 6 ; the untreated group 49 ± 13 ; mean score for 16 - 24 year old females in the general population 49.6 ± 9.8 . Secondary analyses showed no relationship between HRQOL and height . Conclusions We found no benefit or adverse effect on HRQOL either from receiving or not receiving growth hormone injections in a long-term r and omized controlled trial , confirming larger observational studies . We suggest that it remains ethically acceptable as well as necessary to maintain a long-term untreated control group to estimate the effects of pharmacological agents to manipulate adult height . Young adult women with TS have normal HRQOL suggesting that they adjust well to their challenges in life . Trial Registration Clinical Trials.gov Identifier NCT00191113", "Summary As part of a larger prospect i ve study of the influence of environmental factors on pregnancy , birth and the fetus , chromosome examinations have been made in 34910 newborn children in Århus over a 13-year period . Klinefelter 's syndrome was found in 1 per 576 boys , XYY in 1 per 851 boys , triple-X in 1 per 947 girls and Turner 's syndrome in 1 per 1893 girls . Other sex chromosome aberrations were found in 1 per 11637 children . The total incidence of sex chromosome abnormalities was 1 per 426 children or 2.34 per 1000 . The most frequent autosomal abnormalities were that of Down 's syndrome with 1 per 592 children , and reciprocal translocations with 1 per 712 children . The total incidence of autosomal abnormalities was 1 per 164 children . Chromosome abnormalities were found in 276 liveborn children and in 19 fetuses , who were aborted after prenatal chromosome examination . The combined incidence of sex chromosomal and autosomal abnormalities was 1 per 118 children or 8.45 per 1000 children", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "BACKGROUND Most girls with Turner syndrome ( TS ) receive growth hormone ( GH ) treatment during childhood and adolescence , but controlled data on the effects on body composition and glucose metabolism are lacking . OBJECTIVE To study the effects of GH treatment on insulin sensitivity , glucose metabolism , bone turnover , and body composition . METHODS A r and omized , placebo-controlled , crossover study was conducted with girls with TS . All girls with TS were treated with GH 0.1 IU/kg/d subcutaneously at bedtime or with placebo for 2 months and studied at the end of each period . Control subjects were studied once without treatment . Twelve girls with TS , aged 9.5 to 14.8 years ( median : 12.9 years ) and 16 age-matched control subjects ( 10.3 - 16.0 years ; median : 12.1 years ) were studied . Twenty-four-hour sampling of blood was performed ; GH , insulin-like growth factor I ( IGF-I ) , IGF binding proteins ( IGFBPs ) , insulin , glucose , and lipolytic and gluconeogenic precursors were assayed , followed by an oral glucose tolerance test . Body composition was evaluated by dual-energy x-ray absorptiometry scanning and body mass index ( BMI ) . Fasting bone markers were measured . RESULTS Height was reduced in TS as compared with control subjects . In the placebo situation , 24-hour integrated GH as well as IGF-I was significantly reduced in girls with TS compared with control subjects . Controlling for differences in lean body mass ( LBM ; or fat mass [ FM ] ) and sexual development did not explain the difference in 24-hour integrated GH . Differences in sexual development , BMI , FM , insulin sensitivity , and IGFBP-3 could explain the difference in IGF-I between TS and control subjects . Carbohydrate metabolism in TS was comparable with control subjects . GH treatment induced insulin resistance , with increments in fasting glucose and insulin , as well as 24-hour insulin . Circulating levels of lipid and gluconeogenic substrates were comparable in TS and control subjects and unchanged in response to treatment . Bone markers increased in response to GH . Total FM was increased in girls with TS , accounted for by an increased FM in the arms and trunk , whereas LBM was decreased . Especially LBM in the legs was decreased . Overall , bone mineral content was diminished . Treatment with GH reduced FM in TS , especially in the arms and legs , and likewise increased total LBM , primarily in the trunk . CONCLUSION This study documented evidence of impaired GH secretion and action , disproportionate body composition , but a normal carbohydrate metabolism in girls with TS . Short-term GH administration was associated with favorable changes in body composition but also with relative impairment of glucose tolerance and insulin sensitivity . We recommend that glucose metabolism be monitored carefully during long-term GH treatment in these patients", "Twenty‐six one‐year treatment periods on ox and rolone ( 0.1 mg/kg/day ) were studied in 20 patients with Turner 's syndrome . Control patients with Turner 's syndrome were matched by using the following criteria : difference in bone age being not greater than 0.S years and difference in the Bayley‐Pinneau height prediction not greater than 3 cm . Height and height velocity were compared with st and ards of girls with Turner 's syndrome ( 10 ) and expressed in st and ard deviation scores ( SDS ) . On ox and rolone height velocity increased significantly from −0.3 SDS to + 3.0 SDS . The increase in height velocity was negatively correlated to the bone age at onset of treatment ( r= 0.62 , p ) . Height SDS improved by 0.45 SDS in the treated patients whereas it did not change in the control patients . The bone age velocity during the treatment period ( including a six‐month period after treatment ) was 0.75 year/year in the treated , compared to 0.66 year/year in the control patients ( NS ) . 15 of the 20 patients have reached final height . The difference in final height minus predicted height ( Bayley‐Pinneau ) at onset of treatment was taken as a measure of “ gain in final height ” . Seven of those ( mean bone age 12.1 years at onset of treatment ) were treated for one year only and had – compared to the matched controls – a mean net gain in final height of 2.5 cm ( NS ) . Eight patients ( mean bone age 10.1 years at onset of treatment ) were treated for two one‐year periods and had a significant mean net gain in final height of 5.2 cm . Height predictions calculated by the method of Lenko ( 14 ) gave an identical mean net gain in final height ( 5.1 cm", "CONTEXT As of 2005 , the International Committee of Medical Journal Editors required investigators to register their trials prior to participant enrollment as a precondition for publishing the trial 's findings in member journals . OBJECTIVE To assess the proportion of registered trials with results recently published in journals with high impact factors ; to compare the primary outcomes specified in trial registries with those reported in the published articles ; and to determine whether primary outcome reporting bias favored significant outcomes . DATA SOURCES AND STUDY SELECTION MEDLINE via PubMed was search ed for reports of r and omized controlled trials ( RCTs ) in 3 medical areas ( cardiology , rheumatology , and gastroenterology ) indexed in 2008 in the 10 general medical journals and specialty journals with the highest impact factors . DATA EXTRACTION For each included article , we obtained the trial registration information using a st and ardized data extraction form . RESULTS Of the 323 included trials , 147 ( 45.5 % ) were adequately registered ( ie , registered before the end of the trial , with the primary outcome clearly specified ) . Trial registration was lacking for 89 published reports ( 27.6 % ) , 45 trials ( 13.9 % ) were registered after the completion of the study , 39 ( 12 % ) were registered with no or an unclear description of the primary outcome , and 3 ( 0.9 % ) were registered after the completion of the study and had an unclear description of the primary outcome . Among articles with trials adequately registered , 31 % ( 46 of 147 ) showed some evidence of discrepancies between the outcomes registered and the outcomes published . The influence of these discrepancies could be assessed in only half of them and in these statistically significant results were favored in 82.6 % ( 19 of 23 ) . CONCLUSION Comparison of the primary outcomes of RCTs registered with their subsequent publication indicated that selective outcome reporting is prevalent", "Background The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently", " 91 girls with Turner syndrome ( TS ) with a mean chronological age ( CA ) and bone age ( BA ) of 10.3 + /- 2.3 and 8.9 + /- 1.9 years , respectively , were r and omly assigned to subcutaneous treatment with recombinant human growth hormone ( rhGH ) alone ( n = 47 ) , 2.6 IU/m2 body surface area daily or combination treatment ( n = 44 ) with the same dose of rhGH and ox and rolone 0.1 mg/kg body weight orally , for the first 12 months of this study . During the 1st year of therapy , there was a striking increase in height velocity ( HV ) in both groups , from 4.0 + /- 0.8 to 6.3 + /- 1.3 cm/year [ HV st and ard ( st and ards of untreated Turner patients ) deviation score ( SDS ) for CA from 0.0 + /- 0.7 to 2.9 + /- 1.3 ] in the rhGH group and from 4.2 + /- 1.2 to 8.5 + 2- 1.7 cm/year ( HV SDS-CA from + 0.3 + /- 1.0 to 5.6 + /- 1.6 ) in the combination group . The difference between the groups was statistically significant ( p rhGH dose was increased to 3.4 IU/m2 daily for the rhGH-alone group , whereas in the combination treatment group the ox and rolone dose was reduced to 0.05 mg/kg daily . HV was maintained at significantly higher levels than those prior to treatment , at 5.3 + /- 1.1 cm/year ( HV SDS-CA : + 2.1 + /- 1.3 ) and 6.2 + /- 1.5 cm/year ( HV SDS-CA : + 3.6 + /- 1.4 ) in the rhGH-alone and the combination group , respectively ( p < 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVE To assess objective and subjective voice parameters among Turner syndrome ( TS ) women in relation to genotype , hearing , growth , and previous treatment with growth hormone ( GH ) and and rogen given that lowering of speaking fundamental frequency ( SFF ) during treatment is regarded as a negative side effect . STUDY DESIGN Cross-sectional , controlled for karyotype and age . METHODS Voice function was studied objective ly ( SFF ) and subjectively ( question naire ) in 117 women with TS . RESULTS SFF did not differ between treated and nontreated participants or between patients with a spontaneous versus induced puberty . SFF was dependent on karyotype but not age . Subjective voice change was reported four times more often among treated compared with nontreated TS women ( odds ratio [ OR ] = 4.4 ; 95 % confidence interval [ CI ] : 0.9 - 20.10 ) , whereas voice and articulation problems were reported three times more often among untreated compared with treated cases ( OR = 2.9 ; 95 % CI : 1.0 - 8.3 ) . Voice symptoms were over-represented among patients having micrognathia ( OR = 6.0 ; 95 % CI : 1.6 - 22.3 ) , hearing loss ( OR = 8.6 ; 95 % CI : 1.7 - 43.1 ) , and monosomy ( OR = 6.2 ; 95 % CI : 0.8 - 36.2 ) but not among those with an arched palate . CONCLUSIONS When given to TS girls , GH ( 33 - 66 microg/kg/d ) and and rogen ( 0.05 mg/kg/d ) normalized SFF and reduced voice and articulation problems in adulthood . The TS phenotype includes important voice and speech problems , which in turn are associated with hearing problems , although genotypic , monosomic , and isochromosome patients have more voice problems and also more high-pitched voices than mosaic patients . Most TS women , despite their karyotype or age , exhibit a higher frequency of pitched voice than non-TS women", "OBJECTIVE To carry out a multicenter , prospect i ve , r and omized trial of human growth hormone ( GH ) , alone or in combination with ox and rolone ( OX ) , in patients with Turner 's syndrome ( TS ) . METHODS In an initial phase lasting 12 to 24 months , 70 girls with TS , verified by karyotype , were r and omly assigned to one of four groups : ( 1 ) observation , ( 2 ) OX , ( 3 ) GH , or ( 4 ) GH plus OX . After completion of the first phase , group 3 subjects continued to receive GH only . All other subjects were treated with GH plus OX . Subjects were followed up until attainment of adult height and /or cessation of treatment . Data from this trial were compared with growth characteristics of 25 American historical subjects with TS ( matched for age , height , parental target height , and karyotype ) who never received either GH or and rogens . RESULTS Of the 70 subjects enrolled , 60 completed the clinical trial . The 17 subjects receiving GH alone all completed the trial and reached a height of 150.4+/-5.5 cm ( mean + /- SD ) , 8.4+/-4.5 cm taller than their mean projected adult height at enrollment ( 95 % confidence interval [ CI ] : 6.3 to 10.6 cm ) . The 43 subjects receiving GH plus OX attained a mean height of 152.1+/-5.9 cm , 10.3+/-4.7 cm taller than their mean projected adult height ( 95 % CI : 8.9 to 11.7 cm ) . The historical control subjects had a mean adult height of 144.2+/-6.0 cm , precisely matching their original projected adult height of 144.2+/-6.1 cm . CONCLUSIONS GH , either alone or in combination with OX , is capable of stimulating short-term growth and augmenting adult height in girls with TS . With early diagnosis and initiation of treatment , an adult height of more than 150 cm is a reasonable goal for most girls with TS", "A total of 70 subjects with Turner 's syndrome from 11 centres were enrolled in a study of somatrem . After an initial observation period , they were r and omly assigned to one of four groups , receiving no treatment ( Group 1 , control ) ; ox and rolone , 0.125 mg/kg/day ( Group 2 ) ; somatrem , 0.125 mg/kg 3 times/week ( Group 3 ) ; or a combination of somatrem and ox and rolone on the above dose regimens ( Group 4 ) . After 12–20 months , Groups 1 ( control ) , 2 ( ox and rolone ) and 4 ( combination ) were treated with somatrem , 0.125 mg/kg 3 times/week , and ox and rolone , 0.0625 mg/kg/day ; Group 3 remained on somatrem , 0.125 mg/kg 3 times/week . All three treatment groups showed a statistically significant increase during year 1 in growth velocity over both their pretreatment growth rates and the control group growth rate . These increases were slightly less in year 2 for the somatrem and combination therapy groups , but remained significantly higher than the year 1 control group growth rate . Plasma IGF‐1 levels were elevated in years 1 and 2 in the somatrem and combination groups . Adverse events were few with the somatrem group , though mild virilization occurred with ox and rolone , alone or in combination . Bone age advancement was observed with all treatments but was greater with combination therapy ; it was accompanied by height age advancement . The effect of this therapy on predicted adult height was also evaluated", "CONTEXT Pediatric management of patients with Turner syndrome focuses on height , frequently result ing in a delay of pubertal induction . The influence of pubertal management on psychosocial adjustment and sex life has not been evaluated in Turner syndrome patients . OBJECTIVE The objective of the study was to identify the determinants of self-esteem , social adjustment , and initiation of sex life in patients with Turner syndrome , particularly those related to pubertal management . DESIGN This was a prospect i ve evaluation , the StaTur study . SETTING The study was conducted with a population -based registry of GH-treated patients . PARTICIPANTS Participants included 566 young adult women with Turner syndrome , aged 22.6 + /- 2.6 yr ( range , 18.3 - 31.2 ) . MAIN OUTCOME MEASURES Measures used in the study were Coopersmith 's Self-Esteem Inventory , Social Adjustment Scale Self-Report , questions on sexual experience , and extensive data on pediatric management . RESULTS Low self-esteem was associated with otological involvement and limited sexual experience . Low social adjustment was associated with lower paternal socioeconomic class and an absence of sexual experience . Late age at first kiss or date was associated with cardiac involvement and a lack of spontaneous pubertal development . Age at first sexual intercourse was related to age at puberty and paternal socioeconomic class . Delayed induction of puberty had a long-lasting effect on sex life . Height and height gain due to GH treatment had no effect on outcomes . CONCLUSIONS Puberty should be induced at a physiologically appropriate age in patients with Turner syndrome to optimize self-esteem , social adjustment , and initiation of the patient 's sex life . Therapeutic interventions altering normal pubertal development in other groups of patients should be reconsidered in light of these findings", "CONTEXT AND OBJECTIVE GH therapy increases growth and adult height in Turner syndrome ( TS ) . The benefit to risk ratio of adding the weak and rogen ox and rolone ( Ox ) to GH is unclear . DESIGN AND PARTICIPANTS A r and omized , placebo-controlled , double-blind , dose-response study was performed in 10 centers in The Netherl and s. One hundred thirty-three patients with TS were included in age group 1 ( 2 - 7.99 yr ) , 2 ( 8 - 11.99 yr ) , or 3 ( 12 - 15.99 yr ) . Patients were treated with GH ( 1.33 mg/m(2 ) . d ) from baseline , combined with placebo ( Pl ) or Ox in low ( 0.03 mg/kg . d ) or conventional ( 0.06 mg/kg . d ) dose from the age of 8 yr and estrogens from the age of 12 yr . Adult height gain ( adult height minus predicted adult height ) and safety parameters were systematic ally assessed . RESULTS Compared with GH+Pl , GH+Ox 0.03 increased adult height gain in the intention-to-treat analysis ( mean + /- sd , 9.5 + /- 4.7 vs. 7.2 + /- 4.0 cm , P = 0.02 ) and per- protocol analysis ( 9.8 + /- 4.9 vs. 6.8 + /- 4.4 cm , P = 0.02 ) . Partly due to accelerated bone maturation ( P adult height gain on GH+Ox 0.06 was not significantly different from that on GH+Pl ( 8.3 + /- 4.7 vs. 7.2 + /- 4.0 cm , P = 0.3 ) . Breast development was slower on GH+Ox ( GH+Ox 0.03 , P = 0.02 ; GH+Ox 0.06 , P = 0.05 ) , and more girls reported virilization on GH+Ox 0.06 than on GH+Pl ( P GH-treated girls with TS , we discourage the use of the conventional Ox dosage ( 0.06 mg/kg . d ) because of its low benefit to risk ratio . The addition of Ox 0.03 mg/kg . d modestly increases adult height gain and has a fairly good safety profile , except for some deceleration of breast development", "CONTEXT Typically , growth failure in Turner syndrome ( TS ) begins prenatally , and height sd score ( SDS ) declines progressively from birth . OBJECTIVE This study aim ed to determine whether GH treatment initiated before 4 yr of age in girls with TS could prevent subsequent growth failure . Secondary objectives were to identify factors associated with treatment response , to determine whether outcome could be predicted by a regression model using these factors , and to assess the safety of GH treatment in this young cohort . DESIGN This study was a prospect i ve , r and omized , controlled , open-label , multicenter clinical trial ( Toddler Turner Study , August 1999 to August 2003 ) . SETTING The study was conducted at 11 U.S. pediatric endocrine centers . SUBJECTS Eighty-eight girls with TS , aged 9 months to 4 yr , were enrolled . INTERVENTIONS Interventions comprised recombinant GH ( 50 mug/kg.d ; n = 45 ) or no treatment ( n = 43 ) for 2 yr . MAIN OUTCOME MEASURE The main outcome measure was baseline-to-2-yr change in height SDS . RESULTS Short stature was evident at baseline ( mean length/height SDS = -1.6 + /- 1.0 at mean age 24.0 + /- 12.1 months ) . Mean height SDS increased in the GH group from -1.4 + /- 1.0 to -0.3 + /- 1.1 ( 1.1 SDS gain ) , whereas it decreased in the control group from -1.8 + /- 1.1 to -2.2 + /- 1.2 ( 0.5 SDS decline ) , result ing in a 2-yr between-group difference of 1.6 + /- 0.6 SDS ( P 2-yr height gain was the difference between mid-parental height SDS and subjects ' height SDS ( r = 0.32 ; P = 0.04 ) . Although attained height SDS at 2 yr could be predicted with good accuracy using baseline variables alone ( R(2 ) = 0.81 ; P 2-yr change in height SDS required inclusion of initial treatment response data ( 4-month or 1-yr height velocity ) in the model ( R(2 ) = 0.54 ; P safety signals associated with GH treatment were detected . CONCLUSION Early GH treatment can correct growth failure and normalize height in infants and toddlers with TS", "OBJECTIVES /HYPOTHESIS Ox and rolone ( Ox ) increases height gain but may also cause voice deepening in growth hormone (GH)-treated girls with Turner syndrome ( TS ) . We assessed the effect of Ox on objective and subjective speaking voice frequency in GH-treated girls with TS . STUDY DESIGN A multicenter , r and omized , placebo (Pl)-controlled , double-blind study was conducted . METHODS One hundred thirty-three patients were included and treated with GH ( 1.33 mg/m2/d ) from baseline , combined with Pl or Ox in a low ( 0.03 mg/kg/d ) or conventional ( 0.06 mg/kg/d ) dose from the age of 8 years and estrogens from the age of 12 years . Yearly from starting Ox/Pl until 6 months after discontinuing GH+Ox/Pl , voices were recorded and question naires were completed . RESULTS At start , mean ( ±st and ard deviation [ SD ] ) voice frequency SD score ( SDS ) was high for age ( 1.0±1.2 , P measurement , voice frequency SDS was still relatively high in GH+Pl group ( 0.6±0.7 , P=0.002 ) but similar to healthy girls in both GH+Ox groups . Voice frequency became lower than -2 SDS in one patient ( 3 % ) on GH+Ox 0.03 and three patients ( 11 % ) on GH+Ox 0.06 . The percentage of patients reporting subjective voice deepening was similar between the dosage groups . CONCLUSIONS Untreated girls with TS have relatively high-pitched voices . The addition of Ox to GH decreases voice frequency in a dose-dependent way . Although most voice frequencies remain within the normal range , they may occasionally become lower than -2 SDS , especially on GH+Ox 0.06 mg/kg/d", "Seventy girls with Turner syndrome , 4 to 12 years of age , were r and omly assigned to receive either no treatment ( control ) or methionyl human growth hormone ( 0.125 mg/kg three times per week ) , ox and rolone ( 0.125 mg/kg/day ) , or combination hGH plus ox and rolone therapy . Baseline growth rates averaged 4.3 cm/yr , and all were within 2 SD of mean growth velocity for age in girls with Turner syndrome . Sixty-seven girls remained in the study for a minimum of 1 year . Growth rates and growth velocity ( in st and ard deviations for age in girls with Turner syndrome ) were control 3.8 cm/yr ( -0.1 SD ) , hGH 6.6 cm/yr ( + 2.3 SD ) , ox and rolone 7.9 cm/yr ( + 3.7 SD ) , and combination therapy 9.8 cm/yr ( + 5.4 SD ) . Mean bone ages advanced 1.0 years ( hGH ) , 1.3 years ( ox and rolone ) , and 1.6 years ( combination ) . However , median increments in height age/bone age ( delta HA/delta BA ) ratios ranged from 1.0 to 1.1 for treatment groups , compared with 0.8 for the controls . Predicted adult height by the method of Bayley-Pinneau increased 2.5 cm for hGH or ox and rolone alone , and 3.2 cm for combination treatment . These data indicate that both hGH and ox and rolone can significantly stimulate short-term skeletal growth in patients with Turner syndrome , and potentially increase final adult height", "A key component of the Cochrane Collaboration 's risk of bias tool for critically evaluating r and omised trials is the consideration of whether baseline characteristics of the treatment groups being compared are systematic ally different . Considered under the domain of ' selection bias ' , this is currently evaluated by looking at the methods of r and omisation and specifically at the generation of the r and omised allocation sequence and the concealment of this sequence during the process of r and omisation . Assessment of the actual similarity of baseline variables across groups in demographic and clinical characteristics is seldom performed . Even when performed , the link with selection bias is sometimes not considered . Methods of r and omisation and allocation concealment are often poorly reported in published trials , yet baseline data tables are presented in a large majority of trial reports . In this article , we propose that assessment of trial baseline data should form a key and prominent part of selection bias judgements when using the risk of bias tool . We outline the possible benefits from using this approach , including reduced uncertainty in systematic review conclusions , reduced risk of chance findings being ascribed to treatment effects and better use of available evidence by a more considered approach to evaluating studies using imperfect r and omisation and allocation methods", "Objective To explore the hypothesis that ox and rolone may reverse muscle catabolism in cachectic , critically ill pediatric burn patients . Summary Background Data Severe burn causes exaggerated muscle protein catabolism , contributing to weakness and delayed healing . Ox and rolone is an anabolic steroid that has been used in cachectic hepatitis and AIDS patients . Methods Fourteen severely burned children were enrolled during a 5-month period in a prospect i ve cohort analytic study . There was a prolonged delay in the arrival of these patients to the burn unit for definitive care . This neglect of skin grafting and nutritional support result ed in critically ill children with significant malnutrition . On arrival , all patients underwent excision and skin grafting and received similar clinical care . Subjects were studied 5 to 7 days after admission , and again after 1 week of ox and rolone treatment at 0.1 mg/kg by mouth twice daily or no pharmacologic treatment . Muscle protein kinetics were derived from femoral arterial and venous blood sample s and vastus lateralis muscle biopsies during a stable isotope infusion . Results Control and ox and rolone subjects were similar in age , weight , and percentage of body surface area burned . Muscle protein net balance decreased in controls and improved in the ox and rolone group . The improvement in the ox and rolone group was associated with increased protein synthesis efficiency . Muscle protein breakdown was unchanged . Conclusions In burn victims , ox and rolone improves muscle protein metabolism through enhanced protein synthesis efficiency . These findings suggest the efficacy of ox and rolone in impeding muscle protein catabolism in cachectic , critically injured children", "Abstract Final stature in girls with Turner syndrome treated with combination of low dose oestrogen and ox and rolone . Nineteen prepubertal girls with Turner syndrome ( mean age 10.9 years , range , 8.9–14.2 years ) were r and omly assigned to receive either ox and rolone ( 0.05 mg/kg/day ) or ethinyloestradiol ( 40 ng/kg/day ) for 1 year . Subsequently the alternate therapy was added and the combination given until attainment of final height . Ethinyloestradiol was gradually increased at the age of 12.5 years in order to induce secondary sexual characteristics . The duration of treatment was a mean of 5.2 years ( range , 3–7 years ) when the 1st year of monotherapy was included . Therapy produced a sustained acceleration in growth rate for a duration of 4 years and eventually has result ed in an increment of mean adult height of 3 cm relative to pre-treatment projected height with mean values of 146.5 cm versus 143.5 cm respectively . The moderate side-effects observed did not cause any of the girls to discontinue treatment . Nevertheless , amelioration of adult height appears to be modest , notably in comparison to published data of growth hormone treatment and 4 girls had a decrease in final height prediction . Conclusion Combination of low dose of ox and rolone and oestrogen may have a moderate but positive impact on final height in girls with Turner syndrome . However , some girls do worse than predicted in term of final height using this regimen . Oestrogen therapy started at low dose around the age of 10 years and increased gradually at approximately 12.5 years to induce secondary sexual characteristics does not have a deleterious effect on adult height in Turner syndrome . In summary , low dose ox and rolone-oestrogen treatment was found to accelerate the tempo of growth in girls with Turner syndrome , but did not appear to have a consistent effect on final height ", "OBJECTIVE The ability to accurately identify articles about therapy in large bibliographic data bases such as EMBASE is important for research ers and clinicians . Our study aim ed to develop optimal search strategies for detecting sound treatment studies in EMBASE in the year 2000 . METHODS H and search es of journals were compared with retrievals from EMBASE for c and i date search strategies . Six trained research assistants review ed fifty-five journals indexed in EMBASE and rated articles using purpose and quality indicators . C and i date search strategies were developed for identifying treatment articles and then tested , and the retrievals were compared with the h and - search data . The operating characteristics of the strategies were calculated . RESULTS Three thous and eight hundred fifty articles were original studies on treatment , of which 1,256 ( 32.6 % ) were method ologically sound . Combining search terms revealed a top performing strategy ( r and om:.tw . OR clinical trial:.mp . OR exp health care quality ) with sensitivity of 98.9 % and specificity of 72.0 % . Maximizing specificity , a top performing strategy ( double-blind:.mp . OR placebo:.tw . OR blind : .tw . ) achieved a value over 96.0 % , but with compromised sensitivity at 51.7 % . A 3-term strategy achieved the best optimization of sensitivity and specificity ( r and om:.tw . OR placebo:.mp . OR double-blind:.tw . ) , with both these values over 92.0 % . CONCLUSION Search strategies can achieve high performance for retrieving sound treatment studies in EMBASE", "A cardinal clinical feature of Turner syndrome ( TS ) is linear growth failure result ing in extreme short stature : the median adult height of untreated women with TS is 143 cm , 20 cm ( 8 in . ) below that of the general female population . In the largest multicenter , r and omized , long-term , dose-response study conducted in the United States , 232 subjects with TS received either 0.27 or 0.36 mg/kg.wk of recombinant human GH with either low dose ethinyl E2 or oral placebo . The study was placebo-controlled for both GH and estrogen for the first 18 months and remained placebo-controlled for estrogen for its duration . The near-final height of the 99 subjects whose bone age was at least 14 yr was 148.7 + /- 6.1 cm after 5.5 + /- 1.8 yr of GH started at a mean age of 10.9 + /- 2.3 yr ; this represents an average increase of 1.3 + /- 0.6 SD scores from baseline ( TS st and ard ) . Height was greater than 152.4 cm ( 60 in . ) in 29 % of subjects compared with the expected 5 % of untreated patients . Mean near-final heights of subjects who received the lower GH dose , with or without estrogen , were 145.1 + /- 5.4 and 149.9 + /- 6.0 cm , respectively ; those who received the higher GH dose with or without estrogen achieved mean near-final heights of 149.1 + /- 6.0 and 150.4 + /- 6.0 cm , respectively . Factors that most impacted outcome were younger age , lower bone age/chronological age ratio , lower body weight , and greater height SD score at study entry . This study demonstrates significant GH-induced improvement in height SD score , with correction of height to within the normal channels for a significant number of patients , and provides evidence of a GH dose-response effect . These data also indicate that early administration of estrogen , even at relatively low doses , does not improve gain in near-final height in patients with TS", "Objective To examine the effect of ox and rolone and the timing of pubertal induction on final height in girls with Turner ’s syndrome receiving a st and ard dose of growth hormone . Design R and omised , double blind , placebo controlled trial . Setting 36 paediatric endocrinology departments in UK hospitals . Participants Girls with Turner ’s syndrome aged 7 - 13 years at recruitment , receiving recombinant growth hormone therapy ( 10 mg/m2/week ) . Interventions Participants were r and omised to ox and rolone ( 0.05 mg/kg/day , maximum 2.5 mg/day ) or placebo from 9 years of age . Those with evidence of ovarian failure at 12 years were further r and omised to oral ethinylestradiol ( year 1 , 2 µg daily ; year 2 , 4 μg daily ; year 3 , 4 months each of 6 , 8 , and 10 μg daily ) or placebo ; participants who received placebo and those recruited after the age of 12.25 years started ethinylestradiol at age 14 . Main outcome measure Final height . Results 106 participants were recruited , of whom 14 withdrew and 82/92 reached final height . Both ox and rolone and late pubertal induction increased final height : by 4.6 ( 95 % confidence interval 1.9 to 7.2 ) cm ( P=0.001 , n=82 ) for ox and rolone and 3.8 ( 0.0 to 7.5 ) cm ( P=0.05 , n=48 ) for late pubertal induction with ethinylestradiol . In the 48 children who were r and omised twice , the effects on final height ( compared with placebo and early induction of puberty ) of ox and rolone alone , late induction alone , and ox and rolone plus late induction were similar , averaging 7.1 ( 3.4 to 10.8 ) cm ( P No cases of virilisation were reported . Conclusion Ox and rolone had a positive effect on final height in girls with Turner ’s syndrome treated with growth hormone , as did late pubertal induction with ethinylestradiol at age 14 years . However , these effects were not additive , so using both had no advantage . Ox and rolone could , therefore , be offered as an alternative to late pubertal induction for increasing final height in Turner ’s syndrome . Trial registration Current Controlled Trials IS RCT N50343149", "The objective of this study was to find out whether moderate doses of growth hormone ( GH ) in combination with ox and rolone ( Ox ) and late initiation of puberty could improve adult height even in relatively old patients with Ullrich-Turner syndrome ( UTS ) . Ninety-one patients with UTS were r and omly assigned to receive either GH alone ( Saizen , Ares-Serono , Geneva ) 18 IU/m2/week ( 0.2 mg/kg/week ) by daily s.c . injections ( group GH ) or a combination of GH and Ox 0.1 mg/kg/day p.o . ( group GH + Ox ) . Prior to treatment mean age was 10.2 years ( GH ) and 10.5 years ( GH + Ox ) , mean projected adult height ( PAH ) was 146.4 cm ( GH ) and 146.7 cm ( GH + Ox ) . During year 2 the GH dose was increased in the GH group to 24 and later to 28 IU/m2/week ( 0.27 mg and later 0.31 mg/kg/week ) . In group GH + Ox , the Ox dose was reduced to 0.05 mg/kg/day after the first 12 months of therapy , and during the last treatment years the GH dose was raised to 24 - 28 IU/m2/week ( 0.27 - 0.31 mg/kg/week ) due to declining growth promotion . Some of the patients of group GH were later given Ox in addition to GH because of waning growth velocity , whereas some of the patients of group GH + Ox were taken off Ox due to virilizing side-effects of the high Ox dose , thus making up a third group of patients : group GH + transient Ox . Puberty was induced at a mean age of 14.9 years . In group GH + Ox , cumulative growth during 5 years of therapy was twice the growth anticipated from st and ards of untreated patients with UTS . Forty-seven patients are now near or at final height : in group GH ( n = 7 ) , mean final height was 151.7 cm ( PAH 148.1 cm , gain 3.6 cm ) ; in group GH + Ox ( n = 15 ) , 155.1 cm ( PAH 147.2 cm , gain 7.9 cm ) ; and in group GH + transient Ox ( n = 25 ) , 152.8 cm ( PAH 146.4 cm , gain 6.4 cm ) . These results should be regarded as an underestimate of true final height since some the patients are still growing . Moderate doses of GH plus Ox and late induction of puberty definitely improved final height even in patients with UTS treated relatively late", "The Genentech National Cooperative Study of growth hormone ( GH ) therapy in Turner 's syndrome was initiated in 1983 ; 70 girls with Turner 's syndrome were r and omly assigned to observation or to treatment with GH alone , ox and rolone alone , or a combination of GH plus ox and rolone for a period of 12 - 24 months . After completion of this phase , patients receiving GH alone were continued on GH , while all other patients received the combination of GH plus ox and rolone . Data are currently available on the 62 girls who were treated for a minimum of 3 - 6 years . When compared with the height velocities anticipated for girls of comparable ages with untreated Turner 's syndrome , both GH alone and a combination of GH plus ox and rolone result ed in an increase in height velocity , which was most prominent during the first 2 years of treatment and was sustained for at least 6 years . Although GH therapy is continuing at present in half of the patients , 14 of 17 girls ( 82 % ) receiving GH alone and 42 of 45 girls ( 93 % ) receiving combination therapy have exceeded their projected adult heights . For the 30 girls who have stopped therapy , the current mean height is 151.9 cm , compared with their original mean projected adult height of 143.8 cm . These results demonstrate that GH therapy can result in short-term ( 3 - 6 years ) acceleration of growth , as well as in improved adult height", "Seventy girls with Turner syndrome , 4 to 12 years of age , participated in a prospect i ve , r and omized study to determine the effects on growth of methionyl human growth hormone ( met-hGH ) or ox and rolone . Subjects were r and omly assigned to receive either no treatment ( control ) or met-hGH ( 0.125 mg/kg three times per week ) , ox and rolone ( 0.125 mg/kg/day ) , or combination met-hGH plus ox and rolone . At the end of an initial period of 12 to 20 months , patients in the original control and ox and rolone groups were given combination met-hGH plus ox and rolone . At that time the dosage of ox and rolone was lowered to 0.0625 mg/kg/day . Sixty-five subjects have now completed the first 3 years of the study . Compared with the control growth rate for year 1 ( 3.8 cm/yr ) , significant increases in growth rate were seen in all 3 years of combination therapy ( 9.8 , 7.4 , and 6.1 cm/yr , respectively ) and in the first 2 years of treatment with met-hGH alone ( 6.6 , 5.4 , and 4.6 cm/yr ) . When growth velocity was expressed as st and ard deviation for age in girls with Turner syndrome , significant increases relative to the control group for year 1 ( -0.1 SD ) were seen in all three years of both combination therapy and met-hGH alone ( combination , + 6.6 , + 4.3 , + 3.0 SD ; met-hGH , + 3.1 , + 2.0 , + 1.4 SD ) . After 3 years of treatment , predicted adult height by the method of Bayley-Pinneau increased 4.5 cm in the met-hGH group and 8.2 cm in the combination group", "The weak and rogen ox and rolone ( Ox ) increases height gain in growth-hormone ( GH ) treated girls with Turner syndrome ( TS ) , but may also give rise to virilizing side effects . To assess the effect of Ox , at a conventional and low dosage , on behavior , aggression , romantic and sexual interest , mood , and gender role in GH-treated girls with TS , a r and omized , placebo-controlled , double-blind study was conducted . 133 patients were treated with GH ( 1.33 mg/m(2)/d ) from baseline , combined with placebo ( Pl ) , Ox 0.03 mg/kg/d , or Ox 0.06 mg/kg/d from the age of eight , and with estrogens from the age of 12 . The child behavior checklist ( CBCL ) , Junior Dutch Personality Question naire ( DPQ-J ) , State-subscale of the Spielberger 's State-Trait Anger Scale , Romantic and Sexual Interest Question naire , Mood Question naire , and Gender Role Question naire were filled out before , during , and after discontinuing Ox/Pl . The changes during Ox/Pl therapy were not significantly different between the dosage groups . In untreated patients , the mean CBCL total ( P=0.002 ) and internalizing ( P=0.003 ) T scores , as well as the mean DPQ-J social inadequacy SD score ( SDS ) ( P=0.004 ) were higher than in reference girls , but decreased during GH+Ox/Pl therapy ( P mean total ( P=0.01 ) and internalizing ( P T score remained relatively high , the mean social inadequacy SDS became comparable with reference values . We conclude that in GH-treated girls with TS , Ox 0.03 mg/kg/d or 0.06 mg/kg/d does not cause evident psychological virilizing side effects . Problem behavior , frequently present in untreated girls with TS , decreases during therapy , but total and internalizing problem behavior remain increased", "22 girls with Turner syndrome aged 10.8 + /- 2.4 years with bone age 8.58 + /- 1.32 years , r and omized in two groups , were treated for 3 years with either growth hormone ( GH ) , 0.1 U/kg daily ( group A ) , or GH , 0.1 U/kg , plus ox and rolone , 0.06 mg/kg ( group B ) . This result ed in a sharp increase in growth rate for the first year of treatment , followed in the second and third years by a growth rate near to the normal mean for age . The growth velocity was better in group B , the difference being significant during the first year only . After 3 years , the predicted adult height had increased by 2.1 cm as a mean in group A and by 4.5 cm in group B , with important individual variations , result ing in a gain of at least 3 cm in 3/10 patients of group A and 9/12 of group B. No metabolic or other side effects occurred . These 3-year data confirm that GH improves the predictable height in Turner girls . They suggest that it may be useful for at least 3 years and that adding a small dose of ox and rolone for 2 years in girls aged more than 8 years could be of good practice . However , earlier and more protracted treatment with GH has to be studied with the hope to better improve the predictable adult height", "Turner syndrome ( TS ) represents a unique , sex hormone-deficient model in which to study the biological effects of and rogen treatment ( replacement ) on cognition in females because TS girls have gonadal dysgenesis and absent ovarian and rogen and estrogen production . We investigated the effects of and rogen replacement therapy in TS girls , ages 10 - 14 yr , on cognitive function . A total of 64 TS girls were r and omized to receive ox and rolone or placebo for 2 yr . They had a cognitive evaluation of four domains ( verbal abilities , spatial cognition , executive function , and working memory ) at baseline , 1 , and 2 yr of the study . In addition , all subjects were examined for study safety every 6 months . Three of the four domains studied did not change significantly in response to ox and rolone treatment ( verbal abilities , spatial cognition , and executive function ) . In contrast , the working memory summary score had a significant group by time interaction . The ox and rolone-treated group demonstrated improved performance after 2 yr , compared with the placebo group ( P side effects were observed . In conclusion , ox and rolone treatment for 2 yr improves working memory in adolescent girls with TS . What this degree of improvement will mean in real life terms for TS girls remains to be determined", "BACKGROUND Short stature and ovarian failure are characteristic features of Turner 's syndrome . Although recombinant human growth hormone is commonly used to treat the short stature associated with this syndrome , a r and omized , placebo-controlled trial is needed to document whether such treatment increases adult height . Furthermore , it is not known whether childhood estrogen replacement combined with growth hormone therapy provides additional benefit . We examined the independent and combined effects of growth hormone and early , ultra-low-dose estrogen on adult height in girls with Turner 's syndrome . METHODS In this double-blind , placebo-controlled trial , we r and omly assigned 149 girls , 5.0 to 12.5 years of age , to four groups : double placebo ( placebo injection plus childhood oral placebo , 39 patients ) , estrogen alone ( placebo injection plus childhood oral low-dose estrogen , 40 ) , growth hormone alone ( growth hormone injection plus childhood oral placebo , 35 ) , and growth hormone-estrogen ( growth hormone injection plus childhood oral low-dose estrogen , 35 ) . The dose of growth hormone was 0.1 mg per kilogram of body weight three times per week . The doses of ethinyl estradiol ( or placebo ) were adjusted for chronologic age and pubertal status . At the first visit after the age of 12.0 years , patients in all treatment groups received escalating doses of ethinyl estradiol . Growth hormone injections were terminated when adult height was reached . RESULTS The mean st and ard-deviation scores for adult height , attained at an average age of 17.0±1.0 years , after an average study period of 7.2±2.5 years were -2.81±0.85 , -3.39±0.74 , -2.29±1.10 , and -2.10±1.02 for the double-placebo , estrogen-alone , growth hormone-alone , and growth hormone-estrogen groups , respectively ( P effect of growth hormone treatment ( vs. placebo ) on adult height was a 0.78±0.13 increase in the height st and ard-deviation score ( 5.0 cm ) ( P height was greater in the growth hormone-estrogen group than in the growth hormone-alone group , by 0.32±0.17 st and ard-deviation score ( 2.1 cm ) ( P=0.059 ) , suggesting a modest synergy between childhood low-dose ethinyl estradiol and growth hormone . CONCLUSIONS Our study shows that growth hormone treatment increases adult height in patients with Turner 's syndrome . In addition , the data suggest that combining childhood ultra-low-dose estrogen with growth hormone may improve growth and provide other potential benefits associated with early initiation of estrogen replacement . ( Funded by the National Institute of Child Health and Human Development and Eli Lilly ; Clinical Trials.gov number , NCT00001221 . )", "OBJECTIVE Short stature is a prominent feature of Turner syndrome ( TS ) , which is partially overcome by GH treatment . We have previously reported the results of a trial on the effect of ox and rolone ( Ox ) in girls with TS . Ox in a dose of 0.03 mg/kg per day ( Ox 0.03 ) significantly increased adult height gain , whereas Ox mg/kg per day ( 0.06 ) did not , at the cost of deceleration of breast development and mild virilization . The aim of this follow-up study in adult participants of the pediatric trial was to investigate the long-term effects of previous Ox treatment . DESIGN AND METHODS During the previous r and omized controlled trial , 133 girls were treated with GH combined with placebo ( Pl ) , Ox 0.03 , or Ox 0.06 from 8 years of age and estrogen from 12 years . Sixty-eight women ( Pl , n=23 ; Ox 0.03 , n=27 ; and Ox 0.06 , n=18 ) participated in the double-blind follow-up study ( mean age , 24.0 years ; mean time since stopping GH , 8.7 years ; and mean time of Ox/Pl use , 4.9 years ) . We assessed height , body proportions , breast size , virilization , and body composition . RESULTS Height gain ( final minus predicted adult height ) was maintained at follow-up ( Ox 0.03 10.2±4.9 cm , Ox 0.06 9.7±4.4 cm vs Pl 8.0±4.6 cm ) . Breast size , Tanner breast stage , and body composition were not different between groups . Ox-treated women reported more subjective virilization and had a lower voice frequency . CONCLUSION Ox 0.03 mg/kg per day has a beneficial effect on adult height gain in TS patients . Despite previously reported deceleration of breast development during Ox 0.03 treatment , adult breast size is not affected . Mild virilization persists in only a small minority of patients . The long-term evaluation indicates that Ox 0.03 treatment is effective and safe" ]

[ "The effects of the soluble fiber konjac glucomannan ( GM ) on serum cholesterol concentrations were investigated in 63 healthy men in a double-blind crossover , placebo-controlled study . After a 2-wk baseline period , the subjects were given 3.9 g GM or placebo daily for 4 wk . After a washout period of 2 wk , crossover took place , followed by another 4 wk of treatment . The subjects were encouraged not to change their ordinary diets or general lifestyle during the investigation . GM fibers reduced total cholesterol ( TC ) concentrations by 10 % ( P low-density-lipoprotein cholesterol ( LDL-C ) concentrations by 7.2 % ( P triglycerides by 23 % ( P systolic blood pressure by 2.5 % ( P High-density-lipoprotein cholesterol ( HDL-C ) and the ratio of LDL-C to HDL-C did not change significantly . No change in diastolic blood pressure or body weight was observed . No adverse effects were observed . The results of this study show that GM is an effective cholesterol-lowering dietary adjunct", "Background . Few safe and effective dietary supplements are available to promote weight loss . We evaluated the safety and efficacy of glucomannan , a water-soluble fiber supplement , for achieving weight loss in overweight and moderately obese individuals consuming self-selected diets . Methods . Participants were r and omly assigned to take 1.33 grams of glucomannan or identically looking placebo capsules with 236.6 mL ( 8 ounces ) of water one hour before breakfast , lunch , and dinner for 8 weeks . The primary efficacy outcome was change in body weight after 8 weeks . Other efficacy outcomes were changes in body composition , hunger/fullness , and lipid and glucose concentrations . Safety outcomes included gastrointestinal symptoms/tolerance and serum liver enzymes and creatinine levels . Results . A total of 53 participants ( 18–65 years of age ; BMI 25–35 kg/m2 ) were enrolled and r and omized . The two groups did not differ with respect to baseline characteristics and compliance with the study supplement . At 8 weeks , there was no significant difference between the glucomannan and placebo groups in amount of weight loss ( −.40 ± .06 and −.43 ± .07 , resp . ) or other efficacy outcomes or in any of the safety outcomes . Conclusions . Glucomannan supplements administered over 8 weeks were well tolerated but did not promote weight loss or significantly alter body composition , hunger/fullness , or lipid and glucose parameters . This trial is registered with NCT00613600", "BACKGROUND Fiber supplements added to a caloric diet have additional effects on weight reduction in overweight subjects . The aim of this study was to compare the effect of various commercial fiber supplements ( glucomannan , guar gum and alginate ) on weight reduction in healthy overweight subjects . MATERIAL / METHODS One hundred and seventy six men and women were included to receive either active fiber substance or placebo in r and omized placebo-controlled studies . The fiber supplements consisted of the viscous fibers glucomannan ( Chrombalance ) , glucomannan and guar gum ( Appe-Trim ) and glucomannan , guar gum and alginat ( Glucosahl ) . RESULTS All fiber supplements plus a balanced 1200 kcal diet induced significantly weight reduction more than placebo and diet alone , during a five week observation period . However , there were no significant differences between the different fibers in their ability to induce weight reduction , which was approximately 0.8 kg/week ( 3.8 + /- 0.9 , 4.4 + /- 2.0 , 4.1 + /- 0.6 in the Chrombalance , Appe-Trim and Glucosahl group , respectively ) . CONCLUSIONS Glucomannan induced body weight reduction in healthy overweight subjects , whereas the addition of guar gum and alginate did not seem to cause additional loss of weight", "Hydroxycitric acid ( HCA ) , the main compound of Garcinia cambogia extract , is a competitive blocker of ATP-citrate-lyase , presenting a potential inhibition of fatty acid bio synthesis . Glucomannan fibers , abundant in Amorphophallus konjac , seem to reduce the absorption kinetics of dietary fat . Therefore , the aim of this double-blind r and omized study was to evaluate the pharmacotherapeutic efficacy of st and ardized extracts of G. cambogia ( 52.4 % HCA ) plus A. konjac ( 94.9 % glucomannan ) in the treatment of obesity . Fifty-eight obese subjects ( BMI 30.0 - 39.9 kg/m(2 ) ) were assigned to the placebo group ( n = 26 ) or the treatment group ( n = 32 ) ; no dietary restrictions were applied . Over a 12-week period , subjects were given daily doses of either Garcinia ( 2.4 g ) plus Konjac ( 1.5 g ) or placebo prior to their main meals ( 3 times/day ) . Before the start of treatment , and every 4 weeks thereafter , the following were recorded : height , weight , circumferences and body composition , resting energy expenditure ( REE ) , lipid profile and glucose levels . The treatment had no significant effect on anthropometric parameters , REE , triglycerides or glucose levels . However , a significant reduction was observed in total cholesterol ( -32.0 + /- 35.1 mg/dL ) and LDL-c levels ( -28.7 + /- 32.7 mg/dL ) in the treated group , the final levels being significantly lower than those of the placebo group ( p = 0.008 and p = 0.020 , respectively ) . The results obtained suggest that the treatment had a significant hypocholesterolemic effect , without influencing the anthropometric or calorimetric parameters tested", "BACKGROUND AND AIMS Dietary fiber that develops viscosity in the gastrointestinal tract is capable of addressing various aspects of food intake control . The aim of this study was to assess subsequent food intake and appetite in relation to the level of viscosity following three liquid preloads each containing 5 g of either a high ( novel viscous polysaccharide ; NVP ) , medium ( glucomannan ; GLM ) , or low ( cellulose ; CE ) viscosity fiber . METHODS AND RESULTS In this double-blind , r and omized , controlled and crossover trial , 31 healthy weight adolescents ( 25 F:6 M ; age 16.1+/-0.6 years ; BMI 22.2+/-3.7 kg/m(2 ) ) consumed one of the three preloads 90 min prior to an ad libitum pizza meal . Preloads were identical in taste , appearance , nutrient content and quantity of fiber , but different in their viscosities ( 10 , 410 , and 700 poise for CE , GLM , and NVP , respectively ) . Pizza intake was significantly lower ( p=0.008 ) after consumption of the high-viscosity NVP ( 278+/-111 g ) compared to the medium-viscosity GLM ( 313+/-123 g ) and low-viscosity CE ( 316+/-138 g ) preloads , with no difference between the GLM and CE preloads . Appetite scores , physical symptoms and 24-h intake did not differ among treatment groups . CONCLUSION A highly viscous NVP preload leads to reduced subsequent food intake , in terms of both gram weight and calories , in healthy weight adolescents . This study provides preliminary evidence of an independent contribution of viscosity on food intake and may form a basis for further studies on factors influencing food intake in adolescents", "Dietary fibres are frequently used for the treatment of paediatric obesity . The aim of this clinical trial is to evaluate the efficacy of glucomannan in the child obesity management . This experimental design was double blinded with a block r and omisation , alpha = 0.05 , beta = 0.2 and delta = 50 % . The study involved 60 children under 15 years of age ( mean age 11.2 years , mean overweight 46 % ) , 30 of them under glucomannan treatment ( 1 g twice a day for two months ) and 30 under placebo and the same schedule . The drug and the placebo were indistinguishable both for the family and the physician . During the two months study period the children followed a normocaloric diet evaluated every two weeks by a dietetic record book . At the beginning of the study the drug and the placebo groups were comparable in regards to anthropometric data . At the end , the mean overweight of the drug group was decreased from 49.5 % to 41 % and that of the placebo group from 43.9 % to 41.7 % . Both decreases were significant ( p no significant difference was observed between the drug and the placebo groups . The only significant difference concerned the lipid metabolism . The children under glucomannan treatment manifested a significant decrease of alpha-lipoprotein and an increase of pre-beta-lipoprotein and triglycerides ; the children under placebo manifested only a decrease of triglycerides and apo beta-lipoprotein . We suggest that this metabolic alteration may derive from a primary decrease of alpha-lipoprotein , most likely because of an inadequate water intake . ( ABSTRACT TRUNCATED AT 250 WORDS", "Carbohydrate-restricted diets ( CRDs ) promote weight loss , reductions in plasma triacylglycerol ( TAG ) levels , and increases in high-density lipoprotein cholesterol ( HDL-C ) levels but may cause undesirable low-density lipoprotein cholesterol ( LDL-C ) responses in some people . The objective of the present study was to determine the effect of adding soluble fiber to a CRD on plasma LDL-C and other traditionally measured markers of cardiovascular disease . Using a parallel-arm , double-blind , placebo-controlled design , 30 overweight and obese men ( body mass index , 25 - 35 kg/m(2 ) ) were r and omly assigned to supplement a CRD with soluble fiber ( Konjac-mannan , 3g/d ) ( n = 15 ) or placebo ( n = 15 ) . Plasma lipids , anthropometrics , body composition , blood pressure , and nutrient intake were evaluated at baseline and at 6 and 12 weeks . Compliance was excellent as assessed by 7-day weighed dietary records and ketonuria . Both groups experienced decreases in ( P body weight , percent body fat , systolic blood pressure , waist circumference , and plasma glucose levels . After 12 weeks , HDL-C and TAG improved significantly in the fiber ( 10 % and -34 % ) and placebo ( 14 % , -43 % ) groups . LDL-C decreased by 17.6 % ( P LDL-C reductions were significant in the placebo group only after 12 weeks ( -6.0 % , P LDL-C , adding soluble fiber to a CRD during active and significant weight loss provides no additional benefits to the diet alone . Furthermore , a CRD led to clinical ly important positive alterations in cardiovascular disease risk factors", "AIM This paper evaluates the effect of the adjunct of the hydrosoluble fiber glucomannan to a Step-One-Diet in 40 plasma hypercholesterolemic children , during a r and omized controlled trial , to reduce plasma cholesterol . METHODS All the subjects recruited underwent an 8-week run in diet period ; a Step-One-Diet was prescribed . After that , they were r and omly allocated to one of two groups : Step-One-Diet only ( control ) , and Step-One-Diet plus glucomannan in gelatine capsules . After another 8 weeks of treatment , the results were compared within and between the two groups . RESULTS Glucomannan treated group showed decreased values in plasma total cholesterol ( TC ) and low density lipoprotein cholesterol ( LDL-C ) vs. control group after 8 weeks of treatment . The percentage decrease showed a statistically significant difference between sex groups . Decreases were observed in favor of female vs. male children in TC ( 24 % vs. 9 % ) and LDL-C ( 30 % vs. 9 % ) . CONCLUSIONS These results suggest that glucomannan may represent a rationale adjunct to diet therapy in primary prevention in high risk hypercholesterolemic children", "OBJECTIVE Primary dyslipidemias are major risk factors for cardiovascular disease and should be addressed early in life . The aim of this study was to evaluate , in children affected by primary hypercholesterolemia , the efficacy and tolerability of a short-term treatment with a dietary supplement containing glucomannan . METHODS A double-blind , r and omized , placebo-controlled , cross-over trial was conducted in 36 children ( aged 6 - 15 years ) affected by primary hypercholesterolemia . After a 4-week run-in period with dietary counseling , children received glucomannan or placebo twice-daily for 8 weeks , separated by a 4-week washout period . Lipid profile was assessed at baseline and after each treatment period . RESULTS Glucomannan significantly reduced total cholesterol ( TC ) by 5.1 % ( p = 0.008 ) , low-density lipoprotein cholesterol ( LDL-C ) levels by 7.3 % ( p = 0.008 ) and non-high-density lipoprotein cholesterol by 7.2 % ( p = 0.002 ) as compared with placebo . No significant differences were observed in high-density lipoprotein cholesterol , triglyceride , Apolipoprotein B , and Apolipoprotein A-I concentrations . According to sex , glucomannan significantly reduced in females , but not in males , TC ( -6.1 % , p = 0.011 ) and LDL cholesterol ( -9 % , p = 0.015 ) . No major adverse effects were recorded and only few patients experienced transitory intestinal discomfort . CONCLUSION Treatment with glucomannan of children affected by primary dyslipidemia is well-tolerated and effectively lowers total and LDL cholesterol in females and non-high-density lipoprotein cholesterol , but not Apolipoprotein B in both males and females", "Objective : The purpose of this study was to determine whether supplements of plant sterols and /or glucomannan improve lipid profile and cholesterol bio synthesis in mildly hypercholesterolemic type II diabetic and non-diabetic subjects and to compare the response of these two subject groups to the treatments . Design : A r and omized , crossover study consisting of four phases of 21 days , with each phase separated by a 28-day washout . Setting : The Mary Emily Clinical Nutrition Research Unit of McGill University . Subjects : Eighteen non-diabetic individuals and 16 type II diabetic individuals aged 38–74 years . Interventions : Subjects were supplemented with plant sterols ( 1.8 g/day ) , glucomannan ( 10 g/day ) , a combination of glucomannan and plant sterols , and a placebo , provided in the form of bars . Results : Overall plasma cholesterol concentrations were lowered ( P ) . Plasma low-density lipoprotein ( LDL ) cholesterol concentrations were decreased ( P of lipid profiles did not differ between subject groups . Overall plasma lathosterol concentrations , an index of cholesterol bio synthesis , were lowered ( P improves plasma LDL cholesterol concentrations . Sponsorship : Forbes Medi-Tech Inc. , Vancouver , British Columbia , Canada", "An eight-week double-blind trial was conducted to test purified glucomannan fiber as a food supplement in 20 obese subjects . Glucomannan fiber ( from konjac root ) or placebo was given in 1-g doses ( two 500 mg capsules ) with 8 oz water , 1 h prior to each of three meals per d. Subjects were instructed not to change their eating or exercise patterns . Results showed a significant mean weight loss ( 5.5 lbs ) using glucomannan over an eight-week period . Serum cholesterol and low-density lipoprotein cholesterol were significantly reduced ( 21.7 and 15.0 mg/dl respectively ) in the glucomannan treated group . No adverse reactions to glucomannan were reported", " Two groups of 25 severely obese patients underwent 3 months of hypocaloric diet therapy either alone or associated with a glucomannan-based fibrous diet supplement ( approx . 4 g/die in 3 doses ) . The comparative analysis of the results obtained in both groups showed that the diet + glucomannan group had a more significant weight loss in relation to the fatty mass alone , an overall improvement in lipid status and carbohydrate tolerance , and a greater adherence to the diet in the absence of any relevant side effects . Due to the marked ability to satiate patients and the positive metabolic effects , glucomannan diet supplements have been found to be particularly efficacious and well tolerated even in the long-term treatment of severe obesity", "OBJECTIVE A low-fat , fiber-rich diet is the first step in the management for hypercholesterolemic children . Glucomannan ( GM ) is a natural fiber that has been demonstrated to lower total and LDL-cholesterol . The use of high-dose chromium-polynicotinate ( CP ) and policosanol ( PC ) has also shown cholesterol-lowering benefits . We aim ed at investigating the effects of low-dose CP or PC and their GM combination in hypercholesterolemic children . METHODS A double-blind trial was conducted in 120 children ( 60 M , 60 F , 9 ± 4 years , median 9.6 years , range : 3 - 16 years ) r and omly assigned to 5 neutraceutical and 1 placebo ( only resistant starch ) 8-week treatment groups . Fasting blood glucose ( FBG ) , total cholesterol ( CholT ) , triglycerides ( TG ) , HDL and LDL cholesterol were considered . RESULTS GM combination of low-dose CP or PC reduced CholT and LDL without changing HDL , TG and FBG . The highest post-treatment changes were seen after GM combination with CP ( CholT 85 ± 3 % and LDL 85 ± 5 % , of pretreatment ) which was significantly ( p with low-dose CP or PC and starch . When GM was associated with starch , there was no lipid lowering effect , which was an unexpected finding as compared to previous data with GM and no starch . No adverse effects were reported . CONCLUSION This is the first report to show the cholesterol-lowering efficacy of GM combined treatment with low-dose CP or PC . Further studies are needed to investigate the best combinations and doses of nutraceutics to be added to the st and ard GM treatment . The potential negative association of GM and nutraceutics with starch is clearly shown" ]

[ "INTRODUCTION Both grip and knee extension strength are often used to characterize overall limb muscle strength . We sought to determine if the measures actually reflect a common construct . METHODS The isometric grip and knee extension strength of 164 healthy men and women ( range , 18 - 85 years ) were measured bilaterally using st and ard procedures . Pearson correlations ( r ) , Cronbach alpha , principal components analysis , and multiple regression/correlation were used to investigate the dimensionality of the measures . RESULTS Left and right grip forces and knee extension torques were highly correlated , internally consistent , and loaded on a single component . Gender and age explained the variance in both measures , but height added to the explanation of grip strength , whereas weight added to the explanation of knee extension strength . CONCLUSIONS Among healthy adults , grip and knee extension strength reflect a common underlying construct . The measures , however , are affected differently by height and weight", "Although loss of muscle mass is considered a cause of diminished muscle strength with aging , little is known regarding whether composition of aging muscle affects strength . The skeletal muscle attenuation coefficient , as determined by computed tomography , is a noninvasive measure of muscle density , and lower values reflect increased muscle lipid content . This investigation examined the hypothesis that lower values for muscle attenuation are associated with lower voluntary isokinetic knee extensor strength at 60 degrees/s in 2,627 men and women aged 70 - 79 yr participating in baseline studies of the Health ABC Study , a longitudinal study of health , aging , and body composition . Strength was higher in men than in women ( 132.3 + /- 34.5 vs. 81.4 + /- 22.0 N x m , P muscle attenuation values ( 37.3 + /- 6.5 vs. 34.7 + /- 7.0 Hounsfield units ) and muscle cross-sectional area ( CSA ) at the midthigh than women ( 132.7 + /- 22.4 vs. 93.3 + /- 17.5 cm(2 ) , P strength per muscle CSA ( specific force ) was also higher in men ( 1.00 + /- 0.21 vs. 0.88 + /- 0.21 N x m x cm(-2 ) ) . The attenuation coefficient was significantly lower for hamstrings than for quadriceps ( 28.7 + /- 8.7 vs. 41.1 + /- 6.9 Hounsfield units , P Midthigh muscle attenuation values were lowest ( P Higher muscle attenuation values were also associated with greater specific force production ( r = 0.26 , P attenuation coefficient of muscle was independently associated with muscle strength after adjustment for muscle CSA and midthigh adipose tissue in men and women . These results demonstrate that the attenuation values of muscle on computed tomography in older persons can account for differences in muscle strength not attributed to muscle quantity", "Objective The aim of the present study was to analyze the effects of whole-body vibration on lower limb muscle architecture , muscle strength , and balance in stroke patients during a period of 3 mos . Design The inclusion criteria were having had ischemic or hemorrhagic stroke at least 6 mos before the study and a National Institutes of Health Stroke Scale score of greater than 1 and less than 20 . The patients were r and omly divided into two groups : an experimental group ( n = 11 , six men and five women ; age , 62.4 ± 10.7 yrs ; height , 1.64 ± 0.07 m ; mass , 69.4 ± 12.9 kg ) and a sham group ( n = 9 , five men and four women ; age , 64.4 ± 7.6 yrs ; height , 1.62 ± 0.07 m ; mass , 75.0 ± 15.8 kg ) . The experimental group received a whole-body vibration treatment , with an increase in frequency , sets , and time per set during 17 sessions . The sham group performed the same exercises as that of the experimental group but was not exposed to vibration . Outcome variables included the muscle architecture ( the rectus femoris , the vastus lateralis , and the medial gastrocnemius ) , the maximal isometric voluntary contraction of the knee extensors , and the Berg Balance Scale . Results There were no significant differences between the groups on the primary outcomes of lower limb muscle architecture , muscle strength , and balance . Conclusions It seems that whole-body vibration exercise does not augment the increase in neuromuscular performance and lower limb muscle architecture induced by isometric exercise alone in stroke patients", "OBJECTIVES From among physiological attributes commonly targeted in rehabilitation , to identify those in which changes led to clinical ly meaningful differences ( CMDs ) in mobility outcomes . DESIGN Secondary analysis of data collected for a r and omized controlled trial of exercise using binary outcomes defined by recording a large CMD ( Short Physical Performance Battery (SPPB)=1 unit ; gait speed (GS)=0.1 m/s ) . Iterative models were performed to evaluate possible confounding between physiological variables and relevant covariates . SETTING Outpatient rehabilitation centers . PARTICIPANTS Community-dwelling mobility-limited older adults ( n=116 ) participating in a 16-week r and omized controlled trial of two modes of exercise . MEASUREMENTS Physiological measures included leg power , leg strength , balance as measured according to the Performance-Oriented Mobility Assessment ( POMA ) , and rate pressure product at the maximal stage of an exercise tolerance test . Outcomes included GS and SPPB . Leg power and leg strength were measured using computerized pneumatic strength training equipment and recorded in Watts and Newtons , respectively . RESULTS Participants were 68 % female , had a mean age of 75.2 , a mean of 5.5 chronic conditions , and a baseline mean SPPB score of 8.7 . After controlling for age , site , group assignment , and baseline outcome values , leg power was the only attribute in which changes were significantly associated with a large CMD in SPPB ( odds ratio (OR)=1.48 , 95 % confidence interval (CI)=1.09 - 2.02 ) and GS ( OR=1.31 , 95 % CI=1.01 - 1.70 ) . CONCLUSION Improvements in leg power , independent of strength , appear to make an important contribution to clinical ly meaningful improvements in SPPB and GS", "OBJECTIVE To evaluate muscular performance and appearance in patients with prior stroke who were ambulatory . DESIGN Nonr and omized study . SETTING University hospital laboratory . SUBJECTS Sixteen persons ( 11 men , 5 women ) with minor motor impairments , 6 to 24 months after stroke , were included . As reference , data were used from a population -based sample of 144 men and women . MAIN OUTCOME MEASUREMENTS Muscle performance was evaluated using a Kin-Com dynamometer in both the affected and the nonaffected leg . Peak isometric strength was measured at a 60 degree angle in both extension and flexion . Maximal isokinetic strength was measured at 60 degrees/sec and at 180 degrees/sec . Endurance was evaluated during isometric and dynamic knee extensions . Muscle biopsies were taken on nine patients and muscle tissue areas were determined with computed tomography . RESULTS The affected leg was weaker but not different in relative endurance compared with the nonaffected side . The performance of the nonaffected side was somewhat lower than that of a matched reference population . No major difference in fiber composition between the affected and nonaffected legs was noted , except for a lower degree of capillarization in the affected leg . CONCLUSION In well-functioning stroke patients with good motor performance , further muscle training that includes resistance exercise might be indicated", "Objective : To evaluate the feasibility of jump training for nearly ambulatory patients after stroke . Design : Case series . Setting : A rehabilitation centre for adult people with neurological disorders . Subjects : Six subacute , nearly ambulatory patients with hemiparesis due to stroke . Interventions : A modified form of jump training performed over a period of six weeks . Measures : Impairments : We used the Motricity Index to measure strength , the Fugl-Meyer subtest passive joint motion/pain for range of motion and pain and the modified Tardieu Scale to measure spasticity at baseline and after six weeks . Activity level : To assess walking ability we used the Functional Ambulation Category , to measure walking quality we used 10-m gait velocity , stride length and Rivermead Visual Gait Index and to assess walking capacity we used the six-minute walk test . Results : No severe adverse events were observed during the study period . Motricity Index sum score of the affected leg increased from 38±11 points ( mean±SD ) to 56±15 points ; P = 0.028 . Modified Tardieu Scale and Fugl-Meyer subtest passive joint motion/pain remained unchanged over time ( P=1.0 ; P=0.157 , respectively ) . All patients were able to walk at the end of training ( median Functional Ambulation Category grade five , P=0.023 ) . Gait quality improved as shown in increased gait velocity ( from 0.3±0.1 to 1.1±0.5 m/s ; P = 0.028 ) , improved stride length ( from 0.3±0.1 to 0.6±0.2 m ; P = 0.028 ) and improved Rivermead Visual Gait Index score ( from 38.7±5.6 points to 24.8±7.0 points ; P = 0.027 ) . All patient increased gait capacity ( from 97±33 m to 289±134 m ; P = 0.028 ) . Conclusion : Jump exercises are feasible for selected subacute stroke patients with hemiparesis", "To determine the differences between arm and leg muscle quality ( MQ ) across the adult life span in men and women , concentric ( Con ) and eccentric ( Ecc ) peak torque ( PT ) were measured in 703 subjects ( 364 men and 339 women , age range 19 - 93 yr ) and appendicular skeletal muscle mass ( MM ) was determined in the arm and leg in a subgroup of 502 of these subjects ( 224 men and 278 women ) . Regression analysis showed that MQ , defined as PT per unit of MM , was significantly higher in the arm ( approximately 30 % ) than in the leg across age in both genders ( P Arm and leg MQ declined at a similar rate with age in men , whereas leg MQ declined approximately 20 % more than arm MQ with increasing age in women ( P PT , respectively ) . Moreover , the age-associated decrease in arm MQ was steeper in men than in women whether Con or Ecc PT was used ( both P Arm MQ as determined by Con PT showed a linear age-related decline in men and women ( 28 and 20 % , respectively , P arm MQ as determined by Ecc PT showed a linear age-related decline in men ( 25 % , P quadratic decline in leg MQ as determined by Con PT ( approximately 40 % ) and Ecc PT ( approximately 25 % ; both P MQ is affected by age and gender , but the magnitude of this effect depends on the muscle group studied and the type of muscle action ( Con vs. Ecc ) used to assess strength", "BACKGROUND Emerging evidence on the velocity-dependent nature of force impairment in post-stroke hemiparesis has emphasized the complexity of strength and motor performance assessment s in this clinical population . The need to establish reliability and responsiveness of muscle performance measures across a broad range of concentric and eccentric movement speeds is therefore clear , as these metrics will provide benchmarks both for making clinical inference and evaluating meaningful clinical change following interventions . METHODS Isokinetic knee extensor strength was tested at 14 angular velocities in 17 adults with chronic post-stroke hemiparesis ( > 18 months ) , and 13 non-disabled controls . Identical tests were conducted on two occasions separated by two days . Test-retest reliability of maximal isokinetic torque was evaluated using intraclass correlation . Absolute reliability was assessed using st and ard error of measurement from which smallest real differences were derived . FINDINGS Overall , intraclass correlation coefficients were excellent for both hemiparetic ( 0.891 ) and control ( 0.937 ) groups . Intraclass correlation coefficients for each criterion speed were also high for both groups ( > 0.86 ) . Measurement error relative to the mean torque varied between 14.1 % and 26.3 % for hemiparetic subjects and 6.0 - 18.1 % for controls . The smallest real difference relative to mean torque was 39.0 - 72.7 % and 16.6 - 50.2 % for hemiparetic and control subjects , respectively . INTERPRETATION Isokinetic knee extension torque can be measured reliably in persons with chronic post-stroke hemiparesis and in non-disabled controls across a full functional range of concentric and eccentric speeds . Established measurement error and smallest real differences will aid interpretation of longitudinal observations of muscle performance in this clinical population", "OBJECTIVE To determine , using the Muscular Utilization Ratio ( MUR ) method , whether plantarflexor weakness is among the factors preventing stroke subjects from walking at faster speeds . Potential compensations by the hip flexors were also examined . DESIGN A convenience sample of 17 chronic stroke subjects in a context of a descriptive study . BACKGROUND Gait speed is correlated with the residual strength of the muscles involved in gait in stroke subjects . However , it has not been established if this residual strength limits gait speed . METHODS Kinetic and kinematic data for comfortable and maximal gait speeds were collected on the paretic side , and were used to determine the moments in plantarflexion ( mechanical dem and : MUR numerator ) during the push-off phase . The maximal potential moment ( MUR denominator ) of the plantarflexors during gait was predicted using an equation derived from dynamometric data collected with a Biodex system . The MURs of the plantarflexors were then calculated at every 1 % interval of the push-off phase . The pull-off phase of gait and the hip flexor strength were also examined . RESULTS Ten subjects of the sample had a MUR value between 80 and 150 % at maximal gait speed . These subjects produced the lowest peak torques in plantarflexion . Each of the four fastest subjects of this group had a large hip flexion moment during the pull-off phase of gait and produced high hip flexion torque values on the dynamometer . Each of the seven remaining subjects had a MUR value under 70 % when they walked at maximal speed . CONCLUSIONS Weakness of the plantarflexors should be considered as one factor limiting gait speed in 10 hemiparetic subjects . Some subjects with weak plantarflexors could walk rapidly because they compensated with the hip flexors . For the remaining stroke subjects , factors other than weakness of the plantarflexors have to be considered in order to explain the reduction in their gait speed", "The increase of elderly in our society requires simple tools for quantification of sarcopenia in inpatient and outpatient setting s. The aim of this study was to compare parameters determined with musculoskeletal ultrasound ( M-US ) with muscle strength in young and elderly patients . In this prospect i ve , r and omised and observer blind study , 26 young ( 24.2 ± 3.7 years ) and 26 old ( age 67.8 ± 4.8 years ) patients were included . Muscle thickness , pennation angle and echogenicity of all muscles of musculus quadriceps were measured by M-US and correlated with isometric maximum voluntary contraction force ( MVC ) of musculus quadriceps . Reproducibility of M-US measurements as well as simple and multiple regression models were calculated . Of all measured M-US variables the highest reproducibility was found for measurements of thickness ( intraclass correlation coefficients , 85–97 % ) . Simple regression analysis showed a highly significant correlation of thickness measurements of all muscles of musculus quadriceps with MVC in the elderly and in the young . Multiple regression analysis revealed that thickness of musculus vastus medialis had the best correlation with MVC in the elderly . This study showed that measurement of muscle thickness , especially of musculus vastus medialis , by M-US is a reliable , bedside method for monitoring the extent of sarcopenia" ]

[ "BACKGROUND / AIMS This study aim ed to evaluate the efficacy of modified Roux-en-Y gastric bypass for type 2 diabetes mellitus . METHODOLOGY Forty-five type 2 diabetes mellitus patients underwent modified Roux-en-Y gastric bypass at WeiFang People 's Hospital . Data on patient demographics , fasting plasma glucose ( FPG ) , body mass index ( BMI ) , medication use , remission and hemoglobin A1c ( HbAlc ) were prospect ively collected and analyzed . RESULTS At 6 months after surgery , all of these 45 patients obtained remission or a marked improvement . FPG was in the normal range in 39 ( 86.7 % ) patients stopping medicine treatment for their diabetes . Six patients ( 13.3 % ) had an obvious reduced abnormal FPG and they only required lower drug dosage . No statistically significant differences were found between the obese or non-obese groups ( p=0.311 ) . The mean BMI dropped from 28.9±3.0 kg/m2 to 27.4±2.8 kg/m2 ( p=0.000 ) at the third month and 26.3±2.5 kg/m2 ( p=0.000 ) at the sixth month . HbAlc decreased from their preoperative values of 7.4%±2.2 % to 6.3%±1.5 % ( p=0.000 ) at the third month and 5.1%±0.9 % ( p=0.000 ) at the sixth month . CONCLUSIONS Modified Roux-en-Y gastric bypass was effective in treating type 2 diabetes mellitus , independent of body mass index", "OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review", "OBJECTIVE To examine the effect of a large , long st and ing and intentional weight reduction on the incidence of diabetes , hypertension and lipid disturbances in severely obese individuals as compared to weight-stable obese controls . RESEARCH METHODS AND PROCEDURES The ongoing prospect i ve SOS ( Swedish Obese Subjects ) intervention consists of a surgically treated group and a matched control group obtaining conventional obesity treatment . This report is based on 845 surgically treated patients and 845 controls ( BMI 41.0+/-4.6 kg/m2 ( mean+/-st and ard deviation [ S ] ) ) followed for 2 years . RESULTS Surgically treated patients lost 28+/-15 kg and controls 0.5+/-8.9 kg ( p incidence of hypertension , diabetes , hyperinsulinemia , and lipid disturbances was compared in the two treatment groups . Adjusted odds ratios ( 95 % CI ) for the surgically treated group versus controls were 0.38 ( 0.22 , 0.65 ) for hypertension , 0.02 ( 0.00 , 0.16 ) for diabetes , 0.10 ( 0.03 , 0.28 ) for hyperinsulinemia , 0 . 10 ( 0.04 , 0.25 ) for hypertriglyceridemia , 0.28 ( 0.16 , 0.49 ) for low HDL-cholesterol and 1.24 ( 0.84 , 1.8 ) for hypercholesterolemia . Compared to controls , the 2-year recovery rates from hypertension , diabetes , hypo-HDL , and hypertriglyceridemia were significantly higher in the surgically treated group . DISCUSSION Intentional weight loss in the obese causes a marked reduction in the 2-year incidence of hypertension , diabetes and some lipid disturbances . The results suggest that severe obesity can and should be treated", "BACKGROUND Patients who are categorized with class I obesity have a body mass index ( BMI ) of 30 - 34.99 kg/m(2 ) . This population of patients has a predisposition to diabetes , hypertension , and dyslipidemia . The aim of the present study was to investigate the improvements of these co-morbidities in a class I obese population that had undergone a bariatric procedure . METHODS After internal review board approval and with adherence to the Health Insurance Portability and Accountability Act guidelines , a retrospective review was performed of a prospect ively maintained data base of 42 class I obese patients who underwent a bariatric procedure at our institution during a 10-year period , from February 2000 to May 2010 . The fasting glucose level , glycosylated hemoglobin level , lipid profile , initial weight , and BMI were measured in the preoperative and postoperative periods . RESULTS Our patient population consisted of 30 women and 12 men , with a preoperative mean BMI of 33.9 kg/m(2 ) . Laparoscopic sleeve gastrectomy was performed in 24 patients ( 57 % ) , laparoscopic Roux-en-Y gastric bypass in 8 ( 19 % ) , and laparoscopic adjustable gastric b and ing in 10 ( 24 % ) . Of these 42 patients , 25 ( 60 % ) had type 2 diabetes , 1 patient was glucose intolerant , 27 ( 64 % ) had arterial hypertension , 25 ( 60 % ) had dyslipidemia , 17 ( 40 % ) had sleep apnea , and 8 ( 19 % ) had osteoarthritis . The postoperative findings included a mean BMI of 26.5 kg/m(2 ) and a mean weight loss of 41.4 lb . Of the 25 diabetic patients , 5 ( 20 % ) gained remission and 12 ( 48 % ) improvement of their diabetic status . The single patient with glucose intolerance showed improvement . Of the 27 patients with arterial hypertension , 9 ( 33 % ) showed remission and 13 ( 52 % ) improvement . Dyslipidemia resolved in 5 patients ( 20 % ) and improved in 13 ( 52 % ) . Obstructive sleep apnea resolved in 10 ( 59 % ) and improvement was seen in 1 patient ( 6 % ) . Finally , osteoarthritis resolved in 1 patient ( 12 % ) and improved in 5 ( 63 % ) . CONCLUSION Bariatric surgery can significantly improve or resolve co-morbid metabolic conditions in patients with class I obesity ", "BACKGROUND In the 2.8 years of the Diabetes Prevention Program ( DPP ) r and omised clinical trial , diabetes incidence in high-risk adults was reduced by 58 % with intensive lifestyle intervention and by 31 % with metformin , compared with placebo . We investigated the persistence of these effects in the long term . METHODS All active DPP participants were eligible for continued follow-up . 2766 of 3150 ( 88 % ) enrolled for a median additional follow-up of 5.7 years ( IQR 5.5 - 5.8 ) . 910 participants were from the lifestyle , 924 from the metformin , and 932 were from the original placebo groups . On the basis of the benefits from the intensive lifestyle intervention in the DPP , all three groups were offered group-implemented lifestyle intervention . Metformin treatment was continued in the original metformin group ( 850 mg twice daily as tolerated ) , with participants unmasked to assignment , and the original lifestyle intervention group was offered additional lifestyle support . The primary outcome was development of diabetes according to American Diabetes Association criteria . Analysis was by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT00038727 . FINDINGS During the 10.0-year ( IQR 9.0 - 10.5 ) follow-up since r and omisation to DPP , the original lifestyle group lost , then partly regained weight . The modest weight loss with metformin was maintained . Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years ( 95 % CI 4.1 - 5.7 ) in the intensive lifestyle intervention group , 7.8 ( 6.8 - 8.8 ) in the metformin group , and 11.0 ( 9.8 - 12.3 ) in the placebo group . Diabetes incidence rates in this follow-up study were similar between treatment groups : 5.9 per 100 person-years ( 5.1 - 6.8 ) for lifestyle , 4.9 ( 4.2 - 5.7 ) for metformin , and 5.6 ( 4.8 - 6.5 ) for placebo . Diabetes incidence in the 10 years since DPP r and omisation was reduced by 34 % ( 24 - 42 ) in the lifestyle group and 18 % ( 7 - 28 ) in the metformin group compared with placebo . INTERPRETATION During follow-up after DPP , incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group , but the cumulative incidence of diabetes remained lowest in the lifestyle group . Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years . FUNDING National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK )", "Background Most morbidly obese patients who undergo gastric bypass experience rapid remission of type 2 diabetes mellitus ( T2DM ) but the response in non-morbidly obese patients is not clear . This trial prospect ively assessed the effect of diabetes remission , glucose metabolism , and the serial changes of insulin secretion after gastric bypass in inadequately controlled T2DM patients with a BMI of 23–35 kg/m2 . Methods A total of 62 consecutive patients with T2DM and a BMI of 23–35 kg/m2 underwent gastric bypass . Data were prospect ively collected before surgery and 1 , 4 , 12 , 26 , and 52 weeks and 2 years after surgery . Insulin secretion was measured by insulinogenic index and area under the curve ( AUC ) during a st and ard oral glucose tolerance test ( OGTT ) . Remission of type 2 diabetes was defined as fasting glucose level 62 patients , 24 were men and 38 were women ( age 43.1 ± 10.8 years ) . Their preoperative characteristics were as follows : BMI 30.1 ± 3.3 kg/m2 , waist circumference 99.6 ± 9.6 cm , C-peptide 3.1 ± 1.4 ng/ml , and duration of T2DM 5.4 ± 5.1 years . The mean BMI decreased postoperatively to 22.6 ± 2.3 kg/m2 in 1 year and 23.0 ± 2.7 kg/m2 in 2 years . The mean HbA1c decreased from 9.7 ± 1.9 % to 5.8 ± 0.5 % in 1 year and 5.9 ± 0.5 % in 2 years . Complete remission of T2DM was achieved in 57 % in 1 year and 55 % in 2 years after surgery . Before surgery , the OGTT test showed a blunted insulin secretion pattern with an insulinogenic index of 0.1 ± 0.2 and AUC of 2,324 ± 1,015 μIU min/ml . In 1 week after surgery , the insulinogenic index increased to 0.16 and AUC decreased to 1,366 μIU min/ml along with a rapid drop of insulin resistance . The insulinogenic index and AUC gradually increased to 0.27 and 3,220 , respectively , 1 year after surgery and remained stable up to 2 years with a very low insulin resistance . Conclusions Laparoscopic gastric bypass facilitates immediate improvement in the glucose metabolism of inadequately controlled non-severe obese T2DM patients , and the benefit is sustained up to 2 years after surgery . The benefit is regulated by the decrease in insulin resistance , increase in early insulin response , and total insulin secretion to glucose load", "Context Observational studies have shown sustained weight loss after surgery for extreme obesity . No r and omized trial of contemporary surgical methods has been performed . Contribution The authors r and omly assigned 80 mildly to moderately obese ( body mass index , 30 to 35 kg/m2 ) adults to laparoscopic placement of an adjustable gastric b and or to an intensive nonsurgical weight loss program . After 2 years , the surgical group had lost 21.6 % of initial weight , and the nonsurgical group had lost 5.5 % of initial weight . Four patients required laparoscopic revision of the gastric b and . Caution s The study was not design ed to detect uncommon adverse events . Implication s Laparoscopic gastric b and ing is effective treatment for mild to moderate obesity . The Editors The development of a safe and effective treatment for obesity is a leading challenge in health care today . Obesity is an increasing health problem across the world with a prevalence of more than 20 % among the adult population in Western countries and more than 30 % in the United States ( 1 , 2 ) . The increasing prevalence is associated with a parallel increase of several obesity-related diseases , in particular , the diseases of the metabolic syndrome ( 3 , 4 ) , which include type 2 diabetes , hypertension , and dyslipidemia , and are linked to nonalcoholic steatohepatitis , obstructive sleep apnea , and the polycystic ovary syndrome . For obese individuals , the options are limited . Behavioral therapies of reduced energy intake , improved eating practice s , and increased exercise and activity , supplemented by pharmacotherapy , generally achieve only modest and often transient effects ( 5 , 6 ) . Observational studies have shown that bariatric surgical therapies involving gastric restriction by various forms of stapling with or without diversion of the gut to generate malabsorption of food are effective in achieving major weight loss and clinical ly significant improvements in health and quality of life ( 7 - 11 ) . Strong direct evidence from r and omized , controlled trials of the relative benefits of nonsurgical and surgical therapies is lacking . We are aware of only a single study , performed in the 1980s , in which 60 morbidly obese patients were r and omly assigned , without informed consent , to diet plus an early form of gastric stapling or to diet alone ( 12 ) . The maximum weight losses did not differ between the groups . However , the weight regain was greater in the diet-only group . The advent of the laparoscopic adjustable gastric b and has provided a new bariatric surgical option , which has proved to be safe , minimally invasive in its application , gentle in its use through its adjustability and easy reversibility , and similarly effective to the other bariatric procedures ( 10 , 13 , 14 ) . Figure 1 shows the LAP-B AND System ( INAMED Health , Santa Barbara , California ) and demonstrates the key feature of adjustability of the area within the b and through which it induces satiety ( 15 ) . Patients require no more than an overnight hospital stay , and the procedure has been shown to be markedly safer than gastric bypass surgery ( 13 ) . Figure 1 . The laparoscopic adjustable gastric b and ( LAP-B AND System , INAMED Health , Santa Barbara , California ) with no added fluid ( top ) and with 2 mL of fluid added ( bottom ) . We hypothesized that surgical therapy would induce more weight loss , health benefit , and improvement in quality of life than nonsurgical therapy and have conducted a r and omized , controlled trial comparing the effectiveness of current nonsurgical therapy with laparoscopic adjustable gastric b and ing in a group of mildly to moderately obese adults ( body mass index , 30 kg/m2 to 35 kg/m2 ) . We did not study patients with a body mass index greater than 35 kg/m2 because current observational data suggest that outcomes after nonsurgical treatment were unlikely to be equal to those after surgical care for these patients . The principal outcome measures were weight change , health , quality of life , and complications of therapy . Methods Patient Recruitment We recruited patients for the study through a newspaper advertisement . All patient assessment s and outpatient treatments were conducted at a community clinic dedicated to obesity management or in the clinics of a university department of surgery . Surgical procedures were conducted at a private community hospital experienced in the care of bariatric surgical patients . Patients in both groups did not pay any medical costs generated by the study . The human ethics committees of The Alfred Hospital and The Avenue Hospital approved the study in accordance with the guidelines of the National Health and Medical Research Council ( www.nhmrc.gov.au/publications/synopses/e35syn.htm ) and with the Helsinki Declaration of 1975 , as revised in 2000 ( www.wma.net/e/ethicsunit/pdf/draft_historical_contemporary_perspectives.pdf ) . Inclusion Criteria We considered patients to be eligible if they were between 20 and 50 years of age ; had a body mass index of 30 kg/m2 to 35 kg/m2 ; had identifiable problems , including an obesity-related comorbid condition ( such as hypertension , dyslipidemia , diabetes , obstructive sleep apnea , or gastroesophageal reflux disease ) , severe physical limitations , or clinical ly significant psychosocial problems associated with their obesity ; had attempted to reduce weight over at least the previous 5 years ; could underst and the options offered and the r and omization process ; and were willing to comply with the requirements of each program . Exclusion Criteria We excluded c and i date s with a history of bariatric surgery or medical problems that contraindicated treatment in either study group , such as impaired mental status , drug or alcohol addiction , or portal hypertension . In addition , we excluded participants if they had undergone an intensive , physician-supervised program that used very-low-calorie diets or pharmacotherapy or if they did not attend the 2 initial patient information visits . Assessment We provided detailed information about the problems of obesity and about the 2 study groups through at least 2 discussion periods and a patient information booklet . Initial assessment included anthropometric measures ; identification of medical , physical , or psychosocial problems ( both weight-related and other ) ; and a discussion of previous weight loss efforts . The assessment included a detailed dietary history by the trial dietitian and a review by a specialist physician to determine the presence and severity of associated medical conditions . Initial investigations included measurements of fasting blood glucose level ; serum insulin level ; and a lipid profile , including HDL cholesterol and LDL cholesterol levels . After initial assessment , we instituted a program of advice on appropriate eating patterns and exercise and followed each patient on a monthly basis for 3 months . During this time , we assessed the patients ' fulfillment of tasks , such as completion of a food diary , and overall adherence to appointments . R and omization Process We r and omly allocated eligible patients to receive a conventional , intensive , nonsurgical program or laparoscopic adjustable gastric b and ing . A computer-derived r and om allocation sequence , without blocking or stratification , performed the r and omization . This was prepared at the trial office . The trial coordinator enrolled participants and informed them of the trial allocation . After assessment had confirmed a participant 's suitability for r and omization , the coordinator contacted the trial office by telephone for allocation . The study was not blinded . Description of Nonsurgical and Surgical Interventions Common Program We instructed and encouraged all patients to follow appropriate lifestyle behavior of good eating practice s and increased exercise and activity . We also encouraged them to exercise for at least 200 minutes per week . Nonsurgical Program This program centered on the use of behavioral modification , very-low-calorie diet , and pharmacotherapy with education and professional support on appropriate eating and exercise behavior . During the 2-year period , 3 trained physicians developed a program using all the available modalities for each individual on the basis of guidelines prepared and continually review ed by a panel of experienced bariatric physicians . The program began with an intensive 6-month period of very-low-calorie diet ( 500 to 550 kcal/d ) using 1 to 3 packets of Optifast ( Novartis , Fremont , Michigan ) daily for 12 weeks , followed by a transition phase over 4 weeks combining some very-low-calorie meals with 120 mg of orlistat before nonvery-low-calorie diet meals , and then 120 mg of orlistat before all meals until the completion of the intensive phase . This intensive 6-month program was followed by further courses of very-low-calorie diets or orlistat as tolerated , as well as continual behavioral , dietary , and exercise advice to assist the participant in maintaining weight loss over a prolonged period . Sibutramine was not approved for use in Australia during the first 12 months of the study and , therefore , was not incorporated into the medical program . The management program for each individual was design ed to reflect good clinical practice . A physician saw each patient every 2 weeks during the very-low-calorie diet program and every 4 to 6 weeks during the rest of the study . All patients were seen at least every 6 weeks . Surgical Program Two experienced surgeons performed the laparoscopic adjustable gastric b and ( LAP-B AND System ) procedure , by a st and ardized method ( 14 ) , within 1 month of r and omization . The b and was placed along the perigastric pathway in all cases ( 16 ) . The treating surgeon review ed patient progress every 4 to 6 weeks during the study period and made adjustments to the volume of saline within the b and in the office by using st and ard clinical criteria ( 17 ) . Adverse Events All patients in the study were question ed about the occurrence of adverse events at each consultation , and physicians recorded the", "Background Laparoscopic Roux-en-Y gastric bypass ( LRYGB ) can dramatically ameliorate type 2 diabetes mellitus ( T2DM ) in morbidly obese patients . However , there is little evidence supporting the effectiveness of LRYGB in low body mass index ( BMI ) patients . The study was design ed to evaluate the safety and results of LRYGB for achieving T2DM remission in patients with BMI in the range of 25–35 kg/m2 . Methods Twenty-two patients ( two men and 20 women ) with T2DM underwent LRYGB . Data on patient demographics , BMI , co-morbidities , and details of diabetes mellitus , including disease duration , family history , medication use , and remission , were prospect ively collected and analyzed . Results The mean age was 47 years ( range , 28–63 years ) , mean BMI was 30.81 ( range , 25.00–34.80 kg/m2 ) , and mean duration of T2DM onset was 6.57 years ( range , 1–20 years ) . Sixteen ( 72.27 % ) patients had a family history of T2DM . There was no mortality , but two ( 9 % ) patients experienced complications : an early gastrojejunostomy hemorrhage and frequent loose stools that required revision surgery . At 12 months , 14 ( 63.6 % ) patients showed T2DM remission , six ( 27.3 % ) showed glycemic control , and two ( 9.1 % ) showed improvement . The group achieving remission had a higher BMI ( p = 0.001 ) , younger age ( p = 0.002 ) , and shorter duration of diabetes ( p = 0.001 ) . These three factors may be predictors of diabetes resolution at 12 months . Conclusion Early intervention in low- BMI patients yields better remission rates because age , BMI , and duration of T2DM predict glycemic outcomes", "OBJECTIVES To determine the efficacies of 2 weight-reducing operations on diabetic control and the role of duodenum exclusion . DESIGN Double-blind r and omized controlled trial . SETTING Department of Surgery of the Min-Sheng General Hospital , National Taiwan University . PATIENTS We studied 60 moderately obese patients ( body mass index > 25 and 30 to 7.5 % ) after conventional treatment ( > 6 months ) from September 1 , 2007 , through June 30 , 2008 . Patients and observers were masked during the follow-up , which ended in 2009 , 1 year after final enrollment . INTERVENTIONS Gastric bypass with duodenum exclusion ( n = 30 ) vs sleeve gastrectomy without duodenum exclusion ( n = 30 ) . MAIN OUTCOME MEASURES The primary outcome was remission of T2DM ( fasting glucose without glycemic therapy ) . Secondary measures included weight and metabolic syndrome . Analysis was by intention to treat . RESULTS Of the 60 patients enrolled , all completed the 12-month follow-up . Remission of T2DM was achieved by 28 ( 93 % ) in the gastric bypass group and 14 ( 47 % ) in the sleeve gastrectomy group ( P = .02 ) . Participants assigned to gastric bypass had lost more weight , achieved a lower waist circumference , and had lower glucose , HbA(1c ) , and blood lipid levels than the sleeve gastrectomy group . No serious complications occurred in either group . CONCLUSIONS Participants r and omized to gastric bypass were more likely to achieve remission of T2DM . Duodenum exclusion plays a role in T2DM treatment and should be assessed . Trial Registration clinical trials.gov Identifier : NCT00540462 ( http://www . clinical trials.gov )", "CONTEXT Obesity is a risk factor for cardiovascular events . Weight loss might protect against cardiovascular events , but solid evidence is lacking . OBJECTIVE To study the association between bariatric surgery , weight loss , and cardiovascular events . DESIGN , SETTING , AND PARTICIPANTS The Swedish Obese Subjects ( SOS ) study is an ongoing , nonr and omized , prospect i ve , controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care . Patients were recruited between September 1 , 1987 , and January 31 , 2001 . Date of analysis was December 31 , 2009 , with median follow-up of 14.7 years ( range , 0 - 20 years ) . Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women . Exclusion criteria were identical in surgery and control patients . Surgery patients underwent gastric bypass ( 13.2 % ) , b and ing ( 18.7 % ) , or vertical b and ed gastroplasty ( 68.1 % ) , and controls received usual care in the Swedish primary health care system . Physical and biochemical examinations and data base cross-checks were undertaken at preplanned intervals . MAIN OUTCOME MEASURES The primary end point of the SOS study ( total mortality ) was published in 2007 . Myocardial infa rct ion and stroke were predefined secondary end points , considered separately and combined . RESULTS Bariatric surgery was associated with a reduced number of cardiovascular deaths ( 28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group ; adjusted hazard ratio [ HR ] , 0.47 ; 95 % CI , 0.29 - 0.76 ; P = .002 ) . The number of total first time ( fatal or nonfatal ) cardiovascular events ( myocardial infa rct ion or stroke , whichever came first ) was lower in the surgery group ( 199 events among 2010 patients ) than in the control group ( 234 events among 2037 patients ; adjusted HR , 0.67 ; 95 % CI , 0.54 - 0.83 ; P usual care , bariatric surgery was associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese adults", "BACKGROUND Many mild-to-moderately obese individuals ( body mass index [ BMI ] 30 - 35 kg/m(2 ) ) have serious diseases related to their obesity . Nonoperative therapy is ineffective in the long term , yet surgery has never been made widely available to this population . METHODS Between 1996 and 2004 , 93 patients with a BMI of 30 - 35 kg/m(2 ) underwent laparoscopic adjustable gastric b and ing with the LAP-B AND . All patients were referred by their primary physician , entered into a comprehensive bariatric surgery program at one Australian center , and operated on by one surgeon . Data on all patients were collected prospect ively and entered into an electronic registry . The study parameters included preoperative age , gender , BMI , presence of co-morbidities , percentage of excess weight loss , and resolution of co-morbidities . RESULTS The mean age was 44.6 years ( range 16 - 76 ) , mean weight was 98 kg , and the mean BMI was 32.7 kg/m(2 ) ( range 30 - 34 ) . Of the 93 patients , 42 ( 45 % ) had co-morbidities , including asthma , diabetes , hypertension , and sleep apnea . The proportion of patients in follow-up was 79 % , 85 % , and 89 % at 1 , 2 , and 3 years , respectively . The mean weight was reduced to 71 kg at 1 year , 72 kg at 2 years , and 72 kg at 3 years . The mean BMI was reduced to 27.2 + /- 2.2 , 27.3 + /- 3.1 , and 27.6 + /- 3.7 kg/m(2 ) , respectively , and the mean percentage of excess weight loss was 57.9 % + /- 24.5 % , 57.6 + /- 29.3 % , and 53.8 % + /- 32.8 % at 1 , 2 , and 3 years , respectively . At 3 years , the BMI was 18 - 24 kg/m(2 ) in 34 % , 25 - 29 kg/m(2 ) in 51 % , and 30 - 35 kg/m(2 ) in 10 % . At 3 years , the percentage of excess weight loss was 75 % in 10 % . The co-morbidities improved or completely resolved in most patients . No mortality occurred . CONCLUSION We are very encouraged by this series of low BMI patients treated with the LAP-B AND . Their weight loss has been good , the complications have been minimal , and the co-morbidities have partially or wholly resolved . With additional study , it is reasonable to expect the weight guidelines for bariatric surgery to be altered to include patients with a BMI of 30 - 35 kg/m(2 )", "Roux-en-Y bypass surgery is the most common bariatric procedure currently performed in the United States for medically complicated obesity . Although this leads to a marked and sustained weight loss , we have identified an increasing number of patients with episodes of nephrolithiasis afterwards . We describe a case series of 60 patients seen at Mayo Clinic-Rochester that developed nephrolithiasis after Roux-en-Y gastric bypass ( RYGB ) , including a subset of 31 patients who had undergone metabolic evaluation in the Mayo Stone Clinic . The mean body mass index of the patients before procedure was 57 kg/m(2 ) with a mean decrease of 20 kg/m(2 ) at the time of the stone event , which averaged 2.2 years post-procedure . When analyzed , calcium oxalate stones were found in 19 and mixed calcium oxalate/uric acid stones in two patients . Hyperoxaluria was a prevalent factor even in patients without a prior history of nephrolithiasis , and usually presented more than 6 months after the procedure . Calcium oxalate supersaturation , however , was equally high in patients less than 6 months post-procedure due to lower urine volumes . In a small r and om sampling of patients undergoing this bypass procedure , hyperoxaluria was rare preoperatively but common 12 months after surgery . We conclude that hyperoxaluria is a potential complicating factor of RYGB surgery manifested as a risk for calcium oxalate stones", "Background Beneficial effects of BPD on T2DM in BMI > 35 kg/m2 patients are far better than those in patients with BMI 25–35 . This study was aim ed at investigating if a similar difference exists between patients with mild obesity ( OB , BMI 30–35 ) or simple overweight ( OW , BMI 25–30 ) . Methods Fifteen OB ( six M ) and 15 OW ( 13 M ) , diabetic for ≥3 years , with HbA1c ≥7.5 % despite medical therapy , underwent BPD . OB/OW : age 55.1 ± 8.0/57.8 ± 6.7 years , BMI 33.1 ± 1.5/28.0 ± 1.3 kg/m2 , diabetes duration 11.6 ± 8.0/11.1 ± 6.1 years , insulin therapy 4/8 p. FSG and HbA1c were determined preoperatively and up to 2 years . Insulin resistance and beta-cell function were explored by means of HOMA-IR and IVGTT ( AIR ) . Thirty-eight diabetic patients on medical therapy served as controls . Results Mean BMI stabilized around 27 since the 4th month in OB , and 24 since 1st month in OW . FSG in OB/OW preop , 1 , 12 , 24 months : 234 ± 76/206 ± 62 mg/dL , 154 ± 49/176 ± 75 , 131 ± 32/167 ± 48 , 134 ± 41/154 ± 41 ( cross-sectional n.s . at all times ) ; HbA1c : 9.5 ± 1.6/9.1 ± 1.3 , 7.3 ± 1.1/7.3 ± 1.2 , 5.9 ± 0.6/7.1 ± 1.1 ( p 1.1 ( p HOMA-IR , preoperatively 10.7 ± 5.8/7.5 ± 5.4 , went below 3.0 at 1 month and remained such until 2 years in both groups . AIR , preoperatively 1.11 ± 3.17/1.27 ± 2.68 μIU/mL , in OB significantly increased at 4 months to 7.63 ± 5.79 , maintained up to 2 years with 6.95 ± 3.19 , whereas in OW , statistical significance was reached only at 2 years with 5.02 ± 4.87 . Conclusions Significantly different BPD effect , thus biological severity of T2DM , also exists between mildly obese and simply overweight patients . The rise of AIR allows hoping that an increase of beta-cell mass may occur in the long run . Clinical Trials.gov Identifier :", "BACKGROUND Roux-en-Y gastric bypass ( RYGB ) benefits patients with type 2 diabetes mellitus ( T2DM ) and a body mass index ( BMI ) > 35 kg/m(2 ) ; however , its effectiveness in patients with T2DM and a BMI is unclear . Asian Indians have a high risk of T2DM and cardiovascular disease at relatively low BMI levels . We examined the safety and efficacy of RYGB in Asian Indian patients with T2DM and a BMI of 22 - 35 kg/m(2 ) in a tertiary care medical center . METHODS A total of 15 consecutive patients with T2DM and a BMI of 22 - 35 kg/m(2 ) underwent RYGB . The data were prospect ively collected before surgery and at 1 , 3 , 6 , and 9 months postoperatively . RESULTS Of the 15 patients , 8 were men and 7 were women ( age 45.6 + /- 12 years ) . Their preoperative characteristics were BMI 28.9 + /- 4.0 kg/m(2 ) , body weight 78.7 + /- 12.5 kg , waist circumference 100.2 + /- 6.8 cm , and duration of T2DM 8.7 + /- 5.3 years . At baseline , 80 % of subjects required insulin , and 20 % controlled their T2DM with oral hypoglycemic medication . The BMI decreased postoperatively by 20 % , from 28.9 + /- 4.0 kg/m(2 ) to 23.0 + /- 3.6 kg/m(2 ) ( P antidiabetic medications were discontinued by 1 month after surgery in 80 % of the subjects . At 3 months and thereafter , 100 % were euglycemic and no longer required diabetes medication . The fasting blood glucose level decreased from 233 + /- 87 mg/dL to 89 + /- 12 mg/dL ( P hemoglobin A1c decreased from 10.1 % + /- 2.0 % to 6.1 % + /- 0.6 % ( P waist circumference , presence of dyslipidemia , and hypertension improved significantly . The predicted 10-year cardiovascular disease risk ( calculated using the United Kingdom Prospect i ve Diabetes Study equations ) decreased substantially for fatal and nonfatal coronary heart disease and stroke . No mortality , major surgical morbidity , or excessive weight loss occurred . CONCLUSION RYGB safely and effectively eliminated T2DM in Asian Indians with a BMI Larger , longer term studies are needed to confirm this benefit", "Context : Hyperglycemia resolves quickly after bariatric surgery , but the underlying mechanism and the most effective type of surgery remains unclear . Objective : To examine glucose metabolism and β-cell function in patients with type 2 diabetes mellitus ( T2DM ) after two types of bariatric intervention ; Roux-en-Y gastric bypass ( RYGB ) and gastric restrictive ( GR ) surgery . Design : Prospect i ve , nonr and omized , repeated- measures , 4-week , longitudinal clinical trial . Patients : In all , 16 T2DM patients ( 9 males and 7 females , 52±14 years , 47±9 kg m−2 , HbA1c 7.2±1.1 % ) undergoing either RYGB ( N=9 ) or GR ( N=7 ) surgery . Outcome measures : Glucose , insulin secretion , insulin sensitivity at baseline , and 1 and 4 weeks post-surgery , using hyperglycemic clamps and C-peptide modeling kinetics ; glucose , insulin secretion and gut-peptide responses to mixed meal tolerance test ( MMTT ) at baseline and 4 weeks post-surgery . Results : At 1 week post-surgery , both groups experienced a similar weight loss and reduction in fasting glucose ( P However , insulin sensitivity increased only after RYGB , ( P , weight loss remained similar for both groups , but fasting glucose was normalized only after RYGB ( 95±3 mg 100 ml−1 ) . Insulin sensitivity improved after RYGB ( P the disposition index remained unchanged after RYGB and increased 30 % after GR ( P=0.10 ) . The MMTT elicited a robust increase in insulin secretion , glucagon-like peptide-1 ( GLP-1 ) levels and β-cell sensitivity to glucose only after RYGB ( P : RYGB provides a more rapid improvement in glucose regulation compared with GR . This improvement is accompanied by enhanced insulin sensitivity and β-cell responsiveness to glucose , in part because of an incretin effect", "BACKGROUND Intensive lifestyle interventions can reduce the incidence of type 2 diabetes in people with impaired glucose tolerance , but how long these benefits extend beyond the period of active intervention , and whether such interventions reduce the risk of cardiovascular disease ( CVD ) and mortality , is unclear . We aim ed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes , diabetes-related macrovascular and microvascular complications , and mortality . METHODS In 1986 , 577 adults with impaired glucose tolerance from 33 clinics in China were r and omly assigned to either the control group or to one of three lifestyle intervention groups ( diet , exercise , or diet plus exercise ) . Active intervention took place over 6 years until 1992 . In 2006 , study participants were followed-up to assess the long-term effect of the interventions . The primary outcomes were diabetes incidence , CVD incidence and mortality , and all-cause mortality . FINDINGS Compared with control participants , those in the combined lifestyle intervention groups had a 51 % lower incidence of diabetes ( hazard rate ratio [ HRR ] 0.49 ; 95 % CI 0.33 - 0.73 ) during the active intervention period and a 43 % lower incidence ( 0.57 ; 0.41 - 0.81 ) over the 20 year period , controlled for age and clustering by clinic . The average annual incidence of diabetes was 7 % for intervention participants versus 11 % in control participants , with 20-year cumulative incidence of 80 % in the intervention groups and 93 % in the control group . Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group . There was no significant difference between the intervention and control groups in the rate of first CVD events ( HRR 0.98 ; 95 % CI 0.71 - 1.37 ) , CVD mortality ( 0.83 ; 0.48 - 1.40 ) , and all-cause mortality ( 0.96 ; 0.65 - 1.41 ) , but our study had limited statistical power to detect differences for these outcomes . INTERPRETATION Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention . However , whether lifestyle intervention also leads to reduced CVD and mortality remains unclear", "The efficacy of Roux-en-Y gastric bypass ( RYGB ) to control type 2 diabetes mellitus ( T2DM ) has been demonstrated in morbidly obese patients . Surgical procedures primarily focused on T2DM control in patients with body mass index ( BMI ) remission of T2DM . However , only few reports have evaluated the safety and efficacy of RYGB in this group of patients . The aim of this study is to assess the safety and efficacy of RYGB in TD2 M patients with BMI laparoscopic RYGB were included . Safety of the procedure was evaluated according to mortality , need of reoperation/conversion , and complication rates . Metabolic parameters were evaluated at baseline and 6 , 12 , and 24 months after surgery . Thirty patients were included . Seventeen ( 56.6 % ) were women . Age , BMI , and duration of diabetes were 48 ± 9 years , 33.7 ± 1.2 kg/m2 , 4 ± 2.9 years , respectively . No mortality was observed . No conversion/reoperation was needed . Average length of stay was 3.2 ± 0.9 days . Early and late postoperative complications were observed in five ( 16.6 % ) and five ( 16.6 % ) patients , respectively . Twelve months after surgery , remission was observed in 25 of 30 patients ( 83.3 % ) . After 2 years , remission was achieved in 13 of 20 patients ( 65 % ) , and hemoglobin A1c decreased from 8.1 ± 1.8 % to 5.9 ± 1.1 % and homeostasis model assessment of insulin resistance from 5.7 ± 3.2 to 1.9 ± 0.8 after 12 months . RYGB is a safe and effective procedure to induce T2DM remission in otherwise not eligible patients for bariatric surgery . Evidence from prospect i ve studies is needed to vali date this approach", "BACKGROUND Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk , but whether these benefits persist over time is unknown . METHODS The prospect i ve , controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched , conventionally treated obese control subjects . We now report follow-up data for subjects ( mean age , 48 years ; mean body-mass index , 41 ) who had been enrolled for at least 2 years ( 4047 subjects ) or 10 years ( 1703 subjects ) before the analysis ( January 1 , 2004 ) . The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years . RESULTS After two years , the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group ( P weight had increased by 1.6 percent and decreased by 16.1 percent , respectively ( P Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period . Two- and 10-year rates of recovery from diabetes , hypertriglyceridemia , low levels of high-density lipoprotein cholesterol , hypertension , and hyperuricemia were more favorable in the surgery group than in the control group , whereas recovery from hypercholesterolemia did not differ between the groups . The surgery group had lower 2- and 10-year incidence rates of diabetes , hypertriglyceridemia , and hyperuricemia than the control group ; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable . CONCLUSIONS As compared with conventional therapy , bariatric surgery appears to be a viable option for the treatment of severe obesity , result ing in long-term weight loss , improved lifestyle , and , except for hypercholesterolemia , amelioration in risk factors that were elevated at baseline", "Background Laparoscopic gastric bypass result ed in significant weight loss and resolution of type 2 diabetes mellitus ( T2DM ) . The current indication for bariatric surgery is mainly applied for patients with body mass index ( BMI ) > 35 kg/m2 with comorbidity status . However , little is known concerning T2DM patients with BMI Recent studies have suggested that T2DM patients with BMI gastric bypass surgery . Methods From Jan 2002 to Dec 2006 , 820 patients who underwent laparoscopic mini-gastric bypass were enrolled in a surgically supervised weight loss program . We identified 201 ( 24.5 % ) patients who had impaired fasting glucose or T2DM . All the clinical data were prospect ively collected and stored . Patients with BMI 35 kg/m2 . Successful treatment of T2DM was defined by HbA1C 45 kg/m2 . Patients with BMI liver enzyme and C-peptide levels than those with BMI > 35 kg/m2 . The mean total weight loss for the population was 32.1 , 33.4 , 31.9 , and 32.8 % ( at 1 , 2 , 3 , 5 years after surgery ) , and percentage to change in BMI was 31.9 , 34.2 , 32.2 , and 29.5 % at 1 , 2 , 3 , and 5 years . One year after surgery , fasting plasma glucose returned to normal in 89.5 % of BMI 35 kg/m2 patients ( p = 0.087 ) . The treatment goal of T2DM ( HbA1C 350 kg/m2 ( p = 0.059 ) . Conclusion Laparoscopic gastric bypass result ed in significant and sustained weight loss with successful treatment of T2DM up to 87.1 % . Despite a slightly lower response rate of T2DM treatment , patients with BMI acceptable DM resolution , and this treatment option can be offered to this group of patients", "Background Many mildly to moderately obese individuals with a body mass index ( BMI ) lower than 35 kg/m2 have serious diseases related to their obesity . Nonsurgical therapy is ineffective in the long term , yet surgery has never been made widely available to this population . Methods Between 2002 and 2007 , 53 patients with a BMI lower than 35 kg/m2 underwent laparoscopic adjustable gastric b and ing at our institution . Data on all these patients were collected prospect ively and entered into an institutional review board – approved electronic registry . The study parameters included preoperative age , gender , BMI , presence of comorbidities , percentage of excess weight loss ( % EWL ) , and resolution of comorbidities . Results The mean preoperative age of the patients was 46.9 years ( range , 16–68 years ) , and the mean preoperative BMI was 33.1 kg/m2 ( range , 28.2–35.0 kg/m2 ) . Of the 53 patients , 49 ( 92 % ) had at least one obesity-related comorbidity . The mean BMI decreased to 28.1 ± 2.4 kg/m2 , 25.8 ± 2.9 kg/m2 , and 25.8 ± 3.1 kg/m2 and mean % EWL was 48.3 ± 17.6 , 69.9 ± 28.0 , and 69.7 ± 31.7 at 0.5 , 1 , and 2 years , respectively . Substantial improvement occurred for the following comorbidities evaluated : hypertension , depression , diabetes , asthma , hypertriglyceridemia , obstructive sleep apnea , hypercholesterolemia , and osteoarthritis . There was one slip , two cases of b and obstruction ( from food ) , two cases of esophagitis , and two port leaks , but no mortality . Conclusion The authors are very encouraged by this series of low- BMI patients who underwent laparoscopic adjustable gastric b and ing . Their weight loss has been excellent , and their complications have been acceptable . Their comorbidities have partially or wholly resolved . With further study , it is reasonable to expect alteration of the weight guidelines for bariatric surgery to include patients with a BMI lower than 35 kg/m2" ]

[ "Background : Moderate vitamin B-12 deficiency is relatively common in older people . However , there is little robust evidence on the effect of vitamin B-12 supplementation on neurologic and cognitive outcomes in later life . Objective : We investigated whether vitamin B-12 supplementation benefits neurologic and cognitive function in moderately vitamin B-12–deficient older people . Design : We conducted a double-blind , r and omized , placebo-controlled trial in 7 general practice s in South East Engl and , United Kingdom . Study participants were aged ≥75 y and had moderate vitamin B-12 deficiency ( serum vitamin B-12 concentrations : 107–210 pmol/L ) in the absence of anemia and received 1 mg crystalline vitamin B-12 or a matching placebo as a daily oral tablet for 12 mo . Peripheral motor and sensory nerve conduction , central motor conduction , a clinical neurologic examination , and cognitive function were assessed before and after treatment . Results : A total of 201 participants were enrolled in the trial , and 191 subjects provided outcome data . Compared with baseline , allocation to vitamin B-12 was associated with a 177 % increase in serum concentration of vitamin B-12 ( 641 compared with 231 pmol/L ) , a 331 % increase in serum holotranscobalamin ( 240 compared with 56 pmol/L ) , and 17 % lower serum homocysteine ( 14.2 compared with 17.1 μmol/L ) . In intention-to-treat analysis of covariance models , with adjustment for baseline neurologic function , there was no evidence of an effect of supplementation on the primary outcome of the posterior tibial compound muscle action potential amplitude at 12 mo ( mean difference : −0.2 mV ; 95 % CI : –0.8 , 0.3 mV ) . There was also no evidence of an effect on any secondary peripheral nerve or central motor function outcome , or on cognitive function or clinical examination . Conclusion : Results of the trial do not support the hypothesis that the correction of moderate vitamin B-12 deficiency , in the absence of anemia and of neurologic and cognitive signs or symptoms , has beneficial effects on neurologic or cognitive function in later life . This trial was registered at www.is rct n.com as IS RCT N54195799", "BACKGROUND Methylation of genomic DNA is dependent on an adequate supply of folate coenzymes . Previous data support the hypothesis that abnormal DNA methylation plays an integral role in carcinogenesis . To date , no studies assessing the effect of inadequate folate status on DNA methylation in older women ( aged > 63 y ) have been reported . OBJECTIVE The effect of moderate folate depletion followed by folate repletion on leukocyte genomic DNA methylation was investigated in elderly women ( aged 60 - 85 y ) to evaluate whether DNA methylation could be used as a functional indicator of folate status . DESIGN Healthy , postmenopausal women ( n = 33 ) consumed a moderately folate-depleted diet ( 118 microg folate/d ) for 7 wk , followed by 7 wk of folate repletion with 200 or 415 microg/d , each provided as 2 different dietary treatments for a total of 4 treatment groups ( n = 30 ) . Leukocyte DNA methylation was determined on the basis of the ability of DNA to incorporate [(3)H]methyl groups from labeled S:-adenosylmethionine in an in vitro assay . RESULTS Incorporation of [(3)H]methyl groups increased significantly ( P : = 0.0025 ) in response to folate depletion , suggesting undermethylation of DNA . No significant changes were detected in [(3)H]methyl incorporation in any group over the 7-wk repletion period compared with postdepletion values . CONCLUSIONS DNA methylation status may be used as a functional indicator of moderately depleted folate status . The slow response to the repletion diets observed suggests that normalization of DNA methylation after moderate folate depletion may be delayed in older women", "Based on research demonstrating associations between folate , B-12 and B-6 vitamins and cognition and mood , we investigated the effects of short-term supplementation in 211 healthy younger , middle-aged and older women who took either 750 microg of folate , 15 microg of vitamin B-12 , 75 mg of vitamin B-6 or a placebo daily for 35 d. In addition , we examined associations between dietary intake of these vitamins and cognition and mood . Usual dietary intake status was estimated using a retrospective , self-report , quantified food frequency question naire . Participants completed alternate forms of st and ardized tests of cognitive processing re sources , memory , executive function , verbal ability and self-report mood measures before and after supplementation . Supplementation had a significant positive effect on some measures of memory performance only , and no effect on mood . Dietary intake status was associated with speed of processing , recall and recognition and verbal ability", "The relationship of folate status and polyphenol intake to thiamin status was studied in 80 r and omly selected elderly and young Irish women , with key variables affecting thiamin nutrition controlled for . Folate , thiamin , and polyphenol intakes were measured during a 4-wk baseline ( elderly and young ) and 6-wk double-blind ( elderly ) supplementation period . Only elderly subjects were r and omly assigned to placebo , folic acid ( 400 micrograms ) , thiamin ( 10 mg ) , or folic-acid-plus-thiamin groups . Thiamin status ( TPP effect ) was not affected by folate status ( plasma and erythrocyte folate ) during the baseline period or with folic acid supplementation alone . Polyphenol intake was not correlated with thiamin status . Only thiamin intake and thiamin supplementation significantly affected thiamin status . Because the majority of subjects ( 102 of 160 ) were initially thiamin deficient , enrichment of Irish grain products with thiamin is recommended", "INTRODUCTION Observational studies have suggested a causal relationship between hyperhomocysteinemia and cardiovascular complications such as stroke and ischemic heart disease . The Homocysteine Lowering Trialists ' Collaboration has shown that daily administration of folic acid can significantly decrease homocysteine levels up to 25 % . Aim of this study was to investigate the effect of daily supplementation of folic acid ( 5 mg ) on IMT after 18 months of treatment in patients with at least one cardiovascular risk factor . METHODS We enrolled 103 patients with at least one cardiovascular risk factor who were r and omized to receive either a daily dose of 5 mg folic acid ( group I , n=53 ) or placebo ( group II , n=50 ) for 18 months . RESULTS After 18 months of folic acid supplementation , homocysteine levels were significantly reduced in the active treatment group compared to a non-significant increase in the placebo group . Folic acid levels were markedly increased in the former group and non-significantly reduced in the latter . Significant regression of carotid IMT was observed ( 0.961+/-0.092 to 0.933+/-0.077 mm , p IMT progression in the placebo group ( 0.964+/-0.099 to 0.984+/-0.094 mm ) . CONCLUSION Folic acid supplementation results in significant IMT reduction after 18 months in patients with at least one cardiovascular risk", "OBJECTIVE To measure the prevalence of cobalamin ( vitamin B12 ) deficiency in geriatric out patients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment . DESIGN Prospect i ve study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays . In patients with serum cobalamin levels , the response to cobalamin treatment in the group with levels of methylmalonic acid and /or homocysteine > 3 st and ard deviations ( SD ) above the mean for normals was compared with that of those without such elevations . SETTING Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center , Denver , CO . PATIENTS One-hundred and fifty-two consecutive out patients , ages 65 to 99 , were screened . Twenty-nine subjects with serum cobalamin levels were prospect ively evaluated and treated with cobalamin . MAIN OUTCOME MEASURES Cobalamin , methylmalonic acid , homocysteine , complete blood counts , neurologic examination , and neuropsychological testing . RESULTS The prevalence of cobalamin deficiency as defined by a serum cobalamin level levels of serum methylmalonic acid and /or homocysteine elevated to > 3 SD was 14.5 % of the screened out patients . A similar proportion of patients with low normal serum cobalamin levels ( between 201 and 300 pg/mL ) demonstrated elevated metabolites > 3 SD ( 56 % ) compared with patients with low serum cobalamin levels ( elevated methylmalonic acid and homocysteine levels in each patient who was treated prospect ively . Results for complete blood count , lactate dehydrogenase , bilirubin , baseline neurologic score , and baseline neuropsychologic scores did not differ in the group of patients with elevated metabolites compared with those with normal metabolites . The mean red cell volume fell significantly in the patients with elevated metabolites after 6 months of cobalamin treatment . One patient with elevated metabolites had marked improvement in his neurologic abnormalities after 6 months of cobalamin treatment . CONCLUSION There was a high ( 14.5 % ) prevalence of cobalamin deficiency as demonstrated by elevations in serum methylmalonic acid and homocysteine in addition to low or low normal serum cobalamin levels in elderly out patients . The serum cobalamin level was insensitive for screening since similar numbers of patients with low normal serum cobalamin levels of 201 - 300 pg/mL compared with patients with low cobalamin levels ( metabolites which fell with cobalamin treatment . Additional studies will be required to define the full clinical benefit from treatment with Cbl in elderly subjects", "A clinical trial of the effect of vitamin B12 therapy was conducted in 39 elderly subjects who had been found , in a community screening survey , to have low levels of serum B12 without a macrocytic anaemia or neuropathy . The study produced no evidence which suggests that in such subjects B12 is superior to placebo in effecting an improvement in psychiatric state or general well-being . There was a clear tendency for all the subjects to show an improvement during the trial , but this probably represents the therapeutic effect of involvement in a research exercise of this kind", "Cognitive impairment is associated with increased blood concentrations of homocysteine and high blood viscosity . Previous studies have shown that vitamin B supplementation reduces homocysteine and enhances cognitive function in patients with mild dementia and low serum folic acid . However , whether folic acid enhances cognitive function in elderly subjects without dementia and normal serum folic acid is unknown . Twenty-four healthy elderly subjects ( age 73.0+/-5.6 years , mean+/-S.D. ) with normal serum folic acid ( 6.3+/-2.4 microg/l ) and Mini Mental State Examination ( MMSE ) > 27/30 were r and omized to 4-week treatment with folic acid 5mg/day or placebo in a r and omized , placebo-controlled , parallel-group study . Continuous Attention Test ( CAT ) , Four-Choice Reaction Time ( FCRT ) , Digit-Symbol Substitution ( DSS ) , Scanning Memory Sets ( SMS ) , and blood viscosity for different shear rates were measured before and after treatment . Folic acid supplementation induced a significant increase in serum folic acid levels ( + 13.8 versus + 1.6 microg/l , p homocysteine levels ( -1.91 versus -0.41 micromol/l , p=0.05 ) compared to placebo . However , there was no significant change in CAT , FCRT , DSS , SMS , and blood viscosity between the two groups . Short-term folic acid supplementation does not enhance psychomotor performance or reduce blood viscosity in healthy elderly subjects with normal serum folic acid levels and preserved cognitive function", "Background Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125 - 200 pM/l is lacking . We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo . Methods This multicentre ( 13 general practice s , two nursing homes , and one primary care center in western Switzerl and ) , parallel , r and omised , controlled , closed-label , observer-blind trial included 50 patients with serum vitamin B12 levels between 125 - 200 pM/l who were r and omized to receive either oral vitamin B12 ( 1000 μg daily , N = 26 ) or placebo ( N = 24 ) for four weeks . The institution 's pharmacist used simple r and omisation to generate a table and allocate treatments . The primary outcome was the change in serum methylmalonic acid ( MMA ) levels after one month of treatment . Secondary outcomes were changes in total homocysteine and serum vitamin B12 levels . Blood sample s were central ised for analysis and adherence to treatment was verified by an electronic device ( MEMS ; Aardex Europe , Switzerl and ) . Trial registration : IS RCT N 22063938 . Results Baseline characteristics and adherence to treatment were similar in both groups . After one month , one patient in the placebo group was lost to follow-up . Data were evaluated by intention-to-treat analysis . One month of vitamin B12 treatment ( N = 26 ) lowered serum MMA levels by 0.13 μmol/l ( 95%CI 0.06 - 0.19 ) more than the change observed in the placebo group ( N = 23 ) . The number of patients needed to treat to detect a metabolic response in MMA after one month was 2.6 ( 95 % CI 1.7 - 6.4 ) . A significant change was observed for the B12 serum level , but not for the homocysteine level , hematocrit , or mean corpuscular volume . After three months without active treatment ( at four months ) , significant differences in MMA levels were no longer detected . Conclusions Oral vitamin B12 treatment normalised the metabolic markers of vitamin B12 deficiency . However , a one-month daily treatment with1000 μg oral vitamin B12 was not sufficient to normalise the deficiency markers for four months , and treatment had no effect on haematological signs of B12 deficiency", "BACKGROUND Observational studies have shown that low folate and elevated homocysteine concentrations are risk factors for vascular disease in the general population . R and omized controlled trials in vascular patients have failed to show that folic acid reduces the risk of recurrent vascular disease , whereas such trials are lacking in the general population . OBJECTIVE The objective was to determine whether folic acid supplementation reduces the progression of atherosclerosis as measured by common carotid intima-media thickness (CIMT)-a vali date d marker of atherosclerosis and predictor of vascular disease risk . DESIGN A r and omized , double-blind , placebo-controlled study in 819 men and postmenopausal women aged 50 - 70 y , free-living in the Netherl and s , and with a total homocysteine concentration ≥13 μmol/L at screening was conducted . Participants received either 800 μg folic acid or placebo daily for 3 y. Rate of change in CIMT and arterial distensibility were the primary and secondary outcomes , respectively . RESULTS Compared with placebo , serum folate increased by 577 % and plasma total homocysteine concentrations decreased by 26 % after 3 y of folic acid supplementation . The mean ( ±SE ) rate of change in CIMT was 1.9 ± 0.9 μm/y in the folic acid arm and 1.3 ± 0.8 μm/y in the placebo arm ( mean difference : 0.7 μm/y ; 95 % CI : -1.8 , 3.1 μm/y ; P = 0.59 ) . No difference was observed ( P = 0.23 ) between the rates of change in distensibility in the folic acid arm ( -0.53 ± 0.06 × 10(-3 ) kPa(-1 ) ) and in the placebo arm ( -0.62 ± 0.06 × 10(-3 ) kPa(-1 ) ) . CONCLUSION Despite a considerable increase in folate concentrations and a reduction in total homocysteine concentrations , 3-y folic acid supplementation did not slow down atherosclerotic progression or arterial stiffening . This trial was registered at clinical trials.gov as NCT00110604", "BACKGROUND Increased plasma homocysteine is associated with coronary artery disease , peripheral vascular disease and venous thrombosis . Folic acid is the most effective therapy for reducing homocysteine levels . The lowest effective supplement of folic acid is not known , particularly for the elderly who have the highest prevalence of these conditions . AIM To explore the effects of daily supplements of 0 , 50 , 100 , 200 , 400 and 600 microg folic acid on plasma homocysteine in an elderly population . DESIGN R and omized double-blind placebo-controlled trial . METHODS Participants ( n=368 ) aged 65 - 75 years were r and omly allocated to receive one of the treatments for 6 weeks . Plasma homocysteine was recorded after 3 weeks and 6 weeks of supplementation . RESULTS Only the 400 microg and 600 microg groups had significantly lower homocysteine levels compared to placebo ( p=0.038 and p folic acid intake of 926 microg per day would be required to ensure that 95 % of the elderly population would be without cardiovascular risk from folate deficiency . DISCUSSION A daily folic acid intake of 926 microg is unlikely to be achieved by diet alone . Individual supplementation or fortification of food with folic acid will be required to reach this target", "OBJECTIVES To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia ( PA ) . DESIGN R and omized , double-blind , placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month . SETTING Two geriatric hospitals in the North Western Health Care Network , Melbourne , Australia . PARTICIPANTS Thirty-one in patients with serum vitamin B12 levels between 100 and 150 pmol/L , without PA , other malabsorption disorders , or progressive neurological or terminal illness . The mean age was 81.4 years . INTERVENTION After informed consent , a medical and drug history was taken and the Mini-Mental State Examination ( MMSE ) completed . A dietitian made assessment of oral cobalamin intake . Blood was taken for serum vitamin B12 , serum and red cell folate assay , full blood examination , fasting serum gastrin , parietal and intrinsic factor antibodies , fasting serum homocysteine , and creatinine . Patients were then r and omized to receive 10 microg oral cyanocobalamin , 50 microg oral cyanocobalamin , or placebo treatment for 1 month , after which the investigations and clinical examinations were repeated . MEASUREMENTS Percentage change in the level of vitamin B12 , homocysteine , folate , and red cell parameters and absolute changes in MMSE were calculated and compared between groups . The groups were compared on the number of responders who improved their level of B12 by 20 % . Chi-square calculations on changes in serum vitamin B12 concentration were also performed . RESULTS Mean serum vitamin B12 + /- st and ard deviation improved by 51.7 + /- 47.1 % in the 50-microg group , 40.2 + /- 34.4 % in the 10-microg group , and 11.7 + /- 24.5 % in the placebo group . The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group ( P=.044 ) . The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group ( P=.186 ) . Eight of 10 subjects in each treatment group were classified as responders , compared with two of 11 in the placebo group ( P=.004 ) . Homocysteine levels fell in patients receiving cyanocobalamin , but this fall failed to reach statistical significance . There were no significant changes in the other parameters measured . CONCLUSION Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12 . This result has implication s for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12", "BACKGROUND Screening for deficiencies in vitamin B(12 ) and folate is advocated to prevent anemia in very elderly individuals . However , the effects of vitamin B(12 ) and folate deficiency on the development of anemia in old age have not yet been established . METHODS The current study is embedded in the Leiden 85-Plus Study , a population -based prospect i ve study of subjects aged 85 years . Levels of vitamin B(12 ) , folate , and homocysteine were determined at baseline . Hemoglobin levels and mean corpuscular volume ( MCV ) were determined annually during 5 years of follow-up . RESULTS We analyzed data from 423 subjects who did not use any form of cyanocobalamin , hydroxocobalamin , or folic acid supplementation , neither at baseline nor during follow-up . Folate deficiency ( 13.5 mumol/L ; n = 194 ) were associated with anemia at baseline ( adjusted odds ratio [ OR ] , 2.44 ; 95 % confidence interval [ CI ] , 1.06 - 5.61 ; and adjusted OR , 1.82 ; 95 % CI , 1.08 - 3.06 , respectively ) , but vitamin B(12 ) deficiency ( anemia during follow-up ( adjusted HR , 0.92 ; 95 % CI , 0.46 - 1.82 ) or with changes in MCV ( adjusted linear mixed model ; P = .77 ) . Both folate deficiency and elevated homocysteine levels were associated with the development of anemia from age 85 years onward ( adjusted HR , 3.33 ; 95 % CI , 1.55 - 7.14 ; and adjusted HR , 1.70 ; 95 % CI , 1.01 - 2.88 , respectively ) , but not with an increase in MCV over time ( P > .30 ) . CONCLUSION In the general population of very elderly individuals , anemia in 85-year-old subjects is associated with folate deficiency and elevated homocysteine levels but not with vitamin B(12 ) deficiency", "BACKGROUND It has been suggested that oral cobalamin ( vitamin ( B12 ) ) therapy may be an effective therapy for treating cobalamin deficiencies related to food-cobalamin malabsorption . However , the duration of this treatment was not determined . PATIENTS AND METHOD In an open-label , nonplacebo study , we studied 30 patients with established cobalamin deficiency related to food-cobalamin malabsorption , who received between 250 and 1000 microg of oral crystalline cyanocobalamin per day for at least 1 month . ENDPOINTS Blood counts , serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment . RESULTS During the first month of treatment , 87 % of the patients normalized their serum cobalamin levels ; 100 % increased their serum cobalamin levels ( mean increase , + 167 pg/dl ; P medullary regeneration ; 100 % corrected their initial macrocytosis ; and 54 % corrected their anemia . All patients had increased hemoglobin levels ( mean increase , + 0.6 g/dl ) and reticulocyte counts ( mean increase , + 35 x 10(6)/l ) and decreased erythrocyte cell volume ( mean decrease , 3 fl ; all P cyanocobalamin , 250 - 1000 microg/day , given orally for 1 month , may be an effective treatment for cobalamin deficiencies not related to pernicious anemia", "Folic acid deficiency is common in the elderly population , result ing in anaemia , dementia , many neurological sequelae and an indirect role in atheromatous disease . An increase in natural food folate is relatively ineffective at increasing folate status and the use of folate fortification of foodstuffs is recommended . The aim of our study was to assess the benefits of folic acid-fortified milk to the folate status of an elderly institutionalised population . 49 subjects received fortified milk as part of their daily diet for at least 6 months ( active group ) and 40 subjects received unfortified milk ( control group ) . Our results showed a mean serum folate level in the active group of 5.81 ( 1.1–17.6 ) µg/l compared to the control group mean of 2.16 ( 0.5–9.4 ) µg/l ( p for serum folate 2.7–20 µg/l ) . Similarly the mean red cell folate level in the active group of 316.5 ( 130–905 ) µg/l was significantly higher than the control group mean of 196.1 ( 95–490 ) µg/l ( p that folic acid-fortified milk is an efficacious and acceptable method of administration of folic acid in the elderly population and we recommend the use of folic acid-fortified milk in the regular daily diet of the elderly population" ]

[ "Background Clear , transparent , and sufficiently detailed abstract s of conferences and journal articles related to r and omized controlled trials ( RCTs ) are important , because readers often base their assessment of a trial solely on information in the abstract . Here , we extend the CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement to develop a minimum list of essential items , which authors should consider when reporting the results of a RCT in any journal or conference abstract . Methods and Findings We generated a list of items from existing quality assessment tools and empirical evidence . A three-round , modified-Delphi process was used to select items . In all , 109 participants were invited to participate in an electronic survey ; the response rate was 61 % . Survey results were presented at a meeting of the CONSORT Group in Montebello , Canada , January 2007 , involving 26 participants , including clinical trialists , statisticians , epidemiologists , and biomedical editors . Checklist items were discussed for eligibility into the final checklist . The checklist was then revised to ensure that it reflected discussion s held during and subsequent to the meeting . CONSORT for Abstract s recommends that abstract s relating to RCTs have a structured format . Items should include details of trial objectives ; trial design ( e.g. , method of allocation , blinding/masking ) ; trial participants ( i.e. , description , numbers r and omized , and number analyzed ) ; interventions intended for each r and omized group and their impact on primary efficacy outcomes and harms ; trial conclusions ; trial registration name and number ; and source of funding . We recommend the checklist be used in conjunction with this explanatory document , which includes examples of good reporting , rationale , and evidence , when available , for the inclusion of each item . Conclusions CONSORT for Abstract s aims to improve reporting of abstract s of RCTs published in journal articles and conference proceedings . It will help authors of abstract s of these trials provide the detail and clarity needed by readers wishing to assess a trial 's validity and the applicability of its results", "BACKGROUND Carnitine insufficiency is responsible for various co-morbid conditions in maintenance hemodialysis ( MHD ) patients . L-carnitine supplementation is expected to improve the quality of life ( QoL ) of patients on MHD . AIMS To study the effect of L-carnitine supplementation on QoL of Indian patients on MHD . SETTING AND DESIGN This was a single ( patient ) blind , r and omized , placebo-controlled clinical trial conducted on patients on MHD attending hemodialysis unit of the study center . MATERIAL S AND METHODS Twenty patients on MHD suffering from hemodialysis-related symptoms were r and omly assigned to receive intravenous L-carnitine 20 mg/kg or placebo after every dialysis session for 8 weeks . SF36 ( Short Form with 36 questions ) score for QoL , laboratory investigations and dialysis related symptoms were recorded at baseline and after 8 weeks . Improvement in QoL , laboratory parameters and dialysis related symptoms in the two groups after 8 weeks was compared . STATISTICAL ANALYSIS USED Depending on normality of data , unpaired T test or Mann Whitney U test was used for comparison of change ( 8 weeks-baseline ) in SF36 scores and laboratory parameters observed in the two groups . RESULTS L-carnitine supplementation increased total SF36 score by 18.29 + /- 12.71 ( 95 % CI : 10.41 to 26 ) while placebo result ed in reduction in total SF36 score by 6.4 + /- 16.39 ( 95 % CI : -16.59 to 3.73 ) . L-carnitine also result ed in significant increase in hemoglobin and serum albumin and decrease in serum creatinine as compared to placebo . More patients were relieved of dialysis related symptoms in L-carnitine group . CONCLUSION Intravenous L-carnitine supplementation improves QoL in patients on MHD", "In patients on maintenance hemodialysis several factors reduce the body stored carnitine which could lead to dyslipidemia , anemia , and general health in these patients . We evaluated the effect of oral L-carnitine supplementation on lipid profiles , anemia , and quality of life ( QOL ) in hemodialysis patients . In a r and omized , double-blinded , placebo-controlled trial , end-stage renal disease ( ESRD ) patients on hemodialysis received either L-carnitine 1 g/d ( n = 24 ) or placebo ( 27 patients ) for 16 weeks . At the end of the study , there was a significant decrease in triglyceride ( −31.1 ± 38.7 mg/dL , P = 0.001 ) and a significant increase in HDL ( 3.7 ± 2.8 mg/dL , P Decrease in total cholesterol ( −6.6 ± 16.0 mg/dL , P = 0.075 ) and increase in hemoglobin ( 0.7 ± 1.7 g/dL , P = 0.081 ) concentrations in the carnitine group were not significant . There was no statistically significant changes in LDL in any group ( P > 0.05 ) . Erythropoietin dose was significantly decreased in both the carnitine ( −4750 ± 5772 mg , P = 0.001 ) and the placebo group ( −2000 ± 4296 mg , P ) . No improvement was observed in QOL scores of two groups . In ESRD patients under maintenance hemodialysis , oral L-carnitine supplementation may reduce triglyceride and cholesterol and increase HDL and hemoglobin and subsequently reduce needed erythropoietin dose without effect on QOL ", "Carnitine deficiency is a commonly observed problem in maintenance hemodialysis ( MHD ) patients , which results in altered metabolism of fatty acids and subsequently development of dyslipidemia . To evaluate the effect of oral L-carnitine ( LC ) supplementation on lipid profile of adult MHD patients , we studied 30 of them ( 19 males , 11 females ) who received LC supplementation of 250 mg tablets three times a day for eight weeks . They were compared with 30 matched patients as a control group . Serum lipid profiles were compared before and after the intervention between the two groups . There was a significant decrease of the values of the lipid profile in the intervention group before and after carnitine supplementation including the mean values of total cholesterol ( 190 ± 36.8 vs. 177 ± 31.2 mg/dL ) , triglyceride ( 210 ± 64.7 vs. 190 ± 54.1 mg/dL ) and LDL-cholesterol ( 117 ± 30.1 vs. 106 ± 26.3 mg/dL ) , while the values did not change siginificantly from base line in the control group . However , the difference for HDL-cholesterol in intervention group was not statistically significant . None of the patients dropped out of the study due to drug side effects . Oral LC supplementation ( 750 mg/day ) is able to improve lipid profile in patients on MHD . Further long-term studies with adequate sample size are needed to define the population of patients who would benefit more from carnitine therapy and the optimal dose and the most efficient route for administration of the drug", "Scattered reports indicate that L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance either in patients without renal disease or in maintenance hemodialysis ( MHD ) or chronic peritoneal dialysis patients . We conducted an experimental study in MHD patients to evaluate the effects of L-carnitine treatment on inflammatory and protein-energy nutritional status . MHD patients were assigned to receive intravenous injections of L-carnitine 20 mg/kg ( n = 48 ) or placebo ( n = 65 ) thrice weekly at the end of each hemodialysis treatment for 6 months . The carnitine-treated group showed a statistically significant decrease in serum C-reactive protein and increase in serum albumin and transferrin , blood hemoglobin , and body mass index . Conversely , in the placebo-treated group , a significant decrease was reported for serum albumin , serum transferrin , and body mass index , whereas the other considered measures did not change significantly . These preliminary findings suggest that in MHD patients , L-carnitine therapy may suppress inflammation , particularly among those patients with C-reactive protein > or =3 mg/dL , and may improve protein-energy nutritional status", "INTRODUCTION Carnitine supplementation may improve the general health and quality of life of hemodialysis patients by improving adipokines levels . The aim of the study was to investigate the effects of L-carnitine supplementation on leptin levels , adiponectin levels , and body weight of hemodialysis patients . MATERIAL S AND METHODS Fifty hemodialysis patients were r and omly divided into the carnitine group , who received oral L-carnitine , 1 g/L for 3 months , and the control group . Anthropometric measurements and serum levels of adipokines were measured at baseline and at the end of the intervention . RESULTS Forty-two participants completed the study . Serum leptin concentrations decreased after 12 weeks of the intervention in both groups , but these changes were not significant . The mean change of leptin concentration were , -1.7 ± 19.0 µg/mL and -7.1 ± 20.0 µg/mL in the carnitine group and the control group , respectively ( P = .39 ) . The mean adiponectin levels at baseline and after the intervention were 8.6 ± 11.19 µg/mL and 9.8 ± 4.1 µg/mL in the carnitine group ( P = .67 ) and 5.0 ± 2.5 µg/mL and 11.2 ± 5.4 µg/mL in the control group , respectively ( P increased significantly in the control group only . The decrease in body mass index was not significant . CONCLUSIONS This study showed that a daily supplementation of 1000 mg oral syrup of L-carnitine for 12 weeks did not affect leptin and adiponectin levels or the body weight or body mass index of hemodialysis patients", "Exercise capacity in patients with end-stage renal disease ( ESRD ) remains impaired despite correction of anemia . Carnitine insufficiency may contribute to impaired exercise and functional capacities in patients with ESRD . Two r and omized placebo-controlled trials were conducted to test whether intravenous L-carnitine improves exercise capacity ( assessed by maximal rate of oxygen consumption [ VO(2max ) ] ) and quality of life ( measured by the Kidney Disease Question naire [ KDQ ] ) in patients with ESRD . In study A , patients were administered L-carnitine , 20 mg/kg ( n = 28 ) , or placebo ( n = 28 ) intravenously at the conclusion of each thrice-weekly dialysis session for 24 weeks . In study B , a dose-ranging study , patients were administered intravenous L-carnitine , 10 mg/kg ( n = 32 ) , 20 mg/kg ( n = 30 ) , or 40 mg/kg ( n = 32 ) , or placebo ( n = 33 ) as in study A. The prospect i ve primary statistical analysis evaluated changes in VO(2max ) in each study and specified that changes in the KDQ were assessed only in the combined population s. L-Carnitine supplementation increased plasma carnitine concentrations , but did not affect VO(2max ) in either study . Because change in VO(2max ) showed significant heterogeneity , a secondary analysis using a mixture of linear models approach on the combined study population s was performed . L-Carnitine therapy ( combined all doses ) was associated with a statistically significant smaller deterioration in VO(2max ) ( -0.88 + /- 0.26 versus -0.05 + /- 0.19 mL/kg/min , placebo versus L-carnitine , respectively ; P = 0.009 ) . L-Carnitine significantly improved the fatigue domain of the KDQ after 12 ( P = 0.01 ) and 24 weeks ( P = 0.03 ) of treatment compared with placebo using the primary analysis but did not significantly affect the total score ( P = 0.10 ) or other domains of the instrument ( P > 0.11 ) . Carnitine was well tolerated , and no drug-related adverse effects were identified . Intravenous L-carnitine treatment increased plasma carnitine concentrations , improved patient-assessed fatigue , and may prevent the decline in peak exercise capacity in hemodialysis patients . VO(2max ) in the primary analysis and other assessed end points were unaffected by carnitine therapy", "End-stage renal disease affects every aspect of a patient 's life , including perception of health and quality of life . It is likely that a hemodialysis patient 's perceptions of health-related quality of life directly influence compliance with medical , nursing , and nutritional prescriptions . Because L-carnitine supplementation is known to enhance muscle strength and energy in hemodialysis patients , we hypothesized that L-carnitine supplementation would enhance a hemodialysis patient 's perception of health-related quality of life . To test this hypothesis , 1 g L-carnitine or placebo was administered orally to 101 patients immediately before and after every hemodialysis treatment for 6 months . To assess health-related quality of life from the patient 's perspective , the Medical Outcomes Study Short Form 36 instrument was administered before the study and at 1.5-month intervals for the duration of the study . In addition , a 10-item question naire design ed to assess common intradialytic symptoms was administered at the end of each dialysis treatment . Other parameters analyzed included Kt/V(urea ) and level of nutrition . In the 6-month group , oral L-carnitine supplementation had an early positive effect on general health ( P physical function ( P L-carnitine supplementation improved vitality ( P general health ( P ) and perceived health-related quality of life . Serum albumin concentration was directly correlated to how patients perceived the quality of their lives", "AIMS Carnitine is involved in fatty acid metabolism and it is cleared by dialysis . As it plays a role in energy utilization and because malnutrition is a frequent complication of HD treatment , we studied the effects of carnitine supplementation on several nutritional parameters in HD patients . MATERIAL AND METHODS The main selection criterion was a body mass index ( BMI ; body weight/(height)2 ) Fifty-three patients were enrolled to participate in this open and r and omized study . For 6 months , 28 patients received 15 mg/kg of intravenous L-carnitine at the end of each hemodialysis ( HD ) treatment ( Group A ) , the remaining 25 patients were controls ( Group B ) . The measured parameters were the post-dialysis body weight , serum albumin concentration ( nephelemetry ) , food intake assessed by a 3-day food question naire , nPNA ( normalized protein equivalent of nitrogen appearance ) , creatinine generation , and anthropometry . RESULTS Forty-five patients completed the study ( Group A : 14 F/9 M , 66.7 years old ; Group B : 11 F/11 M , 65.2 years old ) . At the beginning of the study , there were no differences between the groups for age , gender , HD duration , BMI , diabetes prevalence , plasma carnitine levels and measured nutritional parameters . 65.2 % and 77.3 % in each group were carnitine-deficient ( plasma total carnitine level L-carnitine supplementation , none of the nutritional parameters had changed in either group , except that serum albumin concentration decreased in both groups . Dividing each group according to their respective median serum albumin concentrations , daily energy and protein intakes , creatinine generation or triceps skinfold thickness did not show any difference in the various nutritional parameters with or without carnitine supplementation . CONCLUSION Carnitine supplementation , despite normalization of plasma carnitine levels , has no effect on the nutritional status of HD patients", "BACKGROUND AND AIMS Advanced glycation end products ( AGEs ) contribute to cardiovascular disease in patients with hemodialysis ( HD ) . We have recently found that carnitine levels are inversely associated with skin AGE levels in HD patients . We examined whether L-carnitine supplementation reduced skin AGE levels in HD patients with carnitine deficiency . METHODS This was a single-center study . One hundred and two HD patients ( total carnitine levels to either oral administration of L-carnitine ( 900 mg/day ) ( n=51 ) or control ( n=51 ) . After 6 months , metabolic and inflammatory variables , including serum levels of carnitine , were measured . Skin AGE levels were determined by evaluating skin auto-fluorescence with an AGE-reader . RESULTS There were no significant differences of clinical variables at baseline between the control and L-carnitine therapy group . Thirty-two patients did not complete the assessment or treatment of the study . Oral L-carnitine supplementation for 6 months significantly increased low-density lipoprotein cholesterol ( LDL-C ) , triglycerides , total , free , and acyl carnitine levels , while it decreased alanine transaminase , acyl/free carnitine ratio , β₂-microglobulin , and skin AGE values . Change in total carnitine values from baseline ( Δtotal carnitine ) and Δfree carnitine were inversely associated with Δskin AGE levels in L-carnitine-treated patients ( p=0.036 and p=0.016 , respectively ) . In multiple regression analysis , Δfree carnitine was a sole independent determinant of Δskin AGEs ( R²=0.178 ) . CONCLUSIONS The present study demonstrated that oral L-carnitine supplementation significantly decreased skin AGE levels in HD patients with carnitine deficiency . These observations suggest that supplementation of L-carnitine might be a novel therapeutic strategy for preventing the accumulation of tissue AGEs in carnitine-deficient patients with HD" ]

[ "BACKGROUND The effectiveness of antipsychotic monotherapy in schizoaffective disorder is limited , and further constrained by safety concerns . AIMS We aim ed to compare the efficacy , tolerability and safety profile of the new pharmaceutical , olanzapine , with haloperidol . METHOD Data were assessed from 300 DSM-III-R schizoaffective subjects from a larger double-blind prospect i ve international study . Subjects were r and omly allocated to six weeks of olanzapine ( 5 - 20 mg ) or haloperidol ( 5 - 20 mg ) treatment ; responders were followed for up to one year of double-blind , long-term maintenance therapy . RESULTS Olanzapine-treated patients achieved a statistically significant greater improvement than haloperidol treated patients on overall measures of efficacy , including clinical response . Significantly fewer olanzapine patients left the study early , and fewer adverse events were observed among those receiving olanzapine . During maintenance , olanzapine-treated patients continued to experience additional improvement , with fewer EPS but more weight gain than those on haloperidol . CONCLUSIONS Olanzapine demonstrated substantial advantages over the conventional antipsychotic haloperidol in the management of schizoaffective disorder", "Background : Generalized social anxiety disorder is a highly prevalent anxiety disorder with deleterious effects on social and family relationships , as well as work performance . We report the results of a multicenter , r and omized , placebo-controlled trial comparing the efficacy , safety , and tolerability of fluvoxamine controlled release ( CR ) to placebo in patients with generalized social anxiety disorder . Methods : A total of 279 adult patients meeting all inclusion /exclusion criteria was recruited at 23 United States sites and r and omly assigned to receive either fluvoxamine CR ( 100 - 200 mg/d ) or placebo for 12 weeks . The dose could be increased , based on efficacy and tolerability , in increments of 50 mg/d at weekly intervals . The dosage remained constant during weeks 6 to 12 . Results : Treatment with fluvoxamine CR result ed in statistically and clinical ly significant improvements in symptoms associated with generalized social anxiety disorder as early as week 4 on the Liebowitz Social Anxiety Scale and the Clinical Global Impression Scale Global Improvement , and at week 6 on the Sheehan Disability Scale , Clinical Global Impression Scale Severity of Illness and the Patient Global Impression of Improvement Scale . The most frequent adverse events reported by patients on fluvoxamine CR were headache , nausea , somnolence , and insomnia . No weight gain was observed for either treatment group , and at end point , there were no differences between treatments on overall sexual function , as measured by the Arizona Sexual Experience Scale . Conclusions : Both physician and patient-rated scales indicate that fluvoxamine CR is effective and safe for the treatment of generalized social anxiety disorder", "PURPOSE Previous analysis of data from CATIE showed that patients r and omly assigned to switch to a new medication were more likely to discontinue study drug than those who stayed on the medication they had been taking prior to r and omization . This study addresses additional outcomes measures evaluating symptoms , neurocognition , quality of life , neurological side effects , weight , and health costs . First , considering patients r and omized to olanzapine or risperidone , outcomes among patients who had been on the drug to which they were r and omized prior to CATIE ( N=129 \" stayers \" ) were compared to outcomes of those who switched to either of these two drugs ( N=269 \" switchers \" ) . A second set of analyses considered patients on baseline monotherapy with olanzapine ( N=297 ) ; risperidone ( N=252 ) or quetiapine ( n=87 ) and compared those r and omly assigned to stay on each of these medications with those assigned to switch to any of the other five phase 1 medications in CATIE . In mixed models of each outcome the independent variable of primary interest represented stay vs. switch , with multivariate adjustment for potential confounding factors . RESULTS With one exception , there were no significant differences between stayers and switchers on any outcome measure in either set of analyses . The exception was that , in the second set of analyses , patients who stayed on olanzapine showed greater weight gain than those who switched from olanzapine to other drugs . CONCLUSION Switching to a new medication yielded no advantage over staying on the previous medication . Staying on olanzapine was associated with greater weight gain", "The objective of this study was to compare the efficacy and safety of valproate and lithium in bipolar I patients experiencing a manic or a mixed episode . This international , r and omized , open-label , parallel-group , equivalence study included 268 patients with bipolar I disorder . The starting dose of valproate was 20 mg/kg/day and that of lithium was 800 mg/day . Treatment duration was 12 weeks . The primary outcome measure was mean change in Young Mania Rating Scale score between baseline and study end . Secondary outcome measures were response and remission rates , change in Montgomery and Åsberg Depression Rating Scale and Clinical Global Impression Bipolar Disorder instrument score , and occurrence of adverse events . The mean change from baseline in Young Mania Rating Scale score was 15.8±5.3 in the lithium group and 17.3±9.4 in the valproate group . The 90 % confidence interval of the intergroup difference ( −0.69 ; 3.31 ) was within prespecified equivalence limits . Response rates were 72.6 % in the lithium group and 79.5 % in the valproate group . Remission rates were 58.5 and 71.9 % , respectively . No intergroup differences were observed in median time to treatment response ( 21 days ) or change in Clinical Global Impression Bipolar Disorder instrument or Montgomery and Åsberg Depression Rating Scale scores . Adverse events were reported in 42.8 % of patients in the lithium group and 41.5 % in the valproate group . Valproate and lithium showed comparable efficacy and tolerability in the treatment of acute mania over 12 weeks", "BACKGROUND Flunarizine is known as a nonspecific calcium channel blocker that has been used for decades for the treatment of migraine , vertigo , and cognitive deficits related to cerebrovascular disorders . Flunarizine also has dopamine D2 receptor blocking properties and was effective in animal models of predictive validity for antipsychotics . However , its clinical antipsychotic efficacy has never been investigated . OBJECTIVE To evaluate the therapeutic efficacy and tolerability of flunarizine compared to haloperidol in out patients with stable and chronic DSM-IV-defined schizophrenia and schizoaffective disorder . METHOD Seventy patients from 2 centers were r and omly assigned and participated in a double-blind , parallel-group , flexible-dose study comparing flunarizine ( 10 - 50 mg/day ) and haloperidol ( 2.5 - 12.5 mg/day ) for 12 weeks . Patients were assessed with the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impressions-Improvement ( CGI-I ) scale , the Extrapyramidal Symptom Rating Scale ( ESRS ) , a battery for cognitive performance , and laboratory examinations . The study was conducted from September 2004 to May 2007 . RESULTS Mean doses at endpoint were 29.7 mg/day for flunarizine and 6.4 mg/day for haloperidol . Both groups showed significant symptom improvement during the study , with a reduction of 21 % in the flunarizine group and 19 % in the haloperidol group in PANSS total scores ( p PANSS overall score and all subscales , CGI-I score , or cognitive performance . Dropout rates , ESRS scores , and prolactin levels were not different between groups , but significantly more patients reported emergence of akathisia in the haloperidol group ( p = .04 ) , and weight gain was significantly higher with flunarizine ( 1.2 kg ) than with haloperidol ( -0.8 kg ) ( p flunarizine , which showed good efficacy and tolerability for the treatment of schizophrenia , with a possible atypical profile . Its unique pharmacokinetic profile as an oral drug with long half-life ( 2 - 7 weeks ) , low cost , and low induction of extrapyramidal symptoms warrants further investigation , particularly in psychiatric patients with low adherence to treatment", "OBJECTIVE The goal of this 5-year naturalistic study of patients treated with clozapine was to examine the incidence of treatment-emergent diabetes mellitus in relation to other factors , including weight gain , lipid abnormalities , age , clozapine dose , and treatment with valproate . METHOD Data on age , gender , race , diagnosis , family history of diabetes , and age at clozapine initiation were collected from medical records of 82 out patients with schizophrenia or schizoaffective disorder . Clozapine dose , data on use of valproate , and laboratory test results were recorded at 6-month intervals . RESULTS The mean age at the time of clozapine initiation of the 82 patients was 36.4 years ; 26.8 % of the patients were women , and 91.5 % were Caucasian . The mean baseline weight was 175.5 lb , and the mean body mass index was 26.9 kg/m(2 ) . Thirty patients ( 36.6 % ) were diagnosed with diabetes during the 5-year follow-up . Weight gain , use of valproate , and total daily dose of clozapine were not significant risk factors for developing diabetes mellitus . Patients experienced significant weight gain that continued until approximately month 46 from initiation of clozapine . There was a nonsignificant increase in total serum cholesterol and a significant increase in serum triglycerides level . CONCLUSIONS The results support the hypotheses that patients treated with clozapine experience significant weight gain and lipid abnormalities and appear to be at increased risk for developing diabetes", "BACKGROUND Carbamazepine is frequently used for treating bipolar disorder , but few large trials have assessed its efficacy in preventing relapse . We evaluated open-label monotherapy with beaded extended-release carbamazepine capsules ( ERC-CBZ ; SPD417 ) as continuation and short-term maintenance therapy in bipolar disorder patients with manic and mixed episodes . METHOD A 6-month , open-label study enrolled 92 patients with DSM-IV bipolar disorder ( most recent episode : 67 % [ N = 62 ] mixed , 33 % [ N = 30 ] manic ) who had participated in 2 previous 3-week , double-blind , placebo-controlled studies . Subjects received beaded ERC-CBZ ( 200 - 1600 mg/day ) , titrated at investigators ' discretion to a final mean dose of 938 mg/day and serum carbamazepine concentration of 6.6 microg/mL. The primary efficacy measure was time to relapse , and secondary efficacy measures included Young Mania Rating Scale ( YMRS ) , Clinical Global Impressions scale ( CGI ) , and Hamilton Rating Scale for Depression ( HAM-D ) scores . Data were gathered from January 2000 to January 2002 . RESULTS Of 77 patients analyzed in the intent-to-treat population , 11 ( 14.3 % ) relapsed . Fifty-three patients ( 68.8 % ) discontinued early , including 18 ( 23.4 % ) due to adverse events . Observed mean time to relapse was 61.1 days , while estimated mean time to relapse based on the Kaplan-Meier model was 141.8 days . Improvements on the YMRS , CGI , and HAM-D from the beginning of prior double-blind treatment were maintained . The most common adverse events were headache , dizziness , and rash . No significant weight gain was noted . CONCLUSION We noted a low relapse rate with beaded ERC-CBZ in this 6-month trial . Adverse events were generally mild to moderate and were typical of those associated with carbamazepine . Controlled studies are warranted to further explore the efficacy of beaded ERC-CBZ in preventing relapse in bipolar disorder", "A double-blind controlled study comparing the effects of bupropion to doxepin in out patients with primary depression was conducted to evaluate efficacy and safety differences between the two drugs . Following a 7-day placebo washout period , patients could be treated for up to 13 weeks on either treatment . Antidepressant response was assessed by the Hamilton Depression and Anxiety Scales , Clinical Global Severity and Improvement Ratings , and the Zung Self-Rating Depression Scale . Comparable efficacy between the compounds was found across the 13-week study . Doxepin differed from bupropion mainly on the sleep factor of the Hamilton Depression Scale , with doxepin improving sleep to a greater extent than bupropion . Doxepin produced a greater incidence of anticholinergic side effects , including dry mouth , constipation , sleepiness , and tiredness , in comparison to bupropion . Also , increased appetite and weight gain were consistent side effects of doxepin relative to bupropion", "OBJECTIVE The authors ' goal was to compare the efficacy and tolerability of 6 months ' treatment with flexible-dose ziprasidone and olanzapine in patients with schizophrenia or schizoaffective disorder . METHOD Brief Psychiatric Rating Scale ( BPRS ) scores and Clinical Global Impression ( CGI ) severity scores were obtained for 126 responders to a 6-week acute study of olanzapine and ziprasidone during a blinded 6-month continuation study and optional extension study . RESULTS Comparable improvements in BPRS and CGI severity scores were seen with both drugs . Olanzapine produced significant increases from acute- study baseline values in weight and body mass index and within-group increases in total cholesterol , low-density lipoprotein cholesterol , and fasting insulin . Between-group differences were not significant for lipids and insulin . Mean QTc values at endpoint were 407.1 msec ( baseline mean=406.0 msec ) and 394.4 msec ( baseline mean=399.7 msec ) for ziprasidone and olanzapine , respectively . No patient had a QTc interval > or = 500 msec . CONCLUSIONS Ziprasidone and olanzapine had comparable long-term efficacy ; olanzapine was associated with significant weight gain and metabolic alterations", " Of 580 patients r and omly assigned to short-term , double-blind treatment with either mirtazapine , amitriptyline or placebo , a total of 217 patients clinical ly judged to be responders subsequently continued on the same medication for up to 2 years in the long-term treatment study ( mirtazapine , n = 74 ; amitriptyline , n = 86 and placebo , n = 57 ) . The efficacy of mirtazapine in relapse prevention was seen in an analysis of the first 20 weeks data . Significantly fewer patients relapsed during treatment with mirtazapine compared with placebo ( p relapse was shown on the survival analysis . There was a significant advantage for amitriptyline compared with placebo in the first 20 weeks , with fewer patients relapsing . There was a significant advantage for mirtazapine compared with amitriptyline at 20 weeks seen on the survival analysis ( p mirtazapine compared with placebo was also seen in the prophylactic phase of treatment after 20 weeks . At the endpoint there were significantly more patients in the placebo group with a return of symptoms and significantly fewer showing sustained response , Amitriptyline was better than placebo with fewer patients suffering a recurrence of symptoms , but there was no difference from placebo in the proportion of patients with sustained response . Mirtazapine was well tolerated with a side-effect profile similar to that of placebo . The only adverse event reported significantly more frequently on mirtazapine than on placebo was weight gain . Objective ly measured weight gain was more frequent with amitriptyline ( 22 % of patients ) compared with mirtazapine ( 13 % of patients ) . Amitriptyline was associated with significantly more adverse events than either mirtazapine or placebo , in particular sedative and anticholinergic side effects . The efficacy of mirtazapine in reducing the risk of relapse and the recurrence of depression , which on some measures showed an advantage compared with amitriptyline , coupled with its improved side-effect profile , commends this antidepressant for the long-term treatment of depression", "BACKGROUND Despite the high prevalence of depression in the United States , 10 few studies have identified which adverse effects ( AEs ) patients are willing or unwilling to tolerate when receiving antidepressants . OBJECTIVE The aim of this study was to identify reasons for discontinuation10 and noncompliance with antidepressant medications , the impact of AEs on compliance and quality of life ( assessed using impact of AEs on activities of daily living ) , and patients ' suggestions for improving their medication , using a patient survey . METHODS Patients aged 18 to 65 years with mild to severe depression were 10 r and omly selected by their physicians to be sent an invitation to complete the 42- question survey . Three hundred physicians nationwide assessed the severity of depression and symptoms of anxiety in each respondent , using their judgment . Patients were asked specific questions to assess reasons for discontinuation/noncompliance . Patients were also asked to rate AEs based on how difficult they were to \" live with , \" and what 2 aspects of their antidepressant medication they would change if they could . RESULTS In a separate , concurrent study , physicians classified 175 ( 50 % ) abd Results :0 mildly to moderately depressed and 84 ( 24 % ) as severely depressed . Ninety-one respondents ( 26 % ) were classified as having symptoms of anxiety . Two hundred seven patients ( 60 % ) indicated they had discontinued treatment with an antidepressant agent at some point in their lives , the most common reason for which was lack of efficacy ( 92 patients [ 44 % ] ) . Of the 344 patients currently being treated with an antidepressant , 75 ( 22 % ) reported noncompliance . The most common reasons for noncompliance were \" have trouble remembering to take it \" ( 19/44 patients [ 43 % ] ) , \" gained a lot of weight \" ( 11/41 [ 27 % ] ) , \" unable to have an orgasm \" ( 8/40 [ 20 % ] ) , and \" lost interest in sex \" ( 8/41 [ 20 % ] ) . The 4 AEs patients expressed as \" extremely difficult to live with \" were \" weight gain \" ( 104 patients [ 31 % ] ) , \" unable to have erection \" ( 83 [ 25 % ] ) , \" difficulty reaching orgasm \" ( 80 [ 24 % ] ) , and \" tired during the day/no energy \" ( 69 patients [ 21 % ] ) . The 3 most frequently cited improvements patients ( n = 327 ) would make to their medications were better efficacy ( 176 patients [ 54 % ] ) and eliminating AEs related to sexual desire and weight gain ( 112 [ 34 % ] and 105 [ 32 % ] patients , respectively ) . CONCLUSIONS The findings of this survey of patients with mild to severe10 depression suggest that compliance , and hence efficacy , can be promoted by ( 1 ) underst and ing what patients expect and desire from the antidepressants they are prescribed and ( 2 ) prescribing antidepressants associated with low rates of weight gain , sexual dysfunction , or tiredness", "BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism", "BACKGROUND The objectives of the study were to compare efficacy and tolerability of venlafaxine ER 75 - 150 mg/day with that of citalopram 10 - 20 mg/day in elderly patients with major depression according to DSM-IV criteria . METHODS A r and omised , double-blind , parallel group 6-month study . Efficacy was assessed by MADRS , CGI Global Improvement , CGI Severity of Illness and GDS-20 scores and safety by physical examinations , vital signs , adverse events and UKU side effect rating . Plasma levels of venlafaxine , its major metabolite O-desmethylvenlafaxine and citalopram were followed . RESULTS One hundred and fifty-one male and female patients ( 64 - 89 years ) were enrolled and 118 patients completed the study . Comparable improvements in MADRS , CGI Severity of Illness , CGI Global Improvement and GDS-20 were observed during venlafaxine and citalopram treatment . The MADRS remission rate was 19 % for venlafaxine and 23 % for citalopram . Side effects were common during both treatments but differed in tremor being more common during citalopram and nausea/vomiting during venlafaxine treatment . There were no clinical ly significant changes in blood pressure or body weight . CONCLUSION The observed benefits of venlafaxine treatment in elderly patients with major depression were similar to those observed in younger adults as were reported adverse events and side effects . Treatment with venlafaxine ER was well tolerated and induced beneficial effects of similar magnitude as those of citalopram", "AIM Perospirone is classified as a second-generation antipsychotic agent for the treatment of schizophrenia . Perospirone binds with high affinity to serotonin 5-HT2A receptors and dopamine D2 receptors . There are no reports of clinical comparisons of perospirone and risperidone in multicenter studies . To clarify the clinical traits of perospirone in the treatment of schizophrenia , the clinical efficacies and side-effects of perospirone and risperidone were compared in a r and omized clinical multicenter trial . METHODS Sixty-six schizophrenia patients were enrolled in the trial . The Positive and Negative Syndrome Scale ( PANSS ) total , positive , negative and general symptoms scores and Drug-Induced Extra-Pyramidal Symptoms Scale ( DIEPSS ) scores were investigated at 0 , 4 , 8 and 12 weeks . RESULTS Significant reductions in the PANSS total and subscale scores were observed in both the perospirone and risperidone groups , with no significant between-group differences at 4 and 12 weeks . Risperidone improved the total scores and overall psychopathologic symptom total scores more effectively than perospirone at week 8 . There were no significant differences in the DIEPSS scores at 0 , 4 , 8 and 12 weeks between the perospirone and risperidone groups . The numbers of patients who dropped out did not differ between the perospirone and risperidone groups . CONCLUSIONS Perospirone was as effective as risperidone against positive and negative symptoms in patients with schizophrenia . Both antipsychotic agents were equally well-tolerated", "The purported advantages of second-generation or ‘ atypical ’ antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia . This flexible-dose study examined efficacy and safety in a r and omized , double-blind , 52-week trial , comparing chlorpromazine ( CPZ ) and clozapine ( CLZ ) in treatment naive patients experiencing their first episode of schizophrenia . In all , 160 in patients with first-episode schizophrenia or schizophreniform disorder were r and omized to CPZ or CLZ and followed them for 52 weeks or until dropout . The primary efficacy measure was time to first remission and proportion of time remaining in remission . The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects . Of these first-episode patients , 80 % achieved remission within 1 year ( 79 % CPZ , 81 % CLZ ) . The Kaplan – Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ ( χ2(1)=5.56 , p=0.02 ) . Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group . At 12 weeks , CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any . These symptom differences remained significant when controlling for EPS differences . By 52 weeks many of the symptom differences between groups were no longer significantly different . Generally , CLZ produced fewer side effects than CPZ , particularly extrapyramidal side effects . There was no significant difference between treatments in weight change or glucose metabolism . For each prior year of untreated psychosis , there was a 15 % decrease in the odds of achieving remission ( OR=0.85 ; CI 0.75–0.95 ) . A high proportion of first-episode patients remitted within 1 year . We detected no difference in the proportion of first-episode patients receiving CLZ or CPZ that achieved remission . However , first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ . While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks , the two treatment groups seemed to converge by 1 year . Longer duration of untreated psychosis was associated with lower odds of achieving remission ", "BACKGROUND The safety and efficacy of the first long-acting injectable atypical antipsychotic , risperidone , were assessed in stable patients with schizophrenia switched from oral antipsychotic medications . METHOD Data were collected between July 1 , 2001 , and October 25 , 2002 . The study population included patients from clinics , hospitals , and physicians ' offices . After a 4-week run-in period , symptomatically stable patients with schizophrenia ( DSM-IV ) who had been taking haloperidol ( N = 46 ) , quetiapine ( N = 45 ) , or olanzapine ( N = 50 ) received 25 mg of long-acting risperidone . The oral antipsychotics were continued for 3 weeks after the first injection of long-acting risperidone . Injections were administered every 2 weeks at 25 mg up to a maximum dose of 50 mg for 12 weeks in this multicenter , open-label study . RESULTS Long-acting risperidone was well tolerated . Of the 141 patients who participated in the study , the most frequently reported adverse events were insomnia ( 16 % ) , headache ( 15 % ) , psychosis ( 11 % ) , and agitation ( 11 % ) . The mean increase in body weight was 0.4 kg . No other clinical ly relevant laboratory abnormalities or significant electrocardiogram changes were observed during the 12-week treatment . Extrapyramidal Symptom Rating Scale total scores were reduced during treatment with long-acting risperidone . Improvements in symptoms of schizophrenia were observed with long-acting risperidone at week 4 and continued through the 12-week treatment with significant reductions in total Positive and Negative Syndrome Scale ( PANSS ) scores at week 8 ( -2.5 , p or = 20 % decrease in PANSS total scores ) . CONCLUSIONS Switching treatment from oral antipsychotics to long-acting risperidone without an intervening period of oral risperidone was safe and well tolerated . Long-acting risperidone also significantly reduced the severity of symptoms in these stable patients with schizophrenia", "Objective : Patients with major depression discontinue taking their antidepressants for many reasons . Although side effects are often cited as the reason for discontinuation , few prospect i ve studies have addressed this question , and none has specifically examined discontinuation in patients with severe depression . Method : In patients and out patients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission . Three months later , patients were contacted and interviewed to determine antidepressant usage and the side effects experienced , including when these were experienced and their severity . Results : Between October 2001 and April 2003 , 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up . One in 4 patients discontinued the index antidepressant . Among specific side effects noted , only \" change in weight \" and \" anxiety \" were significant predictors of discontinuation after controlling for confounders . Experiencing 1 or more \" extremely \" bothersome side effects was associated with more than a doubling of the risk of discontinuation , but the presence of side effects and side effects less severe than \" extremely \" bothersome were not significant predictors . There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates . Conclusion : The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested . Disparate findings from earlier studies may reflect aspects of study design , such as examining population s whose severity of depression varied widely or not controlling for important confounding factors . Future research should separately examine high-risk groups ( or control for severity of depression ) and carefully rule out other potential contributors to discontinuation", "OBJECTIVE This 52-week r and omized , double-blind , flexible-dose , multicenter study evaluated the overall effectiveness ( as measured by treatment discontinuation rates ) of olanzapine , quetiapine , and risperidone in patients early in the course of psychotic illness . METHOD Patients were r and omly assigned to treatment with olanzapine ( 2.5 - 20 mg/day ) , quetiapine ( 100 - 800 mg/day ) , or risperidone ( 0.5 - 4 mg/day ) administered in twice-daily doses . Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks ( primary outcome measure ) based on a prespecified noninferiority margin of 20 % . RESULTS A total of 400 patients were r and omly assigned to treatment with olanzapine ( N=133 ) , quetiapine ( N=134 ) , or risperidone ( N=133 ) . The mean modal prescribed daily doses were 11.7 mg for olanzapine , 506 mg for quetiapine , and 2.4 mg for risperidone . At week 52 , all-cause treatment discontinuation rates were 68.4 % , 70.9 % , and 71.4 % for olanzapine , quetiapine , and risperidone , respectively . Reductions in total score on the Positive and Negative Syndrome Scale ( PANSS ) were similar for the three treatment groups , but reductions in PANSS positive subscale scores were greater in the olanzapine group ( at 12 weeks and at 52 weeks or withdrawal from study ) and the risperidone group ( at 12 weeks ) . The most common elicited adverse events for olanzapine were drowsiness ( 53 % ) , weight gain ( 51 % ) , and insomnia ( 38 % ) ; for quetiapine , drowsiness ( 58 % ) , increased sleep hours ( 42 % ) , and weight gain ( 40 % ) ; and for risperidone , drowsiness ( 50 % ) , menstrual irregularities in women ( 47 % ) , and weight gain ( 41 % ) . CONCLUSIONS Olanzapine , quetiapine , and risperidone demonstrated comparable effectiveness in early-psychosis patients , as indicated by similar rates of all-cause treatment discontinuation", "Abstract : This was a r and omized double-blind placebo-controlled multicenter study to assess the efficacy , safety , and tolerability of fluvoxamine in a controlled release ( CR ) formulation for treatment of generalized social anxiety disorder ( GSAD ) . A total of 300 subjects with GSAD were r and omly assigned to receive either fluvoxamine CR ( N = 149 ) or placebo ( N = 151 ) for 12 weeks . Mean changes from baseline to end point in Liebowitz Social Anxiety Scale ( LSAS ) , Clinical Global Impression Severity of Illness Scale ( CGI-S ) , Sheehan Disability Scale ( SDS ) , as well as the mean end point scores in Clinical Global Impression Improvement Scale ( CGI-I ) and Patient Global Impression of Improvement Scale ( PGI ) were compared between the fluvoxamine CR and placebo treatment groups . Arizona Sexual Experience Scale ( ASEX ) , adverse event , and other safety parameters were also assessed . The results demonstrated that fluvoxamine CR was significantly superior to placebo in decreasing LSAS total score ( primary measure ) starting at week 4 . At end point , there was a mean change from baseline of −36.1 ± 2.7 ( 37 % reduction ) in the LSAS total score in the fluvoxamine CR group compared with −27.3 ± 2.4 ( 28 % reduction ) in the placebo group ( P = 0.020 for mean change ) . Fluvoxamine CR was also significantly superior to placebo in SDS , CGI-S , CGI-I at end point ( secondary measures ) . When compared with placebo , fluvoxamine CR did not cause any significant weight gain or clinical ly significant sexual dysfunction as measured by ASEX . In summary , fluvoxamine CR is an efficacious , safe , and well-tolerated treatment of generalized social anxiety disorder", "Clozapine has been the gold st and ard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities . This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia . The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication . This 18-week , r and omized , double-blind , parallel study compared treatment with either olanzapine ( 5 - 25 mg/day , n=75 ) or clozapine ( 100 - 500 mg/day , n=72 ) in patients with schizophrenia who were nonresponsive to , or intolerant of , st and ard acceptable antipsychotic therapy . At the 18-week endpoint , no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used : Positive and Negative Syndrome Scale ( PANSS ) total , positive , negative , or general psychopathology or Clinical Global Impression severity ( CGI-S ) . Response rates based on the criteria of Kane et al. [ Arch . Gen. Psychiatry 45 ( 1988 ) 789 ] were also not significantly different between olanzapine-treated ( 57.9 % ) and clozapine-treated patients ( 60.8 % ) . There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography , and no clinical ly and statistically significant changes were seen in vital signs or laboratory measures in either group . Both treatments were well tolerated . Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy ( treatment resistance ) or intolerable side effects ( treatment intolerance ) . Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia", "Background and objective Oxcarbazepine , an antiepileptic and a derivative of carbamazepine , has been shown to have clinical utility as an antimanic agent . This study sought to assess the efficacy and tolerability of oxcarbazepine compared with divalproex sodium in the treatment of patients with mania . Patients and methods 57 patients from a large clinical practice who had recently begun treatment with divalproex sodium were r and omly assigned to one of two treatment groups . In this open-label , single (rater)-blind study , group 1 remained on treatment with divalproex sodium and group 2 was switched to oxcarbazepine . Both treatment groups were followed for 10 weeks after the switch . Pharmacotherapeutic efficacy was compared using the Clinician Administered Rating Scale for Mania ( CARS-M ) . Weight and adverse events were monitored throughout the study . Results 83 % of patients using oxcarbazepine showed a decrease in mania as assessed using the CARS-M , and 70 % showed a net decrease in weight over the 10-week course of the study . For the divalproex sodium group , 53 % showed a decrease in mania , as assessed by CARS-M , and 37 % lost weight . Conclusion Oxcarbazepine showed comparable efficacy to divalproex sodium , yet appeared to do so with an equal or more benign side-effect profile , particularly with regard to weight . These results suggest that oxcarbazepine , which has been used in Europe for the treatment of mood disorders for some time ( albeit used off-label for this purpose ) may show promise for use in the US as an agent for maintenance of non-acute mania", "BACKGROUND Weight change and the weight-related health factors of nonfasting serum glucose , serum cholesterol , and diastolic blood pressure levels were analyzed in patients with DSM-III-R schizophrenia and related disorders who received treatment with olanzapine for up to 3 years , and comparisons were made to patients treated with haloperidol . Baseline body mass index ( B BMI ; kg/m2 ) and dose ( mg/day ) were investigated as predictors of long-term weight change experienced during olanzapine treatment . METHOD This analysis retrospectively examined 573 patients receiving olanzapine and 103 patients receiving haloperidol for 39 weeks or more from a study of 1,996 patients r and omly assigned 2:1 to either olanzapine , 5 to 20 mg/day , or haloperidol , 5 to 20 mg/day . After 6 weeks of acute therapy , patients continued for 1 year or more with either double-blind or open-label olanzapine therapy or double-blind haloperidol therapy . RESULTS Mean weight gain for olanzapine-treated patients observed for a median of 2.54 years trended toward a plateau after the first 39 weeks of treatment with a last-observation-carried-forward mean weight change of 6.26 kg ( 13.8 lb ) and a median of 5.90 kg ( 13.0 lb ) . This was significantly higher than that for haloperidol-treated patients , whose mean weight gain was 0.69 kg ( 1.5 lb ) after 1.15 years ( p B BMI ( > 27.6 ) gained significantly less weight during treatment with olanzapine than their lighter counterparts ( B BMI effect of olanzapine dose on weight was not significant ( p > or = . 183 ) . Median serum glucose at endpoint was not significantly associated ( p = .096 ) with weight change for olanzapine . Median serum cholesterol and diastolic blood pressure for olanzapine-treated patients at endpoint showed a relationship with weight change that was statistically ( p elevated serum glucose , cholesterol , or diastolic blood pressure between olanzapine and haloperidol therapy groups was not different ( p > .05 ) . CONCLUSION Mean weight gain during olanzapine treatment trended toward a plateau after the initial 39 weeks of treatment with no further significant gain out to 3 years . Higher B BMI was predictive of a lower long-term weight gain , while dose was not a significant predictor of greater longer term weight change . The relationship between weight change and glucose was not statistically significant . The association between weight change and changes in cholesterol as well as changes in diastolic blood pressure was statistically significant but not considered clinical ly relevant based on the ranges observed", "Antidepressant drugs are frequently prescribed for women and have various side effects , including potential effects on body weight . This experiment examined the effects of information about the weight-related side effects of antidepressants on women 's attitudes toward the drugs . 60 college women were r and omly assigned to read about one of two drugs , fluoxetine ( Prozac ) or Imipramine ( Tofranil ) . Participants were either told or not told about veridical weight-related side effects , namely , weight loss for Prozac and weight gain for Tofranil . As hypothesized , weight-gain information lowered the personal acceptability of Tofranil , and weight-loss information enhanced the acceptability of Prozac . Although research with clinical population s is required , undergraduate women 's decisions about the use of antidepressant medications may be influenced by societal body-image ideals", "Objective : Treatment with second generation antipsychotics ( SGAs ) can increase the risk of patients with schizophrenia developing obesity , hyperlipidaemia and diabetes . Routine monitoring is recommended , but clinical practice suggests monitoring is not conducted at a rate necessary for these comorbidities . The aim was to audit what proportion of patients were having their weight , height , girth , body mass index , lipids and blood sugar levels monitored and recorded . Method : An audit of patients with schizophrenia , discharged from three psychiatric wards , was conducted . Two data sheets were recorded for every patient and inter-rater reliability was calculated . Data were then entered into SPSS and statistical significance calculated . Results : The sample consisted of 93 patients ; SGAs were taken by 31 % of admitted and 88 % of discharged patients . Of these , 65 % had their weight recorded , 61 % height , 31 % r and om blood sugar levels , 3 % postpr and ial blood sugar levels , 2 % glycosylated haemoglobin , and 7.5 % cholesterol and triglycerides . Girth and BMI were not recorded . Abnormalities were detected in 29 % of recorded BSL and 2 % of recorded cholesterol . Conclusions : Patients with schizophrenia on antipsychotics have an alarmingly low rate of monitoring of these common adverse effects and comorbidities . Clinicians need to be aware of this , so that they can improve their practice", "In a double‐blind multicentre trial in general practice , 144 patients with primary anxiety received daily treatment with mianserin or chlordiazepoxide , 30‐60 mg , or placebo . There were no statistically significant differences in efficacy between the three treatments in the 106 patients who completed the 6‐week trial . However , there was a substantial trend in favour of mianserin ( P= 0.1 ) , but not chlordiazepoxide , over placebo as assessed by the difference in overall improvement on the Hamilton Anxiety Scale . This trend may be clinical ly significant since more patients dropped out from the placebo group because of lack of effect or deterioration than did from the active treatment groups , particularly during the latter part of the trial", "A prospect i ve study of schizophrenic patients prescribed injectable depot neuroleptic drugs as maintenance therapy showed a clinical ly significant weight gain in 55 % of patients . No significant difference was shown between flupenthixol decanoate and fluphenazine decanoate , nor was a clinical ly meaningful relationship shown with dose , or the use of anti‐parkinsonian drugs . The weight gain continued for at least 2 years following a mental state relapse . It is suggested that the monitoring of weight and giving of appropriate advice on diet are two essentials in maintenance therapy of chronic schizophrenia", "OBJECTIVE To examine the impact of medication nonadherence on treatment outcome in schizophrenia and potential risk factors for nonadherence . METHOD A post hoc analysis of a r and omized , double-blind , 8-week , fixed-dose study comparing olanzapine 10 , 20 , and 40 mg/day for patients with schizophrenia or schizoaffective disorder ( DSM-IV criteria ) with suboptimal response to current treatment ( N = 599 ) was conducted between September 12 , 2003 , and November 3 , 2005 , at 55 study centers in the United States . Nonadherence was defined as not taking medication as prescribed based on daily pill counts . Because there was no significant difference in nonadherence between dose groups , effects of nonadherence on efficacy and safety outcomes were examined using all 3 groups combined . Baseline demographics and symptom severity were investigated as potential risk factors for nonadherence . RESULTS During the 8-week study , 34.5 % of patients were nonadherent at least once . Nonadherent patients had significantly less improvement compared to adherent patients as measured by change in Positive and Negative Syndrome Scale total score ( -22.57 vs. -26.84 , p = .002 ) . Longer duration of nonadherence was associated with reduced likelihood of treatment response ( odds ratio = 0.94 , 95 % CI = 0.90 to 0.99 , p = .008 ) . The early treatment discontinuation rate was higher in nonadherent compared to adherent patients ( 40.8 % vs. 24.5 % , p measures , except for weight change , for which adherent patients had greater weight gain than nonadherent patients ( 2.63 kg vs. 1.96 kg , p = .02 ) . Greater depression severity at baseline ( p = .01 ) and greater hostility level during the study were significant risk factors for nonadherence ( p = .02 ) . CONCLUSIONS Medication nonadherence had a significantly negative impact on treatment response , highlighting the importance of adherence to achieve satisfactory treatment outcome . Findings may also help clinicians identify patients at risk for nonadherence and utilize interventions to improve adherence . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00100776", "OBJECTIVE This study assessed weight changes in a large cohort of patients with bipolar disorder who were treated with r and omly assigned maintenance monotherapies . METHOD A post hoc analysis was conducted to assess the effects of lamotrigine , lithium , and placebo administration on body weight in obese and nonobese patients with bipolar disorder from two double-blind , placebo-controlled , 18-month studies . RESULTS Mean changes in weight among obese patients ( N=155 ) at week 52 were -4.2 , + 6.1 , and -0.6 kg with lamotrigine , lithium , and placebo , respectively ( lamotrigine versus lithium and lithium versus placebo ) . Among nonobese patients ( N=399 ) , mean changes in weight ( kg ) at week 52 were -0.5 , + 1.1 , and + 0.7 with lamotrigine , lithium , and placebo , respectively , with no significant differences among groups . CONCLUSIONS Obese patients with bipolar I disorder lost weight while taking lamotrigine and gained weight while taking lithium", "AIMS To date there have been no reports of long-term efficacy of aripiprazole in Asian population s. The aim of the present study was therefore to investigate the long-term efficacy , safety and tolerability of aripiprazole in a large number of patients with schizophrenia , schizophreniform disorder , or schizoaffective disorder in Korea . METHODS This study was a prospect i ve , multicenter , single-group , 26-week open study of patients with schizophrenia , schizophreniform disorder , or schizoaffective disorder . A total of 300 Korean patients participated in the study . The primary efficacy measure was the Positive and Negative Syndrome Scale ( PANSS ) total score , and secondary efficacy measures included the PANSS positive and negative subscales , Clinical Global Impression-Severity of Illness ( CGI-S ) . Tolerability and safety were assessed by monitoring the frequency and severity of treatment-emergent adverse events , extrapyramidal symptoms ( EPS ) , vital signs , weight , and laboratory tests . RESULTS Aripiprazole produced rapid and significant improvements on all efficacy measures . As evidence d by PANSS total score , PANSS positive subscales and the CGI-S scores , first-episode drug-naive patients demonstrated significantly greater efficacy relative to patients who had previously experienced one or more episodes of relapse . Aripiprazole was associated with significant decrease of serum prolactin level . The subjects showed mild weight gain . CONCLUSION Aripiprazole is an effective antipsychotic in the long-term treatment of both positive and negative symptoms . This study extends the findings of previous long-term studies , and has found that there is no significant difference with regard to ethnicity in response to aripiprazole", "OBJECTIVES To examine baseline testing and ongoing monitoring of cardiovascular and other risk factors in individuals prescribed atypical antipsychotic medications . METHODS We derived a list of baseline and ongoing monitoring tests from the literature ( Weight , BMI , blood pressure , U&E , LFTs , glucose , HbA1C , FBC , TFTs , prolactin , lipids & ECG ) and then review ed a r and om sample of 80 records of patients prescribed atypical antipsychotics and currently attending an Irish public catchment area service , for evidence of testing . RESULTS Levels of testing for baseline tests ranged from 45 % for blood pressure to 0 % for BMI . Levels of ongoing monitoring tests ranged from 42.5 % for U&E to 0 % for BMI . Patients admitted to hospital were much more likely to have had testing . CONCLUSIONS The need for baseline and ongoing monitoring of certain tests in patients prescribed atypical antipsychotics is increasingly accepted . Levels of such testing are currently quite low and need to increase" ]

[ "BACKGROUND Although patients with chronic kidney disease ( CKD ) are at increased risk of cardiovascular disease ( CVD ) , the roles of lipid-modifying therapies in decreasing CVD risk are unclear . Our aim is to compare the effects of statin and fibrate therapy on arterial function as a risk marker of CVD . STUDY DESIGN Double-blind , r and omized , placebo-controlled , parallel-group study . SETTING & PARTICIPANTS Ambulatory patients with stages 3 to 5 CKD . INTERVENTION 6 weeks of atorvastatin , 40 mg/d , or gemfibrozil , 600 mg twice daily , with placebo . OUTCOMES & MEASUREMENTS Primary outcome was arterial function assessed by means of endothelial-dependent flow-mediated dilatation ( FMD ) and small-artery compliance ( C2 ) . Secondary outcomes included endothelial-independent glyceryl trinitrate-mediated dilatation ( GTNMD ) , large-artery compliance ( C1 ) , and levels of lipids , lipoproteins , and oxidized low-density lipoprotein , as well as markers of insulin resistance and inflammation . RESULTS Compared with placebo , atorvastatin significantly decreased low-density lipoprotein ( -52 % ) , triglyceride ( -30 % ) , and oxidized low-density lipoprotein levels ( -41 % ; P Gemfibrozil significantly decreased triglyceride levels ( -40 % ) and increased high-density lipoprotein levels ( + 20 % ; P atorvastatin nor gemfibrozil had a significant effect on markers of insulin resistance or inflammation . There was no significant change in FMD , GTNMD , or C1 with either atorvastatin or gemfibrozil . There was improvement in C2 with atorvastatin ( + 1.1 mL/mm Hg x 100 ) compared with placebo ( P = 0.024 ) , but not with gemfibrozil compared with placebo . LIMITATIONS Small sample size leading to inadequate power , short duration of therapy , and use of a heterogeneous group of patients with CKD and dialysis patients . CONCLUSION In patients with advanced CKD , atorvastatin is associated with improvement in dyslipidemia and small-artery stiffness , but not endothelial function . Gemfibrozil improves dyslipidemia , but has no effect on arterial function", "This study aim ed to compare the effects of ω-3 fatty acids and fibrate treatment on plasma levels and activities of hemostatic risk factors on glucose and lipid metabolism in subjects with isolated hypertriglyceridemia . Seventy-three subjects with elevated triglyceride levels were allocated into one of the following treatment options : bezafibrate ( 200 mg twice daily ) , ω-3 fatty acids ( 1 g twice daily ) or placebo . Plasma lipids , glucose homeostasis markers ( fasting and 2-h post-glucose load plasma glucose levels and HOMA ) , as well as plasma levels/activities of fibrinogen , factor VII and PAI-1 were determined at baseline , on the day of r and omization , and after 4 and 12 weeks of the treatment . Not only did bezafibrate improve plasma lipids , but it also increased glucose sensitivity and tended to reduce post-glucose loads of plasma glucose . Except for the reduction in plasma triglycerides , ω-3 fatty acids produced no effect on the lipid profile and insulin sensitivity . Both treatment options reduced , to similar extents , plasma levels of fibrinogen and PAI-1 and factor VII coagulant activity . Our study indicates that , although fibrates exhibit more-pronounced metabolic effects than do ω-3 fatty acids , both these treatment options are equipotent in producing a complex beneficial effect on hemostasis in isolated hypertriglyceridemic subjects", "Purpose The aim of this study was to compare the effects of fibrates and omega-3 fatty acids on lymphocyte secretory function and systemic inflammation in patients with isolated hypertriglyceridemia . Methods The study included 107 patients with isolated hypertriglyceridemia who received bezafibrate ( 200 mg twice daily ) , omega-3 fatty acids ( 1 g twice daily ) or placebo for 12 weeks . The lipid profile , fasting and 2-h post-glucose load plasma glucose levels , homeostasis model assessment index ( HOMA ) , plasma high-sensitivity C-reactive protein ( hsCRP ) levels and lymphocyte release of interleukin-2 , interferon-γ and tumor necrosis factor-α were assessed at baseline , on the day of r and omization , and after 4 and 12 weeks of treatment . Results Both bezafibrate and omega-3 fatty acids reduced plasma triglyceride levels . Bezafibrate additionally decreased total and low-density lipoprotein-cholesterol levels and the HOMA and insignificantly decreased post-glucose load plasma glucose , as well as increased high-density lipoprotein-cholesterol . Bezafibrate treatment was associated with a reduction in lymphocyte release of interleukin-2 , interferon-γ and tumor necrosis factor-α , which was accompanied by a reduction in plasma hsCRP levels . Omega-3 fatty acid did not significantly reduce lymphocyte cytokine release and plasma hsCRP . The anti-inflammatory effects of both drugs did not correlate with their action on plasma lipids , but in the case of the former the effect was related to the improvement in insulin sensitivity . Conclusion Our results indicate that bezafibrate is superior to omega-3 fatty acid in inhibiting systemic inflammation and lymphocyte secretory function ", "BACKGROUND Exaggerated postpr and ial lipemia ( PPL ) is a factor in atherogenesis , involving endothelial dysfunction and enhanced oxidative stress . We examined the effect of ciprofibrate therapy on these parameters in type 2 diabetes mellitus . METHODS AND RESULTS Twenty patients entered a 3-month , double-blind , placebo-controlled study . Each subject was studied fasting and after a fatty meal , at baseline , and after 3 months of treatment . Glucose and lipid profiles were measured over an 8-hour postpr and ial period . Endothelial function ( flow-mediated endothelium-dependent vasodilatation [ FMD ] ) and oxidative stress ( electron paramagnetic resonance spectroscopy ) were measured after fasting and 4 hours postpr and ially . At baseline , both groups exhibited similar PPL and deterioration in endothelial function . After ciprofibrate , fasting and postpr and ial FMD values were significantly higher ( from 3.8+/-1 . 8 % and 1.8+/-1.3 % to 4.8+/-1.1 % and 3.4+/-1.1 % ; P fasting and postpr and ial triglycerides ( 3 . 1+/-2.1 and 6.6+/-4.1 mmol/L to 1.5+/-0.8 and 2.8+/-1.3 mmol/L , P Fasting and postpr and ial HDL cholesterol was also elevated ( 0 . 9+/-0.1 and 0.8+/-0.1 mmol/L and 1.2+/-0.2 and 1.2+/-0.1 mmol/L , P total or LDL cholesterol . Fasting and postpr and ial triglyceride enrichment of all lipoproteins was attenuated , with cholesterol depletion of VLDL and enrichment of HDL . There were similar postpr and ial increases in oxidative stress in both groups at baseline , which was significantly attenuated by ciprofibrate ( 0.3+/-0.6 versus 1.5+/-1.1 U , P fibrate therapy improves fasting and postpr and ial endothelial function in type 2 diabetes . Attenuation of PPL and the associated oxidative stress , with increased HDL cholesterol levels , may be important", "BACKGROUND Diabetes mellitus , impaired fasting glucose level , or insulin resistance are associated with increased risk of cardiovascular disease . OBJECTIVES To determine the efficacy of gemfibrozil in subjects with varying levels of glucose tolerance or hyperinsulinemia and to examine the association between diabetes status and glucose and insulin levels and risk of cardiovascular outcomes . METHODS Subgroup analyses from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial , a r and omized controlled trial that enrolled 2531 men with coronary heart disease ( CHD ) , a high-density lipoprotein cholesterol level of 40 mg/dL or less ( . Subjects received either gemfibrozil ( 1200 mg/d ) or matching placebo and were followed up for an average of 5.1 years . In this article , we report the composite end point ( CHD death , stroke , or myocardial infa rct ion ) . RESULTS Compared with those with a normal fasting glucose level , risk was increased in subjects with known diabetes ( hazard ratio [ HR ] , 1.87 ; 95 % confidence interval [ CI ] , 1.44 - 2.43 ; P = .001 ) and those with newly diagnosed diabetes ( HR , 1.72 ; 95 % CI , 1.10 - 2.68 ; P = .02 ) . In persons without diabetes , a fasting plasma insulin level of 39 micro U/mL or greater ( > /=271 pmol/L ) was associated with a 31 % increased risk of events ( P = .03 ) . Gemfibrozil was effective in persons with diabetes ( risk reduction for composite end point , 32 % ; P = .004 ) . The reduction in CHD death was 41 % ( HR , 0.59 ; 95 % CI , 0.39 - 0.91 ; P = .02 ) . Among individuals without diabetes , gemfibrozil was most efficacious for those in the highest fasting plasma insulin level quartile ( risk reduction , 35 % ; P = .04 ) . CONCLUSION In men with CHD and a low high-density lipoprotein cholesterol level , gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level", "CONTEXT Nonalcoholic fatty liver disease is associated with risk factors for cardiovascular disease , particularly increased plasma triglyceride ( TG ) concentrations and insulin resistance . Fenofibrate and extended release nicotinic acid ( Niaspan ) are used to treat hypertriglyceridemia and can affect fatty acid oxidation and plasma free fatty acid concentrations , which influence intrahepatic triglyceride ( IHTG ) content and metabolic function . OBJECTIVE The objective of the study was to determine the effects of fenofibrate and nicotinic acid therapy on IHTG content and cardiovascular risk factors . EXPERIMENTAL DESIGN AND MAIN OUTCOME MEASURES : We conducted a r and omized , controlled trial to determine the effects of fenofibrate ( 8 wk , 200 mg/d ) , Niaspan ( 16 wk , 2000 mg/d ) , or placebo ( 8 wk ) on IHTG content , very low-density lipoprotein ( VLDL ) kinetics , and insulin sensitivity . SETTING AND PARTICIPANTS Twenty-seven obese subjects with nonalcoholic fatty liver disease ( body mass index 36 + /- 1 kg/m(2 ) , IHTG 23 + /- 2 % ) were studied at Washington University . RESULTS Neither fenofibrate nor Niaspan affected IHTG content , but both decreased plasma TG , VLDL-TG , and VLDL-apolipoprotein B concentrations ( P VLDL-TG clearance from plasma ( 33 to 54 ml/min ; P VLDL-TG secretion . Niaspan decreased VLDL-TG secretion ( 27 to 15 micromol/min ; P clearance . Both fenofibrate and Niaspan decreased VLDL-apolipoprotein B secretion ( 1.6 to 1.2 and 1.3 to 0.9 nmol/min , respectively ; P Niaspan reduced hepatic , adipose tissue , and muscle insulin sensitivity ( P insulin action . CONCLUSIONS Fenofibrate and Niaspan decrease plasma VLDL-TG concentration without altering IHTG content . However , the mechanism responsible for the change in VLDL-TG concentration is different for each drug ; fenofibrate increases plasma VLDL-TG clearance , whereas nicotinic acid decreases VLDL-TG secretion", "Abstract Objective : To investigate the effect of fenofibrate on sleep apnoea indices . Methods : Proof-of-concept study comprising a placebo run-in period ( 1 week , 5 weeks if fibrate washout was required ) and a 4-week r and omized , double-blind treatment period . Thirty-four subjects ( mean age 55 years , body mass index 34 kg/m2 , fasting triglycerides 3.5 mmol/L ) with diagnosed sleep apnoea syndrome not treated with continuous positive airways pressure were enrolled and r and omized to once daily treatment with fenofibrate ( 145 mg NanoCrystal ® tablet ) or placebo . Overnight polysomnography , computerized attention/vigilance tests and blood sampling for measurement of lipids , insulin , fasting plasma glucose and fibrinogen were performed at the end of each study period . Clinical trial registration : NCT00816829 . Main outcome measures : As this was an exploratory study , a range of sleep variables were evaluated . The apnoea/hypopnoea index ( AHI ) and percentage of time spent with arterial oxygen saturation ( SpO2 ) included total apnoeas , hypopnoeas and oxygen desaturations , and non-cortical micro-awakenings related to respiratory events per hour . Results : Fenofibrate treatment significantly reduced the percentage of time with SpO2 % ( from 9.0 % to 3.5 % vs. 10.0 % to 11.5 % with placebo , p = 0.007 ) , although there was no significant change in the AHI ( reduction vs. control 14 % ( 95%CI −47 to 40 % , p = 0.533 ) . Treatment reduced obstructive apnoeas ( by 44 % , from 18.5 at baseline to 15.0 at end of treatment vs. 29.0 to 30.5 on placebo , p = 0.048 ) , and non-cortical micro-awakenings per hour ( from 23.5 to 18.0 vs. 24.0 to 25.0 with placebo , p = 0.004 ) . Other sleep variables were not significantly influenced by fenofibrate . Key limitations : Exploratory study in patients with mild to moderate sleep apnoea , limited treatment duration ; concomitant hypnotic treatment ( 35 % ) ; lack of correction for multiplicity of testing . Conclusions : The consistent direction of change in sleep indices in this proof-of-concept study may support further investigation of fenofibrate in moderate to severe sleep apnoea syndrome", "OBJECTIVES We investigated whether the effect of bezafibrate on progression of coronary atherosclerosis in the BEzafibrate Coronary Atherosclerosis Intervention Trial ( BECAIT ) was related to insulin-like growth factor (IGF)-I and glucose-insulin homeostasis . BACKGROUND BECAIT , the first double-blind , placebo-controlled , r and omized , serial angiographic trial of a fibrate compound , demonstrated that progression of focal coronary atherosclerosis in young patients after infa rct ion could be retarded by bezafibrate treatment . METHODS The treatment effects on serum concentrations of IGF-I and insulin-like growth factor binding protein (IGFBP)-1 , as well as on basal and postload glucose and insulin levels , were examined , and on-trial determinations were related to the angiographic outcome measurements . RESULTS Bezafibrate treatment result ed in a significant reduction of serum IGF-I levels , both at two and five years , and on-trial serum IGF-I levels were directly related to changes in both minimal lumen diameter ( r = 0.25 , p mean segment diameter ( r = 0.29 , p ( homeostasis model assessment estimate , basal and postload plasma insulin concentrations and serum IGFBP-1 levels ) were related to the angiographic changes , nor were they significantly affected by bezafibrate treatment . Multiple stepwise regression analysis showed that the relation between on-trial serum IGF-I level and coronary artery disease ( CAD ) progression was independent of baseline angiographic score , age , body mass index , serum lipoprotein and plasma fibrinogen concentrations and measures of glucose-insulin homeostasis . CONCLUSIONS IGF-I could be implicated in the progression of premature CAD , and a reduction of serum IGF-I concentration could account partly for the effect of bezafibrate on progression of focal coronary atherosclerosis", "This study was initiated to 1 ) assess gemfibrozil 's ability to lower plasma triglyceride ( TG ) concentration in patients with NIDDM , and 2 ) determine whether this effect was associated with any changes in glycemic control . Measurements were made of mean hourly plasma glucose , insulin , TG , and FFA concentrations from 1200 - 1600 h in response to a test meal ; hepatic glucose production ( HGP ) ; insulin-stimulated glucose uptake during a hyperinsulinemic glucose clamp study ( MCR ) ; and fasting plasma lipoprotein TG and cholesterol concentrations in 12 patients with NIDDM before and 3 months after gemfibrozil treatment . Although ambient plasma TG and FFA concentrations fell significantly , plasma glucose , insulin , HGP , concentrations fell significantly , plasma glucose , insulin , HGP , and glucose MCR did not change . However , when patients were divided into two groups , those with fasting plasma glucose levels above 9 mmol/L ( fair control ) and those with levels below 9 mmol/L ( good control ) , a different phenomenon was observed . Patients in fair control had significant decreases in mean hourly plasma concentrations of glucose ( 15.1 + /- 1.7 to 12.6 + /- 0.9 mmol/L ; P less than 0.001 ) , insulin ( 523 + /- 59 to 471 + /- 75 pmol/L ; P less than 0.001 ) , FFA ( 652 + /- 150 to 504 + /- 76 mumol/L ) , and HGP ( 9.5 0.4 to 8.1 + /- 0.4 mumol/kg.min ; P less than 0.005 ) , and an increase in glucose MCR ( 2.63 + /- 0.49 to 3.72 + /- 0.54 mL/kg.min ; P less than 0.07 ) in association with a fall in TG from 6.9 + /- 1.3 to 3.5 + /- 0.9 mmol/L ( P less than 0.001 ) . Although fasting low density lipoprotein cholesterol increased ( 1.8 + /- 0.2 to 2.7 + /- 0.2 mmol/L ; P less than 0.05 ) , the ratio of total to high density lipoprotein cholesterol decreased ( 6.84 + /- 0.88 to 5.80 + /- 1.05 ; P less than 0.02 ) . Despite a significant fall in mean hourly TG concentration ( 4.6 + /- 0.7 to 3.8 + /- 0.7 mmol/L ; P less than 0.001 ) , neither insulin , FFA , HGP , nor glucose MCR changed in patients in good control . Furthermore , the mean hourly plasma glucose concentration increased from 9.2 + /- 0.7 to 11.7 + /- 1.4 mmol/L ( P less than 0.001 ) . Low density lipoprotein cholesterol also increased in this group ( 1.9 + /- 0.2 to 2.7 + /- 0.2 mmol/L ; P less than 0.02 ) , but , as before , the ratio of total to high density lipoprotein cholesterol decreased ( 8.15 + /- 1.93 to 6.36 + /- 1.03 ; P less than 0.02 )", "Summary Hypertriglyceridaemia and insulin resistance are closely associated but it is unknown whether hypertriglyceridaemia per se contributes to insulin resistance . In the present study we examined whether gemfibrozil , by lowering triglyceride levels , improves the glucoregulatory and antilipolytic action of insulin in Type 2 ( non-insulin-dependent ) diabetes mellitus . Twenty patients were r and omly allocated to receive either placebo or gemfibrozil 1200 mg daily for 12 weeks in a double-blind study . Very low density lipoprotein triglyceride levels decreased in the gemfibrozil group by 42±12 % ( p ) . Gemfibrozil had no effect on the diurnal concentration of non-esterified fatty acids ( NEFA ) . At the r and omization HbA1c levels were comparable ( 7.6±0.3 vs 7.8±0.2 % , NS ) and increased slightly both in the gemfibrozil ( 8.2±0.4 % , p placebo groups ( 8.0±0.3 % , NS ) . Pre- and post-treatment diurnal glucose and insulin concentrations remained unchanged . Basal pre- and post-treatment hepatic glucose production rates were comparable in both groups and similarly suppressed by insulin . Rate of whole body glucose disposal during a low-dose insulin infusion ( serum insulin ∼90 pmol/l ) ( pre- vs post-gemfibrozil 11.9±1.1 vs 11.1±0.7 , pre- vs post-placebo 9.9±1.1 vs 10.8±0.8 μmol·kg−1·min−1 , NS for both ) and a high-dose insulin infusion ( serum insulin ∼500 pmol/l ) ( 16.2 + -1.7 vs 17.7±2.7 , 17.1±4.2 vs 17.4±2.9 μmol·kg−1·min−1 , respectively , NS for both ) remained unchanged . Basal pre- and post-treatment NEFA turnover rates were comparable in both groups and similarly suppressed by insulin . Also rates of total lipid oxidation , plasma NEFA oxidation and non-oxidative NEFA metabolism remained unchanged in both groups . We conclude that gemfibrozil effectively lowers serum triglycerides but has no effect on insulin sensitivity of glucose and NEFA metabolism . The data suggest that hypertriglyceridaemia is a consequence rather than a cause of insulin resistance in Type 2 diabetic patients", "PPAR-alpha agonists improve insulin sensitivity in rodent models of obesity/insulin resistance , but their effects on insulin sensitivity in humans are less clear . We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-alpha agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate . At baseline , body mass index , serum glucose , triglycerides , glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes , while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group ( n=10 ) . No differences were found in serum resistin levels between obese and control group . Fenofibrate treatment decreased serum triglyceride concentrations , while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration . Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment . All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration . We conclude that administration of PPAR-alpha agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus . The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-alpha expression in human liver and muscle", "The aim of our study was to compare the effect of simvastatin and fenofibrate treatment on the secretory function of human monocytes and lymphocytes and on systemic inflammation in type 2 diabetes and to assess whether their coadministration is superior to treatment with only 1 of these drugs . One hundred ninety-six adult patients with recently diagnosed and previously untreated type 2 diabetes and mixed dyslipidemia , complying throughout the study with lifestyle intervention and treated with metformin , were r and omized in a double-blind fashion to receive simvastatin ( 40 mg ) , fenofibrate ( 200 mg ) , simvastatin plus fenofibrate , or placebo for 90 days . Main outcome measurements were monocyte and lymphocyte release of proinflammatory cytokines and plasma levels of C-reactive protein . One hundred ninety patients completed the study . Simvastatin and fenofibrate decreased monocyte release of tumor necrosis factor-α , interleukin-1β , interleukin-6 , and monocyte chemoattractant protein-1 and lymphocyte release of interleukin-2 , interferon-γ , and tumor necrosis factor-α , which was accompanied by a decrease in plasma C-reactive protein levels . Anti-inflammatory effects of fenofibrate partly correlated with the improvement in insulin sensitivity . Lymphocyte-suppressing , but not monocyte-suppressing , effect was stronger if these 2 agents were administered together . In conclusion , simvastatin and fenofibrate exhibit a similar effect on the secretory function of human monocytes and lymphocytes and on systemic inflammation in type 2 diabetic subjects with mixed dyslipidemia . This effect may be clinical ly relevant in the prevention of vascular complications in metformin- and diet-treated subjects with newly diagnosed diabetic dyslipidemia", "Arteriopathy is the principal complication of type 2 diabetes mellitus . It develops from endothelial dysfunction , which we have hypothesised occurs in diabetes primarily as a consequence of dyslipidaemia and oxidative stress . Fenofibrate and CoQ may improve endothelial function by regulating dyslipidaemia and oxidative stress , respectively . We therefore aim ed to assess the independent and combined effects of fenofibrate and coenzyme Q(10 ) ( CoQ ) on endothelium-dependent and endothelium-independent vasodilator function of the forearm microcirculation in type 2 diabetes . Eighty dyslipidaemic type 2 diabetics were r and omized to receive fenofibrate ( 200 mg/daily ) , CoQ ( 200 mg/daily ) , fenofibrate plus CoQ ( 200 + 200 mg daily ) , or placebo for 12 weeks . Forearm microcirculatory function was assessed with venous occlusion plethysmography during the infusion of acetylcholine ( ACh ) , bradykinin ( BK ) , sodium nitroprusside ( SNP ) and N(G)-monomethyl-L-arginine ( L-NMMA ) into the brachial artery . Blood flow responses were calculated as area under the curve ( AUC ) . Fenofibrate significantly lowered plasma cholesterol , triglyceride and fibrinogen ( P elevated HDL-cholesterol and homocysteine ( P CoQ did not change plasma isoprostanes , but significantly lowered systolic blood pressure and HbA(1c ) ( P AUC for ACh , BK and SNP without significantly altering basal responses to L-NMMA . Fenofibrate or CoQ alone did not significantly alter blood flow responses . Improvements in blood flow were independent of changes in plasma lipids , blood pressure , homocysteine and isoprostanes , but were correlated ( P=0.013 ) with HbA(1c ) . In conclusion , in this factorial trial we found that only the combination of fenofibrate and CoQ markedly improved endothelial and non-endothelial forearm vasodilator function in dyslipidemic type 2 diabetic patients . The favourable vascular effect of this therapeutic combination could be due to increase in the bioactivity of and /or responses to endothelium-derived relaxing factors , including nitric oxide , and this may entail synergistic stimulation of peroxisome proliferator-activated receptors", "BACKGROUND Omega-3 fatty acids and fenofibrate are both used to treat patients with hypertriglyceridemia . However , a head-to-head comparison of the lipoprotein and metabolic effects of these two medicines has not been published . METHODS This was a r and omized , single-blind , placebo-controlled , parallel study . Age , sex , and body mass index were matched among groups . All patients were recommended to maintain a low fat diet . Fifty patients in each group were given placebo , omega-3 fatty acids 2 g ( most commonly used dosage in Korean patients ) , or fenofibrate 160 mg , respectively daily for 2 months . RESULTS Omega-3 fatty acids therapy decreased triglycerides by 21 % and triglycerides/HDL cholesterol and improved flow-mediated dilation ( P insulin , plasma adiponectin levels , and insulin sensitivity ( determined by QUICKI ) relative to baseline measurements . Fenofibrate therapy decreased total cholesterol , triglycerides by 29 % , and triglycerides/HDL-cholesterol ( all P flow-mediated dilation when compared with baseline . When compared with placebo and omega-3 fatty acids , fenofibrate therapy decreased non-HDL cholesterol ( P triglycerides/HDL cholesterol ( P=0.016 ) while increasing HDL cholesterol ( P apolipoprotein AI ( P=0.001 ) . Of note , when compared with omega-3 fatty acids , fenofibrate therapy decreased fasting insulin ( P=0.023 ) and increased plasma adiponectin ( P=0.002 ) and insulin sensitivity ( P=0.015 ) . CONCLUSIONS Omega-3 fatty acids and fenofibrate therapy promoted similar changes in triglycerides and endothelium-dependent dilation . However , fenofibrate therapy had substantially better effects on lipoprotein and metabolic profiles in patients with hypertriglyceridemia", "OBJECTIVE To compare the effect of short-term metformin and fenofibrate treatment , administered alone or in sequence , on glucose and lipid metabolism , cardiovascular risk factors , and monocyte cytokine release in type 2 diabetic patients with mixed dyslipidemia . RESEARCH DESIGN AND METHODS We studied 128 type 2 diabetic patients with mixed dyslipidemia complying throughout the study with lifestyle intervention who were r and omized twice , initially to either metformin or placebo , and then to micronized fenofibrate or placebo . RESULTS Fenofibrate alleviated diabetic dyslipidemia – induced changes in plasma high-sensitivity C-reactive protein , fibrinogen , and plasminogen activator inhibitor (PAI)-1 and in monocyte cytokine release , whereas metformin or lifestyle intervention improved mainly glucose and lipid metabolism . The strongest pleiotropic effect was observed when fenofibrate was added to metformin . CONCLUSIONS Fenofibrate , particularly administered together with metformin , is superior to metformin and lifestyle intervention in exhibiting beneficial effects on systemic inflammation , hemostasis , and monocyte secretory function in type 2 diabetic patients with mixed dyslipidemia", "Obesity is a low grade inflammatory state associated with premature cardiovascular morbidity and mortality . Along with traditional risk factors the measurement of endothelial function , insulin resistance , inflammation and arterial stiffness may contribute to the assessment of cardiovascular risk . We conducted a r and omised placebo controlled trial to assess the effects of 12 weeks treatment with a PPAR alpha agonist ( fenofibrate ) and a PPAR gamma agonist ( pioglitazone ) on these parameters in obese glucose tolerant men . Arterial stiffness was measured using augmentation index and pulse wave velocity ( PWV ) . E-selectin , VCAM-1 and ICAM-1 were used as markers of endothelial function . Insulin sensitivity improved with pioglitazone treatment ( p=0.001 ) and , in keeping with this , adiponectin increased by 85.2 % ( p Pro-inflammatory cytokine levels ( TNFalpha , IL-6 and IL-1 beta ) fell with both treatments ( p VCAM-1 and ICAM-1 were reduced with both treatments ( p E-selectin improved with pioglitazone treatment ( p=0.05 ) . Both treatments result ed in a fall in augmentation index . PWV fell by 17.4 % with fenofibrate treatment ( p pioglitazone treatment ( p Pioglitazone and fenofibrate treatment of obese , glucose tolerant men reduces inflammation , improves markers of endothelial function and reduces arterial stiffness . These results suggest that treatment with PPAR agonists has potential to reduce the incidence of premature cardiovascular disease associated with obesity", "The efficacy of fenofibrate ( FEN ) , rosiglitazone ( RSG ) , or a calorie-restricted diet ( CRD ) to reduce cardiovascular disease risk was compared in 37 overweight/obese insulin-resistant nondiabetic subjects . Insulin sensitivity , fasting lipids and lipoproteins , and postpr and ial plasma glucose , insulin , free fatty acid , and triglycerides were measured before and after 3 months of treatment with FEN , RSG , or CRD . Weight decreased in the CRD group , but did not change significantly after treatment with either drug . Insulin sensitivity improved significantly in the CRD- and RSG-treated groups , but to a greater extent in those administered RSG , without a significant difference comparing FEN treatment with the CRD . Total cholesterol was significantly lower after FEN and CRD treatment . Fasting plasma triglycerides decreased significantly in the FEN- and CRD-treated groups , but postpr and ial concentrations decreased in only FEN-treated subjects . Significant decreases in postpr and ial glucose and insulin were seen in only the RSG- and CRD-treated groups . FEN administration improved dyslipidemia in these subjects without changing insulin sensitivity , whereas insulin sensitivity was enhanced in RSG-treated patients without improvement in dyslipidemia . Weight loss in the CRD group led to improvements in both insulin sensitivity and dyslipidemia , but the change in the former was less than in RSG-treated patients , and improvement in lipid metabolism not as great as with FEN . In conclusion , there did not appear to be 1 therapeutic intervention that effectively treated all metabolic abnormalities present in these patients at greatly increased risk of cardiovascular disease", "BACKGROUND Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease , partly owing to dyslipidaemia , which can be amenable to fibrate therapy . We design ed the Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study to assess the effect of fenofibrate on cardiovascular disease events in these patients . METHODS We did a multinational , r and omised controlled trial with 9795 participants aged 50 - 75 years , with type 2 diabetes mellitus , and not taking statin therapy at study entry . After a placebo and a fenofibrate run-in phase , we r and omly assigned patients ( 2131 with previous cardiovascular disease and 7664 without ) with a total-cholesterol concentration of 3.0 - 6.5 mmol/L and a total-cholesterol/HDL-cholesterol ratio of 4.0 or more or plasma triglyceride of 1.0 - 5.0 mmol/L to micronised fenofibrate 200 mg daily ( n=4895 ) or matching placebo ( n=4900 ) . Our primary outcome was coronary events ( coronary heart disease death or non-fatal myocardial infa rct ion ) ; the outcome for prespecified subgroup analyses was total cardiovascular events ( the composite of cardiovascular death , myocardial infa rct ion , stroke , and coronary and carotid revascularisation ) . Analysis was by intention to treat . The study was prospect ively registered ( number IS RCT N 64783481 ) . FINDINGS Vital status was confirmed on all but 22 patients . Averaged over the 5 years ' study duration , similar proportions in each group discontinued study medication ( 10 % placebo vs 11 % fenofibrate ) and more patients allocated placebo ( 17 % ) than fenofibrate ( 8 % ; p coronary event ( relative reduction of 11 % ; hazard ratio [ HR ] 0.89 , 95 % CI 0.75 - 1.05 ; p=0.16 ) . This finding corresponds to a significant 24 % reduction in non-fatal myocardial infa rct ion ( 0.76 , 0.62 - 0.94 ; p=0.010 ) and a non-significant increase in coronary heart disease mortality ( 1.19 , 0.90 - 1.57 ; p=0.22 ) . Total cardiovascular disease events were significantly reduced from 13.9 % to 12.5 % ( 0.89 , 0.80 - 0.99 ; p=0.035 ) . This finding included a 21 % reduction in coronary revascularisation ( 0.79 , 0.68 - 0.93 ; p=0.003 ) . Total mortality was 6.6 % in the placebo group and 7.3 % in the fenofibrate group ( p=0.18 ) . Fenofibrate was associated with less albuminuria progression ( p=0.002 ) , and less retinopathy needing laser treatment ( 5.2%vs 3.6 % , p=0.0003 ) . There was a slight increase in pancreatitis ( 0.5%vs 0.8 % , p=0.031 ) and pulmonary embolism ( 0.7%vs 1.1 % , p=0.022 ) , but no other significant adverse effects . INTERPRETATION Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events . It did reduce total cardiovascular events , mainly due to fewer non-fatal myocardial infa rct ions and revascularisations . The higher rate of starting statin therapy in patients allocated placebo might have masked a moderately larger treatment benefit", "Background Endothelial dysfunction is an early feature of atherosclerosis . The relationship between insulin action and hypertriglyceridaemia on endothelial function is still debated" ]

[ "Study Design . A prospect i ve clinical and radiologic investigation of two groups of patients presenting with either acute back pain only or acute leg pain only , yet similar restriction in straight leg raising ( SLR ) . Objectives . To highlight a group of patients presenting with acute low back pain only , yet a restricted SLR normally associated with leg pain ( sciatica ) caused by a posterolateral disc prolapse . To determine the anatomic source of the pain in the low back pain only group . Summary of Background Data . A restricted SLR is commonly associated with leg pain ( sciatica ) due to compression of a nerve root by an intervertebral disc prolapse . Previous studies investigating pain patterns on SLR have suggested that central disc prolapses tend to induce back pain whereas the more lateral prolapses induce leg pain . Such research work has involved patients presenting with typical sciatic pain investigated by myelography and undergoing decompressive surgery . There are no studies specifically investigating patients presenting with low back pain only and reduced SLR . Methods . Two groups of patients , one with acute low back pain only and one with acute leg pain only , yet showing similar restriction in SLR underwent MR imaging . The scans were review ed “ blind ” by an experienced spinal radiologist and imaging features recorded according to a detailed protocol . The MR findings were then compared . Results . Significant disc prolapses were seen equally in both groups . The disc prolapses in the back pain only group were more likely to be central , smaller , to compress the theca only , and to be at a higher lumbar level as compared with the leg pain only group . Conclusions . Acute low back pain associated with significant restriction in SLR is likely to be caused by a disc prolapse compressing the anterior theca", "Study Design . Prospect i ve cohort study of r and omly selected Veterans Affairs ( VA ) out patients . Objective . To determine the prevalence of magnetic resonance imaging ( MRI ) findings in the lumbar spine among persons without current low back pain or sciatica and to examine which findings are related to age or previous back symptoms . Summary of Background Information . Previous studies of patients without low back pain have not explored the possible association of various MRI findings to past symptoms . Methods . We r and omly selected an age-stratified sample of subjects without low back pain in the past 4 months from clinics at a VA hospital . We collected information on demographics , comorbidity , functional status , and quality of life . MR images were obtained using a st and ardized protocol through each of the five lumbar disc levels . Results . Of 148 subjects , 69 ( 46 % ) had never experienced low back pain . There were 123 subjects ( 83 % ) with moderate to severe desiccation of one or more discs , 95 ( 64 % ) with one or more bulging discs , and 83 ( 56 % ) with loss of disc height . Forty-eight subjects ( 32 % ) had at least one disc protrusion and 9 ( 6 % ) had one or more disc extrusions . Conclusion . Many MR imaging findings have a high prevalence in subjects without low back pain . These findings are therefore of limited diagnostic use . The less common findings of moderate or severe central stenosis , root compression , and extrusions are likely to be diagnostically and clinical ly relevant", "STUDY DESIGN A prospect i ve 9-year follow-up study involving r and omized matched subgroups of 15-year-old schoolchildren with or without low back pain at baseline . OBJECTIVES To evaluate the long-term persistence of initially reported recurrent low back pain , and to examine the significance of abnormalities found in magnetic resonance imaging of lumbar discs in individuals 15 and 18 years of age as possible contributors to persistently recurrent low back pain . SUMMARY OF BACKGROUND DATA In surveys among children and teenagers during the past few years , as many as half of all children in a community report a history of low back pain . The current results , in accordance with previous findings , indicate that there is a subgroup of adolescents with more chronic symptoms which , in the authors ' opinion , deserves more attention . Disc disease accompanying low back pain is a key issue both in research and clinical practice . The significance of early degenerative findings in the lumbar discs is not known . METHODS In the survey of 14-year-olds ( n = 1503 ) , a subgroup ( 7.8 % ) with recurrent low back pain was found . A r and om sample of individuals with recurrent low back pain ( n = 40 ) and an equal number of completely asymptomatic control subjects were selected for a comparative study . The selected groups were examined by magnetic resonance imaging at 15 and 18 years of age . The participation rate of youth at 14 , 18 , and 23 years of age for all three question naires was 82 % ( 29 boys and 33 girls ) . Imaging data were interpreted by two blinded radiologists experienced in low-field-strength magnetic resonance imaging . In calculations of relative risks , the participants reporting recurrent low back pain in all phases of the study were compared with participants who had no persistently recurrent pain . RESULTS Eleven participants ( 35 % ) in the original group with low back pain persistently reported recurrent pain . In 15-year-old participants with disc degeneration , the relative risk of reporting recurrent low back pain up to the age of 23 years was 16 ( 95 % confidence interval 2.2 - 118 ) compared with those having no disc degeneration . In addition , disc protrusion and Scheuermann-type changes at 15 years contributed to the risk of persistently recurrent low back pain . CONCLUSIONS The authors ' earlier findings already favored the hypothesis of a causal relation between the early evolution of a degenerative process of lower lumbar discs and recurrent low back pain in the near future . The current results further strengthen this hypothesis , indicating that individuals with disc degeneration soon after the phase of rapid physical growth not only have an increased risk of recurrent low back pain at this age , but also a long-term risk of recurrent pain up to early adulthood", "OBJECTIVE To assess the relations between clinical ly recognized lumbar spinal stenosis and the conclusions of masked radiologists and electrodiagnosticians . DESIGN Prospect i ve , masked , double-controlled trial . SETTING University spine center . PARTICIPANTS One hundred fifty persons age 55 to 80 years with or without back pain and with or without magnetic resonance imaging (MRI)-demonstrated stenosis , screened for neuropathy risk , previous surgery , or cancer . INTERVENTIONS Question naires on pain and function ; ambulation testing and physical examination ; and masked electrodiagnotics and MRI . MAIN OUTCOME MEASURE Diagnostic impressions of the examining clinician , radiologist , and electrodiagnostician . RESULTS Following application of post hoc exclusion criteria and elimination of patients due to incomplete or inadequate test data , the clinical diagnosis was lumbar stenosis in 50 subjects , back pain in 44 subjects , and no pain in 32 subjects . Radiologic and clinical impression had no relation ( P = .80 vs asymptomatic , P = .99 vs back pain controls ) . Electrodiagnostic impression trended to relate to clinical impression ( P = .14 vs asymptomatic , P = .09 vs back pain ) . Retrospective application of age-related electrodiagnostic norms for paraspinal electromyographic and limb motor unit changes , established in this study , reclassified 13 of the 17 asymptomatic persons whom the electrodiagnostician thought had stenosis . The clinical impression did correspond to history and physical examination findings typically associated with spinal stenosis and to the independent impression of a neurosurgeon who examined MRI and clinical , but not to the electrodiagnostic data . CONCLUSIONS The impression obtained from an MRI scan does not determine whether lumbar stenosis is a cause of pain . Electrodiagnostic consultation may be useful , especially if age-related norms obtained in this study are applied", "Study Design . Prospect i ve comparative study of pain drawings with findings on lumbar spine magnetic resonance imaging . Objectives . To assess the ability of the pain drawing to predict the presence of nerve root compression . Summary of Background Data . Most research work has concentrated on the ability of the pain drawing to act as a screening method for psychological distress with less work directed at the influence the anatomic abnormality has on the pain drawing . Methods . One hundred thirty‐four consecutive out‐ patients attending for lumbar magnetic resonance imaging in the investigation of back and leg pain completed pain drawings and psychological testing immediately before the examination . The pain drawing was analyzed by previously reported criteria , and the magnetic resonance imaging was assessed independently for the presence of nerve compression by three radiologists . Multivariate stepwise discriminant analysis was used to identify patients with nerve compression on the basis of their pain drawing . Results . Nerve compression was predicted by numbness in the anterolateral aspect of the foot . There was considerable overlap in the appearances of the pain drawings between patients with and without nerve compression , and the pain drawing correctly classified only 58 % of patients with nerve compression . Conclusions . The pain drawing is not a good predictor of nerve compression on magnetic resonance imaging in a group of patients investigated for back and leg pain . It should be interpreted with caution and in light of the full clinical picture", "Background : An association has previously been reported between finger blanching and hearing difficulties , but only in workers with exposure to noise and h and transmitted vibration ( HTV ) . Aims : To explore the association in a community sample , including cases who lacked occupational exposure to noise or HTV . Method : A question naire was mailed to 12 606 subjects aged 35–64 years , chosen at r and om from the age – sex registers of 34 British general practice s. Inquiry was made about years of employment in noisy jobs , lifetime exposure to HTV , hearing difficulties and tinnitus , and lifetime history of cold induced finger blanching . Subjects were classed as having severe hearing difficulty if they used a hearing aid or found it difficult or impossible to hear conversation in a quiet room . Associations of finger blanching with hearing difficulties and tinnitus were analysed by logistic regression . Results : Among 8193 respondents were 185 who reported severe hearing difficulty and 1151 who reported finger blanching . After adjustment for age and years of work in noisy jobs , hearing difficulty was about twice as common in men and women who reported finger blanching , including those who had never been importantly exposed to noise and in those never exposed to HTV . Conclusions : These data support an association between finger blanching and hearing loss , which is not explained by confounding occupational exposure to noise , and suggest that it may extend to causes of blanching other than vibration induced white finger . Further investigations are warranted to confirm the association and explore possible mechanisms , such as sympathetic vasoconstriction in the cochlea", "Study Design This was a prospect i ve study of patients ( study group ) with symptomatic disc herniations and asymptomatic volunteers ( control group ) matched for age , sex , and work-related risk factors . Objective To determine the prevalence of disc herniation in a matched group of asymptomatic volunteers and to access the diagnostic accuracy of magnetic resonance imaging , work perception , and psychosocial factors in identifying symptomatic disc herniations . Summary of Background Data Disc herniations have been reported to occur in 20–36 % of asymptomatic volunteers . A valid comparison of asymptomatic individuals and patients with disc herniations has not been performed . Methods Forty-six patients with low back pain and sciatica severe enough to require a disceclomy were compared with 46 age- , sex- , and risk factor-matched ( heavy lifting , twisting and bending , vibration , and sedentary activity ) asymptomatic voluteers . Both groups had a complete clinical and magnetic resonance imaging examination and completed a question naire to assess differences in the psychosocial and work perception profiles . The prevalence and the severity of morphologic alterations ( disc herniation , disc degeneration , and neural compromise ) was analyzed by two independent radiologists in a blinded fashion . Differences between both groups regarding MRI findings , work perception ( occupational mental stress , intensity of concentration , job satisfaction , and job-related resignation ) and psychosocial factors ( anxiety , depression , self-control , social support , and marital status ) were compared using multivariate techniques . Stepwise discriminate analysis was used to identify the best discriminating variables within the magnetic resonance image , work perception , and psychosocial categories in terms of the diagnostic accuracy to predict group membership ( study [ pain ] or control [ no pain ] group ) . Results Matched controls had significantly more risk factors than a group of normal individuals . The present study has presented evidence that an age- , gender- , and occupational risk factors-matched group of asymptomatic patients shows a high incidence rate of disc herniations ( 76 % ) . Although significantly less than the symptomatic group incidence of 96 % , this represents a much higher prevalence rate than generally expected and reported in other studies of unmatched asymptomatic volunteers . Patients had more severe disc herniations ( disc extrusions ) than asymptomatic volunteers ( 35 % vs. 13 % ) . There was no significant differences regarding disc degeneration between both groups ( 96 % vs. 85 % ) . The only substantial morphologic difference between both groups was the presence of a neural compromise ( 83 % vs. 22 % ) , which was highly significant ( P work perception ( occupational mental stress , intensity of concentration , job satisfaction , and resignation ; P psychosocial factors ( anxiety , depression , self-control , marital status ; P false-negative rate ( potential overtreatment of disc morphology ) was reduced by more than half compared with morphologic factors ( nerve root compression ) alone ( 22 % vs. 11 % ) . Conclusions . In an age- , sex- , and risk factormatched group of asymptomatic individuals , disc herniation had a substatially higher prevalence ( 76 % ) than previously reported in an unmatched group . Individuals with minor disc herniations ( i.e. , protrusion , contained discs ) are at a very high risk that their magnetic resonance images are not a causal explanation of pain because a high rate of asymptomatic subjects ( 63 % ) had comparable morphologic findings . The only highly significant difference between the study group and control group regarding morphologic findings was the criteria of a nerve root compromise . Work perception and psychosocial factors were helpful in discriminating between symptomatic and asymptomatic disc herniations", "Study Design A double-blind prospect i ve study was used to measure interobserver and intraobserver variability when interpreting lumbar spine magnetic resonance imaging studies of disc abnormalities . Objectives To evaluate reader consistercy when interpreting disc extension beyond the interspace , and assess the effect of two distinct nomenclatures on reader consistency . Summary of Background Data Interobserver and intraobserver variability in interpretation of lumbar disc abnormalities is an important consideration in analyzing the technical efficacy of an imaging modality . However , this has not been well measured ( particularly for st and ardized nomenclature ) . Methods Magnetic resonance imaging studies of the lumbar spine performed prospect ively in 98 asymptomatic volunteers , and an additional 27 selected studies from symptomatic patients , were read blindly by two experienced neuroradiologists , using two separate nomenclatures . Only the discs were evaluated ( 625 interspaces ) . Nomenclature I was normal , bulge , herniation . Nomenclature II was normal , bulge , protrusion , extrusion . Intraobserver and interobserver variation were measured with Kappa statistic analysis . Results Interobserver agreement was 80 % for both nomenclatures with a Kappa statistic of 0.58 . Intraobserver agreement was 86 % for each reader , with a Kappa statistic of 0.71 and 0.69 , respectively . The most common disagreement was for normal versus bulge . The next most common disagreement ( 5–6 % ) was for bulge versus herniation ( or protrusion in Nomenclature II ) . Herniation was read in 23 % of the asymptomatic subjects . Using Nomenclature II . protrusion was seen in 27 % of these subjects . Extrusion was read in only two asymptomatic subjects . Conclusions Experienced readers using st and ardized nomenclature showed moderate to substantia agreement when interpreting disc extension beyond the interspace on magnetic resonance imaging", "BACKGROUND Magnetic resonance ( MR ) imaging is frequently used to evaluate first-time episodes of serious low back pain ( LBP ) . Common degenerative findings are often interpreted as recent developments and the probable anatomic cause of the new symptoms . To date no prospect i ve study has established a baseline MR status of the lumbar spine in subjects without significant LBP problems and prospect ively surveyed these subjects for acute changes shortly after new and serious LBP episodes . This method can identify new versus old MR findings possibly associated with the acute symptomatic episode . PURPOSE To determine if new and serious episodes of LBP are associated with new and relevant findings on MRI . STUDY DESIGN Prospect i ve observational study with baseline and post-LBP MRI monitoring of 200 subjects over 5 years . OUTCOME MEASURES Clinical outcomes : LBP intensity ( visual analogue scale ) , Oswestry Disability Index , and work loss . MRI outcomes : disc degeneration , herniation , annular fissures , end plate changes , facet arthrosis , canal stenosis , spondylolisthesis , and root impingement . METHODS 200 subjects with a lifetime history of no significant LBP problems , and a high risk for new LBP episodes were studied at baseline with physical examination , plain radiographs , and MR imaging . Subjects were followed every 6 months for 5 years with a detailed telephone interview . Subjects with a new severe LBP episode ( LBP > or=6/10,>1 week ) were assessed for new diagnostic tests . New MR imaging , taken within 6 to 12 weeks of the start of a new LBP episode , was compared with baseline ( asymptomatic ) images . Two independent and blinded readers evaluated each baseline and follow-up study . RESULTS During the 5-year observation period of 200 subjects , 51 ( 25 % ) subjects were evaluated with a lumbar MRI for clinical ly serious LBP episodes , and 3/51 ( 6 % ) had a primary radicular complaint . These 51 subjects had 67 MR scans . Of 51 subjects , 43 ( 84 % ) had either unchanged MR or showed regression of baseline changes . The most common progressive findings were disc signal loss ( 10 % ) , progressive facet arthrosis ( 10 % ) , or increased end plate changes ( 4 % ) . Only two subjects , both with primary radicular complaints , had new findings of probable clinical significance ( 4 % ) . Subjects having another MR were more likely to have had chronic pain at baseline ( odds ratio [OR]=3.19 ; 95 % confidence interval [ CI ] 1.61 - 6.32 ) , to smoke ( OR=5.81 ; 95 % CI 1.99 - 16.45 ) , have baseline psychological distress ( OR 2.27 ; 95 % CI 1.15 - 4.49 ) , and have previous disputed compensation cl aims ( OR=2.35 ; 95 % CI 0.97 - 5.69 ) . Subjects involved in current compensation cl aims were also more likely to have an MR scan to evaluate the LBP episode ( risk ratio=4.75 , p LBP episodes developing after minor trauma than when LBP developed spontaneously . CONCLUSION Findings on MR imaging within 12 weeks of serious LBP inception are highly unlikely to represent any new structural change . Most new changes ( loss of disc signal , facet arthrosis , and end plate signal changes ) represent progressive age changes not associated with acute events . Primary radicular syndromes may have new root compression findings associated with root irritation", "BACKGROUND The relation between abnormalities in the lumbar spine and low back pain is controversial . We examined the prevalence of abnormal findings on magnetic resonance imaging ( MRI ) scans of the lumbar spine in people without back pain . METHODS We performed MRI examinations on 98 asymptomatic people . The scans were read independently by two neuroradiologists who did not know the clinical status of the subjects . To reduce the possibility of bias in interpreting the studies , abnormal MRI scans from 27 people with back pain were mixed r and omly with the scans from the asymptomatic people . We used the following st and ardized terms to classify the five intervertebral disks in the lumbosacral spine : normal , bulge ( circumferential symmetric extension of the disk beyond the interspace ) , protrusion ( focal or asymmetric extension of the disk beyond the interspace ) , and extrusion ( more extreme extension of the disk beyond the interspace ) . Nonintervertebral disk abnormalities , such as facet arthropathy , were also documented . RESULTS Thirty-six percent of the 98 asymptomatic subjects had normal disks at all levels . With the results of the two readings averaged , 52 percent of the subjects had a bulge at at least one level , 27 percent had a protrusion , and 1 percent had an extrusion . Thirty-eight percent had an abnormality of more than one intervertebral disk . The prevalence of bulges , but not of protrusions , increased with age . The most common nonintervertebral disk abnormalities were Schmorl 's nodes ( herniation of the disk into the vertebral-body end plate ) , found in 19 percent of the subjects ; annular defects ( disruption of the outer fibrous ring of the disk ) , in 14 percent ; and facet arthropathy ( degenerative disease of the posterior articular processes of the vertebrae ) , in 8 percent . The findings were similar in men and women . CONCLUSIONS On MRI examination of the lumbar spine , many people without back pain have disk bulges or protrusions but not extrusions . Given the high prevalence of these findings and of back pain , the discovery by MRI of bulges or protrusions in people with low back pain may frequently be coincidental", "BACKGROUND CONTEXT Assessment of patients with complaints of low back or leg pain varies with the subspecialty of the treating physician . The evaluation of the spine patient may include magnetic resonance imaging ( MRI ) , bone scan , or single-photon emission computed tomography ( SPECT ) imaging . The interpretation of these tests and the examiner 's biases will impact the outcome of patient treatment and the cost to the health-care system . PURPOSE To evaluate interobserver reliability of MRI and nuclear imaging studies and determine the predictability of nuclear medicine results based upon MRI findings . STUDY DESIGN / SETTING Retrospective radiographic review for patients with low back pain . MRI , planar bone scan imaging , and SPECT imaging techniques were evaluated . PATIENT SAMPLE Seventeen patients ( 80 lumbar levels ) who presented to an orthopedic spine specialist with a complaint of mechanical low back or leg pain were r and omly selected . Inclusion criteria were age greater than 21 years and a workup that included MRI , bone scan , and SPECT scan images . OUTCOME MEASURES Interobserver reliability was determined using kappa values ( 0.6 to Interobserver reliability was evaluated for all studies and compared with a \" group consensus . \" METHODS A team of orthopedists and radiologists of varying experience levels were assembled to interpret the imaging studies . All readings were performed independently followed by group interpretation and discussion . The review ers were asked to assess each lumbar level ( L1-L2 through L5-S1 ) . Phase one : Is the level degenerative ? Is there a spondylolisthesis present ? Does the level have Modic changes on MRI ? Phase two : Based on the MRI , will the planar bone scan be positive ? After this prediction , was the planar scan positive ? Identify the lesion location ( anterior column vs. posterior column ) . Phase three : Based on their assessment and predicted results on planar bone scan , was the SPECT scan able to improve this assessment ? RESULTS High kappa values were demonstrated in the identification of a degenerative disc , spondylolisthesis , and Modic change ( 0.773 , 0.728 , and 0.669 , respectively ) . Bone scan and SPECT scan yielded poorer kappa results ( 0.539 and 0.460 , respectively ) . Review er-predicted bone scan results demonstrated a positive predictive value of 68 % and a negative predictive value of 84 % . Predicated SPECT results were similar ( positive predictive value 66 % and negative predictive value 84 % ) . SPECT identified 24 % more lesions in the lumbar spine when compared with bone scan . CONCLUSIONS MRI interpretation of the lumbar spine is comparable between specialties . Nuclear imaging studies ( bone scan/SPECT ) demonstrated a poorer correlation between examiners . The presence of MRI changes enables an accurate prediction of bone scan or SPECT scan findings . SPECT scan demonstrates an increased sensitivity in the detection of spinal abnormalities and the ability to localize a lesion when compared with planar bone scan", "Abstract The authors present a prospect i ve study of quality of life ( SF-36 ) and MRI findings in patients with low back pain ( LBP ) . Disc herniation and nerve root compression contribute to LBP and poor quality of life . However , significant proportions of asymptomatic subjects have disc herniation and neural compromise . Little is known about the influence of disc abnormalities and neural compression on quality of life in symptomatic patients . The purpose of this study was to assess the relationship between the extent of disc abnormality , neural impingement and quality of life . A total of 317 consecutive patients with LBP referred for MRI completed an SF-36 health status question naire immediately before imaging and again 6 months later . Patients were grouped according to the most extensive disc abnormality and any neural compromise reported at MRI . The relationship between symptoms , radiological signs and SF-36 scores was assessed . Eighty percent ( 255/317 ) and 65 % ( 205/317 ) of patients completed the initial and 6-month SF-36 , respectively . Thirty-six percent of patients ( 115/317 ) had one or more herniated discs and 44 % ( 140/317 ) had neural impingement . There was little relationship between the extent of disc abnormality and quality of life . Patients with radiological evidence of neural impingement reported better general health ( P SF-36 scores improved at 6 months in four dimensions , but general health deteriorated ( P pain scores at 6 months ( P pain and dysfunction caused by disc herniation and neural compromise are not sufficiently distinct from other causes of back pain to be distinguished by the SF-36 . Whilst neural compromise may be the best radiological feature distinguishing patients who may benefit from intervention , it can not predict quality of life deficits in the diffuse group of patients with LBP" ]

[ "Background : Prospect i ve population -based follow-up study of 120 individuals with autism followed from childhood to adulthood . Methods : Individuals with autism , diagnosed in childhood , were followed prospect ively for a period of 13–22 years and re-evaluated at ages 17–40 years . The instruments used at follow-up were the DISCO , WAIS-R , WISC-III , Vinel and Adaptive Behavior Scales , psychiatric-medical examination and GAF-scale . A set of criteria was used for the classification of outcomes , taking into consideration employment , higher education/vocational training , independent living and peer relations . Results : Six of the 120 ( 5 % ) had died at the time of follow-up , and six declined participation . Overall outcome was poor in 78 % of cases . Only four individuals were independent albeit leading fairly isolated lives . Childhood IQ-level was positively correlated with better adult outcome , as was the existence of some communicative phrase speech at age six years . Conclusions : Children with autism as diagnosed in the 1960s , 1970s , and 1980s may have an even worse psychosocial outcome than previously believed", "Repetitive behaviors are a core symptom domain in autism that has been linked to alterations in the serotonin system . While the selective serotonin-receptive inhibitor fluvoxamine has been shown to be effective in adults with autism , as yet no published placebo controlled trials with these agents document safety and efficacy in children with autism . This study examines the selective serotonin reuptake inhibitor liquid fluoxetine in the treatment of repetitive behaviors in childhood and adolescent autism spectrum disorders ( ASDs ) . In total , 45 child or adolescent patients with ASD were r and omized into two acute 8-week phases in a double-blind placebo-controlled crossover study of liquid fluoxetine . Study design included two r and omized 8-week fluoxetine and placebo phases separated by a 4-week washout phase . Outcome measures included measures of repetitive behaviors and global improvement . Low-dose liquid fluoxetine ( mean final dose : 9.9±4.35 mg/day ) was superior to placebo in the treatment of repetitive behaviors by CY-BOCS compulsion scale . The effect size was in the moderate to large range , and the doses used were low . Liquid fluoxetine was only slightly , and not significantly , superior to placebo on CGI autism score partially due to a phase order effect . However , fluoxetine was marginally superior to placebo on a composite measure of global effectiveness . Liquid fluoxetine did not significantly differ from placebo on treatment emergent side effects . Liquid fluoxetine in low doses is more effective than placebo in the treatment of repetitive behaviors in childhood autism . Limitations include small sample size and the crossover design of the study . Further replication and long-term maintenance trials are needed", "The Studies to Advance Autism Research and Treatment Network conducted a r and omized trial with citalopram in children with Pervasive developmental disorders ( PDDs ) . We present the rationale , design and sample characteristics of the citalopram trial . Subjects ( 128 boys , 21 girls ) had a mean age of 9.3 ( ±3.12 ) years ; 132 ( 88.6 % ) were diagnosed with autistic disorder ( 4.7 % with Asperger ’s Disorder ; 6.7 % with PDD-not otherwise specified ) . Less than half of the subjects were intellectually disabled ; 117 ( 78.5 % ) were rated Moderate or Marked on the Clinical Global Impression for Severity . Study measures were similar to previous Research Units on Pediatric Psychopharmacology trials . Subjects in this trial were slightly older and more likely to have complaints of repetitive behavior than participants in RUPP trials", "OBJECTIVE . The objective of this study was to provide national estimates of psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders and to examine child and health system characteristics associated with psychotropic medication use . METHODS . This cross-sectional study used Medicaid cl aims for calendar year 2001 from all 50 states and Washington , DC , to examine 60641 children with an autism spectrum disorder diagnosis . Logistic regression with r and om effects was used to examine the child , county , and state factors associated with psychotropic medication use . RESULTS . Of the sample , 56 % used at least 1 psychotropic medication , 20 % of whom were prescribed ≥3 medications concurrently . Use was common even in children aged 0 to 2 years ( 18 % ) and 3 to 5 years ( 32 % ) . Neuroleptic drugs were the most common psychotropic class ( 31 % ) , followed by antidepressants ( 25 % ) and stimulants ( 22 % ) . In adjusted analyses , male , older , and white children ; those who were in foster care or in the Medicaid disability category ; those who received additional psychiatric diagnoses ; and those who used more autism spectrum disorder services were more likely to have used psychotropic drugs . Children who had a diagnosis of autistic disorder or who lived in counties with a lower percentage of white residents or greater urban density were less likely to use such medications . CONCLUSIONS . Psychotropic medication use is common among even very young children with autism spectrum disorders . Factors unrelated to clinical presentation seem highly associated with prescribing practice s. Given the limited evidence base , there is an urgent need to assess the risks , benefits , and costs of medication use and underst and the local and national policies that affect medication use", "We examined the construction of the Yale-Brown Obsessive-Compulsive Scale ( Y-BOCS ) and performance of subscale items based on data from 204 patients with obsessive-compulsive disorder ( OCD ) who participated in a multicenter drug treatment study . Factor analysis was used to examine the relationship among the 10 items that make up the Y-BOCS instrument . Models were computed in which both two- and three-factor solutions were estimated . Within the two-factor solution analyses , the factor distribution was not so consistent as in the three-factor solution analyses , and a shift in the factor distribution was noted after treatment . In the three-factor solution analyses , an independent resistance construct emerged in addition to the obsessive and compulsive constructs . Examination of the postreatment factor scores showed that the Y-BOCS resistance items did not assess OCD symptom change as sensitively as the rest of the Y-BOCS items did", "BACKGROUND Atypical antipsychotic agents , which block postsynaptic dopamine and serotonin receptors , have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances . However , data on the safety and efficacy of atypical antipsychotic agents in children are limited . METHODS We conducted a multisite , r and omized , double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums , aggression , or self-injurious behavior in children 5 to 17 years old . The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement ( CGI-I ) scale at eight weeks . RESULTS A total of 101 children ( 82 boys and 19 girls ; mean [ + /-SD ] age , 8.8+/-2.7 years ) were r and omly assigned to receive risperidone ( 49 children ) or placebo ( 52 ) . Treatment with risperidone for eight weeks ( dose range , 0.5 to 3.5 mg per day ) result ed in a 56.9 percent reduction in the Irritability score , as compared with a 14.1 percent decrease in the placebo group ( P Irritability score and a rating of much improved or very much improved on the CGI-I scale , was 69 percent in the risperidone group ( 34 of 49 children had a positive response ) and 12 percent in the placebo group ( 6 of 52 , P Risperidone therapy was associated with an average weight gain of 2.7+/-2.9 kg , as compared with 0.8+/-2.2 kg with placebo ( P Increased appetite , fatigue , drowsiness , dizziness , and drooling were more common in the risperidone group than in the placebo group ( P Risperidone was effective and well tolerated for the treatment of tantrums , aggression , or self-injurious behavior in children with autistic disorder . The short period of this trial limits inferences about adverse effects such as tardive dyskinesia", "Clomipramine , haloperidol , and placebo were compared with baseline in the treatment of autism , and overall outcome , specific symptoms , and side effects were examined . It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy . Individuals with a DSM-IV diagnosis of autistic disorder ( mean age , 16.3 years ; range , 10–36 years ) were r and omly assigned , by using a Latin square design , to the following 7-week trials : placebo , clomipramine ( mean daily dose , 128.4 mg ; range , 100–150 mg ) , or haloperidol ( mean daily dose , 1.3 mg ; range , 1–1.5 mg ) . Data on 36 subjects were analyzed and taken together ; the results favored haloperidol . In those patients who were able to complete a full therapeutic trial , clomipramine proved comparable to haloperidol in terms of improvement compared with baseline . However , significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial ( 37.5 % vs. 69.7 % , respectively ) for reasons related to both side effects and efficacy or behavior problems . In the intent-to-treat sample , which is perhaps more clinical ly relevant , only haloperidol proved superior to baseline on a global measure of autistic symptom severity , as well as specific measures for irritability and hyperactivity . Clomipramine did not seem more effective on a measure of stereotypy , nor was it better tolerated", "The short-term efficacy and tolerability of sertraline for adults with pervasive developmental disorders ( PDDs ) were assessed in this investigation . Forty-two adults with PDDs ( autistic disorder , N = 22 ; Asperger 's disorder , N = 6 ; and PDD not otherwise specified [ NOS ] , N = 14 ) participated in a 12-week , open-label , systematic trial of sertraline . Behavioral ratings of repetitive symptoms , aggression , and social relatedness were obtained at baseline and after 4 , 8 , and 12 weeks of sertraline administration . Twenty-four ( 57 % ) of 42 patients showed significant improvement , primarily in repetitive and aggressive symptoms . Statistically significant changes in measures of social relatedness did not occur . Patients with autistic disorder and PDD NOS did significantly better than those with Asperger 's disorder . Based on global improvement item criteria from the Clinical Global Impression Scale , 15 of 22 ( 68 % ) patients with autistic disorder , none of six ( 0 % ) patients with Asperger 's disorder , and 9 of 14 ( 64 % ) patients with PDD NOS were categorized as treatment responders . Sertraline was well tolerated ; no adverse cardiovascular effects , extrapyramidal symptoms , or seizures were identified . These findings suggested that sertraline may be an effective treatment for interfering repetitive and aggressive symptoms in adults with PDDs . Definitive statements about the efficacy and tolerability of sertraline for treating adults with PDDs must await results from double-blind , placebo-controlled trials . These preliminary results should not be generalized to include children and adolescents with PDDs", "BACKGROUND Autistic disorder is characterized by a fundamental disturbance in social interaction , impairments in communication , and a markedly restricted repertoire of activities and interests . Abnormalities in the serotonin neurotransmitter system have been identified in some persons with autism . No consistently effective and safe drugs have been developed for treating the symptoms of autism . METHODS Thirty adults with autistic disorder completed a 12-week double-blind , placebo-controlled trial of the potent and selective serotonin uptake inhibitor fluvoxamine maleate . Behavioral ratings were obtained at baseline and after 4 , 8 , and 12 weeks of treatment . RESULTS Eight ( 53 % ) of 15 patients in the fluvoxamine-treated group were categorized as responders compared with none of 15 in the placebo group ( P = .001 ) . Fluvoxamine was superior to placebo in reducing repetitive thoughts and behavior ( P maladaptive behavior ( P aggression ( P aspects of social relatedness ( P language usage ( P mild sedation and nausea in a few patients , fluvoxamine was well tolerated . No dyskinesias , adverse cardiovascular events , or seizures occurred . CONCLUSIONS Fluvoxamine is more effective than placebo in the short-term treatment of the symptoms of autistic disorder in adults . Controlled studies of fluvoxamine and other potent and selective serotonin uptake inhibitors seem warranted in children and adolescents with autism", "OBJECTIVE To assess the short-term efficacy and safety of clomipramine in hospitalized young children with autism . METHOD This was an open pilot study ; after a 1-week placebo baseline , subjects were treated with clomipramine for 5 weeks . Dosage was individually regulated ; starting dose was 25 mg/day ; increments were 25 mg/day . Maximum dose was 250 mg/day or 5.0 mg/kg per day , whichever was less . Multiple raters , under several conditions , used the Children 's Psychiatric Rating Scale , Clinical Global Impressions , Conners Parent Teacher Question naire , and the Clinical Global Consensus Ratings . RESULTS Eight children , aged 3.5 to 8.7 years , were enrolled in the study ; seven of these completed the study . A 3.5-year-old boy was excluded during the third week of treatment after having urinary retention on two occasions . At doses ranging from 2.50 to 4.64 mg/kg per day ( mean = 3.14 ) , one child improved moderately and six were rated as worse on the Clinical Global Consensus Ratings . Untoward effects were common . CONCLUSIONS ; Clomipramine was not therapeutic and was associated with serious untoward effects in this sample . Young autistic children may be more prone to experience untoward effects than older patients", "We studied the correlation between response to fluvoxamine and serotonin transporter gene promoter region polymorphism ( 5-HTTLPR ) . Eighteen children with autistic disorder completed a 12-week double-blind , placebo-controlled , r and omized crossover study of fluvoxamine . Behavioral assessment s were obtained before and at 12 weeks of treatment . 5-HTTLPR ( long ( l ) or short(s ) ) , was analyzed by the PCR method . Ten out of 18 patients responded to fluvoxamine treatment ; allele type analysis revealed that clinical global effectiveness was noted significantly more in the l allele than in the s allele . However , with respect to language use , a significant effectiveness was noted in the s allele . 5-HTTLPR may influence the individual responses to fluvoxamine administration", "CONTEXT Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders . OBJECTIVES To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders . DESIGN National Institutes of Health-sponsored r and omized controlled trial . SETTING Six academic centers , including Mount Sinai School of Medicine , North Shore-Long Isl and Jewish Health System , University of North Carolina at Chapel Hill , University of California at Los Angeles , Yale University , and Dartmouth Medical School . PARTICIPANTS One hundred forty-nine volunteers 5 to 17 years old ( mean [ SD ] age , 9.4 [ 3.1 ] years ) were r and omized to receive citalopram ( n = 73 ) or placebo ( n = 76 ) . Participants had autistic spectrum disorders , Asperger disorder , or pervasive developmental disorder , not otherwise specified ; had illness severity ratings of at least moderate on the Clinical Global Impressions , Severity of Illness Scale ; and scored at least moderate on compulsive behaviors measured with the Children 's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders . INTERVENTIONS Twelve weeks of citalopram hydrobromide ( 10 mg/5 mL ) or placebo . The mean ( SD ) maximum dosage of citalopram hydrobromide was 16.5 ( 6.5 ) mg/d by mouth ( maximum , 20 mg/d ) . MAIN OUTCOME MEASURES Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions , Improvement subscale . An important secondary outcome was the score on the Children 's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders . Adverse events were systematic ally elicited using the Safety Monitoring Uniform Report Form . RESULTS There was no significant difference in the rate of positive response on the Clinical Global Impressions , Improvement subscale between the citalopram-treated group ( 32.9 % ) and the placebo group ( 34.2 % ) ( relative risk , 0.96 ; 95 % confidence interval , 0.61 - 1.51 ; P > .99 ) . There was no difference in score reduction on the Children 's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline ( mean [ SD ] , -2.0 [ 3.4 ] points for the citalopram-treated group and -1.9 [ 2.5 ] points for the placebo group ; P = .81 ) . Citalopram use was significantly more likely to be associated with adverse events , particularly increased energy level , impulsiveness , decreased concentration , hyperactivity , stereotypy , diarrhea , insomnia , and dry skin or pruritus . CONCLUSION Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders . Trial Registration clinical trials.gov Identifier : NCT00086645", "BACKGROUND Obsessive-compulsive disorder responds almost only to potent serotonin reuptake inhibitors . Previous studies have suggested a relation between serotonergic function and clinical outcome in serotonin reuptake inhibitor treatment of obsessive-compulsive disorder . METHODS In a r and omized , double-blind trial , comparing clomipramine , paroxetine , and a placebo in obsessive-compulsive disorder , serotonin levels in whole blood ( WB-5-HT ) were measured at baseline , after 1 week , and after 4 weeks of treatment and related to clinical outcome in 36 patients . RESULTS In patients treated with serotonin reuptake inhibitors there was a pronounced decrease of WB-5-HT , variable after 1 week and uniformly maximal after 4 weeks . The decrease of WB-5-HT after 1 week of serotonin reuptake inhibitor treatment correlated negatively with clinical outcome after 12 weeks ( r = -.61 , p = .0006 ) ; hence , patients with slower WB-5-HT reactivity eventually responded better to treatment . Baseline WB-5-HT , but not WB-5-HT reactivity , was related to season . Depression , autistic traits , and previous serotonin reuptake inhibitor treatment predicted nonresponse . CONCLUSIONS A fast decrease of WB-5-HT was associated with poor clinical outcome . This may be related to faster serotonin efflux from platelets , which has previously been linked to autism . Further studies are necessary to identify the underlying mechanism and discern whether serotonin reuptake inhibitor-induced WB-5-HT decrease is clinical ly useful", "OBJECTIVE To determine whether clomipramine hydrochloride , a serotonin reuptake blocker with unique anti-obsessional properties , is differentially effective for obsessive-compulsive and stereotyped motor behaviors in autistic disorder compared with placebo and with the noradrenergic tricyclic antidepressant agent , desipramine hydrochloride . DESIGN Following a 2-week , single-blind placebo washout phase , 12 autistic subjects completed a 10-week , double-blind , crossover comparison of clomipramine and placebo , and 12 different subjects completed a similar comparison of clomipramine and desipramine . SETTING Outpatient clinic . PATIENTS A referral sample of 30 male and female autistic patients were enrolled , and 24 completed the study . MEASURES Key outcome measures were the Autism Relevant Subscale of the Children 's Psychiatric Rating Scale , the Modified Comprehensive Psychopathological Rating Scale-Obsessive-Compulsive Disorder Subscale , and the Clinical Global Impressions Scale . RESULTS Clomipramine was superior to both placebo and desipramine on ratings of autistic symptoms ( including stereotypies ) , anger , and compulsive , ritualized behaviors ( P placebo . Clomipramine was equal to desipramine and both tricyclic agents were superior to placebo for amelioration of hyperactivity . CONCLUSION Biological links between compulsions and stereotyped , repetitive behaviors in autistic disorder should be explored", "Fifteen children with autism were treated with 60 mg d , l-fenfluramine ( FEN ) or placebo in a double-blind A-B-A protocol followed immediately by double-blind placebo-controlled crossover administration of FEN ( total duration 62 weeks ) . Both biochemical and clinical outcomes were examined . Biochemically , FEN led to an increase in dihydroxyphenylacetic acid ( DOPAC ) and decreases in whole-blood serotonin ( 5-HT ) , plasma norepinephrine ( NE ) , and plasma 3-methoxy-4-hydroxyphenylglycol ( MHPG ) . The decrease in whole-blood 5-HT was seen only during treatment with FEN . However , NE levels did not return to baseline as long as 8 weeks after the first FEN treatment period . Increases in DOPAC were greater during the second FEN treatment period than the first . Persistent changes in catecholamine regulation may be related to previously reported long-term effects on central nervous system 5-HT after FEN . Clinical ly , FEN led to a modest decrease in parent , but not teacher , ratings of hyperactivity and to a small reduction in sensorimotor abnormalities . Abnormal social and affectual responses also decreased , but this was not directly related to FEN treatment . Effects on cognition were equivocal . Hyperserotonemic subjects did not differ from normoserotonemic subjects in clinical response . Overall , no significant advantage for the use of FEN could be established", "OBJECTIVE The effects of fluoxetine and placebo on repetitive behaviors and global severity were compared in adults with autism spectrum disorders ( ASDs ) . METHOD Adults with ASDs were enrolled in a 12-week double-blind placebo-controlled fluoxetine trial . Thirty-seven were r and omly assigned to fluoxetine ( N=22 ) or placebo ( N=15 ) . Dosage followed a fixed schedule , starting at 10 mg/day and increasing as tolerated up to 80 mg/day . Repetitive behaviors were measured with the compulsion subscale of the Yale-Brown Obsessive Compulsive Scale ; the Clinical Global Impression ( CGI ) improvement scale was used to rate improvement in obsessive-compulsive symptoms and overall severity . RESULTS There was a significant treatment-by-time interaction indicating a significantly greater reduction in repetitive behaviors across time for fluoxetine than for placebo . With overall response defined as a CGI global improvement score of 2 or less , there were significantly more responders at week 12 in the fluoxetine group than in the placebo group . The risk ratio was 1.5 for CGI global improvement ( responders : fluoxetine , 35 % ; placebo , 0 % ) and 1.8 for CGI-rated improvement in obsessive-compulsive symptoms ( responders : fluoxetine , 50 % ; placebo , 8 % ) . Only mild and moderate side effects were observed . CONCLUSIONS Fluoxetine treatment , compared to placebo , result ed in significantly greater improvement in repetitive behaviors , according to both the Yale-Brown compulsion subscale and CGI rating of obsessive-compulsive symptoms , as well as on the CGI overall improvement rating . Fluoxetine appeared to be well tolerated . These findings st and in contrast to findings in a trial of citalopram for childhood autism" ]

[ "Objective . To evaluate the quality of life ( QOL ) of untreated children with newly diagnosed attention-deficit/hyperactivity disorder ( ADHD ) , compared with asthmatic and healthy children . Methods . This prospect i ve , case-control study included a group of 120 children , 6 to 12 years of age , with newly diagnosed ADHD according to the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition . Subjects were matched according to age , gender , and health care area with 2 control groups , ie , 93 asthmatic children and 120 healthy children . Sociodemographic characteristics and Child Health Question naire scores were collected . Results . The QOL of children with ADHD was rated worse than that of asthmatic or healthy children for most Child Health Question naire domains . The greatest differences were found in behavior , social limitations attributable to physical problems , emotional impact on parents , and family activities . Almost every psychosocial domain was more affected in comparison with asthmatic children and both psychosocial and physical domains in comparison with healthy children . Conclusions . ADHD interferes with the daily lives of children , parents , and families even more than asthma , primarily in areas related to psychosocial functioning , although evidence of impaired physical functioning also emerged . Delays in recognition , assessment , and management of ADHD may affect negatively the QOL of those children", "OBJECTIVE To investigate the effect of melatonin treatment on sleep , behavior , cognition , and quality of life in children with attention-deficit/hyperactivity disorder ( ADHD ) and chronic sleep onset insomnia . METHOD A total of 105 medication-free children , ages 6 to 12 years , with rigorously diagnosed ADHD and chronic sleep onset insomnia participated in a r and omized , double-blind , placebo-controlled trial using 3 or 6 mg melatonin ( depending on body weight ) , or placebo for 4 weeks . Primary outcome parameters were actigraphy-derived sleep onset , total time asleep , and salivary dim light melatonin onset . RESULTS Sleep onset advanced by 26.9 + /- 47.8 minutes with melatonin and delayed by 10.5 + /- 37.4 minutes with placebo ( p dim light melatonin onset of 44.4 + /- 67.9 minutes in melatonin and a delay of 12.8 + /- 60.0 minutes in placebo ( p Total time asleep increased with melatonin ( 19.8 + /- 61.9 minutes ) as compared to placebo ( -13.6 + /- 50.6 minutes ; p = .01 ) . There was no significant effect on behavior , cognition , and quality of life , and significant adverse events did not occur . CONCLUSION Melatonin advanced circadian rhythms of sleep-wake and endogenous melatonin and enhanced total time asleep in children with ADHD and chronic sleep onset insomnia ; however , no effect was found on problem behavior , cognitive performance , or quality of life", "PURPOSE We determined the effects of a 3-month low-moderate-intensity strength training program ( 2 sessions/week ) on functional capacity , muscular strength , body composition , and quality of life ( QOL ) in 22 young ( 12 - 16 yrs ) anorexic out patients . METHODS Patients were r and omly assigned to a training or control group ( n=11 [ 10 females ] each ) . Training sessions were of low intensity ( loads for large muscle groups ranging between 20%-30 % and 50%-60 % of six repetitions maximum [ 6RM ] at the end of the program ) . We measured functional capacity by the time up and go and the timed up and down stairs tests . Muscular strength was assessed by 6RM measures for seated bench and leg presses . We estimated percent body fat and muscle mass . We assessed patients ' QOL with the Short Form-36 items . RESULTS The intervention was well tolerated and did not have any deleterious effect on patients ' health , and did not induce significant losses in their body mass . The only studied variable for which a significant interaction ( group x time ) effect was found ( p=.009 ) was the 6RM seated lateral row test . CONCLUSIONS Low-moderate-intensity strength training does not seem to add major benefits to conventional psychotherapy and refeeding treatments in young anorexic patients", "Background : Separation anxiety disorder ( SAD ) is one of the earliest and most common mental disorders in childhood , and a strong predictor of adult psychopathology . Despite significant progress in psychotherapy research on childhood anxiety disorders , no r and omized controlled trial has been conducted with a disorder-specific treatment program for young children suffering from SAD . Methods : Forty-three children ( ages 5–7 ) with SAD and their parents were assigned to either a 16-session disorder-specific SAD treatment program including parent training and classical cognitive-behavioral therapy ( CBT ) components , or to a 12-week waiting list group . Categorical and /or continuous data for anxiety , impairment/distress and quality of life were collected at baseline , after treatment/waiting list condition , and at a 4-week follow-up . Results : Intention-to-treat analyses indicate that 76.19 % of children allocated to the treatment group definitively no longer fulfilled DSM-IV criteria for SAD at follow-up , compared to 13.64 % in the waiting list group . Between 91 and 100 % of children rated themselves or were rated by their father , mother or therapist as very much or much improved on the global success rating immediately after treatment . Results indicated large time by treatment condition interaction effect sizes ( d = 0.98–1.41 ) across informants for reduction of distress/avoidance in separation situations after the test for the treatment condition . Further , parents reported significant improvements in impairment/distress in the child ’s major life domains and the child ’s quality of life . Treatment gains were maintained at the 4-week follow-up assessment . Conclusions : Results indicate the short-term efficacy of a disorder-specific treatment approach for SAD , and are among the first to indicate that CBT programs work with young children", "BACKGROUND Although cognitive-behavioral therapy ( CBT ) is established as a first line treatment for anxiety disorders in children and adolescents , there is little evidence about the effectiveness of CBT protocol s in cases identified in the community in low and middle income countries ( LaMICs ) . AIMS To evaluate the effectiveness of group CBT protocol for youths with anxiety disorders identified in a community sample in LaMICs . METHOD A total of 14 sessions of group CBT for youths and 2 concurrent sessions for parents based on Kendall 's Coping Cat program were offered . Participants were selected from a cross-sectional community study ; 45 subjects fulfilled inclusion criteria and 28 agreed to participate in the open clinical trial . Treatment effectiveness was evaluated with st and ard clinical , self- and parent-rated measures of anxiety , depression , externalizing symptoms and quality of life ( QoL ) . RESULTS Twenty youths completed the protocol . All scales showed an improvement of anxiety and reduction in externalizing symptoms over time , with a moderate to large effect size ( d = 0.59 to 2.06 ; p depressive symptoms or QoL. CONCLUSIONS Consistent with previous evidence , group CBT is effective in treating anxiety disorders in youths . Results encourage further r and omized clinical trials using CBT protocol s adapted and developed to be used in LaMICs", "The current study was design ed to investigate the changes that occur in depression , anxiety , obsessive — compulsive symptoms and health-related quality of life during methylpheni date ( MPH ) treatment in children with attention-deficit hyperactivity disorder ( ADHD ) . Forty-five treatment naive children with ADHD , aged 8—14 , were assessed based on self , parent and teacher reports at the baseline and at the end of the first and third month of MPH treatment regarding changes in inattention , hyperactivity , impulsivity , depression , anxiety and obsessive — compulsive symptoms . Changes in the quality of life were also noted . Repeated measures of analysis of variance ( ANOVA ) tests with Bonferroni corrections were conducted in order to evaluate the data . Symptoms of inattention , hyperactivity and impulsivity were significantly reduced ( p MPH treatment . There were significant decreases in depression ( p = 0.004 ) , trait anxiety ( p = 0.000 ) and checking compulsion symptom scores ( p = 0.001 ) . Moreover , parents reported significant improvements in psychosocial ( p = 0.001 ) and total scores ( p = 0.009 ) of quality of life , despite no change in physical health scores ( p > 0.05 ) . Children ’s ratings of quality of life measures showed no significant changes in physical health and psychosocial scores ( p > 0.05 ) , while total scores significantly improved ( p = 0.001 ) after the treatment . Over a three-month MPH treatment , depression , trait anxiety and checking compulsion symptoms decreased and quality of life seemed to improve along with those of inattention , hyperactivity and impulsivity", "BACKGROUND There are limited published data on the impact of treatment on the health-related quality of life ( HRQOL ) in individuals with autistic disorder . OBJECTIVE The aim of this study was to evaluate the impact of aripiprazole on HRQOL in the treatment of irritability in pediatric patients ( aged 6 - 17 years ) with autistic disorder . METHODS This post hoc analysis assessed data from two 8-week , double-blind , r and omized , placebo-controlled studies that compared the efficacy of aripiprazole ( fixed-dose study , 5 , 10 , and 15 mg/d ; flexible-dose study , 2 - 15 mg/d ) with placebo in the treatment of irritability associated with autistic disorder . HRQOL was assessed at baseline and week 8 using 3 Pediatric Quality of Life Inventory ( PedsQL ™ ) scales . Clinical ly relevant improvement in HRQOL was determined using an accepted distribution-based criterion-1 st and ard error of measurement . RESULTS In total , 316 patients were r and omly assigned to receive treatment with aripiprazole ( fixed-dose study , 166 ; flexible-dose study , 47 ) or placebo ( fixed-dose study , 52 ; flexible-dose study , 51 ) . Aripiprazole was associated with significantly greater improvement than placebo in PedsQL combined-scales total score ( difference , 7.8 ; 95 % CI , 3.8 - 11.8 ; P 3 PedsQL scale scores ( differences [ 95 % CI ] : Emotional Functioning , 7.8 [ 3.4 - 12.2 ] ; Social Functioning , 6.2 [ 0.7 - 11.8 ] ; Cognitive Functioning , 9.3 [ 3.8 - 14.9 ] ; all , P received aripiprazole were significantly more likely than those who received placebo to have a clinical ly meaningful improvement on the combined-scales total score ( odds ratio [ OR ] = 1.9 ; 95 % CI , 1.0 - 3.3 ; P ( OR = 2.2 ; 95 % CI , 1.2 - 4.0 ; P 0.05 ) and Social Functioning scale ( OR = 2.2 ; 95 % CI , 1.2 - 4.1 ; P experience deterioration ( OR : 0.3 , 95 % CI : 0.1 - 0.8 ; P improved HRQOL , as assessed using 3 PedsQL scales , in pediatric patients with irritability associated with autistic disorder", "OBJECTIVE Information on psychostimulant treatment in long-term studies for attention-deficit/hyperactivity disorder ( ADHD ) in adolescents is limited . This study aim ed to assess the safety and effectiveness of lisdexamfetamine dimesylate ( LDX ) over 52 weeks in adolescents with ADHD . METHODS This open-label multicenter study enrolled eligible participants after their participation in a r and omized , double-blind , placebo-controlled 4 week trial in adolescents with ADHD . Following a 4 week dose-optimization phase , participants were maintained on treatment for up to ∼48 weeks on an optimal dose . Safety assessment s included treatment-emergent adverse events ( TEAEs ) , vital signs , laboratory findings , and electrocardiograms . Effectiveness measures included the ADHD Rating Scale IV ( ADHD-RS-IV ; primary ) and Clinical Global Impressions-Improvement ( CGI-I ) . The Youth Quality of Life- Research Version ( YQOL-R ) was also included in this study ; raw scores are transformed to a 0 - 100 point scale . RESULTS Of 269 enrolled ( from the antecedent study ) , 265 ( 98.5 % ) were in the safety population and effectiveness population . Common TEAEs ( ≥5 % ) with LDX included upper respiratory tract infection ( 21.9 % ) , decreased appetite ( 21.1 % ) , headache ( 20.8 % ) , decreased weight ( 16.2 % ) , irritability ( 12.5 % ) , insomnia ( 12.1 % ) , nasopharyngitis ( 7.2 % ) , influenza ( 6.8 % ) , dizziness ( 5.3 % ) , and dry mouth ( 5.3 % ) . At end point , for all LDX doses in the overall safety population , mean ( SD ) increase from baseline in systolic blood pressure was 2.3 ( 10.53 ) mm Hg , diastolic blood pressure was 2.5 ( 8.37 ) mm Hg , and pulse rate was 6.3 ( 12.74 ) bpm . No clinical ly meaningful electrocardiogram or vital sign changes were observed . At end point with LDX treatment , the ADHD-RS-IV mean ( SD ) total score change from antecedent study baseline was -26.2 ( 9.75 ) ( p Baseline ( antecedent study ) mean ( SD ) YQOL-R perceptual total score was 79.8 ( 11.28 ) and increased by 3.9 ( 9.73 ) at end point ( p improvements in ADHD symptoms and participant-perceived YQOL , in adolescents with ADHD . CLINICAL TRIAL REGISTRATION NCT00764868 , http://www . clinical trials.gov/ct2/show/NCT00764868?term=SPD489-306&rank=1", "OBJECTIVE Numerous investigations have examined the efficacy of pharmacological treatment for attention-deficit/hyperactivity disorder ( ADHD ) in children . However , relatively few studies have addressed the impact of treatment on long-term subjective , psychosocial outcomes , such as health-related quality of life ( HRQL ) . This study examines the long-term effects of pharmacological treatment with atomoxetine on HRQL in children and adolescents with ADHD . METHODS Participants included 6- to 17-year-old children and adolescents ( n = 912 ) with ADHD enrolled in a 24-month , multicenter , open-label trial of atomoxetine . Outcomes included clinician ratings of ADHD , parent ratings of ADHD , and a widely used measure of HRQL ( The Child Health Question naire ( CHQ ) ) . Treatment response rates were calculated based on a CHQ improvement of at least 1 st and ard error of measurement . RESULTS Significant improvements in HRQL were found following both acute and long-term treatment for psychosocial but not physical health . Of participants who completed treatment ( n = 312 or 34.2 % of those enrolled ) , 81 % responded to acute treatment and 78 % responded to long-term treatment . Improvements noted after acute treatment were maintained during long-term treatment with the majority of participants ( 86 % ) continuing to respond to treatment . CONCLUSIONS Atomoxetine is associated with improvements in HRQL , and the improvements are generally stable over time", "High-functioning autism ( HFA ) is characterized by persistent impairment in social interaction despite the absence of mental retardation . Although an increasing number of group-based programs for the improvement of social skills have been described , r and omized controlled trials are needed to evaluate their efficacy . To compare the effect of a Social Skills Training Group-based Program ( SST-GP ) and a Leisure Activities Group-based Program ( LA-GP ) on the perception of facial emotions and quality of life ( QoL ) in young people with HFA . Eligible patients were children and adolescents with HFA . Participants were r and omized to the SST or LA group . The primary outcome was defined as an improvement of 2 points in error rates for facial emotion labeling ( DANVA2 ) from baseline . After the 6-month training period , the SST Group made fewer errors in labeling anger on adult faces , whereas error rates in the LA Group remained stable . Progress in the ability to recognize anger in the SST Group was due to better recognition of low intensity stimuli on adult faces . QoL increased in the SST Group in the dimension of school environment , as a marker of the transfer of skills acquired in the treatment setting to their use in the community . The SST-GP had higher efficacy than the LA-GP . Data justify replication using larger sample", "To evaluate what determines the increase in quality of life during treatment for ADHD : improvement in core ADHD symptoms or improvement in global psychopathology ratings . A prospect i ve follow-up of ADHD patients in one community clinic . St and ardized evaluation and outcome measures were used , including the Mini International Neuropsychiatric Interview , Child Symptom Inventory , 18 item ADHD rating scale , and the Health and Life Functioning Scale . 75 patients between the ages of 6 and 12 were treated with atomoxetine or stimulants with a stable dose for 10 months . At end point , there were modest improvements in ADHD symptoms , global psychopathology , level of functioning and quality of life . The improvement in quality of life was driven by a decrease in global psychopathology , not by a decrease in ADHD symptoms . The treatment for ADHD may need to be broadened beyond the core symptoms . A chronic disease management model may well be applicable", "Purpose To evaluate the effect of atomoxetine on quality of life ( QoL ) and family burden in children and adolescents with attention deficit/hyperactivity disorder ( ADHD ) and comorbid oppositional defiant ( ODD ) or conduct disorder ( CD ) . Methods This secondary analysis was based on a r and omized , double-blind , 9-week study of atomoxetine ( target dose 1.2 mg/kg body weight ) versus placebo . The study included 180 patients ( atomoxetine 121 , placebo 59 ) , aged 6–17 years . QoL was measured using the KINDL-R question naire . The total score encompasses six dimensions ( or subscales ) measuring QoL in terms of “ physical well-being ” , “ emotional well-being ” , “ self-esteem ” , “ friends ” , “ family ” , and “ school ” . Family burden of illness was measured using the FaBel question naire . Results With atomoxetine , the KINDL-R total score improved significantly ( P = 0.021 ) more than with placebo . This improvement also applied to the subscales except for “ physical well-being ” ( opposite effect ) and “ school ” ( no effect ) . No significant treatment group differences were seen on the FaBel question naire . No differences were found between the fast and slow titration groups in terms of ADHD , ODD , and disruptive behavior severity . Furthermore , no such differences were observed for QoL and family burden . Conclusions This study suggests positive effects of atomoxetine on quality of life , as measured by the KINDL-R scores on emotional well-being , self-esteem , friends and family , in children and adolescents with ADHD and comorbid ODD/CD . No significant treatment effects were seen on family burden , as measured by FaBel total score", "Objective To evaluate change in quality of life in a community clinic ADHD population treated with atomoxetine or stimulants . No direct comparisons between atomoxetine and stimulants to improve quality of life in ADHD are available . Methods A prospect i ve , nonr and omized comparison between ADHD patients treated with atomoxetine or stimulants in one clinic . Structured diagnostic assessment tools and a specific quality of life measure were used . Results 84 patients ( atomoxetine n = 39/stimulants n = 45 ) , between the ages of 5 and 18 , were treated for approximately 8 months . At end point , there were no significant differences in improvements of quality of life between the two groups . Age , participation in psychotherapy , and parental disability were not correlated with quality of life changes . Patients with lower baseline scores improved most . Conclusions Both atomoxetine and stimulants led to a modest increase in quality of life in this community clinic ADHD population", "OBJECTIVE The aim of this study was to examine global functioning , health-related quality of life ( HRQOL ) , and clinical outcome in children and adolescents with bipolar I disorder , schizophrenia , or schizoaffective disorder following ziprasidone treatment . METHODS Sixty-three subjects ( aged 10 - 17 years ) received open-label ziprasidone , titrated from 10 to 40 mg twice a day ( b.i.d . ) ( low-dose group ) or from 20 to 80 mg b.i.d . ( high-dose group ) ; fixed doses were used until week 3 , followed by flexible doses for 6 months . The Children 's Global Assessment Scale ( CGAS ) characterized functional impairment at baseline and following treatment . The Child Health Question naire ( CHQ ) assessed HRQOL at baseline . RESULTS Baseline CHQ showed greater impairment in psychosocial functioning than in physical health . Baseline mean CGAS scores were substantially below normal ( i.e. , functional impairment . Improvement in CGAS scores occurred as early as the first week of treatment . The low correlations between both CHQ and CGAS and the efficacy measures at baseline indicate that these scales measure different constructs . Nevertheless , there was good correlation between improvements in the CGAS and changes in Brief Psychiatric Rating Scale-Anchored ( BPRS-A ) and Young Mania Rating Scale ( YMRS ) during ziprasidone treatment . CONCLUSION CHQ and CGAS scales may be useful together with st and ard efficacy measures for children and adolescents with these disorders", "Measurement of health-related quality of life ( HRQOL ) in attention-deficit-hyperactivity disorder ( ADHD ) gives a more complete picture of day-to-day functioning and treatment effects than behavioural rating alone . The aim of this pilot study was to investigate the impact of the combined diagnoses of developmental coordination disorder ( DCD ) and ADHD on HRQOL , and the effectiveness of methylpheni date ( MPH ) on HRQOL . HRQOL was established using the Dutch-Child-AZL-TNO- Quality -of-Life ( DUX-25 ) and the TNO-AZL-Child- Quality -of-Life ( TACQOL ) question naires , completed by children and parents . HRQOL of these children was compared with that of 23 age- and sex-matched healthy controls . Twenty-three children ( 21 males , two females ; mean age 8 y 6 mo , [ SD 3 mo ] range 7 y-10 y 8 mo ) with ADHD/DCD entered a 4-week , open-label MPH study , after MPH-sensitivity was established , in a double-blind , placebo-controlled trial . In these children 's self- and proxy reports , impact of both DCD and ADHD was reflected in lower general well-being ( self and proxy report p=0.001 ) due to lower functioning in motor ( selfp=0.026 ; proxy 0.001 ) , autonomic ( self p cognitive ( self p=0.001 ; proxy p=0.01 ) , and social ( self and proxy p domains . HRQOL scores improved in 18 children receiving MPH ( p=0.001 ) versus controls . The ADHD /DCD group also demonstrated a significant improvement in ADHD symptoms ( p motor functioning ( p Additional motor therapy will still be needed in about half of the children with ADHD/DCD receiving MPH , within multimodal treatment including educational and psychosocial assistance", "BACKGROUND Anecdotal reports and some studies suggest that equine-assisted activities may be beneficial in autism spectrum disorders ( ASD ) . OBJECTIVE To examine the effects ofequine-assisted activities on overall severity of autism symptoms using the Childhood Autism Rating Scale ( CARS ) and the quality ofparent-child interactions using the Timberlawn Parent-Child Interaction Scale . In addition , this study examined changes in sensory processing , quality of life , and parental treatment satisfaction . DESIGN AND PARTICIPANTS Children with ASD were evaluated at four time points : ( 1 ) before beginning a 3-to-6 month waiting period , ( 2 ) before starting the riding treatment , and ( 3 ) after 3 months and ( 4 ) 6 months of riding . Twenty-four participants completed the waiting list period and began the riding program , and 20 participants completed the entire 6 months of riding . Pretreatment was compared to posttreatment with each child acting as his or her own control . RESULTS A reduction in the severity of autism symptoms occurred with the therapeutic riding treatment . There was no change in CARS scores during the pretreatment baseline period ; however , there was a significant decrease after treatment at 3 months and 6 months of riding . The Timberlawn Parent-Child Interaction Scale showed a significant improvement in Mood and Tone at 3 months and 6 months of riding and a marginal improvement in the reduction of Negative Regard at 6 months of riding . The parent-rated quality of life measure showed improvement , including the pretreatment waiting period . All of the ratings in the Treatment Satisfaction Survey were between good and very good . CONCLUSION These results suggest that children with ASD benefit from equine-assisted activities", "OBJECTIVE To examine ( 1 ) moderating effects of oppositional defiant disorder ( ODD ) on attention-deficit/hyperactivity disorder ( ADHD ) treatment response and ( 2 ) responses of ODD symptoms to atomoxetine . METHOD Children and adolescents ( ages 8 - 18 ) with ADHD were treated for approximately 8 weeks with placebo or atomoxetine ( fixed dosing : 0.5 , 1.2 , or 1.8 mg/kg/day , b.i.d . ) under r and omized , double-blind conditions . Among patients with lifetime diagnostic information ( n = 293 ) , 39 % were diagnosed with comorbid ODD and 61 % were not . Treatment-group differences and differences between patients with and without comorbid ODD were examined post hoc for changes on the Attention-Deficit/Hyperactivity Disorder Rating Scale IV-Parent version , investigator-administered and -scored ; Conners ' Parent Rating Scale-Revised Short Form ; Clinical Global Impressions Severity of ADHD Scale ; and the parent-rated Child Health Question naire . RESULTS Youths with ADHD and comorbid ODD showed statistically significant improvement in ADHD , ODD , and quality -of-life measures . Treatment response was similar in youths with and without ODD , except that the comorbid group showed improvement compared with placebo at 1.8 mg/kg/day but not 1.2 mg/kg/day . In contrast , youths without ODD showed improvement at 1.2 mg/kg/day and no incremental benefit at 1.8 mg/kg/day . CONCLUSIONS Atomoxetine treatment improves ADHD and ODD symptoms in youths with ADHD and ODD , although the comorbid group may require higher doses", "OBJECTIVE To evaluate the feasibility and helpfulness of a behavioral sleep program for children with ADHD , and explore the impact of different program dosages on child and family outcomes . METHODS R and omised trial comparing a brief ( 1 session , n=13 ) and extended ( 2 - 3 sessions , n=14 ) sleep program in children with ADHD ( aged 5 - 14 years ) and at least one behavioral sleep disorder ( American Academy of Sleep Medicine Criteria ) . Outcomes included helpfulness and use of interventions , child sleep ( parent-reported sleep problem ; Child Sleep Habits Question naire ) , ADHD symptoms ( ADHD IV Rating Scale ) , daily functioning ( Daily Parent Rating of Evening and Morning Behavior ) , quality of life ( Pediatric Quality of Life Inventory ) , and caregiver mental health ( Depression Anxiety Stress Scales ) . RESULTS Twenty-seven families ( 63 % of those eligible ) took part . Most parents would recommend the program to others ( 95 % ) and found the strategies helpful . Five months post-r and omisation , 67 % of parents in both groups reported that their child 's sleep problems had resolved . Child quality of life , daily functioning , and parental anxiety also improved in the extended group only ( Cohen 's d : 0.39 , 0.47 and 0.50 , respectively ) . There was minimal change in ADHD symptom scores from baseline to 5 months in either group . CONCLUSIONS A behavioral sleep intervention in children with ADHD is feasible to deliver and improves child sleep by parent report . The extended program result ed in greater improvements in child and caregiver outcomes", "OBJECTIVE The aim of this study was to examine whether quetiapine is superior to placebo in the treatment of adolescents with conduct disorder . METHODS This was a 7-week , r and omized , double-blind , placebo-controlled pilot study with two parallel arms . Nine youths were r and omly assigned to receive quetiapine , and 10 youths were r and omly assigned to receive placebo . Patients were assessed weekly throughout the trial . Quetiapine was dosed twice daily , and medications could be titrated flexibly through the end of study week 5 . The dose was fixed for the final 2 weeks of the study . The primary outcome measures were the clinician-assessed Clinical Global Impressions-Severity ( CGI-S ) and -Improvement ( CGI-I ) scales . Secondary outcome measures included parent-assessed quality of life , the overt aggression scale ( OAS ) , and the conduct problems subscale of the Conners ' Parent Rating Scale ( CPRS-CP ) . RESULTS The final mean dose of quetiapine was 294 + /- 78 mg/day ( range 200 - 600 mg/day ) . Quetiapine was superior to placebo on all clinician-assessed measures and on the parent-assessed quality of life rating scale . No differences were found on the parent-completed OAS and CPRS-CP . Quetiapine was well tolerated . One patient r and omized to quetiapine developed akathisia , requiring medication discontinuation . No other extrapyramidal side effects occurred in patients receiving active drug . CONCLUSIONS This method ologically controlled pilot study provides data that quetiapine may have efficacy in the treatment of adolescents with conduct disorder . Because of the preliminary nature of the study , further research with larger sample s is needed to confirm these findings", "Objective : To explore the clinical outcomes of children/adolescents with attention-deficit/hyperactivity disorder ( ADHD ) who required a therapy switch from atomoxetine to OROS ® methylpheni date ( MPH ) . Methods : This prospect i ve , noninterventional study involved patients aged 6–18 years with a confirmed diagnosis of ADHD who experienced insufficient clinical response and /or poor tolerability during atomoxetine treatment . Patients were transitioned to OROS MPH and followed for 12 weeks . ADHD symptoms , functional outcomes , health-related quality of life ( HRQoL ) and tolerability were assessed throughout the study . Results : 42 patients ( intention-to-treat ) transitioned from atomoxetine 43.2 plus 14.7 mg onto OROS MPH 33.0 plus 17.7 mg ( mean daily starting dose ) , increasing to 38.6 plus 17.6 mg at the final visit . Median treatment duration was 85 days ( range : 3–155 ) . Compared with baseline , symptoms , functional outcome and HRQoL improved after transitioning to OROS MPH as assessed by the Conners ’ Parent Rating Scale ( mean change from baseline : -10.1 ± 11.6 ; p , Children ’s Global Assessment Scale ( 8.7 ± 16.2 ; p = 0.0015 ) and ILC-LQ0–28 scores ( parents ’ rating from 14.9 ± 3.6 [ baseline ] to 17.5 ± 4.8 [ study end ] ; p = 0.0002 ; patients ’ rating from 16.9 ± 3.9 [ baseline ] to 19.3 ± 4.4 [ study end ] ; p = 0.0003 ) . Social interactions and late afternoon tasks ( playing with other children , household chores , school homework and behavior towards visitors/at visits ) improved ( p expressed satisfaction ( ‘ very good ’ or ` good ’ ) with OROS MPH therapy compared with prior atomoxetine with respect to symptom control in the late afternoon . The most common treatment-emergent adverse events after switching were involuntary muscle contractions ( tics ; 16.7 % ) , insomnia ( 14.3 % ) , abdominal pain ( 9.5 % ) and headache ( 9.5 % ) . No clinical ly relevant changes in body weight or vital signs were observed . Conclusion : In this naturalistic setting , transitioning from atomoxetine to OROS MPH was associated with improved ADHD symptoms and impacted positively on patients ’ and parents ’ HRQoL and disease burden in ADHD children who demonstrated an insufficient response and /or poor tolerability to atomoxetine " ]

[ "In a prior study [ Festinger , D.S. , Marlowe , D.B. , Croft , J.R. , Dugosh , K.L. , Mastro , N.K. , Lee , P.A. , DeMatteo , D.S. , Patapis , N.S. , 2005 . Do research payments precipitate drug use or coerce participation ? Drug Alcohol Depend . 78 ( 3 ) 275 - 281 ] we found that neither the mode ( cash vs. gift card ) nor magnitude ( $ 10 , $ 40 , or $ 70 ) of research follow-up payments increased rates of new drug use or perceptions of coercion . However , higher payments and payments in cash were associated with better follow-up attendance , reduced tracking efforts , and improved participant satisfaction with the study . The present study extended those findings to higher payment magnitudes . Participants from an urban outpatient substance abuse treatment program were r and omly assigned to receive $ 70 , $ 100 , $ 130 , or $ 160 in either cash or a gift card for completing a follow-up assessment at 6 months post-admission ( n congruent with 50 per cell ) . Apart from the payment incentives , all participants received a st and ardized , minimal platform of follow-up efforts . Findings revealed that neither the magnitude nor mode of payment had a significant effect on new drug use or perceived coercion . Consistent with our previous findings , higher payments and cash payments result ed in significantly higher follow-up rates and fewer tracking calls . In addition participants receiving cash vs. gift cards were more likely to use their payments for essential , non-luxury purchases . Follow-up rates for participants receiving cash payments of $ 100 , $ 130 , and $ 160 approached or exceeded the FDA required minimum of 70 % for studies to be considered in evaluations of new medications . This suggests that the use of higher magnitude payments and cash payments may be effective strategies for obtaining more representative follow-up sample s without increasing new drug use or perceptions of coercion", "Past studies find that attention deficit hyperactivity disorder ( ADHD ) creates a higher risk for adverse driving outcomes . This study comprehensively evaluated driving in adults with ADHD by comparing 105 young adults with the disorder ( age 17 - 28 ) to 64 community control ( CC ) adults on five domains of driving ability and a battery of executive function tasks . The ADHD group self-reported significantly more traffic citations , particularly for speeding , vehicular crashes , and license suspensions than the CC group , with most of these differences corroborated in the official DMV records . Cognitively , the ADHD group was less attentive and made more errors during a visual reaction task under rule-reversed conditions than the CC group . The ADHD group also obtained lower sceres on a test of driving rules and decision-making but not on a simple driving simulator . Both self- and other-ratings showed the CC group employed safer routine driving habits than the ADHD group . Relationships between the cognitive and driving measures and the adverse outcomes were limited or absent , calling into question their use in screening ADHD adults for driving risks . Several executive functions also were significantly yet modestly related to accident frequency and total traffic violations after controlling for severity of ADHD . These results are consistent with earlier studies showing significant driving problems are associated with ADHD . This study found that these driving difficulties were not a function of comorbid oppositional defiant disorder , depression , anxiety , or frequency of alcohol or illegal drug use . Findings to date argue for the development of interventions to reduce driving risks among adults with ADHD", "Driving performance of adult males with attention-deficit hyperactivity disorder ( ADHD ) was compared with matched controls in a double-blind ( Ritalin vs. placebo ) cross-over design , using a high-fidelity driving simulator . Seven ADHD and six non-ADHD drivers ( mean age 22 ) were screened to rule out comorbidity and assess for ADHD , and then admitted to the General Clinical Research Center to control diet and sleep before testing . At 0800 and 1530 , subjects consumed either a placebo or Ritalin pill in a counter-balanced manner , and at 0930 and 1700 , subjects drove the simulator . After both drives , subjects rated their driving performance . Compared with non-ADHD subjects , ADHD subjects had more career driving accidents ( p motor vehicle violations ( p = .059 ) , drove worse on the simulator under placebo condition ( p demonstrated significant improvement under the Ritalin condition ( p driving poorer during the placebo condition ( p = .05 ) , and tended to perceive their driving to be better during the Ritalin condition ( p = .07 ) . This would suggest that individuals with ADHD should have the therapeutic benefit of a stimulant medication when operating a vehicle", "This study investigated whether ERPs from an inter-modal oddball task could distinguish between adults with Attention-Deficit/Hyperactivity Disorder ( AD/HD ) and controls . Two age-matched groups of young adult males ( 18 AD/HD , 18 controls ) were presented with an inter-modal oddball task in which a counter-phasing checkerboard was the non-target visual stimulus ( r and omly presented on 80 % of trials ) , and a 2000 Hz tone was the auditory target ( 20 % of trials ) . Stimuli were presented at a fixed rate ( stimulus-onset asynchrony 1.03 s ) and participants were required to silently count all targets . The AD/HD group showed globally enhanced P2 and reduced N2 amplitudes to auditory targets , with no differences in target P3 , together with topographic differences in N1 to auditory targets , and P1 , N1 , P2 , N2 and P3 to visual non-targets , compared with controls . These results were interpreted in terms of early sensory-processing impairments in adults with AD/HD , which may be partially overcome through effortful processing , as reflected in the later endogenous ERP components", "This study examined whether adolescent females with attention-deficit/hyperactivity disorder ( ADHD ) are differentially responsive than their male counterparts to extended-release stimulant medications . This investigation may bear special importance for an adolescent ( as opposed to child ) population , because hormonal and metabolism differences between sexes are most likely to emerge at this time . Male ( n = 19 ) and female ( n = 16 ) adolescents , ages 16–19 with ADHD , participated in a r and omized , double-blind crossover study evaluating the effectiveness of osmotic-release methylpheni date , extended release amphetamine salts , placebo , and routine limited medication regimen . Medication efficacy was evaluated using ADHD symptom ratings from adolescent self-report and parent report , along with objective measures of inattention and hyperactivity/impulsivity during driving performance and neuropsychological tasks . Males and females were largely equivalent in impairment , and medication was similarly effective in reducing symptoms . No interactions were found between sex and medication on any measure of effectiveness or side effects . This finding suggests that the efficacy and tolerability of extended-release stimulant medications is equivalent for male and female adolescents with ADHD", "BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement ) combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes", "OBJECTIVE Adolescents with attention-deficit/hyperactivity disorder ( ADHD ) are at high risk for driving accidents . One dose of methylpheni date ( MPH ) improves simulator driving performances of ADHD-diagnosed adolescents at 1.5 hours post-dose . However , little is known about the effects of different MPH delivery profiles on driving performance throughout the day . METHOD This r and omized , crossover , single-blind study compared osmotic , controlled-release oral system ( OROS ) MPH ( Concerta ) given q.d . to immediate-release MPH ( Ritalin ) given in equal doses t.i.d . on driving performance among six male ADHD-diagnosed adolescent drivers aged 16 to 19 years . Under each treatment condition , participants were maintained on their medication dosage for 7 days , then drove a sophisticated driving simulator at 2 p.m. , 5 p.m. , 8 p.m. , and 11 p.m. The primary outcome measure was each participant 's computer-quantified Impaired Driving Score ( IDS ) . RESULTS IDS worsened in the evenings for participants receiving MPH t.i.d . but remained stable when they received once-daily OROS MPH . Participants performed significantly better when receiving OROS MPH q.d . compared with MPH t.i.d . ( F = 9.3 , df = 1 , p = .004 ) . When MPH was given t.i.d . , IDS significantly worsened beginning at 8 p.m. compared to OROS MPH ( p = .01 ) . CONCLUSIONS Participants demonstrated significantly less variability and better driving performance when receiving OROS MPH q.d . compared to MPH t.i.d . , particularly in the evenings", "Although patients with attention-deficit hyperactivity disorder ( ADHD ) have reported improved driving performance on methylpheni date , limited evidence exists to support an effect of treatment on driving performance and some regions prohibit driving on methylpheni date . A r and omized , crossover trial examining the effects of methylpheni date versus placebo on highway driving in 18 adults with ADHD was carried out . After three days of no treatment , patients received either their usual methylpheni date dose ( mean : 14.7 mg ; range : 10—30 mg ) or placebo and then the opposite treatment after a six to seven days washout period . Patients performed a 100 km driving test during normal traffic , 1.5 h after treatment administration . St and ard deviation of lateral position ( SDLP ) , the weaving of the car , was the primary outcome measure . Secondary outcome measurements included the st and ard deviation of speed and patient reports of driving performance . Driving performance was significantly better in the methylpheni date than in the placebo condition , as reflected by the SDLP difference ( 2.3 cm , 95 % CI = 0.8—3.8 , P = 0.004 ) . Variation in speed was similar on treatment and on placebo ( -0.05 km/h , 95 % CI = -0.4 to 0.2 , P = 0.70 ) . Among adults with ADHD , with a history of a positive clinical response to methylpheni date , methylpheni date significantly improves driving performance", "BACKGROUND Attention-deficit/hyperactivity disorder ( ADHD ) is associated with a 3- to 4-fold increase in both driving-related accidents and associated injuries . Methylpheni date ( MPH ) is the most commonly prescribed psychostimulant medication for ADHD . It has been demonstrated to improve performance on a driving simulator . This study investigated whether a once-daily , long-acting , osmotic , controlled-release MPH formulation improves the driving performance of ADHD adolescents while driving their own car on an actual road segment . METHODS Twelve ADHD-diagnosed male adolescent drivers ( mean age , 17.8 years ) prescribed a st and ard dose of 1.0 mg/kg ( if they were not already taking methylpheni date ) of controlled-release MPH participated in this repeated- measures crossover study . On 2 separate occasions ( off/on medication r and omized ) , participants drove a st and ard 16-mile road course incorporating rural , highway , and urban streets . A rater , blind to medication conditions , sat in the back seat and rated impulsive ( eg , \" cutting off \" another driver ) and inattentive ( eg , drove past design ated turn ) driving errors . RESULTS Impulsive driving errors were observed to occur rarely under both medication and no medication conditions . Inattentive driving errors were more common and were significantly reduced while the subject was on medication ( 4.6 versus 7.8 ; P driving performance ( change in number of errors recorded ) from first to second testing was positively correlated with medication dosage ( r = 0.60 ; P MPH improves real-life driving performance of adolescent males diagnosed with ADHD . In particular , it significantly reduces driving errors arising from inattention", "Background : Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder ( ADHD ) . Method : This was a r and omized , double-blind , placebo-controlled , crossover study of simulated driving performance with mixed amphetamine salts — extended release ( MAS XR ) 50 mg/day ( Cohort 1 ) and atomoxetine 80 mg/day ( Cohort 2 ) in young adults with ADHD . Results : Adults aged 19 to 25 years with AD/HD ( N = 19 ) who were administered MAS XR significantly improved overall simulated driving performance versus placebo up to 12 hours after dosing . In contrast , there were no statistically significant differences in simulated-driving-performance scores between atomoxetine and placebo . At endpoint , MAS XR reduced ADHD Rating Scale scores ≥ 30 % in 80 % of subjects , whereas atomoxetine achieved this level of improvement for 40 % . Limitations : Small sample size and use of simulated driving may limit generalizability of the findings . Conclusion : MAS XR in young adults with ADHD yields significant improvements in simulated driving performance and ADHD symptoms . ( J. of Att . Dis . 2009 ; 12(4 ) 316 - 329", "This study investigated whether OROS methylpheni date ( OROS MPH , Concerta ) or extended-release mixed amphetamine salts ( se-AMPH ER , Adderall XR ) were associated with worsening of driving performance , or drug rebound , relative to placebo 16 - 17 hours post-ingestion . Nineteen male adolescent drivers aged 17 - 19 with attention-deficit/hyperactivity disorder ( ADHD ) were compared on a virtual reality driving simulator and an on-road drive after taking 72 mg of OROS MPH , 30 mg of se-AMPH ER , or placebo . Medication was taken at 08:00 in a r and omized , double-blind , placebo-controlled , crossover study . Participants drove a simulator at 17:00 , 20:00 , 23:00 , and 01:00 , and drove their own cars over a 16-mile road course at 24:00 . The main outcome measures were composite scores of driving performance . Neither OROS MPH nor se-AMPH ER was associated with significant worsening of simulator performance relative to placebo 17 hours post-ingestion in group comparisons . However , inattentive on-road driving errors were significantly more common on se-AMPH ER relative to placebo at midnight ( p = 0.04 ) , suggesting possible rebound . During both late simulator and on-road testing , driving performance variance was approximately 300 % greater during the se-AMPH ER compared to the OROS MPH condition", "INTRODUCTION Numerous studies have documented an increased frequency of vehicular crashes , traffic citations , driving performance deficits , and driving-related cognitive impairments in teens and adults with attention deficit hyperactivity disorder . METHOD The present study evaluated the effects of two single , acute doses of methylpheni date ( 10 and 20 mg ) and a placebo on the driving performance of 53 adults with ADHD ( mean age=37 years , range=18 - 65 ) using a virtual reality driving simulator , examiner and self-ratings of simulator performance , and a continuous performance test ( CPT ) to evaluate attention and inhibition . A double-blind , drug-placebo , within-subjects crossover design was used in which all participants were tested at baseline and then experienced all three drug conditions . RESULTS A significant beneficial effect for the high dose of medication was observed on impulsiveness on CPT , variability of steering in the st and ard driving course , and driving speed during the obstacle course . A beneficial effect of the low dose of medication also was evident on turn signal use during the st and ard driving course . An apparent practice effect was noted on some of the simulator measures between the baseline and subsequent testing sessions that may have interacted with and thereby obscured drug effects on those measures . CONCLUSIONS The results , when placed in the context of prior studies of stimulants on driving performance , continue to recommend their clinical use as one means of reducing the driving risks in ADHD teens and adults . IMPACT ON INDUSTRY Given the significantly higher risk of adverse driving outcomes associated with ADHD , industry needs to better screen for ADHD among employees who drive as part of employment so as to improve safety and reduce costs . Use of stimulants to treat the adult ADHD driver may reduce safety risks", "OBJECTIVE . Automobile accidents are the leading cause of death among adolescents , and collisions are 2 to 4 times more likely to occur among adolescents with attention-deficit/hyperactivity disorder . Studies have demonstrated that stimulants improve driving performance . This study compared 2 long-acting stimulant medications during daytime and evening driving evaluations . METHODS . Adolescent drivers with attention-deficit/hyperactivity disorder were compared on a driving simulator after taking 72 mg of OROS methylpheni date , 30 mg of mixed amphetamine salts extended release , or placebo in a r and omized , double-blind , placebo-controlled , crossover study design . During laboratory testing , adolescents drove a driving simulator at 5:00 pm , 8:00 pm , and 11:00 pm . Driving performance was rated by adolescents and investigators . RESULTS . The study included 35 adolescent drivers with attention-deficit/hyperactivity disorder ( 19 boys/16 girls ) . The mean age was 17.8 years . The overall Impaired Driving Score demonstrated that OROS methylpheni date led to better driving performance compared with placebo and mixed amphetamine salts extended release , whereas mixed amphetamine salts extended release demonstrated no statistical improvement over placebo . Specifically , relative to placebo , OROS methylpheni date result ed in less time driving off the road , fewer instances of speeding , less erratic speed control , more time executing left turns , and less inappropriate use of brakes . OROS methylpheni date and mixed amphetamine salts extended release worked equally well for male and female adolescents and equally as well with teenagers who have combined and inattentive subtypes of attention-deficit/hyperactivity disorder . CONCLUSIONS . This study vali date s the use of stimulants to improve driving performance in adolescents with attention-deficit/hyperactivity disorder . In the study , OROS methylpheni date promoted significantly improved driving performance compared with placebo and mixed amphetamine salts extended release", "Abstract This study investigated whether methylpheni date delivered through a long-acting transdermal system ( MTS ) would reduce collision rates of young adult drivers with attention-deficit/hyperactivity disorder ( ADHD ) . Seventeen young adults completing the study ( mean [ SD ] age , 20.82 [ 2.40 ] years ; 14 men and 13 white ) met the following inclusion criteria : ADHD diagnoses but not routinely taking ADHD medication , previously responsive to ADHD medication , active drivers with more than 1 collision or citation in the past 2 years , and no significant comorbidities . In this open-labeled , crossover design drivers were r and omly assigned either to the no-medication condition for 3 months and then MTS for 3 months or to the reverse sequence . In-car video monitoring of routine driving occurred during these 6 months . At baseline and after each condition , participants completed the Conners Adult ADHD Rating Scale and the Cox Assessment of Risky Driving Scale , and their blood pressure , heart rate , and body weight were monitored . Compared with the no-medication condition , participants in the MTS condition self-reported fewer total ADHD ( P and inattentive symptoms ( P = 0.014 ) and a trend for risky driving behaviors ( P = 0.059 ) and had fewer video-recorded collisions ( P driving events . There were no significant changes in blood pressure , heart rate , or body weight across conditions or any significant skin reactions to the MTS patch . This is the first study demonstrating that long-acting methylpheni date improves activities of daily living among young adults with ADHD . Specifically , methylpheni date improved safety in routine driving while reducing ADHD symptoms with minimal adverse effects", "PURPOSE Young adults with ADHD have been shown to be at increased risk for impairment in driving behaviors . Although stimulant medications have proven efficacy in reducing ADHD symptomatology , there is limited knowledge as to their effects on driving behavior . The focus of this report is on assessing the impact of lisdexamfetamine dimesylate ( LDX ) on driving behaviors in young adults with ADHD using a vali date d driving behavior question naire . METHODS This assessment was carried out in the context of a r and omized , double-blind , 6-week , placebo-controlled , parallel- design study of LDX versus placebo . Subjects were 61 out patients of both sexes , 18 - 26 years of age , who met Diagnostic and Statistical Manual of Mental Disorders , fourth edition , criteria for ADHD . Subjects were r and omized to receive LDX or placebo for 6 weeks . Driving behavior was assessed at baseline and at the end of treatment using a U.S. version of the Manchester Driving Behavior Question naire ( DBQ ) . RESULTS Highly significant improvements were documented on LDX , over placebo , in driving behaviors assessed through the DBQ in measures of driving errors , driving lapses , and a trend toward fewer driving violations . There were no meaningful associations between these DBQ results and previously documented changes in a laboratory driving simulation paradigm or with improvement in symptoms of ADHD assessed through the ADHD rating scale . CONCLUSIONS LDX treatment was associated with significant improvements in self-reported driving behaviors that were independent of improvement in symptoms of ADHD . These results suggest that LDX may reduce behaviors associated with driving risks in young adults with ADHD", "PURPOSE To evaluate the motor vehicle driving knowledge , skills , and negative driving outcomes of older teens and young adults with attention deficit hyperactivity disorder ( ADHD ) . LOCATION A university medical center clinic for adult ADHD . SUBJECTS A total of 25 young adults with ADHD and 23 young adults without ADHD 17 to 30 years old drawn from the community and equated for age , gender , and educational level . MEASURES Structured interview , behavior ratings by self- and others , video test of driving knowledge , computer simulated driving test , and official motor vehicle records . RESULTS ADHD young adults were cited more often for speeding , were more likely to have had their licenses suspended , were involved in more crashes , were more likely to have had crashes causing bodily injury , and were rated by themselves and others as using poorer driving habits . Official driving records corroborated these negative outcomes . Although no group differences in driving knowledge were evident , young adults with ADHD had more crashes , scrapes , and erratic steering during the computer-stimulated driving test than did the control subjects . CONCLUSIONS Findings supported previous research suggesting that greater driving risks are associated with ADHD and suggested that ADHD does not interfere with driving knowledge so much as with actual performance ( motor control ) during vehicle operation", "Young adults with Attention Deficit Hyperactivity Disorder ( ADHD ) have been shown to be at increased risk for impairment in driving behaviors . While stimulant medications have proven efficacy in reducing ADHD symptomatology , there is limited knowledge as to their effects on driving impairment . The main aim of this study was to assess the impact of lisdexamfetamine dimesylate ( LDX ) on driving performance in young adults with ADHD using a vali date d driving simulation paradigm . This was a r and omized , double-blind , 6-week , placebo-controlled , parallel- design study of LDX vs. a placebo on driving performance in a vali date d driving simulation paradigm . Subjects were sixty-one out patients of both sexes , 18 - 26 years of age , who met DSM-IV criteria for ADHD . Subjects were r and omized to receive LDX or placebo after a baseline driving simulation and completed a second driving simulation six weeks after beginning drug or placebo . Examination of reaction time across five surprise events at post-treatment showed a significant positive effect of medication status . LDX treatment was also associated with significantly fewer accidents vs. placebo . LDX treatment was associated with significantly faster reaction times and a lower rate of simulated driving collisions than placebo . These results suggest that LDX may reduce driving risks in young adults with ADHD" ]

[ "A clinical trial , aim ed at secondary prevention of low-back pain , was performed in 142 hospital employees reporting at least three annual episodes of this condition . Participants were r and omly assigned to one of three groups : a calisthenics program ( CAL ) for 3 months with biweekly sessions of flexion exercises , a back school program ( 5 sessions ) , and a control group . The effectiveness of the two intervention programs was evaluated over a 1-year period . Baseline preintervention data and evaluation at the end of 3 months of intervention and after an additional 6 months were collected . A monthly surveillance for the whole year showed a mean of 4.5 “ painful months ” in the CAL group versus 7.3 and 7.4 months in the back school and control groups , respectively ( P CAL group was achieved partly because of the significant increase in trunk forward flexion and to initial increment in abdominal muscle strength . The increased trunk flexion was associated with the rate of participation in the CAL sessions . Further research is needed to answer the question of “ intensity versus type of exercise ” by comparing different intervention programs , with similar intensity", "This study was funded in part by NIH grant AR36308 The authors thank the employees of the United States Postal Service and the American Postal Workers Union ( APWU ) , Boston Metro Area Local , and Maith and lers Local 301 for their help and cooperation ; therapists from the Department of Rehabilitation Services , Bngham and Women 's Hospital for help in training workers ; and Ms Nancy Tanner for", "This study was design ed to determine the effect of multimodal intervention and the prevention of back injury , and to evaluate the adverse side effects of using a lumbosacral corset in the workplace . Subjects were 90 male warehouse workers r and omly selected from over 800 employees at a grocery distribution center . Subjects were assigned to three groups : true controls , no back school , no brace orthoses ; back school only ; and back school plus wearing a custom molded lumbosacral orthosis . Comparisons of pre-testing and 6-month follow-up posttesting for abdominal strength , cognitive data , work injury incidence and productivity and use of health care services were evaluated . Controls and training-only group showed no changes in strength productivity or lost time . Orthoses and training-group showed no changes in strength productivity or accident rate ; however , they showed substantially less lost time . This study supports the concept of using education and prophylactic bracing to prevent back injury and reduce time loss . It appears that the use of intermittent prophylactic bracing has no adverse affects on abdominal muscle strength and may contribute to decreased lost time from work injuries", "The personnel at a geriatric hospital were r and omized into two groups . One group was allowed to exercise during working hours to improve back muscle strength , endurance , and coordination . The other group did not participate in the exercise program and received no further advice or information . After 13 months , the training group had increased back muscle strength . One subject had been absent from work 28 days in the training group whereas 12 subjects had been absent 155 days from work because of low back pain in the control group ( P back pain complaints and intensity of back pain in the training group also decreased in a statistically significant way . Every hour spent by the physiotherapist on the training group reduced the work absence among the participants by 1.3 days , result ing in a cost/benefit ratio greater than 10", "To define the cost-effectiveness of a back school program in industry , a controlled longitudinal field study was carried out in a Dutch bus company . The experimental group received a program consisting of information on back care , physical fitness , nutrition , stress , and relaxation . Objective data on absenteeism were collected and compared during a 6-year period for the control and experimental groups . Results showed that a tailor-made back school program reduced absenteeism by at least 5 days per year per employee , therefore being cost-effective to industry . A reduction was not observed in incidence , but in mean length of absenteeism . This effect turned out to be persistent during a 2-year period following the program", "Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor", "OBJECTIVE --To determine the quality of r and omised controlled trials of exercise therapy for back pain . DESIGN --Computer aided search of published papers and blinded assessment of the methods of studies . SUBJECTS--23 r and omised controlled trials , of which 16 studied exercise therapy given by physiotherapists to individual patients with back pain . Other conservative treatments could be included . MAIN OUTCOME MEASURES --Score for quality of methods ( based on four main categories : study population , interventions , measurement of effect , and data presentation and analysis ) and main conclusion of author(s ) with regard to exercise therapy . RESULTS --Only four studies scored more than 50 points ( maximum 100 ) , indicating that most were of poor quality . Six studies found that exercise was better than reference treatments and 10 reported it to be no better or worse than the reference treatment . Those reporting positive results tended to have higher methods scores ( 4/6 positive v 4/10 negative scored greater than or equal to 42 ) . CONCLUSIONS --No conclusion can be drawn about whether exercise therapy is better than other conservative treatments for back pain or whether a specific type of exercise is more effective . Further trials are needed in which greater attention is paid to methods of study", "The purpose s of this study were to evaluate the effect of a weekly exercise program on short-term sick leave ( less than 50 days ) attributable to back pain and to determine whether changes in absenteeism were related to changes in cardiovascular fitness . Subjects were r and omly assigned to an exercise group ( n = 58 ) and a control group ( n = 53 ) . Sick leave attributable to back pain was determined in the intervention period of 1 1/2 years and a comparable 1 1/2-year period prior to the study . In the exercise group , the number of episodes of back pain and the number of sick-leave days attributable to back pain in the intervention period decreased by over 50 % . Absenteeism attributable to back pain increased in the control group . The decrease in sick leave in the exercise group was not accompanied by any change in cardiovascular fitness . Suggestions for establishing exercise programs are given", "This study evaluated the efficacy of a commercially available weightlifting belt in relation to reduction of lumbar injury incident rate and severity of injuries over an 8-month period . The study used 642 baggage h and lers working for a major airline company as participants . Four treatment groups were r and omly selected : a group receiving the belt only , a group receiving a 1 h training class only , a group receiving both a belt and a 1 h training class , and a control group receiving nothing . Two treatment groups were added which contained participants who discontinued use of the belt prior to the end of an 8-month study period . Results indicated that there were no significant differences for total lumbar injury incident rate , restricted workday case injury incident rate , lost workdays and restricted workdays rate , and worker 's compensation rates . There was , however , a marginal significant difference for lost workday case injury incident rate . Groups with participants who wore the belt for a while then discontinued its use had a higher lost day case injury incident rate than did either the group receiving training only or the control group . Compliance was an overriding factor as the belt question naire response indicated that 58 % of participants in the belt groups discontinued use of the belt before the end of 8 months . Comments made on the survey forms indicated that the belt was too hot . Similarly , comments suggested that the belt rubbed , pinched , and bruised ribs . Based on these results , the weightlifting belt used for this study can not be recommended for use in aid of lifting during daily work activities of baggage h and lers . Results indicate that use of the belts may , in fact , increase the risk of injury when not wearing a belt following a period of wearing a belt . As industries are experimenting with the use of belts , it is recommended that great care be taken in any further evaluation and close attention directed towards injuries which occur when not wearing the belt following a period of wearing the belt ( ie , off-the-job injuries )" ]

[ "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Two experiments were conducted to evaluate particle size of calcium carbonate used in diets fed to growing pigs . Experiment 1 was conducted to determine apparent total tract digestibility ( ATTD ) , st and ardized total tract digestibility ( STTD ) , and retention of Ca among diets containing calcium carbonate produced to different particle sizes , and Exp . 2 was conducted to determine if growth performance of weanling pigs is affected by particle size of calcium carbonate . In Exp . 1 , 4 diets based on corn and potato protein isolate were formulated to contain 0.70 % Ca and 0.33 % st and ardized total tract digestible P , but the calcium carbonate used in the diets was ground to 4 different particle sizes ( 200 , 500 , 700 , or 1,125 μm ) . A Ca-free diet was formulated to determine basal endogenous losses of Ca . In Exp . 2 , 4 diets were based on corn and soybean meal and the only difference among diets was that each diet contained calcium carbonate ground to the 4 particle sizes used in Exp . 1 . In Exp . 1 , 40 barrows ( 15.42 ± 0.70 kg initial BW ) were allotted to the 5 diets with 8 replicate pigs per diet using a r and omized complete block design , and in Exp . 2 , 128 pigs with an initial BW of 9.61 ± 0.09 kg were r and omly allotted to 4 experimental diets . Results of Exp . 1 indicated that basal endogenous losses of Ca were 0.329 g/kg DMI . The ATTD of Ca was 70.0 ± 3.2 , 74.3 ± 2.7 , 70.0 ± 2.9 , and 72.1 ± 2.7 and the STTD of Ca was 74.2 ± 3.2 , 78.5 ± 2.7 , 74.1 ± 2.9 , and 76.2 ± 2.7 for calcium carbonate ground to 200 , 500 , 700 , or 1,125 μm , respectively . Retention of Ca was 67.4 ± 3.1 , 70.4 ± 2.6 , 63.9 ± 2.8 , and 67.2 ± 2.2 for diets containing calcium carbonate ground to 200 , 500 , 700 , or 1,125 μm , respectively . There were no differences among diets for ATTD of Ca , STTD of Ca , or retention of Ca . The ATTD of P was 64.5 ± 1.7 , 66.8 ± 2.6 , 64.2 ± 3.0 , and 63.2 ± 1.7 % and retention of P was 61.4 ± 1.4 , 63.8 ± 2.8 , 61.9 ± 2.8 , and 60.9 ± 1.5 for diets containing calcium carbonate ground to 200 , 500 , 700 , or 1,125 μm , respectively . Neither ATTD of P nor retention of P was influenced by the particle size of calcium carbonate . Results of Exp . 2 indicated that ADG , ADFI , and G : F were not impacted by the particle size of calcium carbonate . In conclusion , particle size of calcium carbonate did not affect ATTD of Ca , STTD of Ca , or retention of Ca ; ATTD of P or retention of P ; or growth performance of pigs . Any particle size of calcium carbonate in the range from 200 to 1,125 μm can therefore be used in diets fed to pigs", "Models for the analysis of longitudinal data must recognize the relationship between serial observations on the same unit . Multivariate models with general covariance structure are often difficult to apply to highly unbalanced data , whereas two-stage r and om-effects models can be used easily . In two-stage models , the probability distributions for the response vectors of different individuals belong to a single family , but some r and om-effects parameters vary across individuals , with a distribution specified at the second stage . A general family of models is discussed , which includes both growth models and repeated- measures models as special cases . A unified approach to fitting these models , based on a combination of empirical Bayes and maximum likelihood estimation of model parameters and using the EM algorithm , is discussed . Two examples are taken from a current epidemiological study of the health effects of air pollution", "Sixty-six barrows ( initial BW : 27.4 ± 2.8 kg ) were used to determine the st and ardized total tract digestibility ( STTD ) of P in copra meal ( CM ) , palm kernel expellers from Indonesia ( PKE-IN ) , palm kernel expellers from Costa Rica ( PKE-CR ) , palm kernel meal from Costa Rica ( PKM ) , and soybean meal ( SBM ) without or with exogenous phytase . Pigs were housed individually in metabolism cages and allotted to 11 diets with 6 replicate pigs per diet in a generalized r and omized block design . Five diets were formulated by mixing cornstarch and sugar with CM , PKE-IN , PKE-CR , PKM , or SBM . Five additional diets , which were identical to the initial 5 diets but supplemented with 800 units of phytase , were also formulated . A P-free diet was used to measure basal endogenous losses of P by the pigs . Feces were collected for 5 d using the marker to marker approach after a 5-d adaptation period . Analyzed total P in CM , PKE-IN , PKE-CR , PKM , and SBM was 0.52 , 0.51 , 0.53 , 0.54 , and 0.67 % , respectively . Phytate P was 0.22 , 0.35 , 0.38 , 0.32 , and 0.44 % in CM , PKE-IN , PKE-CR , PKM , and SBM , respectively . Addition of phytase increased ( P from 60.6 to 80.8 , 27.3 to 56.5 , 32.6 to 59.9 , 48.9 to 64.1 , and 41.1 to 72.2 % in CM , PKE-IN , PKE-CR , PKM , and SBM , respectively . The ATTD of P in CM was greater ( P ingredients . The ATTD of P in SBM and PKM was greater ( P . The STTD of P increased ( P 73.5 , and 49.6 to 81.1 % in CM , PKE-IN , PKE-CR , PKM , and SBM , respectively , when microbial phytase was added to the diets . When expressed as a percentage of total P , phytate P concentration in the ingredient negatively affected ( P ATTD of P ( 107.09 - 1.0564 × % phytate P ; R(2 ) = 87.1 ) and the STTD of P ( 116.3 - 1.0487 × % phytate P ; R(2 ) = 89.4 ) . In conclusion , microbial phytase increased P digestibility of CM , PKM , PKE-CR , PKE-IN , and SBM when fed to growing pigs , and the concentration of phytate P affects the response to microbial phytase", "A study was conducted to estimate the accuracy and reliability of review ers when screening records for relevant trials for a systematic review . A sensitive search of ten electronic bibliographic data bases yielded 22 571 records of potentially relevant trials . Records were allocated to four review ers such that two review ers examined each record and so that identification of trials by each review er could be compared with those identified by each of the other review ers . Agreement between review ers was assessed using Cohen 's kappa statistic . Ascertainment intersection methods were used to estimate the likely number of trials missed by review ers . Full copies of reports were obtained and assessed independently by two research ers for eligibility for the review . Eligible reports formed the ' gold st and ard ' against which an assessment was made about the accuracy of screening by review ers . After screening , 301 of 22 571 records were identified by at least one review er as potentially relevant . Agreement was ' almost perfect ' ( kappa>0.8 ) within two pairs , ' substantial ' ( kappa>0.6 ) within three pairs and ' moderate ' ( kappa>0.4 ) within one pair . Of the 301 records selected , 273 complete reports were available . When pairs of review ers agreed on the potential relevance of records , 81 per cent were eligible ( range 69 to 91 per cent ) . If review ers disagreed , 22 per cent were eligible ( range 12 to 45 per cent ) . Single review ers missed on average 8 per cent of eligible reports ( range 0 to 24 per cent ) , whereas pairs of review ers did not miss any ( range 0 to 1 per cent ) . The use of two review ers to screen records increased the number of r and omized trials identified by an average of 9 per cent ( range 0 to 32 per cent ) . Review ers can reliably identify potentially relevant records when screening thous and s of records for eligibility . Two review ers should screen records for eligibility , whenever possible , in order to maximize ascertainment of relevant trials", "This study reevaluated the method of regressing of total P output against dietary P intake to simultaneously estimate true P digestibility and endogenous P loss in growing pigs fed either conventional or low-phytate soybean meal ( SBM ) . Four isocaloric diets were formulated to contain increasing concentrations of each type of SBM ( 8 diets total ) , and therefore contained increasing concentrations of dietary P. Dietary P and Ca concentrations were deficient because they were supplied solely by SBM , and Ca : total P ratios were less than 1:1 . Sixteen barrows ( initial BW 17.7 + /- 1.8 kg ) were surgically fitted with a simple T-cannula at the distal ileum , r and omly assigned to metabolism crates , and fed the experimental diets in a replicated 8 x 8 Latin square design . Feed was provided at 90 g/kg of BW(0.75 ) and fed in 2 equally sized meals at 0800 and 2000 , with diets containing Cr sesquioxide ( 3 g/kg ) as an indigestible marker . As the P concentration increased from 0.9 to 3.9 g/kg of DM , the apparent prececal P digestibility increased for conventional SBM ( P output of total P [ mg/(kg of BW(0.75).d ) ] , either prececal or total tract , exhibited a linear relationship ( P total tract P output from pigs fed low-phytate SBM . True P digestibility was not different between prececal and total tract collection sites ( P > 0.10 ) , but was greater ( P Endogenous P estimates were not different between the SBM varieties and averaged 4.83 mg/(kg of BW(0.75).d ) . However , endogenous P estimates were highly variable between individual animals and , therefore , were not significantly different from zero . In this study , estimates of endogenous P loss from pigs were relatively low compared with previously reported values , and evidence of nonlinearity in P output was observed . These results suggest that the difference in true P digestibility between conventional SBM and low-phytate SBM is influenced by dietary phytate content when growing pigs are fed P-deficient diets ", "An experiment was conducted to test the hypothesis that differences in the apparent total tract digestibility ( ATTD ) and st and ardized total tract digestibility ( STTD ) of Ca exist among Ca supplements and that inclusion of microbial phytase increases the ATTD and STTD of Ca . One hundred and four growing barrows ( average initial BW of 17.73 ± 2.53 kg ) were allotted to a r and omized complete block design with 13 dietary treatments and 8 pigs per treatment . A basal diet containing corn , cornstarch , potato protein isolate , soybean oil , calcium carbonate , monosodium phosphate , vitamins , and minerals was formulated . Five additional diets were formulated by adding monocalcium phosphate ( MCP ) , dicalcium phosphate ( DCP ) , calcium carbonate , Lithothamnium calcareum Ca , or a high-Ca sugar beet co-product to the basal diet at the expense of cornstarch . Six additional diets that were similar to the previous 6 diets with the exception that they also contained 500 units per kilogram of microbial phytase were also formulated . A Ca-free diet was used to determine basal endogenous losses of Ca . Feces were collected using the marker-to-marker approach . Results indicated that regardless of inclusion of microbial phytase , MCP had the greatest ( P . The ATTD and STTD of Ca in DCP were greater ( P among the ATTD and STTD of Ca in calcium carbonate , L. calcareum Ca , or sugar beet co-product . Inclusion of microbial phytase increased ( P of Ca in the diets , but this was not the case in the Ca supplements . Regardless of inclusion of microbial phytase , the ATTD of P was greater ( P ( P of P than pigs fed L. calcareumCa or the sugar beet co-product . Regardless of Ca source , inclusion of microbial phytase increased ( P 0.001 ) the ATTD of P. In conclusion , MCP has the greatest ATTD and STTD of Ca among the calcium supplements used in this experiment , followed by DCP . Basal , MCP , and DCP diets had greater ATTD of P than the other diets , and inclusion of microbial phytase increased the ATTD and STTD of Ca and the ATTD of P in the diets", "A regional experiment was conducted to test the hypothesis that the concentration of dietary Ca does not affect the digestibility of Ca or P in diets fed to growing pigs . Six diets based on corn , potato protein isolate , cornstarch , and soybean oil were formulated . All diets also contained monosodium phosphate , crystalline AA , salt , and a vitamin-micromineral premix . The only difference among the diets was that varying concentrations of calcium carbonate were used to create diets containing 0.33 , 0.46 , 0.51 , 0.67 , 0.92 , and 1.04 % Ca . All diets contained between 0.40 and 0.43 % P. Six universities participated in the experiment and each university contributed 2 replicates to the experiment for a total of 12 replicates ( initial BW : 23.1 ± 4.4 kg ) . Pigs were placed in metabolism cages that allowed total , but separate , collection of feces and urine from the pigs . Pigs within each replicate were r and omly allotted to the 6 diets and fed experimental diets for 14 d with urine and feces being collected over a 5-d period . Diets , feces , and urine sample s were analyzed for Ca and P , and the daily balance , the apparent total tract digestibility ( ATTD ) , and the retention of Ca and P were calculated . Results indicated that intake , fecal excretion , and urinary excretion of Ca increased ( linear , P The daily intake of P was not affected by the dietary concentration of Ca , but fecal excretion of P increased ( linear , P dietary Ca concentrations increased . In contrast , urinary P output was decreased ( linear , P The retention of Ca increased ( linear , P whereas the retention of P decreased ( linear , P dietary Ca concentrations increased . However , if calculated as a percentage of intake , both Ca and P retention were decreased ( linear , P dietary Ca concentration increased ( from 55.4 to 46.1 % and from 48.4 to 43.5 % , respectively ) . The ATTD of Ca was not affected by the dietary concentration of Ca , but the ATTD of P was decreased ( linear , P ATTD of Ca in calcium carbonate , but increased concentrations of dietary Ca may decrease the ATTD of P in diets based on corn , potato protein isolate , and monosodium phosphate", "Two experiments were conducted to determine the requirement for st and ardized total tract digestible ( STTD ) Ca by 25 to 50 kg pigs at different concentrations of STTD P. Twenty corn-soybean meal based diets were formulated with diets containing 4 concentrations of STTD P ( 0.15 , 0.31 , 0.39 , or 0.47 % ) and 5 concentrations of STTD Ca ( 0.13 , 0.27 , 0.42 , 0.57 , or 0.72 % ) . Diets were mixed in 1 batch and were used in both experiments . In Exp . 1 , 240 pigs ( initial average BW : 24.70 ± 1.27 kg ) were r and omly allotted to the 20 diets in 6 blocks with 1 pen per diet in each block using a 4 × 5 factorial design . There was 1 gilt and 1 barrow in each pen . At the conclusion of the 28 d experiment , all barrows were euthanized and the right femur was collected . Results indicated that there were interactions ( concentration of STTD Ca and concentration of STTD P in diets for ADG , G : F , and bone ash . The predicted maximum ADG at STTD P concentrations of 0.15 , 0.31 , 0.39 , and 0.47 % were 0.76 , 0.87 , 0.90 , and 0.92 kg at STTD Ca concentrations of 0.12 , 0.36 , 0.47 , and 0.59 % , respectively , which correspond to STTD Ca : STTD P ratios of 0.80:1 , 1.16:1 , 1.21:1 , and 1.26:1 . The predicted maximum G : F ratio at the 4 STTD P concentrations were 0.43 , 0.46 , 0.48 , and 0.50 kg/kg at STTD Ca concentrations of 0.09 , 0.38 , 0.52 , and 0.67 % , respectively , and these values correspond to STTD Ca : STTD P ratios of 0.60:1 , 1.23:1 , 1.33:1 , and 1.43:1 . The predicted maximum bone ash at the 4 STTD P concentrations were 14.5 , 21.0 , 23.1 , and 24.5 g at STTD Ca concentrations of 0.41 , 0.56 , 0.64 , and 0.72 % , respectively , which correspond to STTD Ca : STTD P ratios of 2.73:1 , 1.81:1 , 1.64:1 , and 1.53:1 . In Exp . 2 , 120 pigs ( initial average BW : 29.45 ± 2.15 kg ) were placed in metabolism crates and r and omly allotted to the 20 diets in 6 blocks with 1 pig per diet in each block . Fecal and urine sample s were collected . Results indicated that the predicted maximum retention of Ca in the body at STTD P concentrations of 0.15 , 0.31 , 0.39 , and 0.47 % were 4.7 , 7.1 , 8.6 , and 10.2 g/d at STTD Ca concentrations of 0.77 , 0.96 , 1.06 , and 1.15 % , respectively , which correspond to STTD Ca : STTD P ratios of 5.13:1 , 3.10:1 , 2.72:1 , and 2.45:1 . These observations indicate that if STTD P meets or exceeds the requirement , the STTD Ca : STTD P ratio needed to maximize ADG and G : F by 25 to 50 kg pigs is between 1.16:1 and 1.43:1 . However , a greater ratio may be needed to maximize bone ash or Ca retention ", "Background Systematic Review s ( SRs ) of experimental animal studies are not yet common practice , but awareness of the merits of conducting such SRs is steadily increasing . As animal intervention studies differ from r and omized clinical trials ( RCT ) in many aspects , the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies . The Cochrane Collaboration developed a Risk of Bias ( RoB ) tool to establish consistency and avoid discrepancies in assessing the method ological quality of RCTs . A similar initiative is warranted in the field of animal experimentation . Methods We provide an RoB tool for animal intervention studies ( SYRCLE ’s RoB tool ) . This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies . To enhance transparency and applicability , we formulated signalling questions to facilitate judgment . Results The result ing RoB tool for animal studies contains 10 entries . These entries are related to selection bias , performance bias , detection bias , attrition bias , reporting bias and other biases . Half these items are in agreement with the items in the Cochrane RoB tool . Most of the variations between the two tools are due to differences in design between RCTs and animal studies . Shortcomings in , or unfamiliarity with , specific aspects of experimental design of animal studies compared to clinical studies also play a role . Conclusions SYRCLE ’s RoB tool is an adapted version of the Cochrane RoB tool . Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies . This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the method ological quality of animal studies" ]

[ "As a follow-up of our study of pregnant women , we report effects of zinc supplementation during pregnancy in another population of 138 Hispanic teenagers in Los Angeles . Teenagers were r and omized ( double-blind ) to a control or zinc-supplemented group and received similar daily vitamin and mineral supplements except for 20 mg zinc added to the zinc-supplemented group 's capsules . Initially , mean dietary zinc intakes of both groups were about 50 % of the Recommended Dietary Allowance and their mean serum zinc levels did not differ significantly ( 69.8 + /- 11.2 micrograms/dl in control and 69.0 + /- 11.4 micrograms/dl in zinc-supplemented group ) . Zinc supplementation did not maintain mean serum zinc levels during pregnancy but , as in our earlier study , it reduced ( p = 0.018 ) the number of low serum zinc values ( less than or equal to 53 micrograms/dl ) in late pregnancy . Zinc supplementation did not affect outcome of pregnancy but serum zinc levels were lower ( p = 0.038 ) in teenagers with pregnancy-induced hypertension than in normotensives", "BACKGROUND Maternal zinc deficiency during pregnancy may be widespread among women in developing countries , but few data are available on whether prenatal zinc supplementation improves maternal and neonatal zinc status . OBJECTIVE We studied whether maternal zinc supplementation improved the zinc status of mothers and neonates participating in a supplementation trial in a shantytown in Lima , Peru . DESIGN Beginning at gestation week 10 - 24 , 1295 mothers were r and omly assigned to receive prenatal supplements containing 60 mg Fe and 250 microg folate , with or without 15 mg Zn . Venous blood and urine sample s were collected at enrollment , at gestation week 28 - 30 , and at gestation week 37 - 38 . At birth , a sample of cord vein blood was collected . We measured serum zinc concentrations in 538 women , urinary zinc concentrations in 521 women , and cord zinc concentrations in 252 neonates . RESULTS At 28 - 30 and 37 - 38 wk , mothers receiving zinc supplements had higher serum zinc concentrations than mothers who did not receive zinc ( 8.8 + /- 1.9 compared with 8.4 + /- 1.5 micromol/L and 8.6 + /- 1.5 compared with 8.3 + /- 1.4 micromol/L , respectively ) . Urinary zinc concentrations were also higher in mothers who received supplemental zinc ( P cord zinc concentrations than neonates of mothers who did not receive zinc ( 12.7 + /- 2.3 compared with 12.1 + /- 2.1 micromol/L ) . Despite supplementation , maternal and neonatal zinc concentrations remained lower than values reported for well-nourished population s. CONCLUSION Adding zinc to prenatal iron and folate tablets improved maternal and neonatal zinc status , but higher doses of zinc are likely needed to further improve maternal and neonatal zinc status in this population", "The effect of zinc supplementation on concentrations of zinc in hair and serum of 213 pregnant Hispanic women attending a clinic in Los Angeles was assessed using a r and om , double-blind experiment . Both the treatment ( T ) and control ( C ) groups received similar vitamin and mineral supplements except that 20 mg zinc was added to the supplements for the treatment group . Nutrient intakes were calculated from 24-h recalls . The initial mean dietary zinc intake of both groups was about 50 % of the Recommended Dietary Allowance ( 9 + /- 5 mg ) . Initially there were no significant differences between the two groups in mean zinc levels in serum ( 66 + /- 11 micrograms/dl , C , and 65 + /- 12 micrograms/dl , T ) or in hair ( 184 + /- 41 micrograms/g , C , and 175 + /- 38 micrograms/g , T ) . Zinc supplementation did not alter mean zinc levels in serum or hair but significantly ( p less than 0.05 ) reduced the number of low serum zinc values ( less than or equal to 53.3 micrograms/dl ) toward the end of pregnancy . Although serum zinc levels do decline in pregnancy , our results suggest that severely depressed levels ( less than or equal to 50 to 55 micrograms/dl ) indicate inadequate zinc status", "Effects of dietary zinc supplement during lactation on maternal zinc plasma and milk zinc concentration through 5 months of lactation were examined . One hundred and thirty eight healthy lactating mothers received a weekly 100 mg elemental zinc supplement ( ZS , n = 67 ) or placebo ( PG , n = 71 ) starting one week postpartum in a double blind , r and omized design . Milk and plasma zinc concentrations were determined by atomic absorption spectrophotometer . During the course of study , there was not a significantly difference between ZG and PG groups in dietary zinc and energy intake . The mean plasma zinc concentration at 1st week and 5th month were 134 + /- 49.1 and 115.6 + /- 23 microg dL(-1 ) ( PV = 0.005 ) for PG group , respectively ; that of the ZG group these figures were 124.9 + /- 52.8 and 121 + /- 27.1 microg dL(-1 ) ( PV = 0.38 ) , respectively . The mean serum alkaline phosphatase concentration at 1st week and 5th month were 94.8 + /- 37 and 92.6 + /- 29.9 iu L(-1 ) for PG group , respectively ; that of the ZG group these fissures were 90.5 + /- 36 and 90 + /- 29 iu L(-1 ) ( PV = 0.21 ) , respectively . Milk zinc concentration declined significantly over the course of study for two groups , with the sharpest decline occurring during the first 2 months . The mean monthly zinc concentration of ZG group declined from 310 + /- 138 at 1st week to 118 + /- 64 microg dL(-1 ) at 5th month ( declined by 52 % ) . Corresponding means for PG group were 322 + /- 161 and 109 + /- 70 microg dL(-1 ) ( declined by 60 % ) , respectively . Milk zinc concentration significantly different between two groups at 3 and 4 months . A similar study , however , with different zinc dose and administration manner , in zinc marginal deficient lactating mothers is needed to assess the impact of zinc supplementation on milk zinc concentrations", "The effects of a zinc supplement on maternal zinc status and milk zinc concentrations through > or = 7 mo of lactation were examined . Seventy-one lactating women received either a daily 15-mg zinc supplement ( ZS , n = 40 ) or placebo ( NZS , n = 31 ) started by 2 wk postpartum in a double-blind , r and omized design . Overall mean zinc intakes were 13.0 + /- 3.4 mg/d for the NZS group and 25.7 + /- 3.9 mg/d ( including supplement ) for the ZS group . Plasma zinc concentrations of the ZS group were significantly higher than those of the NZS group ( P = 0.05 ) . Milk zinc concentrations declined significantly over the course of the study for all subjects but were not affected by zinc supplementation . The mean dietary zinc intake observed in the nonsupplemented group was adequate to maintain normal maternal zinc status and milk zinc concentrations through > or = 7 mo lactation . Similar controlled intervention trials in less well-nourished population s will be required to assess the impact of lower zinc intakes on milk zinc concentrations" ]

[ "A report of a r and omized , controlled trial ( RCT ) should convey to the reader , in a transparent manner , why the study was undertaken and how it was conducted and analyzed . For example , a lack of adequately reported r and omization has been associated with bias in estimating the effectiveness of interventions ( 1 , 2 ) . To assess the strengths and limitations of an RCT , readers need and deserve to know the quality of its methods . Despite several decades of educational efforts , RCTs still are not being reported adequately ( 3 - 6 ) . For example , a review of 122 recently published RCTs that evaluated the effectiveness of selective serotonin-reuptake inhibitors as first-line management strategy for depression found that only 1 ( 0.8 % ) paper described r and omization adequately ( 5 ) . Inadequate reporting makes the interpretation of RCT results difficult if not impossible . Moreover , inadequate reporting borders on unethical practice when biased results receive false credibility . History of CONSORT In the mid-1990s , two independent initiatives to improve the quality of reports of RCTs led to the publication of the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement ( 7 ) , which was developed by an international group of clinical trialists , statisticians , epidemiologists , and biomedical editors . CONSORT has been supported by a growing number of medical and health care journals ( 8 - 11 ) and editorial groups , including the International Committee of Medical Journal Editors ( ICMJE , also known as the Vancouver Group ) ( 12 ) , the Council of Science Editors ( CSE ) , and the World Association of Medical Editors ( WAME ) . CONSORT is also published in Dutch , English , French , German , Japanese , and Spanish . It can be accessed on the Internet , along with other information about the CONSORT group ( 13 ) . The CONSORT statement comprises a checklist and flow diagram for reporting an RCT . For convenience , the checklist and diagram together are called simply CONSORT . They are primarily intended for use in writing , review ing , or evaluating reports of simple two-group , parallel RCTs . Preliminary data indicate that the use of CONSORT does indeed help to improve the quality of reports of RCTs ( 14 , 15 ) . In an evaluation ( 14 ) of 71 RCTs published in three journals in 1994 , allocation concealment was not clearly reported in 43 ( 61 % ) of the RCTs . Four years later , after these three journals required that authors reporting an RCT use CONSORT , the proportion of papers in which allocation concealment was not clearly reported had dropped to 39 % ( 30 of 77 ; mean difference , 22 % [ 95 % CI of the difference , 38 % to 6 % ] ) . The usefulness of CONSORT is enhanced by continuous monitoring of the biomedical literature ; this monitoring allows CONSORT to be modified depending on the merits of maintaining or dropping current items and including new items . For example , when Meinert ( 16 ) observed that the flow diagram did not provide important information about the number of participants who entered each phase of an RCT ( enrollment , treatment allocation , follow-up , and data analysis ) , the diagram could be modified to accommo date the information . The checklist is similarly flexible . This iterative process makes the CONSORT statement a continually evolving instrument . While participants in the CONSORT group and their degree of involvement vary over time , members meet regularly to review the need to refine CONSORT . At the 1999 meeting , the participants decided to revise the original statement . This report reflects changes determined by consensus of the CONSORT group , partly in response to emerging evidence on the importance of various elements of RCTs . Revision of the CONSORT Statement Thirteen members of the CONSORT group met in May 1999 with the primary objective of revising the original CONSORT checklist and flow diagram , as needed . The group discussed the merits of including each item in the light of current evidence . As in developing the original CONSORT statement , our intention was to keep only those items deemed fundamental to reporting st and ards for an RCT . Some items not considered essential may well be highly desirable and should still be included in an RCT report even though they are not included in CONSORT . Such items include approval of an institutional ethical review board , sources of funding for the trial , and a trial registry number ( as , for example , the International St and ard R and omized Controlled Trial Number [ IS RCT N ] used to register an RCT at its inception [ 17 ] ) . Shortly after the meeting , a revised version of the checklist was circulated to the group for additional comments and feedback . Revisions to the flow diagram were similarly made . All these changes were discussed when CONSORT participants met in May 2000 , and the revised statement was finalized shortly afterward . The revised CONSORT statement includes a 22-item checklist ( Table ) and a flow diagram ( Figure ) . Its primary aim is to help authors improve the quality of reports of simple two-group , parallel RCTs . However , the basic philosophy underlying the development of the statement can be applied to any design . In this regard , additional statements for other design s will be forthcoming from the group ( 13 ) . CONSORT can also be used by peer review ers and editors to identify reports with inadequate description of trials and those with potentially biased results ( 1 , 2 ) . Table . Checklist of Items To Include When Reporting a R and omized Trial Figure . Flow diagram of the progress through the phases of a r and omized trial ( enrollment , intervention allocation , follow-up , and data analysis ) . During the 1999 meeting , the group also discussed the benefits of developing an explanatory document to enhance the use and dissemination of CONSORT . The document is patterned on reporting of statistical aspects of clinical research ( 18 ) , which was developed to help facilitate the recommendations of the ICMJE 's Uniform Requirements for Manuscripts Su bmi tted to Biomedical Journals . Three members of the CONSORT group , with assistance from members on some checklist items , drafted an explanation and elaboration document . That document ( 19 ) was circulated to the group for additions and revisions and was last revised after review at the latest CONSORT group meeting . Changes to CONSORT 1 . In the revised checklist , a new column for Paper Section and Topic integrates information from the Subheading column that was contained in the original statement . 2 . The Was It Reported ? column has been integrated into a Reported on Page Number column , as requested by some journals . 3 . Each item of the checklist is now numbered , and the syntax and order have been revised to improve the flow of information . 4 . Title and Abstract are now combined in the first item . 5 . While the content of the revised checklist is similar to that of the original one , some items that previously were combined are now separate . For example , authors had been asked to describe primary and secondary outcome ( s ) measure(s ) and the minimum important difference(s ) , and indicate how the target sample size was projected . In the new version , issues pertaining to outcomes ( item 6 ) and sample size ( item 7 ) are separate , enabling authors to be more explicit about each . Moreover , some items request additional information . For example , for outcomes ( item 6 ) authors are asked to report any methods used to enhance the quality of measurements , such as multiple observations . 6 . The item asking for the unit of r and omization ( for example , cluster ) has been dropped because specific checklists have been developed for reporting cluster RCTs ( 20 ) and other design types ( 13 ) since publication of the original checklist . 7 . Whenever possible , new evidence is incorporated into the revised checklist . For example , authors are asked to be explicit about whether the analysis reported is by intention to treat ( item 16 ) . This request is based in part on the observations ( 21 ) that authors do not adequately describe and apply intention-to-treat analysis and that reports not providing this information are less likely to provide other relevant information , such as losses to follow-up ( 22 ) . 8 . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow-up , and analysis ) . The revised diagram explicitly includes the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers lets the reader know whether the authors have performed an intention-to-treat analysis ( 21 - 23 ) . Because some of the information may not always be known and to accommo date other information , the structure of the flow diagram may need to be modified for a particular trial . Inclusion of the participant flow diagram in the report is strongly recommended but may be unnecessary for simple trials , such as those without any participant withdrawals or dropouts . Discussion Specifically developed to guide authors about how to improve the quality of reporting of simple two-group , parallel RCTs , CONSORT encourages transparency with reporting of the methods and results so that reports of RCTs can be interpreted both readily and accurately . However , CONSORT does not address other facets of reporting that also require attention , such as scientific content and readability of RCT reports . Some authors , in their enthusiasm to use CONSORT , have modified the checklist ( 24 ) . We recommend against such modifications because they may be based on a different process than the one used by the CONSORT group . The use of CONSORT seems to reduce ( if not eliminate ) inadequate reporting of RCTs ( 14 , 15 ) . Potentially , the use of CONSORT should positively influence the manner in which RCTs are conducted . Granting agencies have noted this potential relationship and , in at least in one case ( 25 ) , have encouraged grantees to consider in their application how they have dealt with the CONSORT items . The evidence -based approach used to develop CONSORT has also been used", "Investigations in which statistically significant differences between treatment groups have not been observed are less likely than others to be reported in scientific journals . In clinical research , this selective suppression of \" negative \" results may lead to the adoption of ineffective or hazardous treatments . In an attempt to obtain information about unpublished trials in perinatal medicine , letters were sent to 42,000 obstetricians and pediatricians in 18 countries . As a result , we were notified of 395 unpublished r and omized trials . Only 18 of the trials had been completed more than 2 years before the survey , a period during which at least 2300 reports of perinatal trials had been published . Of the 395 unpublished trials , 125 had ceased recruitment within the 2 years prior to the survey , 193 were actively recruiting at the time of the survey , and 59 were about to begin recruitment . It was concluded that publication bias will not be addressed successfully by attempts to obtain information about unpublished trials retrospectively . However , since the response rate to our request for details about ongoing and planned trials was good , prospect i ve registration of trials at inception appears to be a feasible approach to reducing publication bias and its adverse consequences . An additional merit of prospect i ve registration of clinical trials is that it should reduce unnecessary duplication ( as opposed to necessary replication ) in research and promote more effective collaboration" ]

[ "ABSTRACT Endothelial dysfunction is a surrogate marker of cardiovascular risk . Resveratrol is known to improve endothelial function in animals , however , clinical trials are limited . We hypothesized that the acute trans-resveratrol supplementation improves endothelial function in treated hypertensive patients with endothelial dysfunction . Twenty-four hypertensive patients between 45 and 65 years-old with baseline endothelial dysfunction were enrolled in a r and omized , cross-over , double-blind , placebo-controlled trial . Individuals received either a single dose of trans-resveratrol ( 300 mg ) or placebo and were crossed-over after a one-week washout period . Blood pressure ( BP ) measurements , aortic systolic blood pressure ( SBP ) and brachial flow-mediated dilation ( FMD ) were performed before and 1.5 hours after the intervention . FMD was significantly increased in women ( 4.2 ± 0.5 vs 7.1 ± 1.3 % , p = 0.026 ) but not in men ( 4.4 ± 0.9 vs 4.9 ± 0.8 % , p = 0.588 ) in the trans-resveratrol group . There was no statistical difference between baseline and final values of brachial BP and also no changes in aortic SBP . Patients with higher low-density lipoprotein ( LDL ) cholesterol had better FMD response to trans-resveratrol than patients with lower LDL cholesterol ( 7.4 ± 1.2 vs 4.3 ± 1.0 % , p = 0.004 ) . Our study demonstrated that the acute supplementation of trans-resveratrol promoted an improvement in endothelial function , especially in women and those with higher LDL-cholesterol , despite no changes in BP . List of Abbreviation : Aix : augmentation index ; AP : augmentation pressure ; BP : blood pressure ; BMI : body Mass Index ; CVD : cardiovascular disease ; FMD : flow-mediated dilation ; FRS : Framingham Risk Score ; HDL : high-density lipoprotein ; LDL : low-density lipoprotein ; NO : nitric oxide ; SPSS : Statistical Package for Social Sciences ; ROS : reactive oxygen species ; SBP : systolic blood pressure ; TG : triglycerides", "Background High-fat meals induce postpr and ial inflammation . Resveratrol is a polyphenol known to prevent comorbidities associated with cardiovascular disease and exerts an anti-inflammatory action . There is also an increasing body of evidence supporting the role of curcumin , a polyphenol from the curcuminoid family , as a modulator of proinflammatory processes . Objective The objectives of this study were to investigate the following : 1 ) the bioavailability of resveratrol consumed in combination with curcumin after consumption of a high-fat meal ; and 2 ) the acute combined effects of this combination on the postpr and ial inflammatory response of subjects with abdominal obesity . Methods In a double blind , crossover , r and omized , placebo-controlled study , 11 men and 11 postmenopausal women [ mean ± SD age : 62 ± 5 y ; mean ± SD body mass index ( in kg/m2 ) : 29 ± 3 ] underwent a 6-h oral fat tolerance test on 2 occasions separated by 1 - 2 wk : once after consumption of a dietary supplement ( 200 mg resveratrol and 100 mg curcumin , Res/Cur ) and once after consumption of a placebo ( cellulose ) . Plasma concentrations of total resveratrol and its major metabolites as well as inflammatory markers , adhesion molecules , and whole blood NFκB1 and PPARA gene expression were measured during both fat tolerance tests . Results Kinetics of resveratrol and identified metabolites revealed rapid absorption patterns but also relatively limited bioavailability based on free resveratrol concentrations . Supplementation with Res/Cur did not modify postpr and ial variations in circulating inflammatory markers ( C-reactive protein , IL-6 , IL-8 , monocyte chemoattractant protein-1 ) and adhesion molecules [ soluble E-selectin , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , soluble intercellular adhesion molecule-1 ] compared to placebo ( PTreatment × Time > 0.05 ) . However , Res/Cur significantly decreased the cumulative postpr and ial response of sVCAM-1 , compared to placebo ( incremental area under the curve -4643 % , P = 0.01 ) . Postpr and ial variations of whole-blood PPARA and NFKB1 gene expression were not different between Res/Cur and placebo treatments . Conclusions Acute supplementation with Res/Cur has no impact on the postpr and ial inflammation response to a high-fat meal in abdominally obese older adults . Further studies are warranted to examine how resveratrol and curcumin may alter the vascular response to a high-fat meal . This trial was registered at clinical trials.gov as NCT01964846", "Studies on the effects of the long-term intake of trans-resveratrol on vascular function are conflicting . In addition , postpr and ial effects of long-term trans-resveratrol intake on endothelial function are not known . We therefore supplemented 45 overweight and slightly obese volunteers ( 25 men and 20 women ) with a mean ( ±SD ) age of 61 ± 7 years and body mass index of 28.3 ± 3.2 kg/m2 in r and om order trans-resveratrol ( 2 × 75 mg/day ) or placebo capsules for 4 weeks , separated by a washout period of at least 4 weeks . At the end of each intervention period , brachial artery flow-mediated vasodilation ( FMD ) was measured before and after meal consumption . Plasma biomarkers for endothelial function , inflammation , and glucose and lipid metabolism were also determined . Compared with the placebo , trans-resveratrol did not affect fasting FMD ( 2.9 ± 1.4 % vs. 3.0 ± 1.9 % ; p = 0.69 ) . After the postpr and ial test , changes in FMD ( −0.7 ± 2.3 % vs. 0.2 ± 2.6 % ; p = 0.13 ) were also not significantly different . Postpr and ial changes in biomarkers were also comparable . In conclusion , for overweight and slightly obese volunteers , a daily intake of 150 mg of trans-resveratrol for 4 weeks does not change plasma biomarkers of endothelial function or inflammation in the fasting state or postpr and ial phase", "We performed the largest r and omized , placebo‐controlled clinical trial to date ( N = 112 , 12‐week intervention ) to investigate the effects and safety of resveratrol supplementation on liver fat content and cardiometabolic risk parameters in overweight and obese and insulin‐resistant subjects . At baseline the variability in liver fat content was very large , ranging from 0.09 % to 37.55 % ( median , 7.12 % ; interquartile range , 3.85%‐12.94 % ) . Mean ( SD ) liver fat content was 9.22 ( 6.85 ) % in the placebo group and 9.91 ( 7.76 ) % in the resveratrol group . During the study liver fat content decreased in the placebo group ( −0.7 % ) but not in the resveratrol group ( −0.03 % ) ( differences between groups : P = .018 for the intention‐to‐treat [ ITT ] population ; N = 54 , resveratrol , N = 54 , placebo and P = .0077 for the per protocol [ PP ] population ) . No effects of resveratrol supplementation on cardiometabolic risk parameters were observed . Resveratrol supplementation was well tolerated and safe ", "ABSTRACT Objective “ The obesity epidemic ” has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease ( NAFLD ) , for which effective treatments are in dem and . The polyphenol resveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction . We aim ed to test the hypothesis that resveratrol alleviates NAFLD in a r and omised , clinical trial . Material s and methods A total of 28 overweight patients with transaminasemia and histological NAFLD were r and omised 1:1 to placebo or resveratrol 1.5 g daily for 6 months . Twenty-six participants completed the trial and underwent repeated clinical investigation , blood work , MR spectroscopy ; and 19 participants agreed to a repeat liver biopsy . Results Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury ( primary outcome : alanine transaminase , p = 0.51 ) . Resveratrol-treated patients showed a 3.8 % decrease in liver lipid content ( p = 0.03 ) , with no difference between the two treatment arms ( p = 0.38 ) and no improvement of histological features . Resveratrol treatment was not associated with improvements in insulin sensitivity or markers of the metabolic syndrome , except for a transient decrease in systolic BP . Microarray analysis and qRT-PCR revealed no major changes in expression profile . Also , we report a serious adverse event in a patient who developed fever and bicytopenia . Conclusions In this placebo-controlled , high-dose and long-term study , resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD , though there may be a small ameliorating effect on liver function tests and liver fat accumulation ", "Resveratrol is a naturally occurring polyphenolic compound . Numerous animal studies have been reported on its wide-ranging beneficial effects in the biological system including diabetes mellitus ( DM ) . We hypothesized , therefore , that oral supplementation of resveratrol would improve the glycemic control and the associated risk factors in patients with type 2 diabetes mellitus ( T2DM ) . The present clinical study was therefore carried out to test the hypothesis . Sixty-two patients with T2DM were enrolled from Government Headquarters Hospital , Ootacamund , India , in a prospect i ve , open-label , r and omized , controlled trial . Patients were r and omized into control and intervention groups . The control group received only oral hypoglycemic agents , whereas the intervention group received resveratrol ( 250 mg/d ) along with their oral hypoglycemic agents for a period of 3 months . Hemoglobin A(1c ) , lipid profile , urea nitrogen , creatinine , and protein were measured at the baseline and at the end of 3 months . The results reveal that supplementation of resveratrol for 3 months significantly improves the mean hemoglobin A(1c ) ( means ± SD , 9.99 ± 1.50 vs 9.65 ± 1.54 ; P ( mean ± SD , 139.71 ± 16.10 vs 127.92 ± 15.37 ; P ( mean ± SD , 4.70 ± 0.90 vs 4.33 ± 0.76 ; P ( mean ± SD , 75.6 ± 4.6 vs 72.3 ± 6.2 ; P No significant changes in body weight and high-density lipoprotein and low-density lipoprotein cholesterols were observed . Oral supplementation of resveratrol is thus found to be effective in improving glycemic control and may possibly provide a potential adjuvant for the treatment and management of diabetes", "Resveratrol has been reported to have potent anti-atherosclerotic effects in animal studies . However , there are few interventional studies in human patients with atherosclerogenic diseases . The cardio-ankle vascular index ( CAVI ) reflects arterial stiffness and is a clinical surrogate marker of atherosclerosis . The aim of the present study was to investigate the effect of resveratrol on arterial stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM).In this double-blind , r and omized , placebo-controlled study , 50 patients with T2DM received supplement of a 100 mg resveratrol tablet ( total resveratrol : oligo-stilbene 27.97 mg/100 mg/day ) or placebo daily for 12 weeks . CAVI was assessed at baseline and the end of study . Body weight ( BW ) , blood pressure ( BP ) , glucose and lipid metabolic parameters , and diacron-reactive oxygen metabolites ( d-ROMs ; an oxidative stress marker ) were also measured . Resveratrol supplementation decreased systolic BP ( -5.5 ± 13.0 mmHg ) , d-ROMs ( -25.6 ± 41.8 U.CARR ) , and CAVI ( -0.4 ± 0.7 ) significantly ( P decreased BW ( -0.8 ± 2.1 kg , P = 0.083 ) and body mass index ( -0.5 ± 0.8 kg/m2 , P = 0.092 ) slightly compared to baseline , while there were no significant changes in the placebo group . Decreases in CAVI and d-ROMs were significantly greater in the resveratrol group than in the placebo group . Multivariate logistic regression analysis identified resveratrol supplementation as an independent predictor for a CAVI decrease of more than 0.5.In conclusion , 12-week resveratrol supplementation may improve arterial stiffness and reduce oxidative stress in patients with T2DM . Resveratrol may be beneficial in preventing the development of atherosclerosis induced by diabetes . However , a large-scale cohort study is required to vali date the present findings", "The objective of this study was to examine the effectiveness of resveratrol in lowering blood glucose in the presence of st and ard antidiabetic treatment in patients with type 2 diabetes , in a r and omized placebo-controlled double-blinded parallel clinical trial . A total of 66 subjects with type 2 diabetes were enrolled in this study and r and omly assigned to intervention group which was supplemented with resveratrol at a dose 1 g/day for 45 days and control group which received placebo tablets . Body weight , blood pressure , fasting blood glucose , haemoglobin A1c , insulin , homeostatic assessment s for insulin resistance , triglycerides , total cholesterol , low density lipoprotein , high density lipoprotein , and markers of liver and kidney damage were measured at baseline and after 45 days of resveratrol or placebo supplementation . Resveratrol treatment significantly decreased systolic blood pressure , fasting blood glucose , haemoglobin A1c , insulin , and insulin resistance , while HDL was significantly increased , when compared to their baseline levels . On the other h and , the placebo group had slightly increased fasting glucose and LDL when compared to their baseline levels . Liver and kidney function markers were unchanged in the intervention group . Overall , this study showed that resveratrol supplementation exerted strong antidiabetic effects in patients with type 2 diabetes", "The polyphenol resveratrol is considered to exert many beneficial actions , such as antioxidant , anti-inflammatory , insulin-sensitizer and anticancer effects . Its benefits in patients with type 2 diabetes mellitus ( T2DM ) are controversial . Our aims were to determine whether resveratrol supplementation at two different dosages ( 500 and 40mg/day ) for 6 months i ) reduced the concentrations of C-reactive-protein ( CRP ) and ii ) ameliorated the metabolic pattern of T2DM patients . In the present double-blind , r and omized , placebo-controlled trial , 192 T2DM patients were r and omized to receive resveratrol 500mg/day ( Resv500arm ) , resveratrol 40mg/day ( Resv40arm ) or placebo for 6-months . At baseline and at the trial end , CRP values , anthropometric , metabolic and liver parameters were determined . No serious adverse event occurred . A dose-dependent , though not significant , CRP decrease of 5.6 % ( Resv40arm ) and 15.9 % ( Resv500arm ) was observed vs placebo . We failed to detect significant differences in weight , BMI , waist circumference , and values of arterial blood pressure , fasting glucose , glycated hemoglobin , insulin , C-peptide , free fatty acids , liver transaminases , uric acid , adiponectin , interleukin-6 , in both the Resv500 and Resv40 arms vs placebo . Total cholesterol and triglycerides slightly increased in the Resv500arm . Subgroup analyses revealed that lower diabetes duration ( in both Resv500 and Resv40arms ) , and , in the Resv500arm , younger age , aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo . The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations , nor improve the metabolic pattern of T2DM patients", "OBJECTIVE To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of st and ard diabetes care . RESEARCH DESIGN AND METHODS Seventeen subjects with well-controlled type 2 diabetes ( T2D ) were treated with placebo and 150 mg/day resveratrol ( resVida ) in a r and omized double-blind crossover study for 30 days . The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique . RESULTS Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment . Intrahepatic lipid content also remained unaffected by resveratrol ; however , the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels ( R = −0.68 , P = 0.03 ) . Intramyocellular lipid content increased in type 2 muscle fibers ( P = 0.03 ) , and systolic blood pressure tended to decrease ( P = 0.09 ) upon resveratrol treatment . In addition , resveratrol significantly improved ex vivo mitochondrial function ( state 3 and state U respiration upon malate with octanoyl-carnitine , P between plasma levels of a metabolite of resveratrol ( dihydroresveratrol ) and the metformin dose used by the patients ( R = 0.66 , P = 0.005 ) , suggesting an interaction between metformin and resveratrol . It could be speculated that the lack of a resveratrol-induced insulin-sensitizing effect is caused by this interaction . CONCLUSIONS Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity . Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes", "Non-alcoholic fatty liver disease ( NAFLD ) is usually associated with insulin resistance , central obesity , reduced glucose tolerance , type 2 diabetes mellitus and hypertriacylglycerolaemia . The beneficial effects of resveratrol on metabolic disorders have been shown previously . The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD . In this r and omised double-blinded placebo-controlled clinical trial , fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks . Both groups were advised to follow an energy-balanced diet and physical activity recommendations . resveratrol supplementation reduced alanine aminotransferase ( ALT ) and hepatic steatosis significantly more than placebo ( P0·05 ) . There were no significant changes in blood pressure , insulin resistance markers and TAG in either group ( P>0·05 ) . Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements , insulin resistance markers , lipid profile and blood pressure ; however , it reduced ALT and hepatic steatosis in patients with NAFLD", "BACKGROUND & AIMS Nonalcoholic fatty liver disease ( NAFLD ) , characterized by accumulation of hepatic triglycerides ( steatosis ) , is associated with abdominal obesity , insulin resistance , and inflammation . Although weight loss via calorie restriction reduces features of NAFLD , there is no pharmacologic therapy . Resveratrol is a polyphenol that prevents high-energy diet-induced steatosis and insulin resistance in animals by up-regulating pathways that regulate energy metabolism . We performed a placebo-controlled trial to assess the effects of resveratrol in patients with NAFLD . METHODS Overweight or obese men diagnosed with NAFLD were recruited from hepatology outpatient clinics in Brisbane , Australia from 2011 through 2012 . They were r and omly assigned to groups given 3000 mg resveratrol ( n = 10 ) or placebo ( n = 10 ) daily for 8 weeks . Outcomes included insulin resistance ( assessed by the euglycemic-hyperinsulinemic clamp ) , hepatic steatosis , and abdominal fat distribution ( assessed by magnetic resonance spectroscopy and imaging ) . Plasma markers of inflammation , as well as metabolic , hepatic , and antioxidant function , were measured ; transcription of target genes was measured in peripheral blood mononuclear cells . Resveratrol pharmacokinetics and safety were assessed . RESULTS Eight-week administration of resveratrol did not reduce insulin resistance , steatosis , or abdominal fat distribution when compared with baseline . No change was observed in plasma lipids or antioxidant activity . Levels of alanine and aspartate aminotransferases increased significantly among patients in the resveratrol group until week 6 when compared with the placebo group . Resveratrol did not significantly alter transcription of NQO1 , PTP1B , IL6 , or HO1 in peripheral blood mononuclear cells . Resveratrol was well-tolerated . CONCLUSIONS Eight weeks administration of resveratrol did not significantly improve any features of NAFLD , compared with placebo , but it increased hepatic stress , based on observed increases in levels of liver enzymes . Further studies are needed to determine whether agents that are purported to mimic calorie restriction , such as resveratrol , are safe and effective for complications of obesity . Clinical trials registration no : ACTRN12612001135808", "BACKGROUND Sirtuin 1 ( Sirt1 ) plays an important role in vascular biology , and influences aspects of age-dependent atherosclerosis . In animals , the sirtuin system is strongly influenced by resveratrol and caloric restriction , but its expression in humans is controversial . This study investigated the effects of resveratrol and caloric restriction on Sirt1 serum concentrations and vascular biomarkers in a healthy human population . METHODS AND RESULTS Forty-eight healthy participants ( 24 women ) aged 55 - 65years were r and omized to either 30days of resveratrol administration ( 500mg/day ) or caloric restriction ( 1000cal/day ) . Blood was collected at baseline and day 30 . Laboratory data analyzed were triglycerides , total cholesterol , HDL , VLDL , LDL , apolipoprotein A1 , apolipoprotein B , lipoprotein ( a ) , non-esterified fatty acids ( NEFA ) , glucose , insulin , oxidative stress , C-reactive protein , and Sirt1 . Expression of the Sirt1 gene was analyzed using real-time PCR . Caloric restriction diminished the abdominal circumference and improved the lipid profile , but not resveratrol intervention . Resveratrol and caloric restriction increased serum concentrations of Sirt1 , from 1.06±0.71 to 5.75±2.98ng/mL ; p respectively . Sirt1 increased in women and men in both interventions . On the other h and expression of Sirt1 mRNA was not different after caloric restriction and resveratrol treatment . CONCLUSIONS Caloric restriction and resveratrol significantly increased plasma concentrations of Sirt1 . The long-term impact of these interventions on atherosclerosis should be assessed", "Background : We have previously demonstrated acute dose-dependent increases of flow-mediated dilatation ( FMD ) in the brachial artery after resveratrol consumption in mildly hypertensive , overweight/obese adults . Resveratrol supplementation has also been shown to increase cerebral blood flow acutely , without affecting cognition . Objectives : To evaluate the effects of chronic resveratrol supplementation on both FMD and cognitive performance . Method : Twenty-eight obese but otherwise healthy adults ( BMI : 33.3 ± 0.6 kg/m2 ) were r and omized to take a single 75 mg capsule of trans-resveratrol ( Resvida ) or placebo daily for 6 weeks each in a double-blind crossover supplementation trial . Blood pressure , arterial compliance , FMD , and performance on the Stroop Color-Word Test were assessed at the end of each 6-week intervention period while fasted and at least 18 h after taking the last daily capsule . An additional capsule of the same supplement was then taken . FMD assessment was repeated 1 h later . Results : Chronic resveratrol supplementation for 6 weeks was well tolerated and result ed in a 23 % increase in FMD compared with placebo ( P = 0.021 , paired t-test ) . The extent of increase correlated negatively with baseline FMD ( r = −0.47 , P = 0.01 ) . A single dose of resveratrol ( 75 mg ) following chronic resveratrol supplementation result ed in a 35 % greater acute FMD response than the equivalent placebo supplementation . These FMD improvements remained significant after adjusting for baseline FMD . Blood pressure , arterial compliance , and all components of the Stroop Color-Word Test were unaffected by chronic resveratrol supplementation . Conclusion : Daily resveratrol consumption was well tolerated and has the potential to maintain healthy circulatory function in obese adults", "Chronic low- grade inflammation is the hallmark of type 2 diabetes ( T2D ) . Although in vitro and animal studies have shown that resveratrol exerts anti-inflammatory effects , clinical trials addressing these effects in patients with T2D are limited . Therefore , in the present study , we hypothesized that supplementation of resveratrol might improve inflammatory markers in patients with T2D in a r and omized , double-blind , placebo-controlled clinical trial . A total of 45 T2D patients were supplemented with either of 800 mg/d resveratrol or placebo capsules for 8 weeks . Percentage of CD14+CD16 + monocytes , plasma levels of inflammatory cytokines ( tumor necrosis factor α , interleukin [ IL ] 1β , IL-6 , and monocyte chemoattractant protein-1 ) , the expression levels of genes involved in the inflammatory responses ( toll-like receptor 2 , toll-like receptor 4 , and nuclear factor κB ) , lipopolysaccharide-stimulated cytokine ( tumor necrosis factor α , IL-1β , and IL-6 ) secretion from peripheral blood mononuclear cells , and metabolic and anthropometric parameters were assessed at both the baseline level and the end of the study . Compared with the placebo group , we could not detect any significant difference in the percentage of CD14+CD16 + monocytes , lipopolysaccharide-induced cytokine secretion , plasma levels of inflammatory cytokines , and the expression of inflammatory genes in resveratrol group . Moreover , we did not find any significant change in the metabolic and anthropometric parameters except for a significant reduction in fasting blood glucose and blood pressure . In conclusion , 8-week supplementation of resveratrol reduces blood glucose level in patients with T2D without improving their inflammatory markers ", "OBJECTIVES The aim of this study was to explore the effect of resveratrol supplementation on lipid profile in individuals with dyslipidemia . METHODS Apparently healthy men and non-pregnant women 20 to 65 y of age with new diagnosis of dyslipidemia were enrolled in a r and omized double-blind , placebo-controlled trial and r and omly allocated to receive either resveratrol 100 mg/d or placebo ( sucrose 0.5 g/d ) for 2 mo . Smoking , alcohol intake , diabetes , acute or chronic renal or hepatic diseases , malignancy , cardiovascular disease , serum triacylglycerol levels ≥400 mg/dL , low-density lipoprotein cholesterol levels ≥190 mg/dL , and consumption of lipid-lowering drugs or supplements containing resveratrol were exclusion criteria . RESULTS Seventy-one individuals with new diagnosis of dyslipidemia were enrolled and r and omly allocated to the resveratrol ( n = 35 ) or placebo groups ( n = 36 ) . At baseline , there were no significant differences between the study groups . After intervention period , individuals in the resveratrol group showed a significant decrease in total cholesterol ( 201.4 ± 34.4 versus 220.6 ± 37.4 , P = 0.04 ) and triacylglycerol ( 133.4 ± 55.3 versus 166.7 ± 68.5 , P = 0.04 ) concentrations compared with the placebo group , without significant statistical differences for high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels . CONCLUSION The results suggest that resveratrol supplementation significantly reduces total cholesterol and triacylglycerol concentrations in individuals with dyslipidemia" ]

[ "INTRODUCTION The extrusion of irrigation solutions beyond the apical constriction may result in postoperative pain . Sodium hypochlorite can cause severe tissue irritation and necrosis outside the root canal system if extruded into the periodontal ligament ( PDL ) space . Different delivery techniques were discussed to reduce this potential risk . The aim of this study was to compare the postoperative level of pain after root canal therapy using either endodontic needle irrigation or a negative apical pressure device . MATERIAL AND METHODS In a prospect i ve r and omized clinical trial , 110 asymptomatic single-rooted anterior and premolar teeth were treated endodontically with two different irrigation techniques . The teeth were r and omly assigned to two groups . In the MP group ( n = 55 ) , procedures were performed using an endodontic irrigating syringe ( Max-i-Probe ; Dentsply Rinn , Elgin , IL ) . The EV group ( n = 55 ) used an irrigation device based on negative apical pressure ( EndoVac ; Discus Dental , Culver City , CA ) . Postoperatively , the patients were prescribed ibuprofen 200 mg to take every 8 hours if required . Pain levels were assessed by an analog scale question naire after 4 , 24 , and 48 hours . The amount of ibuprofen taken was recorded at the same time intervals . RESULTS During the 0- to 4- , 4- to 24- , and 24- to 48-hour intervals after treatment , the pain experience with the negative apical pressure device was significantly lower than when using the needle irrigation ( p hours , the intake of analgesics was significantly lower in the group treated by the negative apical pressure device ( p pain intensity and the amount of analgesics . CONCLUSION The outcome of this investigation indicates that the use of a negative apical pressure irrigation device can result in a significant reduction of postoperative pain levels in comparison to conventional needle irrigation", "INTRODUCTION The purpose of this investigation was to determine the effect that apical preparation size and preparation taper had on the volume of irrigant delivered to the working length of a root canal preparation in a clinical ly relevant amount of time . METHODS Forty intact human single-rooted teeth were r and omly distributed into 2 separate phases . The first phase aim ed to determine the smaller apical size that will allow more volume of irrigant at working length . All sample s had the same taper and were sequentially instrumented to sizes of 30.06 , 35.06 , 40.06 , and 45.06 . The second phase aim ed to determine the taper that will allow more volume of irrigant at working length . Teeth were sequentially instrumented to 40.02 , 40.04 , 40.06 , and 40.08 . All sample s were irrigated by using the micro-cannula , and the volume of sodium hypochlorite suctioned at working length under negative pressure was measured during a period of 30 seconds by using a custom recovery device . RESULTS An increase in size from ISO # 35 to ISO # 40 result ed in a percentage gain of approximately 44 % in mean irrigant volume , whereas an increase in size from ISO # 40 to ISO # 45 result ed in a percentage gain of approximately 4 % . An increase in taper from 0.02 through 0.08 result ed in percentage gains of approximately 74 % , 5.4 % , and 2.4 % increase , respectively . CONCLUSIONS The data demonstrated that an increase in apical preparation size and taper result ed in a statistically significant increase in the volume of irrigant . In addition , an apical enlargement to ISO # 40 with a 0.04 taper will allow for tooth structure preservation and maximum volume of irrigation at the apical third when using the apical negative pressure irrigation system", "INTRODUCTION Several irrigation techniques have been recently introduced with the main objective of improving root canal disinfection . This in vitro study aim ed at comparing the intracanal bacterial reduction promoted by chemomechanical preparation with 3 different irrigation techniques . METHODS Root canals from extracted teeth were contaminated with Enterococcus faecalis ATCC 29212 for 7 days and then r and omly distributed into 3 experimental groups of 20 teeth each : group 1 , conventional irrigation with NaviTip needles inserted up to 3 mm short of the working length ; group 2 , same as group 1 , but supplemented with final irrigant activation by the EndoActivator system ; and group 3 , irrigation with the EndoVac system . NaOCl and ethylenediaminetetraacetic acid ( EDTA ) were the irrigants used in all experimental groups . The overall preparation time was kept constant for the groups , but the total volume ranged from 20 mL ( groups 1 and 2 ) to 43 mL ( group 3 ) . The control group was irrigated with saline solution ( total volume , 43 mL ) . Sample s taken before and after chemomechanical procedures were cultured , and the colony-forming units ( CFUs ) were counted . RESULTS Reduction in the bacterial population s was highly significant for all groups . The 3 experimental groups with NaOCl and EDTA as irrigants were significantly more effective than the control group with saline in reducing CFU counts . There were no significant differences between the 3 techniques tested . CONCLUSIONS There was no evident antibacterial superiority of any of the irrigation techniques evaluated in the present in vitro model", "R and omized controlled clinical trials are conducted to determine whether differences of clinical importance exist between selected treatment regimens . When statistical analysis of the study data finds a P value greater than 5 % , it is convention to deem the assessed difference nonsignificant . Just because convention dictates that such study findings be termed nonsignificant , or negative , however , it does not necessarily follow that the study found nothing of clinical importance . Subject sample s used in controlled trials tend to be too small . The studies therefore lack the necessary power to detect real , and clinical ly worthwhile , differences in treatment . Freiman et al. found that only 30 % of a sample of 71 trials published in the New Engl and Journal of Medicine in 1978 - 79 with a P value greater than 10 % were large enough to have a 90 % chance of detecting even a 50 % difference in the effectiveness of the treatments being compared , and they found no improvement in a similar sample of trials published in 1988 . It is therefore wrong and unwise to interpret so many negative trials as providing evidence of the ineffectiveness of new treatments . One must instead seriously question whether the absence of evidence is a valid justification for inaction . Efforts must be made to look for quantification of an association rather than just a P value , especially when the risks under investigation are small . The authors cite a recent trial comparing octreotide and sclerotherapy in patients with variceal bleeding , as well as the overview of clinical trials evaluating fibrinolytic treatment for preventing reinfa rct ion after acute myocardial infa rct ion as examples", "INTRODUCTION This study evaluated the prepared surface areas of oval-shaped canals in distal roots of m and ibular molars using four different instrumentation techniques . METHODS Teeth were prescanned and reconstructed using micro-computed tomography ( MCT ) scans at low resolution ( 68 microm ) . Forty-eight molars with ribbon-shaped/oval distal root canals were selected and r and omly assigned to four groups . Distal canals ( n = 12 each ) were prepared by circumferential filing using Hedström files to apical size # 40 ( group H/CF ) ; with ProTaper nickel-titanium rotaries to finishing file 4 ( F4 ) considering the distal canal as 1 canal ( group PT/1 ) ; ProTaper to F4 considering buccal and oral aspects of the distal canal as 2 individual canals ( group PT/2 ) ; ProTaper to F4 in a circumferential filing motion ( PT/CF ) . Before and after shaping , teeth were evaluated using MCT at 34-microm resolution . The percentage of prepared surface was assessed for the full canal length and the apical 4 mm . Statistical analysis was performed using analysis of variance and Bonferroni/Dunn multiple comparisons . RESULTS Preoperatively , canal anatomy was statistically similar among the groups ( p = 0.56 ) . Mean ( + /- st and ard deviation ) untreated areas ranged from 59.6 % ( + /-14.9 , group PT/2 ) to 79.9 % ( + /-10.3 , PT/1 ) for the total canal length and 65.2 % to 74.7 % for the apical canal portion , respectively . Canals in group PT/1 had greater untreated surface areas ( p amounts of treated surface areas were statistically similar in the apical 4 mm . CONCLUSIONS Preparations of oval-shaped root canals in m and ibular molars left a variable portion of surface area unprepared regardless of the instrumentation technique used . However , considering oval canals as two separate entities during preparation appeared to be beneficial in increasing overall prepared surface", "The present in vivo study was design ed to evaluate the efficacy of apical negative pressure irrigation ( ANP ) , passive ultrasonic irrigation ( PUI ) and positive pressure irrigation ( PP ) in the reduction of intracanal bacteria of dogs ' teeth with pulp necrosis and apical periodontitis . Eighty root canals were r and omly distributed into 3 experimental and 2 control groups according to the irrigation delivery system : group ANP ( n=20 ) , group PUI ( n=20 ) , group PP ( n=20 ) , group PC ( positive control - sterile saline irrigation ; n=10 ) and group NC ( negative control - vital pulps not subjected to bacterial inoculation ; n=10 ) . The first sample ( S1 ) was collected at baseline , and the second sample ( S2 ) was collected after the disinfection protocol s. All sample s were seeded in culture media for anaerobic bacteria . CFU counts were analyzed statistically by the Kruskal-Wallis , Dwass-Steel-Critchlow-Fligner post-hoc and Chi-square followed by Tukey like multiple comparisons for proportions ( α=0.05 ) . All experimental groups were effective in reducing Gram-positive bacteria compared with PC ( p reduction of Gram-negative bacteria , group ANP was significantly better than PP ( p No statistically significant difference could be found between PP and PUI ( p>0.05 ) . In dog 's teeth with apical periodontitis , the use of ANP and PUI can be considered promising disinfection protocol s as both delivery systems promoted a significant bacterial reduction", "Objectives The aim of this study was to compare the efficacy of apical negative pressure irrigation ( ANP ) and passive ultrasonic irrigation ( PUI ) with apical positive pressure irrigation ( PP — conventional irrigation ) in the periapical repair of dogs ’ teeth with apical periodontitis . Methods Forty-nine mesial and distal root canals of premolars of three dogs with experimentally induced periapical lesions were subjected to a single-session root canal treatment . The teeth were r and omly assigned to three groups : ANP , PUI , and PP ( control ) . After 180 days , the animals were euthanized , and the anatomic pieces were removed and subjected to histotechnical processing for morphological and morphometric histological analyses of hematoxylin and eosin (HE)-stained sections under conventional and fluorescence microscopy . Periapical lesion size before and 180 days after root canal treatment was measured by periapical radiographic examination . Tartrate-resistant acid phosphatase ( TRAP ) histoenzymology was performed for osteoclast counting and Brown and Brenn staining to assess bacteria . Data were analyzed statistically by the Kruskal-Wallis test ( α = 5 % ) . Result There were no statistically significant differences among the groups regarding periapical lesion size in the radiographic evaluation ( p = 0.91 ) . In the comparison of histopathological parameters , group ANP presented more homogeneous results . There was a statistically significant difference ( p = 0.02 ) between groups ANP and PP , with better results for group ANP in which milder infiltrate inflammatory was observed . No statistically significant difference ( p > 0.05 ) was found among the groups with respect to periodontal ligament space , presence of mineralized tissue resorption , size of the periapical lesions , and number of osteoclasts . Conclusion Although the three irrigation systems elicited similar periapical tissue response with respect to almost all evaluated parameters , ANP presented the mildest inflammatory infiltrate , suggesting an advantage over PP in the indication for clinical use . Clinical relevance Irrigation of the root canal systems is an extremely important step in root canal treatment . Therefore , it is of relevance to evaluate the efficacy of these systems by in vivo experimental models to provide scientific background for the clinical practice", "INTRODUCTION The purpose of this study was to evaluate the canal isthmus debridement efficacy of a new modified EndoVac ( Discus Dental , Culver City , CA ) irrigation protocol in comparison with EndoVac , passive ultrasonic irrigation ( PUI ) , and conventional needle irrigation in mesial roots of m and ibular molars . METHODS The mesial roots of 64 extracted m and ibular molars mounted in resin using Kuttler 's endodontic cube , sectioned at 2 and 4 mm from the working length , were r and omly divided into 4 groups ( n = 16 ) : group 1 : Max-I-Probe ( Dentsply Tulsa Dental , York , PA ) , group 2 : EndoVac ( EVI ) , group 3 : modified EndoVac , and group 4 : PUI . The specimens were reassembled and instrumented . A st and ard irrigation protocol was used during cleaning and shaping and final irrigation with the 4 irrigation/agitation techniques . Images of the isthmus region were taken before and after cleaning and shaping and after final irrigation . The percentage reduction of debris in the isthmus region was calculated by using the software program Image J ( v1.43 ; National Institutes of Health , Bethesda , MD ) . Intergroup analysis was performed using the Kruskal Wallis and Mann-Whitney U tests . Intragroup analysis was performed using Friedman and Wilcoxon signed rank tests . The level of significance was set at P percentage reduction of debris after cleaning and shaping and after final irrigation protocol in all the groups ( P cleaner canal isthmuses in all the groups ( P EVI group performed significantly better than the other groups . The EVI and PUI groups performed better than the Max-I-Probe group . There was no statistical significance between the EVI and PUI groups . CONCLUSIONS Canal isthmuses were significantly cleaner with the modified EndoVac irrigation technique when compared with the cleanliness seen with the other irrigation systems", "AIMS To devise an ex vivo model to test the efficacy of irrigation ( static/dynamic ) in removing a bio-molecular film from root canal walls . METHODOLOGY Forty human teeth with single straight canals were r and omly allocated to two groups for static ( n = 20 ) or dynamic ( n = 20 ) irrigation . The root canals were prepared to different apical sizes ( 20 , 40 ) and tapers ( 0.04 , 0.08 ) . The teeth were split longitudinally into two , stained collagen was applied to the canal surfaces and the tooth reassembled in a silicone matrix for dynamic or static irrigation . Digital images of the canal surface were taken before and after irrigation with 9 , 18 , 27 and 36 mL solution . The percentage of canal surface covered with stained collagen was quantified ( ipWin4 ) . The data were analysed using paired t-tests and linear regression models . RESULTS All the five explanatory variables : ' volume of irrigant used ' , ' mode of irrigation ' , ' orientation of open port of needle ' , ' corono-apical level of canal ' and ' root canal dimension ' had a significant ( P irrigation . The corono-apical level of canal was the most dominating factor . After irrigation , the apical third had 19.9 % and 33.8 % less area covered with the bio-molecular film than the middle and coronal thirds respectively . CONCLUSIONS The stained collagen bio-molecular film could not be removed completely by either static or dynamic irrigation . Factors influencing removal , in rank order of decreasing priority , were : corono-apical level , apical size and taper of canal preparation , and dynamic/static irrigation", "INTRODUCTION Heating a sodium hypochlorite solution improves its effectiveness . The aim of this study was to measure the in vivo temperature changes of sodium hypochlorite solutions that were initially preheated to 66 ° C or at room temperature inside root canals during routine irrigation . METHODS Thirty-five root canals were prepared to ISO size 40 with 4 % taper . A type K ( nickel-chromium-nickel ) thermocouple microprobe ( Testo NV , Ternat , Belgium ) was positioned within 3 mm of the working length to measure the temperature at 1-second intervals . In each canal , 2 test protocol s were evaluated in a r and omized order with 3 % sodium hypochlorite solutions : ( 1 ) preheated to 66 ° C and ( 2 ) at room temperature . The temperature measurements began 5 seconds before the 25 seconds of irrigant injections and continued for 240 seconds . This result ed in 270 data points for each protocol . RESULTS The temperature of the irrigant at room temperature increased from the initial intracanal temperature after injection of 20.7 ° C ( ±1.2 ° C ) to 30.9 ° C ( ±1.3 ° C ) in 10 seconds and to 35 ° C ( ±0.9 ° C ) after 240 seconds . The temperature of the preheated to 66 ° C solution decreased from 56.4 ° C ( ±2.7 ° C ) to 45.4 ° C ( ±3.0 ° C ) after 5 seconds , reached 37 ° C ( ±0.9 ° C ) after 60 seconds , and reached 35.7 ° C ( ±0.8 ° C ) after 240 seconds . CONCLUSIONS The original temperatures of the sodium hypochlorite solutions were buffered inside the root canal and tended to rapidly evolve to equilibrium . The findings of this study contribute to an improved underst and ing of the thermodynamic behaviors of irrigant solutions inside root canals in vivo", "INTRODUCTION Many in vitro studies have debated over the ability of different irrigant delivery and /or agitation systems to reach the apical third of curved root canals ; however , little is known about irrigant penetration in vivo . Therefore , the purpose of this study was to compare the efficacy of the conventional endodontic irrigation needle , passive ultrasonic irrigation ( PUI ) , and a negative pressure system for irrigant delivery to working length ( WL ) of mesial canals of m and ibular molars . METHODS Thirty mesial canals of 30 vital m and ibular first or second molars were r and omly assigned into 3 groups ( n = 10 ) : ( 1 ) Monoject syringe with 27-gauge needle ; ( 2 ) PUI with IrriSafe tip ; and ( 3 ) EndoVac system . All canals were treated following the same preparation protocol to size 35/0.04 by using 5.25 % NaOCl as irrigant during preparation procedure . Before obturation , canals were irrigated with 1 mL of a radiopaque solution by using the assigned irrigation system , and a digital radiograph was taken by using a parallel technique . With the aid of image editing software the distance between WL and maximum irrigant penetration was measured . RESULTS Mean distances for Monoject , PUI , and EndoVac groups were 1.51 mm , 0.21 mm , and 0.42 mm , respectively . Analysis of variance test showed statistically significant differences between groups ( P Tukey honestly significant difference test showed statistically significant differences between the Monoject group and the other 2 groups ( P irrigant to WL of root canals", "INTRODUCTION The purpose of this in vitro study was to compare the debris removal efficacy of the EndoActivator system , the F file , ultrasonic irrigation , or 6 % NaOCl irrigation alone in human m and ibular molars after h and -rotary instrumentation . METHODS A custom brass cube ( K-Kube ) was used to create a sealed canal system , allowing each tooth to serve as its own control . Forty extracted m and ibular molars were r and omly divided into 4 equal experimental groups . Each tooth was mounted , sectioned at 1 , 3 , and 5 mm from the working length , and then reassembled into the K-Kube , and the mesial roots were similarly prepared by using h and -rotary instrumentation . For final debridement , group 1 used F file for 30 seconds , group 2 used EndoActivator system for 30 seconds , group 3 used ultrasonic irrigation for 30 seconds , and group 4 used irrigation with 6 % NaOCl within 1 mm of working length . All groups received a final irrigation with 6 % NaOCl in each canal . Specimens were evaluated at 1 , 3 , and 5 mm from the working length for cleanliness by capturing a digital image with a stereomicroscope . All specimens had the percent cleanliness for each canal and isthmus calculated both before and after final debridement . Statistical analysis was completed by using a repeated- measures analysis of variance with Tukey post hoc tests . RESULTS AND CONCLUSIONS The results showed no statistically significant difference in canal or isthmus cleanliness among the 4 groups , but there was a statistically significant difference ( P canal cleanliness between the 1-mm level versus the 3-mm and 5-mm levels for all of the groups", "AIM To evaluate the ex vivo efficacy of the EndoVac system and photodynamic treatment ( PDT ) as adjuncts to chemomechanical debridement associated with calcium hydroxide ( CaOH2 ) in reducing the levels of intracanal Enterococcus faecalis . METHODOLOGY One hundred and twenty-five sterile premolar teeth were conventionally accessed , prepared and then contaminated with E. faecalis ( ATCC 29212 ) for 30 days . Teeth were r and omly divided into 4 groups : Control ( chemomechanical debridement with conventional irrigation ) ; Endovac ( chemomechanical debridement with EndoVac system ) ; PDT ( chemomechanical debridement with conventional irrigation and PDT ) and Endovac+PDT ( chemomechanical debridement with EndoVac and PDT ) . The irrigants used in all groups were 5.25 % sodium hypochlorite and 17 % EDTA . After treatment , an intracanal dressing ( CaOH2 ) was applied in all canals for 7 days . Sample s were obtained before ( T1 ) and after the therapeutic procedures ( T2 ) and , after intracanal medication ( T3 ) , plated onto BHI media and incubated ( 37 ° C , 48 h ) to determine the colony-forming units ( CFU mL(-1 ) ) . RESULTS The overall mean cell counts ( CFU mL(-1 ) ) of E. faecalis were high at the initial contamination ( T1 ) . A significant reduction ( P of E. faecalis mean counts was observed in all groups from baseline ( T1 ) to both post-therapy samplings ( T2 and T3 ) ; no differences amongst the groups were detected . No significant change in bacterial counts from T2 to T3 was detected . CONCLUSION The adjunctive use of the EndoVac system and the photodynamic treatment , in combination or not , was as effective as the conventional chemomechanical debridement associated with CaOH2 on reducing the counts of intracanal E. faecalis", "INTRODUCTION This study evaluates radiographically the efficacy of 4 revascularization protocol s in necrotic-infected immature dog teeth with apical periodontitis ( AP ) . METHODS Forty double-rooted immature premolar teeth from 4 female beagle dogs aged 5 months were used . Four teeth were left untouched as negative controls ; the other 36 teeth were infected to develop pulp necrosis and AP following different treatment protocol s. Four teeth were left untreated and assigned to the positive control group , and the last 28 teeth were r and omly assigned into 4 experimental groups of 8 teeth : A1 , sodium hypochlorite ( NaOCl ) + a blood clot ; A2 , NaOCl + platelet-rich plasma ( PRP ) ; B1 , NaOCl + modified triantibiotic paste ( mTAP ) + a blood clot ; and B2 , NaOCl + mTAP + PRP . Teeth were monitored radiographically for 6 months regarding healing of periapical radiolucencies , thickening of the dentinal walls , and apical closure of roots . RESULTS Significant differences ( P periapical radiolucencies ( 62.5 % ) , continued radiographic thickening of radicular walls ( 53.1 % ) , radiographic apical closure ( 43.8 % ) , and deposition of hard tissue on radicular dentin walls ( 53.1 % ) . Group B2 showed maximal improvement in the 3 variables assessed ( P mTAP and the use of PRP as scaffold improves the success rate of the revascularization procedure", "AIM To evaluate the effect of an apical negative pressure system , a passive ultrasonic irrigation system and a combination of both apical negative pressure and passive ultrasonic irrigation on the penetration of the irrigating contrast solution ( ICS ) up to working length and into simulated lateral canals . METHODOLOGY The root canals of 64 single-rooted teeth were instrumented using the ProTaper rotary system . In each sample , three simulated lateral canals were created at 2 , 4 and 6 mm levels from the root apex using a 06-size C+ file ( Dentsply Maillefer , Ballaigues , Switzerl and ) . Sample s were r and omly assigned into 4 experimental groups ( n = 16 ) : group I - conventional needle irrigation , group II - passive ultrasonic irrigation , group III - apical negative irrigation system and group IV - combination of passive ultrasonic irrigation and apical negative pressure irrigation system . To examine irrigating solution penetration , Indian ink was mixed with 5.25 % NaOCl and delivered into the root canals . Sample s were then assessed by direct observation of the images taken using Canon EOS rebel T3 . The depth of penetration of ICS up to the working length and into the simulated lateral canals was analysed using chi-squared tests . RESULTS The combination ( ANP and PUI ) and ANP group had significantly deeper ICS penetration up to the working length ( P combination ( ANP and PUI ) and the PUI group exhibited significantly greater ICS penetration into lateral canals at the 6 mm level ( P combination of ANP and PUI had significantly greater ICS penetration into the lateral canals than the other groups ( P combination of ANP and PUI was the only group able to achieve irrigating contrast solution penetration both up to the working length and into lateral canals", "The aim of this in vitro study was to determine whether irrigation with apical negative pressure was more effective than traditional positive-pressure irrigation in eradicating Enterococcus faecalis from preshaped root canals . Fifty-four extracted m and ibular molars were instrumented to produce either a non-tapered or tapered preparation , sterilized , inoculated with E. faecalis for 30 days , and then r and omly assigned into the following groups : group 1 - -non-tapered preparation and negative-pressure irrigation , group 2 - -non-tapered preparation and positive-pressure irrigation , group 3 - -tapered preparation and positive-pressure irrigation , and group 4 - -tapered preparation and negative-pressure irrigation . Mesial canals were sample d before and after final irrigation and sample s incubated aerobically for 48 hours at 37 degrees C. Scanning electron microscopic analysis confirmed dense bacterial colonies in the positive control , consistent with biofilm formation . A statistically significant difference was evident when comparing apical negative-pressure irrigation to positive-pressure irrigation ( p=0.004 ) . There was no statistically significant difference in colony-forming units ( CFUs ) between sizes # 35 and # 45 , nor between tapered and non-tapered preparation . The results of this in vitro study showed that apical negative-pressure irrigation has the potential to achieve better microbial control than traditional irrigation delivery systems" ]

[ "Background Patients with Parkinson 's disease ( PD ) suffer from a high fall risk . Previous approaches for evaluating fall risk are based on self-report or testing at a given time point and may , therefore , be insufficient to optimally capture fall risk . We tested , for the first time , whether metrics derived from 3 day continuous recordings are associated with fall risk in PD . Methods and Material s 107 patients ( Hoehn & Yahr Stage : 2.6±0.7 ) wore a small , body-fixed sensor ( 3D accelerometer ) on lower back for 3 days . Walking quantity ( e.g. , steps per 3-days ) and quality ( e.g. , frequency-derived measures of gait variability ) were determined . Subjects were classified as fallers or non-fallers based on fall history . Subjects were also followed for one year to evaluate predictors of the transition from non-faller to faller . Results The 3 day acceleration derived measures were significantly different in fallers and non-fallers and were significantly correlated with previously vali date d measures of fall risk . Walking quantity was similar in the two groups . In contrast , the fallers walked with higher step-to-step variability , e.g. , anterior-posterior width of the dominant frequency was larger ( p = 0.012 ) in the fallers ( 0.78±0.17 Hz ) compared to the non-fallers ( 0.71±0.07 Hz ) . Among subjects who reported no falls in the year prior to testing , sensor-derived measures predicted the time to first fall ( p = 0.0034 ) , whereas many traditional measures did not . Cox regression analysis showed that anterior-posterior width was significantly ( p = 0.0039 ) associated with time to fall during the follow-up period , even after adjusting for traditional measures . Conclusions / Significance These findings indicate that a body-fixed sensor worn continuously can evaluate fall risk in PD . This sensor-based approach was able to identify transition from non-faller to faller , whereas many traditional metrics were not successful . This approach may facilitate earlier detection of fall risk and may in the future , help reduce high costs associated with falls", "Background and Purpose — Individuals with chronic stroke often demonstrate a “ plateau , ” or deceleration of motor recovery , which may lead to discharge from physical therapy ( PT ) . However , numerous studies report improvements in motor function when individuals are provided intensive practice of motor tasks . We suggest that reduced task-specific walking practice during clinical PT contributes to limited gains in ambulatory function in those with a perceived plateau poststroke , and suggest that further gains can be realized if intensive stepping , or locomotor training ( LT ) is provided after discharge . Methods — Twenty subjects with chronic stroke completed a repeated baseline measures , r and omized crossover trial in which walking performance was assessed during the last 4 weeks of clinical PT before discharge secondary to reaching a plateau , followed by 4 weeks of intensive LT and 4 weeks of no intervention . Outcome measures included clinical and physiological ( metabolic ) measures of walking overground and on a treadmill , and measures of daily stepping activity in the home and community , including during clinical PT and subsequent LT sessions . Results — Stepping practice was more than 4-fold higher during LT versus clinical PT sessions , with significant improvements in daily stepping and gait efficiency only after LT . Changes in daily stepping after clinical PT and intensive LT were correlated ( P Intensive LT results in improved daily stepping in individuals poststroke who have been discharged from PT because of a perceived plateau in motor function . These improvements may be related to the amount and intensity of stepping practice", "OBJECTIVE This prospect i ve study examined symptoms of depression , fatigue , pain , self-efficacy , and social support as possible intermediaries in the pathway between changes in physical activity and quality of life ( QOL ) across a 6-month period in persons with multiple sclerosis ( MS ) . DESIGN AND MAIN OUTCOME MEASURES Adults with a definite diagnosis of MS wore an accelerometer for 7 days and then completed a battery of question naires at baseline ( n = 292 ) and 6-months follow-up ( n = 276 ) . The data were analyzed using panel analysis and covariance modeling in Mplus 3.0 . RESULTS The initial analysis indicated that change in physical activity was associated with a statistically significant and small residual change in QOL ( beta = .07 ) . The subsequent analysis indicated that change in physical activity was associated with residual changes in fatigue ( gamma = -.17 ) , pain ( gamma = -.13 ) , social support ( gamma = .07 ) , and self-efficacy ( gamma = .11 ) , and , in turn , changes in fatigue ( beta = -.13 ) , pain ( beta = -.09 ) , social support ( beta = .18 ) , and self-efficacy ( beta = .10 ) were associated with a residual change in QOL . CONCLUSION The observed pattern of relationships supports the possibility that physical activity is indirectly associated with improved QOL through pathways that include fatigue , pain , social support , and self-efficacy in individuals with MS", "This study examined the correlation of physical activity with neurological impairment and disability in persons with multiple sclerosis ( MS ) . Eighty individuals with MS wore an accelerometer for 7 days and completed the Symptom Inventory ( SI ) , Performance Scales ( PS ) , and Exp and ed Disability Status Scale . There were large negative correlations between the accelerometer and SI ( r = −0.56 ; ρ = −0.58 ) and Exp and ed Disability Status Scale ( r = −0.60 ; ρ = −0.69 ) and a moderate negative correlation between the accelerometer and PS ( r = −0.39 ; ρ = −0.48 ) indicating that physical activity was associated with reduced neurological impairment and disability . Such findings provide a preliminary basis for using an accelerometer and the SI and PS as outcome measures in large-scale prospect i ve and experimental examinations of the effect of physical activity behavior on disability and dependence in MS", "Background and Purpose — The purpose of this study was to quantitatively measure and describe the amount and pattern of physical activity in patients within the first week after acute ischemic stroke and transient ischemic attack using accelerometers . Methods — A total of 100 patients with acute ischemic stroke or transient ischemic attack admitted to our acute stroke unit wore Actical accelerometers attached to both wrists and ankles and the hip for ⩽7 days . Patients were included within 72 hours of symptom onset . Accelerometer output was measured in activity counts ( AC ) . Patients were tested daily with Sc and inavian Stroke Scale . Results — Physical activity peaked in the morning and declined during the rest of the day . In patients with stroke , total AC were 71 % lower than in patients with transient ischemic attack . AC were 80 % lower in the paretic compared with those in the nonparetic arm in patients with ischemic stroke . For the legs AC were 44 % lower on the paretic side and an overall increase in AC with time was found . There was a significant increase in AC with increasing Sc and inavian Stroke Scale and a decrease in AC with increasing age . Conclusions — This study demonstrates the feasibility of using accelerometers to quantitatively and continuously measure physical activity simultaneously from all 4 extremities and the hip in patients with acute ischemic stroke and transient ischemic attack . Our study provides quantitative evidence of physical inactivity in patients with acute ischemic stroke . The method offers a low cost and noninvasive tool for future clinical interventional physiotherapeutic and early mobilization studies . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01560520", "Background Chronic fatigue and inactivity are prevalent problems among individuals with multiple sclerosis ( MS ) and may independently or interactively have detrimental effects on quality of life and ability to participate in life roles . However , no studies to date have systematic ally evaluated the benefits of an intervention for both managing fatigue and promoting physical activity in individuals with MS . This study involves a r and omized controlled trial to examine the effectiveness of a telehealth intervention that supports individuals with MS in managing fatigue and increasing physical activity levels . Methods / Design A r and omly-allocated , three-parallel group , time-series design with a social support program serving as the control group will be used to accomplish the purpose of the study . Our goal is to recruit 189 ambulatory individuals with MS who will be r and omized into one of three telehealth interventions : ( 1 ) a contact-control social support intervention , ( 2 ) a physical activity-only intervention , and ( 3 ) a physical activity plus fatigue management intervention . All interventions will last 12 weeks and will be delivered entirely over the phone . Our hypothesis is that , in comparison to the contact-control condition , both the physical activity-only intervention and the physical activity plus fatigue management intervention will yield significant increases in physical activity levels as well as improve fatigue and health and function , with the physical activity plus fatigue management intervention yielding significantly larger improvements . To test this hypothesis , outcome measures will be administered at Weeks 1 , 12 , and 24 . Primary outcomes will be the Fatigue Impact Scale , the Godin Leisure-Time Exercise Question naire ( GLTEQ ) , and Actigraph accelerometers . Secondary outcomes will include the SF-12 Survey , Mental Health Inventory , Multiple Sclerosis Impact Scale , the Community Participation Indicator , and psychosocial constructs ( e.g. , self-efficacy ) . Discussion The proposed study is novel , in that it represents a multi-disciplinary effort to merge two promising lines of research on MS : fatigue management and physical activity promotion . Collectively , the proposed study will be the largest r and omized controlled trial to examine the effects of a lifestyle physical activity intervention in people with MS.Trial registration", "Background and Purpose : Relatively little is known about the natural evolution of physical activity – related participation restrictions associated with Parkinson 's disease ( PD ) . We examined this issue prospect ively , using continuous monitoring technology to capture the free-living ambulatory activity of persons with PD engaging in life situations . We specifically sought ( 1 ) to explore natural , long-term changes in daily ambulatory activity and ( 2 ) to compare the responsiveness of ambulatory activity parameters to clinical measures of gait and disease severity . Methods : Thirty-three persons with PD participated ( Hoehn and Yahr range of 1–3 ) . Participants wore a step activity monitor for up to 7 days at baseline and again at 1-year follow-up . Mean daily values were calculated for parameters indicative of amount , intensity , frequency , and duration of ambulatory activity . Clinical measures included the Unified Parkinson Disease Rating Scale , the 6-Minute Walk , and Maximal Gait Speed . Parametric tests for paired sample s were used to investigate changes in ambulatory activity parameters and clinical measures . Results : Participants had significant declines in the amount and intensity of daily ambulatory activity but not in its frequency and duration ( P number of daily minutes participants spent engaging in at least moderate-intensity ambulatory activity . Conclusion : Continuous monitoring of ambulatory activity beyond mere step counts may serve as a distinct and important means of quantifying declining ambulatory behavior associated with disease progression or improved ambulatory behavior result ing from rehabilitation and medical and /or surgical interventions in persons with PD", "Reliability estimates are important parameters for power analyses and sample -size calculations in behavioral interventions for increasing physical activity among persons with multiple sclerosis ( MS ) . This study involved a secondary data analysis for providing reliability estimates for measures of physical activity over a six-month period in MS . On two occasions separated by six months , participants completed the Godin Leisure-Time Exercise Question naire ( GLTEQ ) and wore an ActiGraph model 7164 accelerometer on a belt around the waist for a seven-day period . The outcomes from the accelerometer were total activity counts and minutes of moderate-to-vigorous physical activity ( MVPA ) per day . The main analyses involved two-way , r and om effects intraclass correlation coefficients ( ICCs ) . The ICCs for GLTEQ scores , total activity counts , and minutes of MVPA were .66 , .84 , and .84 , respectively . Additionally , the sample was less physically active than adults without MS , and correlation analyses supported the validity of the measures , but within a substantially larger sample . Overall , the measures had acceptable , but different , reliability over six months in this sample of mostly women with relapsing – remitting MS . Power analyses using the reliability estimates indicated vastly different sample sizes for the measures of physical activity and when compared with the default parameter in software packages", "OBJECTIVE This brief report describes the possibility of reactivity in the baseline assessment of physical activity using accelerometry from two separate r and omized controlled trials of a behavior intervention for increasing physical activity in persons with multiple sclerosis ( MS ) . METHOD The sample s included 18 persons with multiple sclerosis ( MS ) from Study 1 and 20 from Study 2 who were r and omized into treatment arms of the intervention . The participants initially wore an accelerometer over a 7-day period for collection of baseline data , and one week later wore a pedometer over a 7-day period for collection of data for self-monitoring and goal setting in week 1 of the 12-week intervention . The accelerometer and pedometer data were both expressed in average steps per day over a 7-day period . RESULTS There was a moderate ( d = .56 ) , statistically significant ( p = .03 ) difference of 1,822 steps per day between baseline and week 1 of the intervention in Study 1 . There was a large ( d = 1.36 ) , statistically significant ( p = .0001 ) difference of 2,338 steps per day in Study 2 . CONCLUSION We are unaware of other research describing a significant change in physical activity between baseline and the first week of a behavioral intervention and believe that this change reflects reactivity in the baseline assessment using accelerometry", "Background : Exercise training is beneficial , but most persons with multiple sclerosis ( MS ) are sedentary and physically inactive . This has prompted a new focus on the promotion of lifestyle physical activity in MS . We previously design ed , tested , and refined a behavioral intervention delivered through the Internet that successfully increased lifestyle physical activity in MS , but have not evaluated the effects on secondary symptomatic and health-related quality of life ( HRQOL ) outcomes . Objective : We conducted a 6-month r and omized controlled trial ( RCT ) that examined the efficacy of an Internet-delivered , behavioral intervention for improving outcomes of fatigue , depression , anxiety , pain , sleep quality , and HRQOL in 82 ambulatory persons with MS . The secondary aim was to replicate previous results regarding change in free-living physical activity . Results : There was a significant and positive effect of the intervention on fatigue severity ( p=.001 , ηρ2=.15 ) and its physical impact ( p=.008 , ηρ2=.09 ) , depression ( p=.006 , ηρ2=.10 ) , and anxiety ( p=.006 , ηρ2=.10 ) . There were non-significant improvements in pain ( p=.08 , ηρ2=.04 ) , sleep quality ( p=.06 , ηρ2=.05 ) , and physical HRQOL ( p=.06 , ηρ2=.05 ) . We replicated our previous results by demonstrating an increase in self-reported physical activity ( p=.001 , ηρ2=.13 ) . Conclusions : Our results support behavioral interventions targeting lifestyle physical activity as an alternative approach for managing symptoms in MS", "INTRODUCTION Direct-to-consumer mHealth devices are a potential asset to behavioral research but rarely tested as intervention tools . This trial examined the accelerometer-based Fitbit tracker and website as a low-touch physical activity intervention . The purpose of this study is to evaluate , within an RCT , the feasibility and preliminary efficacy of integrating the Fitbit tracker and website into a physical activity intervention for postmenopausal women . METHODS Fifty-one inactive , postmenopausal women with BMI ≥25.0 were r and omized to a 16-week web-based self-monitoring intervention ( n=25 ) or comparison group ( n=26 ) . The Web-Based Tracking Group received a Fitbit , instructional session , and follow-up call at 4 weeks . The comparison group received a st and ard pedometer . All were asked to perform 150 minutes/week of moderate to vigorous physical activity ( MVPA ) . Physical activity outcomes were measured by the ActiGraph GT3X+ accelerometer . RESULTS Data were collected and analyzed in 2013 - 2014 . Participants were aged 60 ( SD=7 ) years with BMI of 29.2 ( 3.5 ) kg/m(2 ) . Relative to baseline , the Web-Based Tracking Group increased MVPA by 62 ( 108 ) minutes/week ( p ) ; 10-minute MVPA bouts by 38 ( 83 ) minutes/week ( p=0.008 ) ; and steps by 789 ( 1,979 ) ( p=0.01 ) , compared to non-significant increases in the Pedometer Group ( between-group p=0.11 , 0.28 , and 0.30 , respectively ) . The Web-Based Tracking Group wore the tracker on 95 % of intervention days ; 96 % reported liking the website and 100 % liked the tracker . CONCLUSIONS The Fitbit was well accepted in this sample of women and associated with increased physical activity at 16 weeks . Leveraging direct-to-consumer mHealth technologies aligned with behavior change theories can strengthen physical activity interventions", "OBJECTIVES Physical activity may reduce the risk of cognitive decline in the elderly , but its effects among the oldest-old ( i.e. , those aged 85 years and older ) are not well known . Our study assessed the association between very late-life physical activity and 5-year risk of mild cognitive impairment ( MCI ) or dementia and neuropsychological test performance among oldest-old women . METHODS This prospect i ve study was conducted at three sites . Participants included 1,249 women ( mean [ st and ard deviation ] age : 83.3 [ 2.8 ] years ) . Baseline physical activity was measured by self-reported blocks walked per week and analyzed according to tertile . Five years later , surviving participants who were 85 years and older ( oldest-old ) completed neuropsychological testing and underwent adjudication of clinical cognitive status ( normal , MCI , or dementia ) . All analyses were adjusted for baseline age , education , cognition , depression , body mass index , hypertension , smoking , and coronary artery disease . RESULTS Compared with women in the lowest tertile , women in the highest tertile were less likely to develop dementia ( 13.0 % versus 23.2 % ; multivariate adjusted odds ratio : 0.54 [ 95 % confidence interval : 0.36 - 0.82 ] ) . However , risk of MCI was not associated with physical activity . Physical activity was also associated with higher performance 5 years later on tests of global cognition , category fluency , and executive function but not phonemic fluency , memory , or attention . CONCLUSIONS Higher level of very late-life physical activity was associated with a lower risk of subsequent dementia in oldest-old women . These findings support future studies for late-life physical activity interventions for the prevention of dementia among oldest-old women", "Objective This study investigated the clinical predictive value of the Fugl-Meyer Assessment ( FMA ) arm score and the upper limb activity assessed by accelerometers in patients with hemiparesis after acute stroke . Design The prospect i ve cohort ( n = 129 ) was recruited from a general hospital ; activity variables and FMA score at intake were related to the FMA , the modified Rankin Scale , and rehabilitation status after 3 mos of follow-up . The prediction model was based on binary logistic regression . Results Although the FMA score at intake has the best overall predictive value for all three outcome measures ( FMA3 , 87.6 % ; modified Rankin Scale , 85.3 % ; RS , 73.6 % ) , the activity of the impaired arm as assessed by the accelerometer has the best predictive value to determine patients who are at risk for continued disability ( modified Rankin Scale score 1 , 95.1 % ) . The most difficult outcome measure for prediction is the rehabilitation status ; specifically , the patients who went home are predicted imprecisely . The ratio variable is the least accurate predictor of all tested variables . Conclusions The FMA arm score at intake is the best predictor for arm recovery and general disability . The activity of the impaired arm is an excellent predictor for prolonged disability and is an alternative to the FMA score when it is impossible to score the FMA in the acute phase of stroke", "The factors determining recovery from hemiparetic stroke are manifold . We studied spontaneous arm movement activity in the acute phase after stroke as a predictor of recovery . Included in this prospect i ve study were 25 patients ( 63 ± 10 years ; 9 women , 16 men ) with acute middle cerebral artery stroke and 7 control patients without neurological disease ( 61 ± 14 years ; 3 women , 4 men ) . Movement activity was measured continuously for 4 days in both arms using Actiwatches and analysed off-line . Movement activity of the nonaffected arm ranged from 16 h per day in the stroke patients . Nine stroke patients with an initial decline in arm movement activity showed no increase in movement activity in either arm over 4 days after stroke , and the other 16 patients improved steadily after admission ( p 0.003 ) . C-reactive protein was elevated in the non-recovering patients ( 4.4 ± 4.9 mg/dl ) related to a low number of waking hours ( r = −0.512 , p 0.01 ) . Stroke severity , location and treatment , as well as arterial blood pressure ( 162 ± 21 mmHg ) and body temperature ( 36.9 ± 06 ° C ) were not different among the groups . The impairment was still different among the two groups 3 months after stroke . Our results support the notion that in the acute stage after middle cerebral artery stroke there are patients with a secondary decline in general motor activity related to an enhanced sleep dem and as assessed with accelerometry . This impairment was related to elevated C-reactive protein", "OBJECTIVE To examine the psychometric properties of an objective method for assessing real-world arm activity in a large sample with subacute stroke . DESIGN Validation study . SETTING Community . PARTICIPANTS Persons 3 to 9 months poststroke ( N=169 ) with mild to moderate motor impairment of their hemiparetic arm enrolled in a multisite , r and omized clinical trial of constraint-induced movement therapy . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Participants wore an accelerometer on each arm outside the laboratory for 3 days before and after treatment or an equivalent no-treatment period . They also completed the Actual Amount of Use Test ( AAUT ) , which is an observational measure of spontaneous more-impaired arm use , and the Motor Activity Log ( MAL ) , which is an interview assessing more-impaired arm use in daily life . RESULTS Low-pass-filtered accelerometer recordings were reliable ( r range , > .8 ) and stable ( P range , > .48 ) . Their validity was also supported . Correlations calculated across all participants at baseline between the ratio of more-impaired to less-impaired arm accelerometer recordings and AAUT and MAL scores were .60 and .52 , respectively . CONCLUSIONS Accelerometry provides an objective , real-world index of more-impaired arm activity with good psychometric properties", "Aim : The aim of the present study was the evaluation of actigraphy as a tool to objectify the recovery process after motor paresis due to stroke . Methods : The motor activity of both arms of patients suffering from stroke was actigraphically recorded at four different time points during the course of rehabilitation : 24–36 h , 5–7 days , 3 months , and 6 months after stroke . Results : Motor activity monitored by wrist-worn actigraphs located at the impaired side revealed an increase in activity between the first two time points and the subsequent ones . Additionally , actigraphic recordings showed lower total motor activity at the impaired side as compared to the nonimpaired side . A significant positive correlation was found between the actigraphically recorded motor activity and the results of the Sc and inavian Stroke scale , the Barthel Index , the Rankin Scale Score and with the Motoricity Index during the 1st week , which corresponds to the time when neurological deficits were most pronounced . Conclusion : Our results suggest that actigraphy is a useful tool in the objective evaluation of motor activity after stroke . Moreover , actigraphy covers additional aspects that are not reflected by the usual stroke scales in a clinical situation", "Background / Objective . This study examined the test-retest reliability of an activity monitor ( AM ) in home and community setting s in individuals with Parkinson 's disease ( PD ) . Methods . Nine independent community dwellers with idiopathic PD were recruited ( 8 males and 1 female ; median age = 66 years , range 46 - 71 ; Hoehn & Yahr score 2 ) . Patients wore the AM for 3 separate sessions in the home and community with 7 days between each session . The first 2 sessions lasted 24 hours each , and the third session lasted 48 hours . Reliability indices and measures of variability were obtained by using intraclass correlation coefficients ( ICC ) and generalizability coefficients . The functional activity measures included the percentage of time spent in sleeping positions , sitting , st and ing , and walking ; the number of transitions between sit and st and ; the total number of transitions ; the number of walking periods lasting 5 and 10 seconds ; and stride frequency . Results . The ICCs for functional activities between the first and second consecutive days for the 48-hour session ( third session ) ranged from .76 to .92 . The ICCs for the 7- and 14-day intervals ranged from .45 to .96 , with walking-related measures showing the highest ICCs ( range = .81 to .96 ) . Across the three 24-hour periods ( sessions 1 and 2 , and the first 24 hours of session 3 ) , the ICCs for walking-related measures were again high ranging from .87 to .92 . Walking-related measures demonstrated the highest generalizability coefficients , indicating these measures have the highest test-retest reliability in comparison to other functional activity measures . Conclusions . The present study shows that 24 hours of recording with an AM is a sufficient duration of time to reliably record patients ' functional activity in the home and community setting s. In addition , the highest test-retest reliability for activities across 7- and 14-day intervals were found for walking-related measures in individuals with PD , indicating these measures have the highest stability compared to the other measures of functional activity", "Purpose This study aims to assess the extent to which accelerometers can be used to determine the effect of robot-supported task-oriented arm-h and training , relative to task-oriented arm-h and training alone , on the actual amount of arm-h and use of chronic stroke patients in their home situation . Methods This single-blind r and omized controlled trial included 16 chronic stroke patients , r and omly allocated using blocked r and omization ( n = 2 ) to receive task-oriented robot-supported arm-h and training or task-oriented ( unsupported ) arm-h and training . Training lasted 8 weeks , 4 times/week , 2 × 30 min/day using the (T-)TOAT ( (Technology-supported)-Task-Oriented-Arm-Training ) method . The actual amount of arm-h and use , was assessed at baseline , after 8 weeks training and 6 months after training cessation . Duration of use and intensity of use of the affected arm-h and during unimanual and bimanual activities were calculated . Results Duration and intensity of use of the affected arm-h and did not change significantly during and after training , with or without robot-support ( i.e. duration of use of unimanual use of the affected arm-h and : median difference of −0.17 % in the robot-group and −0.08 % in the control group between baseline and after training cessation ; intensity of the affected arm-h and : median difference of 3.95 % in the robot-group and 3.32 % in the control group between baseline and after training cessation ) . No significant between-group differences were found . Conclusions Accelerometer data did not show significant changes in actual amount of arm-h and use after task-oriented training , with or without robot-support . Next to the amount of use , discrimination between activities performed and information about quality of use of the affected arm-h and are essential to determine actual arm-h and performance . Trial Registration Controlled-trials.com IS RCT", "UNLABELLED Mudge S , Barber PA , Stott NS . Circuit-based rehabilitation improves gait endurance but not usual walking activity in chronic stroke : a r and omized controlled trial . OBJECTIVE To determine whether circuit-based rehabilitation would increase the amount and rate that individuals with stroke walk in their usual environments . DESIGN Single-blind r and omized controlled trial . SETTING Rehabilitation clinic . PARTICIPANTS Sixty participants with a residual gait deficit at least 6 months after stroke originally enrolled in the study . Two withdrew in the initial phase , leaving 58 participants ( median age , 71.5y ; range , 39.0 - 89.0y ) who were r and omized to the 2 intervention groups . INTERVENTIONS The exercise group had 12 sessions of clinic-based rehabilitation delivered in a circuit class design ed to improve walking . The control group received a comparable duration of group social and educational classes . MAIN OUTCOME MEASURES Usual walking performance was assessed using the StepWatch Activity Monitor . Clinical tests were gait speed ( timed 10-meter walk ) and endurance ( six-minute walk test [ 6MWT ] ) , confidence ( Activities-Based Confidence Scale ) , self-reported mobility ( Rivermead Mobility Index [ RMI ] ) , and self-reported physical activity ( Physical Activity and Disability Scale ) . RESULTS Intention-to-treat analysis revealed that the exercise group showed a significantly greater distance for the 6MWT than the control group immediately after the intervention ( P=.030 ) but that this effect was not retained 3 months later . There were no changes in the StepWatch measures of usual walking performance for either group . The exercise and control groups had significantly different gait speed ( P=.038 ) and scores on the RMI ( P=.025 ) at the 3-month follow-up . These differences represented a greater decline in the control group compared with the exercise group for both outcome measures . CONCLUSIONS Circuit-based rehabilitation leads to improvements in gait endurance but does not change the amount or rate of walking performance in usual environments . Clinical gains made by the exercise group were lost 3 months later . Future studies should consider whether rehabilitation needs to occur in usual environments to improve walking performance ", "The present study adopted an interrupted time-series design for identifying the possibility of behavioral reactivity and examining the effect of an Internet-delivered behavioral intervention for increasing self-reported and objective ly-measured physical activity among persons with multiple sclerosis ( MS ) . Participants ( n = 18 ) wore an accelerometer for 7 days and completed a battery of question naires to measure physical activity at 3 time points ( before and after a 3-month period of no treatment and again after a 3-month period of treatment ) . There was a small change in objective ly-measured , but not self-reported , physical activity in the period of no treatment , whereas there was a large increase in self-reported and objective ly-measured physical activity in the period of treatment . These findings both complement and extend previous research and further support the efficacy of the current Internet behavioral intervention for increasing physical activity in persons with MS", "Abstract Purpose : We conducted a noncontrolled pilot intervention study in stroke survivors to examine the efficacy of lowintensity adaptive physical activity to increase balance , improve walking function , and increase cardiovascular fitness and to determine whether improvements were carried over into activity profiles in home and community . Method : Adaptive physical activity sessions were conducted 3 times/week for 6 months . The main outcomes were Berg Balance Scale , Dynamic Gait Index , 6-Minute Walk Test , cardiovascular fitness ( VO2 peak ) , Falls Efficacy Scale , and 5-day Step Activity Monitoring . Results : Seven men and women with chronic ischemic stroke completed the 6-month intervention . The mean Berg Balance baseline score increased from 33.9 ± 8.5 to 46 ± 6.7 at 6 months ( mean ± SD ; p = .006 ) . Dynamic Gait Index increased from 13.7 ± 3.0 to 19.0 ± 3.5 ( p = .01 ) . Six-minute walk distance increased from 840 ± 110 feet to 935 ± 101 feet ( p = 0.02 ) . VO2 peak increased from 15.3 ± 4.1 mL/kg/min to 17.5 ± 4.7 mL/kg/min ( p = .03 ) . There were no significant changes in falls efficacy or free-living ambulatory activity . Conclusion : A structured adaptive physical activity produces improvements in balance , gait , fitness , and ambulatory performance but not in falls efficacy or free-living daily step activity . R and omized studies are needed to determine the cardiovascular health and functional benefits of structured group physical activity programs and to develop behavioral interventions that promote increased free-living physical activity patterns", "The present study examined the symptom cluster of fatigue , pain , and depression , and its direct and indirect prediction of physical activity behavior in a sample of individuals with multiple sclerosis ( MS ) using a prospect i ve research design and the Theory of Unpleasant Symptoms . The sample included 292 individuals with a definite diagnosis of MS . The participants completed self-report measures of fatigue , depression , pain , self-efficacy , and functional limitations at baseline and six months later , wore an accelerometer for seven days and completed a self-report measure of physical activity behavior . The data analysis indicated that : 1 ) fatigue , depression , and pain represented a symptom cluster ; 2 ) the symptom cluster had a strong and negative predictive relationship with physical activity behavior ; and 3 ) functional limitations , but not self-efficacy , accounted for the predictive relationship between the symptom cluster and physical activity behavior . Such findings provide preliminary support to the importance of considering symptom clusters as a meaningful correlate of physical activity behavior in persons with MS", "Physical inactivity is a major health problem in the United States , particularly in elderly and disabled population s. Little research exists examining the relationships between aspects of the built environment and physical activity in older adults and individuals with multiple sclerosis ( MS ) . We adopted a social cognitive perspective to examine the independent roles of perceptions of the environmental , self-efficacy and functional limitations in underst and ing physical activity levels among elderly women and women with MS . Older women ( n=136 ) and women diagnosed with MS ( n=173 ) were recruited to participate in separate cross-sectional studies . Individuals completed a battery of question naires and wore an activity monitor for 7 days . All measures were issued and collected through the mail with the use of self-addressed , pre-paid envelopes . Initial correlational analyses indicated that self-efficacy , functional limitations and environmental perceptions were significantly related to physical activity . Among older women , self-efficacy , functional limitations and street connectivity demonstrated independent contributions to physical activity behavior . Only self-efficacy and functional limitations demonstrated significant associations among women with MS . The prospect i ve contributions of the environment and individual factors to changes in physical activity need to be determined", "Objective : To examine whether accelerometry provides a measure of physical activity , walking ability or both in a sample of individuals with multiple sclerosis . The secondary purpose was to examine the validity of physical activity measures in people with multiple sclerosis who have ambulatory impairments . Participants : Forty-two individuals with multiple sclerosis without ambulatory impairment ( Exp and ed Disability Status Scale ( EDSS ) score ≤ 4.5 ) and 32 individuals with multiple sclerosis with ambulatory impairment ( EDSS ≥5.0 ) . Method : Participants completed the Multiple Sclerosis Walking Scale-12 and Performance Scales , wore an accelerometer for seven days , and completed the Godin Leisure-Time Exercise Question naire and short-form of the International Physical Activity Question naire . Results : There were significant differences between groups on scores from the five measures . There were large correlations between the accelerometer counts with scores from both the self-report measures of physical activity and the self-report measures of walking mobility in the overall sample . There were large correlations between scores from both measures of physical activity in the overall sample and the sub sample with ambulatory impairment . Conclusion : Our data suggest that accelerometers are measuring both physical activity and walking mobility in individuals with multiple sclerosis , whereas self-report measures are measuring physical activity in individuals with multiple sclerosis , including those with ambulatory impairment" ]

[ "OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered \" mildly ill \" according to the CGI approximately corresponded to a PANSS total score of 58 , \" moderately ill \" to a PANSS of 75 , \" markedly ill \" to a PANSS of 95 and severely ill to a PANSS of 116 . To be \" minimally improved \" according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating \" much improved \" were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate", "Clozapine is associated with significant weight gain and metabolic disturbances . This multicentre , r and omized study comprised a double-blind , placebo-controlled treatment phase of 16 wk , and an open-label extension phase of 12 wk . Out patients who met DSM-IV-TR criteria for schizophrenia , who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or = 2.5 kg while taking clozapine , were r and omized ( n=207 ) to aripiprazole at 5 - 15 mg/d or placebo , in addition to a stable dose of clozapine . The primary endpoint was mean change from baseline in body weight at week 16 ( last observation carried forward ) . Secondary endpoints included clinical efficacy , body mass index ( BMI ) and waist circumference . A statistically significant difference in weight loss was reported for aripiprazole vs. placebo ( -2.53 kg vs. -0.38 kg , respectively , difference=-2.15 kg , p Aripiprazole-treated patients also showed BMI ( median reduction 0.8 kg/m(2 ) ) and waist circumference reduction ( median reduction 2.0 cm ) vs. placebo ( no change in either parameter , p Aripiprazole-treated patients had significantly greater reductions in total and low-density lipoprotein ( LDL ) cholesterol . There were no significant differences in Positive and Negative Syndrome Scale total score changes between groups but Clinical Global Impression Improvement and Investigator 's Assessment Question naire scores favoured aripiprazole over placebo . Safety and tolerability were generally comparable between groups . Combining aripiprazole and clozapine result ed in significant weight , BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine . Improvements may reduce metabolic risk factors associated with clozapine treatment", "OBJECTIVE This prospect i ve , double-blind , multicenter , parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response . METHOD Male or female patients aged 18 - 65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response ( N=273 ) were r and omly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments . The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale ( BPRS ) and Clinical Global Impression ( CGI ) scores . Adverse events were recorded throughout the study . RESULTS The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group . Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures ( Positive and Negative Syndrome Scale , Calgary Depression Scale , Psychotic Depression Scale , and Psychotic Anxiety Scale ) . The adverse event profile was similar for both treatment groups , with a lower risk of extrapyramidal symptoms in the clozapine group . CONCLUSIONS Clozapine showed superior efficacy over risperidone in this patient population . Both treatments were equally well tolerated as demonstrated through their adverse event profiles , although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone", "OBJECTIVE When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug , it is unclear what other antipsychotic to switch to and when to use clozapine . In this study , the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness ( CATIE ) investigation . METHOD Ninety-nine patients who discontinued treatment with olanzapine , quetiapine , risperidone , or ziprasidone in phase 1 or 1B of the trials , primarily because of inadequate efficacy , were r and omly assigned to open-label treatment with clozapine ( N=49 ) or blinded treatment with another newer atypical antipsychotic not previously received in the trial ( olanzapine [ N=19 ] , quetiapine [ N=15 ] , or risperidone [ N=16 ] ) . RESULTS Time until treatment discontinuation for any reason was significantly longer for clozapine ( median=10.5 months ) than for quetiapine ( median=3.3 ) , or risperidone ( median=2.8 ) , but not for olanzapine ( median=2.7 ) . Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine , quetiapine , or risperidone . At 3-month assessment s , Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine . One patient treated with clozapine developed agranulocytosis , and another developed eosinophilia ; both required treatment discontinuation . CONCLUSIONS For these patients with schizophrenia who prospect ively failed to improve with an atypical antipsychotic , clozapine was more effective than switching to another newer atypical antipsychotic . Safety monitoring is necessary to detect and manage clozapine 's serious side effects", "BACKGROUND The treatment of schizophrenia with multiple antipsychotic drugs is common , but the benefits and risks are not known . METHODS In a r and omized , double-blind study , we evaluated patients with schizophrenia and a poor response to treatment with clozapine . The patients continued to take clozapine and were r and omly assigned to receive eight weeks of daily augmentation with 3 mg of risperidone or with placebo . This course of treatment was followed by an optional 18 weeks of augmentation with risperidone . The primary outcome was reduction in the total score for severity of symptoms on the Positive and Negative Syndrome Scale ( PANSS ) . The secondary outcomes included cognitive functioning . RESULTS A total of 68 patients were r and omly assigned to treatment . In the double-blind phase , the mean total score for the severity of symptoms decreased from baseline to eight weeks in both the risperidone and the placebo groups . There was no statistically significant difference in symptomatic benefit between augmentation with risperidone and placebo : 9 of 34 patients receiving placebo and 6 of 34 receiving risperidone responded to treatment ( P=0.38 ) . The mean difference in the change in PANSS scores from baseline to eight weeks between those receiving risperidone and those receiving placebo was 0.1 ( 95 percent confidence interval , -7.3 to 7.0 ) . The verbal working-memory index showed a small decline in the risperidone group and a small improvement in the placebo group ( P=0.02 for the comparison between the two groups in the change from baseline ) . The increase in fasting blood glucose levels was mildly greater in the risperidone group than in the placebo group ( 16.2 vs. 1.8 mg per deciliter [ 0.90 vs. 0.10 mmol per liter ] , P=0.04 ) . The incidence and severity of other side effects did not differ between the two groups . CONCLUSIONS In this short-term study , the addition of risperidone to clozapine did not improve symptoms in patients with severe schizophrenia . ( Clinical Trials.gov number , NCT00272584 )", "BACKGROUND We hypothesised that a combined regimen of clozapine , a relatively weak D2-dopaminergic antagonist , and sulpiride , a selective D2 blocker , would demonstrate a greater antipsychotic efficacy by enhancing the D2 blockade of clozapine . METHOD Twenty-eight people with schizophrenia , previously unresponsive to typical antipsychotics and only partially responsive to current treatment with clozapine , received , double-blind , 600 mg/day sulpiride or placebo , in addition to an ongoing clozapine treatment . The clinical status was evaluated before , during , and at the end of 10 weeks of sulpiride addition using the Brief Psychiatric Rating Scale ( BPRS ) , Scale for the Assessment of Positive Symptoms ( SAPS ) , Scale for the Assessment of Negative Symptoms , and Hamilton Rating Scale for Depression . RESULTS The clozapine-sulpiride group exhibited substantially greater and significant improvements in positive and negative psychotic symptoms . About half of them , characterised by a younger age and lower baseline SAPS scores , had a mean reduction of 42.4 and 50.4 % in their BPRS and SAPS scores , respectively . CONCLUSIONS A subgroup of patients with chronic schizophrenia may substantially benefit from sulpiride addition to clozapine", "OBJECTIVE The authors compared the efficacy and safety of three atypical antipsychotics ( clozapine , olanzapine , and risperidone ) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder . METHOD In a double-blind trial , 157 in patients with a history of suboptimal treatment response were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol for 14 weeks ( an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period ) . RESULTS Clozapine , risperidone , and olanzapine ( but not haloperidol ) result ed in statistically significant improvements in total score on the Positive and Negative Syndrome Scale . Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol . The atypical drugs , particularly olanzapine and clozapine , were associated with weight gain . CONCLUSIONS The effects of atypical antipsychotics in this population were statistically significant but clinical ly modest . The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective . Clozapine was the most effective treatment for negative symptoms . However , the differences among treatments were small", "BACKGROUND The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge . Clozapine has been one treatment option ; however , it is not universally effective and is limited in its use by safety concerns . With the introduction of newer agents , their performance relative to clozapine is of great clinical interest . METHODS The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients . The study was primarily design ed to demonstrate the \" noninferiority \" of olanzapine compared to clozapine after 18 weeks of double-blind treatment . Conclusions were based on the one-sided lower 95 % confidence limit about the treatment effect observed from the primary efficacy variable ( Positive and Negative Syndrome Scale [ PANSS ] Total ) . RESULTS Mean changes from baseline to end point in PANSS Total score , using a last observation carried forward technique , showed that both agents were comparably effective in neuroleptic resistant patients , i.e. , demonstrated the \" noninferiority \" of olanzapine when compared to clozapine . Overall , significantly fewer olanzapine-treated patients ( 4 % ) discontinued for an adverse event than their clozapine-treated ( 14 % ) counterparts ( p = .022 ) . Among spontaneously reported adverse events , increased salivation , constipation , dizziness , and nausea were reported significantly more often among clozapine-treated patients , whereas only dry mouth was reported more often among olanzapine-treated patients . CONCLUSIONS Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinical ly eligible for treatment with clozapine", " Forty‐four chronic schizophrenic in patients participated in this multicentre 12‐week parallel‐group double‐blind trial . After a run‐in period of 2 weeks and a single‐blind placebo wash‐out of 1 week , they were r and omly assigned to treatment with either the serotonin2 and dopamine‐D2 antagonist risperidone or haloperidol . Two patients were excluded from the efficacy analysis . Five patients dropped out in the haloperidol group and 1 in the risperidone group . At the end of the trial , the mean daily dose was 12 mg for risperidone and 10 mg for haloperidol . The risperidone group showed greater improvement on the Positive and Negative Syndrome Scale for Schizophrenia , the Schedule for Affective Disorders and Schizophrenia – change version , and the Nurses ’ Observation Scale for Inpatient Evaluation . The improvement of negative symptoms was more pronounced in the risperidone group until week 8 of double‐blind treatment . The consumption of antiparkinsonian medication was 10 times lower with risperidone . Both drugs were well tolerated and the laboratory , endocrinological and cardiovascular safety parameters were comparable . This study suggests that risperidone is comparable to haloperidol as an antipsychotic , but that it has a safer EPS profile", "INTRODUCTION Only limited data are available on the effectiveness of augmented antipsychotics to clozapine therapy in chronic schizophrenia . We conducted a r and omized , double-blind , placebo-controlled pilot study to evaluate the efficacy and safety of augmentation with the atypical neuroleptic amisulpride to clozapine in a small sample group of patients . METHODS 16 patients with the DSM-IV diagnosis of chronic schizophrenia and partially responsive to clozapine participated in this pilot study . Patients on a steady dose of clozapine r and omly received either clozapine and amisulpride 400 mg/day ( n=7 ) or clozapine and amisulpride 600 mg/day ( n=6 ) or clozapine and placebo for 6 weeks ( n=3 ) . Efficacy measures were BPRS , CGI , GAF and MADRS score . Side effects and prolactin levels were obtained . Primary outcome measure were BPRS score changes . RESULTS The beneficial effect of augmented amisulpride at a daily dose of 600 mg was observed in the mean scores of secondary outcome measures , as assessed by GAF , CGI and MADRS . Measures of primary objectives failed to improve significantly . No reduction in BPRS total score was achieved due to lack of power of the study , whereas the BPRS subscore \" activity \" had a tendency to improve . Amisulpride was more beneficial in a higher than a lower dose . No severe side-effects occurred , but tremor , bradykinesia , akathisia and elevated prolactin levels were recorded . DISCUSSION Augmented amisulpride improved the global outcome of patients suffering from chronic schizophrenia in this pilot study and tended to be a helpful treatment option in cases of partial or non-responsiveness to clozapine . Limitations emerge from the small sample size and lack of power . Further investigation requires a larger number of patients to be included", "BACKGROUND Clozapine , despite its side-effect burden , has been considered to be the drug of choice for patients with schizophrenia whose psychotic symptoms fail to respond adequately to other anti-psychotic drugs . There are conflicting data concerning the potential utility of olanzapine in treatment-resistant schizophrenia at doses beyond the 10- to 20-mg/day range that has proven to be effective for most nonrefractory patients with schizophrenia . OBJECTIVE The main objective of this study was to compare the efficacy and tolerability of high-dose olanzapine ( target dose , 25 - 45 mg/day ) and clozapine ( 300 - 900 mg/day ) in patients with schizophrenia or schizoaffective disorder who had failed to respond adequately to prior treatment with other antipsychotic drugs . STUDY DESIGN / METHOD This 6-month , r and omized , double-blind , parallel-group study compared the efficacy and tolerability of olanzapine ( mean dose , 34 mg/day ; N = 19 ) or clozapine ( mean dose , 564 mg/day ; N = 21 ) in patients with treatment-resistant schizophrenia or schizoaffective disorder , diagnosed according to DSM-IV criteria . Outcome measures included psychopathology , cognitive performance ( as assessed with a comprehensive neuropsychological test battery ) , and tolerability . The study was conducted between May 2000 and December 2003 . RESULTS Robust and significant ( mostly p multiple measures of psychopathology , mainly between 6 weeks and 6 months of treatment , was found in both treatment groups , with no significant difference between the 2 treatments except for the Global Assessment of Functioning score , which favored clozapine ( p = .01 ) . Improvement in some domains of cognition was significant- and equivalent for both drugs , as well . Nonsignificantly different improvement in Verbal List Learning-Immediate Recall ( p Controlled Word Association Test ( p Digit Symbol Substitution Test ( p differences in extrapyramidal symptoms . Weight gain was significantly ( p = .01 ) greater with olanzapine . CONCLUSIONS Olanzapine , at higher than customary doses , demonstrated similar efficacy to clozapine in treatment-resistant schizophrenia and schizoaffective disorder in this study . However , the small sample size precludes definitively concluding that the 2 treatments are equivalent , at these doses , in treatment-resistant schizophrenia . The metabolic side effects of olanzapine are a limitation in its use . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00179231", "OBJECTIVE The authors evaluated the efficacy and safety of augmenting clozapine with risperidone in patients with treatment-resistant schizophrenia . METHOD In a r and omized , double-blind , placebo-controlled 12-week trial , 40 patients unresponsive or partially responsive to clozapine monotherapy received a steady dose of clozapine combined with either placebo ( N=20 ) or up to 6 mg/day of risperidone ( N=20 ) . Patient psychopathology was assessed at 2-week intervals with the Brief Psychiatric Rating Scale ( BPRS ) and the Scale for the Assessment of Negative Symptoms ( SANS ) , among other measures . Movement disorders were assessed with the Simpson-Angus Rating Scale . RESULTS From baseline to week 6 and week 12 , mean BPRS total and positive symptom subscale scores were reduced significantly in both groups , but the reductions were significantly greater with clozapine/risperidone treatment . Reductions in SANS scores were also significantly greater with clozapine/risperidone treatment than with clozapine/placebo . The adverse event profile for clozapine/risperidone treatment was similar to that for clozapine/placebo . Simpson-Angus Rating Scale scores were lower with clozapine/risperidone treatment throughout the trial but increased to approach those of clozapine/placebo treatment at week 12 . Clozapine/risperidone treatment did not induce additional weight gain , agranulocytosis , or seizures compared with clozapine/placebo treatment . CONCLUSIONS In patients with a suboptimal response to clozapine , the addition of risperidone improved overall symptoms and positive and negative symptoms of schizophrenia . The combination appears to be safe and well tolerated . Augmentation of clozapine with risperidone may provide additional clinical benefit for patients who are nonresponsive or only partially responsive to clozapine alone", "OBJECTIVE Combining antipsychotics is common practice in the treatment of schizophrenia . This study investigated aripiprazole adjunctive to risperidone or quetiapine for treating schizophrenia and schizoaffective disorder . METHOD In this multicenter , double-blind , 16-week , placebo-controlled study conducted at 43 American sites from July 2006 to October 2007 , patients with chronic , stable schizophrenia or schizoaffective disorder diagnosed with DSM-IV-TR were r and omly assigned to receive aripiprazole ( 2 - 15 mg/d ) or placebo in addition to a stable regimen of quetiapine ( 400 - 800 mg/d ) or risperidone ( 4 - 8 mg/d ) . The primary outcome measure was the mean change from baseline to endpoint ( week 16 , last observation carried forward ) in the Positive and Negative Syndrome Scale ( PANSS ) total score . RESULTS 323 subjects being treated with either risperidone ( n = 177 ) or quetiapine ( n = 146 ) were r and omly assigned to receive adjunctive aripiprazole ( n = 168 ) or placebo ( n = 155 ) . Baseline characteristics were similar ( mean PANSS total score : aripiprazole , 74.5 ; placebo , 75.9 ) except for history of suicide attempts ( aripiprazole , 27 % ; placebo , 40 % ) . Nearly 70 % of subjects in each arm completed the trial . Adjunctive aripiprazole and placebo groups were similar in the mean change from baseline to endpoint in the PANSS total score ( aripiprazole , -8.8 ; placebo , -8.9 ; P = .942 ) . The incidence of treatment-emergent adverse events was similar between groups . Mean changes in Simpson-Angus Scale , Abnormal Involuntary Movement Scale , and Barnes Akathisia Rating Scale scores were not statistically significantly different . Adjunctive aripiprazole was associated with statistically significantly greater decreases in mean serum prolactin levels from baseline than was adjunctive placebo ( -12.6 ng/mL for aripiprazole vs -2.2 ng/mL for placebo ; P quetiapine subgroup ( -3.01 ng/mL vs + 0.15 ng/mL ; P = .104 ) . CONCLUSIONS The addition of aripiprazole to risperidone or quetiapine was not associated with improvement in psychiatric symptoms but was generally safe and well tolerated . Further research is warranted to explore whether antipsychotic combination therapy offers benefits to particular patient population s-for example , in cases of hyperprolactinemia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00325689", "BACKGROUND The present study evaluated the effectiveness and safety of clozapine versus \" high-dose \" olanzapine in treatment-refractory adolescents with schizophrenia . METHODS Children , ages 10 - 18 years , who met DSM-IV criteria for schizophrenia and who were resistant or intolerant to at least two antipsychotic drugs were r and omized to receive 12 weeks of double-blind flexibly dosed treatment with clozapine ( n = 18 ) or \" high-dose \" olanzapine ( up to 30 mg/day ) ( n = 21 ) . The primary efficacy measure was response ( improvement ) , defined as a decrease of 30 % or more in total Brief Psychiatric Rating Scale score from baseline and a Clinical Global Impression Scale improvement rating of \" 1 \" ( very much improved ) or \" 2 \" ( much improved ) . RESULTS Significantly more clozapine-treated adolescents met response criteria ( 66 % ) compared with olanzapine-treated subjects ( 33 % ) . Clozapine was superior to olanzapine in terms of reduction of the psychosis cluster scores and negative symptoms from baseline to end point . However , both treatments were associated with significant weight-gain and related metabolic abnormalities . CONCLUSIONS This double-blind r and omized comparison of two second-generation antipsychotic drugs for treatment-refractory adolescents with schizophrenia supports clozapine as the agent of choice . The development of interventions to limit weight gain and metabolic side effects are needed to enhance the risk-benefit profile for both study treatments", "Aripiprazole is a novel atypical antipsychotic for the treatment of schizophrenia . It is a D2 receptor partial agonist with partial agonist activity at 5-HT1A receptors and antagonist activity at 5-HT2A receptors . The long-term efficacy and safety of aripiprazole ( 30 mg/d ) relative to haloperidol ( 10 mg/d ) were investigated in two 52-wk , r and omized , double-blind , multicentre studies ( using similar protocol s which were prospect ively identified to be pooled for analysis ) in 1294 patients in acute relapse with a diagnosis of chronic schizophrenia and who had previously responded to antipsychotic medications . Aripiprazole demonstrated long-term efficacy that was comparable or superior to haloperidol across all symptoms measures , including significantly greater improvements for PANSS negative subscale scores and MADRS total score ( p time to discontinuation for any reason was significantly greater with aripiprazole than with haloperidol ( p=0.0001 ) . Time to discontinuation due to adverse events or lack of efficacy was significantly greater with aripiprazole than with haloperidol ( p=0.0001 ) . Aripiprazole was associated with significantly lower scores on all extrapyramidal symptoms assessment s than haloperidol ( p aripiprazole demonstrated efficacy equivalent or superior to haloperidol with associated benefits for safety and tolerability . Aripiprazole represents a promising new option for the long-term treatment of schizophrenia", "OBJECTIVE This study compared the specific antiaggressive effects of clozapine with those of olanzapine , risperidone , and haloperidol . METHODS A total of 157 in patients with schizophrenia or schizoaffective disorder and a history of suboptimal treatment response were r and omly assigned to receive clozapine , olanzapine , risperidone , or haloperidol in a double-blind 14-week trial . The trial was divided into two periods : eight weeks during which the dosage was escalated and then fixed , and six weeks during which variable dosages were used . The hostility item of the Positive and Negative Syndrome Scale ( PANSS ) was the principal outcome measure . Covariates included the items that reflect positive symptoms of schizophrenia ( delusions , suspiciousness or feelings of persecution , gr and iosity , unusual thought content , conceptual disorganization , and hallucinations ) and the sedation item of the Nurses Observation Scale for Inpatient Evaluation ( NOSIE ) . RESULTS Patients differed in their treatment response as measured by the hostility item of the PANSS . The scores of patients taking clozapine indicated significantly greater improvement than those of patients taking haloperidol or risperidone . The effect on hostility appeared to be independent of the antipsychotic effect of clozapine on other PANSS items that reflect delusional thinking , a formal thought disorder , or hallucinations and independent of sedation as measured by the NOSIE . Neither risperidone nor olanzapine showed superiority to haloperidol . CONCLUSION Clozapine has a relative advantage over other antipsychotics as a specific antihostility agent ", "OBJECTIVE The association of hyperglycemia and hypercholesterolemia with use of atypical antipsychotics has been documented in case reports and uncontrolled studies . The authors ' goal was to assess the effects of clozapine , olanzapine , risperidone , and haloperidol on glucose and cholesterol levels in hospitalized patients with schizophrenia or schizoaffective disorder during a r and omized double-blind 14-week trial . METHOD One hundred fifty-seven patients with schizophrenia or schizoaffective disorder who were in patients at four hospitals were originally included in the study . The 14-week trial consisted of an 8-week fixed-dose period and a 6-week variable-dose period . Planned assessment s included fasting glucose and cholesterol , which were collected at baseline and at the end of the 8-week period and the following 6-week period . RESULTS One hundred eight of the 157 patients provided blood sample s at baseline and at least at one point after r and om assignment to clozapine , olanzapine , risperidone , or haloperidol during the treatment trial . Seven of these patients had diabetes ; their glucose levels were > 125 mg/dl at baseline . Data from 101 patients were used for statistical analyses . During the initial 8-week period there was an overall significant increase in mean glucose levels . There were significant increases in glucose levels at the end of the 8-week fixed-dose period for patients given clozapine ( N=27 ) and those given haloperidol ( N=25 ) . The olanzapine group showed a significant increase of glucose levels at the end of the 6-week variable-dose period ( N=22 ) . Fourteen of the 101 patients developed abnormal glucose levels ( > 125 mg/dl ) during the trial ( six with clozapine , four with olanzapine , three with risperidone , and one with haloperidol ) . Cholesterol levels were increased at the end of the 8-week fixed-dose period for the patients given clozapine ( N=27 ) and those given olanzapine ( N=26 ) ; cholesterol levels were also increased at the end of the 6-week variable-dose period for patients given olanzapine ( N=22 ) . CONCLUSIONS In this prospect i ve r and omized trial , clozapine , olanzapine , and haloperidol were associated with an increase of plasma glucose level , and clozapine and olanzapine were associated with an increase in cholesterol levels . The mean changes in glucose and cholesterol levels remained within clinical ly normal ranges , but approximately 14 % of the patients developed abnormally high glucose levels during the course of their participation in the study", "BACKGROUND Prolactin levels are elevated to varying degrees by antipsychotics . Prolactin elevations may result in sexual and other adverse effects , and they may be related to antipsychotic effects . We used the data collected in a trial of antipsychotics to study the differential effect of these drugs on prolactin level , to explore the relation between clinical effects and prolactin level , and to determine the relationship between plasma levels of antipsychotics and prolactin level . METHOD Treatment-resistant patients ( 133 men , 24 women ) diagnosed with DSM-IV schizophrenia or schizoaffective disorder participated in a double-blind , r and omized , 14-week trial comparing clozapine ( N = 40 ) , olanzapine ( N = 39 ) , risperidone ( N = 41 ) , and haloperidol ( N = 37 ) . Plasma levels of prolactin and antipsychotics were determined at baseline and at weeks 5 , 8 , 10 , 12 , and 14 during the trial . Clinical effects were measured with the Positive and Negative Syndrome Scale and the Extrapyramidal Symptom Rating Scale . Statistical analyses were limited to the 75 men for whom repeated prolactin levels were available . Data were gathered from June 1996 to December 1999 . RESULTS Risperidone caused significant elevation of prolactin levels ( p prolactin , whereas haloperidol led to a minor , nonsignificant increase . Plasma olanzapine and prolactin levels were correlated . Prolactin levels were not related to clinical improvement or extrapyramidal side effects . CONCLUSION Antipsychotics show major differences in their effects on prolactin , and risperidone has clearly the most robust effect", "OBJECTIVE The purpose of this study was to evaluate the clinical safety and efficacy of risperidone compared to haloperidol in patients with treatment-refractory schizophrenia . METHOD Sixty-seven medication-unresponsive subjects were r and omly assigned to treatment with risperidone ( N = 34 ) or haloperidol ( N = 33 ) . After a 3 - 7 day-placebo washout period , there was a 4-week , double-blind , fixed-dose comparison trial that was followed by a 4-week , flexible-dose phase . Measures of clinical change were quantified by st and ard psychopathologic and neuromotor instruments . RESULTS Risperidone demonstrated clinical efficacy superior to that of haloperidol on the total Brief Psychiatric Rating Scale ( BPRS ) after the first 4 weeks of treatment . Risperidone did not show any advantage over haloperidol after an additional 4 weeks . Overall improvement on the BPRS at 4 weeks was significantly better for the risperidone group ( 24 % ) than for the haloperidol group ( 11 % ) . Risperidone-treated subjects were significantly less likely than haloperidol-treated subjects to require concomitant anticholinergic medication after 4 weeks ( 20 % versus 63 % ) ; they also had significantly les observable akathisia ( 24 % versus 53 % ) and significantly less severe tardive dyskinesia . Baseline characteristics that correlated significantly with risperidone response were positive symptoms , conceptual disorganization , akathisia , and tardive dyskinesia . CONCLUSIONS Risperidone was better tolerated and more effective in a subset of patients with treatment-refractory schizophrenia . Positive psychotic symptoms and extrapyramidal side effects at baseline appear to be powerful predictors of subsequent response to risperidone", "OBJECTIVE The purpose of this study was to compare the short-term efficacy and safety of risperidone and clozapine in treatment-resistant chronic schizophrenic patients . METHOD In a controlled double-blind , multicenter study , 86 in patients with chronic schizophrenia ( DSM-III-R ) , who were resistant to or intolerant of conventional neuroleptics , were r and omly assigned to receive risperidone or clozapine for 8 weeks after a 7-day washout period . After a 1-week dose-titration phase , doses were fixed at 6 mg/day of risperidone and 300 mg/day of clozapine for 1 week and then adjusted according to each patient 's response . The final mean doses were 6.4 mg/day of risperidone and 291.2 mg/day of clozapine . Treatment efficacy and safety were evaluated with several well-known rating scales . RESULTS Both risperidone and clozapine significantly reduced the severity of psychotic symptoms ( scores on the Positive and Negative Syndrome Scale and the Clinical Global Impression scale ) from baseline , with no significant between-group differences . At endpoint , 67 % of the risperidone group and 65 % of the clozapine group were clinical ly improved ( reduction of 20 % or more in total Positive and Negative Syndrome Scale score ) . Risperidone appeared to have a faster onset of action . In both groups extrapyramidal symptoms and other adverse events were few , and their severity was generally mild . Neither group showed evidence of a relation between drug plasma concentrations and clinical effectiveness . CONCLUSIONS Risperidone was well tolerated and as effective as medium doses of clozapine in patients with chronic schizophrenia who had been resistant to or intolerant of conventional neuroleptics", "Patients with treatment-resistant schizophrenia pose a major challenge to caregivers since only clozapine is documented as having superior efficacy in this population . Although olanzapine is similar to clozapine in structure and receptor profile , it has not been proven to have superior efficacy for this patient group . Nonetheless , olanzapine is being increasingly used in higher doses as clinicians attempt to find a more effective and tolerable therapy for refractory patients . Furthermore , there are little data comparing olanzapine and clozapine in this population . Thirteen patients participated in a r and omized double-blind 16-week crossover study of clozapine therapy ( 450 mg/day ) compared to high doses of olanzapine ( 50 mg/day ) . No patients on olanzapine responded while 20 % responded to clozapine treatment . Olanzapine patients tended to experience higher rates of anticholinergic effects such as dry mouth ( 80 vs. 20 % ) and blurry vision ( 40 vs. 0 % ) . Clozapine-treated patients had higher rates of sialorrhea ( 80 vs. 10 % ) , sweating ( 50 vs. 10 % ) , dyspepsia ( 70 vs. 30 % ) , and lethargy ( 90 vs. 60 % ) . Neither treatment was associated with significant akathisia . Liver enzyme elevation and lipids were higher with clozapine treatment . Mean weight gain in the initial 8 weeks was 3.4 kg for olanzapine and 1.2 kg for clozapine . High doses of olanzapine during 8 weeks of treatment did not increase lipids and liver enzymes like clozapine did . Olanzapine at 50 mg/day may be associated with more anticholinergic effects and weight gain than clozapine", "The large numbers of partial clozapine responders represent a major therapeutic challenge . Unfortunately , there are no clear data to support how best to treat these patients . This study examines the efficacy and safety of adjunctive risperidone in a well-defined treatment-resistant population optimally treated with clozapine . A total of 69 in patients and out patients with DSM-IV schizophrenia or schizoaffective disorder entered a 16-week double-blind , placebo-controlled , r and omized clinical trial . Of them , 33 participants were r and omized to risperidone and 36 were r and omized to placebo . There was no significant group difference in the predefined response criteria . There were modest group differences for Brief Psychiatric Rating Scale ( BPRS ) positive symptoms , which were significant in the completer analysis ( F=5.70 ; df=1 , 70.3 ; p=0.02 ; ES=0.27 ) but not the intent-to-treat ( ITT ) analyses ( F=3.01 ; df=1 , 77.5 ; p=0.09 ; ES=0.19 ) . A similar pattern was found for the BPRS total score , with the completer analysis showing a significant improvement in the risperidone group ( F=5.21 ; df=1 , 64.9 ; p=0.03 ; ES=0.27 ) , whereas the ITT analysis was not significant ( F=3.52 ; df=1 , 71.3 ; p=0.06 ; ES=0.22 ) . In addition , there was a small , but significant , group difference for negative symptoms , as measured by the SANS total score , which favored the risperidone group ( F=5.67 ; df=1 , 78.7 ; p=0.02 ; ES=0.24 ) . There were no significant group differences on safety measures , including neuropsychological test and extrapyramidal symptom scores . A significant elevation of prolactin in the risperidone group was observed . The study results suggest that adjunctive risperidone may have a modest benefit for treatment-resistant clozapine patients . The study results are discussed in the context of previous double-blind studies of adjunctive risperidone . ( clinical trials.gov , trial number : NCT00056498 )", "OBJECTIVE Inadequate response to clozapine poses a substantial problem in the pharmaco-therapy of refractory schizophrenia . This r and omized , double-blind , placebo-controlled study evaluated the efficacy and safety of aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia . METHOD Patients with DSM-IV schizophrenia who had a history of treatment failure or partial response to long-term clozapine treatment were recruited . A total of 62 patients with either a baseline Brief Psychiatric Rating Scale ( BPRS ) score of at least 35 or more than 2 Schedule for Assessment of Negative Symptoms ( SANS ) global rating item scores of at least 3 were r and omly assigned to double-blind augmentation treatment with either aripiprazole ( 5 - 30 mg/day ) or placebo over 8 weeks . The primary outcome measure was change in BPRS total score from baseline . The study was conducted between December 1 , 2005 , and December 10 , 2006 . RESULTS There was no significant difference in the primary outcome measure between the 2 groups . In secondary analyses , improvement was significantly greater with aripiprazole treatment than with placebo for negative symptoms assessed by both the BPRS negative symptom sub-scale and the SANS total score but not for positive symptoms . Prolactin and triglyceride levels were significantly lower in the aripiprazole group than in the placebo group . No significant differences between the 2 groups were observed in adverse effects , including extrapyramidal symptoms and serum glucose levels . CONCLUSION Although aripiprazole augmentation of clozapine did not lead to a significant improvement of total symptom severity in schizophrenia , a favorable change in the negative symptom domain was observed", "OBJECTIVE Quetiapine is often prescribed at higher than approved doses . We investigated the safety , tolerability , and efficacy of quetiapine > 800 mg/d . METHOD A trial was carried out from October 2003-September 2005 in 19 referral centers . Patients with DSM-IV schizophrenia or schizoaffective disorder were r and omized on the basis of persistent symptoms of moderate severity ( quetiapine ) . The 8 week , double-blind study compared continuation of quetiapine 800 mg/d ( n = 43 ) versus 1,200 mg/d ( n = 88 ) . The primary outcome measure was emergent or worsening parkinsonism ( Simpson-Angus Scale ) . Secondary outcomes were adverse events , metabolic side effects , and symptom severity . RESULTS Mean doses obtained were 799 mg/d and 1,144 mg/d in the 800-mg/d and > 800-mg/d groups , respectively . Emergent or deteriorating parkinsonism in the high-dose group was 3.1 % greater ( 95 % CI , -7.8 % to 14.0 % ; P = .76 ) than in the 800-mg/d group , a value that was within the a priori limit of 16 % defined as noninferiority . Both doses of quetiapine were safe and well tolerated . Weight gain was greater in the high-dose group ( 1.7 kg over 12 weeks ; ≥ 7 % body weight , n = 11 [ 12.5 % ] ) versus the 800-mg/d group ( 1.1 kg over 12 weeks ; ≥ 7 % body weight , n = 4 [ 9.3 % ] ) . The mean adjusted difference in weight gain ( 1.3 kg ) was greater in the high-dose group ( 95 % CI , 0.0 - 2.5 ; P = .044 ) . Symptom severity declined , with no significant difference between groups . CONCLUSIONS The results did not demonstrate any advantage for use of quetiapine outside the approved dose range . TRIAL REGISTRATION www . clinical trials.gov Identifier : NCT00328978" ]

[ "Background : Design ing the effective and early interventions can prevent progression of prediabetes to diabetes . Few studies have shown the effect of flaxseed on glycemic control . This study aim ed to assess the effect of flaxseed powder on insulin resistance ( IR ) indices and blood pressure in prediabetic individuals . Material s and Methods : In a r and omized clinical trial , 99 prediabetic individuals were r and omly divided into three groups : two groups received 40 g ( FG40 ) and 20 g ( FG20 ) flaxseed powder daily for 12 weeks and the third group was the control ( CG ) . Before and after the intervention , anthropometric measurements , blood pressure , fasting serum glucose ( FSG ) , insulin , homeostasis model assessment IR index ( HOMA-IR ) , beta-cell function , and insulin sensitivity were measured . Results : FSG significantly declined overall in all groups compared to the baseline ( P = 0.002 in CG and FG20 groups and P = 0.001 in FG40 ) . In contrast , mean of the changes in FSG was not significantly different between groups . Insulin concentration did not change significantly within and between the investigated groups . Although HOMA-IR reduced in FG20 ( P = 0.033 ) , the mean of changes was not significant between the three groups . Mean of beta-cell function increased in CG and FG40 groups compared to the baseline ( P = 0.044 and P = 0.018 , respectively ) , but mean of its changes did not show any difference between the three groups . The mean of changes in IR indices was not significant between the three groups . FG40 group had significantly lowered systolic blood pressure after the intervention ( P = 0.005 ) . Conclusion : Daily intake of flaxseed powder lowered blood pressure in prediabetes but did not improve glycemic and IR indices", "The study hypothesis was that fasting glucose , insulin , fructosamine , C-reactive protein , and interleukin-6 decrease and adiponectin increases with daily flaxseed consumption in overweight or obese individuals with pre-diabetes . In this r and omized , cross-over study overweight or obese men and postmenopausal women ( n = 25 ) with pre-diabetes consumed 0 , 13 , or 26 g ground flaxseed for 12 weeks . Glucose , insulin , homeostatic model assessment ( HOMA-IR ) , and normalized percent of α-linolenic fatty acid ( ALA ) were significantly different by treatment ( multiple analysis of variance , P = .036 , P = .013 , P = .008 , P = .024 respectively ) . Paired t tests showed glucose decreased on the 13 g intervention compared to the 0 g period [ 13 g = -2.10 ± 1.66 mg/L ( mean ± SEM ) , 0 g = 9.22 ± 4.44 mg/L , P = .036 ] . Insulin decreased on the 13 g intervention but not the 26 g ( P = .021 ) and 0 g ( P = .013 ) periods ( 13 g = -2.12 ± 1.00 mU/L , 26 g = 0.67 ± 0.84 mU/L , 0 g = 1.20 ± 1.16 mU/L ) . HOMA-IR decreased on the 13 g period but not on the 26 g ( P = .012 ) and 0 g ( P = .008 ) periods ( 13 g = -0.71 ± 0.31 , 26 g = 0.27 ± 0.24 , 0 g = 0.51 ± 0.35 ) . The α-linolenic fatty acid decrease for the 0 g period was different than the 13 g ( P = .024 ) and 26 g ( P = .000 ) periods ( 13 g = 0.20 ± 0.04 , 26 g = 0.35 ± 0.07 , 0 g = -0.01 ± 0.07 ) . Fructosamine , high sensitivity C-reactive protein , adiponectin , and high-sensitivity interleukin-6 had no significant differences . Flaxseed intake decreased glucose and insulin and improved insulin sensitivity as part of a habitual diet in overweight or obese individuals with pre-diabetes", "Background Flaxseed has received attention for its anti-inflammatory and antioxidant role . The present study hypothesizes if flaxseed added to a weight loss diet could improve the lipid and metabolic profiles and decrease risk factors related to cardiovascular disease . Methods In a prospect i ve , single blinded 42 days protocol , subjects were allocated into two groups with low carbohydrates intake : GriceLC ( 35 % of carbohydrate and 60 g of raw rice powder per day ) and GflaxLC ( 32 % of carbohydrate and 60 g of flaxseed powder per day ) . Blood pressure , anthropometric measures and serum levels of isoprostane , C-reactive protein , Tumor Necrosis Factor-alpha , glucose , lipidic profile , uric acid , adiponectin , leptin and insulin were measured at baseline and at the end of interventions . Serum and urinary enterodiol and enterolactione were also measured . Results A total of 27 men with cardiovascular risk factors were evaluated , with mean age of 33 ± 10 years to GriceLC and 40 ± 9 years to GflaxLC . Both groups experienced weight loss and systolic blood pressure reduction . A decrease in inflammatory markers ( CRP and TNF-α ) was observed after flaxseed intake ( mean decrease of 25 % and 46 % for GflaxLC respectively ) . All groups also showed improvement in levels of total cholesterol , LDL-c , uric acid and adiponectin . Only GflaxLC group showed a decrease in triglyceride levels . Conclusion This study suggests that flaxseed added to a weight loss diet could be an important nutritional strategy to reduce inflammation markers such as CRP and TNF-α . Trial registration Clinical Trials.gov NCT02132728", "The n-6/n-3 fatty acid ( FA ) ratio has increased in the Western-style diet to ~10–15:1 during the last century , which may have contributed to the rise in cardiovascular disease ( CVD ) . Prior studies have evaluated the effects on CVD risk factors of manipulating the levels of n-6 and n-3 FA using food and supplements or investigated the metabolic fate of linoleic acid ( LNA ) and α-linolenic acid ( ALA ) by varying the n-6/n-3 ratios . However , no previous studies have investigated the potential interaction between diet ratios and supplementation with eicosapentaenoic acid ( EPA , 20:5n-3 ) and docosahexaenoic acid ( DHA , 22:6n-3 ) . We used a factorial design approach with adults ( n = 24 ) in a controlled feeding trial to compare the accretion of EPA and DHA into red blood cell membranes ( RBC ) by adding a direct source ( algal oil supplement ) of EPA and DHA in a diet with a 10:1 versus 2:1 ratio of n-6/n-3 FA . Subjects were r and omized into 8-week crossover diet sequences and each subject consumed three of four diets [ 10:1 , 10:1 plus supplement ( 10:1 + S ) , 2:1 and 2:1 + S ] . LNA and ALA intakes were 9.4 and 7.7 % , and 1.0 and 3.0 % during the low and high ALA diets , respectively . Compared to the Western-style 10:1 diet , the 2:1 diet increased EPA by 60 % ( P however , DHA levels increased in both diet ratios only with a direct DHA source . Shifting towards a 2:1 diet is a valid alternative to taking EPA-containing supplements", "Phytoestrogens are increasingly incorporated into the diet of menopausal women . However , there are limited data on the efficacy of flaxseed on the consequences of estrogen deficiency in menopausal women . The purpose of the study was to assess the effects of flaxseed incorporation into the diet of healthy menopausal women . One hundred and ninety-nine menopausal women were r and omly assigned to consume 40 g flaxseed/d ( n = 101 ) or wheat germ placebo ( n = 98 ) for 12 months . At baseline and at month 12 , serum levels of lipids , bone mineral density ( BMD ) , and menopausal symptoms were evaluated . Statistical analysis was performed under the intention to treat principle . Flaxseed reduced serum total ( -0.20 + /- 0.51 mmol/liter ; P = 0.012 ) and high-density lipoprotein ( -0.08 + /- 0.24 mmol/liter ; P = 0.031 ) cholesterol concentrations compared with wheat germ placebo . BMD did not differ significantly between the two arms . Both flaxseed and wheat germ reduced ( P severity scores of menopausal symptoms , but no statistical difference was found between the two arms . Our findings suggest that 1-yr incorporation of flaxseed into the diet produced a favorable , but not clinical ly significant , effect on blood cholesterol and caused no significant change in BMD or symptoms in healthy menopausal women", "Background Obesity leads to an increase in inflammation and insulin resistance . This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people . Methods Using a r and omized crossover design , nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period . Plasma inflammation biomarkers ( CRP , TNF-α , and IL-6 ) , glucose , insulin , and thiobaribituric acid reactive substance ( TBARS ) were measured before and after of each supplementation . Results Flaxseed supplementation decreased TBARS ( p = 0.0215 ) and HOMA-IR ( p = 0.0382 ) . Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers . A positive relationship was found between TBARS and HOMA-IR ( r = 0.62 , p = 0.0003 ) . Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed . However , the mechanism(s ) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan", "ABSTRACT Diabetes mellitus is characterized by hyperglycemia and associated with aberrations in the metabolism of carbohydrate , protein , and lipid that result in development of secondary complications . Extensive studies have indicated that nutritional therapy plays a pivotal role in the controlling or postponing of development of these secondary complications . Several functional foods have been shown to possess hypoglycemic and hypolipidemic properties . Flax seed ( FS ) is a functional food that is rich in omega 3 fatty acids and antioxidants and is low in carbohydrates . In exploratory studies , FS was incorporated in recipes , which result ed in a reduction in the glycemic index of the food items . These observations prompted us to investigate the efficacy of FS supplementation in type 2 diabetics ( n = 29 ) . Subjects were assigned to the experimental ( n = 18 ) or the control group ( n = 11 ) on the basis of their desire to participate in the study . The experimental group 's diet was supplemented daily with 10 g of FS powder for a period of 1 month . The control group received no supplementation or placebo . During the study , diet and drug intake of the subjects remained unaltered . The efficacy of supplementation with FS was evaluated through a battery of clinico-biochemical parameters . Supplementation with FS reduced fasting blood glucose by 19.7 % and glycated hemoglobin by 15.6 % . A favorable reduction in total cholesterol ( 14.3 % ) , triglycerides ( 17.5 % ) , low-density lipoprotein cholesterol ( 21.8 % ) , and apolipoprotein B and an increase in high-density lipoprotein cholesterol ( 11.9 % ) were also noticed . These observations suggest the therapeutic potential of FS in the management of diabetes mellitus", "Abstract Context : The natural health product , BeneFlax , is a st and ardized flaxseed [ Linum usitatissimum L. ( Linaceae ) ] lignan enriched product with evidence of product quality and known quantity of the bioactive component , lignan . The acceptance of this natural health product for its various health benefits requires greater evidence of its safety in the general population . Objective : We determined whether flaxseed lignan causes clinical hypoglycemia or hypotension in healthy older adults as an important aspect of safety . Material s and methods : Participants aged 49–87 years were r and omized in a double-blind trial to receive flaxseed lignan ( 543 mg/day in BeneFlax ) or placebo while completing a 6-month walking program . The 94 participants who completed the study were stratified by age ( to determine whether older adults were more susceptible to adverse effects . Results : After 6 months of treatment , average plasma glucose level ( 5.4 ± 0.6 mmol/L ) , systolic blood pressure ( 127 ± 14 mm Hg ) , and diastolic blood pressure ( 80 ± 9 mm Hg ) were within normal clinical range . Controlling for sex and body mass index covariates result ed in no observed differences between plasma glucose or blood pressure measurements between treatment or age groups ( p > 0.05 ) . No incidents of hypoglycemia or hypotension were observed during BeneFlax treatment , suggesting that 543 mg falls at or below the no observable adverse effect level ( NOAEL ) . Discussion and conclusion : These data suggest the flaxseed lignan product BeneFlax does not pose a risk of hypoglycemia or hypotension in healthy adults aged 49–87 years", "Objective : The omega-3 polyunsaturated fatty acid ( n-3 PUFA ) as well as lignan components of flaxseed ( FLX ) can have beneficial effects . In this 6-week-long , r and omized , double-blinded , placebo-controlled study , we investigated the effects of FLX lignans on cardiovascular risk factors . Methods : Thirty-seven subjects ( 13 men and 24 women , age : 54 ± 7 years , body mass index [ BMI ] : 29.7 ± 1 kg/m2 ) consumed nutrition bars with similar macronutrient contents . The fatty acid composition and the lignan contents of the bars differed significantly . Two FLX bars both contained 3.0 g of alpha linolenic acid ( ALA : 18:3 n-3 ) but different amount of lignans ( 0.15 g vs. 0.41 g ) . Results : High-lignan FLX decreased total cholesterol ( C ) by 12 % ( p = 0.044 ) , LDL-C by 15 % ( p = 0.022 ) , and oxidized (Ox)-LDL by 25 % ( p = 0.035 ) . Regular FLX tended to increase Ox-LDL by 13 % ( p = 0.051 ) . The difference between the effects of high-lignan vs. regular lignan FLX on Ox-LDL was highly significant ( p = 0.004 ) . Conclusion : High-lignan FLX has the unique property of decreasing Ox-LDL , which is an independent risk factor for cardiovascular disease", "OBJECTIVE Supplementation of type II diabetic diets with n-3 fatty acids ( FAs ) from fish oil ( FO ) has been associated with lowered triglyceride and VLDL levels , although reports of impaired glycemic control have limited their use . Effects of n-3FAs from nonmarine sources are less well documented . Therefore , an investigation comparing the effects of linseed oil ( LO ) with FO supplementation was undertaken in subjects with type II diabetes . RESEARCH DESIGN AND METHODS Eleven subjects with type II diabetes were given supplements with LO and FO for 3 months each in a r and omized double-blind crossover fashion after 3 months of olive oil placebo . Oils were given as 35 mg FA · kg body wt−1 · day−1 . After each 3-month period , fasting glucose and insulin levels , HbA1c , lipid profiles , insulin sensitivity ( SI ) , glucose effectiveness ( SG ) , and acute insulin response to glucose ( AIRG ) were evaluated . RESULTS HbA1c and lipid values were within the normal range at r and omization . Repeated measures analysis of variance testing found no significant differences in weight ; fasting glucose and insulin levels ; HbA1c ; total , LDL , and HDL cholesterol levels ; SI ; SG ; or AIRG with either active oil . FO was associated with significant reductions in triglycerides and a trend toward decreased SI . CONCLUSIONS In a population with well-controlled type II diabetes , 3 months of FO but not LO result ed in lowered triglyceride levels . Neither LO nor FO significantly affected glycemic control , cholesterol values , SG , or insulin secretion , while a nonsignificant trend toward decreased insulin sensitivity was found with FO", "Type II diabetic subjects were given 50 g protein , 50 g glucose , or 50 g glucose with 50 g protein as a single meal in r and om sequence . The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34 % when protein was given with the glucose . When protein was given alone , the glucose concentration remained stable for 2 h and then declined . The insulin area following glucose was only modestly greater than with a protein meal ( 97 ± 35 , 83 ± 19 µU · h/ml , respectively ) . When glucose was given with protein , the mean insulin area was considerably greater than when glucose or protein was given alone ( 247 ± 33 µU · h/ml ) . When various amounts of protein were given with 50 g glucose , the insulin area response was essentially first order . Subsequently , subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in r and om sequence . The insulin areas were not significantly different for each meal but were higher when protein + glucose was given . After the second glucose meal the plasma glucose area was 33 % less than after the first meal . Following the second glucose + protein meal the plasma glucose area was markedly reduced , being only 7 % as large as after the first meal . These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons", "Lignans , derived from flaxseed , are phyto-oestrogens being increasingly studied for their health benefits . An 8-week , r and omised , double-blind , placebo-controlled study was conducted in fifty-five hypercholesterolaemic subjects , using treatments of 0 ( placebo ) , 300 or 600 mg/d of dietary secoisolariciresinol diglucoside ( SDG ) from flaxseed extract to determine the effect on plasma lipids and fasting glucose levels . Significant treatment effects were achieved ( P total cholesterol ( TC ) , LDL-cholesterol ( LDL-C ) and glucose concentrations , as well as their percentage decrease from baseline . At weeks 6 and 8 in the 600 mg SDG group , the decreases of TC and LDL-C concentrations were in the range from 22.0 to 24.38 % respectively ( all P TC and LDL-C. A substantial effect on lowering concentrations of fasting plasma glucose was also noted in the 600 mg SDG group at weeks 6 and 8 , especially in the subjects with baseline glucose concentrations > or = 5.83 mmol/l ( lowered 25.56 and 24.96 % ; P = 0.015 and P = 0.012 compared with placebo , respectively ) . Plasma concentrations of secoisolariciresinol ( SECO ) , enterodiol ( ED ) and enterolactone were all significantly raised in the groups supplemented with flaxseed lignan . The observed cholesterol-lowering values were correlated with the concentrations of plasma SECO and ED ( r 0.128 - 0.302 ; P flaxseed lignan extract decreased plasma cholesterol and glucose concentrations in a dose-dependent manner", "The gut microbiota has been implicated in obesity and its progression towards metabolic disease . Dietary interventions that target the gut microbiota have been suggested to improve metabolic health . The aim of the present study was to investigate the effect of interventions with Lactobacillus paracasei F19 or flaxseed mucilage on the gut microbiota and metabolic risk markers in obesity . A total of fifty-eight obese postmenopausal women were r and omised to a single-blinded , parallel-group intervention of 6-week duration , with a daily intake of either L. paracasei F19 ( 9·4 × 1010 colony-forming units ) , flaxseed mucilage ( 10 g ) or placebo . Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota . Diet-induced changes in metabolic markers were explored using adjusted linear regression models . The intake of flaxseed mucilage over 6 weeks led to a reduction in serum C-peptide and insulin release during an oral glucose tolerance test ( P improved insulin sensitivity measured by Matsuda index ( P gut microbiota composition at baseline and after 6 weeks of intervention with flaxseed mucilage showed alterations in abundance of thirty-three metagenomic species ( P including decreased relative abundance of eight Faecalibacterium species . These changes in the microbiota could not explain the effect of flaxseed mucilage on insulin sensitivity . The intake of L. paracasei F19 did not modulate metabolic markers compared with placebo . In conclusion , flaxseed mucilage improves insulin sensitivity and alters the gut microbiota ; however , the improvement in insulin sensitivity was not mediated by the observed changes in relative abundance of bacterial species", "Aim . Animal and human study evidence supports the hypothesis that flaxseed lignan complex ( FLC ) at a dose of 600 mg secoisolariciresinol diglucoside (SDG)/day for three months would combat hyperglycaemia , dyslipidemia , blood pressure , central obesity , prothrombotic state , inflammation , and low density lipoprotein ( LDL ) oxidation . Methods . Sixteen type 2 diabetic patients completed this double-blind , r and omised crossover placebo-controlled study . A univariate repeated measures analysis of covariance ( significance P for multiple comparisons ( MCC ) . Results . Prior to MCC , FLC caused decreased fasting plasma glucose , A1c , inflammation ( c-reactive protein ( CRP ) and interleukin-6 ( IL-6 ) ) , and increased bleeding time . After correction for multiple comparisons , FLC induced a statistically significant increase in bleeding time and smaller waist circumference gain . No treatment effect occurred in the other variables before or after adjustment . Conclusions . It is concluded that FLC significantly increased bleeding time thus reducing the prothrombotic state , reduced central obesity gain as measured by waist circumference , and did not affect significantly the other dependent variables measured after adjustment for multiple comparisons . These findings , not yet published in human type 2 diabetes , suggest that this FLC dose over at least three months , may , subject to further investigation , reduce polypharmacy", "Background Flaxseed consumption has been shown to improve blood lipids in humans and flaxseed-derived lignan has been shown to enhance glycemic control in animals . The study aim ed to investigate the effect of a flaxseed-derived lignan supplement on glycemic control , lipid profiles and insulin sensitivity in type 2 diabetic patients . Methodology /Principal Findings This was a r and omized , double-blind , placebo-controlled , cross-over trial and it was conducted between April and December 2006 in Shanghai , China . Seventy-three type 2 diabetic patients with mild hypercholesterolemia were enrolled into the study . Patients were r and omized to supplementation with flaxseed-derived lignan capsules ( 360 mg lignan per day ) or placebo for 12 weeks , separated by an 8-week wash-out period . HbA1c , lipid profiles , insulin resistance index and inflammatory factors were measured . Sixty-eight completed the study and were included in the analyses . The lignan supplement significantly improved glycemic control as measured by HbA1c ( -0.10±0.65 % vs. 0.09±0.52 % , P = 0.001 ) compared to placebo ; however , no significant changes were observed in fasting glucose and insulin concentrations , insulin resistance and blood lipid profiles . Urinary excretion of lignan metabolites ( enterodiol and enterolactone ) was significantly higher after the lignan supplement intervention compared to baseline ( 14.2±18.1 vs. 1.2±2.4 µg/mL , P improvements in glycemic control in type 2 diabetic patients without apparently affecting fasting glucose , lipid profiles and insulin sensitivity . Further studies are needed to vali date these findings and explore the efficacy of lignans on type 2 diabetes . Trial Registration Clinical Trials.gov", "Type 2 diabetes is characterized partially by elevated fasting blood serum glucose and insulin concentrations and the percentage of hemoglobin as HbA1c . It was hypothesized that each of blood glucose and its co-factors insulin and HbA1c and would show a more favorable profile as the result of flaxseed oil supplementation . Patients were recruited at r and om from a population pool responding to a recruitment advertisement in the local newspaper and 2 area physicians . Completing the trial were 10 flaxseed oil males , 8 flaxseed oil females , 8 safflower ( placebo ) oil males and 6 safflower oil females . Patients visited on two pre-treatment occasions each three months apart ( visits 1 and 2 ) . At visit 2 subjects were r and omly assigned in double blind fashion and in equal gender numbers to take flaxseed oil or safflower oil for three further months until visit 3 . Oil consumption in both groups was approximately 10 g/d . ALA intake in the intervention group was approximately 5.5 g/d . Power was 0.80 to see a difference of 1 mmol of glucose /L using 12 subjects per group with a p Flaxseed oil had no impact on fasting blood serum glucose , insulin or HbA1c levels . It is concluded that high doses of flaxseed oil have no effect on glycemic control in type 2 diabetics ", "Objective : To determine the effects of dietary consumption of milled flaxseed or flaxseed oil on glycemic control , n-3 fatty acid status , anthropometrics , and adipokines in individuals with type 2 diabetes . Design : Thirty-four participants were r and omized into a parallel , controlled trial . Subjects : The participants were adults with type 2 diabetes ( age 52.4 ± 1.5 years , body mass index 32.4 ± 1.0 kg/m2 , n = 17 men and 17 women ) . Interventions : Participants consumed a selection of bakery products containing no flax ( control group [ CTL ] , n = 9 ) , milled flaxseed ( FXS , n = 13 ; 32 g/d ) , or flaxseed oil ( FXO , n = 12 ; 13 g/d ) daily for 12 weeks . The FXS and FXO groups received equivalent amounts of alpha-linolenic acid ( ALA ; 7.4 g/day ) . Measures of Outcome : The primary outcome measures were fasting plasma hemoglobin A1c , glucose , insulin , and phospholipid fatty acid composition . The secondary outcome measures were fasting circulating leptin and adiponectin , as well as body weight , body mass index , and waist circumference . Dietary intake assessment and calculations for homeostasis model assessment for insulin resistance and quantified insulin sensitivity check were also completed . Results : The FXS and FXO groups had increases in plasma phospholipid n-3 fatty acids ( ALA , eicosapentaenoic acid [ EPA ] , or decosapentaenoic acid [ DPA ] , but not docosahexaenoic acid ) , and the FXO group had more EPA and DPA in plasma phospholipids compared to the FXS group . All groups had similar caloric intakes ; however , the CTL group experienced a 4 % weight gain compared to baseline ( p including glycemic control , were unchanged by dietary treatment . Conclusions : Milled FXS and FXO intake does not affect glycemic control in adults with well-controlled type 2 diabetes . Possible prevention of weight gain by flax consumption warrants further investigation", "Objective : Flaxseed is a rich source of alpha linolenic acid ( ALA ) , fiber and lignans , making it a potentially attractive functional food for modulating cardiovascular risk . We studied the effects of flaxseed on markers of cardiovascular risk in hypercholesterolemic adults . Methods : Sixty-two men and post-menopausal women with pre- study low density lipoprotein cholesterol ( LDL-C ) between 130 and 200 mg/dl were r and omized to 40g/day of ground flaxseed-containing baked products or matching wheat bran products for 10 weeks while following a low fat , low cholesterol diet . Fasting lipoproteins , measures of insulin resistance , inflammation , oxidative stress , and safety were assessed at 0 , 5 and 10 weeks . Results : Flaxseed was well-tolerated , and increased serum levels of ALA ( p , flaxseed significantly reduced LDL-C at 5 weeks ( −13 % , p ) . Flaxseed reduced lipoprotein a ( Lp[a ] ) by a net of 14 % ( p = 0.02 ) , and reduced the homeostatic model assessment of insulin resistance ( HOMA-IR ) index by 23.7 % ( p = 0.03 ) compared to wheat at 10 weeks , but did not affect markers of inflammation ( IL-6 , Hs-CRP ) or oxidative stress ( ox LDL , urinary isoprostanes ) at any time points . In men , flaxseed reduced HDL-C concentrations by a net of 16 % ( p = 0.03 ) and 9 % ( p = 0.05 ) at 5 and 10 weeks , respectively . Conclusions : Ground flaxseed has a modest but short lived LDL-C lowering effect , yet reduces Lp(a ) and improves insulin sensitivity in hyperlipidemic adults . The HDL-C lowering effect of flaxseed in men warrants additional study", "OBJECTIVE Due to its high content of lignans , alpha-linolenic acid and fiber , flaxseed may reduce cardiovascular disease risk in humans . The present study evaluated the effect of flaxseed on markers of cardiovascular disease risk in healthy menopausal women . METHODS One hundred ninety-nine women were r and omly assigned to consume 40 g daily of flaxseed or wheat germ placebo for 12 mo . Fatty acids , apolipoproteins A-1 and B , lipoprotein(a ) , low-density lipoprotein particle size , fibrinogen , C-reactive protein , insulin , and glucose were measured at baseline and at 12 mo . RESULTS In total 179 women were available for the intention-to-treat analysis . Flaxseed increased plasma alpha-linolenic ( P 0.0001 ) , docosapentaenoic ( P = 0.001 ) , and total omega-3 fatty ( P = 0.0004 ) acids . Differences between flaxseed and wheat germ were observed for apolipoprotein A-1 ( -0.10 + /- 0.26 g/L , P = 0.011 ) and apolipoprotein B ( -0.05 + /- 0.16 g/L , P = 0.047 ) . From baseline , flaxseed raised apolipoproteins A-1 and B by 4.4 % ( P = 0.006 ) and 3 % ( P = 0.054 ) , whereas wheat germ increased these apolipoproteins by 11.6 % ( P lipoprotein(a ) ( P low-density lipoprotein peak particle size ( P healthy menopausal women , flaxseed increased some omega-3 fatty acids in plasma and had a limited effect on apolipoprotein metabolism", "Summary Background Both hempseed oil ( HO ) and flaxseed oil ( FO ) contain high amounts of essential fatty acids ( FAs ) ; i.e. linoleic acid ( LA , 18:2n-6 ) and alpha-linolenic acid ( ALA , 18:3n-3 ) , but almost in opposite ratios . An excessive intake of one essential FA over the other may interfere with the metabolism of the other while the metabolisms of LA and ALA compete for the same enzymes . It is not known whether there is a difference between n-3 and n-6 FA of plant origin in the effects on serum lipid profile . Aim of the study To compare the effects of HO and FO on the profile of serum lipids and fasting concentrations of serum total and lipoprotein lipids , plasma glucose and insulin , and haemostatic factors in healthy humans . Methods Fourteen healthy volunteers participated in the study . A r and omised , double-blind crossover design was used . The volunteers consumed HO and FO ( 30 ml/day ) for 4 weeks each . The periods were separated by a 4-week washout period . Results The HO period result ed in higher proportions of both LA and gamma-linolenic acid in serum cholesteryl esters ( CE ) and triglycerides ( TG ) as compared with the FO period ( P ALA in both serum CE and TG as compared with the HO period ( P proportion of arachidonic acid in CE was lower after the FO period than after the HO period ( P total-to-HDL cholesterol ratio compared with the FO period ( P = 0.065 ) . No significant differences were found between the periods in measured values of fasting serum total or lipoprotein lipids , plasma glucose , insulin or hemostatic factors . Conclusions The effects of HO and FO on the profile of serum lipids differed significantly , with only minor effects on concentrations of fasting serum total or lipoprotein lipids , and no significant changes in concentrations of plasma glucose or insulin or in haemostatic factors", "OBJECTIVE Olive oil ( OO ) is a rich source of monounsaturated fat and bioactive components that exert strong anti-oxidant and anti-inflammatory properties . Flaxseed oil ( FO ) is rich in α-linolenic n-3 fatty acid ( ALA ) , which also exhibits anti-inflammatory effects . This r and omized , cross-over study aim ed at exploring whether diet 's enrichment with FO could beneficially alter inflammatory markers and lipid profile , compared to OO , in a sample of normal weight , apparently healthy young adults . MATERIAL S AND METHODS Participants were supplied with 15 mL/day of either FO or OO . Each intervention and the wash-out period lasted 6 weeks . Dietary , anthropometric and physical activity variables were recorded at the beginning and the end of each intervention . Serum biochemical and inflammatory markers were measured . Compliance to the intervention was evaluated by fatty acid analysis in erythrocytes . Repeated Measures ANOVA was used to assess the effect of the treatment . RESULTS Thirty seven participants completed the study . No difference between the two interventions was observed in adiponectin , TNF-α , high sensitivity-CRP or glucose levels and lipid profile . At the end of the FO period , participants exhibited significant reductions in total ( -5.0 % ) and LDL-cholesterol ( -6.7 % ) levels ( all P period serum adiponectin changes were significantly correlated with changes in erythrocyte % ALA ( rs=0.34 , P=0.007 ) and in erythrocyte % EPA ( r(s)=0.47 , P=0.01 ) , respectively . CONCLUSIONS Daily consumption of FO did not confer any benefit in inflammatory or biochemical markers in normal weight young adults , who traditionally use olive oil as the main edible oil", "BACKGROUND Flaxseed is a promising alternative to reduce the risk of diseases associated with body weight excess because it is rich in a-linolenic acid , lignans , and dietary fiber . Flaxseed ( Linum usitatissimum ) can be found in brown and golden varieties ; however , questions have arisen as to whether the variety may influence the health effects . OBJECTIVE The objective of this study was to compare the effects of brown and golden flaxseeds on lipid profile , glycemia , blood pressure , inflammatory status , body weight , and body composition in overweight adolescents . METHODS Seventy-five overweight adolescents ( 33 boys , 42 girls ; age 13.7 ! 2.1 y ) , from Alegre-ES , Brazil , were r and omized to one of the three groups ( n ¼ 25 ) on a parallel , single-blind clinical trial . They received 28 g/d of brown flaxseed ( BF ) , golden flaxseed ( GF ) , or the equivalent amount of wheat bran ( Control , CG ) in different preparations at school from Monday to Friday for 11 wk . Blood pressure , anthropometric evaluation , and the analyses of blood total cholesterol , lipoproteins , glucose , and inflammatory markers were performed at the beginning and at the end of the intervention . The data were analyzed by ANCOVA at 5 % significance . RESULTS The groups who consumed brown and golden flaxseed showed significant reduction in diastolic blood pressure . Brown and golden flaxseed did not differentially affect plasma lipid responses , plasma glucose and inflammatory profile , although all groups ( BF , GF , and CG ) showed increased levels of TNF-a . CONCLUSIONS The adolescents consumed about half the daily amount provided , which may not have been sufficient to exert the health benefits of flaxseed reported in the literature , concerning the lipid profile , inflammation biomarkers and body composition ", " Abstract A two-arm r and omized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease ( NAFLD ) . Participants were assigned to take either a lifestyle modification ( LM ) , or LM + 30 g/day brown milled flaxseed for 12 weeks . At the end of the study , body weight , liver enzymes , insulin resistance and hepatic fibrosis and steatosis decreased significantly in both groups ( p took flaxseed supplementation ( p in hepatic markers between flaxseed and control group , respectively : ALT [ −11.12 compared with −3.7 U/L ; P AST [ −8.29 compared with −4 U/L ; p GGT [ −15.7 compared with −2.62 U/L ; p 0.001 ] , fibrosis score [ −1.26 compared with −0.77 kPa ; p = 0.013 ] and steatosis score [ −47 compared with −15.45 dB/m ; p = 0.022 ] . In conclusion , flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management", "Background Morbidly obese patients frequently display asymptomatic chronic activation of acute phase response , with potentially adverse metabolic and cardiovascular consequences . Nutritional preparations to improve this phenomenon have rarely been administered . Aim ing to investigate the supplementation of flaxseed flour , a source of omega-3 fatty acids , a prospect i ve r and omized double-blind cross-over study was design ed . Methods Outpatient obese subjects ( n = 41 ) were clinical ly and biochemically screened , and results for 24 r and omized subjects are shown . Age was 40.8 ± 11.6 years ( 83.3 % females ) and body mass index ( BMI ) was 47.1 ± 7.2 kg/m2 . Flaxseed flour ( Farinha de Linhaca Dourada LinoLive , Cisbra , Brazil ) in the amount of 30 g/day ( 5 g of alpha-linolenic acid – omega-3 ) and an equal mass of placebo ( manioc flour ) were administered for 2 weeks each . Variables included general biochemical investigation , white blood cell count ( WBC ) , C-reactive protein ( CRP ) , serum amyloid A ( SAA ) and fibronectin . Results No intolerance was registered . Body weight and general biochemical indices remained stable . Initial CRP and SAA were elevated ( 13.7 ± 9.9 and 17.4 ± 8.0 ) . WBC ( 8100 ± 2100/mm3 ) and fibronectin ( 463.2 ± 61.3 mg/dL ) were acceptable but in the upper normal range . Corresponding findings after supplementation of flaxseed were 10.6 ± 6.2 mg/L , 14.3 ± 9.2 mg/L , 7300 ± 1800/mm3 and 412.8 ± 38.6 respectively ( P when placebo was r and omized to be given first ; however , when it followed omega-3 supplementation , CRP and SAA recovered , whereas WBC and fibronection remained depressed during those 2 weeks ( 7500 ± 2100/mm3 and 393.2 ± 75.8 mg/dL , P Various inflammatory markers were elevated in the studied population , although not necessarily exceeding the normal range ; 2 ) Significant reduction could be demonstrated ; 3 ) Some persistent effects of flaxseed supplement 2 weeks after discontinuation were observed", "BACKGROUND AND AIM Plant lignans are metabolised by the colonic micro-flora to the mammalian lignans enterodiol and enterolactone , which are hypothesized to be cardioprotective . The aim of this study was to investigate the effects of a plant lignan complex isolated from flaxseed , providing 500 mg/d of secoisolariciresinol diglucoside , on inflammatory markers . METHODS AND RESULTS Healthy postmenopausal women ( n=22 ) completed a r and omised double-blind , placebo-controlled crossover study . Women consumed daily a low-fat muffin , with or without a lignan complex , for 6 weeks , separated by a 6-week washout period . A significant difference of approximately 15 % ( P=0.028 ) was observed for C-reactive protein ( CRP ) concentration between the lignan complex intervention period and placebo period . CRP concentrations ( median ; 25th , 75th percentiles ) were 0.88 ( 0.63 , 2.05 ) mg/L at baseline and 0.92 ( 0.59 , 1.49 ) mg/L after the lignan complex intervention period compared with 0.80 ( 0.62 , 1.62 ) mg/L at baseline and 1.10 ( 0.72 , 1.62 ) mg/L after placebo . No significant differences in interleukin-6 , tumor necrosis factor-alpha , soluble intracellular adhesion molecule-1 , soluble vascular cell adhesion molecule-1 , and monocyte chemoattractant protein-1 were found between the lignan complex intervention period and placebo period . CONCLUSION Daily consumption for 6 week of a low-fat muffin enriched with a lignan complex may reduce CRP concentrations compared to a low-fat muffin with no lignans added", "Objective : Soy-soluble polysaccharides and flaxseed gum are underutilized dietary fibers of interest to the food industry . However , because the ability of soluble fibers to modulate postpr and ial glucose and insulin metabolism has been related to their viscous effects , the utility of these and other low-viscosity soluble fibers remains unproven . The objective of this study was to examine the associations between soy-soluble polysaccharides and flaxseed gum concentration , product viscosity , and the postpr and ial glycemic and insulinemic responses in the context of glucose solutions as well as fluid and gelled dairy products . Methods : Twelve healthy males participated in a r and omized crossover postpr and ial study in which they visited the laboratory following overnight fasts on 11 occasions to consume one of 11 study treatments , each consisting of 50 g available carbohydrates . The study treatments included a glucose reference ( in duplicate ) , glucose solutions containing soy-soluble polysaccharides ( 6 % ) , flaxseed gum ( 0.7 % ) , or guar gum ( 0.23 % ) , all matched for an apparent viscosity of 61 mPa·s at 50 s−1 , as well as dairy-based beverages and puddings with 0 % or 1 % soluble fiber added . Blood sample s were collected at fasting and up to 2 hours postpr and ially for determination of glucose and insulin concentrations . Area under the curve ( AUC ) , peak concentration , and time-to-peak values as well as glycemic index ( GI ) and insulinemic index ( II ) were calculated . Results : Fiber fortification of a 50 g glucose solution had no effect on postpr and ial blood glucose or insulin levels , even at a high concentration ( i.e. , 6 % soy-soluble polysaccharides ) . Glucose AUC and GI values for the dairy-based beverage ( p reference . Glucose AUC and GI values for the soy-soluble polysaccharide-fortified dairy products ( p ) and flaxseed gum – fortified dairy products ( p of the insulin AUC , II , and peak insulin concentration between any of the dairy products . Conclusions : All dairy products had lower glycemic responses relative to the reference , with no effect of beverage versus pudding matrix observed and minimal impact of 1 % flaxseed gum or soy-soluble polysaccharides . Product apparent viscosity , but not fiber concentration , was significantly and inversely correlated with glucose AUC and GI", "SCOPE To investigate the effects of n-3 fatty acid supplements , both marine and plant-based , on glycemic traits in Chinese type 2 diabetes patients . METHOD AND RESULTS In a double-blind r and omized controlled trial , 185 recruited Chinese type 2 diabetes patients were r and omized to either fish oil ( FO , n = 63 ) , flaxseed oil ( FSO , n = 61 ) , or corn oil group ( served as control group , n = 61 ) for 180 days . The patients were asked to take corresponding oil capsules ( four capsules/day ) , which totally provided 2 g/day of eicosapentaenoic acid + docosahexaenoic acid in FO group and 2.5 g/day of alpha-linolenic acid in FSO group . No group × time interaction was observed for homeostatic model assessment of insulin resistance , fasting insulin , or glucose . Significant group × time interaction ( P = 0.035 ) was observed for glycated hemoglobin A1c ( HbA1c ) , with HbA1c decreased in FO group compared with corn oil group ( P = 0.037 ) . We also found significant group × time interactions for lipid traits , including LDL cholesterol ( P = 0.043 ) , total cholesterol ( P = 0.021 ) , total cholesterol/HDL cholesterol ( P = 0.009 ) , and triacylglycerol ( P = 0.003 ) , with the lipid profiles improved in FO group . No significant effects of FSO on glycemic traits or blood lipids were observed . CONCLUSIONS Marine n-3 PUFA supplements may improve glycemic control and lipid profiles among Chinese type 2 diabetic patients" ]

[ "BACKGROUND Most epidemiologic studies of the relationship between alcohol consumption and breast cancer risk over the past decade have shown that persons who consume a moderate amount of alcohol are at 40%-100 % greater risk of breast cancer than those who do not consume alcohol . Dose-response effects have been observed , but no causal relationship has been established . PURPOSE This study examines the hypothesis that alcohol consumption affects levels of reproductive hormones . METHODS A controlled-diet study lasting for six consecutive menstrual cycles was conducted . Participants were r and omly assigned to two groups , and a crossover design was used . During the last three menstrual cycles , alcohol consumption of the two groups was reversed . Thirty-four premenopausal women , aged 21 - 40 years , with a history of regular menstrual cycles , consumed 30 g of ethanol ( equivalent to approximately two average drinks ) per day for three menstrual cycles and no alcohol for the other three . All food and alcohol consumed were provided by the study . Caloric intake was monitored to ensure that each woman would maintain body weight at approximately the baseline level . Hormone assays were performed on pooled plasma or 24-hour urine specimens collected during the follicular ( days 5 - 7 ) , peri-ovulatory ( days 12 - 15 ) , and mid-luteal ( days 21 - 23 ) phases of the third menstrual cycle for subjects on each diet . RESULTS Alcohol consumption was associated with statistically significant increases in levels of several hormones . Plasma dehydroepi and rosterone sulfate levels were 7.0 % higher in the follicular phase ( P = .05 ) . In the peri-ovulatory phase , there were increases of 21.2 % ( P = .01 ) in plasma estrone levels , 27.5 % ( P = .01 ) in plasma estradiol levels , and 31.9 % ( P = .009 ) in urinary estradiol levels . In the luteal phase , urinary estrone levels rose 15.2 % ( P = .05 ) , estradiol levels increased 21.6 % ( P = .02 ) , and estriol levels rose 29.1 % ( P = .03 ) . No changes were found in the percent of bioavailable estradiol , defined by the sum of percent free estradiol and percent albumin-bound estradiol . However , increased total estradiol levels in the peri-ovulatory phase suggest elevated absolute amounts of bioavailable estradiol . CONCLUSION This study has shown increases in total estrogen levels and amount of bioavailable estrogens in association with alcohol consumption in premenopausal women . IMPLICATION This possible explanatory mechanism for a positive association between alcohol consumption and breast cancer risk merits further investigation", "BACKGROUND Heavy alcohol consumption is associated with menstrual irregularities , including anovulation , luteal-phase dysfunction , recurrent amenorrhea , and early menopause . In addition , moderate to heavy alcohol intake has been found to increase the risk of spontaneous abortions and breast cancer . These adverse effects could at least in part originate from alcohol-mediated changes in hormone levels . METHODS The acute effect of alcohol on the hormone balance in women using oral contraceptives ( OC+ ) and also in nonusers ( OC- ) , was evaluated in 30 OC- and 31 OC+ subjects , representing the whole period of the menstrual cycle . It was also evaluated in 40 OC- and 47 OC+ subjects during the midcycle phase and in 10 OC+ subjects with unknown cycle phase . RESULTS We found that among subjects who used oral contraceptives , estradiol levels increased and progesterone levels decreased after intake of alcohol ( 0.5 g/kg ) . No dose effect ( 0.34 - 1.02 g/kg ) on progesterone was observed in a sub study on 10 OC+ subjects . With regard to estrone levels , no effect was observed , although a significant increase was found in the estradiol-to-estrone ratio . Among subjects not using oral contraceptives , progesterone levels decreased after intake of alcohol ( 0.5 g/kg ) . No effect was found in estradiol , estrone , or the estradiol-to-estrone ratio during midcycle in this study group . A transient elevating effect of alcohol ( 0.5 g/kg ) on prolactin levels was observed in both study groups . We found that alcohol ( 0.5 g/kg ) had no significant effect on luteinizing hormone ( LH ) levels among subjects not using oral contraceptives , and observed a decline among subjects using oral contraceptives at midcycle . CONCLUSIONS We suggest that the estradiol and progesterone effects are related to decreased steroid catabolism , result ing from the alcohol-mediated increase in the hepatic NADH-to-NAD ratio . The transient effect on prolactin levels may reflect acute changes in opioid and dopamine levels in the hypothalamus . The present findings regarding female sex steroids may be of relevance in the association between moderate to heavy alcohol consumption and the development of breast cancer", "The reproducibility and validity of self-reported menopausal status were evaluated among the 121,700 female US registered nurses aged 30 - 55 years in 1976 who are participants in the Nurses ' Health Study , a prospect i ve cohort study of diseases in women . When question ed in 1978 , 6,591 of the women who were premenopausal in 1976 reported that their menses had ceased and provided their age at menopause . Two years later , in 1980 , 98.8 per cent of the 6,591 women again reported that they were postmenopausal and again gave the reasons for menopause ( natural or surgical ) . Among those women who reported surgical menopause during the 1976 - 1978 follow-up interval , age at menopause was reported to within one year on both the 1978 and 1980 question naires by 95 per cent of women . Among those reporting natural menopause during the 1976 - 1978 period , 82 per cent of women reported their age at menopause to within one year on the two follow-up question naires . A r and om sample of 255 women reporting surgical menopause between 1982 and 1984 was identified and medical records were obtained for 200 . For all but two women , there was complete agreement between self-report and medical record for details of hysterectomy and extent of ovarian surgery . The reproducibility of self-reported age at menopause was assessed among 31,405 women who were menopausal in 1976 . Reported age at menopause on consecutive question naires showed increasing within-person variance with increasing duration since menopause . ( ABSTRACT TRUNCATED AT 250 WORDS", "Plasma luteinizing hormone ( LH ) , estradiol , prolactin and progesterone levels were measured in nine normal adult women prior to and following administration of naloxone and oral ingestion of ethanol or placebo-control solution . Each subject served as her own control in a double-blind study carried out during the midluteal phase of the menstrual cycle . The mean ( + /- SD ) progesterone level was 13.9 + /- 1.3 during control conditions and 13.9 + /- 1.7 during alcohol conditions . The mean peak blood alcohol level was 100 + /- 13 mg/dl within 45 - 60 min after initiation of drinking . Under placebo-control conditions , naloxone stimulated a significant increase in plasma LH and prolactin but did not increase estradiol or progesterone . Alcohol did not attenuate the significant naloxone stimulation of LH , and progesterone levels were equivalent under alcohol and control conditions . Alcohol significantly enhanced naloxone stimulation of prolactin and estradiol . Alcohol administration significantly augmented the naloxone-induced increase in plasma prolactin levels . After alcohol administration , naloxone also induced a significant increase in plasma estradiol levels , which was sustained throughout the 180-min sampling period . The mechanisms underlying alcohol 's enhancement of naloxone-stimulated prolactin and estradiol remain to be determined . The alcohol-related increase in naloxone-stimulated prolactin secretion may reflect increased hypothalamic and /or pituitary sensitivity to alcohol following endogenous opioid blockade by naloxone or an effect of increased estrogen levels . The significant increase in plasma estradiol levels following concurrent naloxone and alcohol administration may occur as a consequence of alterations in steroid biotransformation associated with intrahepatic ethanol catabolism", "Objective To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study . Design Combination of prospect i ve cohort study with representative population based data on alcohol exposure . Setting Eight countries ( France , Italy , Spain , United Kingdom , the Netherl and s , Greece , Germany , Denmark ) participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . Participants 109 118 men and 254 870 women , mainly aged 37 - 70 . Main outcome measures Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants . Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex . Partial alcohol attributable fractions for consumption higher than the recommended upper limit ( two drinks a day for men with about 24 g alcohol , one for women with about 12 g alcohol ) and the estimated total annual number of cases of alcohol attributable cancer . Results If we assume causality , among men and women , 10 % ( 95 % confidence interval 7 to 13 % ) and 3 % ( 1 to 5 % ) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries . For selected cancers the figures were 44 % ( 31 to 56 % ) and 25 % ( 5 to 46 % ) for upper aerodigestive tract , 33 % ( 11 to 54 % ) and 18 % ( −3 to 38 % ) for liver , 17 % ( 10 to 25 % ) and 4 % ( −1 to 10 % ) for colorectal cancer for men and women , respectively , and 5.0 % ( 2 to 8 % ) for female breast cancer . A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit : 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women . Conclusions In western Europe , an important proportion of cases of cancer can be attributable to alcohol consumption , especially consumption higher than the recommended upper limits . These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer", "BACKGROUND Growth hormone (GH)-insulin-like growth factor-1 ( IGF-1 ) axis and gonadal hormones demonstrate extensively associated regulation ; however , little is known about the effects of acute alcohol exposure on these hormones . This study examined the effects of intravenous alcohol on the GH-IGF-1 axis and gonadal hormone concentrations , and the influence of age and sex on their regulation . METHODS Forty-eight healthy volunteers ( 24 men and 24 women each in the 21 to 25 and 55 to 65 year age groups ) underwent a 2-session single-blinded study . Subjects received in r and omized counter-balanced order , alcohol infusions , individually computed based on a physiologically based pharmacokinetic model , to maintain a steady-state ( \" clamped \" ) exposure of 50 mg% or saline for 3 hours in separate sessions . Blood sample s collected at baseline and postinfusion in each session were assayed for levels of GH , IGF-1 , free testosterone , and estradiol . RESULTS Acute alcohol administration result ed in changes in gonadal hormones that differed by sex . Change in free testosterone showed a significant treatment × baseline interaction ( p change in estradiol showed a significant treatment × sex interaction ( p = 0.028 ) , indicating that alcohol-induced increases in estradiol occurred predominantly in women . There was a trend for alcohol-induced decreases in IGF-1 levels . Change in GH showed a significant main effect of baseline ( p sex ( p = 0.046 ) indicating that men had greater changes in GH across treatment compared with women . CONCLUSIONS Alcohol induced a complex pattern of hormonal responses that varied between younger and older men and women . Some of the observed sex-based differences may help improve our underst and ing of the greater susceptibility to alcohol-related hepatic damage seen in women", "OBJECTIVES The aim of the study was to explore the influence of reproductive and dietary factors on the age at menopause . METHODS During follow-up of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort in Heidelberg ( median duration 5.8 years ) , 1009 women experienced natural menopause . They were compared to 3798 women who did not experience menopause . Baseline dietary intake was obtained by means of vali date d food frequency question naires . Data on reproductive history and medication was collected by means of question naires . Cox ' proportional hazard models were applied in order to identify determinants of the age at natural menopause . RESULTS Increasing age at first full term pregnancy and a longer time interval until occurrences of regular menses are associated with later onset of natural menopause . Compared to never smokers , current smokers have the risk of younger age at menopause . High carbohydrate consumption and high intake of vegetable , fibre and cereal products are inversely related to the age at natural menopause . Women with higher intake of total fat , protein and meat experienced a delayed onset of natural menopause . CONCLUSION Age at natural menopause is influenced by lifestyle and dietary factors . Further studies including biological markers are needed to clarify these associations", "OBJECTIVE We sought to describe the pattern of age at menopause and factors associated with type of menopause . STUDY DESIGN This was a prospect i ve cohort study of 5113 postmenopausal health survey respondents in the Royal College of General Practitioners ' Oral Contraception Study . Logistic regression was used to evaluate associations between sociodemographics , lifestyle , and medical history and menopause type . RESULTS Median age at natural menopause ( n = 3650 ) was 49.0 years ( interquartile range , 45.0 - 51.0 ) , and at surgical menopause ( n = 1463 ) was 42.4 years ( 38.0 - 46.4 ) . Early natural menopause was associated with smoking , ever-use of oral contraception , sterilization , and history of endometriosis ( all increased odds ratios ) and ever-use of hormone replacement therapy ( decreased ) . Surgical menopause was associated with manual social class , sterilization , and having a history of endometriosis , menorrhagia , or painful menstruation ( all increased ) , and ever-use of hormone replacement therapy ( decreased ) . CONCLUSION Age at natural menopause was younger in this cohort than in other studies . More associations were found for surgical menopause than early natural menopause", "Objective Prospect i ve studies on physical activity and diet and the onset of natural menopause are scarce . The aim of this study was to examine the association of physical activity and dietary factors potentially related to endogenous estrogen levels such as fats , dietary fiber , soy isoflavones , and alcohol with the onset of menopause in a cohort of premenopausal women . Methods Study participants were 3,115 premenopausal Japanese women aged 35 to 56 years derived from the participants in the Takayama Study . Physical activity was assessed by a vali date d question naire at baseline , and the metabolic equivalent score was calculated . The dietary intakes were estimated by a vali date d food frequency question naire at baseline and adjusted for total energy . Menopause status was defined as the absence of menstruation for 12 months or more . The Cox proportional hazard model was used to estimate the hazard ratio of the occurrence of menopause after controlling for age , parity , body mass index , smoking status , years of education , and lifelong irregular menstrual cycle . Results During the 10-year follow-up , 1,790 women experienced natural menopause . A high physical activity level and a high intake of polyunsaturated fat were moderately but significantly associated with the earlier onset of menopause ; the hazard ratios for the highest versus lowest quartile were 1.17 ( 95 % CI , 1.02 - 1.34 ) for physical activity and 1.15 ( 95 % CI , 1.01 - 1.31 ) for polyunsaturated fat intake . Total fat , other types of fat , dietary fiber , soy isoflavones , and alcohol were not associated with the onset of menopause . Conclusions These data suggest that high levels of physical activity and polyunsaturated fat intake are associated with earlier onset of menopause", "OBJECTIVES We prospect ively assessed the association between alcohol consumption and onset of perimenopause in women of late reproductive age using data from the Harvard Study of Moods and Cycles . Specific types of alcoholic beverages - red wine , white wine , beer , and liquor - were evaluated . METHODS Among 502 women aged 36 - 45 years residing in seven Boston communities , we assessed self-reported perimenopausal symptoms over a 5-year period . The onset of perimenopause was defined using changes in menstrual characteristics . We administered a semiquantitative food frequency question naire at enrollment to measure regular alcohol consumption during the past year . Hazard ratios ( HRs ) and 95 % confidence intervals were derived from Cox regression models . RESULTS No association was found between total alcohol consumption and time to perimenopause . Compared with women consuming red wine in quantities of 1 - 3 glasses per month , 1 glass per week , or > or=2 glasses per week were all below 1.0 , after accounting for other sources of alcohol . Among never smokers , the inverse association with red wine was stronger and a positive association was observed with liquor consumption although numbers were small . No associations were observed with white wine or beer . CONCLUSION While there was no association between total alcohol consumption and onset of perimenopause , there was some suggestion of an inverse association between red wine and risk of perimenopause , particularly among never smokers", "OBJECTIVES To examine whether a number of nutritional and familial factors were associated with menopausal development . METHODS A prospect i ve postal survey amongst a r and om sample of 1227 women aged 47 to 51 who were premenopausal in a cross-sectional survey 2 years previously . Women were classed into three groups ; premenopause ( regular menstruation ) ; irregular menstruation ; postmenopausal ( absence of menstrual cycle for at least 6 months ) . Proportional odds regression was used to identify those factors which were independently predictive of subsequent menopausal development . RESULTS There was an 80 % ( n = 983 ) survey response rate . After exclusion of current HRT users ( n = 178 ) ; 150 ( 19 % ) women were postmenopausal , 277 ( 34 % ) had erratic menstruation and 378 ( 47 % ) were premenopause . There were significant univariate associations between menopausal status and age ( P maternal menopause ( P = 0.006 ) , alcohol consumption ( P = 0.005 ) and social class ( P = 0.03 ) . Maternal age and alcohol consumption were significantly correlated with estradiol levels ( r = 0.45 , P = 0.02 , and r = 0.61 , P = 0.02 for maternal age and alcohol consumption , respectively ) . In proportional odds regression analyses , age , maternal menopausal age , alcohol consumption and smoking were independently associated with menopausal status . CONCLUSIONS These results suggest that , ( 1 ) there is a strong familial association in menopausal age , and ( 2 ) moderate consumption of alcohol is associated with delayed menopausal development", "This paper uses a cross-sectional sample of women aged 45 - 49 to investigate factors that might be associated with an early menopause . Using logistic regression analysis we found that age , smoking , age of maternal menopause , parity , social class , meat and alcohol consumption were all independently associated with an early natural menopause . Meat , alcohol consumption and maternal menopausal age do not seem to have been previously noted as associated with the timing of the menopause . These associations would merit further study , preferably using prospect i ve data . However , this study in line with much previous work shows that smoking is associated with a reduction in menopausal age", "Objective : Modifiable factors predicting the onset of menopause , a transition with important implication s for women 's health , have not been fully characterized . We evaluated the impact of dietary , lifestyle and reproductive factors on age at natural menopause and reproductive span in Chinese women . Design : Study participants were Chinese women aged 40 to 70 who experienced natural menopause and participated in a population -based , prospect i ve study , the Shanghai Women 's Health Study ( N = 33,054 ) . Dietary intake at the baseline survey was assessed by food-frequency question naire . Regression ( & bgr ; ) coefficients , calculated by multivariable linear regression , were used to estimate the effects of dietary , lifestyle , and reproductive patterns on age at menopause and the number of reproductive years , adjusting for potential confounding factors . Results : Early menarche , younger age at first live birth , older age at last live birth , longer duration of breast-feeding , and higher parity were associated with longer reproductive years ( Ptrend Higher body mass index at age 20 , mid-life weight gain , and leisure-time physical activity during adolescence and adulthood predicted later menopause and longer reproductive span ( Ptrend Total intake of calories , fruits , and protein was positively associated with later menopause ( Ptrend reproductive span ( Ptrend Vegetable , fat , soy , and fiber intakes did not significantly affect reproductive span or age at menopause . Smoking was inversely associated with both early age at menopause and shorter reproductive span ( Ptrend intake of fruits and protein , smoking , tea consumption , lifetime patterns of physical activity , and weight gain influenced the onset of menopause and /or reproductive span in Chinese women", "Late or early menopause has been implicated in risk of several chronic diseases in women . To study factors influencing the onset of natural menopause , the authors analyzed the follow-up data of 4694 premenopausal women who enrolled in the New York University Women Study at ages 34 - 61 . In an average of 5.4 years of observation , there were 2035 incidences of menopause , with the median age of 51.3 years . Current smokers experienced menopause 0.75 years earlier than never-smokers . Those who smoked more than 10 cigarettes per day had a 40 % increase in risk of earlier menopause . In contrast , women who had three or more children experienced menopause 0.86 years later than Noneiparous women , and Jewish women , 0.66 years later than Catholic women . There was also a modest increase in the age at menopause with increasing body mass index . This prospect i ve study provides solid epidemiologic evidence that several factors other than cigarette smoking have impact on the onset of natural menopause", "International comparison data suggest that wine may be more protective against coronary artery disease than beer or liquor . There are potentially protective antioxidants in wine , especially red wine . However , prospect i ve population studies suggest that each beverage type may reduce coronary risk . The role of alcoholic beverage choice in coronary risk remains unresolved . We performed a prospect i ve study of coronary disease hospitalizations among 128,934 adult members of a Northern California prepaid comprehensive health care program . Alcohol data were supplied at health examinations . Using Cox proportional-hazards models with 9 covariates , analyses were performed of the roles of each major beverage type ( wine , beer , and liquor ) and of drinking only table wine ( red , white , or both ) . Generally , coronary risk traits were most favorable for wine drinkers and least favorable for liquor drinkers . Among 3,931 persons hospitalized for coronary disease , total alcohol drinking was inversely related to risk in both sexes . Uncontrolled for total alcohol , each beverage type showed evidence for coronary protection , weakest for liquor and strongest for beer in men and wine in women . Controlled for total alcohol , these relations were much reduced , and lost statistical significance except for beer in men and both red and white wine ( combined ) in all persons . We conclude that ( 1 ) drinking ethyl alcohol apparently protects against coronary disease , and ( 2 ) there may be minor additional benefits associated with drinking both beer and wine , but not especially red wine", "This is the first study of alcohol use , alcohol problems and alcohol dependence in a general population sample of Australian women using a st and ardized screening instrument developed by the World Health Organization , the Alcohol Use Disorders Identification Test ( AUDIT ) . Sixty-six percent of a sample of 6000 women r and omly selected from the electoral rolls responded to the question naire . The majority of women ( 87 % ) had drunk alcohol at some time in their lives , while 82 % had consumed alcohol within the past 12 months . Of the women who currently drank alcohol , 34 % were classified as hazardous drinkers , 4 % as harmful drinkers and 1 % as dependent according to AUDIT definitions . Using a cut-off score of 8 for the AUDIT , 8 % of women were classified as currently having a drinking pattern of hazardous or harmful alcohol consumption . These women were more likely to be younger ( 17 - 44 years ) , single , or living in a de facto relationship . The results of this survey provide important data which can be used as a bench-mark to measure changes in women 's drinking behaviour and drinking related problems", "Objective We examined the association between lifestyle factors and menstrual cycle characteristics among Noneiparous Danish women aged 18–40 years who were participating in an Internet-based prospect i ve cohort study of pregnancy planners . Methods We used cross-sectional data collected at baseline to assess the association of age , body mass index ( BMI ) , physical activity , alcohol and caffeine consumption , and smoking with the prevalence of irregular cycles , short ( ≤25 days ) and long ( ≥33 days ) cycles , and duration and amount of menstrual flow . We used log-binomial and multinomial logistic regression to estimate prevalence ratios and 95 % confidence intervals . Results Low physical activity and heavy alcohol consumption were associated with an increased prevalence of irregular periods . High BMI , smoking , and caffeine and alcohol consumption were related to an increased prevalence of short menstrual cycles and heavy menstrual bleeding . Women in their mid-to-late thirties had shorter and lighter menstrual flow , but a lower prevalence of irregular cycles , compared with women 18–25 years of age . Discussion In this study , increased age , high BMI , and sedentary behavior were associated with menstrual-pattern irregularities . These factors may influence the balance and level of endogenous hormones conducive to optimal menstrual function" ]

[ "OBJECTIVE The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients . METHOD Twenty-eight actively psychotic in patients , aged 20 - 60 years , who were under treatment with neuroleptic agents were selected for the study . Each was r and omly assigned on a double-blind basis to receive either 5 mg i.m . of haloperidol ( N=13 ) or 1 mg i.m . of flunitrazepam ( N=15 ) during an aggressive event . Verbal and physical aggression was measured over time with the Overt Aggression Scale . Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale . RESULTS Both flunitrazepam and haloperidol exhibited acute antiaggressive activity . This beneficial effect , as assessed by the Overt Aggression Scale , was obtained within 30 minutes . CONCLUSIONS Intramuscular flunitrazepam may serve as a convenient , rapid , safe , and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric setting", "Background Recent electroconvulsive therapy ( ECT ) efficacy studies of right unilateral ( RUL ) ECT may not apply to real life clinics with a wide range of patients with major depressive episodes . Methods The study included two groups of patients . In addition to a homogeneous group of patients with major depression according to DSM-IV criteria with severity of the major depressive episode > 16 scores on 17-item Hamilton Rating Scale for Depression ( HDRS ) ( Group 1 , n = 16 ) , we included a heterogeneous group of patients with less severe major depressive episodes or with a variety of comorbid conditions ( Group 2 , n = 24 ) . We r and omly assigned the patients to an RUL ECT treatment dosed at 5 or 2.5 times seizure threshold with an intent-to-treat design . The outcomes measured blindly were HDRS , number of treatments , and Mini-Mental State Examination ( MMSE ) . The patients were considered to have responded to treatment if the improvement in HDRS score was at least 60 % and they had a total score of less than ten . Results The Group 2 patients responded poorer ( 8 % vs. 63 % ) , and had more often simultaneous worsening in their MMSE scores than Group 1 patients . The differences in the outcomes between the two different doses of RUL ECT treatment were not statistically significant . Conclusions ECT effectiveness seems to be lower in real-life heterogeneous patient groups than in homogeneous patient sample s used in experimental efficacy trials", "Background Agitated or violent patients constitute 10 % of all emergency psychiatric treatment . Management guidelines , the preferred treatment of clinicians and clinical practice all differ . Systematic review s show that all relevant studies are small and none are likely to have adequate power to show true differences between treatments . Worldwide , current treatment is not based on evidence from r and omised trials . In Brazil , the combination haloperidol-promethazine is frequently used , but no studies involving this mix exist . Methods TREC-Rio ( Tranquilização Rápida-Ensaio Clínico [ Translation : Rapid Tranquillisation- Clinical Trial ] ) will compare midazolam with haloperidol-promethazine mix for treatment of agitated patients in emergency psychiatric rooms of Rio de Janeiro , Brazil . TREC-Rio is a r and omised , controlled , pragmatic and open study . Primary measure of outcome is tranquillisation at 20 minutes but effects on other measures of morbidity will also be assessed . TREC-Rio will involve the collaboration of as many health care professionals based in four psychiatric emergency rooms of Rio as possible . Because the design of this trial does not substantially complicate clinical management , and in several aspects simplifies it , the study can be large , and treatments used in everyday practice can be evaluated", "OBJECTIVE To determine the incidence and causes of agitation states in patients presenting at the Rouen University Hospital emergency room and to analyze the management scheme . PATIENTS AND METHOD A prospect i ve study was conducted over a 9 month period in 100 consecutive patients presenting a state of agitation assessed using the Overt Aggression Scale . A pre-planned management protocol was applied . RESULTS The incidence of states of agitation was 0.56 % . There were 43 women and 57 men , mean age 33 years . Most of the agitated patients were admitted between 6 p.m. and 4 a.m. ( 69 % ) . Over the 9 month period , 2 patients were admitted twice for agitation and 2 absconded . Low glucose level was the cause of agitation in 4 cases . Alcohol and /or drug use concerned 73 % of the agitated patients and was the most frequently observed triggering factor ( 17 % ) . Only 6 % of the patients had a regular employment . Physical restraining measures and sedation were required in 86 % and 84 % of the cases respectively . Among 67 patients given loxapine for sedation , 2 developed acute dyskinesia and 9 low blood pressure . One out of 4 patients were referred to a psychiatric unit . CONCLUSION Patients in a state of agitation are young , often female , and in a difficult socio-economic situation . Hypoglycemia is the main differential diagnosis . A triggering factor can often be identified . A state of agitation is not a repetitive condition but occurs as a short-lived episode in the patientís history . Such patients need rapid care to avoid further aggravation and disruption of the emergency room activity , and to prevent the patient from fleeing . Loxapine provides effective sedation but requires regular monitoring of blood pressure and can provoke acute dyskinesia in young subjects", "The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas", "Background The medical management of aggressive and violent behaviour is a critical situation for which there is little evidence . In order to prepare for a r and omised trial , due to start in the psychiatric emergency rooms of Rio de Janeiro in 2001 , a survey of current practice was necessary . Methods A seven day survey of pharmacological management of aggressive people with psychosis in the emergency rooms of all four public psychiatric hospitals in Rio de Janeiro , Brazil . Results In one hospital data were not available . Of the 764 people with psychosis attending these ERs , 74 were given IM medication for rapid tranquillisation ( 9.7 % , 2.1/week/100,000 ) . A haloperidol-promethazine mix ( with or without other drugs ) was used for the majority of patients ( 83 % ) . Conclusion The haloperidol-promethazine mix , given intramuscularly for rapid tranquilization , is prevalent in Rio , where it is considered both safe and efficient . However , scientific evaluation of all pharmacological approaches to rapid tranquilization of psychotic people is inadequate or incomplete and a r and omized trial of IM haloperidol-promethazine is overdue", "Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration", "This double-blind clinical trial studied 16 acutely agitated psychotic patients with manic or manic-like symptoms who needed rapid tranquilization and were therefore on maintenance treatment . They were r and omized to receive intramuscular preparations of clonazepam ( 1 to 2 mg ) or haloperidol ( 5 to 10 mg ) at 0 , 0.5 , and 1.0 hours . Both medications produced significant reduction of manic symptoms within two hours of initial treatment ; however , haloperidol produced beneficial results more rapidly than clonazepam . All patients completed the study , with the exception of one haloperidol-treated patient who developed severe parkinsonism . It was concluded that I.M. clonazepam is an effective , safe , but slower-acting alternative to I.M. haloperidol in the treatment of agitated psychiatric patients in need of rapid tranquilization", "Abstract Objective To compare two widely used drug treatments for people with aggression or agitation due to mental illness . Design Pragmatic , r and omised clinical trial . Setting Three psychiatric emergency rooms in Rio de Janeiro , Brazil . Subjects 301 aggressive or agitated people . Interventions Open treatment with intramuscular midazolam or intramuscular haloperidol plus promethazine . Main outcome measures Patients tranquil or se date d at 20 minutes . Secondary outcomes : patients tranquil or asleep by 40 , 60 , and 120 minutes ; restrained or given extra drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; needing extra visits from doctor during first 24 hours ; overall antipsychotic load in first 24 hours ; and not discharged by two weeks . Results 151 patients were r and omised to midazolam , and 150 to haloperidol-promethazine mix . Follow up for the primary outcome was available for 298 ( 99 % ) : 134/151 ( 89 % ) of patients given midazolam were tranquil or asleep after 20 minutes compared with 101/150 ( 67 % ) of those given haloperidol plus promethazine ( relative risk 1.32 ( 95 % confidence interval 1.16 to 1.49 ) ) . By 40 minutes , midazolam still had a statistically and clinical ly significant 13 % relative advantage ( 1.13 ( 1.01 to 1.26 ) ) . After 1 hour , about 90 % of both groups were tranquil or asleep . One important adverse event occurred in each group : a patient given midazolam had transient respiratory depression , and one given haloperidol-promethazine had a gr and e mal seizure . Conclusions Both treatments were effective . Midazolam was more rapidly sedating than haloperidol-promethazine , reducing the time people are exposed to aggression . Adverse effects and re sources to deal with them should be considered in the choice of the treatment", "OBJECTIVE The purpose of the study was to examine the quantitative risk of criminal behavior associated with specific mental disorders . METHOD An unselected 1966 birth cohort ( N = 12,058 ) in Northern Finl and was prospect ively studied until the end of 1992 . The investigation started during the mothers ' pregnancy , and the data on the subjects ' family characteristics , mental and physical development , living habits , psychiatric morbidity , and criminal records were gathered at various times . RESULTS The prevalence of offenses was the highest among males with alcohol-induced psychoses and male schizophrenic subjects with coexisting alcohol abuse , and more than half of the schizophrenic offenders also had problems with alcohol . Eleven ( 7 % ) of the 165 subjects who committed violent crimes were diagnosed as psychotic . Male schizophrenic subjects had a moderately high risk for violent offenses , but the risk for other types of crimes was not elevated significantly . Odds ratios for criminal behavior were adjusted according to the socioeconomic status of the childhood family and were the same as or slightly lower than the crude odds ratios for all disorders except schizophrenia and mood disorders with psychotic features . CONCLUSIONS The results indicate that the risk of criminal behavior was significantly higher among subjects with psychotic disorders , even though the socioeconomic status of the childhood family was controlled . The higher risk for violent behavior was associated especially with alcohol-induced psychoses and with schizophrenia with coexisting substances abuse . The results suggest that schizophrenia without substance abuse may also be associated with a higher risk of offenses , but this finding is tentative and requires further investigation", "A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors", "BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials", "In a non-blind assessment of 3 neuroleptic drugs , chlorpromazine ( Largactil ) , thioridazine ( Melleril ) and clotiapine ( Etomine ) , we found Etomine to be the drug of choice when the diagnosis is in doubt between a toxic psychosis or schizophrenia . This drug also offered the highest discharge rate , 77'7 % at 12 weeks compared with 73'5 % in the thioridazine group , and 55'5 % in the chlorpromazine group . No clouding of consciousness was seen in the clotiapine group , whereas it was troublesome in the chlorpromazine group in patients having received high parenteral doses " ]

[ "BACKGROUND Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans . METHODS We assessed prospect ively whether plasma 25-hydroxyvitamin D ( 25[OH]D ) concentrations are associated with risk of coronary heart disease . A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study ; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection . The blood sample s were returned between April 1 , 1993 , and November 30 , 1999 ; 99 % were received between April 1 , 1993 , and November 30 , 1995 . During 10 years of follow-up , 454 men developed nonfatal myocardial infa rct ion or fatal coronary heart disease . Using risk set sampling , controls ( n = 900 ) were selected in a 2:1 ratio and matched for age , date of blood collection , and smoking status . RESULTS After adjustment for matched variables , men deficient in 25(OH)D ( risk for MI compared with those considered to be sufficient in 25(OH)D ( > or=30 ng/mL ) ( relative risk [ RR ] , 2.42 ; 95 % confidence interval [ CI ] , 1.53 - 3.84 ; P elevated risk relative to those with sufficient 25(OH)D levels ( 22.6 - 29.9 ng/mL : RR , 1.60 [ 95 % CI , 1.10 - 2.32 ] ; and 15.0 - 22.5 ng/mL : RR , 1.43 [ 95 % CI , 0.96 - 2.13 ] , respectively ) . CONCLUSION Low levels of 25(OH)D are associated with higher risk of myocardial infa rct ion in a grade d manner , even after controlling for factors known to be associated with coronary artery disease", "Background —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896", "OBJECTIVE In observational studies , low serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations have been associated with insulin resistance and other risk factors for cardiovascular disease . RESEARCH DESIGN AND METHODS We present 1-year data from an ongoing 5-year trial in 511 individuals with impaired fasting glucose ( IFG ) and /or impaired glucose tolerance ( IGT ) r and omly assigned to 20,000 IU/week vitamin D3 or placebo . An oral glucose tolerance test was performed at baseline and after 1 year . RESULTS Mean baseline serum 25(OH)D was 59.9 nmol/L and 61.1 nmol/L in the vitamin D and placebo groups , respectively , and increased by 45.8 nmol/L and 3.4 nmol/L , respectively . With adjustment for baseline concentrations , no differences in measures of glucose metabolism , insulin secretion or sensitivity , blood pressure , or hs-CRP were found after 1 year . There was a slight , but significant decrease in total and LDL cholesterol in the vitamin D group compared with the placebo group , but as there was also a decrease in HDL cholesterol , the change in the total/HDL cholesterol ratio did not differ significantly . Only analyzing subjects with 25(OH)D vitamin D supplementation does not improve glycemic indices , blood pressure , or lipid status in subjects with IFG and /or IGT ", "CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality . Data from r and omized controlled trials are limited . OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3 ) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease ( CVD ) risk . DESIGN We conducted a parallel-group , double-blind , placebo-controlled r and omized controlled trial . R and omization was computer generated . Participants and study investigators were blinded to intervention groupings throughout the trial . SETTING The study was conducted at the Clinical Research Facility , University of Aberdeen , United Kingdom . PARTICIPANTS A total of 305 healthy postmenopausal women aged 60 - 70 yr were recruited for the study . INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3 ) or placebo r and omly allocated . MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [ total , high-density lipoprotein , and low-density lipoprotein cholesterol ; triglycerides ; and apolipoproteins A-1 and B100 ] , insulin resistance ( homeostatic model assessment ) , inflammatory biomarkers ( high-sensitivity C-reactive protein , IL-6 , soluble intracellular adhesion molecule-1 ) , and blood pressure . RESULTS A total of 265 ( 87 % ) participants completed all study visits . Small differences between groups for serum apolipoprotein B100 change [ repeated measures ANOVA , P=0.04 ; mean ( sd ) , -1.0 ( 10.0 ) mg/dl ( 400 IU ) ; -1.0 ( 10.0 ) mg/dl ( 1000 IU ) ; and + 0.02 ( 10.0 ) mg/dl ( placebo ) ] were not considered clinical ly significant . Other systemic markers for CVD risk remained unchanged . There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose ( P ( sd ) reduction in systolic blood pressure from winter to summer was -6.6 ( 10.8 ) mm Hg . CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors . Confounding of seasonality should be recognized and addressed in future studies of vitamin", "BACKGROUND Studies suggest that vitamin D deficiency is a risk factor for cardiovascular disease and diabetes . Vitamin D deficiency is prevalent in HIV patients but the effect of vitamin D supplementation on cardiovascular risk in this population is unknown . METHODS We conducted a r and omized , double-blind , placebo-controlled trial among 45 HIV-infected adults in Clevel and ( OH , USA ) on stable antiretroviral therapy with durable virological suppression and a baseline serum 25-hydroxyvitamin D level of ≤20 ng/ml . Participants were r and omized 2:1 to vitamin D3 4,000 IU daily or placebo for 12 weeks . The primary outcome was a change in flow-mediated brachial artery dilation ( FMD ) . RESULTS Baseline demographics were similar except for age ( vitamin D versus placebo , mean ±sd 47 ±8 versus 40 ±10 years ; P=0.009 ) . Both groups had reduced FMD at baseline ( median values 2.9 % [ IQR 1.6 - 4.8 ] for vitamin D versus 2.5 % [ IQR 1.7 - 6.4 ] for placebo ; P=0.819 ) . Despite an increase in the concentration of serum 25-hydroxyvitamin D from baseline to 12 weeks ( 5.0 ng/ml [ IQR -0.9 - 7.4 ] versus -1.9 ng/ml [ IQR -4.0 - 0.1 ] for vitamin D versus placebo , respectively ; P=0.003 ) , there was no difference in FMD change ( 0.55 % [ IQR -1.05 - 2.13 ] versus 0.29 % [ IQR -1.61 - 1.77 ] ; P=0.748 ) . Vitamin D supplementation was associated with a decrease in total and non-high-density lipoprotein cholesterol , and an increase in indices of insulin resistance . CONCLUSIONS Among HIV-infected individuals with vitamin D deficiency , supplementation with 4,000 IU vitamin D3 daily for 12 weeks modestly improved vitamin D status and cholesterol but worsened insulin resistance without change in endothelial function . The mechanisms of resistance to st and ard doses of vitamin D and the complex role of vitamin D in glucose metabolism in this population require further investigation", "BACKGROUND Elevated circulating concentrations of proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure ( CHF ) . In vitro studies suggest that vitamin D suppresses proinflammatory cytokines and increases antiinflammatory cytokines . OBJECTIVE We evaluated the effect of vitamin D supplementation on the survival rate and different biochemical variables in patients with CHF . DESIGN One hundred twenty-three patients r and omly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d [ D(+ ) group ] or placebo plus 500 mg Ca/d [ D(- ) group ] for 9 mo . Biochemical variables were assessed at baseline and after 9 mo . The survival rate was calculated for a follow-up period of 15 mo . RESULTS Ninety-three patients completed the study . Significant treatment effects were observed on logarithmic-transformed serum concentrations of 25-hydroxyvitamin D ( P = 0.001 ) , parathyroid hormone ( P = 0.007 ) , tumor necrosis factor alpha ( P = 0.006 ) , and interleukin 10 ( P = 0.042 ) . 25-Hydroxyvitamin D increased by 26.8 ng/mL in the D(+ ) group but increased only by 3.6 ng/mL in the D(- ) group . Compared with baseline , parathyroid hormone was significantly lower and the antiinflammatory cytokine interleukin 10 was significantly higher in the D(+ ) group after 9 mo . The proinflammatory cytokine tumor necrosis factor alpha increased in the D(- ) group but remained constant in the D(+ ) group . The survival rate did not differ significantly between the study groups during the follow-up period . CONCLUSIONS Vitamin D(3 ) reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease . Our data provide evidence for the involvement of an impaired vitamin D-parathyroid hormone axis in the progression of CHF", "BACKGROUND Indirect evidence suggests that optimal vitamin D status is achieved with a serum 25-hydroxyvitamin D [ 25(OH)D ] concentration > 75 nmol/L. OBJECTIVE We aim ed to determine the intake of vitamin D(3 ) needed to raise serum 25(OH)D to > 75 nmol/L. DESIGN The design was a 6-mo , prospect i ve , r and omized , double-blinded , double-dummy , placebo-controlled study of vitamin D(3 ) supplementation . Serum 25(OH)D was measured by radioimmunoassay . Vitamin D(3 ) intake was adjusted every 2 mo by use of an algorithm based on serum 25(OH)D concentration . RESULTS A total of 138 subjects entered the study . After 2 dose adjustments , almost all active subjects attained concentrations of 25(OH)D > 75 nmol/L , and no subjects exceeded 220 nmol/L. The mean ( + /-SD ) slope at 9 wk [ defined as 25(OH)D change/baseline dose ] was 0.66 + /- 0.35 (nmol/L)/(microg/d ) and did not differ statistically between blacks and whites . The mean daily dose was 86 microg ( 3440 IU ) . The use of computer simulations to obtain the most participants within the range of 75 - 220 nmol/L predicted an optimal daily dose of 115 microg/d ( 4600 IU ) . No hypercalcemia or hypercalciuria was observed . CONCLUSIONS Determination of the intake required to attain serum 25(OH)D concentrations > 75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations . Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d ( 3800 IU ) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d ( 5000 IU ) for those below that threshold", "OBJECTIVE Low vitamin D levels and risk factors for vascular disease are both common in South Asian women . This trial evaluated whether vitamin D supplementation could improve markers of vascular health in South Asian women with low 25-hydroxyvitamin D levels . METHODS Parallel-group , double-blind , r and omised placebo-controlled trial . Healthy South Asian women with baseline serum 25-hydroxyvitamin D levels of to receive a single dose of 100,000 units oral vitamin D3 or matching placebo . Outcomes were measured at baseline , 4 and 8 weeks . The primary outcome was change in endothelial function measured using brachial artery flow-mediated dilatation . Secondary outcomes included blood pressure , arterial stiffness , microvascular function measured using laser Doppler iontophoresis , insulin resistance , serum lipids , circulating markers of inflammation , thrombosis and adipokines . RESULTS 50 women were r and omised , 25 to each group . Mean age was 41 years ; mean baseline 25-hydroxyvitamin D level was 27 nmol/L. 25-Hydroxyvitamin D levels rose in the vitamin D group relative to the placebo group by 4 weeks ( 16 nmol/L , 95 % CI 11 to 21 , p flow-mediated dilatation in the vitamin D group relative to placebo at 4 weeks ( 0.1 % , 95 % CI -0.9 to 1.1 , p = 0.84 ) or 8 weeks ( 0.0 % , 95 % CI -1.4 to 1.4 , p = 0.98 ) . There was no improvement in cholesterol , insulin resistance or markers of inflammation . Both platelet activation inhibitor-1 and tissue plasminogen activator levels fell significantly in the vitamin D group relative to placebo at 8 weeks . CONCLUSION A single large dose of vitamin D3 did not improve blood pressure or endothelial function in South Asian women with low baseline 25-hydroxyvitamin D levels . TRIAL REGISTRATION IS RCT N75081811", "The aim of this study was to investigate the effects of vitamin D supplementation on serum aminotransferases , insulin resistance , oxidative stress , and inflammatory biomarkers in adult patients with non-alcoholic fatty liver disease ( NAFLD ) . Fifty-three patients with NAFLD were enrolled in a parallel , double-blind , placebo-controlled study . The patients were r and omly allocated to receive either one oral pearl consisting of 50,000 IU vitamin D3 ( n = 27 ) or a placebo ( n = 26 ) , every 14 days for 4 months . Serum aminotransferases , high-sensitive C-reactive protein ( hs-CRP ) , tumor necrosis factor α , malondialdehyde ( MDA ) , total antioxidant capacity , transforming growth factor β1 , as well as grade of hepatic steatosis and homeostasis model assessment of insulin resistance were assessed pre- and post-intervention . In patients who received vitamin D supplement compared to the controls , the median of serum 25(OH)D3 significantly increased ( 16.2 vs. 1.6 ng/ml , P decrease in serum MDA ( −2.09 vs. −1.23 ng/ml , P = 0.03 ) and near significant changes in serum hs-CRP ( −0.25 vs. 0.22 mg/l , P = 0.06 ) . These between-group differences remained significant even after controlling for baseline covariates . Other variables showed no significant changes . Improved vitamin D status led to amelioration in serum hs-CRP and MDA in patients with NAFLD . This might be considered as an adjunctive therapy to attenuate systemic inflammation and lipid peroxidation alongside other treatments for NAFLD patients", "BACKGROUND Low 25-hydroxy-vitamin D ( 25(OH)D ) levels are inversely related to blood pressure ( BP ) and have been associated with incident hypertension . In people living at northern latitudes diminished cholecalciferol synthesis in the winter increases the risk of vitamin D deficiency . We wanted to test the hypothesis that daily cholecalciferol supplementation in the winter lowers BP in patients with hypertension . METHODS We investigated the effect of 75 µg ( 3,000 IU ) cholecalciferol per day in a r and omized , placebo-controlled , double-blind study in 130 hypertensive patients residing in Denmark ( 56º N ) . Ambulatory BP ( 24-h BP ) and arterial stiffness were measured before and after 20 weeks of treatment , that took place between October and March . RESULTS A total of 112 patients ( mean age 61 ± 10 ) with a baseline p-25(OH)D of 23 ± 10 ng/ml completed the study . Compared with placebo , a nonsignificant 3/1 mm Hg ( P = 0.26/0.18 ) reduction was found in 24-h BP . In patients with vitamin D insufficiency ( 92 ) , 24-h BP decreased by 4/3 mm Hg ( P = 0.05/0.01 ) . Central BP ( CBP ) estimated by applanation tonometry and calibrated with a st and ardized office BP was reduced by 7/2 mm Hg ( P = 0.007/0.15 ) vs. placebo . No differences in carotid-femoral pulse wave velocity ( PWV ) or central augmentation index ( AIx ) were found between treatment arms . CONCLUSIONS Cholecalciferol supplementation , by a dose that effectively increased vitamin D levels , did not reduce 24-h BP , although central systolic BP decreased significantly . In a post-hoc subgroup analysis of 92 subjects with baseline p-25(OH)D levels decreases in 24-h systolic and diastolic BP occurred during cholecalciferol supplementation ", "Background / objectives : Vitamin D has anti-inflammatory and immune-regulating properties . We aim ed to determine if high-dose cholecalciferol supplementation for 1 year in subjects with early chronic kidney disease ( CKD ) improved circulating markers of inflammation and immunity . Subjects/ methods : In this double-blind , r and omized , placebo-controlled trial , 46 subjects with early CKD ( stages 2 and 3 ) were supplemented with oral cholecalciferol ( 50 000 IU weekly for 12 weeks followed by 50 000 IU every other week for 40 weeks ) or a matching placebo for 1 year . Serum tumor necrosis factor-α , interleukin-6 , monocyte chemoattractant protein-1 ( MCP-1 ) , interferon gamma-induced protein-10 and neutrophil gelatinase-associated lipocalin were measured at baseline , 12 weeks and 1 year . Serum cathelicidin ( LL-37 ) was measured at baseline and 12 weeks . An in vitro experiment was performed to investigate the effect of 1,25-dihydroxyvitamin D3 ( 1,25(OH)2D3 ) treatment on MCP-1 secretion in THP-1 monocytes activated with lipopolysaccharide ( LPS ) and Pseudomonas aeruginosa . Results : By 12 weeks , serum MCP-1 decreased in the cholecalciferol group ( 66.2±2.5 to 60.8±2.6 pg/ml , group-by-time interaction P=0.02 ) but was not different from baseline at 1 year . Other markers of inflammation and immunity did not change . In vitro , LPS- and Pseudomonas-activated monocytes treated with 1,25(OH)2D3 had significantly less MCP-1 secretion compared with untreated cells . Conclusions : High-dose cholecalciferol decreased serum MCP-1 concentrations by 12 weeks in patients with early CKD , although the decrease was not maintained for the remainder of the year . In vitro results confirm an MCP-1-lowering effect of vitamin D. Future studies should determine if vitamin D-mediated reductions in MCP-1 concentrations reflect improved clinical outcomes", "Background Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease ( CKD ) . We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients ; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function , endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [ 25(OH)D ] is unknown , which this study investigated . Methods We assessed non-diabetic patients with CKD stage 3/4 , age 17–80 years and serum 25(OH)D Brachial artery Flow Mediated Dilation ( FMD ) , Pulse Wave Velocity ( PWV ) , Augmentation Index ( AI ) and circulating blood biomarkers were evaluated at baseline and at 16 weeks . Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks . Results Clinical characteristics of 26 patients were : age 50±14 ( mean±1SD ) years , eGFR 41±11 ml/min/1.73 m2 , males 73 % , dyslipidaemia 36 % , smokers 23 % and hypertensives 87 % . At 16-week serum 25(OH)D and calcium increased ( 43±16 to 84±29 nmol/L , p and parathyroid hormone decreased ( 10.8±8.6 to 7.4±4.4 ; p = 0.001 ) . FMD improved from 3.1±3.3 % to 6.1±3.7 % , p = 0.001 . Endothelial biomarker concentrations decreased : E-Selectin from 5666±2123 to 5256±2058 pg/mL ; p = 0.032 , ICAM-1 , 3.45±0.01 to 3.10±1.04 ng/mL ; p = 0.038 and VCAM-1 , 54±33 to 42±33 ng/mL ; p = 0.006 . eGFR , BP , PWV , AI , hsCRP , von Willebr and factor and Fibroblast Growth Factor-23 , remained unchanged . Conclusion This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness , serum calcium or FGF-23 . Trial Registration Clinical Trials.gov", "Summary The effect of equivalent oral doses of vitamin D3 600 IU/day , 4200 IU/week and 18,000 IU/month on vitamin D status was compared in a r and omized clinical trial in nursing home residents . A daily dose was more effective than a weekly dose , and a monthly dose was the least effective . Introduction It is assumed that equivalent daily , weekly or monthly doses of vitamin D3 equally influence vitamin D status . This was investigated in a r and omized clinical trial in nursing home residents . Methods The study was performed in ten nursing homes including 338 subjects ( 76 male and 262 female ) , with a mean age of 84 ( ± SD 6.3 years ) . They received oral vitamin D3 either 600 IU/day , or 4200 IU/week , or 18,000 IU/month or placebo . After 4 months , calcium was added during 2 weeks , 320 mg/day or 640 mg/day or placebo . Outcome : serum levels of 25-hydroxyvitamin D ( 25(OH)D ) , parathyroid hormone ( PTH ) and bone turnover markers . Statistical approach : linear multilevel analysis . Results At baseline , mean serum 25(OH)D was 25.0 nmol/L ( SD 10.9 ) , and in 98 % , it was lower than 50 nmol/L. After 4 months , mean serum 25(OH)D levels increased to 62.5 nmol/L ( after daily vitamin D3 69.9 nmol/L , weekly 67.2 nmol/L and monthly 53.1 nmol/L , P groups ) . Median serum PTH levels decreased by 23 % ( p 0.001 ) . Bone turnover markers did not decrease . Calcium supplementation had no effect on serum PTH and bone turnover . Conclusion Daily vitamin D was more effective than weekly , and monthly administration was the least effective", "Background . The role of vitamin D in the body 's ability to fight influenza and URI 's may be dependent on regulation of specific cytokines that participate in the host inflammatory response . The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines . Subjects and Methods . This study was a 3-month prospect i ve placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [ Li-Ng et al. , 2009 ] . 162 volunteers were r and omized to receive either 50 μg/d ( 2000 IU ) of vitamin D3 or matching placebo . 25(OH)D and the levels of 10 different cytokines ( IL-2 , 4 , 5 , 6 , 8 , 10 , 13 , GM-CSF , IFN-γ , TNF-α ) were measured in the serum of participants at baseline and the final visit . There were 6 drop-outs from the active vitamin D group and 8 from the placebo group . Results . In the active vitamin D group , we found a significant median percent decline in levels of GM-CSF ( −62.9 % , P , IFN-γ ( −38.9 % , P , IL-4 ( −50.8 % , P = .001 ) , IL-8 ( −48.4 % , P ) , and IL-10 ( −70.4 % , P for GM-CSF ( −53.2 % , P = .0007 ) and IFN-γ ( −34.4 % , P = .0011 ) . For each cytokine , there was no significant difference in the rate of decline between the two groups . 25(OH)D levels increased in the active vitamin D group from a mean of 64.3 ± 25.4 nmol/L to 88.5 ± 23.2 nmol/L. Conclusions . The present study did not show that vitamin D3 supplementation changed circulating cytokine levels among healthy adults", "Background : Vitamin D deficiency is prevalent among women , including patients with polycystic ovary syndrome ( PCOS ) . Some studies have suggested that vitamin D may have a role in cardiovascular disease ( CVD ) . There is very limited data on the vitamin D effect on CVD risk factors in women with PCOS and vitamin D deficiency . Aim : To investigate the effect of cholecalciferol on CVD risk factors in PCOS women with vitamin D deficiency . Methods : The study was a r and omized , placebo-controlled , double blinded trial . Fifty PCOS women with vitamin D deficiency ( vitamin D , no.=24 ; placebo , no.=26 ) aged 20–40 yr , were r and omly assigned to receive 3 oral capsules of 50 , 000 IU vitamin D3 or a placebo ( one capsule every 20 days ) for two months . Serum vitamin D , PTH , lipid profile , apolipoprotein AI ( APO-AI ) , and high sensitive C- reactive protein ( hs-CRP ) were measured at baseline and after treatment . Results : Vitamin D3 therapy in PCOS patients , increased serum vitamin D ( 7.00±2.80 to 22.9±6.14 ng/ml ) , decreased serum total cholesterol ( 196.6±32.8 to 179.1±34.1 mg/dl ) , triglyceride ( 156.8±73.0 to 130.5±56.5 mg/dl ) , and VLDL ( 31.4±14.6 to 26.1 ±11.3 mg/dl ) levels significantly ( p not affect serum HDL-cholesterol , LDL-cholesterol , APO-AI , and hs-CRP concentrations . There was no change in variables in the placebo group . Conclusions : Our study showed that vitamin D3 therapy had beneficial effects on some CVD risk factors in PCOS patients with vitamin D deficiency . The trial was registered at I RCT .ir ( I RCT 138904113140N2 )", "BACKGROUND AND AIMS Low vitamin D levels are associated with increased incidence of future cardiovascular events and are common in stroke patients . We tested whether vitamin D supplementation could reduce blood pressure and improve markers of vascular health in patients who had previously suffered a stroke . METHODS AND RESULTS R and omised , placebo-controlled , double-blind trial . Community-dwelling patients with a history of stroke and baseline 25-hydroxyvitamin D levels received 100,000 units of oral vitamin D2 or placebo at baseline . Office and 24 h blood pressure , endothelial function measured by flow-mediated dilatation of the brachial artery , cholesterol , oxidised low density lipoprotein , B-type natriuretic peptide and heart rate turbulence were measured at baseline , 8 weeks and 16 weeks . 58 patients were r and omised . Mean age was 67 years , mean baseline blood pressure 128/72 mmHg , mean baseline 25-hydroxyvitamin D level was 38 nmol/L. Serum 25-hydroxyvitamin D levels were higher in the intervention group at 8 weeks compared to placebo ( 54 vs 42 nmol/L , P = 0.002 ) and remained higher at 16 weeks . Office systolic and diastolic blood pressure showed no significant change between groups at 8 weeks ( systolic 126.1 vs 131.3 mmHg ; adjusted P = 0.97 ) ; ( diastolic 73.1 vs 74.9 mmHg , adjusted P = 0.15 ) . Flow mediated dilatation was significantly higher in the intervention group at 8 weeks ( 6.9 % vs 3.7 % , adjusted P = 0.007 ) but was not significantly different at 16 weeks . CONCLUSIONS High dose oral vitamin D supplementation did not improve blood pressure but produced short-term improvement in endothelial function in stroke patients with well-controlled baseline blood pressure . CLINICAL TRIALS REGISTRATION IS RCT N28737567", "Unfavorable metabolic profiles and oxidative stress in pregnancy are associated with several complications . This study was conducted to determine the effects of vitamin D supplementation on serum concentrations of high-sensitivity C-reactive protein ( hs-CRP ) , metabolic profiles , and biomarkers of oxidative stress in healthy pregnant women . This r and omized , double-blind , placebo-controlled clinical trial was conducted in 48 pregnant women aged 18 - 40 y old at 25 wk of gestation . Participants were r and omly assigned to receive either 400 IU/d cholecalciferol supplements ( n = 24 ) or placebo ( n = 24 ) for 9 wk . Fasting blood sample s were taken at study baseline and after 9 wk of intervention to quantify serum concentrations of hs-CRP , lipid concentrations , insulin , and biomarkers of oxidative stress . After 9 wk of intervention , the increases in serum 25-hydroxyvitamin D and calcium concentrations were greater in the vitamin D group ( + 3.7 μg/L and + 0.20 mg/dL , respectively ) than in the placebo group ( -1.2 μg/L and -0.12 mg/dL , respectively ; P ) . Vitamin D supplementation result ed in a significant decrease in serum hs-CRP ( vitamin D vs. placebo groups : -1.41 vs. + 1.50 μg/mL ; P-interaction = 0.01 ) and insulin concentrations ( vitamin D vs. placebo groups : -1.0 vs. + 2.6 μIU/mL ; P-interaction = 0.04 ) and a significant increase in the Quantitative Insulin Sensitivity Check Index score ( vitamin D vs. placebo groups : + 0.02 vs. -0.02 ; P-interaction = 0.006 ) , plasma total antioxidant capacity ( vitamin D vs. placebo groups : + 152 vs. -20 mmol/L ; P-interaction = 0.002 ) , and total glutathione concentrations ( vitamin D vs. placebo groups : + 205 vs. -32 μmol/L ; P-interaction = 0.02 ) compared with placebo . Intake of vitamin D supplements led to a significant decrease in fasting plasma glucose ( vitamin D vs. placebo groups : -0.65 vs. -0.12 mmol/L ; P-interaction = 0.01 ) , systolic blood pressure ( vitamin D vs. placebo groups : -0.2 vs. + 5.5 mm Hg ; P-interaction = 0.01 ) , and diastolic blood pressure ( vitamin D vs. placebo groups : -0.4 vs. + 3.1 mm Hg ; P-interaction = 0.01 ) compared with placebo . In conclusion , vitamin D supplementation for 9 wk among pregnant women has beneficial effects on metabolic status", "IMPORTANCE Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension . No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension , the most common pattern of hypertension in older people . OBJECTIVE To test whether high-dose , intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension . DESIGN Parallel group , double-blind , placebo-controlled r and omized trial . SETTING Primary care clinics and hospital clinics . PARTICIPANTS Patients 70 years and older with isolated systolic hypertension ( supine systolic blood pressure > 140 mm Hg and supine diastolic blood pressure INTERVENTIONS A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year . MAIN OUTCOMES AND MEASURES Difference in office blood pressure , 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , insulin resistance , and b-type natriuretic peptide level during 12 months . RESULTS A total of 159 participants were r and omized ( mean age , 77 years ) . Mean baseline office systolic blood pressure was 163/78 mm Hg . Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group ( + 8 ng/mL at 1 year , P ) office blood pressure ( −1 [ −6 to 4]/−2 [ −4 to 1 ] mm Hg at 3 months and 1 [ −2 to 4]/0 [ −2 to 2 ] mm Hg overall treatment effect ) . No significant treatment effect was evident for any of the secondary outcomes ( 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , glucose level , and walking distance ) . There was no excess of adverse events in the treatment group , and the total number of falls was nonsignificantly lower in the group receiving vitamin D ( 36 vs 46 , P = .24 ) . CONCLUSIONS AND RELEVANCE Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N92186858", "BACKGROUND Low vitamin D levels are common , and are associated with a higher incidence of future vascular events . We tested whether vitamin D supplementation could improve endothelial function and other markers of vascular function in patients with a history of myocardial infa rct ion . METHODS Parallel group , placebo-controlled , double-blind r and omised trial . Patients with a history of myocardial infa rct ion were r and omised to receive 100,000 units of oral vitamin D3 or placebo at baseline , 2 months and 4 months . Outcomes were measured at baseline , 2 and 6 months . Reactive hyperaemia index on fingertip plethysmography was the primary outcome . Secondary outcome measures included blood pressure , cholesterol , C-reactive protein , von Willebr and factor , tumour necrosis factor alpha , E-selectin , B-type natriuretic peptide , thrombomodulin and 25-hydroxyvitamin D levels . RESULTS 75 patients were r and omised , mean age 66 years . 74/75 ( 99 % ) completed 6 month follow-up . 25 hydroxyvitamin D levels increased in the intervention group relative to placebo ( + 13 vs + 1 nmol/L , p=0.04 ) . There was no between-group difference in change in reactive hyperaemia index between baseline and 6 months ( -0.18 vs -0.07 , p=0.40 ) . Of the secondary outcomes , only C-reactive protein showed a significant decline in the intervention arm relative to placebo at 6 months ( -1.3 vs 2.0mg/L , p=0.03 ) . Systolic blood pressure ( + 1.4 vs + 2.3 mmHg , p=0.79 ) , diastolic blood pressure ( + 2.0 vs + 0.8 mmHg , p=0.54 ) and total cholesterol ( + 0.26 vs + 0.24 mmol/L , p=0.88 ) showed no between-group difference at 6 months . CONCLUSIONS Supplementation with vitamin D did not improve markers of vascular function in patients with a history of myocardial infa rct ion", " BACKGROUND AND OBJECTIVES Observational studies suggest that calciferol supplementation may improve laboratory and patient-level outcomes of hemodialysis patients with reduced 25-hydroxyvitamin D [ 25(OH)D ] levels . This r and omized controlled trial examined effects of cholecalciferol supplementation in patients on hemodialysis . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Sixty patients with 25(OH)D levels ≤24 ng/ml ( ≤60 nmol/L ) were r and omized to receive 50,000 IU oral cholecalciferol or placebo , once weekly for 8 weeks and then monthly for 4 months . At baseline ( autumn 2011 ) and 6 months , testing evaluated muscle strength , functional capacity , laboratory parameters , pulse wave velocity ( PWV ) , and health-related quality of life ( HRQOL ) using the Kidney Disease Quality of Life-36 survey . RESULTS Patients were well matched by treatment allocation . Median age was 62 years ( range , 20 - 86 ) , 52 % were women , 55 % had a history of diabetes , and mean serum 25(OH)D was 17±5 ng/ml ( 43±13 nmol/L ) . Patients were assessed over 6 months by repeated- measures ANOVA . Patients allocated to cholecalciferol had significantly higher values of 25(OH)D ( P ) , 1,25-dihydroxyvitamin D ( P=0.04 ) , and tartrate-resistant acid phosphatase-5b ) ( P=0.04 ) and a greater reduction in phosphorus values ( P=0.03 ) than placebo-treated patients Values of serum calcium , intact parathyroid hormone , and episodes of hypercalcemia and hyperphosphatemia did not differ significantly between the groups . No significant differences were detected in muscle strength , functional capacity , PWV , or HRQOL . CONCLUSIONS In this r and omized controlled trial , patients supplemented with cholecalciferol had higher 25(OH)D , 1,25-dihydroxyvitamin D , and tartrate-resistant acid phosphatase-5b levels , without increased calcium or phosphorus values . However , no effects were detected in muscle strength , functional capacity , PWV , or HRQOL ", "Patients with cystic fibrosis ( CF ) suffer from chronic lung infection and inflammation leading to respiratory failure . Vitamin D deficiency is common in patients with CF , and correction of vitamin D deficiency may improve innate immunity and reduce inflammation in patients with CF . We conducted a double-blinded , placebo-controlled , r and omized clinical trial of high-dose vitamin D to assess the impact of vitamin D therapy on antimicrobial peptide concentrations and markers of inflammation . We r and omized 30 adults with CF hospitalized with a pulmonary exacerbation to 250 000 IU of cholecalciferol or placebo , and evaluated changes in plasma concentrations of inflammatory markers and the antimicrobial peptide LL-37 at baseline and 12 weeks post intervention . In the vitamin D group , there was a 50.4 % reduction in tumor necrosis factor-α ( TNF-α ) at 12 weeks ( P reduction in interleukin-6 ( IL-6 ) ( P=0.09 ) . There were no significant changes in IL-1β , IL-8 , IL-10 , IL-18BP and NGAL ( neutrophil gelatinase-associated lipocalin ) . We conclude that a large bolus dose of vitamin D is associated with reductions in two inflammatory cytokines , IL-6 and TNF-α . This study supports the concept that vitamin D may help regulate inflammation in CF , and that further research is needed to eluci date the potential mechanisms involved and the impact on clinical outcomes", "OBJECTIVE To study the effect of estrogen and progesterone on the expression of dihydroxyvitamin D receptor ( VDR ) mRNA in the liver of ovariectomized rats . METHODS Twenty-five adult female SD rats were r and omly divided , with equal numbers , into sham-operated group ( sham ) , ovariectomized group ( OVX ) , ovariectomized group with estrogen treatment ( OVX+E ) , ovariectomized group with progesterone treatment ( OVX+P ) and ovariectomized group with both estrogen and progesterone treatment ( OVX+E+P ) . After 3 months and a half of feeding , all animals were killed to assess VDR mRNA by way of reverse transcriptase-PCR ( RT-PCR ) . RESULTS RT-PCR revealed marked increase in the b and intensity corresponding to VDR mRNA product in Sham , OVX+E , and OVX+E+P groups . CONCLUSION Estrogen may increase the transcription level of VDR gene in the liver of ovariectomized rats", "BACKGROUND Suboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial . The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus ( DM ) . METHODS In a double-blind , placebo-controlled trial , we r and omized 100 type 2 DM patients to vitamin D supplement ( 5000 IU/day , n = 50 ) or placebo ( controls , n = 50 ) for 12 weeks . Assessment of vascular function with brachial artery flow-mediated dilatation ( FMD ) , circulating levels of endothelial progenitor cells ( EPCs ) and brachial-ankle pulse wave velocity , and metabolic parameter , high-sensitivity C-reactive protein ( hsCRP ) and oxidative stress markers were performed before and after the supplementation . RESULTS After 12 weeks , vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [ 25(OH)D ] concentration ( treatment effect 34.7 ng/mL , 95 % CI 26.4 - 42.9 , P serum ionized calcium ( treatment effect 0.037 mmol/L , 95 % CI 0.007 - 0.067 , P = 0.018 ) ; decreased serum parathyroid hormone concentration ( treatment effect -0.55 pmol/L , 95 % CI -1.08 to -0.02 , P = 0.042 ) compared to patients who received placebo . Nevertheless , vitamin D supplementation did not improve vascular function as determined by FMD , circulating EPC count or baPWV ( all P > 0.05 ) . Furthermore , hsCRP , oxidative stress markers , low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups ( all P > 0.05 ) . CONCLUSION In patients with type 2 DM , 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress . CLINICAL TRIAL NUMBER HKCTR-867 , www.hk clinical trials.com", "BACKGROUND Hypovitaminosis D is common in chronic kidney disease ( CKD ) . Effects of 25-hydroxyvitamin D replenishment in CKD are not well described . METHODS An 8-week r and omized , placebo-controlled , double-blind parallel intervention study was conducted in haemodialysis ( HD ) and non-HD CKD patients . Treatment consisted of 40,000 IU of cholecalciferol orally per week . Plasma 25-hydroxyvitamin D ( 25-OHD ) , plasma 1,25-dihydroxyvitamin D ( 1,25-diOHD ) , plasma parathyroid hormone ( PTH ) , serum phosphate , ionized serum calcium and serum fibroblast growth factor 23 ( FGF-23 ) were analysed . We also investigated biomarkers related to cardiovascular disease ( plasma D-dimer , plasma fibrinogen , plasma von Willebr and factor antigen and activity , plasma interleukin 6 , plasma C-reactive protein , blood pressure , aortic augmentation index , aortic pulse wave velocity and 24-h urinary protein loss ) . Objective and subjective health variables were assessed ( muscle function tests , visual analogue scores and Health Assessment Question naire ) . RESULTS Fifty-two CKD patients with 25-OHD Cholecalciferol supplementation led to a significant increase to a median of 155 nmol/L 25-OHD ( interquartile range 137 - 173 nmol/L ) in treated patients ( n = 25 , P 1,25-diOHD ( n = 13 , P lowering of PTH ( n = 13 , P in HD patients . Cholecalciferol supplementation caused a significant increase in serum calcium and FGF-23 . CONCLUSIONS 25-OHD replenishment was effectively obtained with the employed cholecalciferol dosing . In non-HD patients , it had favourable effects on 1,25-diOHD and PTH . Vitamin D-supplemented patients must be monitored for hypercalcaemia . The present study could not identify significant pleiotropic effects of 25-OHD replenishment", "BACKGROUND A growing body of evidence has linked vitamin D deficiency to increased risk of cardiovascular disease . Vitamin D deficiency is also more common in African Americans for whom an increased cardiovascular disease risk exists . This study sought to test the hypothesis that 16 weeks of 60,000 IU monthly supplementation of oral vitamin D(3 ) would improve flow-mediated dilation ( FMD ) in African Americans , whereas no change would be observed in the placebo group . METHODS A r and omized , double-blind , placebo-controlled clinical trial was conducted . Fifty-seven African-American adults were r and omly assigned to either the placebo group or vitamin D group . RESULTS Following 16 weeks of placebo ( n = 23 ; mean age 31 ± 2 years ) or 60,000 IU monthly oral vitamin D(3 ) ( n = 22 ; mean age 29 ± 2 years ) , serum concentrations of 25-hydroxyvitamin D ( 25(OH)D ) increased from 38.2 ± 3.0 to 48.7 ± 3.2 nmol/l and 34.3 ± 2.2 to 100.9 ± 6.6 nmol/l , respectively . No changes in serum parathyroid hormone ( PTH ) , serum calcium , or urine calcium/creatinine were observed following either treatment . Following 16 weeks of treatment , significant improvements in FMD were only observed in the vitamin D group ( 1.8 ± 1.3 % ) , whereas the placebo group had no change ( -1.3 ± 0.6 % ) . Similarly , the vitamin D group exhibited an increase in absolute change in diameter ( 0.005 ± 0.004 cm ) and FMD/shear ( 0.08 ± 0.04 % /s(-1 ) , area under the curve ( AUC ) × 10(3 ) ) following treatment , whereas no change ( -0.005 ± 0.002 cm and -0.02 ± 0.02 % /s(-1 ) , AUC , respectively ) was observed following placebo . CONCLUSION Supplementation of 60,000 IU monthly oral vitamin D(3 ) ( ~2,000 IU/day ) for 16 weeks is effective at improving vascular endothelial function in African-American adults", "BACKGROUND & AIMS Vitamin D supplementation has the potential to alleviate the cardiovascular damage in diabetic patients . The present study was design ed to evaluate long term impact of high doses of vitamin D on arterial properties , glucose homeostasis , adiponectin and leptin in patients with type 2 diabetes mellitus . METHODS AND RESULTS In r and omized , placebo-controlled study 47 diabetic patients were assigned into two groups : Group 1 received oral daily supplementation with vitamin D at a dose of 1000 U/day for 12 months . Group 2 received matching placebo capsules . Blood sampling for metabolic parameters , including fasting glucose , lipid profile , HbA1C , insulin , hs-CRP , 25 OH Vit D , adiponectin and leptin was performed at baseline and at the end of the study . Insulin resistance was assessed by homeostasis model assessment ( HOMA-IR ) . Central aortic augmentation index ( AI ) was evaluated using SphygmoCor . RESULTS The two groups were similar at baseline in terms of hemodynamic parameters . After 12 months , AI decreased significantly during the treatment period in patients received vitamin D ( p Glucose homeostasis parameters , leptin as well as leptin adiponectin ratio did not change in both groups . 25 OH Vit D level significantly increased ( p = 0.022 ) and circulating adiponectin marginally increased ( p = 0.065 ) during 12 month treatment period in active treatment and did not change in placebo group . CONCLUSIONS High doses of vitamin D supplementation in diabetic patients was associated with significant decrease in AI during one year treatment . This beneficial vascular effect was not associated with improvement in glucose homeostasis parameters", "CONTEXT In humans , few studies have compared the potencies of ergocalciferol and cholecalciferol in improving and maintaining vitamin D status . OBJECTIVE Our objective was to evaluate the effects of a single very large dose of both calciferols on serum changes of 25-hydroxyvitamin D [ 25(OH)D ] , 1,25-dihydroxyvitamin D [ 1,25(OH)(2)D ] , ionized calcium , and parathyroid hormone ( PTH ) at baseline , and at 3 , 7 , 30 , and 60 d. DESIGN This was a prospect i ve r and omized intervention study . SETTING The study was performed in a nursing home residence . PARTICIPANTS A total of 32 elderly female patients ( age range 66 - 97 yr ) , with vitamin D deficiency was included in the study . INTERVENTION Participants were r and omized into four groups of eight to receive a single dose of 300,000 IU ergocalciferol or cholecalciferol by oral ( os ) or i m route . RESULTS 25(OH)D levels sharply increased at d 3 only when vitamins were given os . The 30-d basal difference in serum 25(OH)D was significantly greater after cholecalciferol os administration ( 47.8 + /- 7.3 ng/ml ) compared with other forms ( D(3 ) i m : 15.9 + /- 11.3 ; D(2 ) os : 17.3 + /- 4.7 ; D(2 ) i m : 5 + /- 4.4 ; all P area under the curve ( AUC ) of the serum 25(OH)D against time ( AUC(60 ) ) was : D(3 ) os , 3193 + /- 759 ng x d/ml vs. D(2 ) os , 1820 + /- 512 , P PTH levels at 3 ( P ( cholecalciferol ) significantly lowers PTH levels ( P = 0.037 ) . CONCLUSIONS Cholecalciferol is almost twice as potent as ergocalciferol in increasing serum 25(OH)D , when administered either by mouth or i m . 25(OH)D plays a role in modulating serum PTH", "AIMS To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25-hydroxyvitamin D levels . METHODS Double-blind , parallel group , placebo-controlled r and omized trial . A single dose of 100,000 IU vitamin D2 or placebo was administered to patients with Type 2 diabetes over the winter , when levels of circulating 25-hydroxyvitamin D were likely to be lowest . Patients were enrolled if their baseline 25-hydroxyvitamin D level was Endothelial function and blood pressure were measured and fasting blood sample s were taken at baseline and 8 weeks after administration of vitamin D. RESULTS Forty-nine per cent of subjects screened had 25-hydroxyvitamin D levels Vitamin D supplementation increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to placebo and significantly improved flow mediated vasodilatation ( FMD ) of the brachial artery by 2.3 % . The improvement in FMD remained significant after adjusting for changes in blood pressure . Vitamin D supplementation significantly decreased systolic blood pressure by 14 mmHg compared with placebo ; this did not correlate with change in FMD . CONCLUSIONS Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotl and . A single large dose of oral vitamin D2 improves endothelial function in patients with Type 2 diabetes and vitamin D insufficiency", "OBJECTIVE Apart from its role in bone metabolism , vitamin D may also influence cardiovascular disease . The objective of this study was : ( 1 ) to determine the effect of a single , oral , high-dose vitamin D supplementation on endothelial function and arterial stiffness in patients with peripheral arterial disease ( PAD ) and ( 2 ) to investigate the impact of this supplementation on coagulation and inflammation parameters . METHODS In this double-blind , placebo-controlled , interventional pilot study , we screened 76 Caucasian patients with PAD for vitamin D deficiency . Sixty-two were r and omised to receive a single , oral supplementation of 100,000 IU vitamin D3 or placebo . At baseline and after 1 month , we measured serum vitamin D and parathormone levels , and surrogate parameters for cardiovascular disease . RESULTS Sixty-five of 76 patients ( 86 % ) had low 25-hydroxyvitamin D levels ( of those , 62 agreed to participate in the study . At baseline , only parathormone was related to vitamin D. In supplemented patients , vitamin D levels increased from 16.3 ± 6.7 to 24.3 ± 6.2 ng ml(-1 ) ( P vitamin levels did not change . Seasonal factors accounted for a decrease of vitamin D levels by 8 ng ml(-1 ) between summer and winter . After 1 month , none of the measured parameters was influenced by vitamin substitution . CONCLUSION In this pilot study , most patients with PAD were vitamin D deficient . Vitamin D supplementation increased serum 25-hydroxyvitamin D without influencing endothelial function , arterial stiffness , coagulation and inflammation parameters , although the study was underpowered for definite conclusions", "Adequate vitamin D levels may promote cardiovascular health by improving endothelial function and down-regulating inflammation . The objective of this pilot trial was to investigate the effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease ( CAD ) . Using a double-blind placebo wait-list control design , 90 subjects with CAD and vitamin D deficiency ( were r and omized 1:1 to 50,000 IU of oral ergocalciferol or placebo weekly for 12 weeks . Endothelial function ( reactive hyperemia peripheral arterial tonometry , RH-PAT ) , circulating adhesion molecules , and pro-inflammatory cytokines were measured at baseline and 12 weeks . The median increase in serum 25-vitamin D from baseline was 26 ± 17 ng/ml in the active group and 4 ± 8 ng/ml in the placebo group ( between-group difference = 22 ng/ml , p median within-subject change in RH-PAT score was 0.13 ± 0.73 with active treatment and −0.04 ± 0.63 with placebo ( between-group difference = 0.17 , p = 0.44 ) . Within-group and between-group differences in intercellular adhesion molecule levels were greater with placebo ( between-group difference = 6 ng/ml , p = 0.048 ) . Vascular cell adhesion molecule levels decreased in both groups by a similar magnitude ( median difference between groups = 8.5 ng/ml , p = 0.79 ) . There was no difference between groups in magnitude of reduction in interleukin (IL)-12 ( −8.6 ng/ml , p = 0.72 ) and interferon-gamma ( 0.52 ng/ml , p = 0.88 ) . No significant differences in blood pressure , e-selectin , high-sensitivity c-reactive protein , IL-6 or the chemokine CXCL-10 were found with treatment . In conclusion , repleting vitamin D levels in subjects with CAD failed to demonstrate any benefits on surrogate markers of cardiovascular health . These results question the role of vitamin D supplementation in modifying cardiovascular disease" ]

[ "Objectives To assess whether screening improves the detection of atrial fibrillation ( cluster r and omisation ) and to compare systematic and opportunistic screening . Design Multicentred cluster r and omised controlled trial , with subsidiary trial embedded within the intervention arm . Setting 50 primary care centres in Engl and , with further individual r and omisation of patients in the intervention practice s. Participants 14 802 patients aged 65 or over in 25 intervention and 25 control practice s. Interventions Patients in intervention practice s were r and omly allocated to systematic screening ( invitation for electrocardiography ) or opportunistic screening ( pulse taking and invitation for electrocardiography if the pulse was irregular ) . Screening took place over 12 months in each practice from October 2001 to February 2003 . No active screening took place in control practice s. Main outcome measure Newly identified atrial fibrillation . Results The detection rate of new cases of atrial fibrillation was 1.63 % a year in the intervention practice s and 1.04 % in control practice s ( difference 0.59 % , 95 % confidence interval 0.20 % to 0.98 % ) . Systematic and opportunistic screening detected similar numbers of new cases ( 1.62 % v 1.64 % , difference 0.02 % , −0.5 % to 0.5 % ) . Conclusion Active screening for atrial fibrillation detects additional cases over current practice . The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography . Trial registration Current Controlled Trials IS RCT N19633732", "Background Atrial fibrillation ( AF ) has been recognised as an important independent risk factor for thromboembolic disease , particularly stroke for which it provides a five-fold increase in risk . This study aim ed to determine the baseline prevalence and the incidence of AF based on a variety of screening strategies and in doing so to evaluate the incremental cost-effectiveness of different screening strategies , including targeted or whole population screening , compared with routine clinical practice , for detection of AF in people aged 65 and over . The value of clinical assessment and echocardiography as additional methods of risk stratification for thromboembolic disease in patients with AF were also evaluated . Methods The study design was a multi-centre r and omised controlled trial with a study population of patients aged 65 and over from 50 General Practice s in the West Midl and s. These purpose fully selected general practice s were r and omly allocated to 25 intervention practice s and 25 control practice s. GPs and practice nurses within the intervention practice s received education on the importance of AF detection and ECG interpretation . Patients in the intervention practice s were r and omly allocated to systematic ( n = 5000 ) or opportunistic screening ( n = 5000 ) . Prospect i ve identification of pre-existing risk factors for AF within the screened population enabled comparison between high risk targeted screening and total population screening . AF detection rates in systematic ally screened and opportunistically screened population s in the intervention practice s were compared to AF detection rate in 5,000 patients in the control practice ", "BACKGROUND Heart failure and stroke are major causes of morbidity and mortality in older people . Angiotensin converting enzyme inhibitors improve symptoms and survival in left ventricular systolic dysfunction . Anticoagulants are effective in stroke prevention in atrial fibrillation with aspirin being a less effective alternative . OBJECTIVES To determine the prevalence of left ventricular systolic dysfunction , health services utilisation and prescribing of diuretics and angiotensin converting enzyme inhibitors in left ventricular systolic dysfunction , and the prevalence of atrial fibrillation and anti-platelet/thrombotic therapy in atrial fibrillation in older people in the community . METHODS 500 subjects were drawn by two-stage r and om sampling from 5,002 subjects aged 70 years and over living at home . Subjects were screened for atrial fibrillation and left ventricular systolic dysfunction using electrocardiography and echocardiography . RESULTS The population prevalence amongst older people of left ventricular systolic dysfunction was 9.8 % and of atrial fibrillation 7.8 % . More than two-thirds of those with left ventricular systolic dysfunction were not on angiotensin converting enzyme inhibitors . Of those in atrial fibrillation , 35 % were taking aspirin , 24 % were taking warfarin and 41 % were on neither aspirin nor warfarin . Nearly 90 % of older people in the community have had contact with their general practitioner over the past year , and over half of those with left ventricular systolic dysfunction have had contact with hospital-based services over the past 2 years . CONCLUSIONS Left ventricular systolic dysfunction is under-treated in older people in the community . Despite the high level of contact with hospital and community-based services , the majority of those with systolic left ventricular dysfunction are not on angiotensin converting enzyme inhibitors and a significant proportion of those in atrial fibrillation are not on any treatment for stroke prevention", "Objective To assess the accuracy of general practitioners , practice nurses , and interpretative software in the use of different types of electrocardiogram to diagnose atrial fibrillation . Design Prospect i ve comparison with reference st and ard of assessment of electrocardiograms by two independent specialists . Setting 49 general practice s in central Engl and . Participants 2595 patients aged 65 or over screened for atrial fibrillation as part of the screening for atrial fibrillation in the elderly ( SAFE ) study ; 49 general practitioners and 49 practice nurses . Interventions All electrocardiograms were read with the Biolog interpretative software , and a r and om sample of 12 lead , limb lead , and single lead thoracic placement electrocardiograms were assessed by general practitioners and practice nurses independently of each other and of the Biolog assessment . Main outcome measures Sensitivity , specificity , and positive and negative predictive values . Results General practitioners detected 79 out of 99 cases of atrial fibrillation on a 12 lead electrocardiogram ( sensitivity 80 % , 95 % confidence interval 71 % to 87 % ) and misinterpreted 114 out of 1355 cases of sinus rhythm as atrial fibrillation ( specificity 92 % , 90 % to 93 % ) . Practice nurses detected a similar proportion of cases of atrial fibrillation ( sensitivity 77 % , 67 % to 85 % ) , but had a lower specificity ( 85 % , 83 % to 87 % ) . The interpretative software was significantly more accurate , with a specificity of 99 % , but missed 36 of 215 cases of atrial fibrillation ( sensitivity 83 % ) . Combining general practitioners ' interpretation with the interpretative software led to a sensitivity of 92 % and a specificity of 91 % . Use of limb lead or single lead thoracic placement electrocardiograms result ed in some loss of specificity . Conclusions Many primary care professionals can not accurately detect atrial fibrillation on an electrocardiogram , and interpretative software is not sufficiently accurate to circumvent this problem , even when combined with interpretation by a general practitioner . Diagnosis of atrial fibrillation in the community needs to factor in the reading of electrocardiograms by appropriately trained people", "AIMS Atrial fibrillation ( AF ) is a major cause of morbidity , mortality , and health re source consumption . However , as many patients with chronic AF are asymptomatic , rapid , accurate opportunistic screening is needed in primary care to detect AF . Conventional electrocardiogram ( ECG ) technology is too clumsy and time consuming for mass opportunistic screening , thus technology that allows easy , rapid , yet accurate AF screening is required . To address this requirement a prototype h and -held electrode assembly was developed . We hypothesized that a 6-lead frontal-plane ECG acquired from this apparatus in a seated , clothed patient would be as accurate at detecting AF as conventional 12-lead ECG in the undressed , supine patient ( the ' gold st and ard ' ) . METHODS AND RESULTS Electrocardiograms were obtained from 78 patients with AF and 79 with sinus rhythm ( SR ) . All had a conventional 12-lead ECG , a 6-lead ECG from conventionally positioned limb electrodes , a supine 6-lead recording using the prototype recorder placed on the lower thorax/upper abdomen , and a 6-lead prototype recording in the seated patient , the latter with loosened clothing only . Electrocardiograms were r and omly and blindly assessed by two cardiologists for ( i ) diagnosis of AF vs. SR and ( ii ) tracing quality ( subjectively assessed as good , adequate , or bad ) . Compared with conventional 12-lead ECG recordings , all ' new ' recording methods performed satisfactorily with sensitivities ≥90 % ( 90 - 99 % ) , specificities ≥94 % ( 94 - 100 % ) , positive predictive values ≥94 % ( 94 - 100 % ) , negative predictive values ≥90 % ( 90 - 99 % ) , and accuracies ≥93 % ( 93 - 99 % ) . Tracing quality was higher in conventional 12-lead recordings ( 71 and 80 % were assessed as good by the two observers ) compared with conventional 6-lead ( 57 and 59 % ) , supine prototype ( 41 and 31 % ) , and sitting prototype ( 39 and 19 % ) . CONCLUSIONS Despite inferior electrocardiographic quality a 6-lead frontal plane ECG acquired by a simple prototype h and -held electrode assembly allowed reliable differentiation of AF from SR compared with st and ard 12-lead ECG", "Objectives : To assess the demographic and psychological mediators of gender differences in uptake of flexible sigmoidoscopy ( FS ) screening for colorectal cancer . Setting : A sub sample ( n=5462 ) from a large community trial of FS in the UK . Methods : Men and women r and omized to screening as part of the UK Flexible Sigmoidoscopy Trial were sent a postal question naire assessing demographic characteristics and attitudes to screening six months before their screening appointment . Attendance at screening was recorded by the screening centres . Results : More men than women attended screening ( 73 % versus 67 % ) . The higher male attendance was partially explained by their lower levels of socioeconomic deprivation , higher levels of marital status and lower perceived barriers to screening . Conclusions : Contrary to expectations , men weremore likely than women to attend FS screening . This was partially explained by socioeconomic and attitudinal differences to screening , but additional research is needed to underst and the key aspects of FS screening that will maximize screening uptake in men and women", "Background : Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality . We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospect i ve population -based cohort study spanning 2 decades ( the Copenhagen City Heart Study ) . Methods : The study included baseline data collected in 1981 through 1983 on 10,955 persons age 40 to 79 years and baseline data collected in 1991 through 1994 on 7212 persons age 40 to 79 years . We used hospital diagnosis data from the Danish National Hospital Discharge Register to determine the rate of first hospital admission for atrial fibrillation during 7 years following each of the 2 baseline data collecting periods . Changes in admission rates were analyzed using Cox proportional hazard models . Results : During the 2 7-year periods , 379 subjects were admitted with a hospital diagnosis of atrial fibrillation . The rate of hospital admissions for atrial fibrillation increased among both men and women from the first to the second period ( relative risk = 1.6 ; 95 % confidence interval = 1.3–1.9 [ adjusted for age , sex , prior myocardial infa rct ion , arterial hypertension , diabetes mellitus , electrocardiographic left ventricular hypertrophy , decreased lung function , smoking , height , and weight ] ) . Conclusion : During the latest 10 to 20 years , there has been a 60 % increase in hospital admissions for atrial fibrillation independent of changes in known risk factors . This increase could result from changes in admission threshold or coding practice s , or it could reflect a genuine increase in the population incidence of atrial fibrillation", "BACKGROUND AND PURPOSE Stroke occurring with atrial fibrillation ( AF ) is more likely to be fatal or more severe than non-AF stroke based on clinical series , but data from prospect i ve epidemiological studies are sparse and inconsistent . METHODS Over 40-year follow-up of the original 5070 Framingham cohort , 501 initial ischemic strokes , including 103 with AF , were analyzed . Stroke severity was rated as none , mild , moderate , severe , or fatal . Since 1981 , functional status indicated by the Barthel index has been evaluated acutely and at 3 , 6 , and 12 months . Severity and functional status of AF strokes were compared with non-AF strokes using chi 2 test and Student 's t test . Thirty-day mortality was assessed by logistic regression analyses . RESULTS AF was associated with increased stroke severity ( P = .048 ) . Thirty-day mortality was greater in AF strokes than in non-AF strokes ( 25 % versus 14 % ) . The multivariate-adjusted odds ratio for 30-day mortality for AF subjects was 1.84 ( 95 % confidence interval , 1.04 to 3.27 ) . Since 1981 , follow-up was available for 150 initial ischemic strokes , including 30 with AF . Compared with the non-AF group , the AF group had poorer survival and more recurrences during 1 year of follow-up . The AF subjects had lower mean Barthel index scores acutely ( 29.6 versus 58.6 , P fatal as non-AF stroke . Recurrence was more frequent , and functional deficits were more likely to be severe among survivors . Since stroke is usually the initial manifestation of embolism in AF , prevention is critical to reducing disability and mortality", "Atrial fibrillation ( AF ) is a common arrhythmia in elderly persons and a common cause of embolic stroke . Most studies of the prevalence and correlates of AF have used selected , hospital-based population s. The Cardiovascular Health Study is a population -based , longitudinal study of risk factors for coronary artery disease and stroke in 5,201 men and women aged > or = 65 years . AF was diagnosed in 4.8 % of women and in 6.2 % of men at the baseline examination , and prevalence was strongly associated with advanced age in women . Prevalence of AF was 9.1 % in men and women with clinical cardiovascular disease , 4.6 % in patients with evidence of sub clinical but no clinical cardiovascular disease , and only 1.6 % in subjects with neither clinical nor sub clinical cardiovascular disease . A history of congestive heart failure , valvular heart disease and stroke , echocardiographic evidence of enlarged left atrial dimension , abnormal mitral or aortic valve function , treated systemic hypertension , and advanced age were independently associated with the prevalence of AF . The low prevalence of AF in the absence of clinical and sub clinical cardiovascular disease calls into question the existence and clinical usefulness of the concept of so-called \" lone atrial fibrillation \" in the elderly", "Estimates of the risk of stroke for men with non-rheumatic atrial fibrillation were obtained from two large cohort studies --the Whitehall Study of London Civil Servants and the British Regional Heart Study . The first cohort provided an estimated relative risk of stroke of 6.9 compared with controls . This increased risk confirms that of the other prospect i ve estimate , 5.6 , found in the Framingham study . In the second cohort only one of the men at risk had a stroke , and the risk estimate did not differ significantly from unity . The absolute rates of stroke in both cohorts were lower than those reported in the Framingham study , implying a lesser potential benefit from preventive measures . These lower rates should be considered in the planning of trials . The risk of stroke was significantly associated with raised systolic or diastolic blood pressure but not with age or coronary heart disease", "Objective . To evaluate whether routinely performed ECGs in older people from the general population have added value for cardiovascular risk management beyond the information that is already available from their medical records . Design . Observational , prospect i ve cohort study . Setting . General population . Subjects . A total of 566 participants aged 85 years ( 377 women , 189 men ) . Methods . Lifelong history of cardiovascular disease was assessed through medical records obtained from general practitioners . Baseline ECGs were evaluated for prior myocardial infa rct ion and atrial fibrillation . During a 5-year follow-up period , complete cardiovascular mortality and morbidity data were gathered . Results . During 5 years of follow-up , 262/566 ( 46 % ) participants died , of whom 102/262 ( 39 % ) died from cardiovascular disease . Participants with a history of cardiovascular disease at age 85 years ( 284/566 , 50 % ) had an increased cardiovascular mortality ( HR 2.7 , 95 % CI 1.8–4.1 ) and morbidity ( HR myocardial infa rct ion 2.1 , 95 % CI 1.3–3.6 ; HR stroke 2.7 , 95 % CI 1.6–4.9 ) compared with those without such a history . Participants with major ECG abnormalities ( 102/566 , 18 % ) had an increased cardiovascular mortality ( HR 1.8 , 95 % CI 1.1–2.8 ) , but no increase of cardiovascular morbidity compared with those without major ECG abnormalities . In both participants with and without a history of cardiovascular disease , the presence of major ECG abnormalities was not associated with increased cardiovascular mortality or morbidity . Conclusions . In older people from the general population , a history of cardiovascular disease is a strong predictor of cardiovascular mortality and morbidity . Although abnormal findings on routine ECGs predict cardiovascular mortality , they do not provide additional prognostic information beyond the information available from medical records . Therefore , when accurate medical records are available , programmatic ECG recording is not effective in older people", "Objective : To evaluate clinical and cost effectiveness of implementing evidence -based guidelines for the prevention of stroke . Design : Cluster-r and omised trial Setting : Three primary care organisations in the North of Engl and covering a population of 400 000 . Participants : Seventy six primary care teams in four clusters : North , South & West , City I and City II . Intervention : Guidelines for the management of patients with atrial fibrillation and transient ischaemic attack ( TIA ) were developed and implemented using a multifaceted approach including evidence -based recommendations , audit and feedback , interactive educational sessions , patient prompts and outreach visits . Outcomes : Identification and appropriate treatment of patients with atrial fibrillation or TIA , and cost effectiveness . Results : Implementation led to 36 % increase ( 95 % CI 4 % to 78 % ) in diagnosis of atrial fibrillation , and improved treatment of TIA ( odds ratio of complying with guidelines 1.8 ; 95 % CI 1.1 to 2.8 ) . Combined analysis of atrial fibrillation and TIA estimates that compliance was significantly greater ( OR 1.46 95 % CI 1.10 to 1.94 ) in the condition for which practice s had received the implementation programme . The development and implementation of guidelines cost less than £ 1500 per practice . The estimated costs per quality -adjusted life year gained by patients with atrial fibrillation or TIA were both less than £ 2000 , very much less than the usual criterion for cost effectiveness . Conclusions : Implementation of evidence -based guidelines improved the quality of primary care for atrial fibrillation and TIA . The intervention was feasible and very cost effective . Key components of the model include context ual analysis , strong professional support , clear recommendations based on robust evidence , simplicity of adoption , good communication and use of established networks and opinion leaders", "AIMS We aim ed to investigate the prevalence and incidence of atrial fibrillation ( AF ) in a large European population -based study . METHODS AND RESULTS The study is part of the Rotterdam study , a population -based prospect i ve cohort study among subjects aged 55 years and above . The prevalence at baseline was assessed in 6808 participants . Incidence of AF was investigated during a mean follow-up period of 6.9 years in 6432 persons . We identified 376 prevalent and 437 incident cases . Overall prevalence was 5.5 % , rising from 0.7 % in the age group 55 - 59 years to 17.8 % in those aged 85 years and above . The overall incidence rate was 9.9/1000 person-years . The incidence rate in the age group 55 - 59 years was 1.1/1000 person-years , rose to 20.7/1000 person-years in the age group 80 - 84 years and stabilized in those aged 85 years and above . Prevalence and incidence were higher in men than in women . The lifetime risk to develop AF at the age of 55 years was 23.8 % in men and 22.2 % in women . CONCLUSION In this prospect i ve study in a European population , the prevalence and incidence of AF increased with age and were higher in men than in women . The high lifetime risk to develop AF was similar to North American epidemiological data", "BACKGROUND Because palpitations and light headedness often occur paroxysmally these complaints are difficult to diagnose . The hazards for a GP are too many diagnostic interventions for worried well and too few diagnostics for potentially life threatening complaints . OBJECTIVES Patient-activated memo event recorders have proved to be successful in diagnosing episodes of cardiac arrythmias in secondary care . We tested the diagnostic yield of these devices in general practice . METHODS A r and omized clinical trial in general practice . Consecutive patients with complaints of palpitations or light-headedness were r and omized to either usual care or usual care plus event-recorder . The main outcome was the difference in explained episodes . Secondary outcomes were the differences in the number and character of cardiac diagnoses and the feasibility of the event-recorder . RESULTS There were fewer patients without a diagnosis in the intervention group ( 17 % vs 38 % ; RR = 0.5 , 95 % CI 0.3 to 0.7 ) and more patients with a cardiac diagnosis ( 67 % vs. 27 % : RR 2.5 , CI 1.8 to 3,5 ) . More relevant cardiac arrhythmias were detected ( 22 % vs 7 % ) with event recording than with usual care ( RR 3.2 , 95 % CI 1.5 to 6.8 ) . CONCLUSION Patient-activated loop recorders are feasible and effective diagnostic tools in patients with palpitations or light-headedness in primary care . More research into patient characteristics and selection criteria is needed to fine-tune the use of these devices in primary care", "BACKGROUND There are two approaches to the treatment of atrial fibrillation : one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm , and the other is the use of rate-controlling drugs , allowing atrial fibrillation to persist . In both approaches , the use of anticoagulant drugs is recommended . METHODS We conducted a r and omized , multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death . The primary end point was overall mortality . RESULTS A total of 4060 patients ( mean [ + /-SD ] age , 69.7+/-9.0 years ) were enrolled in the study ; 70.8 percent had a history of hypertension , and 38.2 percent had coronary artery disease . Of the 3311 patients with echocardiograms , the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent . There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy ( mortality at five years , 23.8 percent and 21.3 percent , respectively ; hazard ratio , 1.15 [ 95 percent confidence interval , 0.99 to 1.34 ] ; P=0.08 ) . More patients in the rhythm-control group than in the rate-control group were hospitalized , and there were more adverse drug effects in the rhythm-control group as well . In both groups , the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic . CONCLUSIONS Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy , and there are potential advantages , such as a lower risk of adverse drug effects , with the rate-control strategy . Anticoagulation should be continued in this group of high-risk patients", "BACKGROUND Atrial fibrillation ( AF ) is an important public health problem . This arrhythmia is common and associated with a high risk of stroke . Further , appropriate interventions in AF can reduce the risk of stroke by approximately 68 % . Population studies show that a large group of patients have intermittent or chronic AF that remains unrecognized . If a simple screening test for this arrhythmia could be developed and vali date d , application of the technique across population s might identify AF patients for early treatment , potentially reducing the incidence of stroke . In this study , we sought to determine whether individuals taken from the general community could be taught to find and classify the pulse of another as very irregular , implying AF , or regular , implying normal sinus rhythm ( NSR ) . The aim was to establish that pulse examination for potential AF could be performed by individuals with sufficient sensitivity and specificity to be effectively used as a screening procedure for this medically important arrhythmia . METHODS We enrolled 178 subjects selected from the general community from four centers . Subjects received st and ardized education on the medical importance of AF and its signature , a very irregular pulse . A technique for palpating and characterizing the rhythm of the radial pulse was also taught . Without further coaching , subjects were then asked to find their pulse and then to find and classify the pulse of two models r and omly presented who may or may not have had AF . RESULTS Of the 178 subjects tested , 92 % were able to find their own pulse ; 17 ( 9.6 % ) were unable to find the pulse of one or both patient models and were , therefore , excluded from the study . Of the remaining 161 subjects , 76 % ( 122 of 161 ) correctly identified the pulse in an AF model , and 86 % ( 139 of 161 ) correctly identified the pulse in an NSR model . Results did not statistically differ as a function of age , educational status , or location . DISCUSSION This multicenter trial established that given minimal st and ardized instructions , subjects from the general community can reliably and consistently find both their pulse as well as the pulse of another and to differentiate a regular pulse from a very irregular pulse . If similar educational programs were widely applied across large population s , periodic screening for AF might lead to earlier diagnosis and appropriate treatment for patients who have this major risk factor for stroke . These screening programs should be focused on the population over the age of 55 where the risk of stroke in AF increases with each decade", "BACKGROUND Atrial fibrillation is a common and treatable cause of stroke that often remains unrecognised . Screening has been suggested but there is very little evidence concerning the uptake of screening in the elderly population at risk , nor of the optimal method of screening in a general practice setting AIM To compare the uptake and effectiveness of two methods of screening for atrial fibrillation in general practice -- systematic nurse-led screening and prompted opportunistic case finding . DESIGN OF STUDY R and omised controlled trial . SETTING Patients aged 65 to 100 years ( n = 3,001 ) from four general practice s within the MRC general practice framework . METHOD Each of the four study practice s were selected from one quartile , after ranking all framework practice s according to the small area st and ardised mortality ratio of the geographical area served . Patients were r and omised either to nurse-led screening or to prompted opportunistic casefinding . The proportion of patients assessed and the proportion found to have atrial fibrillation were compared . The sensitivity and specificity of clinical assessment of pulse are also reported . RESULTS Substantially more patients had their pulse assessed through systematic screening by invitation ( 1,099/1,499 [ 73 % ] ) than through opportunistic case finding ( 439/1,502 [ 29 % ] , difference = 44 % , 95 % confidence interval [ CI ] = 41 % to 47 % ) . Atrial fibrillation was detected in 67 ( 4.5 % ) and 19 ( 1.3 % ) patients respectively ( difference = 3.2 % , 95 % CI= 2.0 to 4.4 ) . Invitation to nurse-led screening achieved significantly higher assessment rates than case finding in all practice s ; however , the proportion of patients assessed in the case-finding arm varied markedly between practice s ( range = 8 % to 52 % ) . The number needed to screen to identify one additional patient with atrial fibrillation was 31 ( 95 % CI = 23 to 50 ) . The proportion of screened patients with atrial fibrillation receiving anticoagulation treatment was 25 % , although in the majority ( 53/65 [ 82 % ] ) atrial fibrillation had been previously recorded somewhere on their medical record . If the nurse used any irregularity of the pulse as the screening criterion , the sensitivity of screening was 91 % and the specificity was 74 % ; sensitivity fell to 54 % but specificity increased to 98 % if the criterion used was continuous irregularity . CONCLUSIONS Nurse-led screening for atrial fibrillation in UK general practice is both feasible and effective and will identify a substantial number of patients who could benefit from antithrombotic therapy . Although the majority of patients detected at first screening could be identified by careful scrutiny of medical records , review of record summaries was insufficient in the practice s involved in this study and screening may be a more cost-effective option", "Objectives Screening for colorectal cancer by biennial testing for faecal occult blood is being introduced in the UK from 2007 . We examine the likely impact of the programme , in terms of reduced mortality , lives saved and changes in incidence , over the next 20 years . Setting Projections of incidence and mortality of colorectal cancer in Engl and , and the policy that has been adopted for screening in Engl and ( biennial at ages 60–69 from 2007 , then 60–74 in 2010 ) . Methods The results are based on the output of a simulation model that has been used to examine cost-effectiveness of screening policy options , with two scenarios regarding compliance with screening ; both assume that 20 % of the population will never attend for screening , but attendance of those who do is modelled either as a r and om 60 % or 80 % , at each screening round . Results The decrease in mortality rates expected 20 years after introducing screening is 13–17 % in men and 12–15 % in women ( depending on the attendance levels ) . The model predicts an initial rise in incidence , followed ( after six to seven years ) by a fall , so that there is little net change in the number of cases detected over a 20-year period . Conclusion Percentage changes in mortality seem modest , but the projected saving in terms of numbers of lives is not negligible – 1800–2400 per year by 2025 in Engl and ( equivalent numbers are 2200–2700 in all over the UK ) . Newer screening modalities may improve on these projected results" ]

[ "Background — Evidence on economically efficient strategies to lower blood pressure ( BP ) from low- and middle-income countries remains scarce . The Control of Blood Pressure and Risk Attenuation ( COBRA ) trial r and omized 1341 hypertensive subjects in 12 r and omly selected communities in Karachi , Pakistan , to 3 intervention programs : ( 1 ) combined home health education ( HHE ) plus trained general practitioner ( GP ) ; ( 2 ) HHE only ; and ( 3 ) trained GP only . The comparator was no intervention ( or usual care ) . The reduction in BP was most pronounced in the combined group . The present study examined the cost-effectiveness of these strategies . Methods and Results — Total costs were assessed at baseline and 2 years to estimate incremental cost-effectiveness ratios based on ( 1 ) intervention cost ; ( 2 ) cost of physician consultation , medications , diagnostics , changes in lifestyle , and productivity loss ; and ( 3 ) change in systolic BP . Precision of the incremental cost-effectiveness ratio estimates was assessed by 1000 bootstrapping replications . Bayesian probabilistic sensitivity analysis was also performed . The annual costs per participant associated with the combined HHE plus trained GP , HHE alone , and trained GP alone were $ 3.99 , $ 3.34 , and $ 0.65 , respectively . HHE plus trained GP was the most cost-effective intervention , with an incremental cost-effectiveness ratio of $ 23 ( 95 confidence interval , 6–99 ) per mm Hg reduction in systolic BP compared with usual care , and remained so in 97.7 of 1000 bootstrapped replications . Conclusions — The combined intervention of HHE plus trained GP is potentially affordable and more cost-effective for BP control than usual care or either strategy alone in some communities in Pakistan , and possibly other countries in Indochina with similar healthcare infrastructure . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00327574", "Background Intermittent preventive treatment of malaria in children ( IPTc ) involves the administration of a course of anti-malarial drugs at specified time intervals to children at risk of malaria regardless of whether or not they are known to be infected . IPTc provides a high level of protection against uncomplicated and severe malaria , with monthly sulphadoxine-pyrimethamine plus amodiaquine ( SP&AQ ) and sulphadoxine-pyrimethamine plus piperaquine being the most efficacious regimens . A key challenge is the identification of a cost-effective delivery strategy . Methods A community r and omized trial was undertaken in Jasikan district , Ghana to assess IPTc effectiveness and costs using SP&AQ delivered in three different ways . Twelve villages were r and omly selected to receive IPTc from village health workers ( VHWs ) or facility-based nurses working at health centres ' outpatient departments ( OPD ) or EPI outreach clinics . Children aged 3 to 59 months-old received one IPT course ( three doses ) in May , June , September and October . Effectiveness was measured in terms of children covered and adherent to a course and delivery costs were calculated in financial and economic terms using an ingredient approach from the provider perspective . Results The economic cost per child receiving at least the first dose of all 4 courses was US$ 4.58 when IPTc was delivered by VHWs , US$ 4.93 by OPD nurses and US$ 5.65 by EPI nurses . The unit economic cost of receiving all 3 doses of all 4 courses was US$ 7.56 and US$ 8.51 when IPTc was delivered by VHWs or facility-based nurses respectively . The main cost driver for the VHW delivery was supervision , reflecting re sources used for travelling to more remote communities rather than more intense supervision , and for OPD and EPI delivery , it was the opportunity cost of the time spent by nurses in dispensing IPTc . Conclusions VHWs achieve higher IPTc coverage and adherence at lower costs than facility-based nurses in Jasikan district , Ghana . Trial Registration Clinical Trials.gov NCT00119132", "Current World Health Organization ( WHO ) guidelines for severe pneumonia treatment of under-5 children recommend hospital referral . However , high treatment cost is a major barrier for communities . We compared household costs for referred cases with management by lady health workers ( LHWs ) using oral antibiotics . This study was nested within a cluster r and omized trial in Haripur , Pakistan . Data on direct and indirect costs were collected through interviews and record review s in the 14 intervention and 14 control clusters . The average household cost/case for a LHW managed case was $ 1.46 compared with $ 7.60 for referred cases . When the cost of antibiotics provided by the LHW program was excluded from the estimates , the cost/case came to $ 0.25 and $ 7.51 for the community managed and referred cases , respectively , a 30-fold difference . Exp and ing severe pneumonia treatment with oral amoxicillin to community level could significantly reduce household costs and improve access to the underprivileged population , preventing many child deaths", "Background We assessed overall annual and unit cost of delivering package of services and specific services at sub-centre level by CHWs and cost effectiveness of Government of India ’s policy of introducing a second auxiliary nurse midwife ( ANM ) at the sub-centre compared to scenario of single ANM sub-centre . Methods We undertook an economic costing of health services delivered by CHWs , from a health system perspective . Bottom-up costing method was used to collect data on re sources spent in 50 r and omly selected sub-centres selected from 4 districts . Mean unit cost along with its 95 % confidence intervals were estimated using bootstrap method . Multiple linear regression model was used to st and ardize cost and assess its determinants . Results Annually it costs INR 1.03 million ( USD 19,381 ) , or INR 187 ( USD 3.5 ) per capita per year , to provide a package of preventive , curative and promotive services through community health workers . Unit costs for antenatal care , postnatal care , DOTS treatment and immunization were INR 525 ( USD 10 ) per full ANC care , INR 767 ( USD 14 ) per PNC case registered , INR 974 ( USD 18 ) per DOTS treatment completed and INR 97 ( USD 1.8 ) per child immunized in routine immunization respectively . A 10 % increase in human re source costs results in 6 % rise in per capita cost . Similarly , 10 % increment in the ANC case registered per provider through-put results in a decline in unit cost ranging from 2 % in the event of current capacity utilization to 3 % reduction in case of full capacity utilization . Incremental cost of introducing 2nd ANM at sub-centre level per unit percent increase ANC coverage was INR 23,058 ( USD 432 ) . Conclusion Our estimates would be useful in undertaking full economic evaluations or equity analysis of CHW programs . Government of India ’s policy of hiring 2nd ANM at sub-centre level is very cost effective from Indian health system perspective", "BACKGROUND AND METHODS In the setting of a cluster r and omized study to assess impact of the Integrated Management of Neonatal and Childhood Illnesses ( IMNCI ) program in the district of Faridabad in India , we r and omly selected auxiliary nurse midwives ( ANM ) , anganwadi workers ( AWW ) and accredited social health activists ( ASHA ) from intervention and control areas to collect cost data using an economic perspective . Bootstrap method was used to estimate 95 % confidence interval . RESULTS The annual per-child cost of providing health services through an ANM , AWW and ASHA is INR 348 ( USD 7.7 ) , INR 588 ( USD 13.1 ) and INR 87 ( USD 1.9 ) , respectively . The annual per-child incremental cost of delivering IMNCI is INR 124.8 ( USD 2.77 ) , INR 26 ( USD 0.6 ) and INR 31 ( USD 0.7 ) at the ANM , AWW and ASHA level , respectively . CONCLUSION Implementation of IMNCI imposes additional costs to the health system . A comprehensive economic evaluation of the IMNCI is imperative to estimate the net cost implication s in India", "We did a cost-effectiveness analysis alongside a cluster-r and omised controlled trial of a participatory intervention with women 's groups to improve birth outcomes in rural Nepal . The average provider cost of the women 's group intervention was US0.75 dollars per person per year ( 0.90 dollars with health-service strengthening ) in a population of 86,704 . The incremental cost per life-year saved ( LYS ) was 211 dollars ( 251 dollars ) , and expansion could rationalise on start-up costs and technical assistance , reducing the cost per LYS to 138 dollars ( 179 dollars ) . Sensitivity analysis showed a variation from 83 dollars to 263 dollars per LYS for most variables . This intervention could provide a cost-effective way of reducing neonatal deaths", "OBJECTIVE To carry out an economic evaluation of a task-shifting intervention for the treatment of depressive and anxiety disorders in primary -care setting s in Goa , India . METHODS Cost-utility and cost-effectiveness analyses based on generalized linear models were performed within a trial set in 24 public and private primary -care facilities . Subjects were r and omly assigned to an intervention or a control arm . Eligible subjects in the intervention arm were given psycho-education , case management , interpersonal psychotherapy and /or antidepressants by lay health workers . Subjects in the control arm were treated by physicians . The use of health-care re sources , the disability of each subject and degree of psychiatric morbidity , as measured by the Revised Clinical Interview Schedule , were determined at 2 , 6 and 12 months . FINDINGS Complete data , from all three follow-ups , were collected from 1243 ( 75.4 % ) and 938 ( 81.7 % ) of the subjects enrolled in the study facilities from the public and private sectors , respectively . Within the public facilities , subjects in the intervention arm showed greater improvement in all the health outcomes investigated than those in the control arm . Time costs were also significantly lower in the intervention arm than in the control arm , whereas health system costs in the two arms were similar . Within the private facilities , however , the effectiveness and costs recorded in the two arms were similar . CONCLUSION Within public primary -care facilities in Goa , the use of lay health workers in the care of subjects with common mental disorders was not only cost-effective but also cost-saving", "Background Intermittent preventive treatment for malaria in children ( IPTc ) involves the administration of a full course of an anti-malarial treatment to children under 5 years old at specified time points regardless of whether or not they are known to be infected , in areas where malaria transmission is seasonal . It is important to determine the costs associated with IPTc delivery via community based volunteers and also the potential savings to health care providers and caretakers due to malaria episodes averted as a consequence of IPTc . Methods Two thous and four hundred and fifty-one children aged 3–59 months were r and omly allocated to four groups to receive : three days of artesunate plus amodiaquine ( AS+AQ ) monthly , three days of AS+AQ bimonthly , one dose of sulphadoxine-pyrimethamine ( SP ) bi-monthly or placebo . This paper focuses on incremental cost effectiveness ratios ( ICERs ) of the three IPTc drug regimens as delivered by community based volunteers ( CBV ) in Hohoe , Ghana compared to current practice , i.e. case management in the absence of IPTc . Financial and economic costs from the publicly funded health system perspective are presented . Treatment costs borne by patients and their caretakers are also estimated to present societal costs . The costs and effects of IPTc during the intervention period were considered with and without a one year follow up . Probabilistic sensitivity analysis was undertaken to account for uncertainty . Results Economic costs per child receiving at least the first dose of each course of IPTc show SP bimonthly , at US$ 8.19 , is the cheapest to deliver , followed by AS+AQ bimonthly at US$ 10.67 and then by AS+AQ monthly at US$ 14.79 . Training , drug delivery and supervision accounted for approximately 20–30 % each of total unit costs . During the intervention period AS & AQ monthly was the most cost effective IPTc drug regimen at US$ 67.77 ( 61.71–74.75 , CI 95 % ) per malaria case averted based on intervention costs only , US$ 64.93 ( 58.92–71.92 , CI 95 % ) per malaria case averted once the provider cost savings are included and US$ 61.00 ( 54.98 , 67.99 , CI 95 % ) when direct household cost savings are also taken into account . SP bimonthly was US$ 105.35 ( 75.01–157.31 , CI 95 % ) and AS & AQ bimonthly US$ 211.80 ( 127.05–399.14 , CI 95 % ) per malaria case averted based on intervention costs only . The incidence of malaria in the post intervention period was higher in children who were when they received AS+AQ monthly compared to the placebo group leading to higher cost effectiveness ratios when one year follow up is included . The cost per child enrolled fell considerably when modelled to district level as compared to those encountered under trial conditions . Conclusions We demonstrate how cost-effective IPTc is using three different drug regimens and the possibilities for reducing costs further if the intervention was to be scaled up to the district level . The need for effective training , drug delivery channels and supervision to support a strong network of community based volunteers is emphasised", "Background The Lufwanyama Neonatal Survival Project ( “ LUNESP ” ) was a cluster r and omized , controlled trial that showed that training traditional birth attendants ( TBAs ) to perform interventions targeting birth asphyxia , hypothermia , and neonatal sepsis reduced all-cause neonatal mortality by 45 % . This companion analysis was undertaken to analyze intervention costs and cost-effectiveness , and factors that might improve cost-effectiveness . Methods and Findings We calculated LUNESP 's financial and economic costs and the economic cost of implementation for a forecasted ten-year program ( 2011–2020 ) . In each case , we calculated the incremental cost per death avoided and disability-adjusted life years ( DALYs ) averted in real 2011 US dollars . The forecasted 10-year program analysis included a base case as well as ‘ conservative ’ and ‘ optimistic ’ scenarios . Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis . The estimated financial and economic costs of LUNESP were $ 118,574 and $ 127,756 , respectively , or $ 49,469 and $ 53,550 per year . Fixed costs accounted for nearly 90 % of total costs . For the 10-year program , discounted total and annual program costs were $ 256,455 and $ 26,834 respectively ; for the base case , optimistic , and conservative scenarios , the estimated cost per death avoided was $ 1,866 , $ 591 , and $ 3,024 , and cost per DALY averted was $ 74 , $ 24 , and $ 120 , respectively . Outcomes were robust to variations in local costs , but sensitive to variations in intervention effect size , number of births attended by TBAs , and the extent of foreign consultants ' participation . Conclusions Based on established guidelines , the strategy of using trained TBAs to reduce neonatal mortality was ‘ highly cost effective ’ . We strongly recommend consideration of this approach for other remote rural population s with limited access to health care", "by HEWs in the health posts and general health workers at health facility were compared along a community-r and omized trial . Costs were analysed from societal perspective in 2007 in US $ using st and ard methods . We prospect ively enrolled smear positive patients , and calculated cost-effectiveness as the cost per patient successfully treated . The total cost for each successfully treated smear-positive patient was higher in health facility ( $ 158.9 ) compared with community ( $ 61.7 ) . Community-based treatment reduced the total , patient and caregiver cost by 61.2 % , 68.1 % and 79.8 % , respectively . Involving HEWs added a total cost of $ 8.80 ( 14.3 % of total cost ) on health service per patient treated in the community . Conclusions / Significance Community-based treatment by HEWs costs only 39 % of what treatment by general health workers costs for similar outcomes . Involving HEWs in TB treatment is a cost effective treatment alternative to the health service , to the patients and the family . There is an economic and public health reason to consider involving HEWs in TB treatment in Ethiopia . However , community-based treatment requires initial investment to start its implementation , training and supervision . Trial Registration Clinical Trials.gov", "An economic study was conducted alongside a clinical trial at three sites in Pakistan to establish the costs and effectiveness of different strategies for implementing directly observed treatment ( DOT ) for tuberculosis . Patients were r and omly allocated to one of three arms : DOTS with direct observation by health workers ( at health centres or by community health workers ) ; DOTS with direct observation by family members ; and DOTS without direct observation . The clinical trial found no statistically significant difference in cure rate for the different arms . The economic study collected data on the full range of health service costs and patient costs of the different treatment arms . Data were also disaggregated by gender , rural and urban patients , by treatment site and by economic categories , to investigate the costs of the different strategies , their cost-effectiveness and the impact that they might have on patient compliance with treatment . The study found that direct observation by health centre-based health workers was the least cost-effective of the strategies tested ( US dollars 310 per case cured ) . This is an interesting result , as this is the model recommended by the World Health Organization and International Union against Tuberculosis and Lung Disease . Attending health centres daily during the first 2 months generated high patient costs ( direct and in terms of time lost ) , yet cure rates for this group fell below those of the non-observed group ( 58 % , compared with 62 % ) . One factor suggested by this study is that the high costs of attending may be deterring patients , and in particular , economically active patients who have most to lose from the time taken by direct observation . Without stronger evidence of benefits , it is hard to justify the costs to health services and patients that this type of direct observation imposes . The self-administered group came out as most cost-effective ( 164 dollars per case cured ) . The community health worker sub-group achieved the highest cure rates ( 67 % ) , with a cost per case only slightly higher than the self-administered group ( 172 dollars per case cured ) . This approach should be investigated further , along with other approaches to improving patient compliance", "UNLABELLED The incidence of pediatric diarrhea in countries neighboring Myanmar is high ( > 9 % ) . No national data exist in Myanmar , however hospital treatment data indicate that diarrhea is a major cause of morbidity . OBJECTIVE This study seeks to determine diarrhea incidence among children in rural Myanmar and document health-seeking behavior and treatment costs . METHODS We surveyed 2033 caregivers in households with under-five children , in 104 r and omly selected villages in rural Myanmar . FINDINGS The incidence of diarrhea in the 2 weeks prior to the survey was 4.9 % . Home treatment was common ( 50.6 % ) ; among those who consulted a professional 35.6 % went to government clinics , 28.8 % to private clinics and 28.0 % to a community health worker . The cost of treatment was highest ( $ 15 ) at government clinics and lowest ( $ 1.3 ) for self-treatment at home . CONCLUSION Pediatric diarrhea is an important cause of morbidity in rural Myanmar . Self-treatment and treatment by private providers is common", "Aim : To establish the cost-effectiveness of lay health workers ( LHWs ) in conjunction with the current , local tuberculosis ( TB ) control programme , amidst health service contraction . Method : A cost-effectiveness analysis , comparing direct time costs of the current TB management strategy among permanent farm dwellers , with an intervention , whereby LHWs are involved in TB control activities on farms . Measure of effectiveness was case finding and cure rates of adult new smear-positive ( NSP ) TB cases , alongside a r and omized control trial ( RCT ): Results : The observed cost reduction to the Bol and Health District was 74 % per case detected and cured on the intervention farms relative to the control farms . Intervention farms reached 83 % successful treatment completion rate , control farms 65 % . Although the successful treatment adherence was significantly different ( 18 % letter ) . The improved case detection and cure rates were not statistically significant ( chisquared test ) . Direct LHW costs are borne by farmers . Farmers were motivated to bear costs by reduced job absenteeism and other positive side-effects . Even without outcome improvements costs per case cured were 59 % lower on the intervention farms . Conclusion : TB control has suffered from budget reductions in South Africa . It is critically important to develop cost-effective strategies to reduce the TB burden . Costs to public budgets can be substantially reduced while maintaining or improving case detection and treatment outcomes , by using farm-based LHWs", "OBJECTIVE To assess the cost-effectiveness of two strategies of home management of under-five fevers in Ghana - treatment using antimalarials only ( artesunate-amodiaquine - AAQ ) and combined treatment using antimalarials and antibiotics ( artesunate-amodiaquine plus amoxicillin - AAQ + AMX ) . METHODS We assessed the costs and cost-effectiveness of AAQ and AAQ + AMX compared with a control receiving st and ard care . Data were collected as part of a cluster r and omised controlled trial with a step-wedged design . Approximately , 12,000 children aged 2 - 59 months in Dangme West District in southern Ghana were covered . Community health workers delivered the interventions . Costs were analysed from societal perspective , using anaemia cases averted , under-five deaths averted and disability-adjusted life years ( DALYs ) averted as effectiveness measures . RESULTS Total economic costs for the interventions were US$ 204,394.72 ( AAQ ) and US$ 260,931.49 ( AAQ + AMX ) . Recurrent costs constituted 89 % and 90 % of the total direct costs of AAQ and AAQ + AMX , respectively . Deaths averted were 79.1 ( AAQ ) and 79.9 ( AAQ + AMX ) , with DALYs averted being 2264.79 ( AAQ ) and 2284.57 ( AAQ + AMX ) . The results show that cost per anaemia case averted were US$ 150.18 ( AAQ ) and US$ 227.49 ( AAQ + AMX ) and cost per death averted was US$ 2585.58 for AAQ and US$ 3272.20 for AAQ + AMX . Cost per DALY averted were US$ 90.25 ( AAQ ) and US$ 114.21 ( AAQ + AMX ) . CONCLUSION Both AAQ and AAQ + AMX approaches were cost-effective , each averting one DALY at less than the st and ard US$ 150 threshold recommended by the World Health Organisation . However , AAQ was more cost-effective . Home management of under-five fevers in rural setting s is cost-effective in reducing under-five mortality", "Background : The severe shortage of pharmacists is an important limitation to providing antiretroviral treatment ( ART ) in re source -limited countries . Two task-shifting pharmaceutical care models have been developed to address this in South Africa , namely indirectly supervised pharmacist assistant ( ISPA ) and nurse-managed models . This study compared pharmaceutical care quality , patient clinical outcomes , and provider staff costs between these models . Methods : An analysis of pharmaceutical quality audits , patient clinical data , and staff costing data collected at 7 ISPA and 8 nurse-managed facilities was undertaken . Pharmaceutical audits were conducted by pharmacists using a st and ardized tool . Routine clinical data were collected prospect ively at patient visits , and staff human re sources costs were analyzed . Results : Overall pharmaceutical care quality scores were higher at ISPA sites than nurse-managed sites ; 88.8 % vs. 79.9 % , respectively ; risk ratio ( ISPA vs. nurse ) = 1.11 ( 95 % confidence interval : 1.09 to 1.13 ; P Mean provider pharmaceutical-related human re sources costs per patient visit and per item dispensed were 29 % and 49 % lower , respectively , at ISPA facilities . At ISPA facilities , patient attrition was observed to be lower and viral suppression higher than at nurse-managed sites . Conclusion : The ISPA model had a higher quality of pharmaceutical care and was less costly to implement . Further expansion of this model or integrating it with nurse-managed ART may enhance the cost-efficient scale-up of ART programs in Sub-Saharan Africa", "BACKGROUND Early detection and effective case management of tuberculosis ( TB ) among a high-risk group of material ly poor farm workers in an area of the Cape Winel and s , South Africa , presents special challenges to the health community , where re source constraints lead to service reduction . In order to address this problem , local nurses established a collaborative partnership between permanent farm workers and their families , their employers , selected non-governmental organizations and the public health sector . In consultation with stakeholders , they developed an intervention primarily focusing on having peer selected trained lay health workers ( LHWs ) on farms , mentored and managed by nurses . PURPOSE To describe the complex process of implementation and evaluation of the LHW project , and provide a summary of a number of discrete studies evaluating the effectiveness , cost implication s , and the perceptions and experiences of key stakeholders of the intervention . METHODS Quantitative and qualitative research methods conducted within the context of a pragmatic unblinded community cluster r and omized control trial were used . Emphasis was placed on an iterative participatory interaction between the research ers and key stakeholders . RESULTS The intervention contributed to significantly better successful treatment completion rates among adult new smear-positive TB cases . The process implemented proved cost-effective and was pivotal in initiating a community-based social development programme . CONCLUSIONS The use of peer-selected LHWs within a wider programme of integrated care design ed to merge technical biomedical approaches to disease management with more holistic social development activities , appears essential to meet the complex health needs in conjunction with public health of the rural poor" ]

[ "PURPOSE The objectives of this study were to examine 1 ) whether changes in total physical activity ( PA ; counts per minute , cpm ) and time spent in moderate to vigorous PA ( MVPA ) are associated with changes in adiposity and 2 ) whether energy intake influences the relationship between changes in PA and changes in adiposity in overweight Hispanic adolescents . METHODS Analysis included 38 overweight ( body mass index , > 85th percentile ) Hispanic adolescents with complete pretest and posttest data on relevant variables after participating in a 16-wk intervention . The intervention treatment did not influence PA , so the sample was combined and the r and omization group was adjusted for in the analysis . Body composition by dual-energy x-ray absorptiometry , 7-d PA by accelerometry , and dietary intake by 3-d diet records were assessed before and after intervention . RESULTS Within individuals , the mean increase of PA ( n = 19 ) and mean decrease of PA ( n = 19 ) was approximately 105 cpm . A 100-cpm increase in total PA was associated with a decrease of 1.3 kg of fat mass and 0.8 % body fat after adjusting for pretest adiposity , PA , age , sex , and treatment ( P total PA and fat mass and percent body fat . Changes in MVPA were not related to changes in adiposity after controlling for total PA ( P > 0.05 ) . CONCLUSIONS Increasing total PA by 28 % ( 100 cpm ) was associated with a decrease of 1.4 kg of fat mass and 1 % body fat for 16 wk in overweight Hispanic adolescents independent of intervention group assignment . Increases in total PA , compared with MVPA , may be sufficient to improve body composition in overweight Hispanic adolescents", "BACKGROUND Few successful treatment modalities exist to address childhood obesity . Given Latinos ' strong identity with family , a family-focused intervention may be able to control Latino childhood obesity . PURPOSE To assess the feasibility and effectiveness of a family-centered , primary care-based approach to control childhood obesity through lifestyle choices . DESIGN R and omized waitlist controlled trial in which control participants received the intervention 6 months after the intervention group . SETTING / PARTICIPANTS Forty-one Latino children with BMI > 85 % , aged 9 - 12 years , and their caregivers were recruited from an urban community health center located in a predominantly low-income community . INTERVENTION Children and their caregivers received 6 weeks of interactive group classes followed by 6 months of culturally sensitive monthly in-person or phone coaching to empower families to incorporate learned lifestyles and to address both family and social barriers to making changes . MAIN OUTCOMES MEASURES Caregiver report on child and child self-reported health-related quality of life ( HRQoL ) ; metabolic markers of obesity ; BMI ; and accelerometer-based physical activity were measured July 2010-November 2011 and compared with post-intervention assessment s conducted at 6 months and as a function of condition assignment . Data were analyzed in 2012 . RESULTS Average attendance rate to each group class was 79 % . Socio-environmental and family factors , along with knowledge , were cited as barriers to changing lifestyles to control obesity . Caregiver proxy and child self-reported HRQoL improved for both groups with a larger but not nonsignificant difference among intervention vs control group children ( p=0.33 ) . No differences were found between intervention and control children for metabolic markers of obesity , BMI , or physical activity . CONCLUSIONS Latino families are willing to participate in group classes and health coaching to control childhood obesity . It may be necessary for primary care to partner with community initiatives to address childhood obesity in a more intense manner . TRIAL REGISTRATION This study is registered at Clinical trials.partners.org 2009P001721", "A quasi-experimental design was used to test the outcomes of an exercise program directed towards Black and Hispanic college-age women . Forty-four women ( 36 Black , 7 Hispanic , and 1 Black/Hispanic ) attended exercise classes three times per week for 16 weeks . At program completion , women were classified as either high attendees ( n = 26 ) or low attendees ( n = 18 ) . Compared to low attendees , the high attendees had significantly higher exercise self-efficacy ( p ( all p improved significantly in the high attendance group following the program ( p < .001 ) and at 8 weeks post-program completion ( p = .01 )", "The majority of programs design ed to promote physical activity in older Hispanic women includes few innovative theory-based interventions that address cultural relevant strategies . The purpose of this report is to describe the design and baseline data for Mujeres en Accion , a physical activity intervention to increase regular physical activity , and cardiovascular health outcomes among older Hispanic women . Mujeres en Accion [ Women in Action for Health ] , a 12 month r and omized controlled trial to evaluate the effectiveness of a social support physical activity intervention in midlife and older Hispanic women . This study tests an innovative intervention , Mujeres en Accion , and includes the use of a theory-driven approach to intervention , explores social support as a theoretical mediating variable , use of a Promotora model and a Community Advisory group to incorporate cultural and social approaches and re sources , and use of objective measures of physical activity in Hispanic women", "BACKGROUND There is little consensus on how many hours of accelerometer wear time is needed to reflect a usual day . This study identifies the bias in daily physical activity ( PA ) estimates caused by accelerometer wear time . METHODS 124 adults ( age = 41 ± 11 years ; BMI = 27 ± 7 kg·m⁻² ) contributed approximately 1,200 days accelerometer wear time . Five 40 day sample s were r and omly selected with 10 , 11 , 12 , 13 , and 14 h·d⁻¹ of wear time . Four semisimulation data sets ( 10 , 11 , 12 , 13 h·d⁻¹ ) were created from the reference 14 h·d⁻¹ data set to assess Absolute Percent Error ( APE ) . Repeated- measures ANOVAs compared min·d⁻¹ between 10 , 11 , 12 , 13 h·d⁻¹ and the reference 14 h·d⁻¹ for inactivity ( light ( 100 - 1951 cts·min⁻¹ ) , moderate ( 1952 - 5724 cts·min⁻¹ ) , and vigorous ( ≥5725 cts·min⁻¹ ) PA . RESULTS APE ranged from 5.6%-41.6 % ( 10 h·d⁻¹ = 28.2%-41.6 % ; 11 h·d⁻¹ = 20.3%-36.0 % ; 12 h·d⁻¹ = 13.5%-14.3 % ; 13 h·d⁻¹ = 5.6%-7.8 % ) . Min·d⁻¹ differences were observed for inactivity , light , and moderate PA between 10 , 11 , 12 , and 13 h·d⁻¹ and the reference ( P minimum accelerometer wear time of 13 h·d⁻¹ is needed to provide a valid measure of daily PA when 14 h·d⁻¹ is used as a reference", "BACKGROUND Minority girls are disproportionately affected by overweight and obesity . The independent effects of physical activity ( PA ) , sedentary behavior ( SB ) , and diet are not well understood . OBJECTIVE This study examined the individual influences of PA , SB and diet on fat mass in Latina and African American ( AA ) girls , aged 8 - 11 . METHODS Baseline data from a longitudinal cohort study in minority girls is presented . Multiple linear regression analysis assessed the effects of PA , SB , and energy intake on fat mass , adjusting for lean mass , age , Tanner stage and ethnicity . RESULTS Participants were 53 Latina and AA girls ( 77 % Latina ; M age=9.8 + /- .9 ; M ( BMI % ) = 80.8 + /- 23.1 ) . Moderate-to-vigorous physical activity ( MVPA ) by accelerometry ( beta= -.13 , P lean mass ( beta=.69 , P MVPA by 3-day-physical-activity-recall ( beta=-.04 , P=.01 ) and lean mass ( beta=.75 , P SB and energy intake were not associated with fat mass in any model . CONCLUSION Using both objective and subjective measures of PA , MVPA , but not SB or diet , was associated with higher fat mass in Latina and AA girls , independent of lean mass , age , Tanner stage , and ethnicity . Prospect i ve studies are needed to clarify the differential impact of diet and activity levels on adiposity in this population", "OBJECTIVE A r and omized controlled pilot study to test the hypothesis that increasing preschool children 's outdoor free play time increases their daily physical activity levels . METHODS Physical activity was assessed by accelerometers for four consecutive school days in thirty-two Latino children ( 3.6+/-0.5 years ) attending a preschool for low-income families . After two days of baseline physical activity assessment , participants were r and omly assigned to an intervention ( RECESS ; n = 17 ) or control ( CON ; n = 15 ) group . The RECESS group received two additional 30-minute periods of outdoor free play time per day for two days . The CON group followed their normal classroom schedule . Between group differences in physical activity variables were tested with a Wilcoxon rank-sum test . RESULTS There were no statistically significant differences between groups in changes from baseline in average total daily ( CON , 48.2+/-114.5 ; RECESS , 58.2+/-74.6 ) and during school day ( CON , 64.6+/-181.9 ; RECESS , 59.7+/-79.1 ) counts per minute , or total daily ( CON , 0.4+/-1.3 ; RECESS , 0.3+/-0.8 ) and during school day ( CON , 0.6+/-2.1 ; RECESS , 0.5+/-0.8 ) percent of time spent in moderate to vigorous physical activity . CONCLUSIONS Substantially increasing preschoolers ' outdoor free play time did not increase their physical activity levels", "PURPOSE To examine whether components of body composition ( size , fat mass , and fat-free mass ) were related to physical activity . METHODS A r and om sample of 60 eligible sixth grade girls at each of 36 schools ( six schools per region and six regions in total sample ) ; complete measurements on 1,553 girls . Physical activity was assessed over 6 d in each girl using an accelerometer , and body composition was assessed using a multiple regression equation using body mass index and triceps skinfold . Minutes of moderate-to-vigorous and vigorous physical activity were estimated from accelerometer counts per 30 s above threshold values determined from a previous study . RESULTS Significant inverse relationships were found for all measures of body size and composition and all physical activity indices . The combination of fat and fat-free mass expressed as a weight and as an index ( divided by height squared ) along with race , SES , site , and school were most highly associated with physical activity in multiple regression analysis , accounting for 14 - 15 % of the variance in physical activity . Fat mass was more closely related to moderate-to-vigorous physical activity ( MVPA ) and vigorous physical activity ( VPA ) than fat-free mass with higher st and ardized regression coefficients . CONCLUSION We conclude that both fat mass or fat mass index as well as fat-free mass or fat-free mass index make independent contributions in association with physical activity levels . These indices are recommended for future studies", "Acute effects of high-sugar/low-fiber meals vs low-sugar/high-fiber meals on hormones and behavior were studied in 10 overweight Latina females , age 11 to 12 years , using a crossover design . In this exploratory pilot study , participants arrived fasted at an observation laboratory on two occasions and r and omly received either a high-sugar/low-fiber meal or a low-sugar/high-fiber meal at each visit . Glucose , insulin , and leptin were assayed from serum drawn at 0 , 15 , 30 , 60 , 90 , and 120 minutes . Ad libitum snacks were provided at 120 minutes . Physical activity was measured using an observational system that provides data on time spent lying down , sitting , st and ing , walking , and in vigorous activity . Data were collected between March 2005 and July 2006 . In the high-sugar/low-fiber condition , glucose and leptin levels decreased more slowly , glucose levels were higher at 60 minutes ( 111.2 mg/dL vs 95.4 mg/dL , P=0.03 ) , and leptin levels were higher at 90 minutes ( 49.3 ng/mL vs 46.7 ng/mL , P=0.017 ) than in the low-sugar/high-fiber condition . Meals did not affect insulin or ad libitum dietary intake . Sitting , st and ing , lying down , and vigorous activity differed by condition , but not walking . Participants were significantly more active in the first 30 to 60 minutes after the high-sugar/low-fiber meal , but after 60 minutes there was a trend for activity to be lower after the high-sugar/low-fiber meal vs the low-sugar/high-fiber meal . High-sugar meals sustain glucose and leptin levels longer , which may play an important role in modulating levels of physical activity in this group at high risk for obesity-related disease", "BACKGROUND Increasing moderate-to-vigorous-intensity physical activity ( MVPA ) is an important public health goal . Pedometers are evidence -based devices for increasing daily activity , but studies have not evaluated the comparative efficacy of step cadence goals for increasing MVPA . PURPOSE This study aim ed to evaluate the efficacy of three pedometer-based step goals for increasing MVPA . METHODS Latina women ( n = 180 ; 18 - 55 yr , mean body mass index = 31.1 , SD = 6.5 ) were recruited to 12 community centers , which were r and omly assigned to one of three conditions . Each group received an identical 12-wk theory-based physical activity ( PA ) intervention that differed only on the type of daily step goal : 1 ) a self-selected goal ( SELF ) ; 2 ) a goal of 10,000 steps per day ( FREQUENCY ) ; or 3 ) a goal of 3000 steps in 30 min ( CADENCE ) . Accelerometer-based PA was measured at baseline and after 12 wk . RESULTS Adjusted multilevel pattern-mixture models using generalized estimating equations revealed that participants in the CADENCE condition engaged in similar levels of postintervention MVPA to those in the SELF and FREQUENCY goal conditions . However , MVPA of participants in the CADENCE condition was more likely to occur in bouts lasting greater than 10 consecutive minutes compared with the MVPA of participants in the SELF ( P = 0.01 ) or FREQUENCY ( P = 0001 ) conditions . CONCLUSIONS PA interventions should consider including a step cadence goal to help individuals accumulate bout-based MVPA and meet national PA guidelines", "OBJECTIVE : The goal of this study was to examine activity pattern associations between Hispanic parents and their preschool-aged children . METHODS : We examined baseline data collected as part of a r and omized controlled trial . Self-defined Hispanic parents with children aged 3 to 5 years were r and omly assigned to either a weekly healthy lifestyle group ( intervention ) or a monthly school-readiness group ( control ) for 3 months . There were no weight eligibility criteria . All participants were instructed to wear an accelerometer for up to 7 consecutive days to measure physical activity . RESULTS : Of the 106 dyads enrolled in the study , 80 children and 85 parents provided useable actigraphy data . Mean percentage of time spent in sedentary behaviors was 82.0 % ( SD : 10.4 ) for parents and 69.8 % ( SD : 18.5 ) for preschool-aged children . Percentage of awake time per day spent in sedentary behavior was strongly correlated for parents and children ( r = 0.597 ; P activity level were large ( r = 0.895 and 0.739 for low and moderate activity levels , respectively ) , except for vigorous activity level , for which the parent-child correlation was nonsignificant ( P = .64 ) because of a near-0 level of vigorous parental activity . Child 's age ( P = .81 ) and gender ( P = .43 ) were nonsignificant predictors of child activity levels . CONCLUSIONS : These results suggest that parental activity levels are a powerful explanation of preschool-aged child activity levels , except for vigorous activity , which children do on their own without parental participation . Hispanic parents play a critical role in setting physical activity patterns in their children" ]

[ "Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people . Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures , as proved by Decalyos I. Decalyos II is a 2-year , multicenter , r and omized , double-masked , placebo-controlled confirmatory study . The intention-to-treat population consisted of 583 ambulatory institutionalized women ( mean age 85.2 years , SD = 7.1 ) r and omized to the calcium – vitamin D3 fixed combination group ( n= 199 ) ; the calcium plus vitamin D3 separate combination group ( n= 190 ) and the placebo group ( n= 194 ) . Fixed and separate combination groups received the same daily amount of calcium ( 1200 mg ) and vitamin D3 ( 800 IU ) , which had similar pharmacodynamic effects . Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent , with levels returning within the normal range after 6 months . In a subgroup of 114 patients , femoral neck bone mineral density ( BMD ) decreased in the placebo group ( mean = –2.36 % per year , SD = 4.92 ) , while remaining unchanged in women treated with calcium-vitamin D3 ( mean = 0.29 % per year , SD = 8.63 ) . The difference between the two groups was 2.65 % ( 95 % CI = –0.44 , 5.75 % ) with a trend in favor of the active treatment group . No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis . The relative risk ( RR ) of HF in the placebo group compared with the active treatment group was 1.69 ( 95 % CI = 0.96 , 3.0 ) , which is similar to that found in Decalyos I ( RR = 1.7 ; 95 % CI = 1.0 , 2.8 ) . Thus , these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women", "The effects of calcium supplementation ( as calcium citrate malate , 1000 mg elemental Ca/d ) with and without the addition of zinc ( 15.0 mg/d ) , manganese ( 5.0 mg/d ) and copper ( 2.5 mg/d ) on spinal bone loss ( L2-L4 vertebrae ) was evaluated in healthy older postmenopausal women ( n = 59 , mean age 66 y ) in a 2-y , double-blind , placebo-controlled trial . Changes ( mean + /- SEM ) in bone density were -3.53 + /- 1.24 % ( placebo ) , -1.89 + /- 1.40 % ( trace minerals only ) , -1.25 + /- 1.46 % ( calcium only ) and 1.48 + /- 1.40 % ( calcium plus trace minerals ) . Bone loss relative to base-line value was significant ( P = 0.0061 ) in the placebo group but not in the groups receiving trace minerals alone , calcium alone , or calcium plus trace minerals . The only significant group difference occurred between the placebo group and the group receiving calcium plus trace minerals ( P = 0.0099 ) . These data suggest that bone loss in calcium-supplemented , older postmenopausal women can be further arrested by concomitant increases in trace mineral intake", "BACKGROUND Low-energy fractures of the hip , forearm , shoulder , and spine are known consequences of osteoporosis . OBJECTIVE We evaluated the effect of 1 y of treatment with calcium and vitamin D on bone mineral density ( BMD ) and bone markers in patients with a recent low-energy fracture . DESIGN In a double-blinded design , patients with fracture of the hip ( lower-extremity fracture , or LEF ) or upper extremity ( UEF ) were r and omly assigned to receive 3000 mg calcium carbonate + 1400 IU cholecalciferol or placebo ( 200 IU cholecalciferol ) . BMD of the hip ( HBMD ) and lumbar spine ( LBMD ) were evaluated by dual-energy X-ray absorptiometry , and physical performance was assessed by the timed Up & Go test . Serum concentrations of 25-hydroxycholecalciferol , parathyroid hormone ( PTH ) , telepeptide of type I collagen ( ICTP ) , osteocalcin , and N-terminal propeptide of collagen type I were measured . RESULTS A total of 122 patients were included ( 84 % women ; x + /- SD age : 70 + /- 11 y ) ; 68 % completed the study . In an intention-to-treat analysis , LBMD increased in the intervention group and decreased in the placebo group , and the difference between the groups was significant after 12 mo : 0.931 + /- 0.211 compared with 0.848 + /- 0.194 ( P HBMD . The effect of treatment was more pronounced in patients aged The intervention decreased bone turnover . PTH was significantly lower in the intervention group ( P ICTP and change in LBMD were significantly related to physical performance . CONCLUSIONS A 1-y intervention with calcium and vitamin D reduced bone turnover , significantly increased BMD in patients younger than 70 y , and decreased bone loss in older patients . The effect of treatment was related to physical performance", "Three hundred ten normal postmenopausal volunteers were invited to enter a controlled trial of the effects of calcium supplementation on forearm mineral content ( FMC ) ; 269 entered the study and 210 completed it . Of those who completed the study , 158 were allocated to one of three calcium-supplemented treatment regimes and 52 were allocated to a control group . Twenty-two of the subjects allocated to the treatment group were unable to take supplementary calcium but agreed to remain in the study as additional controls . There were therefore 136 treated subjects , 52 strict controls and 74 controls altogether . During the initial observation period of 9 mo , there was a highly significant loss of bone in all groups ( P less than 0.001 ) . During the 9-mo period of treatment , there was a highly significant reduction in the rate of bone loss in the treated subjects ( P less than 0.001 ) , a just significant reduction in the strict controls ( P less than 0.05 ) and a nonsignificant reduction in the rate of loss in all controls . The difference between the treated and strict controls in the second period was not significant but the difference between the treated and all controls in the second period was significant ( P less than 0.025 ) . When the analysis was applied only to women within 10 yr of menopause , the difference between the treated and strict control groups in period 2 was significant ( P less than 0.025 ) and the difference between the treated and all controls was highly significant ( P less than 0.001 )", "The purpose of this study was to ( 1 ) quantify the healing process of the human osteoporotic proximal humerus fracture ( PHF ) expressed in terms of callus formation over the fracture region using BMD scanning , and ( 2 ) quantify the impact of medical intervention with vitamin D3 and calcium on the healing process of the human osteoporotic fracture . The conservatively treated PHF was chosen in order to follow the genuine fracture healing without influence of osteosynthetic material s or casts . Thirty women ( mean age = 78 years ; range = 58–88 ) with a PHF , osteoporosis or osteopenia ( based on a hip scan , WHO criteria ) , and not taking any drugs related to bone formation , including calcium or vitamin D supplementation , were r and omly assigned to either oral 800 IU vitamin D3 plus 1 g calcium or placebo , in a double-blind prospect i ve study . We measured biochemical , radiographic , and bone mineral density effect parameters to evaluate the impact on the healing process . Scanning procedures of the fractured shoulder included use of a fixation device to obtain the highest possible precision . Double scans of the fractured shoulder revealed a coefficient of variation ( CV ) on BMD measurements that improved from 2.8 % immediately after fracture occurrence to 1.7 % at 12 weeks ( P = 0.003 ) approaching the 1.2 % levels observed over the healthy shoulder . BMD was similar in the two groups at baseline ( active 0.534 g/cm2 vs. placebo 0.518 g/cm2 ) , and both increased over the 12-week observation period , with peak levels in week 6 . By week 6 BMD levels were higher in the active group ( 0.623 g/cm2 ) compared with the placebo group ( 0.570 g/cm2 , P = 0.006 ) . Thirty seven percent of the patients presented with vitamin D levels below 30 nmol/l , indicative of mild vitamin D insufficiency . In conclusion , we have demonstrated that it is possible to quantify callus formation of the PHF with sufficiently high precision to demonstrate the positive influence of vitamin D3 and calcium over the first 6 weeks after fracture . Whether this results in more stable fractures , extends to other fracture types , or applies to other osteogenic bone agents such as bisphosphonates remains to be examined", "Abstract : Trabecular bone density at the distal radius and cortical bone density at the midradius were measured in four r and omized groups of women before and after 4 months administration of AAACa , oyster shell heated under reduced pressure with addition of heated algal ingredient ( HAI ) ( group A ) ; AACa , the same preparation without HAI ( group B ) ; CaCO3 ( group C ) ; and placebo ( group D ) in a double-blind system using peripheral quantitative computed tomography ( pQCT ) with lumbar spine density measurement by dual-energy X-ray absorptiometry ( DXA ) . Groups A , B , and C received 900 mg/day elemental calcium and D received none . In subjects of group A , but not B , C , and D , radial trabecular bone density increased significantly , to 106.2 % ± 2.1 % of the initial value ( mean ± SEM ) . The increase of trabecular bone density was significantly different from the placebo group ( D ) only in AAACa ( group A ) and not in AACa ( group B ) and the calcium carbonate ( group C ) . Cortical bone density increase was also greater in group A ( but not in B and C ) than in D. Lumbar spine density did not change significantly . AAACa was apparently more effective , increasing trabecular bone density more than AACa and CaCO3 containing the same amount of elemental calcium", "Ca supplements are used for bone health ; however , they have been associated with increased cardiovascular risk , which may relate to their acute effects on serum Ca concentrations . Microcrystalline hydroxyapatite ( MCH ) could affect serum Ca concentrations less than conventional Ca supplements , but its effects on bone turnover are unclear . In the present study , we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca , phosphate , parathyroid hormone and bone turnover markers . We r and omised 100 women ( mean age 71 years ) to 1 g/d of Ca as citrate or carbonate ( citrate-carbonate ) , one of two MCH preparations , or a placebo . Blood was sample d for 8 h after the first dose , and after 3 months of daily supplementation . To determine whether the acute effects changed over time , eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months . There were no differences between the citrate and carbonate groups , or between the two MCH groups , so their results were pooled . The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h , and this was not diminished after 3 months . MCH increased ionised Ca concentrations less than the citrate-carbonate dose ; however , it raised the concentrations of phosphate and the Ca-phosphate product . The citrate-carbonate and MCH doses produced comparable decreases in bone resorption ( measured as serum C-telopeptide ( CTX ) ) over 8 h and bone turnover ( CTX and procollagen type-I N-terminal propeptide ) at 3 months . These findings suggest that Ca preparations , in general , produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover", "Increased postmenopausal bone turnover leads to bone loss and fragility fracture risk . In the absence of osteoporosis , risk preventive measures , particularly those modifying nutritional lifestyle , are appropriate . We tested the hypothesis that milk supplementation affects bone turnover related to biochemical markers in a direction that , in the long term , may be expected to reduce postmenopausal bone loss . Thirty healthy postmenopausal women aged 59.3 ( SD 3.3 ) years were enrolled in a prospect i ve crossover trial of 16 weeks . After a 4-week period of adaptation with diet providing 600 mg calcium plus 300 mg ingested as 250 ml semi-skimmed milk , participants were maintained during 6 weeks under the same 600 mg calcium diet and r and omized to receive either 500 ml semi-skimmed milk , thus providing a total of 1200 mg calcium , or no milk supplement . In the next 6 weeks they were switched to the alternative regimen . At the end of the each period , i.e. after 4 , 10 and 16 weeks , blood and urinary sample s were collected . The changes in blood variables between the periods of 6 weeks without and with milk supplementation were : for parathyroid hormone , -3.2 pg/ml ( P=0.0054 ) ; for crosslinked telopeptide of type I collagen , -624 pg/ml ( P propeptide of type I procollagen , -5.5 ng/ml ( P=0.0092 ) ; for osteocalcin , -2.8 ng/ml ( P=0.0014 ) . In conclusion , a 6-week period of milk supplementation induced a decrease in several biochemical variables compatible with diminished bone turnover mediated by reduction in parathyroid hormone secretion . This nutritional approach to postmenopausal alteration in bone metabolism may be a valuable measure in the primary prevention of osteoporosis", "During a two-year study , we examined the effect of calcium supplementation on postmenopausal bone loss in 43 women in the early postmenopausal period who were assigned to one of three treatment groups : percutaneous 17 beta-estradiol ( combined with progesterone during the second year ) , oral calcium ( 2000 mg daily ) , and placebo . All participants were examined every three months . Bone mineral content in the forearm ( measured by single-photon absorptiometry ) and in the entire body and spine ( measured by dual-photon absorptiometry ) remained constant in the estrogen-treated group but decreased significantly in the groups receiving calcium and placebo . In the calcium-treated group , we observed a tendency toward a slowed loss of compact bone ( in the proximal forearm and total skeleton ) as compared with the placebo group , while the rate of loss of trabecular bone ( the distal forearm and spine ) was the same as in the placebo group . Our preliminary data suggest that calcium supplementation in the dosage we used is not as effective as estrogen therapy for the prevention of early postmenopausal bone loss . Calcium supplementation may have had a minor effect on the loss of cortical bone , but it had no effect on the trabecular bone", "OBJECTIVE To evaluate three different therapeutic regimens for the prevention of osteoporosis in natural and surgical postmenopausal women who had been found to have rapid bone loss in analytical studies . METHODS A total of 104 naturally or surgically postmenopausal women were studied , and subsequently followed-up during 1 year for avoidance of the influence of seasonal variation on bone mass , a factor overlooked in several studies . They were r and omized into four groups of 26 patients each : the untreated control group ( mean age 50 + /- 5 years ) ; the hormonal replacement treatment ( HRT ) group ( mean age 48 + /- 6 years ) , which was treated for 24 days each month with transdermal 17 beta-estradiol , 50 mg/day , together with medroxiprogesterone , 10 mg during 12 days ; the calcium group ( mean age 50 + /- 4 years ) , which was treated with elemental calcium , 1 g/day ; and the calcitonin group ( mean age 50 + /- 5 years ) , which was treated for 10 days each month with eel calcitonin , 40 IU/day and with elemental calcium , 500 mg/day . Full-body bone densitometry , for measuring total body bone mineral content ( TB BMC ) , was carried out in all the women at baseline and 1 year . TB BMC was corrected for body weight by dividing its value by body weight ( TB BMC /W ) . RESULTS After 1 year TB BMC /W was lower in every group : -2.14 % ( P postmenopausal loss of bone mass", "Postmenopausal bone loss is a major factor in the increasing prevalence of osteoporotic fractures . Evidence is abundant that hormonal replacement therapy prevents the bone loss that follows natural or surgical menopause and reduces the prevalence of osteoporotic fractures in later life [ 1 - 4 ] . However , only about 10 % of American women elect to receive replacement therapy because of attitudes of physicians and patients , the undesirability of menstrual bleeding , and unresolved questions about the relation of the use of estrogen to breast cancer [ 5 ] . Moreover , the duration of hormonal therapy may need to be prolonged because bone loss recurs when therapy is discontinued , yet the incidence of some adverse effects increases with the duration of estrogen use . Safer alternatives to estrogen use have been sought . Epidemiologic and cross-sectional studies have suggested that increasing calcium intake might prevent postmenopausal bone loss , and prospect i ve studies have yielded conflicting results [ 6 - 17 ] . Moreover , some investigators have suggested that effects differ on the various skeletal sites used to determine the rate of bone loss [ 18 ] . We compared the efficacy of calcium augmentation in early postmenopause with calcium augmentation plus hormonal replacement therapy and with placebo . The study had a three-arm , r and omized , parallel design . The patients receiving hormonal replacement therapy were obviously not blinded nor were their physicians , whereas the placebo and calcium groups were double blinded . Methods Healthy , white women between 6 months and 6 years after a natural menopause were recruited to participate in the study . The protocol was approved by the Human Investigation Review Committees of Winthrop-University Hospital and Brookhaven National Laboratory ; written informed consent was obtained from each participant . Participants were recruited by announcements in the local press and in hospital and university publications and through a direct mail campaign . All participants had a history and physical examination . Exclusion characteristics included any disorder known to affect bone metabolism such as glucocorticoid use , gastrointestinal disease , or any chronic illness . Previous or current malignancy was an exclusion characteristic as were absolute contraindications to estrogen replacement or calcium supplements . Absolute contraindications to estrogen replacement therapy included estrogen-dependent neoplasm ( breast or uterus ) , undiagnosed vaginal bleeding , thrombophlebitis or thromboembolism , and acute liver disease . Women with the following problems considered by some investigators to be relative contraindications to estrogen therapy were also excluded : gallbladder disease , history of liver disease , first-degree relatives with breast cancer , and hypertension . Calcium urolithiasis was also an exclusion factor . Women with known osteoporosis or with a vertebral compression fracture were not eligible for the study . One hundred eighteen women entered the study . The women were r and omly assigned to three groups : 1 ) hormonal replacement [ estrogen-progesterone-calcium carbonate ] , 2 ) calcium carbonate , or 3 ) placebo . Assignment to the groups was based on computer-generated r and om numbers provided by the statistician , with stratification for years postmenopause . The women in the hormonal replacement group took conjugated equine estrogens ( Premarin , Wyeth-Ayerst Laboratories , Inc. ; Philadelphia , Pennsylvania ) , 0.625 mg daily for 25 days of the month along with medroxyprogesterone ( Provera , Upjohn ; Kalamazoo , Michigan ) , 10 mg from days 16 to 25 . All women received 400 IU of vitamin D daily in the form of a multivitamin , and calcium supplementation ( as Caltrate , Lederle ; Clifton , New Jersey ) was provided to the two treatment groups . The duration of the study was 2.9 1.1 years ( mean SD ) . A 7-day dietary history was review ed with a nutritionist every 2 months ; calcium was provided as calcium carbonate , 600 mg ( Caltrate ) , and used to supplement the diet to approximate a total daily intake of 1700 mg of elemental calcium ( the mean + 2 SD found by Heaney and colleagues [ 7 ] to result in zero calcium balance in estrogen-deprived women ) . The calcium supplements were taken with meals in divided doses . The placebo appeared identical to the calcium carbonate tablets . No patients took antacids or histamine-2 blockers . All women had a baseline mammogram . Measurements Routine laboratory studies included a complete blood count , urinalysis , and serum fasting calcium , phosphorus , urea nitrogen , creatinine , alkaline phosphatase , cholesterol , and aminotransferase measurements [ 19 , 20 ] . In addition , follicle-stimulating hormone , estradiol , parathyroid hormone , osteocalcin , free thyroxine , and bone alkaline phosphatase were measured , and a urine specimen was collected after an overnight fast for hydroxyproline , calcium , and creatinine determinations , following a 3-day low-hydroxyproline diet [ 21 - 23 ] . Total body calcium was measured annually in the participants , using the delayed neutron activation method at Brookhaven National Laboratory [ 24 , 25 ] . This method uses a whole-body counter to measure the characteristic rays emitted from the neutron capture of Calcium-48 ( natural abundance of 0.187 % ) in the body . The Brookhaven National Laboratory whole-body counter was up grade d in 1987 to use 32 NaI ( T1 ) detectors of 10 cm 10 cm 46 cm positioned symmetrically above and below the patient [ 25 ] . The activated isotope , Calcium-49 , decays with a half-life of 8.72 minutes , emitting a 3.08 MeV characteristic line . More than 99.5 % of the body calcium is contained in the bone [ 26 ] . The method provides total body calcium with a coefficient of variation of about 1.5 % when no substantial change in the body weight occurs during the period of repeated studies . The measurements were made annually . The bone mineral density of the distal radius site was measured using a Lunar Radiation ( Madison , Wisconsin ) single-photon absorptiometer ( SP2 ) . Bone mineral density of the spine ( L2-L4 ) and femur ( neck , trochanter , and Ward triangle ) was measured using a Lunar Radiation DP4 dual-photon absorptiometer . The software version used for the analysis of scans was DP4 Lunar Corporation Version 1.1 . All scans were analyzed using the same software version , which corrects for source decay . Instruments were calibrated daily , and the radioactive source was changed annually . Each measurement was done every 6 months . The coefficient of variation of these measurements was 2 % , except for the Ward triangle ( 2.5 % ) . Activity was measured using activity monitors ( large-scale integrated monitors ) , which were worn about the waist [ 27 ] . The average of 2 weekdays and 1 weekend day was used as an activity score . Activity was measured at baseline and at one other point during the study to ensure that differences among the groups were not due to varied levels of exercise . Statistical Analysis Total body calcium was selected as the primary criterion for efficacy for the following reasons : It measures mass rather than density per unit area ; it measures calcium balance precisely and accurately in the free living state and may be better related to previous studies using the balance technique ; it is more precise than the other measurements ; and it avoids sampling error by measuring the entire skeleton rather than a specific region of the appendicular or axial skeleton . The rate of change in bone mineral was calculated for each woman at each of the sites used in the study . St and ard linear regression procedures were used to estimate the rate of bone mineral change for each woman , and the regression intercept was used as the best estimate of the baseline value . Because some women terminated their participation in the study before others , the rate-of-change data were weighted by the inverse variance to reflect the fit of the regression line for each woman [ 28 ] . Analyses of covariance were done using body mass index , activity scores , cigarette smoking , calcium intake , age , and years postmenopause as covariates . The data reported in this article are based on all women who provided at least three observations for a particular skeletal site . We considered other criteria , such as using data only from women who had participated in the study for at least 2 years , and all data analyses were done for this subgroup as well . The results of these analyses were invariably similar to those reported here and therefore are not presented separately . The mean rates of change in bone mineral for each condition at each site were characterized in terms of both raw units and percentages ; separate analyses were carried out for each . The two indices were similar . Evidence from recent research is substantial that estrogen replacement therapy is effective , whereas the efficacy of calcium supplements is question able . Our expectation was that our data would confirm the efficacy of estrogen-progesterone-calcium therapy , and the critical question was whether or not a beneficial effect of calcium supplements given alone could be shown . A separate one-way analysis of covariance was done for each of the bone mineral measurements to compare the mean rates of change in bone mineral for each of the three conditions . We used two a priori contrasts : the first contrasting women taking estrogen with those receiving calcium and the second comparing women receiving calcium supplements with those on placebo . All P values reported are two-tailed . Results Baseline data for historical data and bone mineral measurements and chemical studies are given in Table 1 . Analysis of variance showed no significant differences in the baseline variables . The initial and final activity scores did not differ significantly . Table 1 . Baseline Values for Patient Characteristics , Bone Mineral Measurements , and Chemical Variables The range of initial daily calcium intake in the overall study group was 150 to 1263 mg ; in the calcium augmentation group , it was 222 to", "This placebo-controlled r and omized trial was conducted to ascertain the value of calcium citrate supplementation in averting bone loss in 63 postmenopausal women , 57 of whom were early postmenopausal ( five years after menopause ) and six of whom were mid-postmenopausal ( five to ten years after menopause ) . Bone density data were available for 25 women who took 800 mg of calcium citrate daily and 31 women who received placebo for one to two years . The two groups were similar in baseline age , years postmenopause ( 3.3 in the calcium citrate group vs 2.7 in the placebo group ) , height , weight , calcium intake , and L2-L4 bone density . L2-L4 bone density did not change during calcium citrate treatment ( + 1.03 % after two years ) , whereas it declined significantly by -2.38 % after two years on placebo ( P Femoral neck bone density did not change in either group . Radial shaft bone density did not change in the calcium citrate group ( -0.02 % after two years ) , but it declined significantly in the placebo group ( -1.79 % after one year and -3.03 % after two years , P in bone density of the L2-L4 vertebrae and radial shaft after two years of treatment was significant between the two groups . An analysis of covariance disclosed no significant effect of calcium citrate on L2-L4 bone density during the first three years after menopause , but a protective effect after three years . Although serum PTH did not change , serum and urinary calcium increased and serum calcitriol and urinary phosphorus decreased in the calcium citrate group , indicative of parathyroid suppression . Serum bone-specific alkaline phosphatase and osteocalcin , and urinary hydroxyproline and N-telopeptide decreased during some calcium citrate treatment periods , indicative of a reduction in bone turnover . Thus , calcium citrate supplementation ( 400 mg of calcium twice daily ) averted bone loss and stabilized bone density in the spine , femoral neck , and radial shaft in women relatively soon after menopause . This bone-sparing action was probably due to the inhibition of bone resorption from parathyroid suppression", "CONTEXT Effects of long-term calcium , with or without vitamin D , on hip bone mineral density ( BMD ) and bone turnover in sunny climates have not been reported . OBJECTIVE The aim was to evaluate the effect of vitamin D added to calcium supplementation on hip dual-energy x-ray absorptiometry BMD and calcium-related analytes . DESIGN , SETTING , AND PARTICIPANTS The study was a 5-yr r and omized , controlled , double-blind trial of 120 community-dwelling women aged 70 - 80 yr . INTERVENTIONS The interventions were 1200 mg/d calcium with placebo vitamin D ( Ca group ) or with 1000 IU/d vitamin D2 ( CaD group ) , or double placebo ( control ) . MAIN OUTCOME MEASURES Hip BMD , plasma 25-hydroxyvitamin D , biomarkers of bone turnover , PTH , and intestinal calcium absorption were measured . RESULTS Hip BMD was preserved in CaD ( -0.17 % ) and Ca ( 0.19 % ) groups but not controls ( -1.27 % ) at yr 1 and maintained in the CaD group only at yr 3 and 5 . The beneficial effects were mainly in those with baseline 25-hydroxyvitamin D levels below the median ( 68 nmol/liter ) . At yr 1 , compared with controls , the Ca and CaD groups had 6.8 and 11.3 % lower plasma alkaline phosphatase , respectively ( P urinary deoxypyridinoline to creatinine ratio , respectively ( P PTH at 3 and 5 yr cf . controls ( 27.8 and 31.3 % , P PTH levels above the median ( 3.6 pmol/liter ) . Therapy did not affect intestinal calcium absorption at high carrier loads . CONCLUSIONS Addition of vitamin D to calcium has long-term beneficial effects on bone density in elderly women living in a sunny climate , probably mediated by a long-term reduction in bone turnover rate", "The effect of dietary calcium supplementation on bone mineral content was studied in 40 postmenopausal women with Colles ' fracture . The participants were divided into two groups which were given either placebo or 1 g of calcium per day . The bone mineral content of the femur was determined before and after 1 year of medication . Women with Colles ' fracture were found to have the same mineral content in the femur as age-matched controls without fractures . Calcium supplementation had no significant effect on the bone mineral content", "CONTEXT Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures , but its effects on fracture risk have not been studied for women without vertebral fractures . OBJECTIVE To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density ( BMD ) but no vertebral fractures . DESIGN R and omized , blinded , placebo-controlled trial . SETTING Eleven community-based clinical research centers . SUBJECTS Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less ( Hologic Inc , Waltham , Mass ) but no vertebral fracture ; 4432 were r and omized to alendronate or placebo and 4272 ( 96 % ) completed outcome measurements at the final visit ( an average of 4.2 years later ) . INTERVENTION All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol . Subjects were r and omly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial . MAIN OUTCOME MEASURES Clinical fractures confirmed by x-ray reports , new vertebral deformities detected by morphometric measurements on radiographs , and BMD measured by dual x-ray absorptiometry . RESULTS Alendronate increased BMD at all sites studied ( P clinical fractures from 312 in the placebo group to 272 in the intervention group , but not significantly so ( 14 % reduction ; relative hazard [ RH ] , 0.86 ; 95 % confidence interval [ CI ] , 0.73 - 1.01 ) . Alendronate reduced clinical fractures by 36 % in women with baseline osteoporosis at the femoral neck ( > 2.5 SDs below the normal young adult mean ; RH , 0.64 ; 95 % CI , 0.50 - 0.82 ; treatment-control difference , 6.5 % ; number needed to treat [ NNT ] , 15 ) , but there was no significant reduction among those with higher BMD ( RH , 1.08 ; 95 % CI , 0.87 - 1.35 ) . Alendronate decreased the risk of radiographic vertebral fractures by 44 % overall ( relative risk , 0.56 ; 95 % CI , 0.39 - 0.80 ; treatment-control difference , 1.7 % ; NNT , 60 ) . Alendronate did not increase the risk of gastrointestinal or other adverse effects . CONCLUSIONS In women with low BMD but without vertebral fractures , 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity . Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD", "A r and omized controlled trial was carried out to determine whether calcium supplementation and load-bearing exercise can increase or maintain bone mass in the elderly . Fifty Chinese women , aged 62–92 years , living in a hostel for the elderly in Hong Kong were r and omized to enter one of four treatment groups : ( I ) calcium supplementation of 800 mg ( as calcium lactate gluconate ) daily ; ( II ) load-bearing exercise four times a week plus a daily placebo tablet ; ( III ) calcium supplementation daily and load-bearing exercise four times a week ; ( IV ) a placebo tablet daily . The interventions went on for 10 months . The bone mineral density ( BMD ) was measured at three sites in the hip ( femoral neck , Ward 's triangle and intertrochanteric area ) and the L2–4 level of the spine . The percentage change in BMD in 10 months was used as the main outcome measurement . The parathyroid hormone level and indices of bone metabolism were also measured before and after 10 months of intervention . The BMD at Ward 's triangle and the intertrochanteric area increased significantly in subjects on calcium supplement ( p on bone loss at any site . However , the results of two-way analysis of variance showed a significant joint effect of calcium supplements and exercise at the femoral neck ( p The parathyroid hormone levels fell significantly in subjects on calcium supplements (p supplement in the form of calcium lactate gluconate was adequately absorbed in elderly Chinese women with a calcium intake of less than 300 mg per day . It was effective in reducing bone loss at the hip , and there may be interaction effects with exercise in maintaining bone density", "Current st and ard-dose calcium supplements ( eg , 1000 mg/d ) may increase the risk for cardiovascular events . Effectiveness of lower-dose supplements in preventing bone loss should thus be considered . This study aim ed to assess whether calcium supplements of 500 or 250 mg/d effectively prevent bone loss in perimenopausal and postmenopausal Japanese women . We recruited 450 Japanese women between 50 and 75 years of age . They were r and omly assigned to receive 500 mg of calcium ( as calcium carbonate ) , 250 mg of calcium , or placebo daily . Medical examinations conducted three times over a 2-year follow-up period assessed bone mineral density ( BMD ) of the lumbar spine and femoral neck . One-factor repeated measures ANOVA was used for statistical tests . Subgroup analyses were also conducted . Average total daily calcium intake at baseline for the 418 subjects who underwent follow-up examinations was 493 mg/d . Intention-to-treat analysis showed less dramatic decreases in spinal BMD for the 500-mg/d calcium supplement group compared to the placebo group ( 1.2 % difference over 2 years , p = 0.027 ) . Per- protocol analysis ( ≥80 % compliance ) revealed that spinal BMD for the 500-mg/d and 250-mg/d calcium supplement groups decreased less than the placebo group ( 1.6 % , p = 0.010 and 1.0 % , p = 0.078 , respectively ) , and that femoral neck BMD for the 500-mg/d calcium supplement group decreased less relative to the placebo group ( 1.0 % , p = 0.077 ) . A low-dose calcium supplement of 500 mg/d can effectively slow lumbar spine bone loss in perimenopausal and postmenopausal women with habitually low calcium intake , but its effect on the femoral neck is less certain . Calcium supplementation dosage should thus be reassessed . ( Clinical Trials Registry number : UMIN000001176 )", "Summary Eighteen months of daily consumption of milk containing 250 mg calcium prevented bone mineral density ( BMD ) loss at the hip and the femoral neck in postmenopausal Chinese women aged 45 to 65 . Introduction Estrogen-related bone loss in postmenopausal women can be prevented by the consumption of milk with high doses of calcium and soymilk with high doses of isoflavones . However , high doses of calcium and isoflavones may not be necessary to attain a beneficial effect of milk and soymilk on BMD . We hypothesized that BMD will increase in postmenopausal Chinese women who consume daily 250 mg calcium in milk or soymilk . Milk prevented bone loss at the hip and the femoral neck in postmenopausal Chinese women . Methods A total of 141 eligible Chinese women without osteoporosis , aged 45–65 , and postmenopausal for more than 2 years were r and omized into groups receiving for 18 months ( A ) milk with 250 mg calcium daily , ( B ) soymilk with 250 mg calcium daily , or ( C ) neither milk nor soymilk . Dual-energy X-ray absorptiometry measured the BMD of the spine and hip at 0 , 6 , 12 , and 18 months . Results The BMD in the hip ( 2.52 % ) and the femoral neck ( 2.82 % ) of the women consuming milk was significantly higher ( hip , P = 0.01 ; femoral neck , P reduction in BMD at all sites ; the reduction in BMD was only significant at the hip during 12 months ( P = 0.008 ) and at the femoral neck during 18 months ( P = 0.005 ) . Conclusions Daily consumption of milk containing 250 mg calcium over 18 months prevents BMD loss at the hip and the femoral neck in postmenopausal Chinese women", "OBJECTIVE To evaluate , in postmenopausal women who refuse hormone replacement therapy ( HRT ) , whether continuous administration of an osseinhydroxyapatite compound ( OHC ) reduces bone loss and protects from osteoporosis . STUDY DESIGN Sixty postmenopausal women were included in an open study and were allocated to three groups . The first group ( n = 19 ) received treatment consisting in 3.32 g/d of OHC per day , the second group ( n = 21 ) received 2.5 g of calcium carbonate per day , and the third group ( n = 20 ) was a treatment-free control group . Bone mineral density ( BMD ) , assessed by dual x-ray absorptiometry , was measured prior to and at 12 and 24 months of treatment . RESULTS Subjects on OHC therapy did not show significant changes related to baseline on bone mass across the study , whereas a significant decrease was detected in the calcium carbonate group during the second year ( -3.7 % , P measurement ( -3.5 % , P OHC prevents bone loss in postmenopausal women , suggesting that this drug may be useful in the management of postmenopausal bone loss", "CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women . All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD", "The effect of calcium supplementation , in patients with osteoporosis is still a matter of controversy . Oyster shell electrolysate ( OSE ) was reported to raise serum calcium and increase urinary calcium excretion in vitamin D-deficient states more readily than calcium carbonate . Since the effect of calcium salts on osteoporosis depends heavily on its bioavailability , the effect of 900 mg/day calcium as OSE was tested in 12 elderly osteoporotic females , using radial bone mineral density measured by single photon absorptiometry and spinal trabecular bone density measured by quantitative computed tomography ( QCT ) as indicated , in comparison with 21 untreated controls in the same geriatric hospital . Radial bone mineral density significantly increased from the pre-test value after 12 and 24 months in subjects given OSE by paired t-test , whereas it fell significantly in the controls . The spinal QCT value on OSE did not change significantly in either the subjects under treatment with OSE , or the controls . Thus OSE may favorably influence osteoporosis by providing a readily available source of calcium", "UNLABELLED Dietary supplementation with vitamin K(1 ) , with vitamin D(3 ) and calcium or their combination , was examined in healthy older women during a 2-year , double-blind , placebo-controlled trial . Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius . INTRODUCTION The putative beneficial role of high dietary vitamin K(1 ) ( phylloquinone ) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind , placebo-controlled trial in healthy Scottish women > or = 60 years of age . MATERIAL S AND METHODS Healthy , nonosteoporotic women ( n = 244 ) were r and omized to receive either ( 1 ) placebo , ( 2 ) 200 microg/day vitamin K(1 ) , ( 3 ) 10 microg ( 400 IU ) vitamin D(3 ) plus 1000 mg calcium/day , or ( 4 ) combined vitamins K(1 ) and D(3 ) plus calcium . Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist , markers of bone turnover , and vitamin status . Supplementation effects were tested using multivariate general linear modeling , with full adjustment for baseline and potential confounding variables . RESULTS Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups . However , women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius . Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years , serum vitamin K(1 ) increased by 157 % ( p percentage of undercarboxylated osteocalcin ( % GluOC ) decreased by 51 % ( p serum 25-hydroxyvitamin D [ 25(OH)D ] increased by 17 % ( p PTH decreased by 11 % ( p = 0.049 ) . CONCLUSIONS These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1 ) together with supplements of calcium plus moderate vitamin D(3 ) to enhance BMC at the ultradistal radius , a site consisting of principally trabecular bone . The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation", "UNLABELLED In this 2-year r and omized controlled study of 167 men > 50 years of age , supplementation with calcium-vitamin D3-fortified milk providing an additional 1000 mg of calcium and 800 IU of vitamin D3 per day was effective for suppressing PTH and stopping or slowing bone loss at several clinical ly important skeletal sites at risk for fracture . INTRODUCTION Low dietary calcium and inadequate vitamin D stores have long been implicated in age-related bone loss and osteoporosis . The aim of this study was to assess the effects of calcium and vitamin D3 fortified milk on BMD in community living men > 50 years of age . MATERIAL S AND METHODS This was a 2-year r and omized controlled study in which 167 men ( mean age + /- SD , 61.9 + /- 7.7 years ) were assigned to receive either 400 ml/day of reduced fat ( approximately 1 % ) ultra-high temperature ( UHT ) milk containing 1000 mg of calcium plus 800 IU of vitamin D3 or to a control group receiving no additional milk . Primary endpoints were changes in BMD , serum 25(OH)D , and PTH . RESULTS One hundred forty-nine men completed the study . Baseline characteristics between the groups were not different ; mean dietary calcium and serum 25(OH)D levels were 941 + /- 387 mg/day and 77 + /- 23 nM , respectively . After 2 years , the mean percent change in BMD was 0.9 - 1.6 % less in the milk supplementation compared with control group at the femoral neck , total hip , and ultradistal radius ( range , p lumbar spine BMD in the milk supplementation group after 12 and 18 months ( 0.8 - 1.0 % , p Serum 25(OH)D increased and PTH decreased in the milk supplementation relative to control group after the first year ( 31 % and -18 % , respectively ; both p Body weight remained unchanged in both groups at the completion of the study . CONCLUSIONS Supplementing the diet of men > 50 years of age with reduced-fat calcium- and vitamin D3-enriched milk may represent a simple , nutritionally sound and cost-effective strategy to reduce age-related bone loss at several skeletal sites at risk for fracture in the elderly", "UNLABELLED Bone metabolism follows a seasonal pattern with high bone turnover and bone loss during the winter . In a r and omized , open-label 2-year sequential follow-up study of 55 healthy adults , we found that supplementation with oral vitamin D3 and calcium during winter abolished seasonal changes in calciotropic hormones and markers of bone turnover and led to an increase in BMD . Supplementation with oral vitamin D3 and calcium during the winter months seems to counteract the effects of seasonal changes in vitamin D and thus may be beneficial as a primary prevention strategy for age-related bone loss . INTRODUCTION Bone metabolism follows a seasonal pattern characterized by high bone turnover and bone loss during winter . We investigated whether wintertime supplementation with oral vitamin D3 and calcium had beneficial effects on the circannual changes in bone turnover and bone mass . MATERIAL S AND METHODS This prospect i ve study comprised an initial observation period of 12 months ( \" year 1 \" ) , followed by an intervention during parts of year 2 . Fifty-five healthy subjects living in southwestern Germany ( latitude , 49.5 degrees N ) were r and omized into two groups : 30 subjects were assigned to the treatment group and received oral cholecalciferol ( 500 IU/day ) and calcium ( 500 mg/day ) during the winter months of year 2 ( October-April ) , while 25 subjects assigned to the control group obtained no supplements . Primary endpoints were changes in calciotropic hormones [ serum 25(OH)D , 1,25(OH)2D , and parathyroid hormone ] , markers of bone formation ( serum bone-specific alkaline phosphatase ) and of bone resorption ( urinary pyridinoline and deoxypyridinoline ) , and changes in lumbar spine and femoral neck BMD . RESULTS Forty-three subjects completed the study . During year 1 , calciotropic hormones , markers of bone turnover , and BMD varied by season in both groups . During the winter months of year 1 , bone turnover was significantly accelerated , and lumbar spine and femoral BMD declined by 0.3 - 0.9 % . In year 2 , seasonal changes in calciotropic hormones and markers of bone turnover were either reversed or abolished in the intervention group while unchanged in the control cohort . In the subjects receiving oral vitamin D3 and calcium , lumbar and femoral BMD increased significantly ( lumbar spine : + 0.8 % , p = 0.04 versus year 1 ; femoral neck : + 0.1 % , p = 0.05 versus year 1 ) , whereas controls continued to lose bone ( intervention group versus control group : lumbar spine , p = 0.03 ; femoral neck , p = 0.05 ) . CONCLUSIONS Supplementation with oral vitamin D3 and calcium during winter prevents seasonal changes in bone turnover and bone loss in healthy adults . It seems conceivable that annually recurring cycles of low vitamin D and mild secondary hyperparathyroidism during the winter months contributes , at least in part and over many years , to age-related bone loss . Supplementation with low-dose oral vitamin D3 and calcium during winter may be an efficient and inexpensive strategy for the primary prevention of bone loss in northern latitudes", "Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures . A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites , bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a r and omized , double-blind , placebo-controlled trial . Bone mineral density ( BMD ) was measured by dual x-ray absorptiometry and bone structure by radiographs . Calcium biochemistry and bone turnover markers were measured in blood and urine . The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr . Baseline median calcium intake was 546 mg/day , and median serum 25OH vitamin D3 was 59 nmol/L. On placebo , loss of BMD at total hip was 2 % and femoral medulla expansion was 3 % over 4 yr . Calcium reduced bone loss , secondary hyperparathyroidism , and bone turnover . 25OH vitamin D3 was intermediate between placebo and calcium . Fracture rates and drop-out rates were similar among groups , and there were no serious adverse events with either supplement . A calcium supplement of 750 mg/day prevents loss of BMD , reduces femoral medullary expansion , secondary hyperparathyroidism , and high bone turnover . A supplement of 15 microg/day 25OH vitamin D3 is less effective , and because its effects are seen only at low calcium intakes , suggests that its beneficial effect is to reverse calcium insufficiency", "Summary We examined the independent and combined effects of a multi-component exercise program and calcium – vitamin-D3-fortified milk on bone mineral density ( BMD ) in older men . Exercise result ed in a 1.8 % net gain in femoral neck BMD , but additional calcium – vitamin D3 did not enhance the response in this group of older well-nourished men . Introduction This 12-month r and omised controlled trial assessed whether calcium – vitamin-D3-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men . Methods Men ( n = 180 ) aged 50–79 years were r and omised into : ( 1 ) exercise + fortified milk ; ( 2 ) exercise ; ( 3 ) fortified milk ; or ( 4 ) controls . Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise . Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D3 . Femoral neck ( FN ) , total hip , lumbar spine and trochanter BMD and body composition ( DXA ) , muscle strength 25-hydroxyvitamin D and parathyroid hormone ( PTH ) were assessed . Results There were no exercise-by-fortified milk interactions at any skeletal site . Exercise result ed in a 1.8 % net gain in FN BMD relative to no-exercise ( p ; lean mass ( 0.6 kg , p and muscle strength ( 20–52 % , p For lumbar spine BMD , there was a net 1.4–1.5 % increase in all treatment groups relative to controls ( all p fortified milk at any skeletal site . Conclusion A multi-component community-based exercise program was effective for increasing FN BMD in older men , but additional calcium – vitamin D3 did not enhance the osteogenic response", "To study the effect of calcium supplementation on perimenopausal bone loss , 295 women were r and omized into a control group and 2 supplementation groups receiving , respectively , 1000 and 2000 mg elemental calcium/day for a period of 2 yr . We observed a significant decrease in lumbar bone loss in relation to the calcium supplementation ( mean loss after 2 yr of 3.5 % in the control group vs. 1.3 % and 0.7 % in the 1000 and 2000 mg groups , respectively ) , a significant increase in urinary calcium excretion , and a significant decrease in the urinary hydroxyproline/creatine ratio , serum alkaline phosphatase , osteocalcin , and 1,25-dihydroxyvitamin D. The effect of calcium supplementation on lumbar bone loss was significant in the first year of supplementation , but not in the second . However , the urinary hydroxyproline/creatinine ratio and the serum alkaline phosphatase level remained significantly decreased in the treatment groups at the end of the study ; this was not the case for serum osteocalcin . Calcium supplementation did not have a significant effect on metacarpal cortical bone loss . The difference in biochemical parameters between the 2 supplementation groups was small . No significant interaction was observed between the menopausal status of the subjects and the effect of calcium supplementation . We conclude that calcium supplementation retards lumbar bone loss in the first year of calcium supplementation by reducing bone turnover . However , the effect on lumbar bone loss over a longer time span is still uncertain", "We tested the spine antifracture and bone sparing efficacy of 1.2 g/day of oral calcium as carbonate in two groups of elderly women , one with prevalent fractures ( PF , n = 94 ) on entry and the other without ( NPF , n = 103 ) . It was a prospect i ve r and omized , double-blind , placebo-controlled trial in mostly rural communities in women over age 60 who were living independently and were consuming calcium . We obtained annual lateral spine radiographs and semiannual forearm bone density over 4.3 + /- 1.1 years and determined vertebral fractures by radiographic morphometry augmented by physician assessment . In the PF group , 15 of 53 subjects on calcium had incident fractures , compared with 21 of 41 on placebo ( p = 0.023 , chi2 ) . Calcium did not reduce the rate of incident fractures in the NPF group . Those with a prevalent fracture on entry and not treated with calcium were 2.8 times more likely to experience an incident fracture than all others . Change in the forearm bone mass on placebo in the PF group was -1.24 + /- 2.41%/year compared with + 0.31 + /- 1.80%/year on calcium ( p elderly postmenopausal women with spine fractures and selfselected calcium intakes of , a calcium supplement of 1.2 g/day reduces the incidence of spine fractures and halts measurable bone loss", "UNLABELLED Overweight postmenopausal women may be more susceptible to bone loss with weight reduction than previously studied obese women . The influence of energy restriction and Ca intake on BMD was assessed in 66 individuals . Weight reduction result ed in bone loss at several sites in women consuming 1 g Ca/day and was mitigated with higher calcium intake at 1.7 g/day . INTRODUCTION Bone loss is associated with weight loss in obese postmenopausal women and can be prevented with calcium ( Ca ) supplementation . However , because bone loss caused by weight loss may be greater in overweight than obese women , it is not clear whether Ca supplementation is also beneficial in overweight women . MATERIAL S AND METHODS We assessed the influence of caloric restriction at two levels of Ca intake on BMD and BMC in 66 overweight postmenopausal women ( age , 61 + /- 6 years ; body mass index , 27.0 + /- 1.8 kg/m2 ) . Subjects completed either a 6-month energy-restricted diet ( WL , n = 47 ) and lost 9.3 + /- 3.9 % weight or maintained weight ( WM ; 1 g Ca/day , n = 19 ) . Participants in the WL group were r and omly assigned to either normal ( 1 g/day ; WL NL-Ca ) or high ( 1.7 g/day ; WL Hi-Ca ) Ca intake . Regional BMD and BMC were measured at baseline and after 6 months . RESULTS During normal Ca intake , trochanter BMD and BMC and total spine BMD were decreased more in WL than WM women ( p trochanter BMD ( -4.2 + /- 4.1 % ) and BMC ( -4.8 + /- 7.1 % ) than the WL Hi-Ca group ( -1.4 + /- 5.6 % and -1.1 + /- 8.1 % , respectively ; p BMD or BMC at the femoral neck in any group . Weight loss correlated with trochanter BMD loss ( r = 0.687 , p bone loss occurred at some sites because of weight loss . Calcium intake of 1.7 g/day will minimize bone loss during weight loss in postmenopausal overweight women", "The etiology of age-related bone loss is unclear but both lack of exercise and dietary calcium deficiency have been implicated in its causation . This 2-year r and omized placebo-controlled study was design ed to examine the effects of increased dietary calcium and exercise in 168 women who were more than 10 years postmenopausal . The subjects were r and omized into one of 4 groups : placebo , milk powder containing 1 g of calcium , calcium tablets 1 g/night , and calcium tablets 1 g/night and an exercise regimen . The exercise group aim ed to undertake 4 h of extra weight-bearing exercise per week and were undertaking 10 % more activity than other groups at 2 years . Bone mineral density at the lumbar spine , three hip sites , and two sites of the tibia close to the ankle joint were measured at 6 month intervals . Dietary intake was evaluated by a weighed food record , exercise was evaluated by an exercise diary , and blood and urine sample s were obtained to examine effects on calcium homeostasis . Individual data points were compared using repeated measures ANOVA and least squares regression . Calcium supplementation by either the calcium tablets or the milk powder result ed in cessation of bone loss at the intertrochanteric hip site ( placebo , calcium tablets , calcium and exercise , milk powder -0.81 , + 0.17 , + 0.23 , and + 0.07 % per year , respectively ; p calcium and exercise group had less bone loss at the femoral neck site when compared with calcium supplementation alone ( placebo , calcium tablets , calcium and exercise , milk powder -0.67 , -0.18 , + 0.28 , and -0.18 % per year , respectively ; p calcium and exercise compared with calcium alone ) . There was a significant reduction in the rate of bone loss at the ultradistal site of the tibia ( placebo , calcium tablets , calcium and exercise , milk powder -2.5 , -1.6 , -1.0 , and -1.5 % per year , respectively ; p < 0.05 for all supplementation groups compared with placebo ) . There was no significant bone loss at the spine site in any group . ( ABSTRACT TRUNCATED AT 250 WORDS", "Dietary studies often report low calcium intake amongst post-menopausal Malaysian women and calcium deficiency has been implicated as part of the etiology of age-related bone loss leading to osteoporosis . Therefore , the objective of this study was to examine the effectiveness of high calcium skimmed milk ( Anlene Gold ™ , New Zeal and Milk , Wellington , New Zeal and ) to reduce bone loss in Chinese postmenopausal women . Two hundred subjects aged 55–65 years and who were more than 5 years postmenopausal were r and omized to a milk group and control group . The milk group consumed 50 g of high calcium skimmed milk powder daily , which contained 1200 mg calcium ( taken as two glasses of milk a day ) . The control group continued with their usual diet . Using repeated measures ANCOVA , the milk supplement was found to significantly reduce the percentage of bone loss at the total body compared to the control group at 24 months ( control −1.04 % , milk −0.13 % ; P the lumbar spine , the percentage of bone loss in the control group was significantly higher ( −0.90 % ) when compared to the milk ( −0.13 % ) supplemented group at 24 months ( P reduced the percentage of bone loss at the femoral neck ( control −1.21 % , milk 0.51 % ) ( P total hip ( control −2.17 % , milk −0.50 % ) ( P significant weight gain over the 24 months . The serum 25-hydroxy vitamin D level improved significantly ( P high calcium skimmed milk was effective in reducing the rate of bone loss at clinical ly important lumbar spine and hip sites in postmenopausal Chinese women in Malaysia . Supplementing with milk had additional benefits of improving the serum 25-hydroxy vitamin D status of the subjects", "BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo . Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . )", "Abstract : We undertook a double-masked , r and omized , placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement and a calcium supplement plus multivitamins on bone loss at the hip , spine and forearm . The study was performed in 240 healthy women , 58–67 years of age . Duration of treatment was 2 years . Bone mineral density ( BMD ) was measured at the lumbar spine , hip and forearm . A dietary question naire was administered twice during the study and revealed a fairly good calcium and vitamin D intake ( 919 mg calcium/day ; 3.8 mg vitamin D/day ) . An increase in lumbar spine BMD of 1.6 % was observed in the treatment group after 2 years ( p50.002 ) . In the placebo group no significant changes were observed during the 2 years . Lumbar spine BMD was significantly higher in the treatment group at both 1 ( p50.01 ) and 2 years ( p50.05 ) compared with the placebo group . Though not significant , the same trend was seen at the hip . No significant changes from baseline values were observed at the distal forearm in either the treatment or the placebo group . In conclusion , we found a significant increase in urinary calcium excretion in the treatment group compared with the placebo group . Together with significant changes in serum calcium and serum parathyroid hormone , this indicates that a long-term calcium and vitamin supplement of 1 g elementary calcium ( calcium carbonate ) and 14 mg vitamin D3 increases intestinal calcium absorption . A positive effect on BMD was demonstrated , even in a group of early postmenopausal age , with a fairly good initial calcium and vitamin D status", "Bone mobilization , lowering of bone mineral density ( BMD ) , and osteoporotic fractures are recognized in postmenopausal women with weight loss . Because a high-calcium intake suppresses bone loss in peri- and postmenopausal women , the present r and omized , double-blind , placebo-controlled study was design ed to test the hypothesis that calcium supplementation prevents net bone mobilization and consequent bone mineral loss during voluntary weight reduction in obese postmenopausal women . Subjects were placed on a moderate energy-restricted diet and either calcium supplementation ( 1 g/day ) or placebo for 6 months . Body weight , bone turnover markers ( pyridinium cross-links ) , osteocalcin , and parathyroid hormone ( PTH ) were measured at treatment weeks 1 - 5 , 7 , 10 , 13 , 16 , 20 , and 25 . Total body BMD , insulin-like growth factor , 25-hydroxyvitamin D , and sex hormone binding globulin ( SHBG ) were measured at baseline and week 25 . The calcium supplemented ( n = 15 ; age 60.9 + /- 9.4 years , body mass index [ BMI ] 33.2 + /- 4.6 kg/m2 ) and placebo ( n = 16 ; age 55.8 + /- 8.3 years , BMI 32.9 + /- 4.5 kg/m2 ) groups lost similar amounts of weight over the study interval ( 10.2 + /- 5.3 % vs. 10.0 + /- 5.2 % ) and both groups increased SHBG ( p pyridinium cross-links , osteocalcin , and PTH ( p Loss of BMD tended to be greater in the placebo group by 1.4 % ( p calcium supplementation normalizes the increased calcium-PTH axis activity and the elevated bone turnover rate observed during moderate voluntary energy restriction in postmenopausal women", "Elderly women are at increased risk for bone loss and fractures . In previous cross-sectional and longitudinal studies of women residing in northern latitudes , bone loss was most pronounced during winter months and in those consuming less than 1 g calcium per day . In this study we sought to test the hypothesis that calcium supplementation by either calcium carbonate or dietary means would prevent seasonal bone loss and preserve bone mass . Sixty older postmenopausal women without osteoporosis were r and omized to one of three treatment arms : Dietary milk supplementation ( D-4 glasses of milk/day ) , Calcium carbonate ( CaCO3 - 1000 mg/day in two divided doses ) , or placebo ( P ) . After 2 yr , placebo-treated women consumed a mean of 683 mg/day of calcium and lost 3.0 % of their greater trochanteric ( GT ) bone mineral density ( BMD ) ( P GT ( -1.5 % ; P = 0.30 ) , whereas CaCO3-treated women ( total Ca intake , 1633 mg/day ) suffered no bone loss from the GT and showed a significant increase in spinal and femoral neck BMD ( P Femoral bone loss occurred exclusively during the two winters of the study ( i.e. total loss , -3.2 % ; P GT BMD during summer . Serum 25-OH vitamin D declined by more than 20 % ( P PTH levels rose approximately 20 % ( P Urine N-telopeptide and osteocalcin levels increased significantly but only in the P-treated women and only during winter . Serum insulin growth factor binding protein 4 , an inhibitory insulin growth factor binding protein , rose 15 % ( P total calcium intake was the strongest predictor of bone loss from the hip . Urinary N-telopeptide also closely correlated with GT BMD but only during winter ( P = 0.003 ) . We conclude that calcium supplementation prevents bone loss in elderly women by suppressing bone turnover during the winter when serum 25-OH vitamin D declines and serum PTH increases . The precise amount of calcium necessary to preserve BMD in elderly women requires further studies , although in this study , at least 1000 mg/day of supplemental calcium was adequate prophylaxis against femoral bone loss", "Objective To determine the effect of calcium supplementation on myocardial infa rct ion , stroke , and sudden death in healthy postmenopausal women . Design R and omised , placebo controlled trial . Setting Academic medical centre in an urban setting in New Zeal and . Participants 1471 postmenopausal women ( mean age 74 ) : 732 were r and omised to calcium supplementation and 739 to placebo . Main outcome measures Adverse cardiovascular events over five years : death , sudden death , myocardial infa rct ion , angina , other chest pain , stroke , transient ischaemic attack , and a composite end point of myocardial infa rct ion , stroke , or sudden death . Results Myocardial infa rct ion was more commonly reported in the calcium group than in the placebo group ( 45 events in 31 women v 19 events in 14 women , P=0.01 ) . The composite end point of myocardial infa rct ion , stroke , or sudden death was also more common in the calcium group ( 101 events in 69 women v 54 events in 42 women , P=0.008 ) . After adjudication myocardial infa rct ion remained more common in the calcium group ( 24 events in 21 women v 10 events in 10 women , relative risk 2.12 , 95 % confidence interval 1.01 to 4.47 ) . For the composite end point 61 events were verified in 51 women in the calcium group and 36 events in 35 women in the placebo group ( relative risk 1.47 , 0.97 to 2.23 ) . When unreported events were added from the national data base of hospital admissions in New Zeal and the relative risk of myocardial infa rct ion was 1.49 ( 0.86 to 2.57 ) and that of the composite end point was 1.21 ( 0.84 to 1.74 ) . The respective rate ratios were 1.67 ( 95 % confidence intervals 0.98 to 2.87 ) and 1.43 ( 1.01 to 2.04 ) ; event rates : placebo 16.3/1000 person years , calcium 23.3/1000 person years . For stroke ( including unreported events ) the relative risk was 1.37 ( 0.83 to 2.28 ) and the rate ratio was 1.45 ( 0.88 to 2.49 ) . Conclusion Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates . This potentially detrimental effect should be balanced against the likely benefits of calcium on bone . Trial registration Australian Clinical Trials Registry ACTRN 012605000242628", "OBJECTIVE To establish whether calcium-enriched milk reduces bone loss in women who are within five years of the menopause and have a basal calcium intake DESIGN Two-year open , crossover study . SETTING A community-based study carried out in Adelaide , South Australia , between September 1997 and June 2000 . PARTICIPANTS 115 women recruited by newspaper advertisement , who were less than five years postmenopausal , were not taking hormone or other therapy that could affect bone and had a usual calcium intake INTERVENTION Participants were r and omly allocated to Group 1 ( who received a supplement of 3 L of calcium-fortified milk weekly in the first year ) or Group 2 ( who followed their usual diets in the first year ) . In the second year , Group 1 reverted to their usual diets , and Group 2 received the milk supplement . MAIN OUTCOME MEASURES Difference in loss of bone mineral density ( BMD ) at the spine and forearm in the same individuals on and off the milk supplement ; urinary excretion of bone resorption markers in a subset of 72 participants in the first year . RESULTS With each woman serving as her own control , the rate of bone loss from the spine was 1.76 percentage points less when the women were taking the milk supplement than when they were on their usual diet ( 95 % CI , 0.54%-2.98 % ; P=0.006 ) . However , there was no significant difference in bone loss in the forearm . Fasting urine levels of two markers of bone resorption ( hydroxyproline and deoxypyridinoline ) were significantly lower in 36 women in the milk group than in 36 women in the usual-diet group ( P=0.03 for both markers ) . CONCLUSION Supplementing the diet with calcium-fortified milk early in the postmenopausal period delays bone loss at the spine but not at the forearm , and reduces the excretion of bone resorption markers", "The efficacy of calcium ( Ca ) in reducing bone loss is debated . In a r and omized placebo-controlled double-masked study , we investigated the effects of oral Ca supplements on femoral shaft ( FS ) , femoral neck ( FN ) and lumbar spine ( LS ) bone mineral density ( BMD ) , and on the incidence of vertebral fracture in vitamin-D-replete elderly . Ninety-three healthy subjects ( 72.1±0.6 years ) were r and omly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months . Sixty-three patients ( 78.4±1.0 years ) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo . FS BMD changes in Ca-supplemented non-fractured women were significantly different from those in the placebo group ( + 0.6±0.5 % v −1.2±0.7%,p of Ca . The changes of + 0.7±0.8 % v −1.7±1.6 % in FN BMD of Ca-supplemented women and the placebo group did not reach statistical significance . In fractured patients , FS , FN and LS BMD changes were −1.3±0.8 , + 0.3±1.6 and + 3.1±1.2 % ( p . The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patient-years in Ca-supplemented non-fractured subjects and in the placebo group , respectively , and 144.0 in Ca-supplemented fractured patients . Thus , oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly", "BACKGROUND The use of calcium supplements slows bone loss in the forearm and has a beneficial effect on the axial bone density of women in late menopause whose calcium intake is less than 400 mg per day . However , the effect of a calcium supplement of 1000 mg per day on the axial bone density of postmenopausal women with higher calcium intakes is not known . METHODS We studied 122 normal women at least three years after they had reached menopause who had a mean dietary calcium intake of 750 mg per day . The women were r and omly assigned to treatment with either calcium ( 1000 mg per day ) or placebo for two years . The bone mineral density of the total body , lumbar spine , and proximal femur was measured every six months by dual-energy x-ray absorptiometry . Serum and urine indexes of calcium metabolism were measured at base line and after 3 , 12 , and 24 months . RESULTS The mean ( + /- SE ) rate of loss of total-body bone mineral density was reduced by 43 percent in the calcium group ( -0.0055 + /- 0.0010 g per square centimeter per year ) as compared with the placebo group ( -0.0097 + /- 0.0010 g per square centimeter per year , P = 0.005 ) . The rate of loss of bone mineral density was reduced by 35 percent in the legs ( P = 0.02 ) , and loss was eliminated in the trunk ( P = 0.04 ) . Calcium use was of significant benefit in the lumbar spine ( P = 0.04 ) , and in Ward 's triangle the rate of loss was reduced by 67 percent ( P = 0.04 ) . Calcium supplementation had a similar effect whether dietary calcium intake was above or below the mean value for the group . Serum parathyroid hormone concentrations tended to be lower in the calcium group , as were urinary hydroxyproline excretion and serum alkaline phosphatase concentrations . CONCLUSIONS Calcium supplementation significantly slowed axial and appendicular bone loss in normal post-menopausal women", "BACKGROUND Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption , but the balance between its long-term risks and benefits remains unclear . Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear . METHODS We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age . An additional 435 women who were prepared to receive a combination of estrogen and progestin were r and omly assigned to one of the above treatments or open-label estrogen-progestin . The main outcome measure was the change in bone mineral density of the lumbar spine , hip , distal forearm , and total body measured annually for two years by dual-energy x-ray absorptiometry . RESULTS The women who received placebo lost bone mineral density at all measured sites , whereas the women treated with 5 mg of alendronate daily had a mean ( + /-SE ) increase in bone mineral density of 3.5+/-0.2 percent at the lumbar spine , 1.9+/-0.1 percent at the hip , and 0.7+/-0.1 percent for the total body ( all P alendronate daily had smaller increases in bone mineral density . Alendronate did not increase bone mineral density of the forearm , but it slowed the loss . The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate . Alendronate was well tolerated , with a safety profile similar to that of placebo or estrogen-progestin . CONCLUSIONS Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin", "Summary Supplementation with elemental calcium 500 mg/day alone for 2 years is able to decrease bone turnover and is effective in retarding bone loss at lumbar spine and slowing bone loss at femoral neck in elderly Thai women who had low dietary calcium intake . Introduction Most elderly Thais have a total dietary calcium intake of less than the recommended amount . The aim of the study was to investigate the effect of calcium supplementation on bone mineral density and biochemical indices of bone remodeling in Thai postmenopausal women . Methods Four hundred and four healthy postmenopausal women 60 years old or older without osteoporosis were recruited and conducted in a r and omized , double-blinded , placebo-controlled trial . They were r and omly given elementary calcium 500 mg/day or placebo for 2 years . Dietary calcium intake was calculated from the nutrient compositional analysis of the 3-day food records . Serum 25 hydroxyvitamin D was measured by radioimmunoassay and bone turnover markers were determined by electrochemiluminescence immunoassay . Results The age of the subjects was 65.8 ± 4.4 years . All baseline characteristics of the subjects in the calcium-supplemented group and the placebo group were not statistically different . At the end of the study , significant decreases in serum C-terminal telopeptide of type I collagen and serum total procollagen type I amino terminal propeptide in the calcium-supplemented group were observed , while there was no change in the placebo group . In addition , plasma parathyroid hormone decreased , although not significantly , only in the calcium-supplemented group . Percent changes from baseline of lumbar spine ( L2–L4 ) bone mineral density increased 2.76 % in the calcium-supplemented group and 0.87 % in the placebo group , whereas the percent changes from baseline of femoral neck decreased 0.21 % in the calcium-supplemented group and 0.90 % in the placebo group . Conclusions Calcium supplementation is necessary for the decrease of bone turnover and prevention of bone loss in Thai elderly women", "BACKGROUND Increased dietary calcium intake has been proposed as a population -based public health intervention to prevent osteoporotic fractures . We have examined whether calcium supplementation decreases clinical fracture risk in elderly women and its mechanism of action . METHODS Five-year , double-blind , placebo-controlled study of 1460 women recruited from the population and older than 70 years ( mean age , 75 years ) who were r and omized to receive calcium carbonate , 600 mg twice per day , or identical placebo . The primary end points included clinical incident osteoporotic fractures , vertebral deformity , and adverse events ascertained in 5 years . Bone structure was also measured using dual x-ray absorptiometry of the hip and whole body , quantitative ultrasonography of the heel , and peripheral quantitative computed tomography of the distal radius . RESULTS Among our patients , 16.1 % sustained 1 or more clinical osteoporotic fractures . In the intention-to-treat analysis , calcium supplementation did not significantly reduce fracture risk ( hazard ratio , 0.87 ; 95 % confidence interval , 0.67 - 1.12 ) . However , 830 patients ( 56.8 % ) who took 80 % or more of their tablets ( calcium or placebo ) per year had reduced fracture incidence in the calcium compared with the placebo groups ( 10.2 % vs 15.4 % ; hazard ratio , 0.66 ; 95 % confidence interval , 0.45 - 0.97 ) . Calcium-treated patients had improved quantitative ultrasonography findings of the heel , femoral neck and whole-body dual x-ray absorptiometry data , and bone strength compared with placebo-treated patients . Of the 92 000 adverse events recorded , constipation was the only event increased by the treatment ( calcium group , 13.4 % ; placebo group , 9.1 % ) . CONCLUSION Supplementation with calcium carbonate tablets supplying 1200 mg/d is ineffective as a public health intervention in preventing clinical fractures in the ambulatory elderly population owing to poor long-term compliance , but it is effective in those patients who are compliant", "Background . The effectiveness of calcium in retarding bone loss in older postmenopausal women is unclear . Earlier work suggested that the women who were most likely to benefit from calcium supplementation were those with low calcium intakes . Methods . We undertook a double-blind , placebo-controlled , r and omized trial to determine the effect of calcium on bone loss from the spine , femoral neck , and radius in 301 healthy postmenopausal women , half of whom had a calcium intake lower than 400 mg per day and half an intake of 400 to 650 mg per day . The women received placebo or either calcium carbonate or calcium citrate malate ( 500 mg of calcium per day ) for two years . Results . In women who had undergone menopause five or fewer years earlier , bone loss from the spine was rapid and was not affected by supplementation with calcium . Among the women who had been postmenopausal for six years or more and who were given placebo , bone loss was less rapid in the group with the higher dietary calcium intake . In those with the lower calcium intake , calcium citrate malate prevented bone loss during the two years of the study ; its effect was significantly different from that of placebo ( P less than 0.05 ) at the femoral neck ( mean change in bone density [ + /- SE ] , 0.87 + /- 1.01 percent vs. -2.11 + /- 0.93 percent ) , radius ( 1.05 + /- 0.75 percent vs. -2.33 + /- 0.72 percent ) , and spine ( -0.38 + /- 0.82 percent vs. -2.85 + /- 0.77 percent ) . Calcium carbonate maintained bone density at the femoral neck ( mean change in bone density , 0.08 + /- 0.98 percent ) and radius ( 0.24 + /- 0.70 percent ) but not the spine ( -2.54 + /- 0.85 percent ) . Among the women who had been postmenopausal for six years or more and who had the higher calcium intake , those in all three treatment groups maintained bone density at the hip and radius and lost bone from the spine . Conclusions . Healthy older postmenopausal women with a daily calcium intake of less than 400 mg can significantly reduce bone loss by increasing their calcium intake to 800 mg per day . At the dose we tested , supplementation with calcium citrate malate was more effective than supplementation with calcium carbonate", "Summary Daily treatment with 30 mg of sodium fluoride ( NaF ) and 1 g of calcium over a 3-year period increased the bone mineral content ( BMC ) in the spines of women ( n=25 ) with osteoporosis . Determination of the BMC was followed with dual photon absorptiometry ( 137Cs-241Am ) in the third lumbar vertebra . No increase in BMC was found with only 10 mg sodium fluoride in combination with calcium ( n=25 ) , with calcium alone ( n=25 ) , or with placebo ( n=25 ) . No serious side effects were registered . There was , however , minor gastrointestinal distress in one-fifth of the patients taking 30 mg NaF daily", "We report a 4-year r and omized , double-blind , placebo-controlled clinical trial in 236 normal postmenopausal women ( mean age + /- SE , 66.3+/-0.2 years ) who were r and omized to a calcium ( 1600 mg/day as the citrate ) or placebo group . The women were seen every 6 months ; 177 completed the trial . Net percentage changes in each group are given relative to baseline . The differences in net percentage changes ( calcium group minus placebo group ) in medians were : for lumbar spine bone density , 2.0 % ( p proximal femur bone density , 1.3 % ( p = 0.003 ) at year 1 and 1.3 % ( p = 0.015 ) at year 4 ; and for total body bone mineral , 0.4 % ( p = 0.002 ) at year 1 and 0.9 % ( p = 0.017 ) at year 4 . Similar differences at year 4 were : -18.9 % ( p = 0.002 ) for parathyroid hormone ( PTH ) , -11.9 % ( p = 0.026 ) for serum osteocalcin , and -32.2 % ( p = 0.003 ) for urine free pyridinoline . We conclude that long-term administration of calcium supplements to elderly women partially reverses age-related increases in serum PTH level and bone resorption and decreases bone loss . However , the effects on bone loss were weaker than those reported for estrogen , bisphosphonates , or calcitonin therapy , indicating that calcium supplements alone can not substitute for these in treating established osteoporosis . Nonetheless , because of their safety , high tolerance , and low expense , calcium supplements may be a useful preventive measure for elderly postmenopausal women whose bone mineral density values are normal for their age", "The Chinese diet is low in calcium ( less than 500 mg/day on average ) , and previous observational studies have suggested an association between a low calcium intake and risk of hip and vertebral fracture . In this study , we r and omly assigned 200 postmenopausal Chinese women ( age range , 55 - 59 years ) to receive 50 g of milk powder containing 800 mg of calcium per day or to a control group . The following are the mean percentage changes ( and SEs ) in height and bone mineral density ( BMD ) over 24 months : for height , -0.1 + /- 0.2 cm in the milk supplementation group and -0.2 + /- 0.1 cm in the control group ; for BMD at the total hip , -0.06 + /- 0.22 % in the milk supplementation group and -0.88 + /- 0.26 % in the control group ; for BMD at the spine ( L1-L4 ) , -0.56 + /- 0.29 % in the milk supplementation group and -1.5 + /- 0.29 % in the control group ; for total body BMD , -0.32 + /- 0.16 % in the milk supplementation group and -1.2 + /- 0.19 % in the control group ( p loss in terms of both height and BMD than the control group ( p Serum parathyroid hormone ( PTH ) concentration was lower and serum 25-hyroxyvitamin D [ 25(OH)D ] level was higher in the milk supplementation group than the control group at 12 months ( p diet of postmenopausal Chinese women with high calcium milk powder retards bone loss", "Sixty postmenopausal women were placed in three groups -- control , sex hormone-treated , and CaCO3-treated-- and followed for 2 years . Skeletal mass decreased by 1.18%/year in the control group , 0.15%/year in the hormone group , and 0.22%/year in the CaCO3 group by radiogrammetry ; and 2.88%/year in the control group , 0.73%/year in the hormone group , and 1.83%/year in the CaCO3 group by photon absorptiometry . The treatment groups differed significantly from the control group except for photon absorptiometry in the CaCO3 group . Bone accretion and resorption decreased in the treatment groups as measured by calcium tracer kinetics , resorption more so than accretion . We conclude that [ 1 ] these techniques are sufficiently sensitive to detect age-related bone loss ; [ 2 ] postmenopausal sex-hormone replacement measurably decreases age-related bone loss by suppressing bone turnover , resorption more than accretion ; and [ 3 ] calcium supplements produce the same effect but at the dose we used were slightly less effective", "OBJECTIVE To determine the rate of bone loss in normal men , and to examine the effects of dietary calcium and cholecalciferol supplementation on bone loss in men . DESIGN Double-blinded , placebo-controlled 3-year trial of supplementation with calcium ( 1000 mg/d ) and cholecalciferol ( 25 micrograms/d ) . SETTING Clinical research center at a university medical facility . SUBJECTS Normal men 30 to 87 years old , recruited from the Portl and community . MEASUREMENTS AND MAIN RESULTS Radial bone mineral content ( assessed by single-photon absorptiometry ) fell by 1.0%/y ( 95 % CI , -1.3 % to 0.7 % ) at a proximal radial site and 1.0%/y ( 95 % CI , -1.4 % to -0.6 % ) at a distal radial site . Vertebral bone mineral content ( assessed by dual-energy quantitative computed tomography ) declined by 2.3%/y ( 95 % CI , -2.8 % to -1.8 % ) . In these healthy men with a high basal dietary calcium intake ( 1159 mg/d ) , calcium and cholecalciferol supplementation did not affect bone loss at any site . CONCLUSIONS Normal men experience a substantial bone loss at both axial and appendicular sites that is not prevented by calcium and vitamin D supplementation in a well-nourished population", "CONTEXT Despite decades of use and considerable research , the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain . OBJECTIVE To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled disease prevention trial ( the estrogen-alone component of the Women 's Health Initiative [ WHI ] ) conducted in 40 US clinical centers beginning in 1993 . Enrolled were 10 739 postmenopausal women , aged 50 - 79 years , with prior hysterectomy , including 23 % of minority race/ethnicity . INTERVENTION Women were r and omly assigned to receive either 0.625 mg/d of conjugated equine estrogen ( CEE ) or placebo . MAIN OUTCOME MEASURES The primary outcome was coronary heart disease ( CHD ) incidence ( nonfatal myocardial infa rct ion or CHD death ) . Invasive breast cancer incidence was the primary safety outcome . A global index of risks and benefits , including these primary outcomes plus stroke , pulmonary embolism ( PE ) , colorectal cancer , hip fracture , and deaths from other causes , was used for summarizing overall effects . RESULTS In February 2004 , after review ing data through November 30 , 2003 , the National Institutes of Health ( NIH ) decided to end the intervention phase of the trial early . Estimated hazard ratios ( HRs ) ( 95 % confidence intervals [ CIs ] ) for CEE vs placebo for the major clinical outcomes available through February 29 , 2004 ( average follow-up 6.8 years ) , were : CHD , 0.91 ( 0.75 - 1.12 ) with 376 cases ; breast cancer , 0.77 ( 0.59 - 1.01 ) with 218 cases ; stroke , 1.39 ( 1.10 - 1.77 ) with 276 cases ; PE , 1.34 ( 0.87 - 2.06 ) with 85 cases ; colorectal cancer , 1.08 ( 0.75 - 1.55 ) with 119 cases ; and hip fracture , 0.61 ( 0.41 - 0.91 ) with 102 cases . Corresponding results for composite outcomes were : total cardiovascular disease , 1.12 ( 1.01 - 1.24 ) ; total cancer , 0.93 ( 0.81 - 1.07 ) ; total fractures , 0.70 ( 0.63 - 0.79 ) ; total mortality , 1.04 ( 0.88 - 1.22 ) , and the global index , 1.01 ( 0.91 - 1.12 ) . For the outcomes significantly affected by CEE , there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years . The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years . CONCLUSIONS The use of CEE increases the risk of stroke , decreases the risk of hip fracture , and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years . A possible reduction in breast cancer risk requires further investigation . The burden of incident disease events was equivalent in the CEE and placebo groups , indicating no overall benefit . Thus , CEE should not be recommended for chronic disease prevention in postmenopausal women", "The effects of a supervised 1-y walking program and increased dietary calcium ( milk supplement , 831 mg/d , vs placebo drink , 41 mg/d ) on bones were examined in 36 postmenopausal women ( 60.2 + /- 6.5 y ) . Trabecular bone-mineral density ( BMD ) of the lumbar spine ( L1-L3 ) , measured by computed tomography , increased by 0.5 % in exercising women ( n = 18 ) and decreased by 7.0 % in sedentary women ( n = 18 ; P = 0.02 ) . Femoral-neck BMD measured by dual-photon absorptiometry ( DPA ) increased by 2.0 % in women consuming high dietary calcium ( n = 18 ) and decreased by 1.1 % in those on moderate calcium intake ( n = 18 ; P = 0.001 ) . Neither exercise nor dietary calcium had an effect on lumbar spine ( L2-L4 ) measured by DPA , distal radius measured by single-photon absorptiometry , or total body calcium measured by in vivo neutron activation . The varying proportions and rates of turnover of trabecular and cortical bone from one site to another suggest that exercise and high dietary calcium may preferentially alter bone density at different skeletal sites", "BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year", "A r and omized , prospect i ve , double-blind test was carried out to compare the effects of heated oyster shell-seaweed calcium ( AAA Ca ) , calcium carbonate , and placebo in 58 elderly , hospitalized women with the mean age of 80 divided into three groups . Group A received 900 mg/day Ca as AAA Ca , Group B 900 mg/day Ca as CaCO3 , and Group C placebo besides regular hospital diet containing approximately 600 mg Ca/day for 24 months . From the 25th to the 30th month , all groups were given AAA Ca . Lumbar spine and radial bone mineral density ( BMD ) were measured at 3-month intervals . Urinary Ca/Cr and serum alkaline phosphatase , intact and midportion serum parathyroid hormone ( PTH ) , and calcitonin were also measured at intervals . From the 6th to the 24th month of the study , the ratio of lumbar spine BMD ( L2–L4 by DPX , Lunar ) to the basal pretest value was consistently and significantly higher in Group A than Group C but not higher in Group B than in Group C. PTH , measured 12 months after the beginning of the study , was lower in Group A than in Group C , but no significant difference was found between Groups B and C. At 3 months after the placebo was switched to AAA Ca in Group C , serum PTH was significantly decreased from the level during placebo supplement . Morning urine Ca/Cr decreased in Groups A after 18 months and in B after 12 months , but not in C. Serum alkaline phosphatase decreased in Group A significantly compared with Group C , but not in Group B. AAA Ca appears to be effective for increasing BMD in elderly subjects", "BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo . Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures", "ABSTRACT Objective : Bisphosphonates such as alendronate are widely used for postmenopausal osteoporosis . Supplemental calcium is also generally recommended . This trial directly compares alendronate to supplemental calcium and examines the effect of calcium supplementation on alendronate treatment . Methods : This 2-year , r and omized , double-blind , multicenter trial enrolled healthy , postmenopausal women with low bone mineral density ( BMD ) . Patients with a dietary calcium intake ≥ 800 mg/day received daily vitamin D 400 IU and alendronate 10 mg/calcium-placebo , alendronate 10 mg/elemental calcium 1000 mg , or alendronate-placebo/calcium 1000 mg ( 2:2:1 ) . Endpoints included BMD , bone turnover markers ( BTMs ) , and adverse events . Results : R and omized patients ( N = 701 ) were an average of 20.4 years postmenopausal . After 24 months , increases in lumbar spine BMD differed significantly between patients receiving calcium alone ( 0.8 % ) and either alendronate alone ( 5.6 % ) or alendronate + calcium ( 6.0 % ) ( p at the trochanter and femoral neck ( p were significantly lower with alendronate-containing treatments than calcium alone ( p Addition of calcium supplementation to alendronate did not significantly increase BMD compared to alendronate alone ( p = 0.29 to 0.97 ) , but did result in a statistically significant , though small , additional reduction in urinary NTx . Adverse events were similar among treatment groups . Limitations include no assessment of vitamin D levels and a discontinuation rate of approximately 30 % , although discontinuation rates were similar among treatment groups . Conclusions : In postmenopausal women with a daily intake of ≥ 800 mg calcium and 400 IU vitamin D , 24-month treatment with alendronate 10 mg daily with or without calcium 1000 mg result ed in significantly greater increases in BMD and reduction of bone turnover than supplemental calcium alone . Addition of supplemental calcium to alendronate treatment had no effect on BMD and result ed in a small , though statistically significant , additional reduction in NTx ", "UNLABELLED A 3-year prospect i ve , r and omized , placebo-controlled trial of oral clodronate 800 mg showed that the incidence of clinical fractures was decreased by 20 % in 5596 elderly women unselected for osteoporosis . The effect occurred in the absence of systematic calcium and vitamin D supplementation and was observed across a wide range of BMDs . INTRODUCTION To date , most studies with bisphosphonates have reported on their use in individuals selected to be at high risk for fracture usually by the presence of low BMD or a prior fragility fracture , usually of the spine . We wished to determine the effect of the bisphosphonate , clodronate , on the rate of fractures in women > or = 75 years of age living in the community . MATERIAL S AND METHODS Women > or = 75 years of age living in the general community in South Yorkshire and North Derbyshire , identified from general practice registers , were recruited by letter of invitation to a r and omized , double-blind , controlled trial of 800 mg oral clodronate ( Bonefos ) or matching placebo daily over 3 years . The main outcomes were the incidences of hip and any clinical fracture . RESULTS Of the 5579 elderly women included in the intention-to-treat analysis of efficacy , 114 had a new hip fracture during the 3-year treatment phase : 56 ( 2.0 % ) women in the clodronate group and 58 ( 2.1 % ) women in the placebo group ( hazard ration [ HR ] , 1.02 ; 95 % CI , 0.71 - 1.47 ) . Clodronate did , however , decrease the incidence of any clinical fracture by 20 % ( 264 women [ 9.5 % ] versus 337 [ 12.1 % ] in the placebo group ; HR , 0.80 ; 95 % CI , 0.68 - 0.94 ) . The incidence of osteoporosis-associated nonhip fractures was also significantly decreased by 29 % ( 5.2 % versus 7.4 % ; HR , 0.71 ; 95 % CI , 0.57 - 0.87 ) . The ability of clodronate to reduce the risk of osteoporotic fracture was independent of baseline BMD , but the number needed-to-treat was lower in the presence of osteoporosis . CONCLUSIONS Oral daily clodronate can prevent fractures without significant adverse effects in elderly women living in the general community . The effect on hip fracture risk is not significant , but an effect similar to that at other nonvertebral sites can not be excluded . This study suggests that antiresorptive therapies can reduce fracture incidence in high-risk individuals even in the presence of a normal or osteopenic BMD", "OBJECTIVE The hypothesis was that the calcium and vitamin D supplementation prevents falls at the population level . STUDY DESIGN The OSTPRE-FPS was a r and omized population -based open-trial with 3-year follow-up . The supplementation group ( n=1566 ) received daily cholecalciferol 800IU+calcium carbonate 1000 mg , while the control group ( n=1573 ) received no supplementation or placebo . A r and omly selected sub sample of 593 subjects underwent a detailed measurement program including serum 25(OH)D measurements . MAIN OUTCOME MEASURE The occurrence of falls was the primary outcome of the study . The participants in the sub sample were telephoned at 4 months intervals and the rest of the trial population was interviewed by phone once a year . RESULTS In the entire trial population ( ETP ) , there were 812 women with 1832 falls in the intervention group and 833 women with 1944 falls in the control group ( risk ratio was 0.98 , 95 % CI 0.92 - 1.05 , P=0.160 ) . The supplementation was not associated with single or multiple falls in the ETP . However , in the sub sample , multiple fall incidence decreased by 30 % ( odds ratio ( OR ) 0.70 , 95 % CI 0.50 - 0.97 , P=0.034 ) in the supplementation group . Further , the supplementation decreased the incidence of multiple falls requiring medical attention ( OR 0.72 , 95 % CI 0.53 - 0.97 , P=0.031 ) in the ETP . The mean compliance in the entire trial population was 78 % and in the sub sample 79 % . DISCUSSION Overall , the primary analysis showed no association between calcium and vitamin D supplementation and risk of falls . However , the results of a post hoc analysis suggested that there was a decreased risk of multiple falls requiring medical attention : this finding requires confirmation", "OBJECTIVE Calcium and vitamin D deficiency is common in older individuals , particularly those who live in nursing homes , and increases the risk of osteoporosis and fractures . METHODS We conducted a r and omized double-blind placebo-controlled study of combined supplementation with 500 mg of elemental calcium , as carbonate , and 400 IU of vitamin D bid for 12 months in women older than 65 years of age with vitamin D deficiency , defined as serum 25(OH)D concentrations RESULTS Mean patient age was 75 + /- 7 years , and median daily dietary intakes of calcium and vitamin D were 697 mg and 66.8 IU in the supplemented group ( n = 95 ) and 671 mg and 61.8 IU in the placebo group ( n = 97 ) . The median serum 25(OH)D level was 7.0 ng/ml in both groups , and the medial intact parathyroid hormone ( PTHi ) levels were 49 and 48 pg/ml in the supplemented and placebo groups , respectively . The median increase in serum 25(OH)D was 22.0 ng/ml in the supplemented group and 4 ng/ml in the placebo group ( P median bone mineral density increase was significantly greater in the supplemented group than in the placebo group : + 2.98 % vs. -0.21 % at L2-L4 ( P = 0.0009 ) , + 1.19 % and -0.83 % at the femoral neck ( P = 0.015 ) , + 0.86 % and -0.56 % at the trochanter ( P = 0.015 ) , and + 0.99 % and + 0.11 % for the whole body ( P = 0.01 ) . Similarly , the median decrease in the main bone markers was significantly greater in the treated group than in the placebo group : -1.35 microg/l vs. + 0.50 microg/l for bone alkaline phosphatase ( P = 0.008 ) , -16.6 nmol/mmol creatinine vs. -2.3 nmol/mmol creatinine for urinary type I amino-terminal telopeptide ( P = 0.001 ) , and -896 pmol/l vs. -201 pmol/l for serum type I carboxy-terminal telopeptide ( P = 0.003 ) . We found no significant differences between the two groups for serum calcium , although urinary calcium excretion changed more in the supplemented group than in the placebo group . In conclusion , bone mass in older women with vitamin D deficiency increases significantly at the lumbar spine , femur , trochanter , and whole body after calcium and vitamin D supplementation for 1 year , and concomitantly bone markers improved as vitamin D levels returned to normal", "This 4-y study investigated the effects of a calcium carbonate supplement on bone loss in 169 women aged 35 - 65 y , r and omly assigned to placebo and treatment ( 1500 mg Ca/d ) groups in a double-blind design . Bone mineral content ( BMC ) and width ( W ) were measured bilaterally on the radius , ulna , and humerus . BMC and BMC /W loss rates were consistently lower in treatment than in control subjects . Loss was significantly reduced in the left and right humerus and the right radius . In premenopausal subjects , only left humerus BMC loss was significantly reduced by Ca supplementation . In postmenopausal treatment subjects , BMC and BMC /W bone loss was reduced in all 12 ( bilateral radius , ulna , and humerus ) of the bone variables measured , 5 at p less than 0.01 and 2 at p less than 0.05 . Ca supplementation counteracted a large portion of the additional bone loss attributable to menopause in this population", "PURPOSE Calcium has been shown to have positive effects on bone mineral density in postmenopausal women . However , these effects are small , it is unknown whether they are sustained with long-term use , they have not been shown with intention-to-treat analyses , and the evidence for fracture prevention with calcium monotherapy is inconsistent . METHODS A r and omized controlled trial of calcium ( 1 g/day as the citrate ) in 1471 healthy postmenopausal women ( aged 74+/-4 years ) was performed to assess the effects on bone density and fracture incidence over 5 years . RESULTS Follow-up was complete in 90 % of subjects , and average medication compliance was 55 % to 58 % . Calcium had a significant beneficial effect on bone density ( intention-to-treat analysis ) , with between-groups differences at 5 years of 1.8 % ( spine ) , 1.6 % ( total hip ) , and 1.2 % ( total body ) . Effects were greater in a per- protocol analysis ( 5-year differences of 2.3 % , 2.8 % , and 1.8 % , respectively ) . A total of 425 fractures occurred in 281 women . Hazard ratios , based on time to first fracture , were 0.90 ( 95 % confidence interval [ CI ] , 0.71 - 1.16 ) for any symptomatic fracture , 0.72 ( 95 % CI , 0.44 - 1.18 ) for vertebral , 3.55 ( 95 % CI , 1.31 - 9.63 ) for hip , and 0.65 ( 95 % CI , 0.41 - 1.04 ) for forearm fracture . Per- protocol analysis found respective hazard ratios of 0.86 ( 95 % CI , 0.64 - 1.17 ) , 0.62 ( 95 % CI , 0.33 - 1.16 ) , 3.24 ( 95 % CI , 0.65 - 16.1 ) , and 0.45 ( 95 % CI , 0.24 - 0.87 ) . Height loss was reduced by calcium in the per- protocol population ( P=.03 ) . Serum alkaline phosphatase and procollagen type-I N-terminal propeptide were lower in the calcium group at 5 years , but constipation was more common . CONCLUSIONS Calcium results in a sustained reduction in bone loss and turnover , but its effect on fracture remains uncertain . Poor long-term compliance limits its effectiveness", "BACKGROUND There is no consistent evidence , to our knowledge , that calcium supplementation affects bone mineral density ( BMD ) in men , despite male osteoporosis being a common clinical problem . METHODS To determine the effects of calcium supplementation ( 600 mg/d , 1200 mg/d , or placebo ) on BMD in men , we conducted a double-blind , r and omized controlled trial for a 2-year period at an academic clinical research center . A total of 323 healthy men at least 40 years old ( mean age , 57 years ) were recruited by newspaper advertisement . Complete follow-up was achieved in 96 % of subjects . RESULTS The BMD increased at all sites in the group receiving calcium , 1200 mg/d , by 1 % to 1.5 % more than those receiving placebo . The results for the group receiving calcium , 600 mg/d , were not different from the placebo group at any BMD site . There was no interaction between the BMD treatment effect and either age or dietary calcium intake . There were dosage-related , sustained decreases in serum parathyroid hormone ( P total alkaline phosphatase activity ( P = .01 ) , and procollagen type 1 N-terminal propeptide ( P Tooth loss , constipation , and cramps were unaffected by calcium supplementation , falls tended to be less frequent in the group receiving calcium , 1200 mg/d , but vascular events tended to be more common in the groups receiving calcium vs the group receiving placebo . CONCLUSION Calcium , 1200 mg/d , has effects on BMD in men comparable with those found in postmenopausal women but a dosage of 600 mg/d is ineffective for treating BMD . TRIAL REGISTRATION actr.org.au Identifier : 012605000274673" ]

[ "Background The benefits of robotic techniques for implanting femoral components during THA are still controversial . Questions / Purpose sThe purpose of this study was to prospect ively compare the results and complications of robotic-assisted and h and -rasping stem implantation techniques . Method The minimum followup was 5 years ( mean , 67 months ; range , 60–85 months ) . One hundred forty-six primary THAs on 130 patients were included in this study . Robot-assisted primary THA was performed on 75 hips and a h and -rasping technique was used on 71 hips . Results At 2 and 3 years postoperatively , the Japanese Orthopaedic Association ( JOA ) clinical score was slightly better in the robotic-assisted group . At 5 years followup , however , the differences were not significant . Postoperative limb lengths of the robotic-milling group had significantly less variance than the h and -rasping group . At 2 years postoperatively , there was significantly more stress shielding of the proximal femur in the h and -rasping group ; this difference was more significant 5 years postoperatively . Conclusions Substantially more precise implant positioning seems to have led to less variance in limb-length ine quality and less stress shielding of the proximal femur 5 years postoperatively . Level of Evidence Level II , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence", "The ROBODOC ® system was design ed to address potential human errors in performing cementless total hip replacement . The system consists of a preoperative planning computer workstation ( called ORTHODOC ) and a five-axis robotic arm with a high speed milling device as an end effector . The combined experience of the United States Food and Drug Administration multicenter trial and the German postmarket use of the system are reported . The United States study is controlled and r and omized with 136 hip replacements performed at three centers ( 65 ROBODOC ® and 62 control ) . Followup was 1 year on 127 hip replacements and 2 years on 93 hip replacements . No differences were found in the Harris hip scores or the Short Form Health Survey outcomes question naire . Length of stay also was not different , but the surgical time and blood loss were greater in the ROBODOC ® group . This was attributed to a learning curve at each center . Radiographs were evaluated by an independent bone radiologist and showed statistically better fit and positioning of the femoral component in the ROBODOC ® group . Complications were not different , except for three cases of intraoperative femoral fracture in the control group and none in the ROBODOC ® group . The German study reports on 858 patients , 42 with bilateral hip replacements and this includes 30 revision cases for a total of 900 hip replacements . The Harris hip score rose from 43.7 to 91.5 . In these cases the surgical time declined quickly from 240 minutes for the first case to 90 minutes . No intraoperative femoral fractures occurred in 900 cases . Other complications were comparable with total hip replacements performed using conventional techniques . The ROBODOC ® system is thought to be safe and effective in producing radiographically superior implant fit and positioning while eliminating femoral fractures", "AIM Robotic assisted total hip arthroplasty remains controversial , since wider exposure of the proximal femur and placement of the leg in maximal hip adduction and external rotation using a rigid leg-holder apparatus may impair significantly the hip abductors . Consequently , it is the purpose of this study to analyse and report both clinical outcome and hip abductor function following robotic assisted versus conventional total hip arthroplasty . MATERIAL AND METHODS 36 robotic-assisted ( CASPAR , Orto-Maquet , Rastatt , Germany ) and 35 conventional cementless total hip arthroplasties were followed on average for 18 months regarding incidence of complications , Harris hip score , the scoring system according to Merle d'Aubigné and Postel , hip abductor function ( using a spring-balance ) , and incidence of Trendelenburg 's sign ( according to the Kuhfuss-classification ) . Statistical analysis was performed in case of continuous data using the t test and the Mann-Whitney test , respectively , and in case of categorical data using Fisher 's exact test and the chi-squared test , respectively . The level of significance was set as p Average duration of surgery ( CASPAR : 100.6 min ; conventional : 51.5 min ; p average loss of haemoglobin ( CASPAR : 4.5 mg/dL ; conventional : 3.3 mg/dL ; p = 0.0002 ) differed significantly , whereas the incidence of complications ( CASPAR : two dislocations , one sciatic paresis , one deep infection ; conventional : one dislocation , two fissures ) , revision rate ( CASPAR : 5.6 % ; conventional : 2.9 % ) , and incidence of heterotopic ossifications ( CASPAR : 30.6 % ; conventional : 17.1 % ) was comparable following both procedures ( p > 0.05 ) . Improvement of the Harris hip score also was comparable in both groups ( CASPAR : 40.9 to 86.1 points ; conventional : 39.5 to 88.0 points ; p = 0.21 ) , whereas improvement of the score according to Merle d'Aubigné and Postel was significantly greater following the manual procedure ( CASPAR : 10.1 to 16.0 points ; conventional : 8.3 to 16.6 points ; p regarding hip abductor function ( CASPAR : 76.1 % ; conventional : 93.8 % of the contralateral hip ; p incidence of Trendelenburg 's sign ( CASPAR : 61.1 % ; conventional : 25.7 % ; p = 0.0014 ) . CONCLUSION The significant functional impairment following robotic assisted THA should be taken critically into consideration prior to initiating such procedure", "The ROBODOC system has provided better fit and fill of the stem and less destruction of the bony architecture than with manual surgery . These benefits might affect femoral periprosthetic bone remodeling . We evaluated the effects of robotic milling in cementless total hip arthroplasty ( THA ) in a longitudinal 24-month follow-up study using dual energy X-ray absorptiometry ( DEXA ) and plain radiographs of 29 patients ( 31 hips ) after ROBODOC THA and 24 patients ( 27 hips ) after manual THA with the same stem design . To minimize the influence of other factors on bone remodeling , only female osteoarthritis patients , who had no drugs that might affect bone metabolism were enrolled . Significantly less bone loss occurred at the proximal periprosthetic areas in the ROBODOC group . In zone 1 , the decrease was 15.5 versus 29.9 % using conventional rasping ; in zone 7 , the loss was 17.0 % with ROBODOC compared to 30.5 % with conventional rasping ( p endosteal spot welds in the proximal medial portion were more pronounced in the ROBODOC group ( 48 vs. 11 % in the conventional group , p milling is effective in facilitating proximal load transfer around the femoral component and minimizing bone loss after cementless THA", "Background Improper acetabular component orientation in THA has been associated with increased dislocation rates , component impingement , bearing surface wear , and a greater likelihood of revision . Therefore , any reasonable steps to improve acetabular component orientation should be considered and explored . Questions / purpose sWe therefore sought to compare THA with a robotic-assisted posterior approach with manual alignment techniques through a posterior approach , using a matched-pair controlled study design , to assess whether the use of the robot made it more likely for the acetabular cup to be positioned in the safe zones described by Lewinnek et al. and Callanan et al. Methods Between September 2008 and September 2012 , 160 THAs were performed by the senior surgeon . Sixty-two patients ( 38.8 % ) underwent THA using a conventional posterior approach , 69 ( 43.1 % ) underwent robotic-assisted THA using the posterior approach , and 29 ( 18.1 % ) underwent radiographic-guided anterior-approach THAs . From September 2008 to June 2011 , all patients were offered anterior or posterior approaches regardless of BMI and anatomy . Since introduction of the robot in June 2011 , all THAs were performed using the robotic technique through the posterior approach , unless a patient specifically requested otherwise . The radiographic cup positioning of the robotic-assisted THAs was compared with a matched-pair control group of conventional THAs performed by the same surgeon through the same posterior approach . The safe zone ( inclination , 30 ° –50 ° ; anteversion , 5 ° –25 ° ) described by Lewinnek et al. and the modified safe zone ( inclination , 30 ° –45 ° ; anteversion , 5 ° –25 ° ) of Callanan et al. were used for cup placement assessment . Matching criteria were gender , age ± 5 years , and ( BMI ) ± 7 units . After exclusions , a total of 50 THAs were included in each group . Strong interobserver and intraobserver correlations were found for all radiographic measurements ( r > 0.82 ; p the robotic-assisted THAs were within the safe zone described by Lewinnek et al. compared with 80 % ( 40/50 ) of the conventional THAs ( p = 0.001 ) . Ninety-two percent ( 46/50 ) of robotic-assisted THAs were within the modified safe zone described by Callanan et al. compared with 62 % ( 31/50 ) of conventional THAs p ( p = 0.001 ) . The odds ratios for an implanted cup out of the safe zones of Lewinnek et al. and Callanan et al. were zero and 0.142 , respectively ( 95 % CI , 0.044 , 0.457 ) . Conclusions Use of the robot allowed for improvement in placement of the cup in both safe zones , an important parameter that plays a significant role in long-term success of THA . However , whether the radiographic improvements we observed will translate into clinical benefits for patients —such as reductions in component impingement , acetabular wear , and prosthetic dislocations , or in terms of improved longevity — remains unproven . Level of Evidence Level III , therapeutic study . See the Instructions for Authors for a complete description of levels of evidence", "BACKGROUND Robotic-assisted total hip replacement has become a common method of implantation , especially in Europe . It frequently has been postulated that robotic reaming would result in an improved clinical outcome due to the better fit of the prosthesis , but that has never been demonstrated in a prospect i ve study , to our knowledge . The purpose of this study was to compare robotic-assisted implantation of a total hip replacement with conventional manual implantation . METHODS One hundred and fifty-four patients scheduled for total hip replacement were r and omly assigned to undergo either conventional manual implantation of an S-ROM prosthesis ( eighty patients ) or robotic-assisted implantation of such a prosthesis ( seventy-four patients ) . The five-axis ROBODOC was used for the robotic-assisted procedures . Preoperatively as well as at three , six , twelve , and twenty-four months after surgery , the scores according to the Harris and Merle d'Aubigné systems and the Mayo clinical score were determined . Radiographs made at these intervals were analyzed for evidence of loosening , prosthetic alignment , and heterotopic ossification . RESULTS Thirteen ( 18 % ) of the seventy-four attempted robotic implantations had to be converted to manual implantations as a result of failure of the system . The duration of the robotic procedures was longer than that of the manual procedures ( mean and st and ard deviation,107.1 + /- 29.1 compared with 82.4 + /- 23.4 minutes , p Limb-length e quality ( mean discrepancy , 0.18 + /- 0.30 compared with 0.96 + /- 0.93 cm , p varus-valgus orientation of the stem ( mean angle between the femur and the shaft of the prosthesis , 0.34 degrees + /- 0.67 degrees compared with 0.84 degrees + /- 1.23 degrees , p robotic procedures . At six months , slightly more heterotopic ossification was seen in the group treated with robotic implantation . The group treated with robotic implantation had a better Mayo clinical score at six and twelve months and a better Harris score at twelve months ; however , by twenty-four months , no difference was found between the groups with regard to any of the three scores . Dislocation was more frequent in the group treated with robotic implantation : it occurred in eleven of the sixty-one patients in that group compared with three of eighty in the other group ( p . Recurrent dislocation and pronounced limping were indications for revision surgery in eight of the sixty-one patients treated with robotic implantation compared with none of the seventy-eight ( excluding two with revision for infection ) treated with manual insertion ( p Rupture of the gluteus medius tendon was observed during all of the revision operations . CONCLUSIONS The robotic-assisted technology had advantages in terms of preoperative planning and the accuracy of the intraoperative procedure . Disadvantages were the high revision rate ; the amount of muscle damage , which we believe was responsible for the higher dislocation rate ; and the longer duration of surgery . This technology must be further developed before its widespread usage can be justified", "BACKGROUND The purpose of this study was to report minimum 2-year outcomes and complications for robotic-arm-assisted total hip arthroplasty ( THA ) . METHODS Data were prospect ively collected and retrospectively review ed between June 2011 and April 2014 . Inclusion criteria were primary robotic-arm-assisted THAs treating idiopathic osteoarthritis with ≥ 2-year follow-up . Demographics , operating time , complications , 2-year outcome scores and satisfaction , and subsequent surgeries were recorded . RESULTS There were 181 cases eligible for inclusion , of which 162 ( 89.5 % ) had minimum 2-year follow-up . At the latest follow-up , the mean visual analogue scale was 0.7 , satisfaction was 9.3 , Harris hip score was 91.1 and forgotten joint score was 83.1 . Six ( 3.7 % ) intraoperative complications and six ( 3.7 % ) postoperative complications were reported . No leg length discrepancies ( LLDs ) or dislocations were reported . CONCLUSIONS Robotic-arm-assisted THA demonstrates favourable short-term outcomes and does not result in a higher complication rate compared to non-robotic THA as reported by the literature", "Abstract Background : Recently , two topical issues in total hip arthroplasty ( THA ) have been robot-assisted surgery and use of a short stem . The purpose of this study was to evaluate the effects of robotic milling on the accuracy of short femoral stem positioning and on the short-term clinical outcome in THA using a prospect i ve , r and omized design . Methods : We r and omized 54 patients into two groups , either robotic milling group or manual rasping group . The patients were assessed clinical ly and radiographically at 8 weeks , 5 months , 12 months , and 24 months . Results : Robotic milling group had a significantly longer operation time , requiring on average 8.9 min for registration and 11.2 min for milling . On the other h and , robotic milling group showed superior results in terms of stem alignment and leg length e quality . Two intraoperative femoral fractures occurred only in manual rasping group . Harris hip scores and WOMAC scores at 24 months postoperatively were similar in both groups . No complications including stem loosening , infection , nerve palsy , or dislocation were encountered in either group during the follow-up period . Conclusions : The present study suggested that robot-assisted short stem THA could increase the accuracy of stem alignment , improve leg length e quality , and help reduce the risk of intraoperative femoral fracture as compared with manual rasping . However , the clinical outcome scores did not differ between the two groups at the time of short-term follow-up . Long-term follow-up is needed to determine whether there will be a long-term clinical relevance of robot-assisted implantation of short femoral stems in THA" ]

[ "IMPORTANCE Despite the frequency of atrial fibrillation ( AF ) in clinical practice , relatively little is known about sex differences in symptoms and quality of life and how they may affect treatment and outcomes . OBJECTIVE To determine whether symptoms , quality of life , treatment , and outcomes differ between women and men with AF . DESIGN , SETTING , AND PARTICIPANTS This observational cohort study included 10 135 patients with AF . The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation is a prospect i ve , nationwide , multicenter outpatient registry of patients with incident and prevalent AF enrolled at 176 sites between June 2010 and August 2011 . MAIN OUTCOMES AND MEASURES Symptoms , quality of life as measured by Atrial Fibrillation Effects on Quality of Life scores , AF treatment , cardiovascular outcomes , stroke or non- central nervous system embolism , and all-cause mortality . RESULTS Overall , 4293 of the cohort ( 42 % ) were female . Compared with men , women were older ( 77 years ; interquartile range [ IQR ] , 69 - 83 , vs 73 years ; IQR , 65 - 80 ; P median CHA2DS2-VASc scores ( 5 ; IQR , 4 - 6 , vs 3 ; IQR , 2 - 5 ; P sleep apnea ( 578 [ 13.5 % ] vs 1264 [ 21.6 % ] ; P asymptomatic ( European Heart Rhythm Association class I ) compared with 42.5 % of men ( n = 2483 ) in unadjusted analyses ( P overall Atrial Fibrillation Effects on Quality of Life scores ( n = 2007 ; 80 ; IQR , 62 - 92 vs 83 ; IQR , 69 - 94 ; P anticoagulation and similar time in therapeutic range . In follow-up , women experienced lower risk-adjusted all-cause mortality ( adjusted hazard ratio , 0.57 ; 95 % CI , 0.49 - 0.67 ) and cardiovascular death ( adjusted hazard ratio , 0.56 ; 95 % CI , 0.44 - 0.72 ) ; however , they had a higher risk for stroke or non- central nervous system embolism ( adjusted hazard ratio , 1.39 ; 95 % CI , 1.05 - 1.84 ; P = .02 ) compared with men . CONCLUSIONS AND RELEVANCE Women with AF have more symptoms and worse quality of life . Despite higher risk , women have lower risk-adjusted all-cause and cardiovascular death compared with men , but higher stroke rates . Future studies should focus on how treatment and interventions specifically affect AF-related quality of life and cardiovascular outcomes in women . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01165710", "ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American – Australian – African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association AND ROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific Heart Rhythm Society aPTT : activated partial thromboplastin time ARB : angiotensin-receptor blocker ARISTOTLE : Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation ATHENA : A placebo-controlled , double-blind , parallel arm Trial to assess the efficacy of dronedarone 400 mg b.i.d . for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ATRIA : AnTicoagulation and Risk factors In Atrial fibrillation AVERROES : Apixaban VErsus acetylsalicylic acid ( ASA ) to Reduce the Rate Of Embolic Stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment AVRO : A prospect i ve , r and omized , double-blind , Active-controlled , superiority study of Vernakalant vs. amiodarone in Recent Onset atrial fibrillation b.i.d : bis in die ( twice daily ) b.p.m . : beats per minute CABANA : Catheter ABlation vs . ANtiarrhythmic drug therapy for Atrial fibrillation CABG : coronary artery bypass graft CAP : Continued Access to Protect AF CHA2DS2-VASc : Congestive heart failure or left ventricular dysfunction Hypertension , Age ≥75 ( doubled ) , Diabetes , Stroke (doubled)-Vascular disease , Age 65–74 , Sex category ( female ) CHADS2 : Congestive heart failure , Hypertension , Age ≥75 , Diabetes , Stroke ( doubled ) CI : confidence interval CRAFT : Controlled R and omized Atrial Fibrillation Trial CrCl : creatinine clearance DAFNE : Dronedarone Atrial FibrillatioN study after Electrical cardioversion DIONYSOS : R and omized Double blind trIal to evaluate efficacy and safety of drOnedarone ( 400 mg b.i.d . ) vs . amiodaroNe ( 600 mg q.d . for 28 daYS , then 200 mg qd thereafter ) for at least 6 mOnths for the maintenance of Sinus rhythm in patients with atrial fibrillation EAST : Early treatment of Atrial fibrillation for Stroke prevention Trial EHRA : European Heart Rhythm Association ECG : electrocardiogram EMA : European Medicines Agency ERATO : Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation EURIDIS : EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm FAST : atrial Fibrillation catheter Ablation vs . Surgical ablation Treatment FDA : Food and Drug Administration Flec-SL : Flecainide Short-Long trial HAS-BLED : Hypertension , Abnormal renal/liver function , Stroke , Bleeding history or predisposition , Labile INR , Elderly , Drugs/alcohol concomitantly HF-PEF : heart failure with preserved ejection fraction HF-REF : heart failure with reduced ejection fraction HR : hazard ratio HRS : Heart Rhythm Society ICH : intracranial haemorrhage INR : international normalized ratio i.v . : intravenous J-RHYTHM : Japanese RHYTHM management trial for atrial fibrillation LAA : left atrial appendage LoE : level of evidence LVEF : left ventricular ejection fraction MANTRA-PAF : Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation NICE : National Institute for Health and Clinical Excellence NOAC : novel oral anticoagulant NSAID : non-steroidal anti-inflammatory drug NYHA : New York Heart Association OAC : oral anticoagulant or oral anticoagulation o.d . : omni die ( every day ) PALLAS : Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of st and ard therapy PCI : percutaneous coronary intervention PREVAIL : Prospect i ve R and omized EVAluation of the LAA closure device In patients with atrial fibrillation v s. Long-term warfarin therapy PROTECT AF : WATCHMAN LAA system for embolic PROTECTion in patients with Atrial Fibrillation PT : prothrombin time RAAFT : Radio frequency Ablation Atrial Fibrillation Trial RE-LY : R and omized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate ROCKET-AF : Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in atrial fibrillation RRR : relative risk reduction TE : thromboembolism TIA : transient ischaemic attack t.i.d . : ter in die ( three times daily ) TOE : transoesophageal echocardiogram TTR : time in therapeutic range VKA : vitamin K antagonist Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition , taking into account the impact on", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Background Atrial fibrillation is very common in people aged 65 or older . This condition increases the risk of death , congestive heart failure and thromboembolic conditions . Many patients with atrial fibrillation are asymptomatic and a cerebrovascular accident ( CVA ) is often the first clinical presentation . Guidelines concerning the prevention of CVA recommend monitoring the heart rate in patients aged 65 or older . Recently , the MyDiagnostick ( Applied Biomedical Systems BV , Maastricht , The Netherl and s ) was introduced as a new screening tool which might serve as an alternative for the less accurate pulse palpation . This study was design ed to explore the diagnostic accuracy of the MyDiagnostick for the detection of atrial fibrillation . Methods A phase II diagnostic accuracy study in a convenience sample of 191 subjects recruited in primary care . The majority of participants were patients with a known history of atrial fibrillation ( n = 161 ) . Readings of the MyDiagnostick were compared with electrocardiographic recordings . Sensitivity and specificity and their 95 % confidence interval were calculated using 2x2 tables . Results A prevalence of 54 % for an atrial fibrillation rhythm was found in the study population at the moment of the study . A combination of three measurements with the MyDiagnostick for each patient showed a sensitivity of 94 % ( 95 % CI 87 – 98 ) and a specificity of 93 % ( 95 % CI 85 – 97 ) . Conclusion The MyDiagnostick is an easy-to-use device that showed a good diagnostic accuracy with a high sensitivity and specificity for atrial fibrillation in a convenience sample in primary care . Future research is needed to determine the place of the MyDiagnostick in possible screening or case-finding strategies for atrial fibrillation", "BACKGROUND AND PURPOSE Stroke occurring with atrial fibrillation ( AF ) is more likely to be fatal or more severe than non-AF stroke based on clinical series , but data from prospect i ve epidemiological studies are sparse and inconsistent . METHODS Over 40-year follow-up of the original 5070 Framingham cohort , 501 initial ischemic strokes , including 103 with AF , were analyzed . Stroke severity was rated as none , mild , moderate , severe , or fatal . Since 1981 , functional status indicated by the Barthel index has been evaluated acutely and at 3 , 6 , and 12 months . Severity and functional status of AF strokes were compared with non-AF strokes using chi 2 test and Student 's t test . Thirty-day mortality was assessed by logistic regression analyses . RESULTS AF was associated with increased stroke severity ( P = .048 ) . Thirty-day mortality was greater in AF strokes than in non-AF strokes ( 25 % versus 14 % ) . The multivariate-adjusted odds ratio for 30-day mortality for AF subjects was 1.84 ( 95 % confidence interval , 1.04 to 3.27 ) . Since 1981 , follow-up was available for 150 initial ischemic strokes , including 30 with AF . Compared with the non-AF group , the AF group had poorer survival and more recurrences during 1 year of follow-up . The AF subjects had lower mean Barthel index scores acutely ( 29.6 versus 58.6 , P fatal as non-AF stroke . Recurrence was more frequent , and functional deficits were more likely to be severe among survivors . Since stroke is usually the initial manifestation of embolism in AF , prevention is critical to reducing disability and mortality", "OBJECTIVES The present study determined the incidence and time course of atrial fibrillation ( AF ) recurrences in patients with a history of AF and fitted with an implantable monitoring device . BACKGROUND The long-term risk of undetected recurrence of AF in patients receiving stable antiarrhythmic therapy remains uncertain . METHODS In 110 patients with a class I indication for physiologic pacing and a history of AF , a pacemaker with dedicated functions for AF detection and electrogram storage was implanted , and antiarrhythmic drug treatment was optimized . Patients were regularly followed up with evaluation of AF-related symptoms , a resting electrocardiogram ( ECG ) , and interrogation of device memory . The incidence of AF recurrences lasting > 48 h in asymptomatic patients presenting in sinus rhythm ( SR ) at the respective follow-up visit constituted the primary end point of this prospect i ve study . RESULTS During 19 + /- 11 months , 678 follow-up visits were performed . Atrial fibrillation was documented in 51 patients ( 46 % ) by ECG recording and in 97 patients ( 88 % ) by a review of stored electrograms ( p AF recurrences lasting > 48 h in 50 patients , 19 of whom ( 38 % ) were completely asymptomatic and in SR at subsequent follow-up . In 11 ( 16 % ) of 67 patients with device-confirmed freedom from AF for > or =3 months , AF lasting > 48 h recurred subsequently . CONCLUSIONS This prospect i ve study demonstrates a high incidence of recurrent AF despite optimized antiarrhythmic therapy . Of particular note , AF relapses > 48 h remained totally asymptomatic in a significant proportion of patients . Freedom from AF for > or =3 months did not preclude subsequent long-lasting AF recurrence", "OBJECTIVES To determine the most cost-effective method of screening for atrial fibrillation ( AF ) in the population aged 65 years and over , as well as its prevalence and incidence in this age group . Also to evaluate the relative cost-effectiveness of different methods of recording and interpreting the electrocardiogram ( ECG ) within a screening programme . DESIGN Multicentred r and omised controlled trial . Purpose fully selected general practice s were r and omly allocated to 25 intervention practice s and 25 control practice s. SETTING Fifty primary care centres across the West Midl and s , UK . PARTICIPANTS Patients aged 65 years and over . INTERVENTIONS GPs and practice nurses in the intervention practice s received education on the importance of AF detection and ECG interpretation . Patients in the intervention practice s were r and omly allocated to systematic ( n = 5000 ) or opportunistic screening ( n = 5000 ) . Prospect i ve identification of pre-existing risk factors for AF within the screened population enabled comparison between targeted screening of people at higher risk of AF and total population screening . MAIN OUTCOME MEASURES AF detection rates in systematic ally screened and opportunistically screened population s in the intervention practice s were compared with AF detection rate in 5000 patients in the control practice s. The screening period was 12 months . RESULTS Baseline prevalence of AF was 7.2 % , with a higher prevalence in males ( 7.8 % ) and patients aged 75 years and over ( 10.3 % ) . The control population demonstrated higher baseline prevalence ( 7.9 % ) than either the systematic ( 6.9 % ) or opportunistic ( 6.9 % ) intervention population . In the control population 47 new cases were detected ( incidence 1.04 % per year ) . In the opportunistic arm 243 patients without a baseline diagnosis of AF were found to have an irregular pulse , with 177 having an ECG , yielding 31 new cases ( incidence 0.69 % per year ) . A further 44 cases were detected outside the screening programme ( overall incidence 1.64 % per year ) . In the systematic arm 2357 patients had an ECG yielding 52 new cases ( incidence 1.1 % per year ) . Of these , 31 were detected by targeted screening and a further 21 by total population screening . A further 22 cases were detected outside the screening programme ( overall incidence 1.62 % per year ) . In terms of ECG interpretation , computerised decision support software ( CDSS ) gave a sensitivity of 87.3 % , a specificity of 99.1 % and a positive predictive value ( PPV ) of 89.5 % compared with the gold st and ard ( cardiologist reporting ) . GPs and practice nurses performed less well . The only difference in performance between intervention population s and controls was that practice nurses from the control arm performed less well than with intervention practice nurses on interpretation of limb-lead ( PPV 38.8 % versus 20.8 % ) and single-lead ( PPV 37.7 % versus 24.0 % ) ECGs . The within-trial economic evaluation results showed the lowest incremental cost to be for the opportunistic arm , with an incremental cost-effectiveness ratio of 337 pounds Sterling for each additional case detected compared to the control arm . Opportunistic screening dominated both more intensive screening strategies . Model-based analyses showed small differences in cost and quality -adjusted life-years for different methods and intensities of screening , but annual opportunistic screening result ed in the lowest number of ischaemic strokes and greatest proportion of cases of AF diagnosed . Probabilistic sensitivity results indicated that there was a probability of approximately 60 % that screening from the age of 65 years was cost-effective in both men and women . CONCLUSIONS The results of the study indicated that in terms of a screening programme for atrial fibrillation in patients 65 and over , the only strategy that improved on routine practice was opportunistic screening , model-based analyses indicated that there was a probability of approximately 60 % of annual opportunistic screening being cost effective . It is suggested that the following topics are worthy of further investigation : the effect of the implementation of a screening programme for AF on the uptake and maintenance of anticoagulation in patients aged 65 years and over ; an evaluation of the role of CDSS in the diagnosis of cardiac arrythmias ; the best method for routinely detecting paroxysmal AF ; ways of improving healthcare professionals ' performance in ECG interpretation ; development of a robust economic model to incorporate data on new therapeutic agents for use as thromboprophylactic agents for patients with AF , and an evaluation of the relative risk of stroke for patients with incident as opposed to prevalent AF", "BACKGROUND Atrial fibrillation ( AF ) may occur without symptoms . Little is known about demographic features and prognostic information in patients with asymptomatic AF . METHODS In the AFFIRM study , 4060 patients were r and omized to either rhythm or rate control . At baseline , patients were identified as asymptomatic if they answered \" no \" to a 15-item question naire related to cardiac symptoms during AF in the 6 months before study entry . RESULTS There were 481 ( 12 % ) asymptomatic patients at baseline . Compared with symptomatic patients , asymptomatic patients were more often men and had a lower incidence of coronary artery disease and congestive heart failure , but had more cerebrovascular events . Asymptomatic patients had a longer duration of AF , a lower maximum heart rate , and better left ventricular function . They received fewer cardiac medications and fewer therapies to maintain sinus rhythm . At 5 years , there was a trend for better survival in asymptomatic patients ( 81 % vs 77 % , P = .058 ) , and they were more likely to be free from disabling stroke or anoxic encephalopathy , major bleeding , and cardiac arrest ( 79 % vs 67 % , P = .024 ) . However , mortality and major events were similar after correction for baseline differences . CONCLUSIONS Patients with asymptomatic AF have less serious heart disease but more cerebrovascular disease . Asymptomatic patients receive different therapies than symptomatic patients . However , the absence of symptoms and the differences in treatment does not confer a more favorable prognosis when differences in baseline clinical parameters are considered . Anticoagulation should be considered in these patients" ]

[ "Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results", "BACKGROUND Reductions in iodine and zinc deficiencies and improvements in hemoglobin were achieved from a micronutrient-fortified seasoning powder consumed in school lunches by children in northeast Thail and . OBJECTIVE The objective was to determine whether fortification with 4 micronutrients in a school lunch results in changes in children 's growth , morbidity , and cognitive function compared with no fortification . DESIGN In a r and omized controlled trial of 569 children aged 5.5 - 13.4 y from 10 schools , we compared the efficacy of a seasoning powder fortified with or without 5 mg Fe , 5 mg Zn , 50 mug I , and 270 mug vitamin A per serving consumed with a school lunch 5 d/wk . Here we report on results of the secondary functional outcomes . RESULTS The groups were comparable concerning compliance and loss to follow-up . The intervention had no statistically significant effect on anthropometric measures over 31 wk , but reduced the incidence of respiratory-related illnesses [ rate ratio ( RR ) : 0.83 ; 95 % CI : 0.73 , 0.94 ] , symptoms of runny nose ( RR : 0.80 ; 95 % CI : 0.70 , 0.92 ) , cough ( RR : 0.80 ; 95 % CI : 0.66 , 0.96 ) , and diarrhea ( RR : 0.38 ; 95 % CI : 0.16 , 0.90 ) . For the visual recall test , those in the fortified group recalled 0.5 more items ( 95 % CI : 0.1 , 0.9 ) than did the controls . There were no statistically significant differences between groups in the results of the digits forward and backward tests or in school grade s at the conclusion of the 2 semesters . CONCLUSION The beneficial effects on morbidity and visual recall over a short period , in addition to some biochemical improvements , highlight the potential of this micronutrient-fortified seasoning powder supplied in a school lunch . This trial was registered at clinical trials.gov as ACTRN12605000341628", "BACKGROUND Little is known about the combined effect of micronutrients and essential fatty acids on cognitive function in school-aged children . OBJECTIVE We assessed the effect of micronutrients , long-chain n-3 fatty acids , or both on indicators of cognitive performance in well-nourished and marginally nourished school-aged children . DESIGN Two 2-by-2 factorial r and omized controlled double-blind trials were performed home-based in Adelaide , South Australia , and at 6 primary schools in Jakarta , Indonesia . A total of 396 children ( aged 6 - 10 y ) in Australia and 384 children in Indonesia were r and omly allocated to receive a drink with a micronutrient mix ( iron , zinc , folate , and vitamins A , B-6 , B-12 , and C ) , with docosahexanoic acid ( DHA , 88 mg/d ) and eicosapentaenoic acid ( EPA , 22 mg/d ) , or with both or placebo 6 d/wk for 12 mo . Biochemical indicators were determined at baseline and 12 mo . Cognitive performance was measured at baseline , 6 mo , and 12 mo . RESULTS The micronutrient treatment significantly improved plasma micronutrient concentrations in Australian and Indonesian children . DHA+EPA treatment increased plasma DHA and total plasma n-3 fatty acids in both countries . The micronutrient treatment result ed in significant increases in scores on tests representing verbal learning and memory in Australia ( estimated effect size : 0.23 ; 95 % CI : 0.01 , 0.46 ) . A similar effect was observed among Indonesian girls ( estimated effect size : 0.32 ; 95 % CI : -0.01 , 0.64 ) . No effects were found on tests measuring general intelligence or attention . No effects of DHA+EPA on the factors of cognitive tests were observed . CONCLUSION In well-nourished school-aged children , fortification with multiple micronutrients can result in improvements in verbal learning and memory", "BACKGROUND Deficiencies of iron , iodine , and vitamin A are prevalent worldwide and can affect the mental development and learning ability of schoolchildren . OBJECTIVE The aim of this study was to determine the effect of micronutrient-fortified biscuits on the micronutrient status of primary school children . DESIGN Micronutrient status was assessed in 115 children aged 6 - 11 y before and after consumption of biscuits ( fortified with iron , iodine , and beta-carotene ) for 43 wk over a 12-mo period and was compared with that in a control group ( n = 113 ) who consumed nonfortified biscuits . Cognitive function , growth , and morbidity were assessed as secondary outcomes . RESULTS There was a significant between-group treatment effect on serum retinol , serum ferritin , serum iron , transferrin saturation , and urinary iodine ( P hemoglobin and hematocrit ( P low serum retinol concentrations ( low serum ferritin concentrations ( anemia ( hemoglobin low urinary iodine concentrations ( cognitive function with the digit span forward task ( short-term memory ) . Fewer school days were missed in the intervention than in the control group because of respiratory- ( P = 0.097 ) and diarrhea-related ( P = 0.013 ) illnesses . The intervention had no effect on anthropometric status [ corrected ] . CONCLUSIONS Fortified biscuits result ed in a significant improvement in the micronutrient status of primary school children from a poor rural community and also appeared to have a favorable effect on morbidity and cognitive function [ corrected ]", "BACKGROUND Iodine is required for the production of thyroid hormones , which are necessary for normal brain development and cognition . Although several r and omized trials examined the effect of iodine supplementation on cognitive performance in schoolchildren , the results were equivocal . OBJECTIVE We aim ed to ascertain whether providing iodized oil to iodine-deficient children would affect their cognitive and motor performance . DESIGN In a double-blind intervention trial , 10 - 12-y-old children ( n = 310 ) in primary schools in rural southeastern Albania were r and omly assigned to receive 400 mg I ( as oral iodized oil ) or placebo . We measured urinary iodine ( UI ) , thyroid-stimulating hormone ( TSH ) , and total thyroxine ( TT4 ) concentrations and thyroid gl and volume ( by ultrasound ) . The children were given a battery of 7 cognitive and motor tests , which included measures of information processing , working memory , visual problem solving , visual search , and fine motor skills . Thyroid ultrasound and the biochemical and psychological tests were repeated after 24 wk . RESULTS At baseline , the children 's median UI concentration was 43 microg/L ; 87 % were goitrous , and nearly one-third had low concentrations of circulating TT4 . Treatment with iodine markedly improved iodine and thyroid status : at 24 wk , median UI in the treated group was 172 microg/L , mean TT4 was approximately 40 % higher , and the prevalence of hypothyroxinemia was placebo , iodine treatment significantly improved performance on 4 of 7 tests : rapid target marking , symbol search , rapid object naming , and Raven 's Coloured Progressive Matrices ( P Information processing , fine motor skills , and visual problem solving are improved by iodine repletion in moderately iodine-deficient schoolchildren", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Adequate levels of vitamins and minerals are essential for optimal neural functioning . A high proportion of individuals , including children , suffer from deficiencies in one or more vitamins or minerals . This study investigated whether daily supplementation with vitamins/minerals could modulate cognitive performance and mood in healthy children . In this r and omised , double-blind , placebo-controlled , parallel groups investigation , eighty-one healthy children aged from 8 to 14 years underwent laboratory assessment s of their cognitive performance and mood pre-dose and at 1 and 3 h post-dose on the first and last days of 12 weeks ' supplementation with a commercially available vitamins/mineral product ( Pharmaton Kiddi ) . Interim assessment s were also completed at home after 4 and 8 weeks at 3 h post-dose . Each assessment comprised completion of a cognitive battery , delivered over the Internet , which included tasks assessing mood and the speed and accuracy of attention and aspects of memory ( secondary , semantic and spatial working memory ) . The vitamin/mineral group performed more accurately on two attention tasks : ' Arrows ' choice reaction time task at 4 and 8 weeks ; ' Arrow Flankers ' choice reaction time task at 4 , 8 and 12 weeks . A single task outcome ( Picture Recognition errors ) evinced significant decrements at 12 weeks . Mood was not modulated in any interpretable manner . Whilst it is possible that the significant improvements following treatment were due to non-significant numerical differences in performance at baseline , these results would seem to suggest that vitamin/mineral supplementation has the potential to improve brain function in healthy children . This proposition requires further investigation", "BACKGROUND The effects of severe iodine deficiency during critical periods of brain development are well documented . There is little known about the consequences of milder forms of iodine deficiency on neurodevelopment . OBJECTIVE The objective was to determine whether supplementing mildly iodine-deficient children with iodine improves cognition . DESIGN A r and omized , placebo-controlled , double-blind trial was conducted in 184 children aged 10 - 13 y in Dunedin , New Zeal and . Children were r and omly assigned to receive a daily tablet containing either 150 microg I or placebo for 28 wk . Biochemical , anthropometric , and dietary data were collected from each child at baseline and after 28 wk . Cognitive performance was assessed through 4 subtests from the Wechsler Intelligence Scale for Children . RESULTS At baseline , children were mildly iodine deficient [ median urinary iodine concentration ( UIC ) : 63 microg/L ; thyroglobulin concentration : 16.4 microg/L ] . After 28 wk , iodine status improved in the supplemented group ( UIC : 145 microg/L ; thyroglobulin : 8.5 microg/L ) , whereas the placebo group remained iodine deficient ( UIC : 81 microg/L ; thyroglobulin : 11.6 microg/L ) . Iodine supplementation significantly improved scores for 2 of the 4 cognitive subtests [ picture concepts ( P = 0.023 ) and matrix reasoning ( P = 0.040 ) ] but not for letter-number sequencing ( P = 0.480 ) or symbol search ( P = 0.608 ) . The overall cognitive score of the iodine-supplemented group was 0.19 SDs higher than that of the placebo group ( P = 0.011 ) . CONCLUSIONS Iodine supplementation improved perceptual reasoning in mildly iodine-deficient children and suggests that mild iodine deficiency could prevent children from attaining their full intellectual potential . The trial was registered with the Australia New Zeal and Clinical Trials Register as ACTRN12608000222347", "Summary Single interventions for helminthic infections and micronutrient deficiencies are effective , but it is not clear whether combined interventions will provide equal , additive or synergistic effects to improve children 's health . The study objective was to determine the impact of single and combined interventions on nutritional status and scholastic and cognitive performance of school children . A double-blind , r and omized , placebo-controlled trial in 11 rural South African primary schools r and omly allocated 579 children aged between 8 and 10 years into six study groups , half of whom received antihelminthic treatment at baseline . The de-wormed and non-de-wormed arms were further divided into three groups and given biscuits , either unfortified or fortified with vitamin A and iron or with vitamin A only , given daily for 16 weeks . The outcome measures were anthropometric , micronutrient and parasite status , and scholastic and cognitive test scores . There was a significant treatment effect of vitamin A on serum retinol ( p micronutrient status in rural primary school children ; vitamin A with de-worming had a greater impact on micronutrient status than vitamin A fortification alone and antihelminthic treatment significantly reduced the overall prevalence of parasite infection . The burden of micronutrient deficiency ( anaemia , iron and vitamin A ) and stunting in this study population was low and , coupled with the restricted duration of the intervention ( 16 weeks ) , might have limited the impact of the interventions", "This study aim ed to determine the effect of a multiple-micronutrient-fortified beverage on the micronutrient status , physical fitness , and cognitive performance of schoolchildren . The study was a r and omized , double-blind , placebo-controlled trial of schoolchildren assigned to receive either the fortified or nonfortified beverage with or without anthelmintic therapy . Data on hemoglobin level , urinary iodine excretion ( UIE ) level , physical fitness , and cognitive performance were collected at baseline and at 16 weeks post-intervention . The fortified beverage significantly improved iron status among the subjects that had hemoglobin levels proportion of children who remained moderately to severely anemic was significantly lower among those given the fortified beverage . In the groups that received the fortified product , the median UIE level increased , whereas among those who received the placebo beverage , the median UIE level was reduced significantly . Iron- and /or iodine-deficient subjects who received the fortified beverage showed significant improvements in fitness ( post-exercise reduction of heart rate ) and cognitive performance ( nonverbal mental ability score ) . The study showed that consumption of a multiple-micronutrient-fortified beverage for 16 weeks had significant effects on iron status , iodine status , physical fitness , and cognitive performance among iron- and /or iodine-deficient Filipino schoolchildren . Anthelmintic therapy improved iron status of anemic children and iodine status of the iron-adequate children at baseline but it had no effect on physical fitness and cognitive performance . The results from the clinical study showed that a multiple-micronutrient-fortified beverage could play an important role in preventing and controlling micronutrient deficiencies", "Limited research suggests that micronutrient supplementation may have a positive effect on the academic performance and behavior of school-aged children . To determine the effect of multivitamin/mineral supplementation on academic performance , students in grade s three through six ( approximate age range=8 to 12 years old ) were recruited from 37 parochial schools in northern New Jersey to participate in a double-blind , placebo-controlled clinical trial conducted during the 2004 - 2005 academic school year . Participants were r and omized to receive either a st and ard children 's multivitamin/mineral supplement ( MVM ) or a placebo . MVM or placebo was administered in school only during lunch or snack period by a teacher or study personnel who were blinded to group assignment . The main outcome measured was change in scores on Terra Nova , a st and ardized achievement test administered by the State of New Jersey , at the beginning of March 2005 compared to March 2004 . Compared with placebo , participants receiving MVM supplements showed no statistically significant improvement for Terra Nova National Percentile total scores by treatment assignment or for any of the subject area scores using repeated measures analysis of variance . No significant improvements were observed in secondary end points : number of days absent from school , tardiness , or grade point average . In conclusion , the in-school daily consumption of an MVM supplement by third- through sixth- grade inner-city children did not lead to improved school performance based upon st and ardized testing , grade point average , and absenteeism", "1 . Behavioural responses of young anaemic Indian children to iron-folic acid supplements were assessed in two separate studies using the Indian adaptation of Wechsler 's ( 1967 ) intelligence scale for children ( WISC ) . 2 . The first study was an exploratory study in which the cognitive behaviour of 5 - 8-year-old children of both sexes was assessed before and after supplementation with 20 mg elemental Fe and 0.1 mg folic acid given daily for a period of 60 d. 3 . The supplemented children showed a significant improvement in haemoglobin ( Hb ) as well as the WISC scores while the control children who did not receive any supplements failed to show an improvement either in Hb or in the WISC scores . However , within the supplemented group when the initially-anaemic children were compared with the initially-non-anaemic ones , only the 7-year-old anaemic children performed significantly poor in the tests than the non-anaemic group of the same age . The study raised the possibility that in addition to increasing the blood Hb levels , Fe-folic acid supplements may have additional benefits in improving the cognitive performance of children . 4 . In the second study , cognitive behaviour of fourteen matched pairs of anaemic children in the age-range of 5 - 6 years was assessed before and after supplementation with 40 mg Fe and 0.2 mg folic acid given daily in two divided doses or sugar placebos for a period of 60 d. The tester did not know the groups to which each child belonged . 5 . The supplemented children showed a significant improvement in Hb as well as in the verbal and performance IQ of WISC . The control children showed no improvement in Hb but their verbal IQ improved significantly . However , there was no significant improvement in their performance IQ . 6 . The results indicated that Fe-folic acid supplements to anaemic children not only raised Hb levels but also improved intelligence test results , particularly in the performance section", "BACKGROUND Fortification with multiple micronutrients has been shown to improve growth and cognitive performance among children in developing countries , but it is unknown whether higher concentrations are more effective than lower concentrations . OBJECTIVE We compared the effect of 2 different concentrations of a combination of micronutrients and n-3 ( omega-3 ) fatty acids on indicators of growth and cognitive performance in low-income , marginally nourished schoolchildren in Bangalore , India . DESIGN In a 2-by-2 factorial , double-blind , r and omized controlled trial , 598 children aged 6 - 10 y were individually allocated to 1 of 4 intervention groups to receive foods fortified with either 100 % or 15 % of the Recommended Dietary Allowance of micronutrients in combination with either 900 mg alpha-linolenic acid plus 100 mg docosahexaenoic acid or 140 mg alpha-linolenic acid for 12 mo . Anthropometric and biochemical assessment s were performed at baseline and 12 mo . Cognitive performance was measured at baseline and at 6 and 12 mo . RESULTS The high micronutrient treatment significantly improved linear growth at 12 mo ( 0.19 cm ; 0.01 , 0.36 ) and short-term memory at 6 mo ( 0.11 SD ; 0.01 , 0.20 ) and was less beneficial on fluid reasoning at 6 ( -0.10 SD ; -0.17 , -0.03 ) and 12 ( -0.12 SD ; -0.20 , -0.04 ) mo than was the low micronutrient treatment , whereas no differences were observed on weight , retrieval ability , cognitive speediness , and overall cognitive performance . No significant differences were found between the n-3 treatments . CONCLUSIONS The high micronutrient treatment was more beneficial for linear growth than was the low micronutrient treatment . However , with some small differential effects , higher micronutrient concentrations were as effective as lower concentrations on cognitive performance . This trial was registered at clinical trials.gov as NCT00467909", "CONTEXT Numerous studies conducted in juvenile correctional institutions have reported that violence and serious antisocial behavior have been cut almost in half after implementing nutrient-dense diets that are consistent with the World Health Organization 's guidelines for fats , sugar , starches , and protein ratios . Two controlled trials tested whether the cause of the behavioral improvements was psychological or biological in nature by comparing the behavior of offenders who either received placebos or vitamin-mineral supplements design ed to provide the micronutrient equivalent of a well-balanced diet . These r and omized trials reported that institutionalized offenders , aged 13 to 17 years or 18 to 26 years , when given active tablets produced about 40 % less violent and other antisocial behavior than the placebo controls . However , generalization could not be made to typical schoolchildren without a controlled trial examining violence and antisocial behavior in public schools . OBJECTIVES To determine if schoolchildren , aged 6 to 12 years , who are given low dose vitamin-mineral tablets will produce significantly less violence and antisocial behavior in school than classmates who are given placebos . DESIGN A stratified r and omized , double-blind , placebo-controlled trial with pretest and post-test measures of antisocial behavior on school property . SETTING S AND SUBJECTS Two \" working class , \" primarily Hispanic elementary schools in Phoenix , Arizona . Approximately half of the potential schoolchildren participated , i.e. , 468 students aged 6 to 12 years . INTERVENTION Daily vitamin-mineral supplementation at 50 % of the U.S. recommended daily allowance ( RDA ) for 4 months versus placebo . The supplement was design ed to raise vitamin-mineral intake up to the levels currently recommended by the National Academy of Sciences for children aged 6 to 11 years . OUTCOME MEASURE Violent and nonviolent delinquency as measured by official school disciplinary records . RESULTS Of the 468 students r and omly assigned to active or placebo tablets , the 80 who were disciplined at least once between September 1st and May 1st served as the research sample . During intervention , the 40 children who received active tablets were disciplined , on average , 1 time each , a 47 % lower mean rate of antisocial behavior than the 1.875 times each for the 40 children who received placebos ( 95 % confidence interval , 29 % to 65 % , rates of antisocial behavior in 8 types of recorded infractions : threats/fighting , v and alism , being disrespectful , disorderly conduct , defiance , obscenities , refusal to work or serve , endangering others , and nonspecified offenses . CONCLUSION Poor nutritional habits in children that lead to low concentrations of water-soluble vitamins in blood , impair brain function and subsequently cause violence and other serious antisocial behavior . Correction of nutrient intake , either through a well-balanced diet or low-dose vitamin-mineral supplementation , corrects the low concentrations of vitamins in blood , improves brain function and subsequently lowers institutional violence and antisocial behavior by almost half . This paper adds to the literature by enabling previous research to be generalized from older incarcerated subjects with a history of antisocial behavior to a normal population of younger children in an educational setting", "OBJECTIVE We evaluated the effect of a micronutrient-fortified beverage on mental function in schoolchildren . METHODS This double-blind , placebo-controlled , matched-pair , cluster , r and omized feeding trial assessed baseline before supplementation and after 14 mo in a cohort of 608 children aged 6 to 15 y who received a micronutrient-fortified beverage or placebo . Children in two classes ( clusters ) in each of nine grade s were assessed for intelligence , attention and concentration , memory , and school achievement . RESULTS Mean intelligence quotient scores of the micronutrient-fortified beverage group and the placebo group at baseline and final follow-up were not significantly different . Mean verbal and performance scores and increments were also not different . After supplementation , attention-concentration increment scores of the micronutrient group were significantly higher ( P Mean and incremental scores of the supplemented group on the memory scale were not significantly different from those of the placebo group . CONCLUSIONS Supplementation with a beverage fortified with a range of micronutrients significantly improved attention-concentration over 14 mo , but not intelligence quotient , memory , or school achievement among middle-income schoolchildren", "Micronutrient deficiencies are associated with impaired growth and cognitive function . A school-based fortification program might benefit schoolchildren but a high prevalence of parasite infestation might affect effectiveness . A r and omized , double-blind , placebo-controlled 2 × 2 factorial trial was conducted to assess the efficacy of multi-micronutrient fortified biscuits with or without de-worming on growth , cognitive function , and parasite load in Vietnamese schoolchildren . Schoolchildren ( n = 510 ) , 6 - 8 years of age were r and omly allocated to receive albendazole or placebo at baseline and four months of multi-micronutrient fortified biscuits ( FB ) or non-fortified biscuits . Children receiving FB for four months scored higher on two cognitive tests : Raven 's Colored Progressive Matrices and the Digit Span Forward test . Children receiving albendazole plus FB had the lowest parasite load after four months . In children receiving FB , mid-upper arm circumference was slightly improved ( + 0.082 cm ) but there were no differences in other indexes of anthropometry . Combining multi-micronutrient fortified biscuits with de-worming is an effective strategy" ]

[ "Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people . Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures , as proved by Decalyos I. Decalyos II is a 2-year , multicenter , r and omized , double-masked , placebo-controlled confirmatory study . The intention-to-treat population consisted of 583 ambulatory institutionalized women ( mean age 85.2 years , SD = 7.1 ) r and omized to the calcium – vitamin D3 fixed combination group ( n= 199 ) ; the calcium plus vitamin D3 separate combination group ( n= 190 ) and the placebo group ( n= 194 ) . Fixed and separate combination groups received the same daily amount of calcium ( 1200 mg ) and vitamin D3 ( 800 IU ) , which had similar pharmacodynamic effects . Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent , with levels returning within the normal range after 6 months . In a subgroup of 114 patients , femoral neck bone mineral density ( BMD ) decreased in the placebo group ( mean = –2.36 % per year , SD = 4.92 ) , while remaining unchanged in women treated with calcium-vitamin D3 ( mean = 0.29 % per year , SD = 8.63 ) . The difference between the two groups was 2.65 % ( 95 % CI = –0.44 , 5.75 % ) with a trend in favor of the active treatment group . No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis . The relative risk ( RR ) of HF in the placebo group compared with the active treatment group was 1.69 ( 95 % CI = 0.96 , 3.0 ) , which is similar to that found in Decalyos I ( RR = 1.7 ; 95 % CI = 1.0 , 2.8 ) . Thus , these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women", "OBJECTIVES A high prevalence of hip and other fractures in elderly patients with Parkinson ’s disease has been linked to reduced bone mass arising from a defect of renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) . Treatment with 1α-hydroxyvitamin D3 ( 1α(OH)D3 ; an active form of vitamin D ) was evaluated for maintaining bone mass and reducing the incidence of hip and other non-vertebral fractures in patients with Parkinson ’s disease . METHODS In a double blind , r and omised trial , 86 elderly patients with Parkinson ’s disease ( mean Hoehn and Yahr stage , 3 ; mean age 70.6 years ) were r and omised to receive either 1 μg 1α(OH)D3 daily ( treatment group , n=43 ) or a placebo ( n=43 ) for 18 months . Bone mineral densities in the second metacarpals were determined by computed radiographic densitometry . Serum bone turnover indices were measured serially , and incidence of non-vertebral fractures was recorded . RESULTS Bone mineral densities decreased 1.2 % in the treatment group compared with 6.7 % in the placebo group during 18 months ( p groups , the serum concentration of 1 , 25-[OH]2D was reduced . Parathyroid hormone was abnormally increased in 15 patients ( 17 % ) and correlated negatively with serum 25-hydroxyvitamin D , indicating compensatory hyperparathyroidism . Eight patients sustained fractures ( six at the hip and two at other sites ) in the placebo group , and one hip fracture occurred among treated patients ( odds ratio 9.8 ; p=0.0028 ) . CONCLUSION By increasing serum 1 , 25-[OH]2D concentrations , treatment with 1α(OH)D3 can reduce the risk of hip and other non-vertebral fractures in osteoporotic elderly patients with Parkinson ’s disease by slowing the loss of bone mineral densities", "OBJECTIVES Estrogen deficiency is the most common cause of postmenopausal osteoporosis and estrogen replacement is well known to retard postmenopausal bone loss . Calcium supplement alone is generally considered to be insufficient for the prevention of bone loss associated with estrogen deficiency while the role of calcitriol is unclear . In the present study we examined the efficacy different doses of estrogen or calcitriol in the prevention of postmenopausal bone loss in Thais . METHODS The subjects consisted of 146 Thai women no more than 6 years postmenopausal . The subjects were r and omly allocated to receive 750 mg supplemental calcium alone , calcium and conjugated equine estrogen ( CEE ) at 0.3 or 0.625 mg , calcium and calcitriol at 0.25 or 0.5 microg daily . Those receiving CEE also took 5 mg medrogestone for 12 days each month . BMD at L2 - 4 and femoral neck were measured at baseline 1 year and 2 years after treatments . Data were expressed as mean + /- S.E. RESULTS Subjects on supplemental calcium alone had approximately 2.5 % decreases in L2 - 4 ( P femoral BMD ( P vertebral BMD ( P BMD was demonstrated at the femoral neck . Likewise , 0.625 mg of CEE induced 5.4 + /- 1.4 % increase in vertebral BMD at 2 years ( P femoral BMD . In regard to calcitriol , no significant change in vertebral or femoral BMD was demonstrated with either 0.25 or 0.5 microg calcitriol . CONCLUSION We concluded that calcitriol is effective in the prevention of early postmenopausal bone loss in Thais . It represents an option for the prevention of osteoporosis in postmenopausal women who are contraindicated for estrogen replacement", "An unexplained loss of muscle strength occurs with aging . Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [ 1,25-(OH2)D3 ] to persons with low serum concentrations can improve strength . To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [ 1,25-(OH2)D3 ] , we conducted a r and omized , controlled , double blinded trial in 98 men and women volunteers over 69 yr old . Treatment consisted of 0.25 micrograms 1,25-(OH)2D3 , orally , twice per day or identical placebo for 6 months . Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer . There was no difference between the two groups at 1 week , 1 month , or 6 months of treatment in any of the measures of muscle strength . We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons . Further research is needed to determine the etiology of the decline in muscle strength associated with aging", "Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol , are important factors in the pathogenesis of age-related bone loss . The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on bone loss in elderly women . Four hundred eighty-nine elderly women with normal bone density for their age , aged 65 - 77 yr , were entered into a r and omized double blind , placebo-controlled trial . Women were r and omized to one of four groups : conjugated estrogens ( 0.625 mg , daily ) to women without a uterus ( estrogen replacement therapy ) plus medroxyprogesterone acetate ( 2.5 mg , daily ) to women with a uterus ( hormone replacement therapy ) , calcitriol ( 0.25 microg twice daily ) , a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol , or placebos for 3 yr . The primary outcome was the change in bone mineral density of the femoral neck and spine . In the intent to treat analysis , hormone therapy ( hormone replacement therapy/estrogen replacement therapy ) produced a mean ( + /-1 SD ) increase in bone mineral density of 2.98 % ( + /-5.45 % ) at the femoral neck ( P total hip and trochanter bone mineral density . Calcitriol increased bone mineral density 0.10 % ( + /- 4.27 % ) at the femoral neck ( P = 0.57 ) and 1.65 % ( + /- 4.83 % ) at the spine ( P of hormone replacement therapy/estrogen replacement therapy + calcitriol increased bone mineral density 3.80 % ( + /-4.95 % ) at the femoral neck ( P hip and trochanter . All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck , spine , total hip and trochanter . There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis . In a secondary analysis of the effect in women who were adherent to treatment , calcitriol had a more significant effect on spine ( P = 0.003 ) and total hip ( P = 0.004 ) . The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups . Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter ( P = 0.007 ) and total hip bone mineral density ( P = 0.0017 ) . In summary , hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinical ly relevant sites in a group of elderly women , with normal bone density for their age . Calcitriol was effective in increasing spine bone mineral density . In the adherent women , combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone", "The necessity and safety of an oral calcium ( Ca ) and vitamin D regimen was evaluated in a population of 66 independently living and 73 institutionalized elderly women over an 11-week winter period . The members of both groups were r and omly assigned into trial and control groups . Serum Ca , creatinine , and calcidiol levels were measured before and after the trial . The regimen consisted of 1.558 g of Ca and 45 micrograms ( equal to 1,800 IU ) of vitamin D administered daily in addition to the normal diet . The controls received no treatment . A majority of the elderly subjects living independently had ensured their Ca , and a quarter of them also their vitamin D intake on their own initiative . The mean serum calcidiol concentration before the trial was 24.1 nmol/L in the institutionalized and 38.5 nmol/L in the elderly subjects living independently ( P less than .001 ) . After the trial , serum calcidiol was 10.4 nmol/L in the institutionalized control subjects and had decreased ( P less than .001 ) in both control groups , but increased ( P less than .001 ) in both treatment groups . The safety indicators , serum Ca , creatinine , and calcidiol , did not indicate any group or individual side effect", "A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side , correlating with the degree of paralysis and vitamin D deficiency due to malnutrition , sunlight deprivation , and immobilization-induced hypercalcemia , and increases the risk of hip fracture . We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [ 1alpha(OH)D3 ; vitamin D3 ] administration on bone mineral density preservation as compared with untreated controls . In a r and omized and prospect i ve study of 103 patients with hemiplegia after stroke ( the mean duration of illness was 4.8 yr ) , 68 ( 34 patients in each group ) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo , whereas the remaining 35 patients received no drug . Bone mineral density on the hemiplegic side decreased by 1.4 % in the ipriflavone group , 3.8 % in the vitamin D3 group , and 5.4 % in the control group ( P 25-hydroxyvitamin D insufficiency , increased serum ionized calcium , and low levels of 1 , 25-dihydroxyvitamin D , suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1 , 25-dihydroxyvitamin D. After treatment , the serum 1 , 25-dihydroxyvitamin D level increased by 139.9 % in the ipriflavone group and by 26.9 % in the vitamin D3 group . Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen , and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group , whereas no changes occurred in the other two groups . One patient in the untreated group suffered a hip fracture , compared with none in the ipriflavone and vitamin D3 groups . These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1 , 25-dihydroxyvitamin D concentration", "BACKGROUND The Food and Nutrition Board of the National Academy of Sciences states that 95 microg vitamin D/d is the lowest observed adverse effect level ( LOAEL ) . OBJECTIVE Our objective was to assess the efficacy and safety of prolonged vitamin D3 intakes of 25 and 100 microg ( 1000 and 4000 IU)/d . Efficacy was based on the lowest serum 25-hydroxyvitamin D [ 25(OH)D ] concentration achieved by subjects taking vitamin D3 ; potential toxicity was monitored by measuring serum calcium concentrations and by calculating urinary calcium-creatinine ratios . DESIGN Healthy men and women ( n = 61 ) aged 41 + /- 9 y ( mean + /- SD ) were r and omly assigned to receive either 25 or 100 microg vitamin D3/d for 2 - 5 mo , starting between January and February . Serum 25(OH)D was measured by radioimmunoassay . RESULTS Baseline serum 25(OH)D was 40.7 + /- 15.4 nmol/L ( mean + /- SD ) . From 3 mo on , serum 25(OH)D plateaued at 68.7 + /- 16.9 nmol/L in the 25-microg/d group and at 96.4 + /- 14.6 nmol/L in the 100-microg/d group . Summertime serum 25(OH)D concentrations in 25 comparable subjects not taking vitamin D3 were 46.7 + /- 17.8 nmol/L. The minimum and maximum plateau serum 25(OH)D concentrations in subjects taking 25 and 100 microg vitamin D3/d were 40 and 100 nmol/L and 69 and 125 nmol/L , respectively . Serum calcium and urinary calcium excretion did not change significantly at either dosage during the study . CONCLUSIONS The 100-microg/d dosage of vitamin D3 effectively increased 25(OH)D to high-normal concentrations in practically all adults and serum 25(OH)D remained within the physiologic range ; therefore , we consider 100 microg vitamin D3/d to be a safe intake", "BACKGROUND Supplementation with calcium and vitamin D reduces bone loss and prevents fractures in elderly people , but it is not known whether any lasting benefit remains if the supplements are discontinued . OBJECTIVE The objective was to determine whether gains in bone mineral density ( BMD ) induced by calcium and vitamin D supplementation persist after supplement withdrawal . DESIGN Two-hundred ninety-five healthy , elderly men and women ( aged > /=68 y ) who had completed a 3-y r and omized , placebo-controlled trial of calcium and vitamin D supplementation were followed for an additional 2 y during which no study supplements were given . BMD was measured by dual-energy X-ray absorptiometry , and biochemical variables related to calcium metabolism and bone turnover were measured . RESULTS In the 128 men , supplement-induced increases in spinal and femoral neck BMD were lost within 2 y of supplement discontinuation , but small benefits in total-body BMD remained . In the 167 women , there were no lasting benefits in total-body BMD or at any bone site . Consistent with the observations on BMD , the bone turnover rates in both men and women ( as measured by serum osteocalcin concentrations ) returned to their original higher concentrations within the same 2-y period . CONCLUSION Discontinued calcium and vitamin D supplementation has limited cumulative effect on bone mass in men and women aged > /=68", "BACKGROUND There is currently no consensus on the effect of dietary protein intake on the skeleton , but there is some indication that low calcium intakes adversely influence the effect of dietary protein on fracture risk . OBJECTIVE The objective of the present study was to determine whether supplemental calcium citrate malate and vitamin D influence any associations between protein intake and change in bone mineral density ( BMD ) . DESIGN Associations between protein intake and change in BMD were examined in 342 healthy men and women ( aged > or = 65 y ) who had completed a 3-y , r and omized , placebo-controlled trial of calcium and vitamin D supplementation . Protein intake was assessed at the midpoint of the study with the use of a food-frequency question naire and BMD was assessed every 6 mo by dual-energy X-ray absorptiometry . RESULTS The mean ( + /-SD ) protein intake of all subjects was 79.1 + /- 25.6 g/d and the mean total calcium intakes of the supplemented and placebo groups were 1346 + /- 358 and 871 + /- 413 mg/d , respectively . Higher protein intake was significantly associated with a favorable 3-y change in total-body BMD in the supplemented group ( in a model containing terms for age , sex , weight , total energy intake , and dietary calcium intake ) but not in the placebo group . The pattern of change in femoral neck BMD with increasing protein intake in the supplemented group was similar to that for the total body . CONCLUSION Increasing protein intake may have a favorable effect on change in BMD in elderly subjects supplemented with calcium citrate malate and vitamin", "BACKGROUND Adequate intakes of calcium and vitamin D reduce bone loss and fracture risk in the elderly . Other nutrients also affect bone health , and adequate intakes may influence bone turnover and balance . OBJECTIVE We compared the long-term effects on bone turnover markers and calciotropic hormones of a multinutrient supplement , a calcium and vitamin D supplement , and dietary instruction aim ed at increasing calcium intake through foods . DESIGN Ninety-nine healthy postmenopausal women participated in a 3-y , r and omized trial , receiving either 1 ) supplemental calcium ( 1450 mg/d ) and vitamin D [ 10 microg ( 400 IU)/d ] , 2 ) calcium , vitamin D , and other nutrients ( multinutrient supplement ) , or 3 ) dietary instruction ( dietary control group ) . Data are from 83 subjects who completed the trial . RESULTS Increases over baseline in calcium intakes and serum 25-hydroxyvitamin D concentrations were sustained over 3 y in all treatment groups . Circulating parathyroid hormone concentrations were reduced at year 1 in all treatment groups but trended toward baseline thereafter . Bone turnover markers followed a similar pattern , and none of the changes in biochemical concentrations differed significantly between groups . CONCLUSIONS All 3 interventions offer long-term feasibility for increasing calcium intake and serum 25-hydroxyvitamin D concentrations . The dietary addition of micronutrients implicated in skeletal physiology confers no obvious bone-sparing effect in healthy postmenopausal women beyond that of calcium and vitamin D alone . The attenuation over time in suppression of parathyroid hormone and bone turnover might help explain why nutrient intervention tends to have less of a bone-sparing effect than do skeletally active medications such as estrogen or bisphosphonates", "A r and omized double-blind controlled trial of a single oral dose of 2.5 mg ( 100,000 IU ) cholecalciferol ( vitamin D3 ) was conducted in the winter in 189 healthy free-living men and women aged 63 - 76 y. The mean baseline serum concentration for 25-hydroxyvitamin D was 34.5 nmol/L and for parathyroid hormone 3.18 pmol/L. After 5 wk , mean serum 25-hydroxyvitamin D concentrations were 60 % higher in the treated than in the placebo group ( P parathyroid hormone concentrations in the treated compared with the placebo group ( P serum calcium were seen . Findings suggest that 25-hydroxyvitamin D has a physiological role in the regulation of parathyroid secretion independent of serum calcium in healthy elderly people . Parathyroid concentrations rise and 25-hydroxyvitamin D concentrations decline with age . These results may have implication s for the prevention of osteoporotic fractures that occur with increased frequency in winter and in elderly people", "An ongoing r and omized clinical trial of 3 years duration is being undertaken to evaluate the recurrent fracture rate and safety profile associated with low-dose calcitriol versus calcium supplementation in women with at least 3 years postmenopausal osteoporosis who are under the age of 80 years . A total of 856 patients were su bmi tted for possible inclusion in the study by 123 primary care physicians , and 636 met all entry requirements . Each patient was r and omly allocated to receive either 0.25 micrograms of calcitriol twice daily or calcium supplementation of 1,000 mg/d . If significant hypercalcemia developed ( greater than 2.6 mmol/L ) or a deterioration in renal function was observed , the dose of trial medication was to be halved or stopped if laboratory values did not return to normal . Patients were given no specific instructions regarding dietary calcium intake . To date , 528 patient-years experience with calcitriol and 527 patient-years experience with calcium the calcium supplementation have been accumulated . Thus far , low-dose calcitriol has not been observed to cause hypercalcemia , deterioration in renal function , or nephrocalcinosis . At 1 year , a loss in total anterior height ( P less than .05 ) has been detected in the calcium-treated group compared with the calcitriol-treated group . Thus , calcitriol appears to preserve spinal height . Long-term follow-up of all patients for 2 or 3 years will be continued", "The Women 's Health Initiative ( WHI ) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women , including cancer , cardiovascular disease , and osteoporotic fractures . The WHI was initiated in 1992 , with a planned completion date of 2007 . Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial ( CT ) that will include about 64,500 women or an observational study ( OS ) that will include about 100,000 women . The CT is design ed to allow r and omized controlled evaluation of three distinct interventions : a low-fat eating pattern , hypothesized to prevent breast cancer and colorectal cancer and , secondarily , coronary heart disease ; hormone replacement therapy , hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and , secondarily , to reduce the risk of hip and other fractures , with increased breast cancer risk as a possible adverse outcome ; and calcium and vitamin D supplementation , hypothesized to prevent hip fractures and , secondarily , other fractures and colorectal cancer . Overall benefit-versus-risk assessment is a central focus in each of the three CT components . Women are screened for participation in one or both of the components -- dietary modification ( DM ) or hormone replacement therapy (HRT)--of the CT , which will r and omize 48,000 and 27,500 women , respectively . Women who prove to be ineligible for , or who are unwilling to enroll in , these CT components are invited to enroll in the OS . At their 1-year anniversary of r and omization , CT women are invited to be further r and omized into the calcium and vitamin D ( CaD ) trial component , which is projected to include 45,000 women . The average follow-up for women in either CT or OS is approximately 9 years . Concerted efforts are made to enroll women of racial and ethnic minority groups , with a target of 20 % of overall enrollment in both the CT and OS . This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component . Some detail is provided on specific study design choices , including eligibility criteria , recruitment strategy , and sample size , with attention to the partial factorial design of the CT . Some aspects of the CT monitoring approach are also outlined . The scientific and logistic complexity of the WHI implies particular leadership and management challenges . The WHI organization and committee structure employed to respond to these challenges is also briefly described", "Women with vertebral deformities caused by osteoporosis have more back pain and disability and are at higher risk for subsequent vertebral deformities than women without deformities . Despite the importance of vertebral deformities , there has been a great deal of controversy about how to identify or define them . In order to compare methods for defining vertebral deformities , we studied spinal radiographs from women in the Study of Osteoporotic Fractures ( SOF ) , a cohort study of 9704 non-black women over age 65 recruited from population -based listings in four clinical centers . Using radiographs obtained at the baseline exam , we compared five methods for defining vertebral deformities : one based on a semiquantitative reading by a radiologist and four using vertebral morphometry . The semiquantitative method was compared with the other methods in a r and om sample of 503 films , while the morphometric methods were compared with each other in a larger sample of 9575 films . We tested a system of \" triage \" in which only those films with evidence of deformity were assessed by morphometry . We compared the relationship between deformity , defined by each method , and a variety of clinical criteria including bone mineral density at the lumbar spine , height loss since age 25 , back pain , and incidence of subsequent deformity . Semiquantitative reading and three of the four morphometry-based methods provided similar relationships to clinical criteria . The fourth morphometry method ( based on ratios of each vertebral height to the corresponding height at T4 ) produced significantly weaker relationships for several of the clinical validation criteria . Triage of radiographs rarely result ed in missed deformities and did not reduce the performance of any of the methods . We conclude that use of any of the similar methods , with or without triage , provides a valid approach to defining vertebral deformities", "The effects on general and bone metabolism of femoral neck fracture patients of 0.25 μg α-calcoid given orally twice daily ( n=9 ) and 25 μg calcitonin given subcutaneously 30 times ( n=10 ) in 10 weeks were studied against a control ( n = ll ) . Bone histology and histomorphometry showed non-age related osteoporosis in 30 % and osteomalacia in 22 % of the patients studied . Impaired serum vitamin D status was found in 47 – 88 % of patients , secondary hyperparathyroidism and increased serum parathyroid hormone in 59 % and decreased serum calcitonin levels in 69 % . On histology , normal findings and non-age related osteoporosis on histology were associated with low serum levels of 25-hydroxyvitamin D3,1,25- and 24,25-dihydroxy vitamin D3 . Very high serum levels of 1,25-dihydroxyvitamin D3 and low levels of 25-hydroxyvitamin D3 occurred in fracture patients with osteomalacia . Calcitonin improved calcium balance , reduced osteoporosis and increased the serum 1,25- and 24,25-dihydroxyvitamin D3 levels but had no effect on osteomalacia . Vitamin D reduced osteomalacia , slightly increased the serum 1,25-dihydroxyvitamin D3 concentration and decreased serum levels of parathyroid hormone . Both treatments gave a similar slight decrease in serum calcitonin concentrations . A mechanism of action for the treatments is suggested", "OBJECTIVES To investigate the therapeutic effect of combined use of vitamin K(2 ) and D(3 ) on vertebral bone mineral density in postmenopausal women with osteopenia and osteoporosis . SUBJECTS AND METHODS We enrolled 172 women with vertebral bone mineral density X-ray absorptiometry . In this study , we employed the criteria for diagnosis of osteopenia and osteoporosis using dual energy X-ray absorptiometry proposed by the Japan Society of Bone Metabolism in 1996 . Subjects were r and omized into four groups ( each having 43 subjects in vitamin K(2 ) therapy group , vitamin D(3 ) therapy group , vitamin K(2 ) and D(3 ) combined therapy group , or a control group receiving dietary therapy alone ) and treated with respective agents for 2 years , with bone mineral density was measured prior to therapy and after 6 , 12 , 18 , and 24 months of treatment . The bone metabolism markers analyzed were serum type 1 collagen carboxyterminal propeptide ( P1CP ) , serum intact osteocalcin , and urinary pyridinoline . Tests of blood coagulation function consisted of measurement of activated partial thromboplastin time ( APTT ) and analysis of concentrations of antithrombin III ( AT III ) , fibrinogen , and plasminogen . RESULTS Combined therapy with vitamin K(2 ) and D(3 ) for 24 months markedly increased bone mineral density ( 4.92 + /- 7.89 % ) , while vitamin K(2 ) alone increased it only 0.135 + /- 5.44 % . The bone markers measured , revealed stimulation of both bone formation and resorption activity . We observed an increase in coagulation and fibrinolytic activity that was within the normal range , suggesting that balance was maintained in the fibrinolysis-coagulation system . CONCLUSIONS Continuous combination therapy with vitamin K(2 ) and D(3 ) may be useful for increasing vertebral bone mass in postmenopausal women . Furthermore , the increase in coagulation function observed during this therapy was within the physiological range , and no adverse reactions were observed", "In a double-blind trial , 327 patients ( 57 men ) over 65 ( mean age 79.5 ) years received all possible combinations of calcium carbonate 3 g , vitamin D3 1000 iu , meth and ienone 2.5 mg and /or placebos daily for 9 months . The higher incidence of bone fractures in the placebo group was not significant . Serum calcium , phosphorus , creatinine , aspartate aminotransferase and alkaline phosphatase were followed : the greatest changes occurred with meth and ienone , which thus reduced osteoporotic activity and increased the muscular mass most effectively ; calcium carbonate had the poorest effect . Surprisingly , coronary mortality was higher among those taking all three active substances . With two treatments the increase was not significant , but when both the groups receiving a combination of any two of the treatments were compared with those taking only one or neither of these two treatments , a significant increase in coronary deaths was seen , most significant ( P less than 0.001 ) in those receiving vitamin D3 and meth and ienone", "OBJECTIVE To study the efficacy of synthetic 1,25 dihydroxyvitamin D3 ( calcitriol ) in the treatment of osteoporosis . DESIGN Two-year , double-blind , r and omized clinical trial . SETTING University medical center . PATIENTS Fifty postmenopausal women with vertebral fractures recruited by referral . INTERVENTION Calcium intake was adjusted to 25 mmol/d ( 1000 mg/d ) at baseline . Patients were then r and omized to treatment with either calcitriol or placebo . During the study , calcium intake was reduced to 15 mmol/d ( 600 mg/d ) and the dose of calcitriol was adjusted to maintain serum calcium less than 2.74 mmol/L ( less than 11.0 mg/dL ) or urine calcium less than 9.96 mmol/d ( less than 400 mg/d ) . MEASUREMENTS AND MAIN RESULTS After 2 years , the mean dose of calcitriol in the treated group was 0.62 micrograms/d . Bone mineral density of the spine increased 1.94 % with calcitriol therapy and decreased 3.92 % with placebo ( P = 0.001 ) . Total body calcium increased 0.21 % with calcitriol therapy and decreased 1.85 % with placebo ( P = 0.004 ) . Patients receiving placebo had significant decreases in spine density ( P = 0.0007 ) and total body calcium ( P = 0.0004 ) . There were no differences in vertebral fracture rates between the groups . Renal function studies were not statistically different between the groups after 2 years . CONCLUSION The treatment of postmenopausal osteoporotic women with synthetic calcitriol for 2 years was associated with increases in spine density and total body calcium . No adverse effects on renal function were seen after long-term calcitriol therapy", "In a 5-yr r and omized prospect i ve study we examined the treatment effect of estrogen replacement therapy/hormone replacement therapy ( ERT/HRT ) , calcitriol , ERT/HRT and calcitriol , or placebo for 3 yr and the effect of discontinuation of therapy for 2 more yr on bone mineral density ( BMD ) , calciotropic hormones , markers of bone remodeling , and calcium absorption in 489 elderly women . The treatment phase of the study was double-blinded . After discontinuing therapy for 2 yr , there was rapid bone loss in all 3 treatment groups , and most of the decrease in BMD occurred in the first year . In the ERT/HRT group , spine BMD increased 5.5 % in yr 3 , decreased 3.2 % in yr 4 , and decreased 0.7 % in yr 5 ; femoral neck BMD increased 3.7 % in yr 3 , decreased 2.5 % in yr 4 , and decreased 0.4 % in yr 5 ; total body BMD increased 2.1 % in yr 3 , decreased 1.4 % in yr 4 , and decreased 0.6 % in yr 5 . In the combination group , spine BMD increased 7.1 % in yr 3 , decreased 4.3 % in yr 4 , and decreased 0.3 % in yr 5 ; femoral neck BMD increased 4.5 % in yr 3 , decreased 3.0 % in yr 4 , and decreased 0.01 % in yr 5 ; total body BMD increased 2.2 % in yr 3 , decreased 1.5 % in yr 4 , and decreased 0.6 % in yr 5 . In the calcitriol group , spine BMD increased 1.8 % in yr 3 , decreased 1.8 % in yr 4 , and showed no change in yr 5 ; femoral neck BMD increased 0.2 % in yr 3 , decreased 0.2 % in yr 4 , and decreased 0.6 % in yr 5 ; total body BMD decreased 0.4 % in yr 3 , decreased 0.6 % in yr 4 , and decreased 0.4 % in yr 5 . Compared with placebo , all treated groups at yr 5 had significantly higher total body BMD ; only the combination group had significantly higher spine BMD ( 3.4 % ; P total hip BMD ( 2.4 % ; P only spine BMD in the combination group was significantly higher ( 2.6 % ; P calcium absorption and the decrease in serum PTH levels in the calcitriol groups were reversed after discontinuation of treatment , and the decrease in bone markers was reversed in the hormone-treated groups . These results suggest that discontinuation of ERT/HRT and /or calcitriol therapy in elderly women leads to a decrease in much of the BMD gained on treatment ; however , in the combination group there was a statistically significant residual effect on spine BMD", "Radiographically detected vertebral fractures ( hereafter referred to as vertebral fractures ) are a hallmark of postmenopausal osteoporosis and an important end point in clinical trials of osteoporosis treatment . Women with vertebral fractures have low bone mass compared with women without these fractures and , independently of bone mass , have an increased risk for additional vertebral and other fractures [ 1 - 4 ] . Vertebral fractures are common : Five percent of 50-year-old white women and 25 % of 80-year-old women have had at least one vertebral fracture [ 5 ] . Surprisingly , however , the manner in which vertebral fractures affect health remains uncertain . Cross-sectional studies in community-derived sample s of older women have demonstrated only a modest association [ 6 - 8 ] or no association [ 9 - 11 ] between prevalent vertebral fractures and back pain or disability . Cross-sectional studies do not distinguish more recent fractures from older vertebral fractures and may fail to capture transient increases in pain or disability [ 12 ] , a limitation that may underestimate the clinical effect of these fractures [ 13 ] . Back pain is common among elderly women [ 14 ] , and frequent causes of back pain , such as degenerative disc disease , facet joint osteoarthritis , spinal stenosis , and scoliosis , may obscure the impact of vertebral fracture . Only about one third of new vertebral fractures come to medical attention [ 15 , 16 ] , suggesting that most vertebral fractures are asymptomatic . However , attitudes toward back pain in older women and access to health care may also play a role in determining whether vertebral fractures come to medical attention . We examined the effect of incident vertebral fractures on back pain and back-related functional limitations in a large community-based sample of elderly women who underwent serial spinal radiography and annual assessment s of back pain and disability over the same period . Methods Participants Study patients were participants in the Study of Osteoporotic Fractures , a cohort recruited from population -based listings in four U.S. metropolitan areas . Details of the design of this study are published elsewhere [ 17 ] . Lateral spine radiographs were obtained for 9677 white women between the ages of 65 and 99 years ( median age , 70 years ) who underwent baseline examination between 1986 and 1988 . Repeated spinal radiographs suitable for morphometry were obtained for 7223 women ( 75 % of the original cohort ) at a follow-up clinic visit held an average of 3.7 years ( range , 1.3 to 5.1 years ) later . All participants gave informed consent . Vertebral Morphometry Lateral radiographs of the thoracic and lumbar spine were obtained in accordance with current guidelines [ 18 ] . Quantitative vertebral morphometry was performed using six-point digitization as described elsewhere [ 3 , 19 ] to calculate the anterior ( Ha ) , mid- ( Hm ) , and posterior ( Hp ) height for each vertebral body from T4 to L4 . A system of triage of radiographs , described elsewhere [ 3 , 20 ] , was used to reduce the number of radiographs requiring morphometric measurements . Briefly , trained technicians separated sets of radiographs into normal , uncertain , or probably fractured groups on the basis of a limited semiquantitative grading scheme that categorized women by the most abnormal vertebral level [ 20 ] . Uncertain grade s were further categorized by the study radiologist as normal or probably fractured . Morphometry was done on the radiograph pairs that were categorized as probably fractured ( 42 % ) . In a r and om sample of 503 women whose radiographs were triaged and then digitized , triage missed no incident fractures according to the study definition . Definition of Vertebral Fracture A vertebra was classified as having a prevalent fracture on the baseline radiograph if any of the following ratios were more than 3 SDs ( > 4 SDs for severe fractures ) below the normal mean for that vertebral level : ( Ha/Hp ) , ( Hm/Hp ) , or a combination of ( H/H [ ] 1 ) and ( Hai/Hai 1 ) [ 3 , 21 ] . A new ( incident ) fracture was identified if any of the three vertebral heights ( Ha , Hm , or Hp ) on follow-up radiographs decreased by 20 % or more and by at least 4 mm compared with the baseline height . Incident fractures identified by morphometry were review ed by a radiologist to exclude imaging artifacts or such conditions as osteophytosis and Scheuermann disease ; 7 % of vertebrae meeting the morphometric criteria for incident fracture were reclassified as not fractured . Incident Clinical Fractures We used previously described methods [ 22 ] to assess the occurrence of clinical fractures of any bone during follow-up . Women were considered to have a clinical vertebral fracture if they reported a new diagnosis of spinal fracture and a clinical radiology report confirmed that a vertebral fracture was present . Measurements of Pain , Disability , and Limited Activity We evaluated outcome measures by using a previously described question naire [ 7 , 23 ] that asked about back pain and back-related disability in the past 12 months and the number of days of limited activity due to back pain . The question naire was administered at baseline and at three annual follow-up contacts held before assessment of vertebral fractures . The third follow-up contact coincided with follow-up radiography . Back pain was assessed on scales of frequency ( 0 , never or rarely ; 1 , some of the time ; 2 , most of the time ; or 3 , all of the time ) and severity ( 0 , no pain ; 1 , mild pain ; 2 , moderate pain ; or 3 , severe pain ) . The two pain questions had high internal consistency ( Cronbach = 0.81 ) and were summed for a total score that could range from 0 to 6 . We defined clinical ly significant back pain as pain that was experienced most or all of the time or pain that was moderate or severe . Women without significant back pain at baseline were considered to have increased back pain if clinical ly significant pain had developed between any follow-up contacts . For women with clinical ly significant back pain at baseline , increased back pain was defined as an increase in total pain score of at least two points . Both types of increase had a similar association with incident fractures and thus were combined for a single outcome . Back-related disability was assessed with questions about the degree of difficulty ( 0 , no difficulty ; 1 , some difficulty ; 2 , much difficulty ; or 3 , unable to perform activity ) in six activities of daily living that involved the back ( bending down to pick up light-weight objects , lifting a 10-pound object from the floor , reaching for objects just above the head , putting on socks or stockings , getting in and out of an automobile , and st and ing for 2 hours ) . These measures were combined in a back-related disability score ranging from 0 to 18 . As reported elsewhere [ 7 ] , this scale has high internal consistency ( Cronbach = 0.82 ) and is highly correlated ( Spearman r = 0.73 ) with a more extensive instrument used to assess disability caused by low back pain [ 24 ] . We defined clinical ly significant disability as much difficulty or unable in one or more of the six activities . Women without significant disability at baseline were considered to have increased disability if clinical ly significant disability had developed between any follow-up contacts . For women with clinical ly significant disability at baseline , increased disability was defined as an increase in disability score of at least three points . Both types of increase had a similar association with incident fractures and thus were combined for a single outcome . We also asked participants if they had limited their activities because of back pain since the last contact ; if the answer was yes , we asked for the number of days they had stayed in bed and the number of days on which activity was limited ( not including days in bed ) because of back pain . Questions were adapted from previous surveys [ 25 , 26 ] . For all follow-up contacts , we summed the number of days of bed rest and , in a separate measure , the number of days of limited activity ; we then divided these numbers by the total years of follow-up to estimate the average number of affected days per year . Other Measurements The baseline question naire assessed potential confounding factors that may be associated with the risk for incident vertebral fracture and with back pain or disability , including smoking ( current or past smoker ) ; inactivity , defined as walking less than one block daily ( yes or no ) ; a previous physician diagnosis of osteoporosis or spinal fracture ( yes or no ) ; current use of estrogen ( yes or no ) ; hip pain in the past 12 months ( yes or no ) ; and height at 25 years of age . At the baseline examination , we assessed height and weight and calculated body mass index ( kg/m2 ) . We assessed grip strength by using an isometric dynamometer ( Jamar Hydraulic H and Dynamometer , JA Preston , Jackson , Mississippi ) at baseline and at the follow-up examination and calculated change in grip strength between the two measurements . A r and om sample of 16 % of baseline spine radiographs was assessed for spinal disc degeneration by using previously published methods [ 27 ] . Statistical Analysis Unless otherwise indicated , analyses were done separately in groups stratified by the presence of one or more baseline prevalent vertebral fractures . Descriptive and bivariate associations were assessed by using the t-test for continuous variables and the chi-square test for dichotomous variables . The association between incident vertebral fractures and dichotomous outcomes ( increased back pain and increased back disability ) was analyzed with logistic regression techniques . We analyzed the association of incident vertebral fracture with days of bed rest and days of limited activity per year by using Poisson regression . The distribution of days of bed rest ( mean SD , 0.44 5.15 ) and limited-activity days ( 16.3 53.7 ) indicate that considerable overdispersion is present . Poisson regression allowing for this overdispersion provides a good estimation and inferential scheme [", "STUDY OBJECTIVE To determine if calcitriol is an effective treatment in postmenopausal osteoporosis . DESIGN Double-blind , r and omized clinical trial of 2 years ' duration . SETTING University medical center with patients recruited by media announcements . PATIENTS Eighty-six postmenopausal women with vertebral compression fractures . INTERVENTIONS Patients were treated with calcitriol or placebo . Mean dose was 0.43 micrograms/d . Dietary calcium was 1000 mg/d ( 24.9 mmol/d ) . The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia . MEASUREMENTS AND MAIN RESULTS No significant differences between placebo and control groups were seen in the percent change in total body calcium ( 0.4 % + /- 1.0 compared with 0.0 % + /- 0.9 ) , single photon absorptiometry ( -0.5 % + /- 1.2 compared with -3.1 % + /- 0.9 ) or dual photon absorptiometry ( 0.0 % + /- 1.7 compared with -1.0 % + /- 2.2 ) . New fractures were seen in 16 % of the placebo group and 26 % of the calcitriol groups , so the difference in percent fractures was 10 % ( 95 % CI , -5.7 % to 25.7 % ) . Bone biopsies did not show changes in either group . The calcitriol group had significantly higher serum and urine calcium values , but renal function was not worse than in the placebo group . CONCLUSIONS Calcitriol is not an effective treatment for established postmenopausal osteoporosis", "BACKGROUND Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospect i ve study . METHODS We assessed potential risk factors , including bone mass , in 9516 white women 65 years of age or older who had had no previous hip fracture . We then followed these women at 4-month intervals for an average of 4.1 years to determine the frequency of hip fracture . All reports of hip fractures were vali date d by review of x-ray films . RESULTS During the follow-up period , 192 women had first hip fractures not due to motor vehicle accidents . In multivariable age-adjusted analyses , a maternal history of hip fracture doubled the risk of hip fracture ( relative risk , 2.0 ; 95 percent confidence interval , 1.4 to 2.9 ) , and the increase in risk remained significant after adjustment for bone density . Women who had gained weight since the age of 25 had a lower risk . The risk was higher among women who had previous fractures of any type after the age of 50 , were tall at the age of 25 , rated their own health as fair or poor , had previous hyperthyroidism , had been treated with long-acting benzodiazepines or anticonvulsant drugs , ingested greater amounts of caffeine , or spent four hours a day or less on their feet . Examination findings associated with an increased risk included the inability to rise from a chair without using one 's arms , poor depth perception , poor contrast sensitivity , and tachycardia at rest . Low calcaneal bone density was also an independent risk factor . The incidence of hip fracture ranged from 1.1 ( 95 percent confidence interval , 0.5 to 1.6 ) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 ( 95 percent confidence interval , 20 to 34 ) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age . CONCLUSIONS Women with multiple risk factors and low bone density have an especially high risk of hip fracture . Maintaining body weight , walking for exercise , avoiding long-acting benzodiazepines , minimizing caffeine intake , and treating impaired visual function are among the steps that may decrease the risk", "A controlled therapeutic trial on seventy‐four 70‐year‐old women was carried out with the purpose of finding the optimal treatment for post menopausal osteoporosis . The bone mineral content ( BMC ) was measured by 125I‐photonabsorptiometry at two sites in the distal part of the forearms , where the trabecular/cortical ratio is 0·25 and 1·5 , respectively . Radiographs were done on the right h and to measure the metacarpal bone mass ( cortical area/total area = CA/TA )", "A r and omized double-blind controlled trial of the effect of vitamin D supplementation on the abilities of elderly hospital patients to carry out basic activities of daily life is described . Those patients included in the trial had plasma 25-hydroxyvitamin D concentrations which were low or low normal as judged by the normal range in young adults . After 2 to 9 months on the trial there was no significant difference in the performance of the control and treatment groups", "In this prospect i ve study , the authors determined intrinsic risk factors for falls and recurrent falls and constructed a risk profile that indicated the relative contribution of each risk factor and also estimated the probabilities of falls and recurrent falls . In 1992 , over a 28-week period , falls were recorded among 354 elderly subjects aged 70 years or over who were living in homes or apartments for the elderly in Amsterdam and the vicinity . During the study period , 251 falls were reported by 126 subjects ( 36 % ) , and recurrent falls ( > or = 2 falls ) were reported by 57 subjects ( 16 % ) . Associations of falls and recurrent falls with potential risk factors were identified in logistic regression models . Mobility impairment regarding one or more of the tested items ( i.e. , impairment of balance , leg-extension strength , and gait ) was associated with falls ( adjusted odds ratio ( OR ) = 2.6 ) and was strongly associated with recurrent falls ( OR = 5.0 ) . Dizziness upon st and ing was associated with falls ( OR = 2.1 ) and recurrent falls ( OR = 2.1 ) . However , several risk factors were associated with recurrent falls only : history of stroke ( OR = 3.4 ) , poor mental state ( OR = 2.4 ) , and postural hypotension ( OR = 2.0 ) . The authors constructed a risk profile for recurrent falls that included the five risk factors mentioned above . Inclusion of all risk factors in the profile implied an 84 % probability of recurrent falls over a period of 28 weeks , compared with 3 % when no risk factor was present . The probability of recurrent falls ranged only from 11 % to 29 % when predicted by number of falls occurring in the previous year . Physical activity , use of high-risk medication , and the use of vitamin D3 , which was r and omly allocated to the participants , were not strongly related to either falls or recurrent falls . In conclusion , a large range of probabilities of falls , especially of recurrent falls , was estimated by the risk profiles , in which mobility impairment was the major risk factor . Recurrent fallers may therefore be especially amenable to prevention based on mobility improvement", "Abstract : Vitamin D status is known to be an important determinant of bone mineral density ( BMD ) . There is a significant seasonal variation in serum vitamin D , and some studies have reported an associated seasonal variation in BMD . The present study was devised to investigate whether a seasonal variation in BMD could be detected in healthy normal subjects , along with associated variations in serum parathyroid hormone ( PTH ) , intestinal calcium absorption and biochemical markers of bone turnover . A second aim was to investigate whether , if such variations were identified , they could be suppressed by vitamin D supplementation . The subjects were 70 healthy female volunteers ( mean age 47.2 years , range 24–70 years ) recruited into a double-masked crossover study and followed over 2 years . During the first year 35 subjects received a daily oral supplement containing 800 IU ( 20 mg ) cholecalciferol ( group 1 ) and 35 subjects received a placebo preparation ( group 2 ) . During the second year the treatment each group received was reversed . Lumbar spine ( L1–L4 ) , left proximal femur and total body BMD were measured by DXA at 3-month intervals . Serum 25-hydroxyvitamin D ( 25-OHD ) , serum PTH , bone markers ( bone-specific ALP ( BSAP ) and urinary crosslinks ( DYPD/creatinine ) ) and calcium absorption were also measured at each visit . Cholecalciferol treatment increased serum 25-OHD by 25.4 nmol/l ( p serum PTH of 6.6 ng/l ( p = 0.011 ) was seen in subjects in the lowest quartile of baseline serum 25-OHD . The treatment had no significant effect on spine , femur or total body BMD , calcium absorption or bone markers . When Fourier analysis was used to analyze the data for seasonal effect ( defined as twice the amplitude of the 1-year period variation ) a highly significant effect for 25-OHD of 18 nmol/l ( p for BMD , PTH , calcium absorption or bone markers . The analysis set a 95 % confidence limit to the seasonal effect of less than 0.6 % for spine , total hip and total body BMD . It was concluded that in the population of healthy women studied there was no evidence of seasonal variation in spine , femur or total body BMD , serum PTH , calcium absorption or bone markers . Vitamin D supplementation was found to have no effect on BMD ", "PURPOSE Oral bone and tooth loss are correlated with bone loss at nonoral sites . Calcium and vitamin D supplementation slow the rate of bone loss from various skeletal sites , but it is not known if intake of these nutrients affects oral bone and , in turn , tooth retention . SUBJECTS AND METHODS Tooth loss was examined in 145 healthy subjects aged 65 years and older who completed a 3-year , r and omized , placebo-controlled trial of the effect of calcium and vitamin D supplementation on bone loss from the hip , as well as a 2-year follow-up study after discontinuation of study supplements . Teeth were counted at 18 months and 5 years . A comprehensive oral examination at 5 years included assessment of caries , oral hygiene , and periodontal disease . The odds ratio ( OR ) and 95 % confidence interval ( CI ) of tooth loss were estimated by stepwise multivariate logistic regression . Initial age ( mean + /- SD ) of subjects was 71 + /- 5 years , and the number of teeth remaining was 22 + /- 7 . RESULTS During the r and omized trial , 11 of the 82 subjects ( 13 % ) taking supplements and 17 of the 63 subjects ( 27 % ) taking placebo lost one or more teeth ( OR = 0.4 ; 95 % CI : 0.2 to 0.9 ) . During the 2-year follow-up period , 31 of the 77 subjects ( 40 % ) with total calcium intake of at least 1000 mg per day lost one or more teeth compared with 40 of the 68 subjects ( 59 % ) who consumed less ( OR = 0.5 ; 95 % CI : 0.2 to 0.9 ) . CONCLUSION These findings suggest that intake levels of calcium and vitamin D aim ed at preventing osteoporosis have a beneficial effect on tooth retention", "Abstract The effect of the combined administration of vitamin D3 and vitamin K2 on bone mineral density ( BMD ) of the lumbar spine was examined in postmenopausal women with osteoporosis . Ninety-two osteoporotic women who were more than 5 years after menopause , aged 55–81 years , were r and omly divided into four administration groups : vitamin D3 ( 1α hydroxyvitamin D3 , 0.75 μg/day ) ( D group ; n = 29 ) , vitamin K2 ( menatetrenone , 45 mg/day ) ( K group ; n = 22 ) , vitamin D3 plus vitamin K2 ( DK group , n = 21 ) , and calcium ( calcium lactate , 2 g/day ) ( C group ; n = 20 ) . BMD of the lumbar spine ( L2–L4 ) was measured by dual energy X-ray absorptiometry at 0 , 1 , and 2 years after the treatment started . There were no significant differences in age , body mass index , years since menopause , and initial BMD among the four groups . One-way analysis of variance ( ANOVA ) with repeated measurements showed a significant decrease in BMD in the C group ( P increase in BMD in the D and K groups compared with that in the C group ( P in BMD in the DK group compared with that in the C , D , and K groups ( P of vitamin D3 and vitamin K2 , compared with calcium administration , appears to be useful in increasing the BMD of the lumbar spine in postmenopausal women with osteoporosis", "Abstract . To assess the efficacy and acceptability of vitamin D-fortified liquid milk in the management of hypovitaminosis D we carried out a double-blind , r and omized , controlled trial on 51 community-based , elderly subjects with serum 25 hydroxyvitamin D ( 25OHD ) levels of less than 12.9 ng/ml ( normal range 10–80 ng/ml ) . Each subject had a dietary assessment , mental test score , outdoor score , serum 25 hydroxyvitamin D level , and a general biochemical screening at baseline in April 1993 which was repeated in September 1993 , April 1994 , and September 1994 . All subjects received 500 ml of milk per day , delivered to their homes in specially manufactured , blank , tetrapak cartons , from June 1993 to June 1994 : 23 subjects received unfortified milk ( control group ) and 28 subjects received fortified milk ( active group ) . Our results showed a baseline mean 25OHD level in the active group of 9.6 ( range mean 25OHD level in the active group had risen significantly from its baseline to 18.5 ( range 9.6–26.7 ) ng/ml ( P ) . Serum calcium levels in the active group also showed a significant rise over the 1-year period ( P vitamin D-fortified liquid milk is a safe , effective , and acceptable method of administering vitamin D to the elderly , community-based population", "Abstract : We undertook a double-masked , r and omized , placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement and a calcium supplement plus multivitamins on bone loss at the hip , spine and forearm . The study was performed in 240 healthy women , 58–67 years of age . Duration of treatment was 2 years . Bone mineral density ( BMD ) was measured at the lumbar spine , hip and forearm . A dietary question naire was administered twice during the study and revealed a fairly good calcium and vitamin D intake ( 919 mg calcium/day ; 3.8 mg vitamin D/day ) . An increase in lumbar spine BMD of 1.6 % was observed in the treatment group after 2 years ( p50.002 ) . In the placebo group no significant changes were observed during the 2 years . Lumbar spine BMD was significantly higher in the treatment group at both 1 ( p50.01 ) and 2 years ( p50.05 ) compared with the placebo group . Though not significant , the same trend was seen at the hip . No significant changes from baseline values were observed at the distal forearm in either the treatment or the placebo group . In conclusion , we found a significant increase in urinary calcium excretion in the treatment group compared with the placebo group . Together with significant changes in serum calcium and serum parathyroid hormone , this indicates that a long-term calcium and vitamin supplement of 1 g elementary calcium ( calcium carbonate ) and 14 mg vitamin D3 increases intestinal calcium absorption . A positive effect on BMD was demonstrated , even in a group of early postmenopausal age , with a fairly good initial calcium and vitamin D status", "OBJECTIVES We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin ( Vit ) D3 supplementation in a 5-year prospect i ve trial . METHODS A total of 464 early postmenopausal women , ( a subgroup of the Kuopio Osteoporosis Study , n = 13100 ) were r and omized to four groups : ( 1 ) HRT , a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ; ( 2 ) Vit D ( 300 IU/day and 100 IU/day during the fifth year ) ; ( 3 ) HRT + Vit D ; and ( 4 ) placebo . Lumbar ( L2 - 4 ) and femoral neck bone mineral densities ( BMD ) were determined by dual X-ray absorptiometry ( DXA ) at baseline , after 2.5 and 5 years of treatment . All new symptomatic non-vertebral , radiographically defined fractures were recorded . RESULTS Altogether , 368 women ( 79 % ) completed the 5 year treatment . In all , 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up ( HRT 4 , Vit D 10 , HRT + Vit D 8 and placebo 17 ) . The reduction in the incidence of new non-verterbral fractures was significant in women with HRT alone ( P = 0.032 ) when adjusted by baseline BMD and previous fractures ; observed also with the intention-to-treat principle ( P = 0.048 ) . When the HRT groups were pooled , HRT showed a significantly lower incidence of new non-vertebral fractures ( P = 0.042 ) than women receiving placebo and also after adjusting as above ( P = 0.016 ) ; both in valid-case and in the intention-to-treat analysis . In the Vit D group , the fracture incidence was non-significantly decreased ( P = 0.229 ) in comparison with the placebo group . The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 ( 95 % CI , 0.10 - 0.90 ) and with Vit D 0.47 ( 95 % CI , 0.20 - 1.14 ) and with HRT + Vit D 0.44 ( 95 % CI , 0.17 - 1.15 ) , in comparison with the placebo group ( adjusted by femoral BMD and previous fractures ) . CONCLUSIONS This study is the first prospect i ve trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women . The effect of low-dose Vit D remains to be proved", "Twenty-eight women with postmenopausal osteoporosis were studied in a double-blind trial aim ed to compare the effects of a one-year treatment with 1,25-dihydroxyvitamin D3 ( 1,25(OH)2D3 ) , estradiol valerate ( E2 ) and placebo . Patients were divided into 4 groups : group 1 was given 1,25(OH)2D3 alone , group 2 was given E2 alone , group 3 was given 1,25(OH)2D3 + E2 , group 4 received a placebo . The evaluation of the effects of the treatments included clinical examination of patients , the measurement of a number of biochemical parameters , such as plasma and urinary calcium and phosphate , urinary hydroxyproline , serum alkaline phosphatase , the measurement of intestinal calcium absorption and bone mineral content ( BMC ) and a histomorphometric study of bone biopsies from the iliac crest . The best clinical results were obtained in the patients who were given 1,25(OH)2D3 alone ; appreciable results were also noticed in the patients who were given E2 alone or in combination with 1,25(OH)2D3 , while patients in the placebo group worsened . BMC decreased in the placebo group and increased , although non significantly , in the patients treated with 1,25(OH)2D3 or E2 or both . The histomorphometric study showed a significant increase in the mean trabecular diameter in patients treated with 1,25(OH)2D3 alone or in combination with E2 . Changes in the volume density of trabecular bone paralleled those in BMC . The results of the trial indicate that 1,25(OH)2D3 is an effective therapeutic agent in postmenopausal osteoporosis", "OBJECTIVES To determine whether relative vitamin D deficiency during the winter months contributes to age-related bone loss and whether rates of change in hard- and soft-tissue mass vary during the year . DESIGN Double-blind , placebo-controlled , 1-year trial in 249 women in which equal numbers of women were r and omized to either placebo or 400 IU of vitamin D daily . All women received 377 mg/d of supplemental calcium largely as calcium citrate malate . PATIENTS Healthy , ambulatory postmenopausal women with usual intakes of vitamin D of 100 IU/d . MEASUREMENTS Duplicate spine and whole-body scans were done by dual energy x-ray absorptiometry at 6-month intervals that were timed to periods when 25-hydroxyvitamin D levels were highest and lowest . Period 1 was June-July to December-January and period 2 was December-January to the next June-July . Serum parathyroid hormone and plasma 25-hydroxyvitamin D levels were measured during periods 1 and 2 . MAIN RESULTS In the placebo group , spinal bone mineral density increased in period 1 , decreased in period 2 , and sustained no net change . Women treated with vitamin D had a similar spinal increase in period 1 ( 1.46 % compared with 1.40 % in placebo ) , less loss in period 2 ( -0.54 % compared with -1.22 % , CI for the difference , 0.05 % to 1.31 % , P = 0.032 ) and a significant overall benefit ( 0.85 % compared with 0.15 % , CI for the difference , 0.03 % to 1.37 % , P = 0.04 ) . In period 2 , 25-hydroxyvitamin D levels were lower and parathyroid hormone levels were higher in the placebo than in the vitamin D group . Whole-body lean and fat tissue and bone mineral density varied during the year but did not change overall . CONCLUSIONS At latitude 42 degrees , healthy postmenopausal women with vitamin D intakes of 100 IU daily can significantly reduce late wintertime bone loss and improve net bone density of the spine over one year by increasing their intake of vitamin D to 500 IU daily . A long-term benefit of preventing vitamin D insufficiency in the winter seems likely although it remains to be shown . Observed changes in bone as well as in fat and lean tissue appear to be related to season", "Background and aims : Supplementation of postmenopausal women with calcium alone or calcium-vitamin D association was suggested to have positive effects on bone turnover and bone density , as well as to lower fracture incidence . The beneficial effect appears to be mediated by a reduction in parathyroid hormone secretion . Our aim was to compare the respective efficacy of calcium and calcium-vitamin D supplements in reducing serum parathyroid hormone levels in postmenopausal women with prevalent low 25(OH)vitamin D levels . Methods : One hundred consecutive ambulatory postmenopausal women with serum 25(OH)vitamin D levels below 18 ng/mL were included in a r and omized , prospect i ve , open label study . For a duration of 90 days , the women were r and omly assigned to a daily supplementation of either one tablet of calcium gluconolactate and carbonate ( 500 mg calcium ) , or one powder-pack of an association of calcium carbonate ( 500 mg calcium ) , citric acid ( 2.175 gr ) and cholecalciferol ( 200 IU ) . Changes observed during the 90 days of the study in circulating PTH levels were the primary endpoint , while changes in serum 25(OH)D levels were assessed as secondary endpoint . Results : A significant difference was observed between the calcium-vitamin D ( CaD ) and the calcium ( Ca ) only groups for changes occurring during the 90 days of the study in PTH ( −14.5±40 % and + 2.5±46 % ) ( p=0.009 ) and 25(OH)D ( + 67±77 % and + 18±55 % ) ( p levels . PTH changes between baseline and day 90 were significant in the CaD group , but not in the Ca group . The odds ratio for a patient in group Ca to experience an absolute ( in circulating 25(OH)vitamin D levels , compared to a group CaD patient was statistically increased ( OR : 3.22 , 95 % CI : 1.33–7.80 ) . Conclusions : Our results support the recommendation of supplementing postmenopausal women with low circulating levels of 25(OH)vitamin D with a combination of calcium and vitamin D , rather than with calcium alone", "Vitamin D deficiency is common in elderly persons , especially those with hip fracture [ 1 , 2 ] . It is caused by low exposure to sunshine , decreased synthesis of vitamin D3 in the aging skin , and a diet low in vitamin D [ 3 , 4 ] . The mean vitamin D intake in elderly persons in the Netherl and s is about 100 IU/d , half that of elderly persons in the United States [ 5 ] . Most of this vitamin D comes from margarine , which is the only vitamin D-supplemented food in the Netherl and s ( 3 IU/g ) . In vitamin D deficiency , the low serum concentration of 25-hydroxyvitamin D [ 25(OH)D ] leads to a low 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] concentration and then to a higher serum parathyroid hormone concentration , especially in the winter [ 6 - 10 ] . Histologically , the increased parathyroid activity is associated with high bone turnover , leading to cortical bone loss and low density bone [ 5 , 11 ] , which may lead to hip fracture . We previously studied the effects of vitamin D supplementation in residents of a home for the elderly and residents of a nursing home [ 10 ] . Vitamin D3 , 400 IU/d , led to an adequate increase of the serum 25(OH)D concentration , to a small but significant increase of the serum 1,25(OH)2D concentration , and to a decrease of the serum concentration of intact parathyroid hormone . It was recently observed [ 12 , 13 ] that bone mineral density at the hip is positively related to serum 25(OH)D concentration in postmenopausal and elderly women . Therefore , it might be expected that vitamin D supplementation would increase bone mineral density in elderly persons deficient in vitamin D. In line with this expectation , it was shown that vitamin D supplementation prevented bone loss from the spine during the winter in postmenopausal women [ 14 ] . These results suggest that vitamin D supplementation may reduce the incidence of hip fractures , because bone strength shows a strong correlation with bone mineral density [ 15 ] . However , increasing bone mineral density through a therapeutic intervention does not necessarily lead to increased bone strength , as has been shown with sodium fluoride [ 16 ] . Bone structure and bone quality are also determinants of bone strength [ 17 ] , and falls are a risk factor for hip fractures [ 18 ] . Therefore , hip fracture should be the outcome criterion in studies on the effect of vitamin D supplementation . Intervention studies on the prevention of osteoporotic fractures necessitate large numbers of patients , because the outcome has an annual incidence of 0.5 % to 4 % in the elderly population [ 19 ] . We report the results of a large-scale , prospect i ve study on the effect of vitamin D supplementation on the incidence of hip and other osteoporotic fractures . Methods Participants The study included 2578 persons ( 1916 women and 662 men ) 70 years of age and older ( mean age SD , 80 6 years ; range , 70 to 97 years ) . Participants were recruited from general practitioners , from apartment houses for elderly persons , and from homes for elderly persons in Amsterdam and its vicinity . Persons recruited from practitioners were living independently ; those recruited from apartment houses and homes were receiving some care , but less than they would have received in a nursing home . Participants had to be reasonably healthy and able to give informed consent . Persons with a history of hip fracture or total hip arthroplasty , known hypercalcemia , sarcoidosis , or recent urolithiasis ( were not excluded . The spontaneous use of vitamin D supplements and multivitamins was discouraged , but the prescription practice s of the general practitioners were not altered . All vitamin use was carefully documented . The study was approved by the Ethical Review Board of the Vrije Universiteit Hospital , and all participants gave informed consent . Study Design After checking the inclusion and exclusion criteria and obtaining informed consent , the participants were r and omly assigned to receive either active treatment with vitamin D3 or placebo . The study was double-blind , and r and omization was done in blocks of 10 per general practice , apartment house , or home . R and omization lists were made using a computerized r and om-number generator . Lists in sealed envelopes were sent to the hospital pharmacy for assignment . Each participant took either one tablet per day that contained vitamin D3 , 400 IU , or one placebo tablet per day that was identical in appearance and taste to the vitamin tablet . After enrollment , the participants received the first container of tablets ( 210 tablets ) . The container was replaced every 6 months with a full container . All participants were also advised in writing to consume at least three servings of dairy products per day ( for example , 1 glass of milk , 1 cup of yogurt , and 1 slice of cheese ) to ensure a calcium intake of at least 800 to 1000 mg/d . The study was started in August 1988 . The last participant was enrolled in December 1990 , and all participants had stopped using study medication by December 1993 . The follow-up period had been planned to last no more than 3 years , but because the number of hip fractures during the study was lower than expected , a 6-month extension was planned . The study participants thus received medication for 3 to 3.5 years ; those who received it for 3.5 years were those who consented to the 6-month extension . Total follow-up was to a maximum of 4 years . Data collected at baseline included an outdoor activity score ( 1 equals going outdoors less than once a week ; 2 equals going outdoors 1 or 2 times per week ; and 3 equals going outdoors 3 times per week or more ) and a score for sunshine exposure ( when outside : 1 equals in the shade as much as possible ; 2 equals sometimes in sunshine ; 3 equals much exposure to sunshine ) . These scores show a positive relation with serum 25(OH)D concentration [ 3 ] . Mobility was estimated by a walking score that ranged from 1 ( unable to walk ) to 5 ( walks independently a fair distance on any surface ) [ 20 ] . The dietary calcium intake from dairy products was estimated in a subset of 348 women by using a question naire , as described previously [ 21 ] . The participants were evaluated annually with a question naire on hip fractures , other peripheral fractures , outdoor score , sunshine exposure score , use of vitamin supplements , and walking score . Each general practitioner or caretaker was asked to immediately report change of address , hip fracture , or death . Hip fracture and death were verified by the general practitioner . All participants were followed for the maximal period of 4 years if possible , even if they had stopped using the trial medication , had sustained a fracture , or had moved to another city . To investigate possible selection bias , 267 potential participants in a home for the elderly and its adjunct apartments ( all residents of the institution ) were studied for baseline characteristics , including age , sex , sunshine exposure score , outdoor score , walking score , and reasons for nonparticipation . Compliance was checked when the tablet containers were replaced ( every 6 months ) , by question naire ( every year ) , and by measurement of the serum 25(OH)D concentration . Serum 25(OH)D concentration was measured at baseline and after 1 year in 270 persons who participated in a sub study investigating the effect of vitamin D supplementation on bone mineral density and bone turnover variables . This sub study included a nonr and om sample of participants from several apartment houses and homes for the elderly and is described in detail elsewhere [ 21 ] . In the same sub study , dietary calcium intake from diary products was assessed . Serum 25(OH)D concentration was also estimated during the third year of the study in February and March in a r and om sample of 96 participants drawn from the remaining study population . These participants received a letter giving them an appointment within 10 days ; the blood sample s were drawn at home . Serum 25(OH)D concentration was measured by competitive protein binding assay after being purified by gradient high-pressure liquid chromatography . The intra- and interassay coefficients of variation were 5 % and 6 % , respectively [ 22 ] . Statistical Analysis Baseline data of the vitamin D group and the placebo group were compared using t-tests ( age , calcium intake ) , chi-square tests ( sex , residence ) , and Wilcoxon rank-sum tests ( scores ) . The serum 25(OH)D concentrations of both groups were compared using t-tests . Data on fractures and mortality were analyzed by survival analysis using log-rank tests , Cox proportional-hazards regression , and hazard rate ratios [ 23 ] . Hip fractures are presented using the Kaplan-Meier method . All participants were kept in the study as long as possible . The data were analyzed in two ways . The intention-to-treat analysis included all r and omly assigned participants for either the total follow-up period or until fracture , death , or loss to follow-up . The active treatment analysis included the participants as long as they stated that they were using the trial medication . Thus , the participants were included in the active treatment analysis until they stopped using the trial medication , regardless of whether a fracture occurred after they had stopped . Age , sex , and residence were added in both analyses as covariates to the Cox regression model . Because outdoor score , sunshine score , and walking score were interrelated ( correlation coefficients ranging from 0.21 to 0.59 ) and were likely to indicate general health or mobility , they were averaged over the years and added up to a sum score . For this purpose , the walking score was simplified ( 1 , 2 , or 3 equals 1 ; 4 equals 2 ; 5 equals 3 ) , because the lower walking scores applied to a few participants only . The result ing total score , ranging from 3 to 9 , was entered as a covariate in the model . The level of compliance ( weekly intake as reported on", "The long term effects of hormone replacement therapy ( HRT ) and vitamin D3 ( Vit D ) on bone mineral density ( BMD ) were studied . A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study ( n = 13100 ) were r and omized to four groups : 1 ) HRT ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate , 2 ) Vit D3 ( 300 and 100 IU/day during the fifth year ) , 3 ) HRT and Vit D combined , and 4 ) placebo . Lumbar ( L2-L4 ) and femoral neck BMD were determined by dual x-ray absorptiometry ( DXA ) at baseline and after 2.5 and 5 yr of treatment . Intention to treat analysis ( n = 464 ) showed that after 5 yr , lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [ + 0.2 % ( P = 0.658 ) and + 0.9 % ( P = 0.117 ) , respectively ] , whereas lumbar BMD decreased by 4.6 % in the Vit D group and by 4.5 % in the placebo group ( P loss of femoral neck BMD was less in the HRT ( -1.4 % ; P = 0.005 ) and HRT plus Vit D ( -1.3 % ; P = 0.003 ) groups than in the Vit D and placebo groups ( -4.3 % ; P 370 women who complied with the 5-yr treatment , the effect was more pronounced : lumbar BMD had increased by 1.5 % in the HRT ( P = 0.009 ) and by 1.8 % in the HRT plus Vit D group ( P = 0.005 ) , with a plateau after 2.5 yr , whereas lumbar BMD had decreased in both the Vit D and placebo groups ( 4.6 % and 4.7 % ; P Femoral neck BMD decreased again less in the HRT ( -0.4 % ) and HRT plus Vit D ( -0.6 % ) groups than in the Vit D and placebo groups ( -4.4 % in both ) . This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis . The data suggest that low dose vitamin D3 supplementation does not prevent bone loss in healthy , nonosteoporotic , early postmenopausal women , and it confers no benefit additional to that of HRT alone ", "A two-year double-blind study monitored and evaluated the effects of 1 alpha-hydroxy vitamin D3 ( 1 alpha(OH)D3 ) on the lumbar ( L2 - 4BMD ) and total body bone mineral densities ( TBBMD ) and occurrence of fracture in 113 female osteoporotic patients receiving 0.75 micrograms/day of 1 alpha(OH)D3 ( n = 57 ) or a placebo ( n = 56 ) with calcium supplementation in both groups . L2 - 4BMD increased 1.81.% and 2.32 % after one and 2 years in the 1 alpha (OH)D3 group , but decreased 1.89 % ( P TBBMD decreased significantly in the placebo group by 3.34 % ( P new fractures occurred in the control group , but only two in the 1 alpha(OH)D3 group ( Odd 's ratio = 0.343 , 95 % confidence range ; 0.0648 - 1.815 ) . There were no serious adverse effects of the 1 alpha(OH)D3 treatment . It was concluded that two-year treatment with 1 alpha(OH)D3 increased the lumbar BMD and inhibited the decrease in TBBMD . Although it was not significant , new fracture occurrence in the 1 alpha(OH)D3 group was around 1/3 of that in the control group", "The therapeutic effect of 1,25-dihydroxycholecalciferol ( 1,25(OH)2D3 ) in postmenopausal osteoporosis was tested in a single blind , r and omized prospect i ve study . Thirty-nine women , 50 - 65 years of age , were treated for three years with 0.5 microgram 1,25(OH)2D3 daily . In a control group , 37 women were given 400 IU vitamin D3 daily . There was no significant difference in annual bone loss from the distal or proximal forearm between the groups . New vertebral fractures were evaluated , and in the treatment group , the annual increase in vertebral fractures was 0.18 + /- 0.387 and in the control group 0.13 + /- 0.330 . New long bone fractures were 7 and 5 , respectively . None of the observed differences were statistically significant . In the 1,25(OH)2D3 group , 28 % had to reduce the dose because of slight hypercalcaemia . We conclude that 1,25(OH)2D3 as used in this study is not effective in the treatment of osteoporosis", "To examine whether the administration of 1 alpha (OH)-vitamin D3 ( 1 alpha (OH)D3 ) could prevent the occurrence of vertebral crush fractures in senile osteoporosis , crush fractures of the thoracic or lumbar spine in senile osteoporosis treated with 1 alpha (OH)D3 , 1.0 microgram/day ( 22 cases ) , 1 alpha (OH)D3 1.0 microgram/day + Ca 1.0 g/day ( 16 cases ) or Ca 1.0 g/day ( 23 cases ) were compared with those in non-treated controls ( 25 cases ) . The average treatment periods were 1.7 + /- 0.7 years in the 1 alpha (OH)D3 group , 2.1 + /- 1.0 years in the 1 alpha (OH)D3 + Ca group and 1.7 + /- 0.9 years in the Ca group . Occurrence of spinal crush fractures per 1000 patient years was significantly less in the 1 alpha (OH)D3 + Ca group ( P less than 0.01 ) than in the non-treated control group . These findings suggest that administration of 1 alpha (OH)D3 is effective in preventing the occurrence of pathological fractures in senile osteoporosis", "To evaluate the effects of calcium and 25-OHD in the therapy of senile osteoporosis , we studied a group of 39 women aged 69 + /- 7 ( st and ard deviation , SD ) years with severe osteoporosis . The group was characterized histomorphometrically by depressed bone remodeling rates without hyperosteoidosis . No subject had risk factors for osteopenia other than their age and postmenopausal status , and no subject was receiving therapy for bone disease at the onset of the study . Subjects were followed for 2 years after r and omization to receive either 1200 mg/day of calcium ( as calcium carbonate ) and 40 micrograms/day of 25-OHD ( calcium-25-OHD group ) , or 1200 mg/day of calcium plus placebo ( calcium-placebo group ) . Calcium-25-OHD result ed in a clear increase in 25-OHD levels ( p less than 0.001 ) and an increase in calcium absorption as indicated by urinary calcium excretion . Nevertheless , there was no significant change in fasting serum calcium , phosphorus , alkaline phosphatase , PTH , or 1,25-(OH)2D in either group . Radial and phalangeal bone mineral content and trabecular bone volume in the biopsied patients remained stable in both groups over the 2 year period . Unexpectedly , repeat bone biopsies revealed a clear improvement in the rate of mineralization in both groups , presumably as a result of the calcium supplementation alone . In summary , calcium-placebo and calcium-25-OHD treatment were both associated with stable appendicular bone mineral content in women with senile osteopenia . The finding of an effect of calcium supplementation on the rate of mineralization indicates that relative calcium deficiency may impair the mineralization phase of remodeling . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVES To investigate the effect of vitamin K2 treatment for a year on spinal bone mineral density ( BMD ) in postmenopausal women , comparing with vitamin D3 hormone replacement therapy and to determine the factors which affect the efficacy of vitamin K2 therapy . SUBJECTS AND METHODS Seventy-two postmenopausal women were r and omized into four groups and treated with respective agents . Before the therapy , 6 and 12 months after the treatment , their lumbar spine BMD were measured by dual energy X-ray absorptiometry . The rates of change in BMD ( delta BMD ) were calculated . Correlations of BMD with age , year since menopause and the initial BMD were determined . RESULTS Vitamin K2 suppressed the decrease in spinal BMD as compared with no treatment group . BMD in women treated with vitamin K2 was inversely correlated with their age ( r = -0.54 ; P Vitamin K2 therapy may be a useful method for preventing postmenopausal spinal bone mineral loss . In addition , the therapy should be started early in postmenopausal period", "Malabsorption of calcium is a common finding in patients with postmenopausal osteoporosis ( 1 , 2 ) . In a number of studies serum 1,25 dihydroxyvitamin D levels were found to be significantly lower in osteoporotic patients , which could account for the calcium absorptive defect ( 3–6 ) . Based on these findings , we studied the effects of synthetic calcitriol ( Rocaltrol ) in women with osteoporosis . We showed that calcitriol , 0.25 μg twice daily , improved and normalized the absorption of calcium in all patients and improved calcium balance ( 7 ) . Urine hydroxyproline , which is a measure of bone resorption , decreased significantly after 2 years of treatment with Rocaltrol . Because of these preliminary findings , further clinical studies were carried out at two centers using a variable dose of Rocaltrol . In these studies we focused on the effectiveness of Rocaltrol in preventing vertebral fractures in patients with spinal osteoporosis . Methods The results from two centers have been analyzed both as separate groups and as one combined group . One study was performed at the Mayo Clinic ( Protocol 861 ) and the other at Creighton University ( Protocol 860 ) . In both centers the studies performed were double blind and r and omized , and compared the effect of placebo against Rocaltrol for a period of 1 year . At the end of 1 year all patients on placebo were crossed over to treatment with Rocaltrol and followed for 2 more years . Patients initially treated with Rocaltrol were followed for an additional 2 years , thus yielding treatment data extending to 3 years in a number of patients . In the study design , patients were given Rocaltrol at a starting dose of 0.25 μg twice daily , if hypercalcemia and hypercalciuria did not occur the dose then was increased to 0.75 μg or 1.0 μg daily at the discretion of the investigator", "Osteoporosis in men is an emerging public health problem . As calcitriol reduces the rate of vertebral fractures in osteoporotic postmenopausal women , we conducted a prospect i ve study of this treatment in men with primary osteoporosis . Our study was a 2-yr , r and omized , double masked , double placebo-controlled trial of calcitriol ( 0.25 microg twice daily ) or calcium ( 500 mg twice daily ) in 41 men with primary osteoporosis and at least 1 baseline fragility fracture . Thirty-three men ( 85 % ) completed the study . There were no differences in baseline characteristics . Spinal and femoral neck bone mineral densities at 2 yr were unchanged in both groups . Serum osteocalcin decreased in both groups by 30 % ( P urine N-telopeptide cross-links decreased only in the calcium group by 30 % ( P fractional calcium absorption increased by 34 % ( P fragility fractures occurred ( 14 vertebral and 5 nonvertebral ) in 7 men . Over 2 yr , the number of men with vertebral fractures ( 6 vs. 1 ; P = 0.097 ) was similar in both groups . In conclusion , the efficacy of calcitriol remains unproven as a single agent for the treatment of osteoporosis in men", "R and omized controlled trials have shown that a combination of vitamin D and calcium can prevent fragility fractures in the elderly . Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known . We studied if an intervention with 10 microg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double-blinded r and omized controlled trial . Residents from 51 nursing homes were allocated r and omly to receive 5 ml of ordinary cod liver oil ( n = 569 ) or 5 ml of cod liver oil where vitamin D was removed ( n = 575 ) . During the study period of 2 years , fractures and deaths were registered , and the principal analysis was performed on the intention-to-treat basis . Biochemical markers were measured at baseline and after 1 year in a sub sample . Forty-seven persons in the control group and 50 persons in the vitamin D group suffered a hip fracture . The corresponding figures for all nonvertebral fractures were 76 persons ( control group ) and 69 persons ( vitamin D group ) . There was no difference in the incidence of hip fracture ( p = 0.66 , log-rank test ) , or in the incidence of all nonvertebral fractures ( p = 0.60 , log-rank test ) in the vitamin D group compared with the control group . Compared with the control group , persons in the vitamin D group increased their serum 25-hydroxyvitamin D concentration with 22 nmol/liter ( p = 0.001 ) . In conclusion , we found that an intervention with 10 microg of vitamin D3 alone produced no fracture-preventing effect in a nursing home population of frail elderly people", "The effect of two different estrogen/gestagen regimens and 24R,25-(OH)2-cholecalciferol on bone formation was studied in a r and omized trial with 144 healthy postmenopausal women . Urinary excretion ( UE ) of 99m-technetium-diphosphonate and serum alkaline phosphatase ( AP ) was determined before and then once a year for 2 years of treatment . Both estimates of bone formation showed highly significant decreases ( p less than .001 ) to normal premenopausal levels in women receiving unopposed 17 beta-estradiol or in a sequential combination with progestagen , whereas unchanged high values were found in the groups receiving 24R,25-(OH)2D3 and placebo . The data show that bone turnover increases in early postmenopausal women concomitantly with the loss of bone mass , and that hormonal substitutional therapy normalizes the total skeletal turnover as well as preventing bone loss", "OBJECTIVE To evaluate functional improvement in a population of frail , homebound older persons with low vitamin D status as vitamin D stores improve . DESIGN R and omized , controlled intervention study . SETTING Subjects ' homes and a nursing facility in Baltimore , Maryl and . PARTICIPANTS The first 32 subjects ( community-dwelling , homebound older subjects from the Johns Hopkins Elder Housecall Program and nursing home residents from the Johns Hopkins Geriatrics Center ) entered in a longitudinal study of vitamin D replacement . MEASUREMENTS Baseline 25-hydroxyvitamin D levels were measured and repeated at least 1 month after therapy with either placebo or vitamin D ( ergocalciferol ) . Subjects were also administered the Frail Elderly Functional Assessment ( FEFA ) question naire , an instrument demonstrated to be reliable , valid , and sensitive to small increments of functional change in this population . MAIN RESULTS All subjects started with 25-hydroxyvitamin D levels less than 15 ng/mL. Those subjects whose levels improved by at least 3 ng/mL ( > assay coefficient of variation ) also demonstrated improvement in FEFA score . Regression analysis between change in FEFA score compared with change in 25-hydroxyvitamin D was significant ( r = .4 ; P = .02 ) . CONCLUSIONS In this cohort of homebound older people , improvement in vitamin D status was associated with functional improvement as measured by the FEFA question naire", "BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo . Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures", "BACKGROUND AND PURPOSE It has been demonstrated that bone mass was significantly reduced on the hemiplegic side of stroke patients , which might increase their risk of hip fracture . We evaluated the efficacy of 1 alpha-hydroxyvitamin D3 [ 1 alpha (OH)D3 ] and supplemental elemental calcium in maintaining bone mass and decreasing the incidence of hip fractures after hemiplegic stroke . METHODS In a r and omized study , 64 patients with hemiplegia after stroke with a mean duration of illness of 4.8 years received either 1 microgram 1 alpha (OH)D3 daily ( treatment group , n = 30 ) or an inactive placebo ( placebo group , n = 34 ) for 6 months and were observed for this duration . Both groups received 300 mg of elemental calcium daily . The bone mineral density ( BMD ) and metacarpal index ( MCI ) in the second metacarpals were determined by computed x-ray densitometry . The incidence of hip fractures in these patients was recorded . RESULTS BMD on the hemiplegic side decreased by 2.4 % in the treatment group and 8.9 % in the placebo group ( P = .0021 ) , while BMD on the intact side increased by 3.5 % and decreased by 6.3 % in the treated and placebo groups , respectively ( P = .0177 ) . In the treatment group , the difference in BMD between hemiplegic and nonhemiplegic sides decreased significantly compared with that before r and omization . This difference increased in the placebo group . We observed a similar improvement in MCI in the treatment group but not in the placebo group . Four patients in the placebo group suffered a hip fracture compared with none in the treatment group ( P = .0362 ) . CONCLUSIONS Treatment with 1 alpha (OH)D3 and supplemental elemental calcium can reduce the risk of hip fractures and can prevent further decreases in BMD and MCI on the hemiplegic side of patients with a long-st and ing stroke . Treatment also may improve these indices on the intact side", "Treatment with 1,25-(OH)2D3 ( calcitriol ) was compared with placebo in a double-blind , r and omized , parallel clinical trial of 24 months ' duration . Subjects were white women with postmenopausal osteoporosis . The study was completed by 15 patients who received placebo and 12 patients who received calcitriol . Positive slopes were observed in the active treatment group for total body calcium , bone mineral content of the radius , bone mineral density of the lumbar spine , and radiographic absorptiometry of the middle phalanges . In contrast , negative slopes were observed for the bone mineral measurements in the placebo group . Measurement of urinary hydroxyproline and of serum alkaline phosphatase and osteocalcin suggested that the mechanism of action of 1,25-(OH)2D3 involved reduction of bone resorption . Hypercalciuria occurred regularly and preceded hypercalcemia by about 2 weeks . A decline in creatinine clearance was observed in two patients , one of whom had nephrolithiasis on sonography . Calcitriol is effective in preventing bone loss , but must be used with caution", "Calcitriol was compared with placebo in the treatment of postmenopausal osteoporosis in a double-blind , r and omized , parallel clinical trial of 24 months ' duration . Adjustment was made in dietary calcium to maximize the dose of calcitriol . The study was completed by 15 patients who received placebo and 12 patients who received calcitriol . The calcitriol group had positive slopes ( compared with negative slopes for the placebo group ) for total body calcium , bone mineral content of the radius , bone mineral density of the lumbar spine , and radiographic absorptiometry of the middle phalanges . The difference between the two groups was statistically significant for each of these measurements . The fracture rate in the treatment group was 250 per 1,000 patient-years as compared with 333 for the placebo group . The mean dose of calcitriol was 0.8 micrograms per day . Hypercalcemia , hypercalciuria , and perhaps nephrolithiasis were observed as complications of treatment . Calcitriol increased bone mineral density by decreasing bone resorption , but not by increasing bone formation . Future studies should concentrate on treatment with oral calcitriol in lower doses . It would also be of interest to examine parenteral administration of calcitriol . It is possible that bone formation can be increased by achieving higher serum levels of the drug , whereas complications may be avoided by using a non-oral route of administration", " A cross-section of an elderly population was assessed in a double-blind trial for the effects of prophylactic vitamin D. The subjects who completed the trial were assessed clinical ly , by physiotherapy tests of muscle function and by biochemical analysis , before and after a course of vitamin D or placebo . A significant fall in serum phosphate was found in the placebo group but not in the vitamin D group . The fall was maximal between the months of October and March which correspond to maximum and minimum amounts of circulating 25-hydroxy-vitamin D during the year . No difference in muscle function between treated and untreated groups was shown . Two out of 63 individuals on vitamin D developed hypercalcaemia . It is concluded that , although there appears to be improvement in the phosphate status of treated patients over the short term of this trial , hypercalcaemia after vitamin D administration precludes the continuous prophylactic use of vitamin D at the levels employed in this trial", "To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results" ]

[ "Background —Hypertension is a leading mortality risk factor yet inadequately controlled in most affected subjects . Effective programs to address this problem are lacking . We hypothesized that an information technology – supported management program could help improve blood pressure ( BP ) control . Methods and Results —This r and omized controlled trial included 223 primary care hypertensive subjects with mean 24-hour BP > 130/80 and daytime BP > 135/85 mm Hg measured with ambulatory monitoring ( ABPM ) . Intervention subjects received a BP monitor and access to an information technology – supported adherence and BP monitoring system providing nurses , pharmacists , and physicians with monthly reports . Control subjects received usual care . The mean ( ±SD ) follow-up was 348 ( ±78 ) and 349 ( ±84 ) days in the intervention and control group , respectively . The primary end point of the change in the mean 24-hour ambulatory BP was consistently greater in intervention subjects for both systolic ( −11.9 versus −7.1 mm Hg ; P ) and diastolic BP ( −6.6 versus −4.5 mm Hg ; P=0.007 ) . The proportion of subjects that achieved Canadian Guideline target BP ( 46.0 % versus 28.6 % ) was also greater in the intervention group ( P=0.006 ) . We observed similar BP declines for ABPM and self-recorded home BP suggesting the latter could be an alternative for confirming BP control . The intervention was associated with more physician-driven antihypertensive dose adjustments or changes in agents ( P=0.03 ) , more antihypertensive classes at study end ( P=0.007 ) , and a trend toward improved adherence measured by prescription refills ( P=0.07 ) . Conclusions —This multidisciplinary information technology – supported program that provided feedback to patients and healthcare providers significantly improved blood pressure levels in a primary care setting", "Background Lifestyle modification is recommended for management of prehypertension , yet finding effective interventions to reach rural women is a public health challenge . This community-based clinical trial compared the effectiveness of st and ard advice to two multi-component theory-based tailored interventions , using web-based or print-mailed delivery , in reducing blood pressure among rural women , ages 40–69 , with prehypertension . Methods 289 women with prehypertension enrolled in the Wellness for Women : DASHing towards Health trial , a 12-month intervention with 12-month follow-up . Women were r and omly assigned to groups using a 1:2:2 ratio , comparing st and ard advice ( 30-minute counseling session ) to two interventions ( two 2-hour counseling sessions , 5 phone goal - setting sessions , strength-training video , and 16 tailored newsletters , web-based or print-mailed ) . Linear mixed model methods were used to test planned pairwise comparisons of marginal mean change in blood pressure , healthy eating and activity , adjusted for age and baseline level . General estimating equations were used to examine the proportion of women achieving normotensive status and meeting health outcome criteria for eating and activity . Results Mean blood pressure reduction ranged from 3.8 ( SD = 9.8 ) mm Hg to 8.1 ( SD = 10.4 ) mm Hg . The 24-month estimated marginal proportions of women achieving normotensive status were 47 % for web-based , and 39 % for both print-mailed and st and ard advice groups , with no group differences ( p = .11 and p = .09 , respectively ) . Web-based and print-mailed groups improved more than st and ard advice group for waist circumference ( p = .017 and p = .016 , respectively ) ; % daily calories from fat ( p = .018 and p = .030 ) and saturated fat ( p = .049 and p = .013 ) ; daily servings of fruit and vegetables ( p = .008 and p and low fat dairy ( p and ard advice groups in systolic blood pressure ( p = .048 ) and estimated VO2max ( p = .037 ) . Dropout rates were 6 % by 6-months , 11.4 % by 24 months , with no differences across groups . Conclusions Rural women with prehypertension receiving distance-delivery theory-based lifestyle modifications can achieve a reduction of blood pressure and attainment of normotensive status . Trial registration Clinical Trials.gov", "Lowering blood pressure reduces cardiovascular risk , yet hypertension is poorly controlled in diabetic patients . In a pilot study we demonstrated that a home blood pressure telemonitoring system , which provided self-care messages on the smartphone of hypertensive diabetic patients immediately after each reading , improved blood pressure control . Messages were based on care paths defined by running averages of transmitted readings . The present study tests the system 's effectiveness in a r and omized , controlled trial in diabetic patients with uncontrolled systolic hypertension . Of 244 subjects screened for eligibility , 110 ( 45 % ) were r and omly allocated to the intervention ( n=55 ) or control ( n=55 ) group , and 105 ( 95.5 % ) completed the 1-year outcome visit . In the intention-to-treat analysis , mean daytime ambulatory systolic blood pressure , the primary end point , decreased significantly only in the intervention group by 9.1±15.6 mmHg ( SD ; P not affect anxiety but worsened depression on the Hospital Anxiety and Depression Scale ( baseline , 4.1±3.76 ; exit , 5.2±4.30 ; P=0.014 ) . This study demonstrated that home blood pressure telemonitoring combined with automated self-care support reduced the blood pressure of diabetic patients with uncontrolled systolic hypertension and improved hypertension control . Home blood pressure monitoring alone had no effect on blood pressure . Promoting patient self-care may have negative psychological effects ", "OBJECTIVE To assess the effects of web-based care management on glucose and blood pressure control over 12 months in patients with poorly controlled diabetes . RESEARCH DESIGN AND METHODS For this study , 104 patients with diabetes and HbA(1c ) ( A1C ) > or = 9.0 % who received their care at a Department of Veterans Affairs medical center were recruited . All participants completed a diabetes education class and were r and omized to continue with their usual care ( n = 52 ) or receive web-based care management ( n = 52 ) . The web-based group received a notebook computer , glucose and blood pressure monitoring devices , and access to a care management website . The website provided educational modules , accepted uploads from monitoring devices , and had an internal messaging system for patients to communicate with the care manager . RESULTS Participants receiving web-based care management had lower A1C over 12 months ( P care . Persistent website users had greater improvement in A1C when compared with intermittent users ( -1.9 vs. -1.2 % ; P = 0.051 ) or education and usual care ( -1.4 % ; P website data uploads was associated with a larger decline in A1C ( highest tertile -2.1 % , lowest tertile -1.0 % ; P Hypertensive participants in the web-based group had a greater reduction in systolic blood pressure ( P HDL cholesterol rose and triglycerides fell in the web-based group ( P Web-based care management may be a useful adjunct in the care of patients with poorly controlled diabetes", "OBJECTIVE : To determine if home-centered monitoring through telemedicine has an impact on clinical characteristics , metabolic profile and quality of life in overweight and obese patients . DESIGN : R and omized controlled trial , 6-month duration . SETTING : Tertiary care academic hospital . SUBJECTS : A total of 122 patients were eligible to participate as they met the inclusion criteria of increased body mass index ( BMI > 25 kg/m2 ) , age>18 and INTERVENTIONS : All patients in the control group ( n=77 ) received st and ard hospital care . Patients in the intervention group ( n=45 ) , additionally , measured three times a week , for 6 months , their blood pressure and body weight and transmitted them to an automated call center . These values were not shared with the patients ’ physician or dietician . MAIN OUTCOME MEASURES : Clinical ( body weight , BMI , blood pressure ) , laboratory ( fasting plasma glucose , triglycerides , HDL-cholesterol , total cholesterol ) and quality of life parameters ( SF-36 ® , Visual Analog Scale of European Quality -5 Dimensions , Obesity Assessment Survey ) . Data were analyzed in an intention-to-treat-way ( last observation carried forward ) . RESULTS : Drop-out rate was similar in the control and intervention groups : 12 vs 11 percent , respectively , P = NS . There were no significant differences at baseline between intervention and control groups in all main outcome parameters . There were significant decreases for patients in the intervention group in body weight ( from 101.6±22.4 to 89.2±14.7 kg , P=0.002 , P=0.05 vs controls at 6 months ) , total cholesterol ( from 247.6±42.0 to 220.7±42.6 mg/dl , P=0.002 , P=0.05 vs controls at 6 months ) and triglycerides ( from 148.4±35.0 to 122.3±31.4 mg/dl , P=0.001 , P=0.01 vs controls at 6 months ) . Intervention group patients made a total of 1997 phone contacts . The number of phone contacts was correlated positively with Social Functioning ( SF ) , Vitality ( VT ) and Mental Health ( MH ) scores of SF-36 ® at baseline ( r=0.48 , r=0.41 , r=0.41 , respectively , P=0.05 ) but not with weight loss . CONCLUSIONS : Home-centered , intense treatment through the use of telemedicine can be effective in improving short-term obesity outcomes", "Background Blood pressure ( BP ) control remains elusive for many Americans . Although home health nurses are uniquely positioned to help vulnerable individuals achieve BP control , hypertension ( HTN ) management has not been a high priority in post-acute care . Objective To examine the effects of two home-based interventions design ed to improve BP outcomes among high-risk African-American patients . Design Cluster r and omized controlled trial . Participants A total of 845 newly admitted patients with uncontrolled HTN ( JNC7 stages 1 or 2 ) . Interventions The “ basic ” intervention delivered key HTN information to clinicians and patients , and a home BP monitor to patients , while the patients received usual post-acute care . The “ augmented ” intervention provided more intensive and extensive HTN information , monitoring and feedback for 3 months beyond the index home care admission . Measures Primary : BP control . Secondary : reductions in mmHG SBP and DBP , improvements in proportions improving JNC7 stage or achieving clinical ly meaningful reductions in SBP and DBP . Methods Multivariate regression models . Key Results The basic intervention produced no significant BP improvements ; the augmented intervention significantly improved stage 2 patients ’ outcomes . Among stage 2 patients , the augmented intervention increased BP control by 8.7 percentage points relative to usual care ( 8.9 % vs. 17.6 % ; p = 0.01 ) , yielded an 8.3 mmHG relative reduction in SBP ( p = 0.01 ) , and increased the proportion achieving at least a 20 mmHG reduction in SBP by 16.4 percentage points ( p = 0.01 ) . Conclusion Among stage 2 patients , a nurse-led intervention providing additional HTN medication review and patient self-management support during the 3-month post-acute care period yielded significant improvements in 3-month BP control , plus improvements in secondary BP outcomes", "BACKGROUND Web-based interventions for weight control could promote more-widespread dissemination of weight-loss opportunities ; however , they remain limited in effectiveness . Incorporating weight-control practice s used by individuals with long-term weight-loss success ( \" positive deviants \" ) may improve the efficacy of web-based weight control interventions . PURPOSE To evaluate the efficacy of AchieveTogether , a web-based weight-loss intervention for adults based on user-generated weight-loss strategies from successful weight losers . DESIGN In 2009 - 2010 , participants were r and omized to either a 12-week web-based intervention , AchieveTogether , or a wait-list control condition . SETTING / PARTICIPANTS 100 overweight or obese adults participated in the study . INTERVENTION AchieveTogether was design ed to help individuals implement weight control practice s used by others who successfully lost and maintained weight . MAIN OUTCOME MEASURES The primary outcome was change in weight . Secondary outcomes included blood pressure , daily caloric intake , quality of life , and use of weight control practice s. ANCOVA , with adjustment for baseline values on outcome measures , was used to assess differences between groups in primary and secondary outcomes . Statistical analyses were conducted in 2010 - 2011 . RESULTS Most participants were women ( 69.7 % ) and white ( 90.8 % ) , with a mean age of 50.3 years and baseline BMI of 33.2 ; 88 % completed post-program assessment s. Mean weight loss among intervention participants was -1.4 kg ( 95 % CI= -2.2 , -0.5 ) , compared with a mean weight gain of 0.6 kg ( 95 % CI= -0.3 , 1.4 ) in control participants ( p<0.01 ) . CONCLUSIONS User-generated weight-loss practice s from \" positive deviants \" could promote weight control in web-based interventions ; however , further research is needed to improve program efficacy . TRIAL REGISTRATION This study is registered at Clinical Trials.govNCT00709501", "The effectiveness of remote patient monitoring and physician care for the treatment of hypertension has not been demonstrated in a r and omized clinical trial . The objective of this study was to evaluate the effectiveness of remote patient monitoring with or without remote physician care in reducing office blood pressure in patients with hypertension . A total of 374 hypertensive patients over 20 years of age were r and omized into the following three groups : group ( 1 ) control , the patients received usual clinical care with home BP monitoring ; group ( 2 ) the patients were remotely monitored and received office follow-up ; and group ( 3 ) the patients received remote monitoring without physician office care using the remote monitoring device . For each group , in-office follow-up care was scheduled every 8 weeks for 24 weeks . The primary end point was the difference in sitting SBP at the 24-week follow-up . No difference between the three groups was observed in the primary end point ( adjusted mean sitting SBP was as follows : group 1 : −8.9±15.5 mm Hg , group 2 : −11.3±15.9 mm Hg , group 3 : −11.6±19.8 mm Hg , ( NS ) . Significant differences in achieving the target BP at the 24th week of follow-up were observed between groups 1 and 2 . The subjects over 55-years old had a significant decrease in the adjusted mean sitting SBP in groups 2 and 3 compared with that of the control group . Remote monitoring alone or remote monitoring coupled with remote physician care was as efficacious as the usual office care for reducing blood pressure with comparable safety and efficacy in hypertensive patients", "Background Only approximately half of patients with hypertension have their blood pressure controlled , due in large part to the tendency of primary care providers ( PCPs ) not to intensify treatment when blood pressure values are elevated . Objective This study tested the effect of an intervention design ed to help patients ask questions at the point of care to encourage PCPs to appropriately intensify blood pressure treatment . Methods PCPs and their patients with hypertension ( N=500 ) were recruited by letter and r and omized into 2 study groups : ( 1 ) intervention condition in which patients used a fully automated website each month to receive tailored messages suggesting questions to ask their PCP to improve blood pressure control , and ( 2 ) control condition in which a similar tool suggested questions to ask about preventive services ( eg , cancer screening ) . The Web-based tool was design ed to be used during each of the 12 study months and before scheduled visits with PCPs . The primary outcome was the percentage of patients in both conditions with controlled blood pressure . Results Of 500 enrolled patients ( intervention condition : n=282 ; control condition : n=218 ) , 418 ( 83.6 % ) completed the 12-month follow-up visit . At baseline , 289 ( 61.5 % ) of participants had controlled blood pressure . Most ( 411/500 , 82.2 % ) participants used the intervention during at least 6 of 12 months and 222 ( 62.5 % ) reported asking questions directly from the Web-based tool . There were no group differences in asking about medication intensification and there were no differences in blood pressure control after 12 months between the intervention condition ( 201/282 , 71.3 % ) and control condition ( 143/218 , 65.6 % ; P=.27 ) groups . More intervention condition participants discussed having a creatinine test ( 92 , 52.6 % vs 49 , 35.5 % ; P=.02 ) and urine protein test ( 81 , 44.8 % vs 21 , 14.6 % ; P discussion s about tetanus and pneumonia vaccines and reported more tetanus ( 30 , 13.8 % vs 15 , 5.3 % ; P=.02 ) and pneumonia ( 25 , 11.5 % vs 16 , 5.7 % ; P=.02 ) vaccinations after 12 months . Conclusions The use of an interactive website design ed to overcome clinical inertia for hypertension care did not lead to improvements in blood pressure control . Participant adherence to the intervention was high . The control intervention led to positive changes in the use of preventive services ( eg , tetanus immunization ) and the intervention condition led to more discussion s of hypertension-relevant tests ( eg , serum creatinine and urine protein ) . By providing patients with individually tailored questions to ask during PCP visits , this study demonstrated that participants were likely to discuss the questions with PCPs . These discussion s did not , however , lead to improvements in blood pressure control . Trial Registration Clinical Trials.gov NCT00377208 ; http:// clinical trials.gov/ct2/show/NCT00377208 ( Archived by WebCite at http://www.webcitation.org/6IqWiPLon )", "Background —Hypertension is a leading risk factor for cardiovascular disease . Although control rates have improved over time , racial/ethnic disparities in hypertension control persist . Self-blood pressure monitoring , by itself , has been shown to be an effective tool in predominantly white population s , but less studied in minority , urban communities . These types of minimally intensive approaches are important to test in all population s , especially those experiencing related health disparities , for broad implementation with limited re sources . Methods and Results —The New York City Health Department in partnership with community clinic networks implemented a r and omized clinical trial ( n=900 , 450 per arm ) to investigate the effectiveness of self-blood pressure monitoring in medically underserved and largely black and Hispanic participants . Intervention participants received a home blood pressure monitor and training on use , whereas control participants received usual care . After 9 months , systolic blood pressure decreased ( intervention , 14.7 mm Hg ; control , 14.1 mm Hg ; P=0.70 ) . Similar results were observed when incorporating longitudinal data and calculating a mean slope over time . Control was achieved in 38.9 % of intervention and 39.1 % of control participants at the end of follow-up ; the time-to-event experience of achieving blood pressure control in the intervention versus control groups were not different from each other ( logrank P value = 0.91 ) . Conclusions —Self-blood pressure monitoring was not shown to improve control over usual care in this largely minority , urban population . The patient population in this study , which included a high proportion of Hispanics and uninsured persons , is understudied . Results indicate these groups may have additional meaningful barriers to achieving blood pressure control beyond access to the monitor itself . Clinical Trial Registration : http:// clinical trials.gov . Unique Identifier :", "Failing to reach blood pressure ( BP ) goals is one of the main problems in hypertension management . Especially in high-risk patients , intensive monitoring including frequently office visits or new techniques to monitor home BP is required . A total of 60 patients with uncontrolled hypertension were included and r and omized into a group with telemetric BP monitoring ( TBPM ) ( n=30 ) and a control group receiving st and ard care ( n=30 ) . During the 3-month study period , patients received in addition to their antihypertensive pre-treatment up to 2 × 300 mg irbesartan to achieve the required target BP . All patients were instructed to measure their BP once daily in the morning . In the TBPM group automatic alerts were generated by the central data base server using pre-defined algorithms and patients were subsequently contacted by the physician . At baseline mean 24-h ambulant BP monitoring ( ABPM ) was 143.3±11.1/82.6±9.9 mm Hg in the TBPM group and 141.4±12.6/82.1±6.5 mm Hg in the st and ard care group . During treatment mean systolic BP showed a more intensive decrease in the TBPM vs control group ( −17.0±11.1 mm Hg vs −9.8±13.7 mm Hg ; P=0.032 ) . Patients in the TBPM group had a more pronounced night dipping and a higher reduction of mean pulse pressure than controls ( −8.1±5.9 mm Hg vs −2.8±7.4 mm Hg , P=0.004 ) . After 3 months , TBPM-treated patients were given a higher mean daily dose of irbesartan ( 375±187 mg vs 222±147 mg in controls ; P= more effective and faster titration of the antihypertensive agent is possible . The alarm criteria chosen were useful to improve BP control ", "IMPORTANCE Only about half of patients with high blood pressure ( BP ) in the United States have their BP controlled . Practical , robust , and sustainable models are needed to improve BP control in patients with uncontrolled hypertension . OBJECTIVES To determine whether an intervention combining home BP telemonitoring with pharmacist case management improves BP control compared with usual care and to determine whether BP control is maintained after the intervention is stopped . DESIGN , SETTING , AND PATIENTS A cluster r and omized clinical trial of 450 adults with uncontrolled BP recruited from 14,692 patients with electronic medical records across 16 primary care clinics in an integrated health system in Minneapolis-St Paul , Minnesota , with 12 months of intervention and 6 months of postintervention follow-up . INTERVENTIONS Eight clinics were r and omized to provide usual care to patients ( n = 222 ) and 8 clinics were r and omized to provide a telemonitoring intervention ( n = 228 ) . Intervention patients received home BP telemonitors and transmitted BP data to pharmacists who adjusted antihypertensive therapy accordingly . MAIN OUTCOMES AND MEASURES Control of systolic BP to less than 140 mm Hg and diastolic BP to less than 90 mm Hg ( change in BP , patient satisfaction , and BP control at 18 months ( 6 months after intervention stopped ) . RESULTS At baseline , enrollees were 45 % women , 82 % white , mean ( SD ) age was 61.1 ( 12.0 ) years , and mean systolic BP was 148 mm Hg and diastolic BP was 85 mm Hg . Blood pressure was controlled at both 6 and 12 months in 57.2 % ( 95 % CI , 44.8 % to 68.7 % ) of patients in the telemonitoring intervention group vs 30.0 % ( 95 % CI , 23.2 % to 37.8 % ) of patients in the usual care group ( P = .001 ) . At 18 months ( 6 months of postintervention follow-up ) , BP was controlled in 71.8 % ( 95 % CI , 65.0 % to 77.8 % ) of patients in the telemonitoring intervention group vs 57.1 % ( 95 % CI , 51.5 % to 62.6 % ) of patients in the usual care group ( P = .003 ) . Compared with the usual care group , systolic BP decreased more from baseline among patients in the telemonitoring intervention group at 6 months ( -10.7 mm Hg [ 95 % CI , -14.3 to -7.3 mm Hg ] ; P , diastolic BP decreased more from baseline among patients in the telemonitoring intervention group at 6 months ( -6.0 mm Hg [ 95 % CI , -8.6 to -3.4 mm Hg ] ; P BP control compared with usual care during 12 months of intervention that persisted during 6 months of postintervention follow-up . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00781365", "The relationship between ambulatory blood pressure and mortality in a general Western population is unknown . Therefore , we conducted this prospect i ve study of a r and om sample of 1700 Danish men and women , aged 41 to 72 years , without major cardiovascular diseases . At baseline , ambulatory blood pressure , office blood pressure , and other risk factors were recorded . After a mean period of 9.5 years , 174 had died : 63 were cardiovascular deaths . In multivariate proportional hazards models , adjusted for other risk factors of significance , the relative risk of cardiovascular mortality ( 95 % confidence interval ) associated with 10 mm Hg increments in systolic and 5 mm Hg increments in diastolic ambulatory blood pressure were 1.51 ( 1.28 to 1.77 ) and 1.43 ( 1.26 to 1.61 ) . The corresponding figures for all cause mortality were 1.18 ( 1.06 to 1.31 ) and 1.18 ( 1.09 to 1.28 ) . The relative risks of cardiovascular mortality were lower for office blood pressure , and office blood pressure did not predict all cause mortality . When ambulatory and office blood pressures were entered in the same multivariate models , only the ambulatory blood pressures were significant predictors of all cause mortality and cardiovascular mortality . The relationship between ambulatory blood pressures and risk of mortality was log-linear , with no indication of a threshold . The absolute risk of mortality was also dependent on age and smoking status , and an upper “ acceptable ” ambulatory blood pressure based on risk of mortality could only be defined when other risk factors were taken into account . In conclusion , ambulatory blood pressure provided prognostic information on mortality above and beyond that of office blood pressure", "PURPOSE The present study evaluated whether an intervention using a short message service ( SMS ) by personal cellular phone and Internet would reduce cardiovascular risk factors in post-menopausal women with abdominal obesity over 12 weeks . METHODS This is a quasi-experimental design with pre and post tests . Participants were recruited from the gynecology outpatient and family medicine departments of a tertiary care hospital located in an urban city of South Korea . Only 67 subjects completed the entire study , 34 in the intervention group and 33 controls . The goal of intervention was to reduce waist circumference ( WC ) , body weight ( BW ) and blood pressure ( BP ) levels . Before the intervention , demographic variables , WC , BW , BP , fasting plasma glucose ( FPG ) and serum lipids were measured as pre-test data . The WC , BW , BP , FPG and serum lipids were measured again 12 weeks later . Patients in the intervention group were requested to record their WC , BW , BP , type and amount of diet and exercise in a weekly web-based diary through the Internet or by cellular phone . The research ers sent weekly recommendations on diet and exercise as an intervention to each patient , by both cellular phone and Internet . The intervention was applied for 12 weeks . RESULTS WC and BW significantly decreased by 3.0 cm and 2.0 kg , respectively , at 12 weeks compared with the baseline in the intervention group . However , the mean changes in the control group significantly increased by 0.9 cm and 0.7 kg . Systolic BP ( SBP ) and diastolic BP ( DBP ) significantly decreased by 6.5 and 4.6 mmHg in the intervention group , respectively . The mean changes in the control group were not significant in either SBP or DBP . A significant mean decrease in total cholesterol ( TC ) was observed for the intervention group by 12.9 mg/dl , while the control group showed a significant mean increase by 1.5mg/dl . Low-density lipoprotein-cholesterol ( LDL-C ) for the intervention group showed a significant mean decrease 11.3mg/dl . The mean change in the control group was , however , not significant . CONCLUSION Web-based individual intervention using both SMS and Internet improved WC , BW , BP , TC , and LDL-C during 12 weeks in post-menopausal women with abdominal obesity", "BACKGROUND We evaluated an Internet- and telephone-based telemedicine system for reducing blood pressure ( BP ) in underserved subjects with hypertension . METHODS A total of 241 patients with systolic BP ≥140 mm Hg were r and omized to usual care ( C ; n = 121 ) or telemedicine ( T ; n = 120 ) . The T group reported BP , heart rate , weight , steps/day , and tobacco use twice weekly . The primary outcome was BP control at 6 months . RESULTS Average age was 59.6 years , average body mass index was 33.7 kg/m(2 ) , 79 % were female , 81 % were African American , 15 % were white , 53 % were at or below the federal poverty level , 18 % were smokers , and 32 % had diabetes . Six-month follow-up was achieved in 206 subjects ( C : 107 , T : 99 ) . Goal BP was achieved in 52.3 % in C and 54.5 % in T ( P = .43 ) . Systolic BP change ( C : -13.9 mm Hg , T : -18.2 ; P = .118 ) was similar in both groups . Subjects in the T group reported BP 7.7 ± 6.9 d/mo . Results were not affected by age , sex , ethnicity , education , or income . In nondiabetic T subjects , goal BP was achieved in 58.2 % compared with 45.2 % of diabetic T subjects ( P = .024 ) . Nondiabetic T subjects demonstrated a greater reduction in systolic BP ( T : -19 ± 20 mm Hg , C : -12 ± 19 mm Hg ; P = .037 ) . No difference in BP response between C and T was noted in patients with diabetes . CONCLUSION In hypertensive subjects , engagement in a system of care with or without telemedicine result ed in significant BP reduction . Telemedicine for nondiabetic patients result ed in a greater reduction in systolic BP compared with usual care . Telemedicine may be a useful tool for managing hypertension particularly among nondiabetic subjects", "Aim . To compare the effectiveness of antihypertensive treatment based on telemonitoring of home blood pressure ( BP ) and conventional monitoring of office BP . Methods . Hypertensive patients ( n = 236 ) participated in a r and omized , controlled study . In the intervention group , antihypertensive treatment was based on home BP monitoring . BP readings were registered by a PDA and automatically transmitted to a server , by which the patient and doctor could communicate . In the control group , patients received usual care with office visits to adjust antihypertensive treatment as needed . Primary outcome was difference in systolic daytime ambulatory BP monitoring ( ABPM ) change between baseline and 6 months . Results . In both groups , systolic daytime ABPM decreased significantly from baseline to follow‐up . The decrease in systolic daytime ABPM was −11.9 mmHg in the intervention group and −9.6 mmHg in the control group ( mean difference −2.3 [ 95 % CI −6.1 to −1.5 ] , p = 0.225 ) . The likelihood of daytime ABPM normalization was similar in the two groups [ 32/113 ( 28 % ) vs 46/123 ( 37 % ) , p = 0.139 ] . Conclusion . Antihypertensive treatment based on telemonitoring of home BP was as effective as usual monitoring of office BP with regards to reduction of BP . Trial registration : Clinical Trials.gov identifier : NCT00282334", "The evaluation in real-life setting s of services for the follow-up and control of hypertensive patients is a complex intervention , which still needs analysis of the roles , tasks , and re sources involved in the basic items : patient , healthcare professional , and the interaction between the two . To evaluate the impact of patient-general practitioner ( GP ) short-messages-based interaction , isolated from other items , on the degree of hypertension control in the follow-up of medium-to-low-risk patients in primary care , a r and omized controlled trial has been performed : 38 GPs enrolled 285 hypertensive patients who recorded the results of self-blood-pressure ( BP ) monitoring , heart rate , and body weight , and completed an optional question naire in an identical manner over a six-month period . The telemedicine group ( TmG ) sent the data to a telemedicine-based system that enabled patient-GP interaction ; the control group ( CG ) recorded the data on paper and could only deliver it to their GP personally in the routine visits . In the TmG , the results were better , but not significantly so , for : 1 ) degree of hypertension control , in terms of the percentage of uncontrolled hypertensives at the final visit ( TmG versus CG : 31.7 % versus 35.6 % ; p = 0.47 ) ; 2 ) reduction in hypertension during follow-up , comparing measurements ( performed by a professional ) at the initial and final visits of systolic BP ( 15.5 versus 11.9 ; p = 0.13 ) and diastolic BP ( 9.6 versus 4.4 ; p = 0.40 ) ; and 3 ) adherence to the protocol within compliance levels of interest in a real-life follow-up service : Gt50 % ( 84.8 % versus 73.3 % ) and Gt25 % ( 92.4.8 % versus 75.4 % ) ( p = 0.053 ) . Other factors such as average values of self-measured systolic BP , diastolic BP and heart rate , acceptability of the protocol , and median number of consultations and hospital admissions were similar in both groups . Outcomes show that , taken alone , the patient-GP short-messages-based interaction has very little impact on the degree of hypertension control in patients with this profile . In complex interventions , to discriminate the impact of each of its components in isolation will enable us to design an efficient follow-up service , little dem and ing in terms of healthcare professional dedication , and optimized in other basic aspects", "Background —To determine whether a pharmacist-led , Heart360-enabled , home blood pressure monitoring ( HBPM ) intervention improves blood pressure ( BP ) control compared with usual care ( UC ) . Methods and Results —This r and omized , controlled trial was conducted in 10 Kaiser Permanente Colorado clinics . Overall , 348 patients with BP above recommended levels were r and omized to the HBPM ( n=175 ) or UC ( n=173 ) groups . There were no statistically significant differences in baseline characteristics between the groups ; however , there was a trend toward a higher baseline BP for the HBPM group compared with the UC group ( 148.8 versus 145.5 mm Hg for systolic BP ; 89.6 versus 88.0 mm Hg for diastolic BP ) . At 6 months , the proportion of patients achieving BP goal was significantly higher in the HBPM group ( 54.1 % ) than in the UC group ( 35.4 % ; P to −8.6 ) reduction in systolic BP and a −5.7-mm Hg larger ( 95 % confidence interval , −7.8 to −3.6 ) reduction in diastolic BP . The impact of the intervention on BP reduction was even larger for the subgroup of patients with diabetes mellitus or chronic kidney disease . The HBPM group had more e-mail and telephone contacts and greater medication regimen intensification . The proportion of patients reporting high satisfaction with hypertension care was significantly greater in the HBPM group ( 58 % ) than in the UC group ( 42 % ) , P BP monitoring intervention led to greater BP reductions , superior BP control , and higher patient satisfaction than UC . Clinical Trial Registration —URL : http://www . clinical trials.gov/ct2/show/NCT01162759 . Unique identifier : NCT01162759", "Background Good blood pressure ( BP ) control reduces the risk of recurrence of stroke/transient ischaemic attack ( TIA ) . Although there is strong evidence that BP telemonitoring helps achieve good control , none of the major trials have considered the effectiveness in stroke/TIA survivors . We therefore conducted a feasibility study for a trial of BP telemonitoring for stroke/TIA survivors with uncontrolled BP in primary care . Method Phase 1 was a pilot trial involving 55 patients stratified by stroke/TIA r and omised 3:1 to BP telemonitoring for 6 months or usual care . Phase 2 was a qualitative evaluation and comprised semi-structured interviews with 16 trial participants who received telemonitoring and 3 focus groups with 23 members of stroke support groups and 7 carers . Results Overall , 125 patients ( 60 stroke patients , 65 TIA patients ) were approached and 55 ( 44 % ) patients were r and omised including 27 stroke patients and 28 TIA patients . Fifty-two participants ( 95 % ) attended the 6-month follow-up appointment , but one declined the second daytime ambulatory blood pressure monitoring ( ABPM ) measurement result ing in a 93 % completion rate for ABPM − the proposed primary outcome measure for a full trial . Adherence to telemonitoring was good ; of the 40 participants who were telemonitoring , 38 continued to provide readings throughout the 6 months . There was a mean reduction of 10.1 mmHg in systolic ABPM in the telemonitoring group compared with 3.8 mmHg in the control group , which suggested the potential for a substantial effect from telemonitoring . Our qualitative analysis found that many stroke patients were concerned about their BP and telemonitoring increased their engagement , was easy , convenient and reassuring . Conclusions A full-scale trial is feasible , likely to recruit well and have good rates of compliance and follow-up . Trial Registration IS RCT N61528726 15/12/2011", "CONTEXT Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions and lower access to care . OBJECTIVES To examine the effectiveness of a telemedicine intervention to achieve clinical management goals in older , ethnically diverse , medically underserved patients with diabetes . DESIGN , Setting , and Patients A r and omized controlled trial was conducted , comparing telemedicine case management to usual care , with blinded outcome evaluation , in 1,665 Medicare recipients with diabetes , aged > /= 55 years , residing in federally design ated medically underserved areas of New York State . Interventions Home telemedicine unit with nurse case management versus usual care . Main Outcome Measures The primary endpoints assessed over 5 years of follow-up were hemoglobin A1c ( HgbA1c ) , low density lipoprotein ( LDL ) cholesterol , and blood pressure levels . RESULTS Intention-to-treat mixed models showed that telemedicine achieved net overall reductions over five years of follow-up in the primary endpoints ( HgbA1c , p = 0.001 ; LDL , p systolic and diastolic blood pressure , p = 0.024 ; p HgbA1c , 3.84 ( -0.08 , 7.77 ) mg/dL for LDL cholesterol , and 4.32 ( 1.93 , 6.72 ) mm Hg for systolic and 2.64 ( 1.53 , 3.74 ) mm Hg for diastolic blood pressure . There were 176 deaths in the intervention group and 169 in the usual care group ( hazard ratio 1.01 [ 0.82 , 1.24 ] ) . CONCLUSIONS Telemedicine case management result ed in net improvements in HgbA1c , LDL-cholesterol and blood pressure levels over 5 years in medically underserved Medicare beneficiaries . Mortality was not different between the groups , although power was limited . Trial Registration http:// clinical trials.gov Identifier : NCT00271739", "OBJECTIVE Hypertension and other noncommunicable diseases represent a growing threat to low/middle-income countries ( LMICs ) . Mobile health technologies may improve noncommunicable disease outcomes , but LMICs lack re sources to provide these services . We evaluated the efficacy of a cloud computing model using automated self-management calls plus home blood pressure ( BP ) monitoring as a strategy for improving systolic BPs ( SBPs ) and other outcomes of hypertensive patients in two LMICs . SUBJECTS AND METHODS This was a r and omized trial with a 6-week follow-up . Participants with high SBPs ( ≥140 mm Hg if nondiabetic and ≥130 mm Hg if diabetic ) were enrolled from clinics in Honduras and Mexico . Intervention patients received weekly automated monitoring and behavior change telephone calls sent from a server in the United States , plus a home BP monitor . At baseline , control patients received BP results , hypertension information , and usual healthcare . The primary outcome , SBP , was examined for all patients in addition to a preplanned subgroup with low literacy or high hypertension information needs . Secondary outcomes included perceived health status and medication-related problems . RESULTS Of the 200 patients recruited , 181 ( 90 % ) completed follow-up , and 117 of 181 had low literacy or high hypertension information needs . The median annual income was $ 2,900 USD , and average educational attainment was 6.5 years . At follow-up intervention patients ' SBPs decreased 4.2 mm Hg relative to controls ( 95 % confidence interval -9.1 , 0.7 ; p=0.09 ) . In the subgroup with high information needs , intervention patients ' average SBPs decreased 8.8 mm Hg ( -14.2 , -3.4 , p=0.002 ) . Compared with controls , intervention patients at follow-up reported fewer depressive symptoms ( p=0.004 ) , fewer medication problems ( p , better general health ( p , and greater satisfaction with care ( p≤0.004 ) . CONCLUSIONS Automated telephone care management plus home BP monitors can improve outcomes for hypertensive patients in LMICs . A cloud computing model within regional telecommunication centers could make these services available in areas with limited infrastructure for patient-focused informatics support", "BACKGROUND Control of blood pressure is a key component of cardiovascular disease prevention , but is difficult to achieve and until recently has been the sole preserve of health professionals . This study assessed whether self-management by people with poorly controlled hypertension result ed in better blood pressure control compared with usual care . METHODS This r and omised controlled trial was undertaken in 24 general practice s in the UK . Patients aged 35 - 85 years were eligible for enrolment if they had blood pressure more than 140/90 mm Hg despite antihypertensive treatment and were willing to self-manage their hypertension . Participants were r and omly assigned in a 1:1 ratio to self-management , consisting of self-monitoring of blood pressure and self-titration of antihypertensive drugs , combined with telemonitoring of home blood pressure measurements or to usual care . R and omisation was done by use of a central web-based system and was stratified by general practice with minimisation for sex , baseline systolic blood pressure , and presence or absence of diabetes or chronic kidney disease . Neither participants nor investigators were masked to group assignment . The primary endpoint was change in mean systolic blood pressure between baseline and each follow-up point ( 6 months and 12 months ) . All r and omised patients who attended follow-up visits at 6 months and 12 months and had complete data for the primary outcome were included in the analysis , without imputation for missing data . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N17585681 . FINDINGS 527 participants were r and omly assigned to self-management ( n=263 ) or control ( n=264 ) , of whom 480 ( 91 % ; self-management , n=234 ; control , n=246 ) were included in the primary analysis . Mean systolic blood pressure decreased by 12.9 mm Hg ( 95 % CI 10.4 - 15.5 ) from baseline to 6 months in the self-management group and by 9.2 mm Hg ( 6.7 - 11.8 ) in the control group ( difference between groups 3.7 mm Hg , 0.8 - 6.6 ; p=0.013 ) . From baseline to 12 months , systolic blood pressure decreased by 17.6 mm Hg ( 14.9 - 20.3 ) in the self-management group and by 12.2 mm Hg ( 9.5 - 14.9 ) in the control group ( difference between groups 5.4 mm Hg , 2.4 - 8.5 ; p=0.0004 ) . Frequency of most side-effects did not differ between groups , apart from leg swelling ( self-management , 74 patients [ 32 % ] ; control , 55 patients [ 22 % ] ; p=0.022 ) . INTERPRETATION Self-management of hypertension in combination with telemonitoring of blood pressure measurements represents an important new addition to control of hypertension in primary care . FUNDING Department of Health Policy Research Programme , National Coordinating Centre for Research Capacity Development , and Midl and s Research Practice s Consortium", "PURPOSE The present study evaluated whether an intervention using a short message service ( SMS ) by cellular phone and Internet would improve blood pressure , weight control , and serum lipids of obese patients with hypertension during 8 weeks . METHODS This is a quasi-experimental design with pre- and follow-up tests . Participants were recruited from the family medicine outpatient department of tertiary care hospital located in an urban city of South Korea . Twenty-eight patients were assigned to an intervention group and 21 to a control group . The goal of intervention was to bring blood pressure , body weight , and serum lipids levels close to normal ranges . Patients in the intervention group were requested to record their blood pressure and body weight in a weekly web based diary through the Internet or by cellular phones . The research ers sent optimal recommendations as an intervention to each patient , by both cellular phone and Internet weekly . The intervention was applied for 8 weeks . RESULTS Systolic ( SBP ) and diastolic blood pressures ( DBP ) significantly decreased by 9.1 and 7.2 mmHg respectively at 8 weeks from the baseline in the intervention group ( p SBP and DBP in the control group had not changed significantly . Yet , There were significant mean decreases in body weight and waist circumference by 1.6 kg ( p body weight and waist circumference ( p High density lipoprotein cholesterol ( HDL-C ) significantly increased , with a mean change of 3.7 mg/dl at 8 weeks from baseline in the intervention group ( p change of HDL-C in the control group was , however , not significant . CONCLUSION During 8 weeks using this web-based intervention by way of cellular phone and Internet SMS improved blood pressure , body weight , waist circumference , and HDL-C in patients with obese hypertension", "IMPORTANCE Self-monitoring of blood pressure with self-titration of antihypertensives ( self-management ) results in lower blood pressure in patients with hypertension , but there are no data about patients in high-risk groups . OBJECTIVE To determine the effect of self-monitoring with self-titration of antihypertensive medication compared with usual care on systolic blood pressure among patients with cardiovascular disease , diabetes , or chronic kidney disease . DESIGN , SETTING , AND PATIENTS A primary care , unblinded , r and omized clinical trial involving 552 patients who were aged at least 35 years with a history of stroke , coronary heart disease , diabetes , or chronic kidney disease and with baseline blood pressure of at least 130/80 mm Hg being treated at 59 UK primary care practice s was conducted between March 2011 and January 2013 . INTERVENTIONS Self-monitoring of blood pressure combined with an individualized self-titration algorithm . During the study period , the office visit blood pressure measurement target was 130/80 mm Hg and the home measurement target was 120/75 mm Hg . Control patients received usual care consisting of seeing their health care clinician for routine blood pressure measurement and adjustment of medication if necessary . MAIN OUTCOMES AND MEASURES The primary outcome was the difference in systolic blood pressure between intervention and control groups at the 12-month office visit . RESULTS Primary outcome data were available from 450 patients ( 81 % ) . The mean baseline blood pressure was 143.1/80.5 mm Hg in the intervention group and 143.6/79.5 mm Hg in the control group . After 12 months , the mean blood pressure had decreased to 128.2/73.8 mm Hg in the intervention group and to 137.8/76.3 mm Hg in the control group , a difference of 9.2 mm Hg ( 95 % CI , 5.7 - 12.7 ) in systolic and 3.4 mm Hg ( 95 % CI , 1.8 - 5.0 ) in diastolic blood pressure following correction for baseline blood pressure . Multiple imputation for missing values gave similar results : the mean baseline was 143.5/80.2 mm Hg in the intervention group vs 144.2/79.9 mm Hg in the control group , and at 12 months , the mean was 128.6/73.6 mm Hg in the intervention group vs 138.2/76.4 mm Hg in the control group , with a difference of 8.8 mm Hg ( 95 % CI , 4.9 - 12.7 ) for systolic and 3.1 mm Hg ( 95 % CI , 0.7 - 5.5 ) for diastolic blood pressure between groups . These results were comparable in all subgroups , without excessive adverse events . CONCLUSIONS AND RELEVANCE Among patients with hypertension at high risk of cardiovascular disease , self-monitoring with self-titration of antihypertensive medication compared with usual care result ed in lower systolic blood pressure at 12 months . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N87171227", "BACKGROUND Hypertension is a major risk factor for the long-term complications of diabetes . Mobile , self-measurement of blood pressure is emerging as a method to manage blood pressure in general , but its impact in patients with diabetes is unclear . METHODS We r and omized 137 patients with diabetes and hypertension to either mobile telemonitoring ( n = 72 ) or usual care ( n = 65 ) . Clinic blood pressure was recorded at baseline and after 6 months . Patients in the intervention arm transmitted weekly blood pressure readings wirelessly , using adapted sensors via mobile phones to a central server . Clinicians received the data in real-time and using a web-based application provided management advice to the patient and their physicians . RESULTS Systolic blood pressure fell significantly in the patients in the intervention group ( mean [ 95 % confidence interval ] , -6.5 [ -0.8 to -12.2 ] mm Hg ; P = 0.027 ) and remained unchanged in the control group ( 2.1 [ 9.3 to -5.0 ] mm Hg ; P = 0.57 ) . Patients within the intervention arm of African origin seemed to benefit more from the intervention . In addition , those who achieved a systolic blood pressure of average blood sugars than those with higher readings ( 7.8 [ SD 1.6 ] vs. 8.9 [ SD 2.2 ] mmol/L ; P = 0.02 ) . CONCLUSIONS In patients with diabetes , mobile telemonitoring has potential for delivering intensified care to improve blood pressure control , and its use may be associated with reduced exposure to hyperglycemia", "BACKGROUND The emergence of the World Wide Web in the last decade has made it feasible for the Internet to be a vehicle for chronic disease management . METHODS A r and omized controlled trial ( n = 62 ) testing the effects of a 6-month web-based intervention plus usual care , compared with usual care alone , among adults 60 years of age and older with diabetes . The outcomes were hemoglobin A1c ( HbA1c ) , blood pressure , weight , cholesterol , and high-density lipoprotein ( HDL ) levels . RESULTS A multivariate analysis of covariance controlling for all baseline outcome variables , age , gender , and number of years with diabetes showed significant ( P = 0.001 ) reductions in HbA1c , weight , and cholesterol level and significant improvement in HDL levels in the intervention versus the control group . CONCLUSIONS Findings show a web-based intervention was effective in improving HbA1c , weight , cholesterol , and HDL levels at a 6-month follow-up . Future research is needed to investigate the long-term effectiveness of web-based interventions", "AIMS The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide . To improve the quality and efficiency of chronic disease care , we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care ( UCDC ) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension . METHODS We conducted a r and omized , controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre . RESULTS After 12 weeks , there were significant improvements in HbA(1c ) in the intervention group ( 7.6 + /- 0.9 % to 7.1 + /- 0.8 % , P systolic and diastolic blood pressure , as well as improvements in total cholesterol , low-density lipoprotein-cholesterol and triglyceride levels in the intervention group . Furthermore , there was a significant increase in adiponectin levels in the intervention group compared with the control group , although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group . CONCLUSIONS The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension", "Background : Nearly one in three adults in the United States has hypertension . Hypertension is one of the largest risk factors for cardiovascular diseases , and it is growing in prevalence , especially among African Americans . Objectives : To test the hypothesis that individuals who participate in usual care ( UC ) plus blood pressure ( BP ) telemonitoring ( TM ) will have a greater reduction in BP from baseline to 12-month follow-up than would individuals who receive UC only . Methods : A two-group , experimental , longitudinal design with block stratified r and omization for antihypertensive medication use was used . African Americans with hypertension were recruited through free BP screenings offered in the community . Data were collected through a structured interview and brief physical exam . Cross tabs , repeated measures analysis of variance , and independent t tests were used to analyze the study 's hypothesis . Results : The TM intervention group had a greater reduction in systolic BP ( 13.0 mm Hg ) than the enhanced UC group ( 7.5 mm Hg ; t = −2.09 , p = .04 ) from baseline to the 12-month follow-up . Although the TM intervention group had a greater reduction in diastolic BP ( 6.3 mm Hg ) compared with the enhanced UC group ( 4.1 mm Hg ) , the differences were not statistically significant ( t = −1.56 , p = .12 ) . Discussion : Telemonitoring of BP result ed in clinical ly and statistically significant reductions in systolic BP over a 12-month period ; if maintained over a longer period of time , the reductions could improve care and outcomes significantly for African Americans with hypertension", "BACKGROUND To determine which of 3 interventions was most effective in improving blood pressure ( BP ) control , we performed a 4-arm r and omized trial with 18-month follow-up at the primary care clinics at a Veterans Affairs Medical Center . METHODS Eligible patients were r and omized to either usual care or 1 of 3 telephone-based intervention groups : ( 1 ) nurse-administered behavioral management , ( 2 ) nurse- and physician-administered medication management , or ( 3 ) a combination of both . Of the 1551 eligible patients , 593 individuals were r and omized ; 48 % were African American . The intervention telephone calls were triggered based on home BP values transmitted via telemonitoring devices . Behavioral management involved promotion of health behaviors . Medication management involved adjustment of medications by a study physician and nurse based on hypertension treatment guidelines . RESULTS The primary outcome was change in BP control measured at 6-month intervals over 18 months . Both the behavioral management and medication management alone showed significant improvements at 12 months-12.8 % ( 95 % confidence interval [ CI ] , 1.6%-24.1 % ) and 12.5 % ( 95 % CI , 1.3%-23.6 % ) , respectively-but not at 18 months . In subgroup analyses , among those with poor baseline BP control , systolic BP decreased in the combined intervention group by 14.8 mm Hg ( 95 % CI , -21.8 to -7.8 mm Hg ) at 12 months and 8.0 mm Hg ( 95 % CI , -15.5 to -0.5 mm Hg ) at 18 months , relative to usual care . CONCLUSIONS Overall intervention effects were moderate , but among individuals with poor BP control at baseline , the effects were larger . This study indicates the importance of identifying individuals most likely to benefit from potentially re source intensive programs . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00237692", "OBJECTIVE To determine if a multimodal intervention composed of patient education , home blood pressure ( BP ) monitoring , BP measurement reporting to an interactive voice response ( IVR ) phone system , and clinical pharmacist follow-up improves BP control compared with usual care . STUDY DESIGN Prospect i ve study with patient enrollment , medication consultation and adjustment , remote BP monitoring , and follow-up at 6 months . METHODS This r and omized controlled trial was conducted at 3 healthcare systems in Denver , Colorado , including a large health maintenance organization , a Veterans Affairs medical center , and a county hospital . At each site , patients with uncontrolled BP were r and omized to the multimodal intervention vs usual care for 6 months , with the primary end point of BP reduction . RESULTS Of 338 patients r and omized , 283 ( 84 % ) completed the study , including 138 intervention patients and 145 usual care patients . Baseline BP was higher in the intervention group vs the usual care group ( 150.5/89.4 vs 143.8/85.3 mm Hg ) . At 6 months , BPs were similar in the intervention group vs the usual care group ( 137.4 vs 136.7 mm Hg , P = .85 for systolic ; 82.9 vs 81.1 mm Hg , P = .14 for diastolic ) . However , BP reductions were greater in the intervention group vs the usual care group ( −13.1 vs −7.1 mm Hg , P = .006 for systolic ; −6.5 vs −4.2 mm Hg , P = .07 for diastolic ) . Adherence to medications was similar between the 2 groups , but intervention patients had a greater increase in medication regimen intensity . CONCLUSIONS A multimodal intervention of patient education , home BP monitoring , BP measurement reporting to an IVR system , and clinical pharmacist follow-up achieved greater reductions in BP compared with usual care", "Abstract Effective antihypertensive care is not possible without regular and reliable blood pressure measurements . The use of blood pressure home measurement has increased a lot during the last years . Various methods have been used in communication between the patients and physicians . In a r and omized study we compared traditional office-based hypertension treatment protocol ( n=68 ) to the home-based blood pressure measurement protocol ( n=89 ) in which the patient mailed their home-measured BP diary in a letter to the office of their physician . The studied home-based antihypertensive care system was not more effective than the ordinary office-based treatment . The results highlight the importance of continuous home measurement data interpretation by the physician . The system based on mailing the results to the physician office does not seem to be a suitable method in communication between the patient and the physician . Online or other telemedicine-aided means of communication might yield better antihypertensive control", "This study was conducted to evaluate the effect of automated telephone patient monitoring and counseling on patient adherence to antihypertensive medications and on blood pressure control . A r and omized controlled trial was conducted in 29 greater Boston communities . The study subjects were 267 patients recruited from community sites who were > or= 60 years of age , on antihypertensive medication , with a systolic blood pressure ( SBP ) of > or= 160 mm Hg and /or a diastolic blood pressure ( DBP ) of > or= 90 mm Hg . The study compared subjects who received usual medical care with those who used a computer-controlled telephone system in addition to their usual medical care during a period of 6 months . Weekly , subjects in the telephone group reported self-measured blood pressures , knowledge and adherence to antihypertensive medication regimens , and medication side-effects . This information was sent to their physicians regularly . The main study outcome measures were change in antihypertensive medication adherence , SBP and DBP during 6 months , satisfaction of patient users , perceived utility for physicians , and cost-effectiveness . The mean age of the study population was 76.0 years ; 77 % were women ; 11 % were black . Mean antihypertensive medication adherence improved 17.7 % for telephone system users and 11.7 % for controls ( P = .03 ) . Mean DBP decreased 5.2 mm Hg in users compared to 0.8 mm Hg in controls ( P = .02 ) . Among nonadherent subjects , mean DBP decreased 6.0 mm Hg for telephone users , but increased 2.8 mm Hg for controls ( P = .01 ) . For telephone system users , mean DBP decreased more if their medication adherence improved ( P = .03 ) . The majority of telephone system users were satisfied with the system . Most physicians integrated it into their practice s. The system was cost-effective , especially for nonadherent patient users . Therefore , weekly use of an automated telephone system improved medication adherence and blood pressure control in hypertension patients . This system can be used to monitor patients with hypertension or with other chronic diseases , and is likely to improve health outcomes and reduce health services utilization and costs", "BACKGROUND Increased emphasis is being placed on the critical need to control hypertension ( HTN ) in patients with diabetes . OBJECTIVE The objective of this study was to evaluate the efficacy of a nurse-managed home telehealth intervention to improve outcomes in veterans with comorbid diabetes and HTN . DESIGN A single-center , r and omized , controlled clinical trial design comparing two remote monitoring intensity levels and usual care in patients with type 2 diabetes and HTN being treated in primary care was used . MEASUREMENTS Primary outcomes were hemoglobin A1c and systolic blood pressure ( SBP ) ; secondary outcome was adherence . RESULTS Intervention subjects experienced decreased A1c during the 6-month intervention period compared with the control group , but 6 months after the intervention was withdrawn , the intervention groups were comparable with the control group . For SBP , the high-intensity subjects had a significant decrease in SBP compared with the other groups at 6 months and this pattern was maintained at 12 months . Adherence improved over time for all groups , but there were no differences among the three groups . LIMITATIONS Subjects had relatively good baseline control for A1c and SBP ; minorities and women were underrepresented . CONCLUSIONS Home telehealth provides an innovative and pragmatic approach to enhance earlier detection of key clinical symptoms requiring intervention . Transmission of education and advice to the patient on an ongoing basis with close surveillance by nurses can improve clinical outcomes in patients with comorbid chronic illness", "BACKGROUND African Americans have a higher prevalence and greater severity of hypertension than do other minorities and whites . This fact is particularly problematic when one realizes that the rate of control and treatment of hypertension in the US population is getting worse rather than better . Alternative strategies to promote blood pressure control need to be tested . OBJECTIVES The purpose of this pilot study was to test the following hypothesis : Persons who participate in nurse-managed home telemonitoring ( HT ) plus usual care or who participate in nurse-managed community-based monitoring ( CBM ) plus usual care will have greater improvement in blood pressure from baseline to 3 months ' follow-up than will persons who receive usual care only . METHODS This study used a r and omized controlled design ; participants were r and omly assigned to 1 of 3 groups that were stratified by use or nonuse of antihypertension medication . One-way analysis of variance ( ANOVA ) and analysis of covariance ( ANCOVA ) controlling for age and body weight were used to determine changes in blood pressure from baseline to 3 months . The sample contained 26 African Americans with a mean age of 59 years . RESULTS Both the HT group and the CBM group had clinical ly and statistically significant ( P systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) at 3 months ' follow-up , with participants in the HT group demonstrating the greatest improvement ( HT : baseline SBP 148.8 + /- 13.8 , DBP 90.2 + /- 5.79 ; 3 months ' follow-up SBP 124.1 + /- 13.82 , DBP 75.58 + /- 11.4 ; CBM : baseline SBP 155.25 + /- 17.014 , DBP 89.42 + /- 10.95 ; 3 months ' follow-up SBP 142.3 + /- 12.1 , DBP 78.25 + /- 6.86 ) . There was little change in SBP or DBP at 3 months ' follow-up in the usual care only group . CONCLUSION These are important pilot results , which if replicated in a larger sample will significantly improve care for urban African Americans with hypertension", "The objective of this study was to determine whether a hypertension management program in which patients monitor their own blood pressure ( BF ) at home can reduce costs without compromising BP control . The prospect i ve , r and omized , controlled 1-year clinical trial was conducted at four medical centers of the Kaiser Permanente Medical Care Program in the San Francisco Bay Area . Of 467 patients with uncomplicated hypertension who were referred by their physicians , 37 declined to participate in the study ; 215 were r and omly assigned to a Usual Care ( UC ) group and 215 to a Home BP group . Twenty-five UC patients and 15 Home BP patients did not return for year-end BP measurements . Patients in the UC group were referred back to their physicians . Patients in the Home BP group were trained to measure their own BP and return the readings by mail . Patients were given a st and ard procedure to follow in case of unusually high or low BP readings at home . The number and type of outpatient medical services used were obtained from patient medical records for the study year and the prior year . Costs of care for hypertension were calculated by assigning relative value units to each outpatient service . Trained technicians measured each patient 's BP at entry into the study and 1 year later . Home BP patients made 1.2 fewer hypertension-related office visits than UC patients during the study year ( 95 % confidence interval ( CI ) : 0.8,1.7 ) . Mean adjusted cost for physician visits , telephone calls , and laboratory tests associated with hypertension care was $ 88.76 per patient per year in the Home BP group , 29 % less than in the UC group ( 95 % CI : $ 16.11 , $ 54.74 ) . The annualized cost of implementing the home BP system was approximately $ 28 per patient during the study year and would currently be approximately $ 15 . After 1 year , BP control in men in the Home BP group was better than in men in the UC group ; BP control was equally good in women in both groups . Management of uncomplicated hypertension based on periodic home BP reports can achieve BP control with fewer physician visits , result ing in substantial cost savings", "Many Korean American persons have hypertension , but competing life priorities often prevent them from attending health-promotion educational activities . Using principles of community-based participatory research , the authors conducted a prospect i ve clinical trial to determine the effectiveness of a mailed vs an in-class culturally tailored education intervention . A total of 380 hypertensive Korean American persons from the Baltimore/Washington area were assigned to a more intense in-class education group or a less intensive mail education group . Evaluation of postintervention blood pressure ( BP ) outcomes revealed that significant reductions in systolic BP ( 13.3 mm Hg and 16.1 mm Hg , respectively ) and diastolic BP ( 9.5 mm Hg and 10.9 mm Hg ) and increases in BP control rates ( 42.3 % and 54.3 % ) were achieved in both groups . No significant differences in BP outcomes between groups , however , were found . In conclusion , education by mail was an effective strategy for improving BP control and may be a viable approach for other immigrant groups if the education material s address their cultural needs", "Objective Older adults with chronic kidney disease have a high rate of uncontrolled hypertension . Home monitoring of blood pressure ( BP ) is an integral part of management , but requires that patients bring records to clinic visits . Telemonitoring interventions , however , have not targeted older , less technologically-skilled population s. Methods Veterans with stage 3 or greater chronic kidney disease and uncontrolled hypertension were r and omized to a novel telemonitoring device pairing a Bluetooth-enabled BP cuff with an Internet-enabled hub , which wirelessly transmitted readings ( n=28 ) , or usual care ( n=15 ) . Home recordings were review ed weekly and telemonitoring participants were contacted if BP was above goal . The prespecified primary endpoints were improved data exchange and device acceptability . Secondary endpoint was BP change . Results Forty-three participants ( average age 68 years , 75 % white ) completed the 6-month study . Average start-of- study BP was 147/78 mmHg . Those in the intervention arm had a median of 29 ( IQR 22 , 53 ) transmitted BP readings per month , with 78 % continuing to use the device regularly , whereas only 20 % of those in the usual care group brought readings to in-person visits . The median number of telephone contacts triggered by the wireless monitoring was 2 ( IQR 1 , 4 ) per patient . Both groups had a significant improvement in systolic BP ( P systolic BP fell a median of 13 mmHg in monitored participants compared with 8.5 mmHg in usual care participants ( P for comparison 0.31 ) . Conclusion This low-cost wireless monitoring strategy led to greater sharing of data between patients and clinic and produced a trend toward improvements in BP control over usual care at 6 months", "Objective To determine if an intervention consisting of telemonitoring and supervision by usual primary care clinicians of home self measured blood pressure and optional patient decision support leads to clinical ly important reductions in daytime systolic and diastolic ambulatory blood pressure in patients with uncontrolled blood pressure . Design Multicentre r and omised controlled trial . Setting 20 primary care practice s in south east Scotl and . Participants 401 people aged 29 - 95 years with uncontrolled blood pressure ( mean daytime ambulatory measurement ≥135/85 mm Hg but ≤210/135 mm Hg ) . Intervention Self measurement and transmission of blood pressure readings to a secure website for review by the attending nurse or doctor and participant , with optional automated patient decision support by text or email for six months . Main outcome measures Blinded assessment of mean daytime systolic ambulatory blood pressure six months after r and omisation . Results 200 participants were r and omised to the intervention and 201 to usual care ; primary outcome data were available for 90 % of participants ( 182 and 177 , respectively ) . The mean difference in daytime systolic ambulatory blood pressure adjusted for baseline and minimisation factors between intervention and usual care was 4.3 mm Hg ( 95 % confidence interval 2.0 to 6.5 ; P=0.0002 ) and for daytime diastolic ambulatory blood pressure was 2.3 mm Hg ( 0.9 to 3.6 ; P=0.001 ) , with higher values in the usual care group . The intervention was associated with a mean increase of one general practitioner ( 95 % confidence interval 0.5 to 1.6 ; P=0.0002 ) and 0.6 ( 0.1 to 1.0 ; P=0.01 ) practice nurse consultations during the course of the study . Conclusions Supported self monitoring by telemonitoring is an effective method for achieving clinical ly important reductions in blood pressure in patients with uncontrolled hypertension in primary care setting s. However , it was associated with increase in use of National Health Service re sources . Further research is required to determine if the reduction in blood pressure is maintained in the longer term and if the intervention is cost effective . Trial registration Current Controlled Trials IS RCT N72614272", "OBJECTIVE The purpose of this study was to evaluate the short-term motivational effect of a technology-based weight reduction program for obese adults . METHODS One hundred and eleven obese ( 37.0+/-5.8 kg/m(2 ) ) middle aged ( 45.5+/-10.8 years ) adults ( 62 % female ) were r and omly assigned to a usual care or experimental ( SMART : self-monitoring and resting metabolic rate technology ) group . The usual care group received a st and ard nutritional program in accordance to national guidelines . All participants received a comprehensive weight management program consisting of motivational interviewing ( MI ) sessions and automated e-mail behavioral newsletters . Bodyweight , arterial blood pressure , and psychobehavioral constructs were assessed over 12 weeks . RESULTS Completer analysis ( n=80 ) indicated a significant improvement in bodyweight ( -3.9 % ) , systolic arterial pressure ( -4 mmHg ) , and all motivational constructs following the 12-week study ( p MI and automated e-mail behavioral newsletters with or without SMART is efficacious in treating obese adults . PRACTICE IMPLICATION S Although both treatment programs were equally effective , clinicians should consider a treatment program that meets the need of the patient . This study was registered at Clinical Trials.gov NCT00750022", "BACKGROUND Pharmacist- or nurse-led team care decreases patient blood pressure ( BP ) and cardiovascular disease ( CVD ) risk . PURPOSE To evaluate whether a Web-based dietitian-led ( WD ) team care intervention was feasible and result ed in decreased BP , CVD risk , and weight compared to usual care ( UC ) . METHODS Electronic health record ( EHR ) data identified patients aged 30 - 69 years with BMI > 26 , elevated BP , and 10%-25 % 10-year Framingham CVD risk who were registered patient website users . Patients with uncontrolled BP at screening were r and omized to UC or WD , which included a home BP monitor , scale , and dietitian team care . WD participants had a single in-person dietitian visit to obtain baseline information and create a plan to reduce CVD risk . Planned follow-up occurred via secure messaging to report BP , weight , and fruit and vegetable intake and receive ongoing feedback . If needed , dietitians encouraged patients and their physicians to intensify antihypertensive and lipid-lowering medications . Primary outcomes were change in systolic BP and weight loss ≥4 kg at 6 months . Feasibility outcomes included intervention utilization and satisfaction . RESULTS Between 2010 and 2011 , a total of 90 of 101 participants completed 6-month follow-ups . The WD group had higher rates of secure messaging utilization and patient satisfaction . The WD group lost significantly more weight than the UC group ( adjusted net difference=-3.2 kg , 95 % CI=-5.0 , -1.5 , p lose ≥4 kg ( adjusted relative risk [RRadj]=2.96 , 95 % CI=1.16 , 7.53 ) . BP control and CVD risk reduction were greater in WD than UC , but differences were not statistically significant . CONCLUSIONS WD intervention was feasible and result ed in decreased weight , BP , and CVD risk . A larger trial is justified . TRIAL REGISTRATION NUMBER Trial Registration Number : NCT01077388", "Objective To evaluate the efficacy of a programme of home blood pressure measurement ( HBPM ) on therapeutic compliance in mild-to-moderate hypertension . Design A prospect i ve controlled multicentre clinical trial . Setting Forty primary care centres in Spain , with a duration of 6 months . Patients A total of 250 patients with newly diagnosed or uncontrolled hypertension were included . Interventions The patients were r and omly selected and distributed in two groups : ( 1 ) the control group ( CG ) who received st and ard health intervention ; ( 2 ) the intervention group ( IG ) : the patients in this group received an OMRON in their homes for a programme of HBPM . Main outcome measure Four visits were scheduled , for the measurement of blood pressure ( BP ) . They were provided with an electronic monitor for measuring compliance ( monitoring events medication system ; MEMS ) . Therapeutic compliance was defined as a drug consumption of 80–110 % . A number of variables were calculated using the MEMS . The mean BP were calculated and the percentage of controlled patients . Results A total of 200 patients completed the study ( 100 in each group ) . Compliance was observed in 74 and 92 % , respectively , in the CG and IG [ 95 % confidence interval ( CI ) 63.9–84.1 and 86.7–97.3 ; P = 0.0001 ] , the mean percentage compliances were 87.6 and 93.5 % ( 95 % CI 81.2–94 and 80.7–98.3 ; P = 0.0001 ) , the percentages of correct days were 83.6 and 89.4 % , the percentages of subjects who took the medication at the prescribed time were 79.89 and 88.06 % , and the levels of therapeutic cover were 86.7 and 93.1 % . The number needed to treat to avoid one case of non-compliance was 5.6 patients . The differences in the mean decreases in BP were significant for diastolic BP , with a greater decrease observed in the IG . Conclusions An HBPM programme using electronic monitors is effective in improving compliance in arterial hypertension , measured using the MEMS", "Although the use of telecommunication systems in medicine has been increasing , few trials have assessed the efficacy of such technology for improving blood pressure in patients with essential hypertension ( 1 , 2 ) . Friedman and colleagues ( 1 ) found that when hypertensive patients used a telephone-linked computer system to report blood pressure , diastolic blood pressure decreased significantly . Bondmass and colleagues ( 2 ) also found a significant decrease in both diastolic and systolic blood pressure , although their trial lacked controls . In these studies and in other trials of home monitoring , self-report of blood pressure was the basic mechanism for transmission of information to physicians ( 1 - 8 ) . This may have consequences for patient care , since it has recently been shown that patients often erroneously report blood pressure , especially patients whose blood pressure is uncontrolled ( 9 ) . Johnson and colleagues ( 9 ) found that in approximately 20 % of instances , self-report of blood pressure differed from the electronic reading by more than 10 mm Hg . Another limitation of previous trials is accurate assessment of the outcome . In some studies , the outcome was determined by one or two blood pressure readings taken during an office visit or by a technician in the home setting ( 1 , 4 - 7 ) . Only one study of 31 patients used automatic ambulatory blood pressure monitoring ( ABPM ) to assess usual blood pressure at baseline and exit ( 3 ) . Twenty-fourhour ABPM recordings yield a more reliable assessment of usual blood pressure levels during the course of daily activities ( 10 ) . To improve on the previous studies , we design ed a r and omized , controlled trial that used 24-hour ABPM measurements at baseline and at exit to determine change in blood pressure more accurately . The intervention was a service provided to physicians that used electronic transmission of results and did not rely on self-report of blood pressure . Methods Study Protocol From May 1999 to April 2000 , five internists from the Department of Medicine at the State University of New York Upstate Medical University in Syracuse recruited patients from internal medicine outpatient practice s affiliated with the general medicine division . Out patients seen by these physicians were covered by private insurance plans or Medicare . Eligible patients were adults who had previously received a diagnosis of essential hypertension and were under evaluation for a change in antihypertensive therapy because of 1 ) elevated blood pressure [ systolic pressure 140 or diastolic pressure 90 mm Hg ] despite current antihypertensive therapy , 2 ) undesirable side effects of current antihypertensive medication , or 3 ) office systolic pressure of at least 180 mm Hg or diastolic pressure of at least 110 mm Hg with no current use of antihypertensive medication . For patients with diabetes mellitus , heart disease , stroke , nephropathy , peripheral arterial disease , or hypertensive retinopathy , an office systolic pressure of at least 130 mm Hg or an office diastolic pressure of at least 85 mm Hg was a criterion for eligibility . Patients who were younger than 18 years of age , were pregnant , had secondary hypertension , or did not have the mental or physical capacity to monitor blood pressure at home were excluded . All patients were informed of the study procedures , the risks and benefits of participation , confidentiality , rights , and personnel to contact for additional information . The institutional review board at Upstate Medical University approved the trial , and all patients gave written consent before participation . Patients received printed educational material s on nonpharmacologic approaches to blood pressure control from the National Heart , Lung , and Blood Institute ( 11 ) . These approaches included reducing weight , increasing physical activity , and changing diet if necessary . At baseline , height and weight were recorded at the clinic for all patients . Body mass index was calculated as kg/m2 . Printed information on the treatment of hypertension from the Sixth Report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( National High Blood Pressure Education Program ) ( 12 ) was available at each clinical site as a reference for physicians and clinical staff . Study Group Assignment We conducted a r and omized trial with concurrent controls . The two study groups were home service and usual care . To ensure an equal number of patients in both study groups , we used a blocking procedure with r and om permuted blocks of varying size to reduce predictability . R and omization was stratified by the number of prescription medications patients were taking ( 0 to 2 or 3 ) at study entry , which served as a general indicator of morbidity . Sequentially numbered , sealed , opaque envelopes were used for assignment . The r and omization procedure was concealed to physicians and clinical research staff , but physicians , investigators , and patients were aware of group assignment when r and omization was complete . In addition , adherence to the protocol was monitored independently of the clinicians . A priori sample size was calculated to detect a mean ( SD ) difference in blood pressure of 3 5 mm Hg between the two study groups . This yielded 60 patients per group with 90 % power ( = 0.05 [ two-tailed ] ) . Intervention The intervention was a telecommunication service consisting of three components : automatic blood pressure recording at home , central processing , and electronic reports provided weekly to the primary physician and patient . We used a home blood pressure monitoring device that transmitted data over analog telephone lines ( Model 52500 , Welch Allyn , Inc. , Skaneateles Falls , New York ) and was vali date d according to the st and ards of the American National St and ard Institute , Inc. , and the Association for the Advancement of Medical Instrumentation ( 13 ) . The oscillometric device ( 16.26 cm 10.92 cm 6.6 cm ) had a digital display for blood pressure and pulse and used automatic pressurization and exhaust for cuff inflation and deflation . Patients were instructed to take their blood pressure three times in the morning before eating or drinking and three times in the evening before going to bed . After each reading , the device automatically dialed the Service and Support Center at Welch Allyn and transmitted the data . Patients were asked to conduct this routine at least three days each week for a minimum of 8 weeks and could take additional readings if they desired . A computer program was developed to display the results in a report form , which was then faxed to each patient 's physician . The report form contained information on the mean systolic pressure , mean diastolic pressure , and heart rate ( overall , morning , and evening ) . It also graphed the pressure by date and displayed individual readings in tabular form . Both physicians and patients received a report form each week , as well as a summary report form at the end of the trial . When physicians received report forms that indicated elevated pressure , they adjusted antihypertensive medications through a telephone call , an office visit , or both . At the time of the trial , the service cost $ 24.95 per month . Patients assigned to usual care were treated for hypertension according to the guidelines of the Joint National Committee on Prevention , Detection , and Treatment of High Blood Pressure ( 12 ) . Question naire Information Information about patients ' medical histories , past diagnoses of disease , and use of medications was obtained from question naires . The Baecke question naire of habitual physical activity was used to assess usual activity levels ( 14 ) . Subscales included a work index , a sports index , and a nonsports leisure index , as well as a total physical activity score . Dietary intake was estimated by using the Block screening question naire , which consists of two subscales : intake of highly saturated fatty foods and intake of fruit , vegetables , and high-fiber grains ( 15 ) . Questions about smoking and stress were taken from the previously vali date d Health Habits and History Question naire ( 16 ) . The study question naire was collected at the time of the second 24-hour ambulatory readings . Outcome Measures The primary end point was the change in mean arterial pressure during the trial ( baseline to exit ) for home service compared with usual care . A clinical research nurse ( the study manager ) fitted participants with a 24-hour ABPM device at baseline and at exit . The nurse gave the patients detailed instructions for using the device . The ABPM device automatically recorded blood pressure every half-hour from 7:00 a.m. to 11:00 p.m. and every hour from 11:00 p.m. to 7:00 a.m. Information from baseline and exit ABPM readings was given to physicians only after the patient exited the trial . All blood pressure measurements indicated in this report refer to these 24-hour readings . Means and SDs were recorded for systolic pressure , diastolic pressure , arterial pressure , and heart rate by using 24-hour ABPM . Mean arterial pressure was measured as ( diastolic pressure + 1/3 [ systolic pressure diastolic pressure ] ) . The ABPM device also recorded the percentage of readings above the desired target levels ( 140 mm Hg systolic or 90 mm Hg diastolic for patients without target organ damage ; 130 mm Hg systolic or 85 mm Hg diastolic for patients with target organ damage ) . Patients were scheduled to remain in the trial for a minimum of 8 weeks . During the sixth and seventh weeks , appointments were made to schedule second 24-hour ABPM sessions . For both the home service and usual care groups , the median time from baseline to exit was 11 weeks . The final patient receiving usual care exited at 20 weeks , and the final patient receiving home service exited at 28 weeks . Statistical Analysis All information was entered into an Excel data base ( Microsoft Corp. , Redmond , Washington ) and was manually rechecked for errors . Statistical analyses were conducted by using STATISTICA software (", "Home blood pressure monitoring ( HBPM ) overcomes many of the limitations of traditional office blood pressure ( BP ) measurement and is both cheaper and easier to perform than ambulatory BP monitoring . Monitors that use the oscillometric method are currently available that are accurate , reliable , easy to use , and relatively inexpensive . An increasing number of patients are using them regularly to check their BP at home , but although this has been endorsed by national and international guidelines , detailed recommendations for their use have been lacking . There is a rapidly growing literature showing that measurements taken by patients at home are often lower than readings taken in the office and closer to the average BP recorded by 24-hour ambulatory monitors , which is the BP that best predicts cardiovascular risk . Because of the larger numbers of readings that can be taken by HBPM than in the office and the elimination of the white-coat effect ( the increase of BP during an office visit ) , home readings are more reproducible than office readings and show better correlations with measures of target organ damage . In addition , prospect i ve studies that have used multiple home readings to express the true BP have found that home BP predicts risk better than office BP ( Class IIa ; Level of Evidence A ) . This call-to-action article makes the following recommendations : ( 1 ) It is recommended that HBPM should become a routine component of BP measurement in the majority of patients with known or suspected hypertension ; ( 2 ) Patients should be advised to purchase oscillometric monitors that measure BP on the upper arm with an appropriate cuff size and that have been shown to be accurate according to st and ard international protocol s. They should be shown how to use them by their healthcare providers ; ( 3 ) Two to 3 readings should be taken while the subject is resting in the seated position , both in the morning and at night , over a period of 1 week . A total of ≥12 readings are recommended for making clinical decisions ; ( 4 ) HBPM is indicated in patients with newly diagnosed or suspected hypertension , in whom it may distinguish between white-coat and sustained hypertension . If the results are equivocal , ambulatory BP monitoring may help to establish the diagnosis ; ( 5 ) In patients with prehypertension , HBPM may be useful for detecting masked hypertension ; ( 6 ) HBPM is recommended for evaluating the response to any type of antihypertensive treatment and may improve adherence ; ( 7 ) The target HBPM goal for treatment is HBPM is useful in the elderly , in whom both BP variability and the white-coat effect are increased ; ( 9 ) HBPM is of value in patients with diabetes , in whom tight BP control is of paramount importance ; ( 10 ) Other population s in whom HBPM may be beneficial include pregnant women , children , and patients with kidney disease ; and ( 11 ) HBPM has the potential to improve the quality of care while reducing costs and should be reimbursed", "CONTEXT Treating hypertension decreases mortality and disability from cardiovascular disease , but most hypertension remains inadequately controlled . OBJECTIVE To determine if a new model of care that uses patient Web services , home blood pressure ( BP ) monitoring , and pharmacist-assisted care improves BP control . DESIGN , SETTING , AND PARTICIPANTS A 3-group r and omized controlled trial , the Electronic Communications and Home Blood Pressure Monitoring study was based on the Chronic Care Model . The trial was conducted at an integrated group practice in Washington state , enrolling 778 participants aged 25 to 75 years with uncontrolled essential hypertension and Internet access . Care was delivered over a secure patient Web site from June 2005 to December 2007 . INTERVENTIONS Participants were r and omly assigned to usual care , home BP monitoring and secure patient Web site training only , or home BP monitoring and secure patient Web site training plus pharmacist care management delivered through Web communications . MAIN OUTCOME MEASURES Percentage of patients with controlled BP ( mm Hg ) and changes in systolic and diastolic BP at 12 months . RESULTS Of 778 patients , 730 ( 94 % ) completed the 1-year follow-up visit . Patients assigned to the home BP monitoring and Web training only group had a nonsignificant increase in the percentage of patients with controlled BP ( Web-based pharmacist care to home BP monitoring and Web training significantly increased the percentage of patients with controlled BP ( 56 % ; 95 % CI , 49%-62 % ) compared with usual care ( P Systolic BP was decreased stepwise from usual care to home BP monitoring and Web training only to home BP monitoring and Web training plus pharmacist care . Diastolic BP was decreased only in the pharmacist care group compared with both the usual care and home BP monitoring and Web training only groups . Compared with usual care , the patients who had baseline systolic BP of 160 mm Hg or higher and received home BP monitoring and Web training plus pharmacist care had a greater net reduction in systolic BP ( -13.2 mm Hg [ 95 % CI , -19.2 to -7.1 ] ; P diastolic BP ( -4.6 mm Hg [ 95 % CI , -8.0 to -1.2 ] ; P improved BP control ( relative risk , 3.32 [ 95 % CI , 1.86 to 5.94 ] ; P Pharmacist care management delivered through secure patient Web communications improved BP control in patients with hypertension . Trial Registration clinical trials.gov Identifier : NCT00158639", "Self-monitoring of blood glucose is an integral part of diabetes care which may be extended to other biometrics . Cellular and short range communication technologies will be important for the routine usage of these systems . However , the issues of follow-up and patient compliance with these emerging systems have not been yet studied evaluated but could be critical to the adoption of these technologies . We evaluated the impact of mobile telemonitoring on the intensification of care on blood pressure control and exposure to hyperglycaemia in patients with diabetes . We r and omised 137 patients with diabetes to either mobile telemonitoring ( n = 3D72 ) or usual care patients ( n = 3D65 ) for 9 months . In this paper we present some of the clinical results with focus on blood pressure control hypertension and highlight some of the technical and compliance issues that were encountered" ]

[ "Background Elevated total white blood cell ( WBC ) count is associated with an increased risk of coronary heart disease and death . Aerobic exercise is associated with lower total WBC , neutrophil , and monocyte counts . However , no studies have evaluated the effect of the amount of aerobic exercise ( dose ) on total WBC and WBC subfraction counts . Purpose To examine the effects of 3 different doses of aerobic exercise on changes in total WBC and WBC subfraction counts and independent effects of changes in fitness , adiposity , markers of inflammation ( IL-6 , TNF-α , C-reactive protein ) , fasting glucose metabolism , and adiponectin . Methods Data from 390 sedentary , overweight/obese postmenopausal women from the DREW study were used in these analyses . Women were r and omized to a non-exercise control group or one of 3 exercise groups : energy expenditure of 4 , 8 , or 12 kcal kg−1⋅week−1 ( KKW ) for 6 months at an intensity of 50 % VO2peak . Results A dose-dependent decrease in total WBC counts ( trend P = 0.002 ) was observed with a significant decrease in the 12KKW group ( −163.1±140.0 cells/µL ; mean±95%CI ) compared with the control ( 138.6±144.7 cells/µL ) . A similar response was seen in the neutrophil subfraction ( trend P = 0.001 ) with a significant decrease in the 12KKW group ( −152.6±115.1 cells/µL ) compared with both the control and 4KKW groups ( 96.4±119.0 and 21.9±95.3 cells/µL , respectively ) and in the 8KKW group ( −102.4±125.0 cells/µL ) compared with the control . When divided into high/low baseline WBC categories ( median split ) , a dose-dependent decrease in both total WBCs ( P = 0.003 ) and neutrophils ( P women with high baseline WBC counts . The effects of exercise dose on total WBC and neutrophil counts persisted after accounting for significant independent effects of change in waist circumference and IL-6 . Conclusion Aerobic exercise training reduces total WBC and neutrophil counts , in a dose-dependent manner , in overweight/obese postmenopausal women and is especially beneficial for those with systemic low grade inflammation . Clinical Trials Identifier :", "CONTEXT Adiponectin and leptin are closely related to weight control and energy balance , whereas exercise affects elderly metabolic regulation and functional capacity . OBJECTIVE The objective of this study was to investigate leptin and adiponectin responses in elderly males after exercise training and detraining . DESIGN The study design was a 1-yr r and omized controlled trial . SETTING The study was performed at the Laboratory of Physical Education and Sport Science Department . PARTICIPANTS Fifty inactive men [ age , 65 - 78 yr ; body mass index ( BMI ) , 28.7 - 30.2 kg/m2 ] were recruited from a volunteer data base by word of mouth and fliers sent to medical practitioners , physiotherapists , and nursing homes in the local community . INTERVENTION(S ) Participants were r and omly assigned to a control ( n = 10 ) , low-intensity ( n = 14 ) , moderate-intensity ( n = 12 ) , or high-intensity training ( HI ; n = 14 ) group . Resistance training ( 6 months , 3 d/wk , 10 exercises/three sets ) was followed by 6 months of detraining . MAIN OUTCOME MEASURE(S ) Strength , exercise energy cost , skinfold sum , body weight , maximal oxygen consumption , resting metabolic rate ( RMR ) , and plasma leptin and adiponectin were determined at baseline and after training and detraining . RESULTS Strength , maximal oxygen consumption , RMR , and exercise energy cost increased ( P Skinfold sum and BMI were reduced by resistance training ( P Leptin was diminished ( P adiponectin increased ( P percent leptin decrease was associated ( P percent BMI decrease and the percent RMR increase , whereas the percent adiponectin increase was associated ( P BMI decrease . CONCLUSIONS Resistance training and detraining may alter leptin and adiponectin responses in an intensity-dependent manner . Leptin and adiponectin changes were strongly associated with RMR and anthropometric changes", "OBJECTIVE : To determine the effect of weight loss and exercise interventions on serum leptin and to investigate the relationship of physical function and osteoarthritis ( OA ) severity with serum leptin in older overweight and obese adults with knee OA . In addition , the study examined if serum leptin predicts weight loss . DESIGN : Longitudinal , controlled clinical trial of weight loss and exercise interventions .SUBJECTS : Community dwelling , older , overweight and obese adults ( n=316 ; > 60 years of age ; body mass index ≥28.0 kg m−2 ) with symptomatic knee OA and self-reported difficulty in performing selected physical activities were recruited . INTERVENTIONS : Participants were r and omized into one of four groups for the 18-month study duration : Healthy Lifestyle Controls , Dietary Weight Loss ( Diet ) , Exercise Training ( Exercise ) , and a combination of Dietary Weight Loss and Exercise Training ( Diet+Exercise ) . The weight loss goal for the two Diet groups was 5 % from baseline at 18 months . Participants in the Exercise groups were trained for 3 days week−1 , 60 min day−1 . MEASUREMENTS : Body weight , body mass index , serum leptin , physical function , and OA severity were measured at baseline , 6 months , and 18 months . RESULTS : Diet and Diet+Exercise groups lost 5.3 and 6.1 % of their weight , respectively , at 18 months with the Exercise group losing 2.9 % . There was a significant main effect of weight loss on serum leptin with a decrease in serum leptin averaged across the 6- and 18-month time points for the Diet and Diet+Exercise groups compared to the other two groups ( β=0.245 ; P for exercise training was observed . Serum leptin was related to self-reported physical function . In all participants , a mixed model analysis demonstrated that lower levels of baseline serum leptin predict larger weight loss ( β=−2.779 ; P=0.048 ) . CONCLUSION : Decreases in serum leptin may be one mechanism by which weight loss improves physical function and symptoms in OA patients", "Abstract Background . Dysfunction of adipose tissue is one of the major factors leading to insulin resistance . Altered adipokine concentration is an early sign of adipose tissue dysfunction . The aim of this study was to assess the impact of exercise intervention on adipokine profile , glycemic control , and risk factors of the metabolic syndrome ( MeS ) in men with impaired glucose regulation ( IGR ) . Methods . Overweight and obese men with IGR ( n = 144 ) aged 40–65 years were studied at baseline and at 12 weeks in a r and omized controlled multicenter intervention study . BMI varied from 25.1 to 34.9 . The subjects were r and omized into one of three groups : 1 ) a control group ( C ; n = 47 ) , 2 ) a Nordic walking group ( NW ; n = 48 ) , or 3 ) a resistance training group ( RT ; n = 49 ) . Results . Leptin concentrations decreased in the NW group compared to both other groups . Both types of exercise intervention significantly decreased serum chemerin concentrations compared to the C group . In the NW group also body fat percentage , fatty liver index ( FLI ) , and total and LDL cholesterol concentrations decreased compared to the RT group . Conclusions . Nordic walking intervention seems to decrease chemerin and leptin levels , and subjects in this intervention group achieved the most beneficial effects on components of", "The purpose of present study was to investigate the impacts of endurance , resistance and concurrent training on adiponectin resting levels of sedentary men . Forty-four sedentary students were r and omly assigned to one of four groups : endurance training ( ET ; 22 ± 0.89 yr , n=12 ) , resistance training ( RT , 21 ± 1.57 yr , n=9 ) , concurrent training ( CT , 21.38 ± 2.6 yr , n=14 ) and control group ( CG , n=10 ) . After primary measurements , blood sample s were drawn with subjects in fasting and resting state for determination of the basic level of adiponectin . The subjects participated in E , R and C training for 8 weeks . The ET group ran 3d/w at 65 - 85 % of maximum heart rate . The exercise training session for the RT group consisted of 3 sets of 10 - 15 repetitions of weight training exercise that increase progressively , and repeated 3 sessions per week . The CT group trained exactly the sum of ET and RT groups . Correlated sample s t-test and ANOVA were used . The results of the present study showed that after the eight-week training , the adiponectin levels of subjects increased in 3 groups of training but this increase was not significant . The level of adiponectin in CT group increased more than in ET and RT groups . Also , there were no significant differences in content of adiponectin among groups . In general , slight increases in adiponectin levels in training groups especially in CT group may indicate the most potential of CT group in increasing the levels of adiponectin in sedentary men . However more research es are needed to identify the effects of concurrent training ( Tab . 4 , Ref . 27 )", "We assessed the major factors regulating adiponectin levels and the influence of exercise training on adiponectin levels in young obese men ( 19.2±1.1 yrs , BMI : 31.1±4.2 , % fat : 27.2±3.9 % ) . Subjects were separated into three groups ( aerobic exercise group [ AE : n=7 ] , aerobic and resistance exercise group [ AE+RE : n=7 ] , control group [ n=7 ] ) . AE underwent an 8-week training program ( three times per week , more than 30 min endurance exercise at ventilatory threshold ( VT ) intensity ) . AE+RE went through resistance exercise two or three times per week together with the above endurance exercise for 5 months . Prior to intervention ( n=21 ) , adiponectin levels were significantly correlated with percentage of fat . Stepwise multiple regression analysis revealed that percent body fat was an independent predictor of basal adiponectin levels ( r2=0.370 ; P , fat mass , and VT were significantly improved in AE . AE+RE exhibited significant reduction in weight , BMI , percent body fat and fat mass , and had significantly increased VT , $ $ \\ifmmode\\exp and after\\dot\\else\\exp and after\\.\\fi{V}{\\text{O}}_{2 } \\max , $ $ cycling power and torque . Insulin was not changed in both groups . The control group exhibited no significant change in any variables . Although adiponectin levels were unchanged in the three groups , a significant negative correlation between delta fat mass and delta adiponectin levels was observed ( n=21 , r=−0.461 , P delta percent body fat was an independent predictor of delta adiponectin levels ( r2=0.327 , P the adiponectin level , improvement of the body composition of young obese men is more important than the way training is performed", "The aim of the present study was to examine the effect of exercise training on adipokines , inflammatory markers , and oxidative stress in overweight children . Nineteen overweight children were r and omly assigned to an aerobic exercise training or sedentary control group for 8 weeks . Measurements included peak oxygen uptake ( V o(2)max ) , body weight and composition , adipokines ( C-reactive protein , interleukin 6 , tumor necrosis factor alpha , adiponectin , leptin , and resistin ) , and oxidative stress ( 8-isoprostane ) . There were no differences between groups for change in body weight or composition over the 8 weeks . Exercise training improved V o(2)max ( exercise group , 1.64 + /- 0.13 to 1.85 + /- 0.17L/min vs control group , 1.83 + /- 0.12 to 1.60 + /- 0.13 L/min , P measured adipokines or the marker of systemic oxidative stress , 8-isoprostane . These data suggest that in the absence of weight loss , exercise training alone does not improve the adipokine profile or levels of oxidative stress in overweight children", "Little is known about the effects of different intensities of physical training on plasma leptin . This study examined the effect of two intensities of physical training on leptin in obese teenagers , and explored correlates at baseline and in response to 8 months of physical training . The participants were 55 obese youths 12 - 16 years of age who completed both baseline and posttesting . The youths were r and omized to engage in lifestyle education only ( LSE ) , moderate-intensity physical training and LSE , or high-intensity physical training and LSE . Baseline leptin was positively associated with fat mass . Girls had higher leptin levels at lower levels of fasting insulin than boys . The 8-mo physical training doses prescribed to obese teenagers did not result in significant group differences in mean change in leptin , although there was large variability in individual response . The change in leptin was inversely associated with baseline leptin and change in cardiovascular fitness . Diet , physical activity level , visceral adiposity , and glucose concentrations were not associated with leptin , neither at baseline nor in response to physical training . At baseline , total fat mass rather than visceral adiposity was associated with higher leptin levels . Over the 8-mo intervention period , regardless of group membership , youths who had the lowest increase in cardiovascular fitness tended to have the highest increase in leptin", "Abstract It has been demonstrated that leptin concentrations in obese patients may be altered by weight loss . We examined the effects of a 9-week aerobic exercise program on serum leptin concentrations in overweight women ( 20–50 % above ideal body mass ) under conditions of weight stability . Sixteen overweight women , mean ( SE ) age 42.75 ( 1.64 ) years , comprised the exercise group which adhered to a supervised aerobic exercise program . A grade d exercise treadmill test was conducted before and after the exercise program to determine maximal oxygen uptake ( V˙O2max ) using open-circuit spirometry . The women demonstrated improved aerobic fitness ( V˙O2max increased 12.29 % ) , however , body fat and the body mass index did not change significantly [ 42.27 (1.35)–41.87 (1.33)% ] . Fourteen women , age 40.57 ( 2.80 ) years , did not exercise over the same time period and served as a control group . Serum leptin levels were not significantly altered for either the exercise [ 28.00 (2.13)–31.04 ( 2.71 ) ng · ml−1 ] or the control group [ 33.24 (3.78)–34.69 ( 3.14 ) ng · mg−1 ] . The data indicate that 9 weeks of aerobic exercise improves aerobic fitness , but does not affect leptin concentrations in overweight women", "Objective To investigate the feasibility and safety of a 24-week exercise intervention , compared to control , in males with Barrett ’s oesophagus , and to estimate the effect of the intervention , compared to control , on risk factors associated with oesophageal adenocarcinoma development . Methods A r and omized controlled trial of an exercise intervention ( 60 minutes moderate-intensity aerobic and resistance exercise five days/week over 24 weeks ; one supervised and four unsupervised sessions ) versus attention control ( 45 minutes stretching five days/week over 24 weeks ; one supervised and four unsupervised sessions ) in inactive , overweight/obese ( 25.0–34.9 kg/m2 ) males with Barrett ’s oesophagus , aged 18–70 years . Primary outcomes were obesity-associated hormones relevant to oesophageal adenocarcinoma risk ( circulating concentrations of leptin , adiponectin , interleukin-6 , tumour necrosis factor-alpha , C-reactive protein , and insulin resistance [ HOMA ] ) . Secondary outcomes included waist circumference , body composition , fitness , strength and gastro-oesophageal reflux symptoms . Outcomes were measured at baseline and 24-weeks . Intervention effects were analysed using generalised linear models , adjusting for baseline value . Results Recruitment was difficult in this population with a total of 33 participants recruited ( target sample size : n = 80 ) ; 97 % retention at 24-weeks . Adherence to the exercise protocol was moderate . No serious adverse events were reported . A statistically significant intervention effect ( exercise minus control ) was observed for waist circumference ( -4.5 [ 95 % CI -7.5 , -1.4 ] cm ; p combined dietary and exercise intervention to achieve greater weight loss in this population and relax inclusion criteria to maximize recruitment . Trial Registration Australian New Zeal and Clinical Trials Registry ( ANZCTR )", "Our aim of the present work was to study the effect of serum adiponectin on incident diabetes and HbA1c values . We measured baseline serum adiponectin levels in a nested case-control selection ( n=140 ) of the Whitehall II Cohort . Participants ( mean [ SD ] age 50.9 [ 6.3 ] years ) had no prevalent diabetes or CHD at baseline . Cases ( n=55 ) had incident diabetes according to an oral glucose tolerance test during follow-up ( mean : 11.5+/-3.0 years ) . Adiponectin levels were lower among cases ( 9.3 microg/ml , 3.2 [ median ; IQR ] vs. 10.5 ; 3.6 , p=0.01 ) . The risk of incident diabetes decreased by 11 % ( p=0.03 ) for 1 microg/ml higher adiponectin levels . Higher adiponectin levels were associated with lower HbA1c at follow-up ( p adiponectin is an independent predictor of diabetes and the degree of glycaemic impairment", "This prospect i ve , r and omized study investigated the effect of exercise on leptin , insulin , cortisol and lipid profiles in obese children . A total of 40 obese boys aged 10 - 12 years with a body mass index ( BMI ) ≥ 30 kg/m2 were r and omly separated into an exercise group ( n = 20 ) that underwent a 12-week aerobic exercise programme and a non-exercise ( control ) group ( n = 20 ) . The BMI , low-density lipoprotein , cortisol , leptin and insulin levels were significantly lower in the exercise group after 12 weeks compared with baseline values , whereas high-density lipoprotein levels were significantly higher . In contrast , in the control group , low-density lipoprotein , cortisol and leptin levels were significantly higher after 12 weeks compared with baseline values while high-density lipoprotein levels were significantly lower . These findings indicate the importance of regular exercise in the regulation of body weight and protection against cardiovascular risk factors in obese children", "Obese individuals are characterized by low circulating adiponectin concentrations and an increased number of macrophages in adipose tissue , which is believed to be causally associated with chronic low- grade inflammation and insulin resistance . Regular physical exercise decreases overall morbidity in obese subjects , which may be due to modulations of inflammatory pathways . In this r and omized clinical trial we investigated the separate effects of endurance training-induced weight loss , diet-induced weight loss , and endurance training per se ( without weight loss ) on plasma adiponectin multimer composition ( Western blotting ) and adipose tissue macrophage content ( immunohistochemistry ) in young , moderately overweight men . Weight loss and endurance training per se decreased whole body fat percentage in an additive manner . No intervention-induced changes were observed for plasma total adiponectin . Surprisingly , endurance training , irrespectively of any associated weight loss , shifted the adiponectin multimer distribution toward a lower molecular weight ( 21 % decrease in HMW/LMW , P = 0.015 ) , whereas diet-induced weight loss shifted the distribution toward a higher molecular weight ( 42 % increase in HMW/MMW , P increased the number of anti-inflammatory CD163⁺ macrophages [ from 12.7 ± 2.1 ( means ± SE ) to 16.1 ± 3.1 CD163⁺ cells/100 adipocytes , P = 0.013 ] , whereas diet-induced weight loss tended to decrease CD68⁺ macrophages in subcutaneous abdominal adipose tissue . Thus regular physical exercise influences systemic and adipose tissue inflammatory pathways differently than diet-induced weight loss in younger , moderately overweight men . Our data suggest that some of the health benefits of a physically active lifestyle may occur through modulations of anti- rather than pro-inflammatory pathways in young , overweight men", "OBJECTIVE To investigate the effects of : I ) short- ( 8 weeks ) , II ) long-term ( 3 years ) weight loss , and III ) the degree of weight loss on circulating levels of adiponectin , high sensitive-C reactive protein ( hs-CRP ) , and fibrinogen in obese subjects . Moreover , to evaluate the effect of the lipase inhibitor , orlistat , on these parameters . DESIGN Weight loss induced in 93 obese subjects ( mean weight : 108.9+/-15.8 kg ) through 8-week very-low-energy diet ( VLED , 800 kcal/day ) followed by r and omization to orlistat or placebo together with lifestyle intervention for further 3 years . Adiponectin and hs-CRP were measured at baseline , after 8 weeks of VLED and 6 , 12 , and 36 months after the VLED by flowmetric xMAP technology ( Luminex Multi-Analyte Profiling System , Luminex Corp. , Austin , TX , USA ) . Fibrinogen was measured in a coagulation assay . RESULTS Weight loss after VLED treatment was 14.3+/-4.5 kg and after 3 years 7.7+/-8.7 kg . Orlistat-treated subjects regained 3.9 kg less than placebo-treated from the end of the VLED to 3 years ( P=0.01 ) . No differences were detected between the two groups regarding changes in adiponectin , hs-CRP , or fibrinogen . Accordingly , the groups were combined for further analyses . Serum adiponectin increased by 22 % ( P weight losses needed to be in excess of 10 % ( approximately 12 kg ) in order to increase adiponectin levels significantly . Weight loss was associated with a significant decrease in hs-CRP . Fibrinogen decreased by 12 % ( P obese subjects , weight loss was associated with an increase in serum adiponectin and a decrease in hs-CRP and plasma fibrinogen . Long-term weight loss ( 3 years ) must exceed 10 % to induce a combined significant improvement in these inflammatory markers", "OBJECTIVE : To examine the effect of experimental changes in children ’s sleep duration on self-reported food intake , food reinforcement , appetite-regulating hormones , and measured weight . METHODS : Using a within-subjects , counterbalanced , crossover design , 37 children , 8 to 11 years of age ( 27 % overweight/obese ) completed a 3-week study . Children slept their typical amount at home for 1 week and were then r and omized to either increase or decrease their time in bed by 1.5 hours per night for 1 week , completing the alternate schedule on the third week . Primary outcomes were dietary intake as assessed by 24-hour dietary recalls , food reinforcement ( ie , points earned for a food reward ) , and fasting leptin and ghrelin . The secondary outcome was child weight . RESULTS : Participants achieved a 2 hour , 21 minute difference in the actigraph defined sleep period time between the increase and decrease sleep conditions ( P fasting morning leptin values ( P weights were 0.22 kg lower during the increase sleep than the decrease sleep condition ( P food reinforcement or in fasting ghrelin . CONCLUSIONS : Compared with decreased sleep , increased sleep duration in school-age children result ed in lower reported food intake , lower fasting leptin levels , and lower weight . The potential role of sleep duration in pediatric obesity prevention and treatment warrants further study", "Evidence suggests that exercise affects breast cancer risk and outcomes , but little is known about the mechanisms through which this effect may be mediated . This study examines the impact of exercise upon levels of adiponectin , high molecular weight adiponectin ( HMWA ) , and leptin in breast cancer survivors . Methods One hundred and one sedentary , overweight breast cancer survivors were r and omized to a 16-week exercise intervention or usual care control group . Anthropometric measurements were taken and fasting levels of adiponectin , HMWA and leptin were collected at baseline and 16 weeks . Results Baseline and week-16 measurements were available for 81 patients . The exercise group experienced a significant decrease in hip measurements , with no change in weight or body composition . There were no significant changes in adiponectin , HMWA , or leptin in either group . Modeling analyses demonstrated a significant inverse relationship between changes in leptin and adiponectin , but no relationship between changes in BMI , waist or hip circumference , or body fat percentage and change in leptin or adiponectin . Conclusions This study did not demonstrate a significant change in adipocytokine levels in breast cancer survivors participating in an exercise intervention , suggesting that further work is needed to explore the mechanisms through which exercise may impact breast cancer", "The purpose of this study was to determine the effect of exercise training on the levels of C-reactive protein ( CRP ) and adiponectin , and to assess whether exercise-induced changes in insulin resistance could be explained in part by changes in these inflammation markers . Study participants included 51 middle-aged ( 45.3+/-8.3 years ; mean+/-SD ) , overweight ( 33.7+/-4.8 BMI ) , insulin-resistant , nondiabetic individuals . Subjects had their insulin sensitivity , body fat , CRP , and adiponectin levels measured , and their predicted maximal fitness calculated before and after 16 weeks of moderate , intense , or no exercise training . Modest improvements in fitness , body composition , and insulin sensitivity were observed , but these changes were not associated with decreased CRP or increased adiponectin levels , even when subjects were stratified by their change in fitness or obesity . Regression analysis demonstrated that the change in percentage of body fat was significantly related to changes in insulin sensitivity , whereas changes in VO2 MAX , CRP , and adiponectin were not . Participation in moderate to intense exercise was not associated with improved measures of chronic inflammation markers , as measured by CRP and adiponectin . Moreover , improvements in insulin sensitivity result ing from exercise or modest weight loss did not appear to be related to changes in these markers", "Osteocalcin has been proposed to be a novel link between bone and energy metabolism . Previous studies showed its relations to exercise , body fat and glucose metabolism , but their interrelationship remains inconslusive . We evaluated the changes in osteocalcin level following 8‐week exercise programme and assessed how they are related to concomitant changes in body fat composition , insulin resistance and various adipocytokines in a single centre , r and omized and prospect i ve design", "Abstract Adiponectin mRNA and plasma concentrations were reduced in obesity . Exercise training may reduce the adipose tissue ( AT ) , although it is not well known , whether exercise – induced change in AT , increases adiponectin mRNA expression and plasma concentrations or not . Therefore , the purpose of this study was to examine the effects of short-term lifestyle activity modification ( LAM ) on adiponectin mRNA and plasma concentrations . Sixteen obese and overweight middle-aged men ( age , 35–50 years ) with type 2 diabetes participated in this study . The subjects were r and omly assigned to LAM group ( n=8 ) or control group ( n=8 ) . The subjects in LAM group walked two miles in 30 min on a treadmill on 4 days per week for 12 weeks according to the guidelines of the Centers for Disease Control and Prevention and American College of Sports Medicine . The results showed that body mass , body mass index , central visceral adipose tissue and subcutaneous adipose tissue volume and hip and thigh subcutaneous adipose tissue ( hip and thigh SAT ) volume were decreased in the LAM group compared to the control group ( P . Adiponectin mRNA in abdominal and gluteal subcutaneous AT were increased significantly in the LAM group compared to the control group ( P while plasma adiponectin concentrations , hs-CRP and insulin resistance did not change significantly . In conclusion , adiponectin mRNA levels increase after 12 weeks of LAM ; however , plasma adiponectin levels were not affected by this protocol in obese and overweight middle-aged men with type 2 diabetes", "OBJECTIVE To determine whether an exercise intervention using an active video game ( Dance Dance Revolution [ DDR ] ) is effective in improving endothelial dysfunction ( EDF ) and other risk factors in overweight children . DESIGN Thirty-five children ( Body mass index > or = 85(th ) percentile , mean age 10.21+/-1.67 years , 17 females ) with EDF were assessed for flow-mediated dilation ( FMD ) , lipids , insulin , glucose , NO(2)+NO(3 ) , asymmetric dimethylarginine , symmetric dimethylarginine , l-arginine , height , weight , aerobic fitness , and blood pressure . In a sub sample , tumor necrosis factor alpha , interleukin-6 , C-reactive protein , and adiponectin were also assessed . Subjects were r and omly assigned to 12-weeks of aerobic exercise ( EX ) using DDR or to a non-exercising delayed-treatment control group ( DTC ) . RESULTS EX had significant improvements in FMD ( 5.56+/-5.04 % compared with 0.263+/-4.54 % , p=0.008 ) , exercise time on the grade d exercise test ( 53.59+/-91.54 compared with -12.83+/-68.10 seconds , p=0.025 ) , mean arterial pressure ( MAP ) ( -5.62+/-7.03 compared with -1.44+/-2.16 mmHg , p=0.05 ) , weight ( 0.91+/-1.53 compared with 2.43+/-1.80 kg , p=0.017 ) and peak VO(2 ) ( 2.38+/-3.91 compared with -1.23+/-3.18 mg/kg/min , p=0.005 ) compared with the DTC . Thirteen EX subjects achieved normal EDF while ten did not . These groups differed at baseline with regard to total cholesterol ( TC ) and low-density lipoprotein ( LDL ) . CONCLUSION Twelve weeks of DDR-use improved FMD , aerobic fitness , and MAP in overweight children . Improvements occurred without changes in inflammatory markers or nitric oxide production . The results document the need to explore relationships between obesity , endothelial function , inflammation , lipids , exercise intensity , and gender in a larger sample of overweight children", "BACKGROUND Excess body weight and a sedentary lifestyle are associated with the development of several diseases , including cardiovascular disease , diabetes and cancer in women . One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels . We investigated the effects of 12-month reduced calorie , weight loss and exercise interventions on adiponectin and leptin concentrations . METHODS Overweight/obese postmenopausal women ( n = 439 ) were r and omized as follows : ( i ) a reduced calorie , weight-loss diet ( diet ; N = 118 ) , ( ii ) moderate-to-vigorous intensity aerobic exercise ( exercise ; N = 117 ) , ( iii ) a combination of a reduced calorie , weight-loss diet and moderate-to-vigorous intensity aerobic exercise ( diet + exercise ; N = 117 ) , and ( iv ) control ( N = 87 ) . The reduced calorie diet had a 10 % weight-loss goal . The exercise intervention consisted of 45 min of moderate-to-vigorous aerobic activity 5 days per week . Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay . RESULTS Adiponectin increased by 9.5 % in the diet group and 6.6 % in the diet + exercise group ( both P ≤ 0.0001 vs. control ) . Compared with controls , leptin decreased with all interventions ( diet + exercise , -40.1 % , P diet , -27.1 % , P exercise , -12.7 % , P = 0.005 ) . The results were not influenced by the baseline body mass index ( BMI ) . The degree of weight loss was inversely associated with concentrations of adiponectin ( diet , P-trend = 0.0002 ; diet + exercise , P-trend = 0.0005 ) and directly associated with leptin ( diet , P-trend diet + exercise , P-trend through diet or diet + exercise increased adiponectin concentrations . Leptin concentrations decreased in all of the intervention groups , but the greatest reduction occurred with diet + exercise . Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin", "Purpose We investigate the effects of 12-week interval training of moderate- or high-intensity exercise on blood lipids and plasma levels of adiponectin . Methods Thirty-four obese adolescent females [ age = 15.9 ± 0.3 years ; BMI and BMI -Z-score = 30.8 ± 1.6 kg/m2 and 3 ± 0.3 , respectively ] , were r and omized to high-intensity interval training ( HIIT , n = 11 ) , moderate-intensity interval training ( MIIT , n = 11 ) , or a control group ( CG , n = 12 ) . Maximal oxygen uptake ( $ $ \\mathop V\\limits^{. } { \\text{O}}_{{2{\\text{peak}}}}$$V.O2peak ) , maximal aerobic speed ( MAS ) , plasma lipids and adiponectin levels were measured in all subjects before and after training . Results Following the training program , in both training groups , body mass , BMI -Z-score , and percentage body fat ( % BF ) decreased , while $ $ \\mathop V\\limits^{. } { \\text{O}}_{{2{\\text{peak}}}}$$V.O2peak and MAS increased . Low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , and adiponectin levels were positively altered ( −12.6 and −7.4 % ; 6.3 and 8.0 % ; 35.8 and 16.2 % ; high to moderate training program , respectively ) . Waist circumference , triglyceride and total cholesterol decreased only in HIIT group ( −3.5 ; −5.3 and −7.0 % , respectively , in all P usual index of insulin resistance ( HOMA-IR ) occurred in HIIT and MIIT groups ( −29.2 ± 5.3 and −18.4 ± 8.6 % , respectively ; P changes blood lipids and adiponectin variables in obese adolescent girls , result ing in improved insulin sensitivity , as attested by a lower HOMA-IR , and achieving better results compared to moderate-intensity exercise" ]