Datasets:

---

ahmedselhady

/

ms2_dataset_restructured

like 0

[ "Importance Sleeve gastrectomy is increasingly used in the treatment of morbid obesity , but its long-term outcome vs the st and ard Roux-en-Y gastric bypass procedure is unknown . Objective To determine whether there are differences between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss , changes in comorbidities , increase in quality of life , and adverse events . Design , Setting , and Participants The Swiss Multicenter Bypass or Sleeve Study ( SM-BOSS ) , a 2-group r and omized trial , was conducted from January 2007 until November 2011 ( last follow-up in March 2017 ) . Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers , 217 patients were enrolled and r and omly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period . Interventions Patients were r and omly assigned to undergo laparoscopic sleeve gastrectomy ( n = 107 ) or laparoscopic Roux-en-Y gastric bypass ( n = 110 ) . Main Outcomes and Measures The primary end point was weight loss , expressed as percentage excess body mass index ( BMI ) loss . Exploratory end points were changes in comorbidities and adverse events . Results Among the 217 patients ( mean age , 45.5 years ; 72 % women ; mean BMI , 43.9 ) 205 ( 94.5 % ) completed the trial . Excess BMI loss was not significantly different at 5 years : for sleeve gastrectomy , 61.1 % , vs Roux-en-Y gastric bypass , 68.3 % ( absolute difference , −7.18 % ; 95 % CI , −14.30 % to −0.06 % ; P = .22 after adjustment for multiple comparisons ) . Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass ( 60.4 % ) than after sleeve gastrectomy ( 25.0 % ) . Gastric reflux worsened ( more symptoms or increase in therapy ) more often after sleeve gastrectomy ( 31.8 % ) than after Roux-en-Y gastric bypass ( 6.3 % ) . The number of patients with reoperations or interventions was 16/101 ( 15.8 % ) after sleeve gastrectomy and 23/104 ( 22.1 % ) after Roux-en-Y gastric bypass . Conclusions and Relevance Among patients with morbid obesity , there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery . Trial Registration clinical trials.gov Identifier :", "BACKGROUND There are few studies of long-term outcomes for either laparoscopic adjustable gastric b and ing ( LAGB ) or laparoscopic Roux-en-Y gastric bypass ( LRYGB ) . The objective of this study was to compare outcomes of patients r and omly assigned to undergo LAGB or LRYGB at 10 years . METHODS LAGB , using the pars flaccida technique , and st and ard LRYGB were performed . From January 2000 to November 2000 , 51 patients ( mean age 34.0 ± 8.9 years ; range 20 - 49 ) were r and omly allocated to undergo either LAGB ( n = 27 , 5 men and 22 women ; mean age 33.3 years ; mean weight 120 kg ; mean body mass index [ BMI ] 43.4 kg/m(2 ) ) or LRYGB ( n = 24 , 4 men and 20 women ; mean age 34.7 ; mean weight 120 kg ; mean BMI 43.8 kg/m(2 ) ) . Data on complications , reoperations , weight , BMI , percentage of excess weight loss , and co-morbidities were collected yearly . The data were analyzed using Student 's t test and Fisher 's exact test , with P died . Conversion to laparotomy was performed in 1 ( 4.2 % ) of 24 LRYGB patients . Reoperations were required in 9 ( 40.9 % ) of 22 LAGB patients and in 6 ( 28.6 % ) of the 21 LRYGB patients . At 10-year follow-up , the LRYGB patients had a greater percentage of mean excess weight loss than did the LAGB patients ( 69±29 % versus 46±27 % ; P = .03 ) . CONCLUSION LRYGB was superior to LAGB in term of excess weight loss results ( 76.2 % versus 46.2 % ) at 10 years . However , LRYGB exposes patients to higher early complication rates than LAGB ( 8.3 % versus 0 % ) and potentially lethal long-term surgical complications ( internal hernia and bowel obstruction rate : 4.7 % )", "BACKGROUND For over a decade , the laparoscopic adjustable gastric b and ( LAGB ) was 1 of the most performed bariatric procedures in Europe . This study is a retrospective analysis with prospect ively collected data of the experience in 1 specialized Dutch center with the adjustable gastric b and over 14 years . METHODS Between 1995 and 2003 , 201 patients underwent an LAGB for morbid obesity in our hospital . Data on preoperative clinical characteristic , postoperative outcome and weight loss patterns , and co-morbidities for up to 18 years are presented and evaluated using the Bariatric Analysis and Reporting Outcome System ( BAROS ) . RESULTS Average follow-up was 13.6 ( ± 2.0 ) years ( 163 mo ) and 99 % of patients with complete follow-up . Two thirds of patients reached an excess weight loss (EWL)>50 % at some point after LAGB placement . However , due to insufficient weight loss or complications in 53 % of patients , the LAGB had to be removed or converted to a Roux-en-Y gastric bypass . Additionally , half of the remaining patients had disappointing results according to the BAROS score . In total , less than one quarter ( 22 % ) of patients had a functioning b and with a good result after the follow-up period . Although initially the number of patients experiencing co-morbidities was reduced , most of them returned and a large number of patients developed new co-morbidities . Complications , other than weight regain , were numerous as 47 % of patients experienced at least 1 . In total , 204 reoperations were performed in 137 ( 68 % ) patients . Furthermore , patients who were lost to follow-up did almost twice as bad in terms of EWL compared to patients who had regular follow-up . CONCLUSION Morbid obesity is a chronic disease that can be resolved with bariatric surgery . One of the treatment options is the LAGB , which in the short term shows good results in terms of EWL and co-morbidity reduction . In the long term , however , EWL and co-morbidity reduction are disappointing , and the LAGB does not seem to live up to expectations . Besides the decrease in EWL over time , the number of reoperations required is alarming . In total , less than a quarter of patients still had a functioning b and after a mean 14 years of follow-up", "Background . Gastric b and ing ( GB ) is a common bariatric procedure that is performed worldwide . Weight loss can be substantial after this procedure , but it is not sufficient in a significant portion of patients . Long-term rates for associated complications increase with every year of follow up , and only a few long-term studies have been published that examine these rates . We present our results after 14 years of postoperative follow up . Methods . Two hundred patients were operated upon form 01.02.1995 to 31.01.2009 . Data collection was performed prospect ively . In retrospective analysis , we analyzed weight loss , short- and long-term complications , amelioration of comorbidities and long-term outcome . Results . The mean postoperative follow up time was 94.4 months ( range 2–144 ) . The follow up rate was 83.5 % . The incidence of postoperative complications for slippage was 2.5 % , for pouch dilatation was 9.5 % , for b and migration was 5.5 % and 12.0 % for overall b and removal . After 14 years , the reoperation rate was 30.5 % with a reoperation rate of 2.2 % for every year of follow up . Excess weight loss was 40.2 % after 1 year , 46.3 % after 2 years , 45.9 % after 3 years , 41.9 % after five years , 33.3 % after 8 years , 30.8 % after 10 years , 33.3 % after 12 years and 15.6 % after 14 years of follow up . Conclusion . The complication and reoperation rate after GB is high . Nevertheless , GB is still a therapeutic option in morbid obese patients , but the criteria for patient selection should be carefully evaluated", "BACKGROUND Obesity is associated with increased mortality . Weight loss improves cardiovascular risk factors , but no prospect i ve interventional studies have reported whether weight loss decreases overall mortality . In fact , many observational studies suggest that weight reduction is associated with increased mortality . METHODS The prospect i ve , controlled Swedish Obese Subjects study involved 4047 obese subjects . Of these subjects , 2010 underwent bariatric surgery ( surgery group ) and 2037 received conventional treatment ( matched control group ) . We report on overall mortality during an average of 10.9 years of follow-up . At the time of the analysis ( November 1 , 2005 ) , vital status was known for all but three subjects ( follow-up rate , 99.9 % ) . RESULTS The average weight change in control subjects was less than + /-2 % during the period of up to 15 years during which weights were recorded . Maximum weight losses in the surgical subgroups were observed after 1 to 2 years : gastric bypass , 32 % ; vertical-b and ed gastroplasty , 25 % ; and b and ing , 20 % . After 10 years , the weight losses from baseline were stabilized at 25 % , 16 % , and 14 % , respectively . There were 129 deaths in the control group and 101 deaths in the surgery group . The unadjusted overall hazard ratio was 0.76 in the surgery group ( P=0.04 ) , as compared with the control group , and the hazard ratio adjusted for sex , age , and risk factors was 0.71 ( P=0.01 ) . The most common causes of death were myocardial infa rct ion ( control group , 25 subjects ; surgery group , 13 subjects ) and cancer ( control group , 47 ; surgery group , 29 ) . CONCLUSIONS Bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality", "Objective : To evaluate the long-term results of laparoscopic vertical b and ed gastroplasty ( VBG ) for morbid obesity . Background : Laparoscopic VBG , a safe and straightforward bariatric procedure characterized by good short-term results , has been progressively replaced by other more complex procedures on the basis of a presumed high rate of long-term failure . Nevertheless , some authors have recently reported long-term efficacy in selected patients . Methods : All patients who underwent laparoscopic VBG were included in a prospect i ve data base . Patients reaching 10-year follow-up received a complete evaluation including clinical , endoscopic , and biochemical examinations . Results : Between January 1996 and March 1999 , 266 morbidly obese patients underwent bariatric procedures . Among them , 213 were selected for laparoscopic VBG ; exclusion criteria were as follows : contraindications to pneumoperitoneum , gastroesophageal reflux disease , and psychological contraindications to restrictive procedures . Mean age , preoperative weight , and body mass index were 36.9 years , 123.6 kg , and 45.4 kg/m2 , respectively . Intraoperative complication rate and conversion rate were 0.9 % and 0.9 % , respectively . Early postoperative complication rate was 4.2 % and early reoperation rate was 0.5 % . Mean hospital length of stay was 6.3 days . Mortality was nil . The 10-year follow-up rate was 70.4 % ( 150 patients ) . Late postoperative complication rate was 14.7 % , and 10-year revisional surgery rate was 10.0 % . The excess weight loss percentages at 3 , 5 , and 10 years were 65.0 % , 59.9 % , and 59.8 % , respectively . The resolution and /or improvement rate for comorbidity were 47.5 % for hypertension , 55.6 % for diabetes , 75 % for sleep apnea , and 47.4 % for arthritis . Mean Moorehead-Ardelt Quality of Life Question naire and BAROS values were 1.4 and 3.8 , respectively . Conclusions : The present study demonstrates that laparoscopic VBG in carefully selected patients leads to long-term results comparable with more complex and invasive procedures . Given the low postoperative morbidity for laparoscopic VBG , its present clinical role should be , in our opinion , reevaluated", "Laparoscopic adjustable gastric b and ing ( LAGB ) has been considered by many as the treatment of choice for morbid obesity because of its simplicity and encouraging early results . The aim of this prospect i ve study was to critically assess the effects , complications , and outcome after LAGB in the long-term , based on a 12-year experience . Between June 1998 and June 2009 , all patients with implantation of a LAGB have been enrolled in a prospect i ve clinical trial . Results were recorded and classified , with special regard to long-term complications , re-operation rate , and graft survival . LAGB was performed in 167 patients ( 120 female , 47 male ) with a mean age of 40.1 ± 5.2 years . Operative mortality was 0 % , overall 1.2 % ( not b and -related ) . Overall patient follow-up was 94.0 % . Mean excess weight loss ( EWL ) after 1 , 2 , 5 , 8 , and 10 years was 31.1 ± 7.5 % ( p The non-responder rate ( EWL respectively . The early complication rate ( three major complications . Late complications ( > 30 days ) occurred in 40.1 % ( 67/167 ) , of whom seven were minor and 60 were major complications ( three b and infections , two b and migrations , 11 b and leakages , two slippings/pouch dilatations , two b and intolerances , and 40 esophageal dilatations ) . The overall re-operation rate was 20.4 % ( 34/167 ) . The graft survival of the implanted b and after 2 , 5 , 8 , 10 , and 12 years was 98.8 % , 94.0 % , 86.8 % , 85.0 % , and 85.0 % , respectively . The failure rate of the procedure after 2 , 5 , 8 , and 10 years was 25.7 % , 24.3 % , 25.7 % , and 31.6 % , respectively . In the present long-term high-participation follow-up study , LAGB is a safe and effective surgical treatment for morbid obesity . However , the high complication , re-operation , and long-term failure rates lead to the conclusion that LAGB should be performed in selected cases only , until reliable criteria for patients at low risk for long-term complications are developed", "Abstract Introduction Vertical b and ed gastroplasty ( VBG ) has been the procedure of choice for bariatric surgeries since the 1980s . However , long-term results of VBG have been reported with different opinions , and new restrictive procedures have been innovated and showing variable results . The aim of this study is to analyze the long-term results of our VBG patients .Patient and methods Between June 1998 and May 2002 , 652 morbidly obese patients received VBG , with the initial 40 patients having open procedures and the subsequent 612 patients using a laparoscopic approach . Operative complications , weight loss , and late complications were followed and compared with groups of laparoscopic adjustable gastric b and ing ( LAGB ) and sleeve gastrectomy ( LSG ) . Results Mean age , preoperative weight , and body mass index ( BMI ) were 30.96 years , 108.83 kg , and 40.63 kg/m2 , respectively . The overall early postoperative complication rate was 3.4 % ( 22/652 ) . The excess weight loss percentages at 1 , 2 , 5 , and 10 years were 61.04 , 59.70 , 51.11 , and 42.0 % , respectively . BMI at 1 , 2 , 5 , and 10 years were 29.64 , 29.71 , 31.33 , and 31.73 kg/m2 , respectively . This result is inferior to the 67 % excess weight loss in the LSG group , but is higher than the 38 % excess weight loss of the LAGB group . The revision rate is 13.19 % ( 86/652 ) up to now . Revision surgery was required in 28 ( 14.0 % ) patients in the LAGB group and 8 ( 1.3 % ) in the LSG group . Conclusion VBG was an operation with acceptable outcome for treating morbid obesity and metabolic disorders . It sets a st and ard for new restrictive procedures", "BACKGROUND The short-term benefits of bariatric surgery are well documented ; however , few reports with data beyond 10 years exist . Those that have been published have described only open procedures . We present our 10-year follow-up results with laparoscopic Roux-en-Y gastric bypass with h and -sewn gastrojejunal anastomosis in a group private practice . METHODS We performed an institutional review board-approved retrospective review of a prospect ively maintained data base , combined with office visits and telephone question naires , for patients who underwent laparoscopic Roux-en-Y gastric bypass between February 1998 and April 1999 . RESULTS A total of 242 patients underwent surgery from February 1998 to April 1999 . The office follow-up rate was 33 % at 2 years and 7 % at 10 years . An additional 19 % had telephone follow-up at 10 years . The mean excess weight loss was 57 % at 10 years . Of the 242 patients , 65 ( 33.2 % ) failed to achieve an excess weight loss of > 50 % ; 86 ( 35 % ) had ≥1 complication during follow-up . However , 83 % , 87 % , 67 % , and 76 % of patients with diabetes , hypertension , dyslipidemia , and obstructive sleep apnea , respectively , experienced improvement or resolution . The internal hernia rate was 16 % , and the gastrojejunal stenosis rate was 4.9 % . No surgery-related deaths occurred . Of the 242 patients , 136 ( 51 % ) had nutritional testing at least once after postoperative year 1 . Of these 136 patients , only 24 ( 18 % ) had remained nutritionally intact during follow-up . CONCLUSION The obstacles to follow-up have continued to impede the collection of accurate long-term data . Of the 26 % of patients with data , laparoscopic Roux-en-Y gastric bypass provided sustainable weight loss and resolution of co-morbidities . However , nutritional deficiencies presented sporadically over time and underscore the importance of routine testing", "Objective This report documents that the gastric bypass operation provides long-term control for obesity and diabetes . Summary Background Data Obesity and diabetes , both notoriously resistant to medical therapy , continue to be two of our most common and serious diseases . Methods Over the last 14 years , 608 morbidly obese patients underwent gastric bypass , an operation that restricts caloric intake by ( 1 ) reducing the functional stomach to approximately 30 mL , ( 2 ) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet , and ( 3 ) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy . Even though many of the patients were seriously ill , the operation was performed with a perioperative mortality and complication rate of 1.5 % and 8.5 % , respectively . Seventeen of the 608 patients ( Gastric bypass provides durable weight control . Weights fell from a preoperative mean of 304.4 lb ( range , 198 to 615 lb ) to 192.2 lb ( range , 104 to 466 ) by 1 year and were maintained at 205.4 lb ( range , 107 to 512 lb ) at 5 years , 206.5 lb ( 130 to 388 lb ) at 10 years , and 204.7 lb ( 158 to 270 lb ) at 14 years . The operation provides long-term control of non-insulin-dependent diabetes mellitus ( NIDDM ) . In those patients with adequate follow-up , 121 of 146 patients ( 82.9 % ) with NIDDM and 150 of 152 patients ( 98.7 % ) with glucose impairment maintained normal levels of plasma glucose , glycosylated hemoglobin , and insulin . These antidiabetic effects appear to be due primarily to a reduction in caloric intake , suggesting that insulin resistance is a secondary protective effect rather than the initial lesion . In addition to the control of weight and NIDDM , gastric bypass also corrected or alleviated a number of other comorbidities of obesity , including hypertension , sleep apnea , cardiopulmonary failure , arthritis , and infertility", "Background By su bmi tting obese people to surgical treatment , we hope they lose weight and stay slim . Long-term monitoring is essential to assess effectiveness of surgery . This study aims to evaluate weight loss over 10 years in an obese population undergoing b and ed Roux-en-Y gastric bypass ( B-RYGBP ) . Methods The surgery was performed in 211 obese between May 1999 and December 2000 . This prospect i ve study evaluated excess weight loss ( % EWL ) and body mass index ( BMI ) during the period . We considered surgical treatment failure if % EWL was less than 50 % . Results We followed 54.9 % of the population ( 116 patients ) . Patients ' % EWL was 67.6 ± 14.9 % 1 year after surgery , 72.6 ± 14.9 % after 2 years , 69.7 ± 15.1 % after 5 years , 66.8 ± 7.6 % after 8 years , and 67.1 ± 11.9 % after 10 years postoperatively . Surgical treatment failure occurred in 16 patients ( 14.6 % ) over 10 years . Conclusions B-RYGBP is a good technique to promote and maintain weight loss 10 years after surgery with low failure rate", "Background Proven short-term effectiveness of obesity therapy should be re-evaluated in the long-term . The objective of this paper is to determine the long-term ( 10 years ) outcome for patients from a r and omised controlled trial ( RCT ) . Methods A RCT in 2002 compared laparoscopic adjustable gastric b and ( LAGB ) for obesity with non-surgical therapy . Follow-up has been conducted at 10 years . Eighty patients ( BMI 30–35 ) were r and omised to a non-surgical or a surgical program . Outcome data are available on 37 ( 92.5 % ) of the surgical patients and 27 ( 62.5 % ) of the non-surgical patients at 10 years . Results Weight change , the metabolic syndrome , quality of life , adverse events and direct costs of the surgical cohort were the main results of the study . A durable weight loss is present in the surgical group with a mean ( SD ) 10-year weight loss of 14.1 ( 7.7 ) kg ( 63.4 % EWL ) , better than the non-surgical group ( mean ( SD ) = 0.4 ( 10.5 ) kg ; p ) . The metabolic syndrome was reduced from 14 to 4 of the 37 patients who completed 10 years within the LAGB groups . Proximal gastric enlargements occurred in 17 ( 30 % ) of the 57 who had LAGB and removal of the b and occurred in 7 ( 12 % ) . The annual maintenance costs including additional surgery was AUD $ 765 per patient per year . Conclusions Bariatric surgery with the LAGB can achieve long-term weight reduction which is better than a program of non-surgical therapy . There is also a sustained reduction of the metabolic syndrome . There is a significant maintenance requirement after LAGB", "BACKGROUND Vertical b and ed gastroplasty ( VBG ) has been in clinical use since 1979 and adjustable gastric b and ing ( AGB ) since 1985 . Because promising results were achieved with the adjustable gastric b and s available in the market , some surgeons came to the conclusion that VBG might be entirely ab and oned and replaced by the adjustable gastric b and . The aim of this study was to compare the long-term outcome of the 2 restrictive procedures . METHODS Within a 7-year period ( 1994 - 2001 ) , 1117 gastric restrictive procedures were performed in the course of a prospect i ve nonr and omized comparative trial . We report the outcomes of 563 VBG and 554 AGB procedures performed by 2 surgeons . The mean body mass index was 46.9 + /- 09.9 kg/m(2 ) for VBG and 46.7 + /- 07.8 kg/m(2 ) for AGB . Patient selection was performed by acceptance by 1 of the 2 surgeons . VBG was performed by laparotomy and AGB using laparoscopy . The Bariatric Analysis and Reporting Outcome System ( BAROS ) was used to evaluate the postoperative health status and quality of life . RESULTS The mean duration of follow-up was 92 months ( range 60 - 134 ) , with a minimum of 5 years . The overall follow-up rate was 92 % . In the short-term 3-year follow-up , no statistically significant difference was registered between AGB and VBG in terms of weight loss , reduction of co-morbidities , or improvement in quality of life . The 30-day mortality rate was .4 % ( 2 patients ) for VBG and .2 % ( 1 patient ) for AGB . The overall reintervention rate in the long term was 49.7 % for VBG and 8.6 % for AGB ( P reoperation rate was 39.9 % for VBG and 7.5 % for AGB ( P excess weight loss was significantly greater in the VBG group after 12 months ( 58 % for VBG versus 42 % for AGB , P weight loss was registered between the 2 study groups ( 59 % for VBG and 62 % for AGB , P = .923 ) . The BAROS score in the short term ( 3 years ) was good to excellent in 94 % and 90 % of the VBG and AGB groups , respectively . In the long-term follow-up period , the BAROS score was significantly in favor of the AGB group ( 83.9 % versus 57.8 % , P overall resolution rate of co-morbidities was 80 % in both groups . CONCLUSION This long-term follow-up study shows that VBG and AGB are effective restrictive procedures to achieve weight loss , and loss of co-morbidities . A statistically significant lower re-intervention and re-operation rate and an improved health status and quality of life were registered for AGB", "Background : Laparoscopic adjustable gastric b and ing ( LAGB ) is a safe and effective method for the treatment of obesity . The most common problem after LAGB has been the occurrence of prolapse ( slippage ) of the stomach through the b and . It has been proposed that the pars flaccida ( PF ) pathway ( dissection from the base of the right crus , along the left crus to the angle of His ) is less likely to be associated with prolapse than the traditional perigastric ( PG ) pathway ( dissection between the lesser curvature of stomach and lesser omentum , across the apex of the lesser sac , to the angle of His ) . We have tested this hypothesis using a r and omized controlled trial format . Methods : We have performed a r and omized controlled trial to compare the outcomes after LAGB using PF and PG pathways . 202 patients ( mean age 40 years , mean weight 123 kg , mean BMI 45 ) were r and omly allocated to the PF or PG pathway and followed for 2 years . Results : At 24 months , there have been 16 revisional procedures for prolapse , 4 in the PF group ( all anterior prolapse ) and 15 in the PG group ( 12 posterior and 3 anterior ) . This difference is significant ( P mean % excess weight lost was 53 % for the PF group and 46 % for the PG group . There was equally significant improvements in the metabolic syndrome in both groups ( 59 % preoperatively and 19 % at 2 years ) . All 8 paired domain scores of the SF-36 measures of quality of life were improved significantly in both group ( P substantial weight loss , improved health and improved quality of life and is significantly less likely to be associated with prolapse ( slippage ) . It is recommended as the primary dissection pathway", "Objective : To define the changing prevalence of erosion after Laparoscopic Adjustable Gastric B and ing ( LAGB ) , describing the range of clinical presentations , the approaches to treatment and the outcomes from these approaches over a 15-year study period . Background : A recent systematic review of the literature of erosion after LAGB identified 25 relevant studies and reported a total of 231 erosions in 15,775 patients giving an overall incidence of 1.46 % . The review highlighted a broad variation of incidence from 0.2 % to 33 % . The review was unable to identify either common presentations or an optimal pattern of management . Methods : Patients who underwent a primary LAGB operation between September 1994 and January 2010 by 2 surgeons ( P.O.B. and W.B. ) were identified in a prospect ively maintained data base . Those patients who had an erosion of their LAGB were identified . Presentation , operative details , demographics , body mass index , weight history , and perioperative problems were analyzed . Results : In total , 2986 patients were identified . All b and s placed were Lap-B and s ( Allergan , CA ) . Hundred erosions were experienced by 85 patients ( 2.85 % ) at a median time of 33 months from initial surgery to the erosion ( range : 11–170 months ) . The rate of erosion was highest when the b and was placed by the perigastric approach at 6.77 % . Since the adoption of the pars flaccida approach , the rate of erosion has dropped to 1.07 % . The majority of patients who had experienced an erosion ( 71 patients ; 83.5 % ) experienced only 1 erosion , 13 patients ( 15.3 % ) had 2 erosions , and 1 patient had 3 erosions . The most common presentation was loss of satiety . The b and has been successfully replaced in 56 patients . It has been explanted in 27 patients and 2 patients were converted to other bariatric procedures . The weight loss in patients who had a LAGB reinserted after erosion was not significantly different to the background cohort . Conclusions : Erosion of LAGB is uncommon and its clinical course is benign . It is best treated with a staged surgical approach ; initially , with removal and repair followed later by replacement . With this approach , weight loss is maintained and reerosion is uncommon", "In 1982 , a prospect i ve study to evaluate and compare the operations for treatment of morbid obesity , vertical b and ed gastroplasty ( VBG ) and gastric bypass ( GBP ) , was carried out at the Center for Surgical Treatment of Obesity in Los Angeles . The VBG was performed as described by Dr Mason with a 5.0 cm circumference Marlex b and . The GBP was the horizontal GBP with ≤ 50 cc pouch as described by Mason and modified by Printen and Griffen . One hundred patients had the VBG and 100 had the GBP . At 10 years follow-up , only 43 of the VBG patients and 46 of the GBP patients can be found . The groups are compared as to the perioperative complications , late complications and weight loss . VBG compared favorably with GBP for control of morbid obesity . GBP yields better weight loss and maintenance at all times of follow-up . Both procedures are equal in terms of morbidity and mortality", "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 In the past , laparoscopic adjustable gastric b and ing ( LAGB ) seemed to be a promising bariatric procedure . However , many studies showed high rates of reoperation due to complications or insufficient weight loss . There is a lack of long-term studies with follow-up beyond 15 years . OBJECTIVE To conduct long-term follow-up of patients after LAGB and analyze their weight loss as a primary endpoint . SETTING Tertiary referral center for bariatric surgery , St. Claraspital , Switzerl and . METHODS A retrospective analysis of prospect ively collected clinical data in a cohort of 405 patients having undergone LAGB was performed . RESULTS A total of 405 patients ( age 41±10 years , body mass index [ BMI ] 44.3±6 kg/m2 ) were treated with LAGB between 1996 and 2010 . Mean follow-up was 13±3 years , with a follow-up rate of 85 % ( range 8 - 18 years ) , corresponding to 343 patients . One hundred patients exceeded 15-year follow-up . In 216 patients ( 63 % ) , sleeve gastrectomy , gastric bypass , or biliopancreatic diversion with duodenal switch was performed as revisional surgery . Twenty-seven patients ( 8 % ) refused revisional surgery after b and removal . Finally , 100 patients ( 29 % ) still have the b and in place , with a mean BMI of 35±7 kg/m2 , corresponding to an excess BMI loss of 48±27 % . Among these , the failure rate was 25 % , according to the Bariatric Analysis and Reporting Outcome System ( BAROS ) ; 50 % had a good to excellent outcome . CONCLUSION More than 10 years after LAGB , 71 % of patients lost their b and s and only 15 % of the 343 followed patients with the b and in place have a good to excellent result , according to BAROS", "Importance Laparoscopic sleeve gastrectomy for treatment of morbid obesity has increased substantially despite the lack of long-term results compared with laparoscopic Roux-en-Y gastric bypass . Objective To determine whether laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are equivalent for weight loss at 5 years in patients with morbid obesity . Design , Setting , and Participants The Sleeve vs Bypass ( SLEEVEPASS ) multicenter , multisurgeon , open-label , r and omized clinical equivalence trial was conducted from March 2008 until June 2010 in Finl and . The trial enrolled 240 morbidly obese patients aged 18 to 60 years , who were r and omly assigned to sleeve gastrectomy or gastric bypass with a 5-year follow-up period ( last follow-up , October 14 , 2015 ) . Interventions Laparoscopic sleeve gastrectomy ( n = 121 ) or laparoscopic Roux-en-Y gastric bypass ( n = 119 ) . Main Outcomes and Measures The primary end point was weight loss evaluated by percentage excess weight loss . Prespecified equivalence margins for the clinical significance of weight loss differences between gastric bypass and sleeve gastrectomy were −9 % to + 9 % excess weight loss . Secondary end points included resolution of comorbidities , improvement of quality of life ( QOL ) , all adverse events ( overall morbidity ) , and mortality . Results Among 240 patients r and omized ( mean age , 48 [ SD , 9 ] years ; mean baseline body mass index , 45.9 , [ SD , 6.0 ] ; 69.6 % women ) , 80.4 % completed the 5-year follow-up . At baseline , 42.1 % had type 2 diabetes , 34.6 % dyslipidemia , and 70.8 % hypertension . The estimated mean percentage excess weight loss at 5 years was 49 % ( 95 % CI , 45%-52 % ) after sleeve gastrectomy and 57 % ( 95 % CI , 53%-61 % ) after gastric bypass ( difference , 8.2 percentage units [ 95 % CI , 3.2%-13.2 % ] , higher in the gastric bypass group ) and did not meet criteria for equivalence . Complete or partial remission of type 2 diabetes was seen in 37 % ( n = 15/41 ) after sleeve gastrectomy and in 45 % ( n = 18/40 ) after gastric bypass ( P > .99 ) . Medication for dyslipidemia was discontinued in 47 % ( n = 14/30 ) after sleeve gastrectomy and 60 % ( n = 24/40 ) after gastric bypass ( P = .15 ) and for hypertension in 29 % ( n = 20/68 ) and 51 % ( n = 37/73 ) ( P = .02 ) , respectively . There was no statistically significant difference in QOL between groups ( P = .85 ) and no treatment-related mortality . At 5 years the overall morbidity rate was 19 % ( n = 23 ) for sleeve gastrectomy and 26 % ( n = 31 ) for gastric bypass ( P = .19 ) . Conclusions and Relevance Among patients with morbid obesity , use of laparoscopic sleeve gastrectomy compared with use of laparoscopic Roux-en-Y gastric bypass did not meet criteria for equivalence in terms of percentage excess weight loss at 5 years . Although gastric bypass compared with sleeve gastrectomy was associated with greater percentage excess weight loss at 5 years , the difference was not statistically significant , based on the prespecified equivalence margins . Trial Registration clinical trials.gov Identifier :", "BACKGROUND Laparoscopic adjustable gastric b and ing ( LAGB ) is a common bariatric surgery . Although it is a safe and effective method of weight reduction in short term , it may result in some problems in long term . The purpose of this study was to investigate the consequences of LAGB in long term among morbid obese patients . METHODS In this prospect i ve study , 80 patients underwent LAGB using pars flaccida technique from 2001 to 2006 . Long-term postoperative consequences and complications of these patients were recorded . RESULTS The preoperative mean values of weight and body mass index were 125.5 ± 22.5 kg and 44.5 ± 6.5 kg/m(2 ) , respectively . Over the 13-year follow-up period , 56 patients ( 84.8 % ) experienced at least one complication . The most common complications were b and erosion ( 20 patients ) and weight regains ( 13 patients ) . Fifty-one patients ( 78.5 % ) required reoperation . The b and of 48 patients ( 72.7 % ) was removed ; of these , twenty patients ( 30.3 % ) underwent other bariatric surgeries . Percent of excess weight loss was 47.1 % ± 30.1 % , and the success rate was 48.7 % . CONCLUSIONS LAGB is a successful method with low complications in short term ; however , over long term , it results in various complications", "BACKGROUND Long‐term results from r and omized , controlled trials that compare medical therapy with surgical therapy in patients with type 2 diabetes are limited . METHODS We assessed outcomes 5 years after 150 patients who had type 2 diabetes and a body‐mass index ( BMI ; the weight in kilograms divided by the square of the height in meters ) of 27 to 43 were r and omly assigned to receive intensive medical therapy alone or intensive medical therapy plus Roux‐en‐Y gastric bypass or sleeve gastrectomy . The primary outcome was a glycated hemoglobin level of 6.0 % or less with or without the use of diabetes medications . RESULTS Of the 150 patients who underwent r and omization , 1 patient died during the 5‐year follow‐up period ; 134 of the remaining 149 patients ( 90 % ) completed 5 years of follow‐up . At baseline , the mean ( ±SD ) age of the 134 patients was 49±8 years , 66 % were women , the mean glycated hemoglobin level was 9.2±1.5 % , and the mean BMI was 37±3.5 . At 5 years , the criterion for the primary end point was met by 2 of 38 patients ( 5 % ) who received medical therapy alone , as compared with 14 of 49 patients ( 29 % ) who underwent gastric bypass ( unadjusted P=0.01 , adjusted P=0.03 , P=0.08 in the intention‐to‐treat analysis ) and 11 of 47 patients ( 23 % ) who underwent sleeve gastrectomy ( unadjusted P=0.03 , adjusted P=0.07 , P=0.17 in the intention‐to‐treat analysis ) . Patients who underwent surgical procedures had a greater mean percentage reduction from baseline in glycated hemoglobin level than did patients who received medical therapy alone ( 2.1 % vs. 0.3 % , P=0.003 ) . At 5 years , changes from baseline observed in the gastric‐bypass and sleeve‐gastrectomy groups were superior to the changes seen in the medical‐therapy group with respect to body weight ( ‐23 % , ‐19 % , and ‐5 % in the gastric‐bypass , sleeve‐gastrectomy , and medical‐therapy groups , respectively ) , triglyceride level ( ‐40 % , ‐29 % , and ‐8 % ) , high‐density lipoprotein cholesterol level ( 32 % , 30 % , and 7 % ) , use of insulin ( ‐35 % , ‐34 % , and ‐13 % ) , and quality ‐of‐life measures ( general health score increases of 17 , 16 , and 0.3 ; scores on the R AND 36‐Item Health Survey ranged from 0 to 100 , with higher scores indicating better health ) ( P comparisons ) . No major late surgical complications were reported except for one reoperation . CONCLUSIONS Five‐year outcome data showed that , among patients with type 2 diabetes and a BMI of 27 to 43 , bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing , or in some cases resolving , hyperglycemia . ( Funded by Ethicon Endo‐Surgery and others ; STAMPEDE Clinical Trials.gov number , NCT00432809 .", "BACKGROUND Laparoscopic Roux-en-Y gastric bypass ( LRYGB ) has been the \" gold st and ard \" for weight loss surgery . Long-term data are limited , and reporting methods for LRYGB outcomes vary in the literature . In addition , follow-up compliance within bariatric centers is poor due to insurance and access to care issues , making long-term follow-up evaluation difficult . OBJECTIVE Evaluate long-term LRYGB outcomes using st and ard outcome reporting definitions . SETTING Integrated multispecialty health system . METHODS A retrospective review of our institution 's prospect i ve bariatric surgery registry and integrated multispecialty electronic medical record system was completed for patients who underwent LRYGB from 2001 to 2015 . Data were defined according to the 2015 St and ards for Outcome Reporting . RESULTS During the study period , 1402 patients underwent primary LRYGB ; mean age and preoperative body mass index were 44.5±10.3 years and 47.5±6.2 kg/m2 , respectively . Early complications included anastomotic leak ( 0.2 % ) , venous thromboembolism ( 0.6 % ) , surgical site infections ( 1.4 % ) , and urinary tract infections ( 1.6 % ) . The 30-day readmission rate was 3.5 % . There were no 30-day mortalities . Follow-up weight data were available for>70 % of eligible patients through 12 years postoperative . The highest mean percent excess weight loss and lowest body mass index were reached at 18 months postoperative at 79 % and 30.1 kg/m2 , respectively . Remission of diabetes , dyslipidemia , and hypertension were observed through 8 years postoperatively . CONCLUSION This is the first report of long-term ( > 10-year ) outcomes from a single integrated health system using the 2015 St and ards for Outcome Reporting . LRYGB results in significant , sustained weight loss and durable improvement and remission of obesity-related co-morbidities . Integrated healthcare systems provide an optimal environment for data collection and long-term follow-up" ]

[ "Background Recent findings suggest that executive function ( EF ) plays a critical role in the regulation of gait in older adults , especially under complex and challenging conditions , and that EF deficits may , therefore , contribute to fall risk . The objective of this study was to evaluate if reduced EF is a risk factor for future falls over the course of 5 years of follow-up . Secondary objectives were to assess whether single and dual task walking abilities , an alternative window into EF , were associated with fall risk . Methodology /Main Results We longitudinally followed 256 community-living older adults ( age : 76.4±4.5 yrs ; 61 % women ) who were dementia free and had good mobility upon entrance into the study . At baseline , a computerized cognitive battery generated an index of EF , attention , a closely related construct , and other cognitive domains . Gait was assessed during single and dual task conditions . Falls data were collected prospect ively using monthly calendars . Negative binomial regression quantified risk ratios ( RR ) . After adjusting for age , gender and the number of falls in the year prior to the study , only the EF index ( RR : .85 ; CI : .74–.98 , p = .021 ) , the attention index ( RR : .84 ; CI : .75–.94 , p = .002 ) and dual tasking gait variability ( RR : 1.11 ; CI : 1.01–1.23 ; p = .027 ) were associated with future fall risk . Other cognitive function measures were not related to falls . Survival analyses indicated that subjects with the lowest EF scores were more likely to fall sooner and more likely to experience multiple falls during the 66 months of follow-up ( p community-living older adults , the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier . The present results link falls among older adults to cognition , indicating that screening EF will likely enhance fall risk assessment , and that treatment of EF may reduce fall risk", "In developed countries , falls in older people represent a rising problem . As effective prevention should start before the risk becomes evident , an early predictor is needed . Single stance instability would appear as a major risk factor . Aims of the study were to describe single stance stability , its sensory components , and their correlation with age and gender . A r and om sample of 597 older adults ( 319 men , 278 women ) living at home , aged 65–84 , was studied . Stability tests were performed with an electronic postural station . The single stance test showed the impairment of single stance stability in older individuals ( 75–84 yrs ) . The significant decline of stability in the older subjects may be explained by the impairment of proprioceptive control together with the decrease in compensatory visual stabilization and emergency responses . Younger subjects ( 65–74 yrs ) exhibited better , but still inadequate , proprioceptive control with compensatory visual stabilization . Gender differences appeared in older subjects : women were significantly less stable than men . The measurement of the sensory components of single stance stability could aid in the early detection of a decay in antigravity movements many years before the risk of falling becomes evident . Adequate proprioceptive control could mitigate the effects of all other risks of falling", "BACKGROUND Falls occur mainly while walking or performing concurrent tasks . We determined whether a music-based multitask exercise program improves gait and balance and reduces fall risk in elderly individuals . METHODS We conducted a 12-month r and omized controlled trial involving 134 community-dwelling individuals older than 65 years , who are at increased risk of falling . They were r and omly assigned to an intervention group ( n = 66 ) or a delayed intervention control group scheduled to start the program 6 months later ( n = 68 ) . The intervention was a 6-month multitask exercise program performed to the rhythm of piano music . Change in gait variability under dual-task condition from baseline to 6 months was the primary end point . Secondary outcomes included changes in balance , functional performances , and fall risk . RESULTS At 6 months , there was a reduction in stride length variability ( adjusted mean difference , -1.4 % ; P Balance and functional tests improved compared with the control group . There were fewer falls in the intervention group ( incidence rate ratio , 0.46 ; 95 % confidence interval , 0.27 - 0.79 ) and a lower risk of falling ( relative risk , 0.61 ; 95 % confidence interval , 0.39 - 0.96 ) . Similar changes occurred in the delayed intervention control group during the second 6-month period with intervention . The benefit of the intervention on gait variability persisted 6 months later . CONCLUSION In community-dwelling older people at increased risk of falling , a 6-month music-based multitask exercise program improved gait under dual-task condition , improved balance , and reduced both the rate of falls and the risk of falling . Trial Registration clinical trials.gov Identifier : NCT01107288", "OBJECTIVES To define clinical ly relevant cutpoints for usual gait speed and to investigate their predictive value for health-related events in older persons . DESIGN Prospect i ve cohort study . SETTING Health , Aging and Body Composition Study . PARTICIPANTS Three thous and forty-seven well-functioning older persons ( mean age 74.2 ) . MEASUREMENTS Usual gait speed on a 6-m course was assessed at baseline . Participants were r and omly divided into two groups to identify ( Sample A ; n=2,031 ) and then vali date ( Sample B ; n=1,016 ) usual gait-speed cutpoints . Rates of persistent lower extremity limitation events ( mean follow-up 4.9 years ) were calculated according to gait speed in Sample A. A cutpoint ( defining high- ( or = 1 m/s ) groups ) was identified based on persistent lower extremity limitation events . The predictive value of the identified cutpoints for major health-related events ( persistent severe lower extremity limitation , death , and hospitalization ) was evaluated in Sample B using Cox regression analyses . RESULTS A grade d response was seen between risk groups and health-related outcomes . Participants in the high-risk group had a higher risk of persistent lower extremity limitation ( rate ratio (RR)=2.20 , 95 % confidence interval (CI)=1.76 - 2.74 ) , persistent severe lower extremity limitation ( RR=2.29 , 95 % CI=1.63 - 3.20 ) , death ( RR=1.64 , 95 % CI=1.14 - 2.37 ) , and hospitalization ( RR=1.48 , 95 % CI=1.02 - 2.13 ) than those in the low-risk group . CONCLUSION Usual gait speed of less than 1 m/s identifies persons at high risk of health-related outcomes in well-functioning older people . Provision of a clinical ly meaningful cutpoint for usual gait speed may facilitate its use in clinical and research setting", "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", "AIM To examine the role of disease-related factors and age-related physiological changes in affecting gait speed and stride length in the elderly . SUBJECTS 925 men and 890 women aged 70 years and above who were ambulant , recruited by r and om sampling stratified according to age and sex , from all recipients of Old Age and Disability Allowance in Hong Kong . DESIGN Gait was assessed by measuring the time taken and the number of steps required to complete a 16-foot walk . Information on health and functional status , cognitive function , and depressive symptoms was collected , and anthropometric indices obtained . Factors affecting walking speed and stride were examined in the overall population and also after excluding those with physical disability or diseases . RESULTS Results were analyzed separately for men and women since mean walking speed was slower in women , who also took a larger number of steps . Age , coexisting disease , leg or back pain , poor vision , low level of physical activity , functional and cognitive impairment , high depressive symptom score , and anthropometric indices were all negatively associated with walking speed . Fallers also had slower speed . After excluding those with diseases or physical impairment , multivariate analysis showed that the only factors affecting speed were age in men , and age , height , and level of physical activity in women . Age and height were factors associated with stride length in men , and height only for women . CONCLUSION Both disease-related factors as well as age-related physiological changes contribute to the decline in walking speed and stride length", "Objective : To evaluate the effects of a new , individually adjusted , progressive and specific balance group training programme on fear of falling , step execution , and gait in healthy elderly people with fear of falling and tend to fall . Design : R and omized controlled trial . Setting : The study was conducted in Stockholm County , Sweden . Subjects : Fifty-nine community dwelling elderly people were recruited by advertisement , and allocated at r and om to an intervention group ( n = 38 ) or a control group ( n = 21 ) . Intervention : Individually adjusted , progressive and specific balance group training was given three times a week for three months . The training incorporated elements included in , and required for , independent activities of daily living , and for reactions to loss of balance during dual or multiple tasks . Main measures : Fear of falling was assessed with Falls Efficacy Scale International ( FES-I ) . The reaction time of step execution was measured with the step-execution test , and gait was measured with GAITRite ® . Results : After three months the intervention group showed significant positive changes in the FES-I ( P = 0.008 ) , in the step-execution phase of dual-task performance ( P = 0.012 ) , and in gait at preferred speed during single-task performance ; in cadence ( P = 0.030 ) and , at fast speed , in velocity ( P = 0.004 ) and cadence ( P = 0.001 ) . Significant decreases were also found for the likelihood of depression after participating in the training programme . Conclusion : This new balance training programme is feasible and leads to decreased fear of falling , decreased time for step execution during dual-task performance and increased velocity during fast walking ", "OBJECTIVE To determine , in a cohort of ambulatory older adults , whether spatial-temporal measures of foot placement during gait can predict the likelihood of future falls or whether these measures are more likely to be indicative of adaptations associated with pre-existing fear of falling . DESIGN Prospect i ve cohort study . SETTING Baseline gait measurements were performed in a gait and balance laboratory ; subsequent history of falling was monitored prospect ively for 1 year in two self-care facilities . PARTICIPANTS Fourteen male and 61 female consecutive volunteers ( mean age = 82 , SD = 6 ) who were independent in activities of daily living and able to walk 10 m unaided . MEASUREMENTS Spatial gait parameters were derived from digitized \" footprints \" ; temporal parameters were derived using footswitches . A clinical activity-based gait assessment was also performed . The dependent variables were pre-existing fear of falling ( reported at baseline ) and future falling ( experiencing one or more falls during the 1-year follow-up ) . MAIN RESULTS Reduced stride length , reduced speed , increased double-support time , and poorer clinical gait scores were associated with fear but showed little evidence of an independent association with falling . Conversely , increased stride-to-stride variability in stride length , speed , and double-support was associated independently with falling but showed little evidence of relationship to fear . Increased stride width showed some evidence of association with both falling and fear . Stride-to-stride variability in speed was the single best independent predictor of falling . CONCLUSIONS Changes in gait cited previously as risk factors for falling , i.e. , decreased stride length and speed and prolonged double support , may in fact be stabilizing adaptations related to fear of falling . Stride-to-stride variability in the control of gait is an independent predictor of falling and may be a useful measure for identifying high-risk individuals and evaluating preventive interventions . Stride width may also be a useful outcome measure . Contrary to common expectation , a wider stride does not necessarily increase stability but instead seems to predict an increased likelihood of experiencing falls", "BACKGROUND it is uncertain as to which measures of gait best predict those who are likely to fall . Our aim was to investigate the associations of gait and gait variability measures with incident falls risk . METHODS individuals aged 60 - 86 years ( n = 412 ) were r and omly selected from the Tasmanian electoral roll . Average gait and gait variability measures were collected on a computerised walkway . Falls were recorded prospect ively over 12 months . Log multinomial regression was used to estimate the relative risk of single and multiple falls associated with gait measures . Covariates included age , sex , sensorimotor and cognitive measures , mood and medications . RESULTS in this population -based study greater intra-individual variability in step length and double-support phase were linearly associated with increased risk of multiple falls ( P = 0.04 ) . Non-linear associations with multiple falls were found for gait speed P = 0.002 , cadence P = 0.004 and step time variability P = 0.03 . None of the gait measures predicted risk of single falls . CONCLUSION there is an increased risk of multiple falls , but not single falls , in older people with poorer gait . Specific measures of gait and gait variability seem to confer this risk and may be amenable to interventions design ed to reduce the risk of multiple falls in older people", "Tests of vision , vestibular function , peripheral sensation , strength , reaction time , balance and gait were administered to 183 community-dwelling women aged 22 - 99 years . Walking speed , stride length and cadence declined with age with corresponding increases in stance duration and percentage of the stride in the stance phase . Visual acuity and contrast sensitivity , tactile and vibration sense in the lower limb , vestibular function ( as assessed by the vestibular X Writing Test ) , quadriceps and ankle dorsiflexion strength and reaction time were significantly associated with all five gait parameters . Postural sway measures were associated with walking speed , stride length and percentage of the stride in the stance phase . Multiple regression analyses revealed seven sensori-motor measures as significant predictors for one or more of the gait parameters : low contrast visual acuity , tactile sensitivity , vibration sense , vestibular X-test writing performance , quadriceps strength , reaction time and sway . Quadriceps strength was included as a predictor variable for every gait parameter and in each case had the strongest beta weight . Women who fell on two or more occasions in a one-year prospect i ve period had significantly reduced and more variable cadence and significantly increased stance duration ( measured in absolute terms and as a percentage of stride ) than those who did not fall or fell on one occasion only . The study findings eluci date the relative importance of specific physiological systems in the maintenance of normal gait and identify temporal gait measures that are associated with falling in older people ", "Decline in dual-task walking performance is associated with increased risk of falls among older adults . The objective of this study is to determine whether 18 hr of participation in EnhanceFitness ( EF ) , an evidence -based group exercise program , improves dual-task walking performance among community-dwelling older adults . Twenty-eight healthy , community-dwelling older adults were evaluated before participating in EF and after 18 hr of participation . Gait speed was evaluated under single task and dual tasks using the TUG ( Timed Up and Go ) and 1-min walk tests . Dual-task costs ( DTC ) , the relative cost of dual-task performance compared to single-task performance , were calculated for both cognitive and motor tasks . Postural control and executive functions were evaluated as well . After 18 hr of EF , dual-task walking performance improved . Single-task performance improved as well as postural control and executive function . There was no significant change in DTC across all measurements , except for the cognitive task of the TUG" ]

[ "Background The CONSORT statement is intended to improve reporting of r and omised controlled trials and focuses on minimising the risk of bias ( internal validity ) . The applicability of a trial ’s results ( generalisability or external validity ) is also important , particularly for pragmatic trials . A pragmatic trial ( a term first used in 1967 by Schwartz and Lellouch ) can be broadly defined as a r and omised controlled trial whose purpose is to inform decisions about practice . This extension of the CONSORT statement is intended to improve the reporting of such trials and focuses on applicability . Methods At two , two-day meetings held in Toronto in 2005 and 2008 , we review ed the CONSORT statement and its extensions , the literature on pragmatic trials and applicability , and our experiences in conducting pragmatic trials . Recommendations We recommend extending eight CONSORT checklist items for reporting of pragmatic trials : the background , participants , interventions , outcomes , sample size , blinding , participant flow , and generalisability of the findings . These extensions are presented , along with illustrative examples of reporting , and an explanation of each extension . Adherence to these reporting criteria will make it easier for decision makers to judge how applicable the results of r and omised controlled trials are to their own conditions . Empirical studies are needed to ascertain the usefulness and comprehensiveness of these CONSORT checklist item extensions . In the meantime we recommend that those who support , conduct , and report pragmatic trials should use this extension of the CONSORT statement to facilitate the use of trial results in decisions about health care . Pragmatic trials are design ed to inform decisions about practice , but poor reporting can reduce their usefulness . The CONSORT and Practihc groups describe modifications to the CONSORT guidelines to help readers assess the applicability of the", "The present study has been conducted to evaluate selected yogic procedures on individuals with low back pain . The underst and ing of back pain as one of the commonest clinical presentations during clinical practice made the path to the present study . It has also been calculated that more than three-quarters of the world 's population experience back pain at some time in their lives . Twelve patients were selected and r and omly divided into two groups , viz . , group A yogic group and group B control group . Advice for life style and diet was given for all the patients . The effect of the therapy was assessed subjectively and objective ly . Particular scores drawn for yogic group and control group were individually analyzed before and after treatment and the values were compared using st and ard statistical protocol s. Yogic intervention revealed 79 % relief in both subjective and objective parameters ( i.e. , 7 out of 14 parameters showed statistically highly significant P , while 4 showed significant results P 79 % relief in both subjective and objective parameters . ( i.e. , total 6 out of 14 parameters showed statistically highly significant ( P , while 5 showed significant results ( P < 0.05 )", "OBJECTIVE To conduct a pilot trial of yoga for the treatment of chronic low back pain ( LBP ) to inform the feasibility and practicality of conducting a full-scale trial in the UK ; and to assess the efficacy of yoga for the treatment of chronic low back pain . DESIGN A pragmatic r and omised controlled trial was undertaken comparing yoga to usual care . PARTICIPANTS Twenty participants who had presented to their GP with chronic low back pain in the previous 18 months were recruited via GP records from one practice in York , UK . INTERVENTIONS Twenty patients were r and omised to either 12 weekly 75-min sessions of specialised yoga plus written advice , or usual care plus written advice . Allocation was 50/50 . MAIN OUTCOME MEASURES Recruitment rate , levels of intervention attendance , and loss to follow-up were the main non- clinical outcomes . Change as measured by the Rol and and Morris disability question naire was the primary clinical outcome . Changes in the Aberdeen back pain scale , SF-12 , EQ-5D , and pain self-efficacy were secondary clinical outcomes . Data were collected via postal question naire at baseline , 4 weeks , and 12 weeks follow-up . RESULTS Of the 286 patients identified from the GP data base , 52 ( 18 % ) consented and returned the eligibility question naire , out of these 20 ( 6.9 % ) were eligible and r and omised . The total percentage of patients r and omised from the GP practice population was 0.28 % . Ten patients were r and omised to yoga , receiving an average of 1.7 sessions ( range 0 - 5 ) , and 10 were r and omised to usual care . At 12 weeks follow-up data was received from 60 % of patients in the yoga group and 90 % of patients in the usual care group ( 75 % overall ) . No significant differences were seen between groups in clinical outcomes apart from on the Aberdeen back pain scale at four weeks follow-up where the yoga group reported significantly less pain . CONCLUSION This pilot study provided useful data and information to inform the design and development of a full-scale trial of yoga for CLBP in the UK . A key finding is the calculation of GP practice total list size required for patient recruitment in a full-scale trial , and the need to implement methods to increase class attendance", "Background . Previous studies have demonstrated that once-weekly yoga classes are effective for chronic low back pain ( cLBP ) in white adults with high socioeconomic status . The comparative effectiveness of twice-weekly classes and generalizability to racially diverse low income population s are unknown . Methods . We conducted a 12-week r and omized , parallel-group , dosing trial for 95 adults recruited from an urban safety-net hospital and five community health centers comparing once-weekly ( n = 49 ) versus twice-weekly ( n = 46 ) st and ardized yoga classes supplemented by home practice . Primary outcomes were change from baseline to 12 weeks in pain ( 11-point scale ) and back-related function ( 23-point modified Rol and -Morris Disability Question naire ) . Results . 82 % of participants were nonwhite ; 77 % had annual household incomes The sample 's baseline mean pain intensity [ 6.9 ( SD 1.6 ) ] and function [ 13.7 ( SD 5.0 ) ] reflected moderate to severe back pain and impairment . Pain and back-related function improved within both groups ( P pain reduction [ −2.1 ( 95 % CI −2.9 , −1.3 ) versus −2.4 ( 95 % CI −3.1 , −1.8 ) , P = 0.62 ] or back-related function [ −5.1 ( 95 % CI −7.0 , −3.2 ) versus −4.9 ( 95 % CI −6.5 , −3.3 ) , P = 0.83 ] . Conclusions . Twelve weeks of once-weekly or twice-weekly yoga classes were similarly effective for predominantly low income minority adults with moderate to severe chronic low back pain . This trial is registered with Clinical Trials.gov NCT01761617", "Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field", "Context Yoga combines exercise with achieving a state of mental focus through breathing . In the United States , 1 million people practice yoga for low back pain . Contribution The authors recruited patients who had a recent primary care visit for low back pain and r and omly assigned 101 to yoga or conventional exercise or a self-care book . Patients in the yoga and exercise groups reported good adherence at 26 weeks . Compared with self-care , symptoms were milder and function was better with yoga . The exercise group had intermediate outcomes . Symptoms improved between 12 and 26 weeks only with yoga . Implication s Yoga was a more effective treatment for low back pain than a self-care book . The Editors Most treatments for chronic low back pain have modest efficacy at best ( 1 ) . Exercise is one of the few proven treatments for chronic low back pain ; however , its effects are often small , and no form has been shown to be clearly better than another ( 2 - 5 ) . Yoga , which often couples physical exercise with breathing , is a popular alternative form of mindbody therapy . An estimated 14 million Americans practice d yoga in 2002 ( 6 ) , including more than 1 million who used it as a treatment for back pain ( 7 , 8) . Yoga may benefit patients with back pain simply because it involves exercise or because of its effects on mental focus . We found no published studies in western biomedical literature that evaluated yoga for chronic low back pain ; therefore , we design ed a clinical trial to evaluate its effectiveness and safety for this condition . Methods Study Design and Setting This r and omized , controlled trial compared the effects of yoga classes with conventional exercise classes and with a self-care book in patients with low back pain that persisted for at least 12 weeks . The study was conducted at Group Health Cooperative , a nonprofit , integrated health care system with approximately 500000 enrollees in Washington State and Idaho . The Group Health Cooperative institutional review board approved the study protocol , and all study participants gave oral informed consent before the eligibility screening and written consent before the baseline interview and r and omization . Patients Patients from Group Health Cooperative were recruited for 12-week sessions of classes that were conducted between June and December 2003 . We mailed letters describing the study to 6913 patients between 20 and 64 years of age who had visited a primary care provider for treatment of back pain 3 to 15 months before the study ( according to electronic visit records ) . We also advertised the study in the health plan 's consumer magazine . Patients were informed that we were comparing 3 approaches for the relief of back pain and that each was design ed to help reduce the negative effects of low back pain on people 's lives . A research assistant telephoned patients who returned statements of interest to assess their eligibility . After we received their signed informed consent forms , eligible patients were telephoned again for collection of baseline data and r and omization to treatment . We excluded individuals whose back pain was complicated ( for example , sciatica , previous back surgery , or diagnosed spinal stenosis ) , potentially attributable to specific underlying diseases or conditions ( for example , pregnancy , metastatic cancer , spondylolisthesis , fractured bones , or dislocated joints ) , or minimal ( rating of less than 3 on a bothersomeness scale of 0 to 10 ) . We also excluded individuals who were currently receiving other back pain treatments or had participated in yoga or exercise training for back pain in the past year , those with a possible disincentive to improve ( such as patients receiving workers ' compensation or those involved in litigation ) , and those with unstable medical or severe psychiatric conditions or dementia . Patients who had contraindications ( for example , symptoms consistent with severe disk disease ) or schedules that precluded class participation , those who were unwilling to practice at home , or those who could not speak or underst and English were also excluded . R and omization Protocol Participants were r and omly assigned to participate in yoga or exercise classes or to receive the self-care book . We r and omly generated treatment assignments for each class series by using a computer program with block sizes of 6 or 9 . A research er who was not involved in patient recruitment or r and omization placed the assignments in opaque , sequentially numbered envelopes , which were stored in a locked filing cabinet until needed for r and omization . Interventions The yoga and exercise classes developed specifically for this study consisted of 12 weekly 75-minute classes design ed to benefit people with chronic low back pain . In addition to attending classes held at Group Health facilities , participants were asked to practice daily at home . Participants received h and outs that described home practice s , and yoga participants received auditory compact discs to guide them through the sequence of postures with the appropriate mental focus ( examples of postures are shown in the Appendix Figure ) . Study participants retained access to all medical care provided by their insurance plan . Appendix Figure . Yoga postures Yoga We chose to use viniyoga , a therapeutically oriented style of yoga that emphasizes safety and is relatively easy to learn . Our class instructor and a senior teacher of viniyoga , who has + written a book about its therapeutic uses ( 9 ) , design ed the yoga intervention for patients with back pain who did not have previous yoga experience . Although all the sessions emphasized use of postures and breathing for managing low back symptoms , each had a specific focus : relaxation ; strength-building , flexibility , and large-muscle movement ; asymmetric poses ; strengthening the hip muscles ; lateral bending ; integration ; and customizing a personal practice . The postures were selected from a core of 17 relatively simple postures , some with adaptations ( Appendix Table ) , and the sequence of the postures in each class was performed according to the rudiments of viniyoga ( 9 ) . Each class included a question - and -answer period , an initial and final breathing exercise , 5 to 12 postures , and a guided deep relaxation . Most postures were not held but were repeated 3 or 6 times . Exercise Because we could not identify a clearly superior form of therapeutic exercise for low back pain from the literature , a physical therapist design ed a 12-session class series that was 1 ) different from what most participants would have probably experienced in previous physical therapy sessions ( to maximize adherence ) and 2 ) similar to the yoga classes in number and length . We included a short educational talk that provided information on proper body mechanics , the benefits of exercise and realistic goal setting , and overcoming common barriers to developing an exercise routine ( for example , fear ) . Each session began with the educational talk ; feedback from the previous week ; simple warm-ups to increase heart rate ; and repetitions of a series of 7 aerobic exercises and 10 strengthening exercises that emphasized leg , hip , abdominal , and back muscles . Over the course of the 12-week series , the number of repetitions of each aerobic and strength exercise increased from 8 to 30 in increments of 2 . The strengthening exercises were followed by 12 stretches for the same muscle groups ; each stretch was held for 30 seconds . Classes ended with a short , unguided period of deep , slow breathing . Self-Care Book Participants were mailed a copy of The Back Pain Helpbook ( 10 ) , an evidence -based book that emphasized such self-care strategies as adoption of a comprehensive fitness and strength program , appropriate lifestyle modification , and guidelines for managing flare-ups . Although we did not provide any instructions for using the book , many of the chapters concluded with specific action items . Outcome Measures Interviewers who were masked to the treatment assignments conducted telephone interviews at baseline and at 6 , 12 , and 26 weeks after r and omization . The baseline interview collected information regarding sociodemographic characteristics , back pain history , and the participant 's level of knowledge about yoga and exercise . Participants were asked to describe their current pain and to rate their expectations for each intervention . The primary outcomes were back-related dysfunction and symptoms , and the primary time point of interest was 12 weeks . We used the modified Rol and Disability Scale ( 11 ) to measure patient dysfunction by totaling the number of positive responses to 23 questions about limitations of daily activities that might arise from back pain . This scale has been found to be valid , reliable , and sensitive to change ( 12 - 14 ) ; research ers estimate that the minimum clinical ly significant difference on the Rol and scale ranges from 2 to 3 points ( 13 , 15 ) . Participants rated how bothersome their back pain had been during the previous week on an 11-point scale , in which 0 represented not at all bothersome and 10 represented extremely bothersome ; a similar measure demonstrated substantial construct validity in earlier research ( 13 ) . Estimates of the minimum clinical ly significant difference on the bothersomeness scale were approximately 1.5 points ( 16 , 17 ) . Secondary outcome measures were general health status , which we assessed by conducting the Short Form-36 Health Survey ( 18 ) ; degree of restricted activity as determined by patient responses to 3 questions ( 19 ) ; and medication use . After all outcomes data were collected , we asked questions related to specific interventions ( for example , Did you practice at home ? ) . At the 12-week interview , we asked class participants about any pain or substantial discomfort they experienced as a result of the classes . We assessed adherence to the home practice recommendations by asking class participants to complete weekly home practice logs and by asking about home practice during the follow-up", "Low back pain is a significant public health problem and one of the most commonly reported reasons for the use of Complementary Alternative Medicine . A r and omized control trial was conducted in subjects with non‐specific chronic low back pain comparing Iyengar yoga therapy to an educational control group . Both programs were 16 weeks long . Subjects were primarily self‐referred and screened by primary care physicians for study of inclusion /exclusion criteria . The primary outcome for the study was functional disability . Secondary outcomes including present pain intensity , pain medication usage , pain‐related attitudes and behaviors , and spinal range of motion were measured before and after the interventions . Subjects had low back pain for 11.2±1.54 years and 48 % used pain medication . Overall , subjects presented with less pain and lower functional disability than subjects in other published intervention studies for chronic low back pain . Of the 60 subjects enrolled , 42 ( 70 % ) completed the study . Multivariate analyses of outcomes in the categories of medical , functional , psychological and behavioral factors indicated that significant differences between groups existed in functional and medical outcomes but not for the psychological or behavioral outcomes . Univariate analyses of medical and functional outcomes revealed significant reductions in pain intensity ( 64 % ) , functional disability ( 77 % ) and pain medication usage ( 88 % ) in the yoga group at the post and 3‐month follow‐up assessment s. These preliminary data indicate that the majority of self‐referred persons with mild chronic low back pain will comply to and report improvement on medical and functional pain‐related outcomes from Iyengar yoga therapy", "& NA ; A mounting body of literature recommends that treatment for fibromyalgia ( FM ) encompass medications , exercise and improvement of coping skills . However , there is a significant gap in determining an effective counterpart to pharmacotherapy that incorporates both exercise and coping . The aim of this r and omized controlled trial was to evaluate the effects of a comprehensive yoga intervention on FM symptoms and coping . A sample of 53 female FM patients were r and omized to the 8‐week Yoga of Awareness program ( gentle poses , meditation , breathing exercises , yoga‐based coping instructions , group discussion s ) or to wait‐listed st and ard care . Data were analyzed by intention to treat . At post‐treatment , women assigned to the yoga program showed significantly greater improvements on st and ardized measures of FM symptoms and functioning , including pain , fatigue , and mood , and in pain catastrophizing , acceptance , and other coping strategies . This pilot study provides promising support for the potential benefits of a yoga program for women with FM", "OBJECTIVE The aim of this study was to compare the effect of a short-term intensive residential yoga program with physical exercise ( control ) on pain and spinal flexibility in subjects with chronic low-back pain ( CLBP ) . DESIGN This was a wait-list , r and omized controlled study . SETTING The study was conducted at a residential integrative health center in Bangalore , South India . SUBJECTS Eighty ( 80 ) subjects ( females , n = 37 ) with CLBP , who consented were r and omly assigned to receive yoga or physical exercise if they satisfied the selection criteria . INTERVENTION The intervention consisted of a 1-week intensive residential yoga program comprised of asanas ( physical postures ) design ed for back pain , pranayamas ( breathing practice s ) , meditation , and didactic and interactive sessions on philosophical concepts of yoga . The control group practice d physical exercises under a trained physiatrist and also had didactic and interactive sessions on lifestyle change . Both of the groups were matched for time on intervention and attention . OUTCOME MEASURES Pain-related outcomes were assessed by the Oswestry Disability Index ( ODI ) and by spinal flexibility , which was assessed using goniometer at pre and post intervention . Data were analyzed using repeated measures analysis of variance ( RMANOVA ) . RESULTS Data conformed to a Gaussian distribution . There was a significant reduction in ODI scores in the yoga group compared to the control group ( p = 0.01 ; effect size 1.264 ) . Spinal flexibility measures improved significantly in both groups but the yoga group had greater improvement as compared to controls on spinal flexion ( p = 0.008 ; effect size 0.146 ) , spinal extension ( p = 0.002 ; effect size 0.251 ) , right lateral flexion ( p = 0.059 ; effect size 0.006 ) ; and left lateral flexion ( p = 0.006 ; effect size 0.171 ) . CONCLUSIONS Seven ( 7 ) days of a residential intensive yoga-based lifestyle program reduced pain-related disability and improved spinal flexibility in patients with CLBP better than a physical exercise regimen", "OBJECTIVES To assess whether a specifically design ed yoga intervention can reduce hyperkyphosis . DESIGN A 6-month , two-group , r and omized , controlled , single-masked trial . SETTING Community research unit . PARTICIPANTS One hundred eighteen women and men aged 60 and older with a kyphosis angle of 40 degrees or greater . Major exclusions were serious medical comorbidity , use of assistive device , inability to hear or see adequately for participation , and inability to pass a physical safety screen . INTERVENTION The active treatment group attended hour-long yoga classes 3 days per week for 24 weeks . The control group attended a monthly luncheon and seminar and received mailings . MEASUREMENTS Primary outcomes were change ( baseline to 6 months ) in Debrunner kyphometer-assessed kyphosis angle , st and ing height , timed chair st and s , functional reach , and walking speed . Secondary outcomes were change in kyphosis index , flexicurve kyphosis angle , Rancho Bernardo Blocks posture assessment , and health-related quality of life ( HRQOL ) . RESULTS Compared with control participants , participants r and omized to yoga experienced a 4.4 % improvement in flexicurve kyphosis angle ( P=.006 ) and a 5 % improvement in kyphosis index ( P=.004 ) . The intervention did not result in statistically significant improvement in Debrunner kyphometer angle , measured physical performance , or self-assessed HRQOL ( each P>.1 ) . CONCLUSION The decrease in flexicurve kyphosis angle in the yoga treatment group shows that hyperkyphosis is remediable , a critical first step in the pathway to treating or preventing this condition . Larger , more-definitive studies of yoga or other interventions for hyperkyphosis should be considered . Targeting individuals with more-malleable spines and using longitudinally precise measures of kyphosis could strengthen the treatment effect", "Context : In two of the earlier R and omized Control Trials on yoga for chronic lower back pain ( CLBP ) , 12 to 16 weeks of intervention were found effective in reducing pain and disability . Aim : To study the efficacy of a residential short term intensive yoga program on quality of life in CLBP . Material s and Methods : About 80 patients with CLBP ( females 37 ) registered for a week long treatment at SVYASA Holistic Health Centre in Bengaluru , India . They were r and omized into two groups ( 40 each ) . The yoga group practice d a specific module for CLBP comprising of asanas ( physical postures ) , pranayama ( breathing practice s ) , meditation and lectures on yoga philosophy . The control group practice d physical therapy exercises for back pain . Perceived stress scale ( PSS ) was used to measure baseline stress levels . Outcome measures were WHOQOL Bref for quality of life and straight leg raising test ( SLR ) using a Goniometer . Results : There were significant negative correlations ( Pearson ’s , P0.30 ) between baseline PSS with all four domains and the total score of WHOQOLBref . All the four domains ’ WHOQOLBref improved in the yoga group ( repeated measures ANOVA P=0.001 ) with significant group*time interaction ( P SLR increased in both groups ( P=0.001 ) with higher increase in yoga ( 31.1 % right , 28.4 % left ) than control ( 18.7 % right , 21.5 % left ) group with significant group*time interaction ( SLR right leg P=0.044 ) . Conclusion : In CLBP , a negative correlation exists between stress and quality of life . Yoga increases quality of life and spinal flexibility better than physical therapy exercises", "PURPOSE The purpose of this r and omized pilot study was to evaluate a possible design for a 6-week modified hatha yoga protocol to study the effects on participants with chronic low back pain . PARTICIPANTS Twenty-two participants ( M = 4 ; F = 17 ) , between the ages of 30 and 65 , with chronic low back pain ( CLBP ) were r and omized to either an immediate yoga based intervention , or to a control group with no treatment during the observation period but received later yoga training . METHODS A specific CLBP yoga protocol design ed and modified for this population by a certified yoga instructor was administered for one hour , twice a week for 6 weeks . Primary functional outcome measures included the forward reach ( FR ) and sit and reach ( SR ) tests . All participants completed Oswestry Disability Index ( ODI ) and Beck Depression Inventory ( BDI ) question naires . Guiding questions were used for qualitative data analysis to ascertain how yoga participants perceived the instructor , group dynamics , and the impact of yoga on their life . ANALYSIS To account for drop outs , the data were divided into better or not categories , and analyzed using chi-square to examine differences between the groups . Qualitative data were analyzed through frequency of positive responses . RESULTS Potentially important trends in the functional measurement scores showed improved balance and flexibility and decreased disability and depression for the yoga group but this pilot was not powered to reach statistical significance . Significant limitations included a high dropout rate in the control group and large baseline differences in the secondary measures . In addition , analysis of the qualitative data revealed the following frequency of responses ( 1 ) group intervention motivated the participants and ( 2 ) yoga fostered relaxation and new awareness/learning . CONCLUSION A modified yoga-based intervention may benefit individuals with CLB , but a larger study is necessary to provide definitive evidence . Also , the impact on depression and disability could be considered as important outcomes for further study . Additional functional outcome measures should be explored . This pilot study supports the need for more research investigating the effect of yoga for this population", "Aim : This study was design ed to evaluate the efficacy of addition of integrated yoga therapy to therapeutic exercises in osteoarthritis ( OA ) of knee joints . Material s and Methods : This was a prospect i ve r and omized active control trial . A total of t participants with OA of knee joints between 35 and 80 years ( yoga , 59.56 ± 9.54 and control , 59.42 ± 10.66 ) from the outpatient department of Dr. John 's Orthopedic Center , Bengaluru , were r and omly assigned to receive yoga or physiotherapy exercises after transcutaneous electrical stimulation and ultrasound treatment of the affected knee joints . Both groups practice d supervised intervention ( 40 min per day ) for 2 weeks ( 6 days per week ) with followup for 3 months . The module of integrated yoga consisted of shithilikaranavyayama ( loosening and strengthening ) , asanas , relaxation techniques , pranayama , meditation and didactic lectures on yama , niyama , jnana yoga , bhakti yoga , and karma yoga for a healthy lifestyle change . The control group also had supervised physiotherapy exercises . A total of 118 ( yoga ) and 117 ( control ) were available for final analysis . Results : Significant differences were observed within ( P all domains of the Short Form-36 ( P approach of yoga therapy is better than therapeutic exercises as an adjunct to transcutaneous electrical stimulation and ultrasound treatment in improving knee disability and quality of life in patients with OA knees", "BACKGROUND Several studies suggest yoga may be effective for chronic low back pain ; however , trials targeting minorities have not been conducted . PRIMARY STUDY OBJECTIVES : Assess the feasibility of study ing yoga in a predominantly minority population with chronic low back pain . Collect preliminary data to plan a larger powered study . STUDY DESIGN Pilot r and omized controlled trial . SETTING Two community health centers in a racially diverse neighborhood of Boston , Massachusetts . PARTICIPANTS Thirty English-speaking adults ( mean age 44 years , 83 % female , 83 % racial/ethnic minorities ; 48 % with incomes INTERVENTIONS St and ardized series of weekly hatha yoga classes for 12 weeks compared to a waitlist usual care control . OUTCOME MEASURES Feasibility measured by time to complete enrollment , proportion of racial/ethnic minorities enrolled , retention rates , and adverse events . Primary efficacy outcomes were changes from baseline to 12 weeks in pain score ( 0=no pain to 10=worst possible pain ) and back-related function using the modified Rol and -Morris Disability Question naire ( 0 - 23 point scale , higher scores reflect poorer function ) . Secondary efficacy outcomes were analgesic use , global improvement , and quality of life ( SF-36 ) . RESULTS Recruitment took 2 months . Retention rates were 97 % at 12 weeks and 77 % at 26 weeks . Mean pain scores for yoga decreased from baseline to 12 weeks ( 6.7 to 4.4 ) compared to usual care , which decreased from 7.5 to 7.1 ( P=.02 ) . Mean Rol and scores for yoga decreased from 14.5 to 8.2 compared to usual care , which decreased from 16.1 to 12.5 ( P=.28 ) . At 12 weeks , yoga compared to usual care participants reported less analgesic use ( 13 % vs 73 % , P=.003 ) , less opiate use ( 0 % vs 33 % , P=.04 ) , and greater overall improvement ( 73 % vs 27 % , P=.03 ) . There were no differences in SF-36 scores and no serious adverse events . CONCLUSION A yoga study intervention in a predominantly minority population with chronic low back pain was moderately feasible and may be more effective than usual care for reducing pain and pain medication use", "OBJECTIVE Yoga and relaxation techniques have traditionally been used by nonmedical practitioners to help alleviate musculoskeletal symptoms . The objective of this study was to collect controlled observations of the effect of yoga on the h and s of patients with osteoarthritis ( OA ) . METHODS Patients with OA of the h and s were r and omly assigned to receive either the yoga program or no therapy . Yoga techniques were supervised by one instructor once/week for 8 weeks . Variables assessed were pain , strength , motion , joint circumference , tenderness , and h and function using the Stanford H and Assessment question naire . RESULTS The yoga treated group improved significantly more than the control group in pain during activity , tenderness and finger range of motion . Other trends also favored the yoga program . CONCLUSION This yoga derived program was effective in providing relief in h and OA . Further studies are needed to compare this with other treatments and to examine longterm effects", "The growing use of unsubstantiated complementary and alternative medicine therapies by people in the United States1 along with its increasing coverage by third party payers2 encouraged Congress to create the National Center for Complementary and Alternative Medicine ( NCCAM ) at the National Institutes of Health . The centre 's mission is “ to explore complementary and alternative healing practice s in the context of rigorous science ; to educate and training CAM research ers ; and to disseminate authoritative information to the public and professionals.”3 To complete this mission , NCCAM supports publicly relevant and scientifically rigorous research to identify those complementary and alternative medicine practice s that are safe and effective . The centre 's re sources , although generous ( $ 68.3 m ( £ 46 m ) for fiscal year 2000 ) , are not sufficient to study all complementary and alternative medicine practice s. NCCAM therefore developed criteria to help prioritise the many possible research opportunities ( box ) . As part of the evaluation process , NCCAM seeks advice from its national advisory council , complementary and alternative medicine and conventional clinicians , members of the scientific research community , the public , sister federal agencies , and other stakeholders . # # # # Summary points Many early clinical trials investigating complementary and alternative medicine have had serious flaws Clinical investigations of complementary and alternative medicine are made difficult by factors such as use of complex , individualised treatments and lack of st and ardisation of herbal medicines Other problems include difficulties in accruing , r and omising , and retaining patients and in identifying appropriate placebo interventions Despite these complexities , rigorously design ed clinical trials are possible , including pragmatic studies of complete complementary and alternative medicine systems Strong commitment is required from the research community to provide information about complementary and alternative medicines to the public and health professionals Staff at the centre are often asked why limited re sources are being spent on research that is perceived as replicating previously published work , especially when other western countries have", "BACKGROUND Chronic low back pain is a common problem lacking highly effective treatment options . Small trials suggest that yoga may have benefits for this condition . This trial was design ed to determine whether yoga is more effective than conventional stretching exercises or a self-care book for primary care patients with chronic low back pain . METHODS A total of 228 adults with chronic low back pain were r and omized to 12 weekly classes of yoga ( 92 patients ) or conventional stretching exercises ( 91 patients ) or a self-care book ( 45 patients ) . Back-related functional status ( modified Rol and Disability Question naire , a 23-point scale ) and bothersomeness of pain ( an 11-point numerical scale ) at 12 weeks were the primary outcomes . Outcomes were assessed at baseline , 6 , 12 , and 26 weeks by interviewers unaware of treatment group . RESULTS After adjustment for baseline values , 12-week outcomes for the yoga group were superior to those for the self-care group ( mean difference for function , -2.5 [ 95 % CI , -3.7 to -1.3 ] ; P symptoms , -1.1 [ 95 % CI , -1.7 to -0.4 ] ; P function for the yoga group remained superior ( mean difference , -1.8 [ 95 % CI , -3.1 to -0.5 ] ; P conventional stretching exercises at any time point . CONCLUSION Yoga classes were more effective than a self-care book , but not more effective than stretching classes , in improving function and reducing symptoms due to chronic low back pain , with benefits lasting at least several months . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00447668", "Low back pain is the fifth most common reason for all physician visits in the United States ( 1 , 2 ) . Approximately one quarter of U.S. adults reported having low back pain lasting at least 1 whole day in the past 3 months ( 2 ) , and 7.6 % reported at least 1 episode of severe acute low back pain ( see Glossary ) within a 1-year period ( 3 ) . Low back pain is also very costly : Total incremental direct health care costs attributable to low back pain in the U.S. were estimated at $ 26.3 billion in 1998 ( 4 ) . In addition , indirect costs related to days lost from work are substantial , with approximately 2 % of the U.S. work force compensated for back injuries each year ( 5 ) . Many patients have self-limited episodes of acute low back pain and do not seek medical care ( 3 ) . Among those who do seek medical care , pain , disability , and return to work typically improve rapidly in the first month ( 6 ) . However , up to one third of patients report persistent back pain of at least moderate intensity 1 year after an acute episode , and 1 in 5 report substantial limitations in activity ( 7 ) . Approximately 5 % of the people with back pain disability account for 75 % of the costs associated with low back pain ( 8) . Many options are available for evaluation and management of low back pain . However , there has been little consensus , either within or between specialties , on appropriate clinical evaluation ( 9 ) and management ( 10 ) of low back pain . Numerous studies show unexplained , large variations in use of diagnostic tests and treatments ( 11 , 12 ) . Despite wide variations in practice , patients seem to experience broadly similar outcomes , although costs of care can differ substantially among and within specialties ( 13 , 14 ) . The purpose of this guideline is to present the available evidence for evaluation and management of acute and chronic low back pain ( see Glossary ) in primary care setting s. The target audience for this guideline is all clinicians caring for patients with low ( lumbar ) back pain of any duration , either with or without leg pain . The target patient population is adults with acute and chronic low back pain not associated with major trauma . Children or adolescents with low back pain ; pregnant women ; and patients with low back pain from sources outside the back ( nonspinal low back pain ) , fibromyalgia or other myofascial pain syndromes , and thoracic or cervical back pain are not included . These recommendations are based on a systematic evidence review summarized in 2 background papers by Chou and colleagues in this issue ( 15 , 16 ) from an evidence report by the American Pain Society ( 17 ) . The evidence report ( 17 ) discusses the evidence for the evaluation , and the 2 background papers ( 15 , 16 ) summarize the evidence for management . Methods The literature search for this guideline included studies from MEDLINE ( 1966 through November 2006 ) , the Cochrane Data base of Systematic Review s , the Cochrane Central Register of Controlled Trials , and EMBASE . The literature search included all English- language articles reporting on r and omized , controlled trials of nonpregnant adults ( age > 18 years ) with low back pain ( alone or with leg pain ) of any duration that evaluated a target medication and reported at least 1 of the following outcomes : back-specific function , generic health status , pain , work disability , or patient satisfaction . The American College of Physicians ( ACP ) and the American Pain Society ( APS ) convened a multidisciplinary panel of experts to develop the key questions and scope used to guide the evidence report , review its results , and formulate recommendations . The background papers by Chou and colleagues ( 15 , 16 ) provide details about the methods used for the systematic evidence review . This guideline grade s its recommendations by using the ACP 's clinical practice guidelines grading system , adapted from the classification developed by the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) work group ( Appendix Table 1 ) ( 18 ) . The evidence in this guideline was first evaluated by the ACP/APS panel by using a system adopted from the U.S. Preventive Services Task Force for grading strength of evidence , estimating magnitude of benefits , and assigning summary ratings ( Appendix Tables 2 , 3 , and 4 ) ( 19 ) . The evidence was independently review ed by the ACP 's Clinical Efficacy Assessment Subcommittee . The ratings for individual low back pain interventions discussed in this guideline are summarized in Appendix Table 5 for acute low back pain ( 4 weeks ' duration ) . This guideline considered interventions to have proven benefits only when they were supported by at least fair- quality evidence and were associated with at least moderate benefits ( or small benefits but no significant harms , costs , or burdens ) . Figures 1 and 2 present an accompanying algorithm . Appendix Table 1 . The American College of Physicians Clinical Practice Guidelines Grading System Appendix Table 2 . Methods for Grading the Strength of the Overall Evidence for an Intervention Appendix Table 3 . Definitions for Estimating Magnitude of Effects Appendix Table 4 . Recommendations and Summary Ratings Appendix Table 5 . Level of Evidence and Summary Grade s for Noninvasive Interventions in Patients with Acute Low Back Pain Appendix Table 6 . Level of Evidence and Summary Grade s for Noninvasive Interventions in Patients with Chronic or Subacute Low Back Pain Figure 1 . Initial evaluation of low back pain ( LBP Figure 2 . Management of low back pain ( LBP Recommendations : Evaluation of Low Back Pain Recommendation 1 : Clinicians should conduct a focused history and physical examination to help place patients with low back pain into 1 of 3 broad categories : nonspecific low back pain , back pain potentially associated with radiculopathy or spinal stenosis , or back pain potentially associated with another specific spinal cause . The history should include assessment of psychosocial risk factors , which predict risk for chronic disabling back pain ( strong recommendation , moderate- quality evidence ) . More than 85 % of patients who present to primary care have low back pain that can not reliably be attributed to a specific disease or spinal abnormality ( nonspecific low back pain [ see Glossary ] ) ( 20 ) . Attempts to identify specific anatomical sources of low back pain in such patients have not been vali date d in rigorous studies , and classification schemes frequently conflict with one another ( 21 ) . Moreover , no evidence suggests that labeling most patients with low back pain by using specific anatomical diagnoses improves outcomes . In a minority of patients presenting for initial evaluation in a primary care setting , low back pain is caused by a specific disorder , such as cancer ( approximately 0.7 % of cases ) , compression fracture ( 4 % ) , or spinal infection ( 0.01 % ) ( 22 ) . Estimates for prevalence of ankylosing spondylitis in primary care patients range from 0.3 % ( 22 ) to 5 % ( 23 ) . Spinal stenosis ( see Glossary ) and symptomatic herniated disc ( see Glossary ) are present in about 3 % and 4 % of patients , respectively . The cauda equina syndrome ( see Glossary ) is most commonly associated with massive midline disc herniation but is rare , with an estimated prevalence of 0.04 % among patients with low back pain ( 24 ) . A practical approach to assessment is to do a focused history and physical examination to determine the likelihood of specific underlying conditions and measure the presence and level of neurologic involvement ( 24 , 25 ) . Such an approach facilitates classification of patients into 1 of 3 broad categories : nonspecific low back pain , back pain potentially associated with radiculopathy ( see Glossary ) or spinal stenosis ( suggested by the presence of sciatica [ see Glossary ] or pseudoclaudication ) , and back pain potentially associated with another specific spinal cause . The latter category includes the small proportion of patients with serious or progressive neurologic deficits or underlying conditions requiring prompt evaluation ( such as tumor , infection , or the cauda equina syndrome ) , as well as patients with other conditions that may respond to specific treatments ( such as ankylosing spondylitis or vertebral compression fracture ) . Diagnostic triage into 1 of these 3 categories helps guide subsequent decision making . Clinicians should inquire about the location of pain , frequency of symptoms , and duration of pain , as well as any history of previous symptoms , treatment , and response to treatment . The possibility of low back pain due to problems outside the back , such as pancreatitis , nephrolithiasis , or aortic aneurysm , or systemic illnesses , such as endocarditis or viral syndromes , should be considered . All patients should be evaluated for the presence of rapidly progressive or severe neurologic deficits , including motor deficits at more than 1 level , fecal incontinence , and bladder dysfunction . The most frequent finding in the cauda equina syndrome is urinary retention ( 90 % sensitivity ) ( 24 ) . In patients without urinary retention , the probability of the cauda equina syndrome is approximately 1 in 10000 . Clinicians should also ask about risk factors for cancer and infection . In a large , prospect i ve study from a primary care setting , a history of cancer ( positive likelihood ratio , 14.7 ) , unexplained weight loss ( positive likelihood ratio , 2.7 ) , failure to improve after 1 month ( positive likelihood ratio , 3.0 ) , and age older than 50 years ( positive likelihood ratio , 2.7 ) were each associated with a higher likelihood for cancer ( 26 ) . The posttest probability of cancer in patients presenting with back pain increases from approximately 0.7 % to 9 % in patients with a history of cancer ( not including nonmelanoma skin cancer ) . In patients with any 1 of the other 3 risk factors , the likelihood of cancer only increases to approximately 1.2 % ( 26 ) . Features predicting the presence of vertebral infection have not been well studied", "UNLABELLED Yoga has been found effective in the treatment of chronic low back pain . We aim ed to evaluate the effectiveness of Iyengar yoga in chronic neck pain by means of a r and omized clinical trial . Seventy-seven patients ( aged 47.9 ± 7.9 , 67 female ) with chronic neck pain who scored > 40 mm on a 100-mm visual analog scale ( VAS ) were r and omized to a 9-week Iyengar yoga program with weekly 90-minute classes ( n = 38 ) or to a self-care/exercise program ( n = 38 ) . Patients were examined at baseline and after 4 and 10 weeks . The primary outcome measure was change of mean pain at rest ( VAS ) from baseline to week 10 . Secondary outcomes included pain at motion , functional disability , quality of life ( QOL ) , and psychological outcomes . Twelve patients in the yoga group and 11 patients in the self-care/exercise group were lost to follow-up , with higher study nonadherence in the self-care group ( 5 versus 10 patients ) . Mean pain at rest was reduced from 44.3 ± 20.1 to 13.0 ± 11.6 at week 10 by yoga and from 41.9 ± 21.9 to 34.4 ± 21.1 by self-care/exercise ( group difference : -20.1 , 95 % confidence interval : -30.0 , -10.1 ; P was reduced from 53.4 ± 18.5 to 22.4 ± 18.7 at week 10 by yoga and from 49.4 ± 22.8 to 39.9 ± 21.5 by self-care/exercise ( group difference : -18.7 , 95 % confidence interval : -29.3 , -8.1 ; P . Significant treatment effects of yoga were also found for pain-related apprehension , disability , QOL , and psychological outcomes . Sensitivity analyses suggested minimal influence of dropout rates . Both programs were well tolerated . In this preliminary trial , yoga appears to be an effective treatment in chronic neck pain with possible additional effects on psychological well-being and QOL . The effectiveness of yoga in chronic neck pain should be further tested by comparative effectiveness studies with longer observation periods . PERSPECTIVE This article presents the results of a r and omized controlled trial on the clinical effects of a 9-week yoga program or self-care exercise in patients with chronic neck pain . Yoga led to superior pain relief and functional improvements and might be a useful treatment option for chronic neck pain", "Objectives : Chronic neck pain is a significant public health problem with only very few evidence -based treatment options . There is growing evidence for the effectiveness of yoga for relieving musculoskeletal disorders . The aim of this study was to evaluate the effect of Iyengar yoga compared with exercise on chronic nonspecific neck pain . Methods : Patients were r and omly assigned to either yoga or exercise . The yoga group attended a 9-week yoga course and the exercise group received a self-care manual on home-based exercises for neck pain relief . The main outcome measure was the present neck pain intensity ( 100 mm visual analog scale ) . Secondary outcome measures included functional disability ( Neck Disability Index ) , pain at motion ( visual analog scale ) , health-related quality of life ( Short Form-36 question naire ) , cervical range of motion , proprioceptive acuity , and pressure pain threshold . Results : Fifty-one patients ( mean age 47.8 y ; 82.4 % female ) were r and omized to yoga ( n=25 ) and exercise ( n=26 ) intervention . After the study period , patients in the yoga group reported significantly less neck pain intensity compared with the exercise group [ mean difference : −13.9 mm ( 95 % CI , −26.4 to −1.4 ) , P=0.03 ] . The yoga group reported less disability and better mental quality of life . Range of motion and proprioceptive acuity were improved and the pressure pain threshold was elevated in the yoga group . Discussion : Yoga was more effective in relieving chronic nonspecific neck pain than a home-based exercise program . Yoga reduced neck pain intensity and disability and improved health-related quality of life . Moreover , yoga seems to influence the functional status of neck muscles , as indicated by improvement of physiological measures of neck pain", "Study Design . The effectiveness and efficacy of Iyengar yoga for chronic low back pain ( CLBP ) were assessed with intention-to-treat and per- protocol analysis . Ninety subjects were r and omized to a yoga ( n = 43 ) or control group ( n = 47 ) receiving st and ard medical care . Participants were followed 6 months after completion of the intervention . Objective . This study aim ed to evaluate Iyengar yoga therapy on chronic low back pain . Yoga subjects were hypothesized to report greater reductions in functional disability , pain intensity , depression , and pain medication usage than controls . Summary of Background Data . CLBP is a musculoskeletal disorder with public health and economic impact . Pilot studies of yoga and back pain have reported significant changes in clinical ly important outcomes . Methods . Subjects were recruited through self-referral and health professional referrals according to explicit inclusion /exclusion criteria . Yoga subjects participated in 24 weeks of biweekly yoga classes design ed for CLBP . Outcomes were assessed at 12 ( midway ) , 24 ( immediately after ) , and 48 weeks ( 6-month follow-up ) after the start of the intervention using the Oswestry Disability Question naire , a Visual Analog Scale , the Beck Depression Inventory , and a pain medication-usage question naire . Results . Using intention-to-treat analysis with repeated measures ANOVA ( group × time ) , significantly greater reductions in functional disability and pain intensity were observed in the yoga group when compared to the control group at 24 weeks . A significantly greater proportion of yoga subjects also reported clinical improvements at both 12 and 24 weeks . In addition , depression was significantly lower in yoga subjects . Furthermore , while a reduction in pain medication occurred , this was comparable in both groups . When results were analyzed using per- protocol analysis , improvements were observed for all outcomes in the yoga group , including agreater trend for reduced pain medication usage . Although slightly less than at 24 weeks , the yoga group had statistically significant reductions in functional disability , pain intensity , and depression compared to st and ard medical care 6-months postintervention . Conclusion . Yoga improves functional disability , pain intensity , and depression in adults with CLBP . There was also a clinical ly important trend for the yoga group to reduce their pain medication usage compared to the control group" ]

[ "A prospect i ve , r and omized , multicenter study was conducted on the efficacy and safety of two prophylactic antibiotic regimens in both abdominal and vaginal hysterectomy . Patients received three intravenous doses of clindamycin ( 900 mg ) plus either aztreonam ( 1 g ) or cefotaxime ( 1 g ) ; the doses were given at the induction of anesthesia and 8 and 16 hours later . A total of 170 patients undergoing abdominal hysterectomy and 142 patients undergoing vaginal hysterectomy completed the trial and were evaluated . Following abdominal hysterectomy infections occurred at the operative site in 1.2 % of patients given a regimen including aztreonam and in 4.7 % of those given a regimen including cefotaxime ; the difference between the two groups was not significant . Neither were significant differences observed in the incidence of fever , the incidence of bacteriuria , the need for postoperative antibiotics , or the duration of postoperative hospitalization , although results were slightly better for patients receiving clindamycin plus aztreonam . Following vaginal hysterectomy , slightly but not significantly better results for the same parameters were obtained in the group given clindamycin plus cefotaxime . Diarrhea was the only adverse reaction attributable to antibiotic treatment and occurred more frequently in patients given cefotaxime . It was concluded that the two regimens were similarly effective and safe in preventing infections following hysterectomy", "Abstract .Fram KM . Laparoscopically assisted vaginal hysterectomy versus abdominal hysterectomy in stage I endometrial cancer . The purpose of this study was to evaluate and compare laparoscopic treatment for stage I endometrial cancer with the traditional transabdominal approach . From July 1996 to July 1998 , 61 patients with clinical stage I endometrial cancer were treated at the Gynaecology Oncology Unit at the Royal North Shore of Sydney , Australia . Twenty-nine patients were treated with laparoscopic assisted vaginal hysterectomy ( LAVH ) and bilateral salpingo-oophrectomy ( BSO ) ± laparoscopic pelvic lymphadenectomy ( LPLA ) , while 32 patients were treated with the traditional laparotomy and underwent total abdominal hysterectomy ( TAH ) and BSO ± pelvic lymphadenectomy ( PLA ) . The main outcomes studied were operative time , blood loss , blood transfusion , intraoperative complications , postoperative complications , duration of hospital stay , and number of lymph nodes obtained . In conclusion , laparoscopic treatment of endometrial cancer is safe in the h and s of experienced operators with minimal intraoperative and postoperative complications . This procedure is associated with significantly less blood loss and shorter hospitalization ; however , it is associated with significantly longer operating time . Proper selection of patients for the laparoscopic procedure is the vital step in achieving the major goals of this approach", "OBJECTIVE The purpose of this study was to determine if antibiotic prophylaxis with nitrofurantoin monohydrate macrocrystals ( study drug ) after pelvic organ prolapse and /or urinary incontinence surgery with suprapubic catheterization ( SPC ) decreases urinary tract infection ( uti ) compared with placebo in a r and omized , double-blind , multicenter trial . STUDY DESIGN Six centers participated in this study . After a negative preoperative urine culture , history , surgical and postoperative course , urine culture and symptoms at SPC removal , and at 6 to 8 weeks postoperative , any other UTI and adherence were recorded . To demonstrate a 50 % decrease in the bacteruria rate from 20 % , with 80 % power and alpha of 0.05 , 438 patients were required . Data were evaluated with Student t test and Fisher exact test . RESULTS Of 449 patients enrolled , 211 r and omized to study drug , and 224 r and omized to placebo . No pre- or perioperative differences existed between groups ( all P>.05 ) . Antibiotic prophylaxis decreased positive urine cultures compared with placebo ( 46 % vs 61 % , P=.002 ) , symptomatic UTI at SPC removal ( 7.2 % vs 19.8 % , P=.001 ) , and any other symptomatic UTI 6 to 8 weeks postoperatively ( 18.9 % vs 32.6 % , P=.002 ) . Antibiotic prophylaxis did not decrease symptomatic UTI at the 6- to 8-week postoperative visit ( 1.8 % vs 5.4 % , P=.10 ) . CONCLUSION Antibiotic prophylaxis with nitrofurantoin monohydrate macrocrystals decreases UTI compared with placebo after pelvic organ prolapse and /or urinary incontinence surgery with suprapubic catheterization", "OBJECTIVE To compare the effectiveness of ceftriaxone versus cefazolin for the prevention of febrile morbidity and postoperative infections among patients after abdominal hysterectomy . METHODS In a double-blind , r and omized , controlled trial in Bangkok , Thail and , 320 patients undergoing abdominal hysterectomy between July 2008 and July 2009 were r and omly assigned to receive 1 g of either ceftriaxone or cefazolin intravenously in a single dose before surgery . The participants were evaluated for postoperative fever and infection for up to 4 weeks . χ(2 ) or Fisher exact tests were used for statistical analysis . RESULTS There was no significant difference between the ceftriaxone and cefazolin groups in incidence of febrile morbidity ( 9.4 % versus 11.2 % ) , wound infection ( 3.8 % versus 1.9 % ) , vaginal cuff infection ( 3.8 % versus 1.9 % ) , or urinary tract infection ( 1.9 % versus 1.9 % ) . CONCLUSION There was no difference between the use of single-dose preoperative ceftriaxone and cefazolin in preventing infectious morbidity among patients undergoing hysterectomy", "Two hundred fourteen women having vaginal or abdominal hysterectomy were entered into a prospect i ve , r and omized , blind clinical trial comparing a preoperative intravenous dose of piperacillin to three perioperative intravenous doses of cefoxitin given over an eight-hour period . Interregimen clinical , surgical , and outcome variables of the 207 evaluable subjects were statistically similar , but there were significant interprocedure differences in a variety of categories ; many benefits exist when vaginal hysterectomy is possible . Efficacy of a single dose of piperacillin was similar to that of three cefoxitin doses . Seven women ( 3.4 % ) had major postoperative infection requiring parenteral antimicrobial therapy , two ( 1.9 % ) after vaginal hysterectomy and five ( 4.8 % ) after abdominal hysterectomy . Three of the latter five infections ( 60 % ) occurred after discharge from the hospital . Even with prophylaxis , postoperative anemia was associated with increased frequency of infection at the operative site after both procedures , and diabetes was associated with late infection of the abdominal incision after abdominal hysterectomy", "A r and omized double-blind prospect i ve study on the efficacy of single-dose antibiotic prophylaxis compared cefuroxime versus metronidazole versus the combination of both agents in vaginal hysterectomy . Overall antibiotic prophylaxis was effective in abscess prevention ( one abscess in 68 patients ) . In the metronidazole group a significantly higher grade of morbidity was observed : febrile morbidity 41 % versus 4 % in the two other groups ; bacteriuria 73 % versus 17 % in the cefuroxime group , versus 13 % in the combined group ; urinary tract infection 23 % , versus 0 % in the two other groups ; post-operative prescription of antibiotics 41 % , versus 0 % in the two other groups . Febrile morbidity and bacteriuria correlated positively withEscherichia coli and Proteus spp . These micro-organisms were recovered significantly more often from the vagina of patients in the metronidazole group . Cefuroxime was successful , metronidazole failed in the prevention of minor morbidity . We could not observe any effect from the addition of metronidazole to the cefuroxime prophylaxis", "Antimicrobial prophylaxis is recommended in all clean-contaminated surgery where the critical threshold of number and virulence of the contaminating organisms with respect to host resistance is reached . Obstetric and gynaecological surgery is clean-contaminated and risk of infection due to aerobic and anaerobic bacteria without prophylaxis can be quantified at 30 - 40 % for vaginal hysterectomy , 10 - 35 % for abdominal hysterectomy and 10 - 34 % for caesarean section . To assess the role of two different cephalosporins as short term prophylaxis , we carried out a multicentre r and omised study involving a single 2 g i.v . dose of cefotetan in comparison with two doses of cefazolin ( 2 g i.v . before surgery and after 8 hours ) . Criteria for exclusion were : exposure to antibiotics within 7 days , preoperative infection , hypersensitivity to beta-lactams . Four hundred and sixty patients entered the study , of which 229 received cefotetan and 231 cefazolin . No significant differences in mean age , obesity , preoperative weight loss , diabetes , type of disease , type of surgery ( vaginal or abdominal hysterectomies and caesarean sections ) and number of pregnancies and abortions existed between the two groups of patients . The total rate of infected patients undergoing hysterectomy was 8.6 % ( 13/151 ) in the cefotetan group and 17.4 % ( 29/167 ) in the cefazolin group ( p less than 0.05 ) . This difference was due to cases of symptomatic bacteriuria and antibiotic retreatment , while wound infections were not significantly different ( 2.6 % and 1.8 % respectively ) . Among patients undergoing caesarean section , 9 of 78 ( 11.5 % ) and 7 of 64 ( 10.9 % ) were infected following cefotetan and cefazolin , respectively ( not significant ) . Cefotetan mean tissue concentrations in gynaecological organs were higher than those of cefazolin ( 25.5 - 44.8 vs. 7.4 - 9.5 mg/kg ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "Abstract Numerous studies have been published in recent years about antimicrobial prophylaxis in gynecologic surgery , but the optimal drug and schedule for the different surgical procedures is still a matter of debate . The aim of the present study was to compare two ultra-short term antimicrobial prophylaxis regimens ( amoxicillin-clavulanic acid and cefazolin ) in preventing infections following laparoscopic gynecologic operations . Three hundred sixty women hospitalized for a laparoscopic gynecologic surgery procedure were included in the study between January 1999 , and December 2001 . Patients were r and omly allocated to receive amoxicillin-clavulanic acid ( 2.2 g ) [ Group A ] or cefazolin ( 2 g ) [ Group B ] as a single dose 30 minutes before surgery . Each patient was assessed daily until discharge to evidence febrile status and the presence of infections at the operative site , urinary tract and respiratory tract . In the amoxicillin-clavulanic acid ( Group A ) and cefazolin ( Group B ) groups , overall 164 and 172 patients , respectively , were evaluable for prophylactic efficacy at hospital discharge . Infectious complications were infrequent in both groups with febrile morbidity occurring in only one patient ( 0.6 % ) in the amoxicillin- clavulanic group . No sign of infections at the surgical site , urinary tract and respiratory tract was observed in either group . No death due to sepsis was recorded . It is concluded that ultra-short term prophylaxis with both amoxicillin-clavulanic acid and cefazolin is safe and effective in elective laparoscopic gynecologic surgery", "Although hysterectomy was the most frequently performed major surgical procedure among women of reproductive age during the past decade , few recent studies have been conducted to determine the risk of complications . We examined data from the Collaborative Review of Sterilization , a prospect i ve , multicenter , observational study coordinated by the Centers for Disease Control , to assess the comparative risks of complications among women undergoing hysterectomy by the abdominal and vaginal approaches . Between September , 1978 , and August , 1981 , 1,851 women from nine institutions were included in the study . Women who underwent vaginal hysterectomy experienced significantly fewer complications than women who had undergone abdominal hysterectomy . The difference was probably attributable to the prevalence and efficacy of prophylactic antibiotic use among the former group . Vaginal hysterectomy was associated with more unintended major surgical procedures but less febrile morbidity , bleeding requiring transfusion , hospitalization , and convalescence than abdominal hysterectomy . Vaginal hysterectomy with prophylactic antibiotics should be strongly considered for those women of reproductive age for whom either surgical approach is clinical ly appropriate", "A double-blind , placebo-controlled and r and omized trial involving a total of 295 patients was carried out to define the role of chemoprophylaxis in major gynaecological surgery in our hospital . Perioperative administration of a single dose of ampicillin ( 500 mg ) plus sulbactam ( 500 mg ) ( regimen A ) , or ampicillin ( 500 mg ) plus metronidazole ( 1 g suppository ) ( regimen B ) , gave similar results . After abdominal hysterectomy , the rates of post-operative wound infection and febrile morbidity were significantly reduced from 24 % ( 12/49 ) and 20 % ( 10/49 ) in the placebo group to 3 - 4 % ( A = 2/51 , B = 3/58 ) and 2 % ( A = 1/51 , B = 1/58 ) respectively . After vaginal hysterectomy , pelvic/vaginal infection or febrile morbidity was found in 30 % ( 3/10 ) of patients in the placebo group but none in either treatment group ( A = 10 , B = 8) . After other types of operation , the rates of infectious complications were reduced , but not statistically significantly , from 11 % ( 4/38 ) to 4 % ( A + B 2/71 ) . However , the rates of post-operative urinary tract infection remained similar in the placebo and treatment groups ( 12 - 16 % )", "OBJECTIVE To evaluate whether a short course of prophylactic antibiotics is as efficacious as a longer course in laparoscopically assisted vaginal hysterectomy ( LAVH ) . STUDY DESIGN A total of 156 patients who underwent LAVH were included in the study ; 82 received a long course of combined prophylactic antibiotics , and 74 received a short course , administered for . The subjects were r and omly assigned using a computer-generated schedule . Data regarding re source consumption were collected from the hospital 's electronic data base . Patient characteristics and medical care process data were collected from the patient charts . Student 's t test was used to determine the statistical significance of the differences between continuous variables in the 2 groups of patients . The chi2 test was used to measure the statistical significance of differences between nominal variables in the 2 groups . RESULTS The short course significantly influenced the number of injected vials of antibiotics , the antibiotic fee and the total admission fee . The average total admission fee decreased by 2.3 % ( p = 0.034 ) , and the average antibiotic-fee dropped by 68.4 % ( p average injected vials of cephalothin decreased by 4.3 , and the vials of gentamycin decreased by 3.3 ( p rate of operative site infection and urinary tract infection during hospitalization and within 7 days of discharge , no statistical differences were found between the 2 groups ( p = 0.735 ; p = 0.917 ) . CONCLUSION This pilot study revealed that a short course of prophylactic antibiotics was as efficacious as a longer course in preventing postoperative infection . It was also cost-effective", "The aim of this study was to determine specific pattern of port site microbial colonisation , sensitivity and resistance to different antibiotics of bacteria isolated from port site infection ( PSI ) in low risk patients after elective laparoscopic cholecystectomy in surgical wards at tertiary care hospital of Kashmir . This is a prospect i ve study . The study included 675 consecutive patients of postoperative PSI after elective laparoscopic cholecystectomy for symptomatic cholelithiasis over a period of 12 months . Culture swabs were taken from port sites with signs of PSI and transported to the microbiology laboratory . The positive swab cultures were subjected to antibiotic susceptibility test . The data obtained was analysed by using appropriate statistical analytical tests . The incidence of PSI after elective laparoscopic cholecystectomy is 6·7 % . The commonest organism responsible for PSI is pseudomonas , 19 ( 42·2 % ) cases . Most of the strains of organisms isolated were resistant to commonly used antibiotics in the hospital , pseudomonas was found 100 % resistant to the combination of ampicillin + sulbactum and ceftriaxone and it was sensitive to imipenem , amikacin and vancomycin in 89·47,57 and 52·63 % of cases respectively . Our study will be helpful in choosing effective empirical prophylactic antibiotic therapy in cases of elective laparoscopic cholecystectomy and will have a great impact on morbidity and mortality in them because of PSI", "BACKGROUND Trovafloxacin is a new fourth-generation fluoroquinolone whose pharmacokinetics and in vitro activity suggest that it is well suited for antibiotic prophylaxis in elective hysterectomy . METHODS In a r and omized , double-blind , multicenter study , parallel groups of women 18 years of age or older received either 200 mg trovafloxacin by mouth and intravenous ( i.v . ) placebo or 2 g cefoxitin by i.v . infusion and placebo by mouth before elective vaginal or abdominal hysterectomy for nonmalignant disease . RESULTS In the 103 and 97 patients in the trovafloxacin and cefoxitin groups , respectively , who were evaluable for efficacy , the prophylactic success rates at hospital discharge ( 96 % in both groups ) and 30 + /- 6 days after hysterectomy ( 88 % and 91 % in the trovafloxacin and cefoxitin groups , respectively ) were statistically equivalent . Both antibiotics were well tolerated . CONCLUSION A single oral 200 mg dose of trovafloxacin is as effective and safe as a st and ard cefoxitin parenteral regimen in the prevention of primary bacterial infection after elective vaginal or abdominal hysterectomy for nonmalignant disease", "METHODS In a r and omized double-blind study , 134 patients were given 500 mg metronidazole as an intravenous infusion immediately before operation for abdominal total hysterectomy and again 8 hours later and 124 patients received placebo . RESULTS There was more wound infection , postoperative hospitalization was longer and the sedimentation rate on the sixth postoperative day was significantly higher in the placebo group . There was no difference in postoperative temperature . Postoperative wound infections occurred in 12 % in the placebo group and 6 % in the metronidazole group . Eight percent in the total material had urinary tract infections , the diagnosis was based on urine cultures . CONCLUSIONS Prophylaxis with intravenous infusion of metronidazole is recommended in total hysterectomies", "The purpose of this prospect i ve , r and omized , double-blind clinical trial was to compare the efficacy of 1-g doses of intravenous cefazolin with that of 1-g doses of intravenous cefotetan in preventing major operative site infections after elective abdominal hysterectomy . A major operative site infection requiring parenteral antimicrobial therapy developed in 46 ( 9 % ) of 511 evaluable women : 30 ( 11.6 % ) of 258 women given cefazolin prophylaxis and 16 ( 6.3 % ) of 253 women given cefotetan prophylaxis ( relative risk , 1.84 ; 95 % confidence interval , 1.03 to 3.29 ; P cefazolin prophylaxis had a postoperative pelvic abscess ; two of these women required additional surgical procedures , compared with two ( 0.8 % ) of 253 women given cefotetan prophylaxis who had an abscess but did not require surgery ( relative risk , 4.9 ; 95 % confidence interval , 1.09 to 22.16 ; P = .04 ) . A greater number of infections and more serious infections occurred following cefazolin prophylaxis ; this treatment result ed in 234 additional hospital days for administration of parenteral antimicrobial therapy", "Background . To compare amoxicillin‐clavulanic acid with cefazolin as ultra‐short‐term prophylaxis in laparotomic gynecologic surgery", "Using a r and om table of numbers , 100 premenopausal women undergoing vaginal hysterectomy were assigned to a short-term or long-term antibiotic prophylaxis regimen . The short-term regimen patients received a total of 3 Gm . of cephaloridine in divided doses on the day of operation , while the long-term regimen patients also received oral cephalexin postoperatively . The preoperative profiles of the two study groups were similar , and the postoperative results were not significantly different . A quantitative evaluation of aerobic and anaerobic bacteria recovered from the surface of the vagina was done , and cephaloridine content of vaginal washings , serum , and vaginal tissue was determined . This information was utilized to suggest guidelines for antibiotic prophylaxis in gynecology", "used as antibiotic prophylaxis in abdominal and gynecologic surgery being effective against most bacteria , including anaerobes w1,2x . Different reported protocol s of antibiotic prophylaxis tend to reduce doses and it is now usual to give a single administration before the start of the surgery w3x . To evaluate this concept , we compared the efficacy of a single preoperative dose of amoxycillinyclavulanate ( AyC ) with a two-dose administration , one 30 min before the operation and the other 8 h later . The study included 358 women admitted to our Department for surgery . Exclusion criteria were : allergy to the study drug , serious renal and yor hepatic diseases , antibiotic or corticosteroid treatment in the 14 days before surgery . Subjects were assigned r and omly to one of the two treatment groups : 190 patients received 2.2 g of AyC i.v . before surgery ( group 1 ) , while 168 patients received a second dose after 8 h ( group 2 ) . St and ard preoperative and postoperative assessment was carried out in all patients . All operations were performed by the same gynecologists . The subjects were divided according to : type of surgery", "The efficacy of single-dose prophylaxis with intravenous cefuroxime 1,500 mg plus 500 mg metronidazole in vaginal or abdominal hysterectomies was investigated in a r and omized , double-blind , placebo-controlled study , involving 396 evaluable patients . A significant reduction of the number in urinary tract infections was observed in the groups undergoing abdominal hysterectomy or vaginal hysterectomy with vaginal repair . The incidence of wound infections and the duration of hospitalization were significantly reduced in patients undergoing vaginal hysterectomy with or without vaginal repair . Body temperature normalized faster in all three groups receiving peri-operative antibiotic prophylaxis . It is concluded that a single injection of antimicrobial prophylaxis is sufficient and useful in both abdominal and vaginal hysterectomies", "One hundred patients undergoing vaginal hysterectomy were enrolled in a r and omized double-blind comparative antibiotic prophylaxis study . Forty-six patients received mezlocillin and 54 patients received cefoxitin . No significant difference was found among patients who developed febrile morbidity . Failure rate for mezlocillin was 17 per cent and for cefoxitin , 15 per cent . There was an increase in colonization of Streptococcus faecalis and Enterobacter species in patients receiving three doses of cefoxitin prophylaxis", "To assess the efficacy of a single dose of ampicillin or cefazolin in preventing fever and infection after elective abdominal hysterectomy , we conducted a multicentre , r and omized , double-blind , controlled trial at Srinagarind Hospital , Faculty of Medicine , Khon Kaen University and Khon Kaen Regional Hospital . Three hundred and thirty patients scheduled for elective abdominal hysterectomy were r and omly allocated into either placebo , ampicillin or cefazolin groups . Patients received sterile water ( 3 mL ) or ampicillin ( 1 g ) or cefazolin ( 1 g ) intravenously according to r and om assignment 30 min before the operation . After the operation , all patients were assessed by blinded independent evaluators until discharged from the hospitals . Our main outcome measures were postoperative fever and infectious morbidity . We found that 321 patients ( 97.3 % of recruited patients ) were available for data analysis , 108 in placebo , 106 in ampicillin and 107 in cefazolin group . Febrile morbidity occurred in 13/108 ( 12.0 % ) , 14/106 ( 13.2 % ) and 12/107 ( 11.2 % ) of patients in the placebo , ampicillin and cefazolin groups , respectively . There was no statistically significant difference in febrile morbidity between the three groups . Infectious morbidity was found in 29/108 ( 26.9 % ) , 24/106 ( 22.6 % ) and 11/107 ( 10.3 % ) of patients in the placebo , ampicillin and cefazolin groups , respectively . There was a statistically significant difference between the placebo and cefazolin groups ( P = 0.002 ) . Between the placebo and ampicillin groups , the result was not significantly different ( P = 0.476 ) . There was a statistically significant difference between the cefazolin and ampicillin groups ( P = 0.015 ) . The common causes of infectious morbidity were urinary tract infection , vaginal cuff infection and surgical wound infection . We concluded that antibiotic prophylaxis by cefazolin should be recommended for elective total abdominal hysterectomy", "Twenty-one women who underwent radical abdominal hysterectomy and pelvic lymphadenectomy were enrolled in a prospect i ve , comparative , r and omized , placebo-controlled clinical trial of antimicrobial prophylaxis . Preoperative endocervical flora was identified and was similar in pre- and postmenopausal private and clinic service women ; 46 % of the 119 preoperative isolates produced beta-lactamase enzyme . Women were given three doses of either placebo or cefoperazone plus sulbactam , an irreversible beta-lactamase enzyme inhibitor . Three women ( 27 % ) given placebo developed abdominal incision infections ; one women given placebo also developed a pelvic infection . None given antibiotic developed operative site infection , but one women developed a drain site infection . A major operative site infection rate of 27 % observed with placebo is high enough to warrant prophylaxis . Although antimicrobial prophylaxis at radical hysterectomy and pelvic lymphadenectomy eradicted operative site infection in our patient population s , a literature review indicates that individual determination of a requirement for prophylaxis is necessary", "The value of preoperative prophylactic parenteral treatment with ceftriaxone at elective abdominal hysterectomy was investigated in a prospect i ve , r and omized , double-blind study , in which 157 women participated , 77 in the antibiotic group and 80 in the control group . Increased febrile morbidity and a significant preponderance of women with urinary tract infections were observed in the untreated group , whereas there was no significant difference between the two groups regarding wound infections or infiltration at the top of the vagina . We find no indication for routine prophylactic use of antibiotics at elective abdominal hysterectomy", "Summary A prospect i ve r and omised multicentre study was design ed to assess the efficacy of 2 different cephalosporins as short term prophylactic treatment in obstetric and gynaecological surgery . A single dose of cefotaxime ( 2 g IV before surgery ) was compared with 2 doses of cephazolin ( 2 g IV before surgery and after 8 hours ) . Patients exposed to antibacterial drugs within 7 days , who had preoperative infections , or with known β-lactam hypersensitivity were excluded . 612 patients entered the study , of whom 552 were evaluable . 276 were given cephazolin ( group A ) and 276 cefotaxime ( group B ) . Groups A and B were similar for mean age , obesity , diabetes , types of diseases and obstetric history . No significant differences were observed in type of surgery ( vaginal hysterectomy , abdominal hysterectomy , myomectomy and caesarean section ) between the 2 groups . The mean duration of surgery was 89 and 85 minutes in group A and B , respectively . 25 patients ( 9.1 % ) in group A and 20 ( 7.2 % ) in group B developed wound infections ( not statistically significantly different ) . The percentages of patients with infections other than surgical infections were similar ( i.e. 13.0 and 11.2 for the cefotaxime and the cephazolin groups , respectively ) . These preliminary data show that a single 2 g IV dose of cefotaxime and two 2 g IV doses of cephazolin have equal antimicrobial prophylactic activity in obstetric and gynaecological surgery", "We report the results of a r and omized , double-blind comparison of short-term versus long-term cefoxitin prophylaxis against infections after radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy . Of 113 evaluable patients , 54 ( 47.8 % ) received short-term ( three doses ) and 59 ( 52.2 % ) long-term ( 12 doses ) prophylaxis with intravenous cefoxitin ( 2 g per dose ) . No significant differences demographics , preoperative risk factors , or clinical course were detected between the two groups ; nor did we detect significant differences in the incidence of surgical-siterelated infections ( 7.4 versus 5.1 % , respectively , P=.61 ) , postoperative urinary tract infection , or other febrile morbidity . We conclude that short-term and long-term cefoxitin prophylaxis are equally effective for the prevention of postoperative surgical-site-related infections after radical hysterectomy" ]

[ "This article reports the psychometric properties of two scales for rating positive and negative schizophrenic signs and symptoms . These Positive and Negative Syndrome Scales consist of items selected from the Children 's Psychiatric Rating Scale ( CPRS ) , which contains items covering a wide range of childhood psychopathology . CPRS rating data were analyzed for 19 schizophrenic children , 16 males and 3 females , mean age 8.9 years ( range 5.5 - 11.7 ) , evaluated in a double-blind , placebo-controlled crossover study of haloperidol . We describe the item composition and coherence of each scale , the interrater reliabilities of clinicians using the scales , and the sensitivity of the scales for resolving treatment response . Schizophrenic children showed both positive and negative signs and symptoms , and both improved with neuroleptic treatment", "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", "Despite the proven efficacy of neuroleptic drugs in the acute and maintenance pharmacotherapy of schizophrenia , practical methods for identifying patients who require neuroleptic treatment to prevent relapse are lacking . This study evaluated the use of a methylpheni date challenge test to predict the outcome in 34 stable out patients with schizophrenia receiving neuroleptic treatment . Patients received two infusions , one of methylpheni date and one of placebo , in r and omized order one week apart while receiving neuroleptic treatment and again three weeks after drug withdrawal . Behavioral , cardiovascular , and neurologic responses were evaluated before and after infusion under double-blind conditions . Patients were then followed up without medication for 52 weeks or until symptom recurrence . The results indicate that specific measures , including behavioral response to methylpheni date , presence of tardive dyskinesia , and , under specific pharmacologic conditions , tardive dyskinesia , blink-rate , and pulse-rate responses to methylpheni date , are associated with time and propensity to relapse following neuroleptic withdrawal . These measures may be potentially useful in the identification of c and i date s for neuroleptic withdrawal and /or dosage-reduction treatment strategies", "A modified neural network based on adaptive resonance theory ( ART ) was trained with the records of 211 psychiatric in patients ( 74 schizophrenic , 50 unipolar depressed , 34 bipolar depressed , 20 bipolar manic , 33 other ) who improved by at least 40 points of the GAFS during 8 weeks of treatment . Thereafter , a comparison was made between the clinical response of another 26 schizophrenic patients and 28 unipolar depressed in patients , to treatment suggestd by the trained ART ( N=21 ) and by the consensus of two senior psychiatrists ( N=33 ) . The patients were allocated blindly and r and omly to the two treatment groups . The BPRS ( for the schizophrenic patients ) or the HDRS ( for the unipolar depressed patients ) was completed weekly for 5 weeks . Results showed no difference between decisions regarding treatment by the ART network and by the experts . Length of hospital stay was also similar . All ART suggestions included supportive psychotherapy . High potency antipsychotics were suggested for 7 schizophrenic in patients , clozapine for one and the addition of community therapy for another . Depressed patients got a variety of treatment suggestions . No contraindicated treatment was suggested by ART ; however , two incomplete treatment suggestions were dropped from the study . In conclusion , in a prospect i ve study ART was successful in learning treatment strategies and performed under supervision similar to experts", "A controlled crossover study of lithium and chlorpromazine involving 10 severely disturbed children , 3 to 6 years of age , of which 6 were schizophrenic and 1 autistic , is reported in detail . Patients were matched for motor activity ( hyper- and hypoactivity ) and prognosis . More symptoms diminished on chlorpromazine than on lithium . However , improvements were only slight on both , except in one child whose autoaggressiveness and explosiveness practically ceased on lithium ( nonblind evaluations ) . Blind ratings indicated no statistically significant difference between the two drugs as well as absence of statistically significant change from baseline to treatment with either . Lithium diminished the severity of individual symptoms , though not statistically significant , such as explosiveness , hyperactivity , aggressiveness , and psychotic speech . Its effect in adult schizophrenia is compared to responses of schizophrenic children . Also discussed is the relationship of EEG to clinical improvement and toxicity , and effect of lithium on hyperactivity and aggressiveness . It is suggested that lithium may prove of some value in treatment of severe psychiatric disorders in childhood involving aggressiveness , explosive affect and hyperactivity" ]

[ "Background — Data regarding the long-term efficacy of atrial fibrillation ( AF ) ablation are still lacking . Methods and Results —Two hundred four consecutive patients symptomatic for paroxysmal or persistent/permanent AF were r and omly assigned to 2 different ablation schemes : pulmonary vein isolation ( PVI ) and PVI plus left linear lesions ( LL ) . Primary end point was to assess the maintenance of sinus rhythm ( SR ) after procedures 1 and 2 in the absence of antiarrhythmic drugs in a long-term follow-up of at least 3 years . Paroxysmal AF — With a single procedure at 12-month follow-up , 46 % of patients treated with PVI maintained SR , whereas at 3-year follow-up , 29 % were in SR ; using the “ PVI plus LL ” at the 12-month follow-up , 57 % of patients were in SR , whereas at the 3-year follow-up , 53 % remained in SR . After a second procedure , the long-term overall success rate without antiarrhythmic drugs was 62 % with PVI and 85 % with PVI plus LL . Persistent/Permanent AF — With a single procedure at the 12-month follow-up , 27 % of patients treated with PVI were in SR , whereas at the 3-year follow-up , 19 % maintained SR ; using the PVI plus LL with a single procedure at the 12-month follow-up 45 % of patients were in SR , whereas at the 3-year follow-up , 41 % remained in SR . After a second procedure , the long-term overall success rate without antiarrhythmic drugs was 39 % with PVI and 75 % with PVI plus LL . Conclusions —A long-term follow-up of AF ablation shows that short-term results can not be considered permanent because AF recurrences are still present after the first year especially in patients who have had “ PVI ” strategy . PVI isolation plus LL is superior to the PVI strategy in maintaining SR without antiarrhythmic drugs after procedures 1 and 2 both in paroxysmal and persistent AF", "Background — Information on comparative outcome between radiofrequency catheter ablation ( RFA ) and antiarrhythmic drugs ( AADs ) > 1 year after r and omization is important for clinical decision-making . Methods and Results — A total of 198 patients ( age , 56±10 years ) with paroxysmal atrial fibrillation were r and omly assigned to RFA ( 99 patients ) or to AADs ( 99 patients ) . We evaluated efficacy of RFA or AADs in a comparable 48-month follow-up period according to intention-to-treat analysis . Cardiac rhythm was assessed with daily transtelephonic transmissions . Quality of life was also analyzed . At 4 years , among the 99 patients first assigned to RFA , the procedure was repeated because of recurrent atrial fibrillation/atrial tachycardia in 27 patients ( 27.3 % ) . Among the 99 patients r and omly assigned to AADs , 87 ( 87.9 % ) crossed over to undergo RFA and 4 years after r and om assignment only 12 ( 12.1 % ) were in sinus rhythm with AAD alone without ablation . Despite the high level of crossovers , at 4 years the intention-to-treat analysis showed that 72.7 % of patients in the ablation arm and 56.5 % of those initially r and omly assigned to AADs were free of recurrent atrial fibrillation/atrial tachycardia ( P=0.017 ) . During the follow-up , 19.2 % of AAD patients progressed to persistent atrial fibrillation before switching to RFA . RFA significantly improved quality of life ( P poorer quality of life . Except for new left atrial tachycardia , there were no serious complications caused by RFA . Conclusions — With follow-up extended to 4 years after r and omly assigned , ablation remains superior to antiarrhythmic drug in these patients with paroxysmal atrial fibrillation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00340314", "OBJECTIVES The purpose of this study was to investigate long-term outcomes of freedom from atrial fibrillation ( AF ) after pulmonary vein ( PV ) isolation using cryoballoon ablation with balloon-size selection based on individual PV diameters . BACKGROUND Data are lacking on long-term outcomes from cryoablation and on the most effective balloon size . METHODS This was a prospect i ve observational study involving 605 consecutively enrolled patients with symptomatic paroxysmal AF ( n = 579 ) or persistent AF . Cryoballoon size was based on magnetic resonance imaging and /or conventional angiograms . Patients were followed up every 3 months during the first year after discharge and every 6 months in the second year . After 24 months , follow-up was on an outpatient basis with documented AF episodes recorded . RESULTS The PV isolation was achieved without touch-up in 91.1 % of patients , using the smaller balloon in 26.7 % , the larger balloon in 25.6 % , and both balloons in 47.7 % of patients . Follow-up data for > 12 months ( median 30 months ; interquartile range 18 to 48 months ) were available for 451 patients , 278 ( 61.6 % ) of whom were free of AF recurrence with no need for repeat procedures after the 3-month blanking period . Rates of freedom from AF after 1 , 2 , and 3 repeat procedures ( using cryoballoon or radiofrequency ablation with similar success rates ) were 74.9 % , 76.2 % , and 76.9 % , respectively . Use of the smaller balloons or both balloons produced the highest rates of long-term freedom from AF . Phrenic nerve palsy occurred in 12 patients ( 2 % ) , resolving within 3 to 9 months . CONCLUSIONS Rates of long-term freedom from AF after cryoballoon ablation are similar to those reported for radiofrequency ablation . A choice between balloons may improve outcomes", "AIMS The Atrial Fibrillation Ablation Pilot Study is a prospect i ve registry design ed to describe the clinical epidemiology of patients undergoing an atrial fibrillation ( AFib ) ablation , and the diagnostic/therapeutic processes applied across Europe . The aims of the 1-year follow-up were to analyse how centres assess in routine clinical practice the success of the procedure and to evaluate the success rate and long-term safety/complications . METHODS AND RESULTS Seventy-two centres in 10 European countries were asked to enrol 20 consecutive patients undergoing a first AFib ablation procedure . A web-based case report form captured information on pre-procedural , procedural , and 1-year follow-up data . Between October 2010 and May 2011 , 1410 patients were included and 1391 underwent an AFib ablation ( 98.7 % ) . A total of 1300 patients ( 93.5 % ) completed a follow-up control 367 ± 42 days after the procedure . Arrhythmia documentation was done by an electrocardiogram in 76 % , Holter-monitoring in 52 % , transtelephonic monitoring in 8 % , and /or implanted systems in 4.5 % . Over 50 % became asymptomatic . Twenty-one per cent were re-admitted due to post-ablation arrhythmias . Success without antiarrhythmic drugs was achieved in 40.7 % of patients ( 43.7 % in paroxysmal AF ; 30.2 % in persistent AF ; 36.7 % in long-lasting persistent AF ) . A second ablation was required in 18 % of the cases and 43.4 % were under antiarrhythmic treatment . Thirty-three patients ( 2.5 % ) suffered an adverse event , 272 ( 21 % ) experienced a left atrial tachycardia , and 4 patients died ( 1 haemorrhagic stroke , 1 ventricular fibrillation in a patient with ischaemic heart disease , 1 cancer , and 1 of unknown cause ) . CONCLUSION The AFib Ablation Pilot Study provided crucial information on the epidemiology , management , and outcomes of catheter ablation of AFib in a real-world setting . The methods used to assess the success of the procedure appeared at least suboptimal . Even in this context , the 12-month success rate appears to be somewhat lower to the one reported clinical trials", "AIMS Pioglitazone , one of the peroxisome proliferator-activated receptor-gamma activators , possesses anti-inflammatory and antioxidant properties . In the present study , we sought to identify the impact of pioglitazone on the outcome of catheter ablation for paroxysmal atrial fibrillation ( PAF ) . METHODS AND RESULTS We conducted a prospect i ve observational cohort study of 150 consecutive patients undergoing catheter ablation of drug-refractory PAF . All patients had a history of type 2 diabetes mellitus ( T2DM ) and were divided based on whether they received pioglitazone before ablation or not . After grouping , 51 patients treated with pioglitazone and 99 control subjects were followed up at least 15 months after ablation . After a single ablation , sinus rhythm was maintained in 44 patients ( 86.3 % ) of the pioglitazone group vs. 70 patients ( 70.7 % ) of the control group ( P = 0.034 ) without antiarrhythmic drug during a mean follow-up of 22.9 ± 5.1 months . The second ablation was performed in 5 patients ( 9.8 % ) from the pioglitazone group and in 24 patients ( 24.2 % ) from the control group ( P = 0.034 ) . Multivariate logistic analysis showed left atrium diameter was associated with a high risk of atrial tachyarrhythmias recurrence , and treatment with renin-angiotensin system inhibitor as well as pioglitazone was associated with a reduced atrial tachyarrhythmias recurrence rate . CONCLUSION Pioglitazone improved the preservation of sinus rhythm and reduced the reablation rate in patients with PAF and T2DM after catheter ablation", "OBJECTIVES This study was design ed to investigate the potential of circumferential pulmonary vein ( PV ) ablation for atrial fibrillation ( AF ) to maintain sinus rhythm ( SR ) over time , thus reducing mortality and morbidity while enhancing quality of life ( QoL ) . BACKGROUND Circumferential PV ablation is safe and effective , but the long-term outcomes and its impact on QoL have not been assessed or compared with those for medical therapy . METHODS We examined the clinical course of 1,171 consecutive patients with symptomatic AF who were referred to us between January 1998 and March 2001 . The 589 ablated patients were compared with the 582 who received antiarrhythmic medications for SR control . The QoL of 109 ablated and 102 medically treated patients was measured with the SF-36 survey . RESULTS Median follow-up was 900 days ( range 161 to 1,508 days ) . Kaplan-Meier analysis showed observed survival for ablated patients was longer than among patients treated medically ( p all-cause mortality , of 0.45 ( 95 % CI , 0.31 to 0.64 ; p morbidities mainly due to heart failure and ischemic cerebrovascular events , and of 0.30 ( 95 % CI , 0.24 to 0.37 ; p AF recurrence . Ablated patients ' QoL , different from patients treated medically , reached normative levels at six months and remained unchanged at one year . CONCLUSIONS Pulmonary vein ablation improves mortality , morbidity , and QoL as compared with medical therapy . Our findings pave the way for r and omized trials to prospect a wider application of ablation therapy for AF", "INTRODUCTION Atrial fibrillation ( AF ) and diabetes mellitus type 2 ( DM2 ) often coexist ; however , a small number of patients with DM2 undergoing catheter ablation ( CA ) of AF have been included in previous studies . The aim of this study was to evaluate safety and efficacy of ablation therapy in DM2 patients with drug refractory AF . METHODS AND RESULTS From January 2005 to September 2006 , 70 patients with a diagnosis of DM2 and paroxysmal ( n = 29 ) or persistent ( n = 41 ) AF were r and omized to receive either pulmonary vein isolation or a new antiarrhythmic drug treatment ( ADT ) with a 1-year follow-up . The primary endpoint was the time to first AF recurrence . By Kaplan-Meier analysis , at the end of follow-up , 42.9 % of patients in the ADT group and 80 % of patients who received a single ablation procedure and were without medications were free of AF ( P = 0.001 ) . In the ablation group , a significant improvement in quality -of-life ( QoL ) scores as compared with ADT group was observed . Six patients in the ADT group ( 17.1 % ) developed significant adverse drug effects . Hospitalization rate during follow-up was higher in the ADT group ( P = 0.01 ) . The only complication attributable to ablation was one significant access-site hematoma . CONCLUSION In patients with DM2 , CA of AF provides significant clinical benefits over the ADT and appears to be a reasonable approach regarding feasibility , effectiveness , and low procedural risk", "AIMS The Atrial Fibrillation Ablation Pilot Study is a prospect i ve , multinational registry conducted by the European Heart Rhythm Association of the European Society of Cardiology that has been design ed to describe the clinical epidemiology of patients undergoing an atrial fibrillation ( AFib ) ablation procedure , and the diagnostic/therapeutic processes applied in these patients across Europe . We present the results of the short-term ( in-hospital ) analysis . METHODS AND RESULTS A total of 72 centres in 10 European countries were asked to enrol 20 consecutive patients scheduled for a first AFib ablation procedure . Between October 2010 and May 2011 , 1410 patients were included , of which 1391 underwent an AFib ablation ( 98.7 % ) . The median age was 60 years [ inter-quartile range ( IQR ) 52 - 66 ] , and 28 % were females . Two-thirds presented paroxysmal AFib and 38 % lone AFib . Symptoms were present in 86 % . The indications for ablation were mostly symptomatic AFib , but in over a third of patients there was also a desire for a drug-free lifestyle and the maintenance of sinus rhythm . Pulmonary vein isolation was attempted in 98.4 % of patients , the roof line in 21.3 % and the mitral isthmus line in 12.8 % . Complex-fractionated atrial electrograms were targeted in 17.9 % and the ganglionated plexi in 3.3 % . Complications occurred in 7.7 % , of which 1.7 % was major ( i.e. cardiac perforation , myocardial infraction , endocarditis , cardiac arrest , stroke , hemothorax , pneumothorax , and sepsis ) . The median duration of hospitalization was 3 days ( IQR 2 - 4 ) . At discharge , 91.4 % of patients were in sinus rhythm , 88.3 % of patients were given vitamin K antagonists , and 67 % antiarrhythmic medication . There was one death after the ablation procedure . CONCLUSION The AFib Ablation Pilot Study provides crucial information on AF ablation in clinical practice across Europe . These data are relevant for further improvement of the management strategies of patients suffering from atrial fibrillation", "INTRODUCTION Atrial fibrillation ( AF ) adversely impacts mortality , stroke , heart failure , and dementia . AF ablation eliminates AF in most patients . We evaluated the long-term impact of AF ablation on mortality , heart failure ( HF ) , stroke , and dementia in a large system-wide patient population . METHODS A total of 4,212 consecutive patients who underwent AF ablation were compared ( 1:4 ) to 16,848 age/gender matched controls with AF ( no ablation ) and 16,848 age/gender matched controls without AF . Patients were enrolled from the large ongoing prospect i ve Intermountain AF study and were followed for at least 3 years . RESULTS Of the 37,908 patients , mean age 65.0 ± 13 years , 5,667 ( 14.9 % ) died , 1,296 ( 3.4 % ) had a stroke , and 1,096 ( 2.9 % ) were hospitalized for HF over > 3 years of follow-up . AF ablation patients were less likely to have diabetes , but were more likely to have hypertension , HF , and significant valvular heart disease . AF ablation patients had a lower risk of death and stroke in comparison to AF patients without ablation . Alzheimer 's dementia occurred in 0.2 % of the AF ablation patients compared to 0.9 % of the AF no ablation patients and 0.5 % of the no AF patients ( P Other forms of dementia were also reduced significantly in those treated with ablation . Compared to patients with no AF , AF ablation patients had similar long-term rates of death , dementia , and stroke . CONCLUSIONS AF ablation patients have a significantly lower risk of death , stroke , and dementia in comparison to AF patients without ablation . AF ablation may eliminate the increased risk of death and stroke associated with AF", "AIMS Clinical benefit from ablation for long-st and ing persistent atrial fibrillation has remained unknown . We hypothesized that successful ablation of long-st and ing persistent atrial fibrillation would improve haemodynamics , functional status , and quality of life . METHODS AND RESULTS A total of 160 patients ( aged 59 ± 9 years , 23 % females ) undergoing ablation of long-st and ing ( median of 28 months ) persistent atrial were enrolled in this prospect i ve study . Morphological and functional echocardiographic parameters , N-terminal prohormone of brain natriuretic peptide ( NT-proBNP ) , maximum oxygen consumption during exercise test ( VO2 max ) , and quality of life were assessed at baseline and 1 year after the ablation . At the 1-year follow-up visit , 81 % patients were examined in sinus rhythm ( after repeat ablation in 38 % patients ) . Left atrial appendage outflow velocity increased from 44 ± 20 to 58 ± 23 cm/s , left ventricular ejection fraction from 54 ± 9 to 59 ± 5 % , and VO2 max from 20.4 ± 6.4 to 23.7 ± 8.1 mL/kg/min ; NT-proBNP decreased from median 897 ( interquartile range 603 - 1424 ) to 230 ( interquartile range 120 - 420 ) pg/mL ( all P presence of sinus rhythm . Quality of life ( range 0 - 100 ) increased significantly ( EQ-5D index : from 68.8 ± 12.5 to 75.4 ± 14.4 ; EQ-VAS score : from 62.8 ± 13.2 to 70.6 ± 13.8 ; both P CONCLUSION Ablation of long-st and ing persistent atrial fibrillation was associated with significant recovery of haemodynamics and exercise capacity that projected onto the long-term improvement in quality of life ", "Background and objective Little is known about the outcome of catheter ablation of atrial fibrillation ( AF ) in patients with diabetes mellitus ( DM ) . We investigated the safety and efficacy of catheter ablation of AF in patients with DM . Material s and methods Thirty one patients with DM from a group of 263 consecutive patients undergoing a first-time catheter ablation of AF procedure were enrolled in a prospect i ve study . The ablation protocol ( guided by CARTO system ) consisted in two continuous circular lesions around ipsilateral pulmonary veins . Results The following clinical characteristics differed between DM and no-DM patients : age ( 62.0 ± 10.8 vs. 56.1 ± 10.6 years , P = 0.004 ) , longer AF history ( 9.6 ± 9.3 vs. 6.7 ± 6.3 years , P = 0.024 ) , significantly larger left atrium size ( 41.1 ± 7.8 vs. 38.3 ± 5.8 mm , P = 0.021 ) , hypertension ( 58.1 vs. 35.8 % , P = 0.018 ) and structural heart disease ( 67.7 vs. 43.5 % , P = 0.011 ) . Despite a similar AF recurrence rate in DM and no-DM patients ( 32.3 vs. 22.4 % , P = 0.240 ) , the ablation procedure was complicated in 28 patients ( 11 hematomas , three cardiac tamponades and three strokes ) and the incidence of complications was significantly higher in DM than in no-DM patients ( 29.0 vs. 8.2 % , respectively , P = 0.002 ) . Multivariate analysis showed that DM was an independent risk factor for complications occurrence ( odd ratio 5.936 , 95 % confidence interval 2.059 to 17.112 , P = 0.001 ) . Conclusions First catheter ablation of AF procedure in DM patients was equally efficacious than in no-DM patients . However , DM patients had a higher incidence of complications , mostly thrombotic or hemorrhagic", "AIMS The aim of this study was to investigate serious clinical outcomes associated with atrial fibrillation ( AF ) and the effects of routine blood pressure lowering on such outcomes in the presence or absence of AF , among individuals with type 2 diabetes . METHODS AND RESULTS About 11 140 patients with type 2 diabetes ( 7.6 % of whom had AF at baseline ) were r and omized to a fixed combination of perindopril and indapamide or placebo in the Action in Diabetes and Vascular Disease : preterAx and diamicroN-MR Controlled Evaluation ( ADVANCE ) study . We compared total mortality and cardiovascular disease outcomes and effects of r and omized treatment for 4.3 years on such outcomes between patients with and without AF at baseline . After multiple adjustments , AF was associated with a 61 % ( 95 % confidence interval 31 - 96 , P of all-cause mortality and comparable higher risks of cardiovascular death , stroke , and heart failure ( all P perindopril and indapamide produced similar relative , but greater absolute , risk reductions for all-cause and cardiovascular mortalities in patients with AF , compared with those without AF . The number of patients needed to be treated with perindopril-indapamide for 5 years to prevent one cardiovascular death was 42 for patients with AF and 120 for patients without AF at baseline . CONCLUSION Atrial fibrillation is relatively common in type 2 diabetes and is associated with substantially increased risks of death and cardiovascular events in patients with type 2 diabetes . This arrhythmia identifies individuals who are likely to obtain greater absolute benefits from blood pressure-lowering treatment . Atrial fibrillation in diabetic patients should be regarded as a marker of particularly adverse outcome and prompt aggressive management of all risk factors" ]

[ "OBJECTIVE Blood pressure control can reduce the risk of coronary heart disease ( CHD ) among diabetic patients ; however , it is not known whether the lowest risk of CHD is among diabetic patients with the lowest blood pressure level . RESEARCH DESIGN AND METHODS We performed a prospect i ve cohort study ( 2000–2009 ) on diabetic patients including 17,536 African Americans and 12,618 whites . Cox proportional hazards regression models were used to estimate the association of blood pressure with CHD risk . RESULTS During a mean follow-up of 6.0 years , 7,260 CHD incident cases were identified . The multivariable-adjusted hazard ratios of CHD associated with different levels of systolic/diastolic blood pressure at baseline ( of isolated systolic and diastolic blood pressure at baseline as well as blood pressure during follow-up with CHD risk was observed among both African American and white diabetic patients ( all Ptrend blood pressure and the risk of CHD , and aggressive blood pressure control ( blood pressure < 120/70 mmHg ) is associated with an increased risk of CHD among both African American and white patients with diabetes", "BACKGROUND AND OBJECTIVES The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown ; neither is it clear whether in patients with a previous cardiovascular event , the optimal values are lower than in the low-to-moderate risk hypertensive patients , or a more cautious blood pressure ( BP ) reduction should be obtained . Because of the uncertainty whether ' the lower the better ' or the ' J-curve ' hypothesis is correct , the European Society of Hypertension and the Chinese Hypertension League have promoted a r and omized trial comparing antihypertensive treatment strategies aim ing at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack . As the optimal level of low-density lipoprotein cholesterol ( LDL-C ) level is also unknown in these patients , LDL-C-lowering has been included in the design . PROTOCOL DESIGN The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospect i ve multinational , r and omized trial with a 3 × 2 factorial design comparing : three different SBP targets ( 1 , 7500 patients aged at least 65 years ( 2500 in Europe , 5000 in China ) with hypertension and a stroke or transient ischaemic attack 1 - 6 months before r and omization . Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators , in order to maintain patients within the r and omized SBP and LDL-C windows . All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly . OUTCOMES Primary outcome is time to stroke ( fatal and non-fatal ) . Important secondary outcomes are : time to first major cardiovascular event ; cognitive decline ( Montreal Cognitive Assessment ) and dementia . All major outcomes will be adjudicated by committees blind to r and omized allocation . A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety . SAMPLE SIZE CALCULATION It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up , and this should provide at least 80 % power to detect a 25 % stroke difference between SBP targets and a 20 % difference between LDL-C targets", "CONTEXT Medical evidence may be biased over time if completion and publication of r and omized efficacy trials are delayed when results are not statistically significant . OBJECTIVE To evaluate whether the time to completion and the time to publication of r and omized phase 2 and phase 3 trials are affected by the statistical significance of results and to describe the natural history of such trials . DESIGN Prospect i ve cohort of r and omized efficacy trials conducted by 2 trialist groups from 1986 to 1996 . SETTING Multicenter trial groups in human immunodeficiency virus infection sponsored by the National Institutes of Health . PATIENTS A total of 109 efficacy trials ( total enrollment , 43708 patients ) . MAIN OUTCOME MEASURES Time from start of enrollment to completion of follow-up and time from completion of follow-up to peer- review ed publication assessed with survival analysis . RESULTS The median time from start of enrollment to publication was 5.5 years and was substantially longer for negative trials than for results favoring an experimental arm ( 6.5 vs 4.3 years , respectively ; P ratio for time to publication for positive vs negative trials , 3.7 ; 95 % confidence interval [ CI ] , 1.8 - 7.7 ) . This difference was mostly attributable to differences in the time from completion to publication ( median , 3.0 vs 1.7 years for negative vs positive trials ; P<.001 ) . On average , trials with significant results favoring any arm completed follow-up slightly earlier than trials with nonsignificant results ( median , 2.3 vs 2.5 years ; P=.045 ) , but long-protracted trials often had low event rates and failed to reach statistical significance , while trials that were terminated early had significant results . Positive trials were su bmi tted for publication significantly more rapidly after completion than were negative trials ( median , 1.0 vs 1.6 years ; P=.001 ) and were published more rapidly after su bmi ssion ( median , 0.8 vs 1.1 years ; P=.04 ) . CONCLUSION Among r and omized efficacy trials , there is a time lag in the publication of negative findings that occurs mostly after the completion of the trial follow-up", "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", "Although the benefits of antihypertensive treatment in \" young \" elderly ( under 70 years ) hypertensive patients are well established , the value of treatment in older patients ( 70 - 84 years ) is less clear . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omised , double-blind , intervention study set up to compare the effects of active antihypertensive therapy ( three beta-blockers and one diuretic ) and placebo on the frequency of fatal and non-fatal stroke and myocardial infa rct ion and other cardiovascular death in hypertensive Swedish men and women aged 70 - 84 years . We recruited 1627 patients at 116 health centres throughout Sweden , who were willing to participate , and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg , or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure . The total duration of the study was 65 months and the average time in the study was 25 months . 812 patients were r and omly allocated active treatment and 815 placebo . The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint , death , or study termination was 19.5/8.1 mm Hg . Compared with placebo , active treatment significantly reduced the number of primary endpoints ( 94 vs 58 ; p = 0.0031 ) and stroke morbidity and mortality ( 53 vs 29 ; p = 0.0081 ) . Although we did not set out to study an effect on total mortality , we also noted a significantly reduced number of deaths in the active treatment group ( 63 vs 36 ; p = 0.0079 ) . The benefits of treatment were discernible up to age 84 years . We conclude that antihypertensive treatment in hypertensive men and women aged 70 - 84 confers highly significant and clinical ly relevant reductions in cardiovascular morbidity and mortality as well as in total mortality", "CONTEXT The effect of antihypertensive drugs on cardiovascular events in patients with coronary artery disease ( CAD ) and normal blood pressure remains uncertain . OBJECTIVE To compare the effects of amlodipine or enalapril vs placebo on cardiovascular events in patients with CAD . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , multicenter , 24-month trial ( enrollment April 1999-April 2002 ) comparing amlodipine or enalapril with placebo in 1991 patients with angiographically documented CAD ( > 20 % stenosis by coronary angiography ) and diastolic blood pressure A sub study of 274 patients measured atherosclerosis progression by intravascular ultrasound ( IVUS ) . INTERVENTIONS Patients were r and omized to receive amlodipine , 10 mg ; enalapril , 20 mg ; or placebo . IVUS was performed at baseline and study completion . MAIN OUTCOME MEASURES The primary efficacy parameter was incidence of cardiovascular events for amlodipine vs placebo . Other outcomes included comparisons of amlodipine vs enalapril and enalapril vs placebo . Events included cardiovascular death , nonfatal myocardial infa rct ion , resuscitated cardiac arrest , coronary revascularization , hospitalization for angina pectoris , hospitalization for congestive heart failure , fatal or nonfatal stroke or transient ischemic attack , and new diagnosis of peripheral vascular disease . The IVUS end point was change in percent atheroma volume . RESULTS Baseline blood pressure averaged 129/78 mm Hg for all patients ; it increased by 0.7/0.6 mm Hg in the placebo group and decreased by 4.8/2.5 mm Hg and 4.9/2.4 mm Hg in the amlodipine and enalapril groups , respectively ( P Cardiovascular events occurred in 151 ( 23.1 % ) placebo-treated patients , in 110 ( 16.6 % ) amlodipine-treated patients ( hazard ratio [ HR ] , 0.69 ; 95 % CI , 0.54 - 0.88 [ P = .003 ] ) , and in 136 ( 20.2 % ) enalapril-treated patients ( HR , 0.85 ; 95 % CI , 0.67 - 1.07 [ P = .16 ] . Primary end point comparison for enalapril vs amlodipine was not significant ( HR , 0.81 ; 95 % CI , 0.63 - 1.04 [ P = .10 ] ) . The IVUS sub study showed a trend toward less progression of atherosclerosis in the amlodipine group vs placebo ( P = .12 ) , with significantly less progression in the subgroup with systolic blood pressures greater than the mean ( P = .02 ) . Compared with baseline , IVUS showed progression in the placebo group ( P enalapril group ( P = .08 ) , and no progression in the amlodipine group ( P = .31 ) . For the amlodipine group , correlation between blood pressure reduction and progression was r = 0.19 , P = .07 . CONCLUSIONS Administration of amlodipine to patients with CAD and normal blood pressure result ed in reduced adverse cardiovascular events . Directionally similar , but smaller and nonsignificant , treatment effects were observed with enalapril . For amlodipine , IVUS showed evidence of slowing of atherosclerosis progression", "To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications , we compared glomerular filtration rate ( GFR ; primary outcome ) , cardiovascular events , retinopathy , and neuropathy in 380 hypertensive type 2 diabetics with albuminuria DEM AND [ Delapril and Manidipine for Nephroprotection in Diabetes ] ) and r and omized to 3-year treatment with manidipine/delapril combination ( 10/30 mg/d ; n=126 ) , delapril ( 30 mg/d ; n=127 ) , or placebo ( n=127 ) . GFR was central ly measured by iohexol plasma clearance . Median monthly GFR decline ( interquartile range [ IQR ] ) was 0.32 mL/min per 1.73 m2 ( IQR : 0.16–0.50 mL/min per 1.73 m2 ) on combined therapy , 0.36 mL/min per 1.73 m2 ( IQR : 0.18–0.53 mL/min per 1.73 m2 ) on delapril , and 0.30 mL/min per 1.73 m2 ( IQR : 0.12–0.50 mL/min per 1.73 m2 ) on placebo ( P=0.87 and P=0.53 versus combined therapy or delapril , respectively ) . Similar findings were observed when baseline GFR values were not considered for slope analyses . Albuminuria was stable in the 3 treatment groups . The hazard ratio ( 95 % CI ) for major cardiovascular events between combined therapy and placebo was 0.17 ( 0.04–0.78 ; P=0.023 ) . Among 192 subjects without retinopathy at inclusion , the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 ( 0.07–0.99 ; P=0.048 ) . Among 200 subjects with central ized neurological evaluation , the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 ( 0.24–0.87 ; P=0.017 ) and 0.52 ( 0.27–0.99 ; P=0.048 ) , respectively . Glucose disposal rate decreased from 5.8±2.4 to 5.3±1.9 mg/kg per min on placebo ( P=0.03 ) but did not change on combined or delapril therapy . Treatment was well tolerated . In hypertensive type 2 diabetic patients , combined manidipine and delapril therapy failed to slow GFR decline but safely ameliorated cardiovascular disease , retinopathy , and neuropathy and stabilized insulin sensitivity", "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", "Summary Background The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared . In this study , we aim ed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease . Methods We used linked electronic health records from 1997 to 2010 in the CALIBER ( CArdiovascular research using LInked Bespoke studies and Electronic health Records ) programme to assemble a cohort of 1·25 million patients , 30 years of age or older and initially free from cardiovascular disease , a fifth of whom received blood pressure-lowering treatments . We studied the heterogeneity in the age-specific associations of clinical ly measured blood pressure with 12 acute and chronic cardiovascular diseases , and estimated the lifetime risks ( up to 95 years of age ) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30 , 60 , and 80 years . This study is registered at Clinical Trials.gov , number NCT01164371 . Findings During 5·2 years median follow-up , we recorded 83 098 initial cardiovascular disease presentations . In each age group , the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90–114 mm Hg and diastolic blood pressure of 60–74 mm Hg , with no evidence of a J-shaped increased risk at lower blood pressures . The effect of high blood pressure varied by cardiovascular disease endpoint , from strongly positive to no effect . Associations with high systolic blood pressure were strongest for intracerebral haemorrhage ( hazard ratio 1·44 [ 95 % CI 1·32–1·58 ] ) , subarachnoid haemorrhage ( 1·43 [ 1·25–1·63 ] ) , and stable angina ( 1·41 [ 1·36–1·46 ] ) , and weakest for abdominal aortic aneurysm ( 1·08 [ 1·00–1·17 ] ) . Compared with diastolic blood pressure , raised systolic blood pressure had a greater effect on angina , myocardial infa rct ion , and peripheral arterial disease , whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure . Pulse pressure associations were inverse for abdominal aortic aneurysm ( HR per 10 mm Hg 0·91 [ 95 % CI 0·86–0·98 ] ) and strongest for peripheral arterial disease ( 1·23 [ 1·20–1·27 ] ) . People with hypertension ( blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs ) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3 % ( 95 % CI 62·9–63·8 ) compared with 46·1 % ( 45·5–46·8 ) for those with normal blood pressure , and developed cardiovascular disease 5·0 years earlier ( 95 % CI 4·8–5·2 ) . Stable and unstable angina accounted for most ( 43 % ) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years , whereas heart failure and stable angina accounted for the largest proportion ( 19 % each ) of years of life lost from index age 80 years . Interpretation The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range , and that diastolic and systolic associations are concordant , are not supported by the findings of this high-resolution study . Despite modern treatments , the lifetime burden of hypertension is substantial . These findings emphasise the need for new blood pressure-lowering strategies , and will help to inform the design of r and omised trials to assess them . Funding Medical Research Council , National Institute for Health Research , and Wellcome Trust", "Background : Analyses of the risks of stroke were conducted for subjects with and without diabetes , participating in a r and omized , double‐blind , placebo‐controlled trial of a perindopril‐based blood pressure lowering regimen in 6105 people with prior stroke or transient ischaemic attack ( TIA ) , followed for a median of 3.9 years . Findings : Seven hundred and sixty‐one patients had diabetes at baseline . Diabetes increased the risk of recurrent stroke by 35 % ( 95 % CI 10–65 % ) principally through an effect on ischaemic stroke ( 1.53 , 95 % CI 1.23–1.90 ) . Active treatment reduced blood pressure by 9.5/4.6 mmHg in patients with diabetes and by 8.9/3.9 mmHg in patients without diabetes . The proportional risk reductions achieved for stroke in patients with diabetes , 38 % ( 95 % CI 8–58 % ) , and patients without diabetes , 28 % ( 95 % CI 16–39 % ) , were not significantly different ( p homogeneity = 0.5 ) . The absolute reduction in the risk of recurrent stroke in the patients with diabetes was equivalent to one stroke avoided among every 16 ( 95 % CI 9–111 ) patients treated for 5 years . Conclusions : Diabetes is an important risk factor for stroke in patients with established cerebrovascular disease . Treatment with the ACE inhibitor perindopril with discretionary use of the diuretic indapamide produced reductions in the risk of recurrent stroke in patients with diabetes that were at least as great as those achieved in patients without diabetes", "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 The risks and benefits of treating hypertension in individuals older than 80 years are uncertain . A meta- analysis has suggested that a reduction in stroke events of 36 % may have to be balanced against a 14 % increase in total mortality . Objectives To report the results of the pilot study of the Hypertension in the Very Elderly Trial ( HYVET ) , which is in progress to address these issues . Methods The HYVET-Pilot was a multicentre international open pilot trial . In 10 European countries , 1283 patients older than 80 years and with a sustained blood pressure of 160–219/90–109 mmHg were allocated r and omly to one of three treatments : a diuretic-based regimen ( usually bendroflumethiazide ; n = 426 ) , an angiotensin-converting enzyme inhibitor regimen ( usually lisinopril ; n = 431 ) or no treatment ( n = 426 ) . The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment . Target blood pressure was the reduction in stroke events relative hazard rate ( RHR ) was 0.47 [ 95 % confidence interval ( CI ) 0.24 to 0.93 ] and the reduction in stroke mortality RHR was 0.57 ( 95 % CI 0.25 to 1.32 ) . However , the estimate of total mortality supported the possibility of excess deaths with active treatment ( RHR 1.23 , 95 % CI 0.75 to 2.01 ) . Conclusions The preliminary results support the need for the continuing main HYVET trial . It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 ( nine non-fatal ) , but may be associated with 20 extra non-stroke deaths ", "Hypertension guidelines recommend blood pressure self-measurement at home ( HBP ) , but no previous trial has assessed cardiovascular outcomes in hypertensive patients treated according to HBP . The multicenter Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure ( HOMED-BP ; 2001–2010 ) trial involved 3518 patients ( 50 % women ; mean age 59.6 years ) with an untreated systolic/diastolic HBP of 135–179/85–119 mm Hg . In a 2 × 3 design , patients were r and omized to usual control ( 125–134/80–84 mm Hg ( UC ) ) vs. tight control ( ( TC ) ) of HBP and to initiation of drug treatment with angiotensin converting enzyme inhibitors , angiotensin receptor blockers or calcium channel blockers . During follow-up , a computer algorithm automatically generated treatment recommendations based on HBP . At the last follow-up ( median 5.3 years ) , TC patients used more antihypertensive drugs than UC patients ( 1.82 vs. 1.74 defined daily doses , P=0.045 ) and had a greater HBP reduction ( 21.3/13.1 mm Hg vs. 22.7/13.9 mm Hg , P=0.018/0.020 ) , but they less frequently achieved the lower HBP targets ( 37.4 vs. 63.5 % , P , cardiovascular death plus stroke and myocardial infa rct ion , occurred in 25 UC and 26 TC patients ( hazard ratio , 1.02 ; 95 % confidence interval , 0.59–1.77 ; P=0.94 ) . Rates were similar ( P⩾0.13 ) in the three drug groups . In all patients combined , the risk of the primary end point independently increased by 41 % ( 6–89 % ; P=0.019 ) and 47 % ( 15–87 % ; P=0.0020 ) for a 1-s.d . increase in baseline ( 12.5 mm Hg ) and follow-up ( 13.2 mm Hg ) systolic HBP . The 5-year risk was minimal ( ⩽1 % ) if on-treatment systolic HBP was 131.6 mm Hg or less . HOMED-BP proved the feasibility of adjusting antihypertensive drug treatment based on HBP and suggests that a systolic HBP level of 130 mm Hg should be an achievable and safe target", "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 risk of cardiovascular events among patients with atrial fibrillation is high . We evaluated whether irbesartan , an angiotensin-receptor blocker , would reduce this risk . METHODS We r and omly assigned patients with a history of risk factors for stroke and a systolic blood pressure of at least 110 mm Hg to receive either irbesartan at a target dose of 300 mg once daily or double-blind placebo . These patients were already enrolled in one of two trials ( of clopidogrel plus aspirin versus aspirin alone or versus oral anticoagulants ) . The first co primary outcome was stroke , myocardial infa rct ion , or death from vascular causes ; the second was this composite outcome plus hospitalization for heart failure . RESULTS A total of 9016 patients were enrolled and followed for a mean of 4.1 years . The mean reduction in systolic blood pressure was 2.9 mm Hg greater in the irbesartan group than in the placebo group , and the mean reduction in diastolic blood pressure was 1.9 mm Hg greater . The first co primary outcome occurred at a rate of 5.4 % per 100 person-years in both groups ( hazard ratio with irbesartan , 0.99 ; 95 % confidence interval [ CI ] , 0.91 to 1.08 ; P=0.85 ) . The second co primary outcome occurred at a rate of 7.3 % per 100 person-years among patients receiving irbesartan and 7.7 % per 100 person-years among patients receiving placebo ( hazard ratio , 0.94 ; 95 % CI , 0.87 to 1.02 ; P=0.12 ) . The rates of first hospitalization for heart failure ( a prespecified secondary outcome ) were 2.7 % per 100 person-years among patients receiving irbesartan and 3.2 % per 100 person-years among patients receiving placebo ( hazard ratio , 0.86 ; 95 % CI , 0.76 to 0.98 ) . Among patients who were in sinus rhythm at baseline , there was no benefit of irbesartan in preventing hospitalization for atrial fibrillation or atrial fibrillation recorded on 12-lead electrocardiography , nor was there a benefit in a subgroup that underwent transtelephonic monitoring . More patients in the irbesartan group than in the placebo group had symptomatic hypotension ( 127 vs. 64 ) and renal dysfunction ( 43 vs. 24 ) . CONCLUSIONS Irbesartan did not reduce cardiovascular events in patients with atrial fibrillation . ( Funded by Bristol-Myers Squibb and Sanofi-Aventis ; Clinical Trials.gov number , NCT00249795 . )", "BACKGROUND In patients who have vascular disease or high-risk diabetes without heart failure , angiotensin-converting-enzyme ( ACE ) inhibitors reduce mortality and morbidity from cardiovascular causes , but the role of angiotensin-receptor blockers ( ARBs ) in such patients is unknown . We compared the ACE inhibitor ramipril , the ARB telmisartan , and the combination of the two drugs in patients with vascular disease or high-risk diabetes . METHODS After a 3-week , single-blind run-in period , patients underwent double-blind r and omization , with 8576 assigned to receive 10 mg of ramipril per day , 8542 assigned to receive 80 mg of telmisartan per day , and 8502 assigned to receive both drugs ( combination therapy ) . The primary composite outcome was death from cardiovascular causes , myocardial infa rct ion , stroke , or hospitalization for heart failure . RESULTS Mean blood pressure was lower in both the telmisartan group ( a 0.9/0.6 mm Hg greater reduction ) and the combination-therapy group ( a 2.4/1.4 mm Hg greater reduction ) than in the ramipril group . At a median follow-up of 56 months , the primary outcome had occurred in 1412 patients in the ramipril group ( 16.5 % ) , as compared with 1423 patients in the telmisartan group ( 16.7 % ; relative risk , 1.01 ; 95 % confidence interval [ CI ] , 0.94 to 1.09 ) . As compared with the ramipril group , the telmisartan group had lower rates of cough ( 1.1 % vs. 4.2 % , P angioedema ( 0.1 % vs. 0.3 % , P=0.01 ) and a higher rate of hypotensive symptoms ( 2.6 % vs. 1.7 % , P rate of syncope was the same in the two groups ( 0.2 % ) . In the combination-therapy group , the primary outcome occurred in 1386 patients ( 16.3 % ; relative risk , 0.99 ; 95 % CI , 0.92 to 1.07 ) ; as compared with the ramipril group , there was an increased risk of hypotensive symptoms ( 4.8 % vs. 1.7 % , P syncope ( 0.3 % vs. 0.2 % , P=0.03 ) , and renal dysfunction ( 13.5 % vs. 10.2 % , P CONCLUSIONS Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema . The combination of the two drugs was associated with more adverse events without an increase in benefit . ( Clinical Trials.gov number , NCT00153101 [ Clinical Trials.gov ] . )", "Background The prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure study addresses the issue of whether progression to manifest hypertension in patients with high-normal blood pressure can be prevented with treatment . Methods A total of 1008 participants with high-normal office blood pressure were r and omized to ramipril treatment group ( n = 505 ) and a control group ( n = 503 ) . The patients were followed up for 3 years . Primary endpoint was to prevent or delay the progression to manifest hypertension . Secondary endpoints were reduction in the incidence of cerebrovascular and cardiovascular events , as well as the development of hypertension as defined by ambulatory blood pressure monitoring . Findings One hundred and fifty-five patients ( 30.7 % ) in the ramipril group , and 216 ( 42.9 % ) in the control group reached the primary endpoint ( relative risk reduction 34.4 % , P = 0.0001 ) . Ramipril also proved to be more effective in reducing the incidence of manifest office hypertension in patients with baseline ambulatory blood pressure monitoring high-normal blood pressure . The incidence of cerebrovascular and cardiovascular events showed no statistically significant differences between the two groups . Cough was more frequent in the ramipril group ( 4.8 vs. 0.4 % ) . Interpretation There is now good clinical evidence that patients with high-normal blood pressure ( prehypertension ) are more likely to progress to manifest hypertension than patients with optimal or normal blood pressure . Additional ambulatory blood pressure monitoring seems to be essential to achieve correct diagnosis . Treatment of patients with high-normal office blood pressure with the angiotensin-converting enzyme inhibitor was well tolerated , and significantly reduced the risk of progression to manifest hypertension", "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 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", "BACKGROUND Previous studies have suggested that blockade of the renin-angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension . METHODS In a double-blind , r and omized clinical trial with a 2-by-2 factorial design , we r and omly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels ( after an 8-hour fast ) or impaired glucose tolerance to receive ramipril ( up to 15 mg per day ) or placebo ( and rosiglitazone or placebo ) and followed them for a median of 3 years . We studied the effects of ramipril on the development of diabetes or death , whichever came first ( the primary outcome ) , and on secondary outcomes , including regression to normoglycemia . RESULTS The incidence of the primary outcome did not differ significantly between the ramipril group ( 18.1 % ) and the placebo group ( 19.5 % ; hazard ratio for the ramipril group , 0.91 ; 95 % confidence interval [ CI ] , 0.81 to 1.03 ; P=0.15 ) . Participants receiving ramipril were more likely to have regression to normoglycemia than those receiving placebo ( hazard ratio , 1.16 ; 95 % CI , 1.07 to 1.27 ; P=0.001 ) . At the end of the study , the median fasting plasma glucose level was not significantly lower in the ramipril group ( 102.7 mg per deciliter [ 5.70 mmol per liter ] ) than in the placebo group ( 103.4 mg per deciliter [ 5.74 mmol per liter ] , P=0.07 ) , though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the ramipril group ( 135.1 mg per deciliter [ 7.50 mmol per liter ] vs. 140.5 mg per deciliter [ 7.80 mmol per liter ] , P=0.01 ) . CONCLUSIONS Among persons with impaired fasting glucose levels or impaired glucose tolerance , the use of ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia . ( Clinical Trials.gov number , NCT00095654 [ Clinical Trials.gov ] . )", "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 Prehypertension is associated with higher cardiovascular risk , target organ damage , and incidence of hypertension . The Prevention of Hypertension in Patients with PreHypertension ( PREVER‐Prevention ) trial aim ed to evaluate the efficacy and safety of a low‐dose diuretic for the prevention of hypertension and end‐organ damage . Methods and Results This r and omized , parallel , double‐blind , placebo‐controlled trial was conducted in 21 Brazilian academic medical centers . Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were r and omized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment . The primary outcome was incidence of hypertension . Development or worsening of microalbuminuria , new‐onset diabetes mellitus , and reduction of left ventricular mass were secondary outcomes . Participant characteristics were evenly distributed by trial arms . The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo ( hazard ratio 0.56 , 95 % CI 0.38–0.82 ) , result ing in a cumulative incidence of 11.7 % in the diuretic arm versus 19.5 % in the placebo arm ( P=0.004 ) . Adverse events ; levels of blood glucose , glycosylated hemoglobin , creatinine , and microalbuminuria ; and incidence of diabetes mellitus were no different between the 2 arms . Left ventricular mass assessed through Sokolow‐Lyon voltage and voltage‐ duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo ( P=0.02 ) . Conclusions A combination of low‐dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension . Clinical Trial Registration URL : http://www . Clinical Trials.gov , www.ensaiosclinicos.gov . Unique identifiers : NCT00970931 , RBR‐74rr6s", "BACKGROUND Calcium antagonists are widely prescribed for angina pectoris but their effect on clinical outcome is controversial . We aim ed to investigate the effect of the calcium antagonist nifedipine on long-term outcome in patients with stable angina pectoris . METHODS We r and omly assigned 3825 patients with treated stable symptomatic coronary disease to double-blind addition of nifedipine GITS ( gastrointestinal therapeutic system ) 60 mg once daily and 3840 to placebo . The primary endpoint was the combination of death , acute myocardial infa rct ion , refractory angina , new overt heart failure , debilitating stroke , and peripheral revascularisation . Mean follow-up was 4.9 years ( SD 1.1 ) . Analysis was by intention to treat . FINDINGS 310 patients allocated nifedipine died ( 1.64 per 100 patient-years ) compared with 291 people allocated placebo ( 1.53 per 100 patient-years ; hazard ratio 1.07 [ 95 % CI 0.91 - 1.25 ] , p=0.41 ) . Primary endpoint rates were 4.60 per 100 patient-years for nifedipine and 4.75 per 100 patient-years for placebo ( 0.97 [ 0.88 - 1.07 ] , p=0.54 ) . With nifedipine , rate of death and any cardiovascular event or procedure was 9.32 per 100 patient-years versus 10.50 per 100 patient-years for placebo ( 0.89 [ 0.83 - 0.95 ] , p=0.0012 ) . The difference was mainly attributable to a reduction in the need for coronary angiography and interventions in patients assigned nifedipine , despite an increase in peripheral revascularisation . Nifedipine had no effect on the rate of myocardial infa rct ion . INTERPRETATION Addition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival . Nifedipine GITS is safe and reduces the need for coronary angiography and interventions", "BACKGROUND It has been suggested that low diastolic blood pressure ( BP ) while receiving antihypertensive treatment ( hereinafter called on-treatment BP ) is harmful in older patients with systolic hypertension . We examined the association between on-treatment diastolic BP , mortality , and cardiovascular events in the prospect i ve placebo-controlled Systolic Hypertension in Europe Trial . METHODS Elderly patients with systolic hypertension were r and omized into the double-blind first phase of the trial , after which all patients received active study drugs ( phase 2 ) . We assessed the relationship between outcome and on-treatment diastolic BP by use of multivariate Cox regression analysis during receipt of placebo ( phase 1 ) and during active treatment ( phases 1 and 2 ) . RESULTS Rates of noncardiovascular mortality , cardiovascular mortality , and cardiovascular events were 11.1 , 12.0 , and 29.4 , respectively , per 1000 patient-years with active treatment ( n = 2358 ) and 11.9 , 12.6 , and 39.0 , respectively , with placebo ( n = 2225 ) . Noncardiovascular mortality , but not cardiovascular mortality , increased with low diastolic BP with active treatment ( P lower diastolic BP , that is , 65 to 60 mm Hg , were , respectively , 1.15 ( 95 % confidence interval , 1.00 - 1.31 ) and 1.28 ( 95 % confidence interval , 1.03 - 1.59 ) . Low diastolic BP with active treatment was associated with increased risk of cardiovascular events , but only in patients with coronary heart disease at baseline ( P cardiovascular events when systolic BP is not under control in older patients with systolic hypertension , at least until diastolic BP reaches 55 mm Hg . However , a prudent approach is warranted in patients with concomitant coronary heart disease , in whom diastolic BP should probably not be lowered to less than 70 mm Hg", "Abstract Objective : To determine whether tight control of blood pressure with either a β blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes . Design : R and omised controlled trial comparing an angiotensin converting enzyme inhibitor ( captopril ) with a β blocker ( atenolol ) in patients with type 2 diabetes aim ing at a blood pressure of Setting : 20 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Subjects : 1148 hypertensive patients with type 2 diabetes ( mean age 56 years , mean blood pressure 160/94 mm Hg ) . Of the 758 patients allocated to tight control of blood pressure , 400 were allocated to captopril and 358 to atenolol . 390 patients were allocated to less tight control of blood pressure . Main outcome measures : Predefined clinical end points , fatal and non-fatal , related to diabetes , death related to diabetes , and all cause mortality . Surrogate measures of microvascular and macrovascular disease included urinary albumin excretion and retinopathy assessed by retinal photography . Results : Captopril and atenolol were equally effective in reducing blood pressure to a mean of 144/83 mm Hg and 143/81 mm Hg respectively , with a similar proportion of patients ( 27 % and 31 % ) requiring three or more antihypertensive treatments . More patients in the captopril group than the atenolol group took the allocated treatment : at their last clinic visit , 78 % of those allocated captopril and 65 % of those allocated atenolol were taking the drug ( P Captopril and atenolol were equally effective in reducing the risk of macrovascular end points . Similar proportions of patients in the two groups showed deterioration in retinopathy by two grade s after nine years ( 31 % in the captopril group and 37 % in the atenolol group ) and developed clinical grade albuminuria ≥300 mg/l ( 5 % and 9 % ) . The proportion of patients with hypoglycaemic attacks was not different between groups , but mean weight gain in the atenolol group was greater ( 3.4 kg v 1.6 kg ) . Conclusion : Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications . This study provided no evidence that either drug has any specific beneficial or deleterious effect , suggesting that blood pressure reduction in itself may be more important than the treatment used", "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", "Abstract Objective To investigate whether a low dose of the angiotensin converting enzyme ( ACE ) inhibitor ramipril lowers cardiovascular and renal events in patients with type 2 diabetes who have microalbuminuria or proteinuria . Design R and omised , double blind , parallel group trial comparing ramipril ( 1.25 mg/day ) with placebo ( on top of usual treatment ) for cardiovascular and renal outcomes for at least three years . Setting Multicentre , primary care study conducted mostly by general practitioners in 16 European and north African countries . Participants 4912 patients with type 2 diabetes aged > 50 years who use oral antidiabetic drugs and have persistent microalbuminuria or proteinuria ( urinary albumin excretion 20 mg/l in two consecutive sample s ) , and serum creatinine ≤ 150 μmol/l . Main outcome measures The primary outcome measure was the combined incidence of cardiovascular death , non-fatal myocardial infa rct ion , stroke , heart failure leading to hospital admission , and end stage renal failure . Results Participants were followed for 3 to 6 ( median 4 ) years . There were 362 primary events among the 2443 participants taking ramipril ( 37.8 per 1000 patient years ) and 377 events among the 2469 participants taking placebo ( 38.8 per 1000 patient years ; hazard ratio 1.03 ( 95 % confidence interval 0.89 to 1.20 , P = 0.65 ) ) . None of the components of the primary outcome was reduced . Ramipril lowered systolic and diastolic blood pressures ( by 2.43 and 1.06 mm Hg respectively after two years ) and favoured regression from microalbuminuria ( 20 - 200 mg/l ) or proteinuria ( > 200mg/l ) to normal level ( ) in 1868 participants who completed the study . Conclusions Low dose ( 1.25 mg ) ramipril once daily has no effect on cardiovascular and renal outcomes of patients with type 2 diabetes and albuminuria , despite a slight decrease in blood pressure and urinary albumin . The cardiovascular benefits of a daily higher dose ( 10 mg ) ramipril observed elsewhere are not found with an eightfold lower daily dose", "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 ] . )", "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 Microalbuminuria in diabetes is strongly predictive of nephropathy , end-stage renal disease , and premature cardiovascular morbidity and mortality . Effective preventive therapies are therefore a clinical priority . OBJECTIVE To determine whether the angiotensin-receptor blocker c and esartan compared with placebo affects microalbuminuria incidence or rate of change in albuminuria in type 1 and type 2 diabetes . DESIGN 3 r and omized trials of the DIRECT ( Diabetic Retinopathy C and esartan Trials ) Program . SETTING 309 secondary care centers . PATIENTS 3326 and 1905 patients with type 1 and type 2 diabetes , respectively . Most were normotensive , and all had normoalbuminuria ( median urinary albumin excretion rate , 5.0 microg/min ) . INTERVENTION C and esartan , 16 mg/d increasing to 32 mg/d , versus placebo . Assignment was done central ly using an interactive voice-response system . Patients , caregivers , and research ers were blinded to treatment assignment . During a median follow-up of 4.7 years , 793 patients discontinued therapy and 63 were lost to follow-up . MEASUREMENTS Urinary albumin excretion rate , assessed annually by 2 overnight collection s ; if it was 20 microg/min or greater , then 2 further collection s were done . The primary end point was new microalbuminuria ( 3 or 4 collection s of urinary albumin excretion rate > or=20 microg/min ) . The secondary end point was rate of change in albuminuria . RESULTS Individual and pooled results of the 3 trials showed that c and esartan had little effect on risk for microalbuminuria ( pooled hazard ratio , 0.95 [ 95 % CI , 0.78 to 1.16 ] ; P = 0.60 ) . Pooled results showed that the annual rate of change in albuminuria was 5.53 % lower ( CI , 0.73 % to 10.14 % ; P = 0.024 ) with c and esartan than with placebo . LIMITATIONS Investigators recruited mainly normotensive patients or patients with well-controlled hypertension who were at low overall vascular risk , which result ed in a low rate of microalbuminuria . Studies were powered for retinal and not renal end points . CONCLUSION C and esartan , 32 mg/d , for 4.7 years did not prevent microalbuminuria in mainly normotensive patients with type 1 or type 2 diabetes", "BACKGROUND Lowering of blood pressure prevents stroke but optimum target levels to prevent recurrent stroke are unknown . We investigated the effects of different blood-pressure targets on the rate of recurrent stroke in patients with recent lacunar stroke . METHODS In this r and omised open-label trial , eligible patients lived in North America , Latin America , and Spain and had recent , MRI-defined symptomatic lacunar infa rct ions . Patients were recruited between March , 2003 , and April , 2011 , and r and omly assigned , according to a two-by-two multifactorial design , to a systolic-blood-pressure target of 130 - 149 mm Hg or less than 130 mm Hg . The primary endpoint was reduction in all stroke ( including ischaemic strokes and intracranial haemorrhages ) . Analysis was done by intention to treat . This study is registered with Clinical Trials.gov , number NCT 00059306 . FINDINGS 3020 enrolled patients , 1519 in the higher-target group and 1501 in the lower-target group , were followed up for a mean of 3·7 ( SD 2·0 ) years . Mean age was 63 ( SD 11 ) years . After 1 year , mean systolic blood pressure was 138 mm Hg ( 95 % CI 137 - 139 ) in the higher-target group and 127 mm Hg ( 95 % CI 126 - 128 ) in the lower-target group . Non-significant rate reductions were seen for all stroke ( hazard ratio 0·81 , 95 % CI 0·64 - 1·03 , p=0·08 ) , disabling or fatal stroke ( 0·81 , 0·53 - 1·23 , p=0·32 ) , and the composite outcome of myocardial infa rct ion or vascular death ( 0·84 , 0·68 - 1·04 , p=0·32 ) with the lower target . The rate of intracerebral haemorrhage was reduced significantly ( 0·37 , 0·15 - 0·95 , p=0·03 ) . Treatment-related serious adverse events were infrequent . INTERPRETATION Although the reduction in stroke was not significant , our results support that in patients with recent lacunar stroke , the use of a systolic-blood-pressure target of less than 130 mm Hg is likely to be beneficial . FUNDING National Institutes of Health-National Institute of Neurological Disorders and Stroke ( NIH-NINDS )", "Objectives To evaluate the risk of bias tool , introduced by the Cochrane Collaboration for assessing the internal validity of r and omised trials , for inter-rater agreement , concurrent validity compared with the Jadad scale and Schulz approach to allocation concealment , and the relation between risk of bias and effect estimates . Design Cross sectional study . Study sample 163 trials in children . Main outcome measures Inter-rater agreement between review ers assessing trials using the risk of bias tool ( weighted κ ) , time to apply the risk of bias tool compared with other approaches to quality assessment ( paired t test ) , degree of correlation for overall risk compared with overall quality scores ( Kendall ’s τ statistic ) , and magnitude of effect estimates for studies classified as being at high , unclear , or low risk of bias ( metaregression ) . Results Inter-rater agreement on individual domains of the risk of bias tool ranged from slight ( κ=0.13 ) to substantial ( κ=0.74 ) . The mean time to complete the risk of bias tool was significantly longer than for the Jadad scale and Schulz approach , individually or combined ( 8.8 minutes ( SD 2.2 ) per study v 2.0 ( SD 0.8 ) , P correlation between risk of bias overall compared with the Jadad scores ( P=0.395 ) and Schulz approach ( P=0.064 ) . Effect sizes differed between studies assessed as being at high or unclear risk of bias ( 0.52 ) compared with those at low risk ( 0.23 ) . Conclusions Inter-rater agreement varied across domains of the risk of bias tool . Generally , agreement was poorer for those items that required more judgment . There was low correlation between assessment s of overall risk of bias and two common approaches to quality assessment : the Jadad scale and Schulz approach to allocation concealment . Overall risk of bias as assessed by the risk of bias tool differentiated effect estimates , with more conservative estimates for studies at low risk", "BACKGROUND This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease , cardiovascular disease , or both . METHODS In a double-blind fashion , we r and omly assigned 8561 patients to aliskiren ( 300 mg daily ) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker . The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation ; nonfatal myocardial infa rct ion ; nonfatal stroke ; unplanned hospitalization for heart failure ; end-stage renal disease , death attributable to kidney failure , or the need for renal-replacement therapy with no dialysis or transplantation available or initiated ; or doubling of the baseline serum creatinine level . RESULTS The trial was stopped prematurely after the second interim efficacy analysis . After a median follow-up of 32.9 months , the primary end point had occurred in 783 patients ( 18.3 % ) assigned to aliskiren as compared with 732 ( 17.1 % ) assigned to placebo ( hazard ratio , 1.08 ; 95 % confidence interval [ CI ] , 0.98 to 1.20 ; P=0.12 ) . Effects on secondary renal end points were similar . Systolic and diastolic blood pressures were lower with aliskiren ( between-group differences , 1.3 and 0.6 mm Hg , respectively ) and the mean reduction in the urinary albumin-to-creatinine ratio was greater ( between-group difference , 14 percentage points ; 95 % CI , 11 to 17 ) . The proportion of patients with hyperkalemia ( serum potassium level , ≥6 mmol per liter ) was significantly higher in the aliskiren group than in the placebo group ( 11.2 % vs. 7.2 % ) , as was the proportion with reported hypotension ( 12.1 % vs. 8.3 % ) ( P addition of aliskiren to st and ard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful . ( Funded by Novartis ; ALTITUDE Clinical Trials.gov number , NCT00549757 . )", "BACKGROUND Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease . We investigated whether treatment with an angiotensin-receptor blocker ( ARB ) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria . METHODS In a r and omized , double-blind , multicenter , controlled trial , we assigned 4447 patients with type 2 diabetes to receive olmesartan ( at a dose of 40 mg once daily ) or placebo for a median of 3.2 years . Additional antihypertensive drugs ( except angiotensin-converting-enzyme inhibitors or ARBs ) were used as needed to lower blood pressure to less than 130/80 mm Hg . The primary outcome was the time to the first onset of microalbuminuria . The times to the onset of renal and cardiovascular events were analyzed as secondary end points . RESULTS The target blood pressure ( olmesartan and 71 % taking placebo ; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group . Microalbuminuria developed in 8.2 % of the patients in the olmesartan group ( 178 of 2160 patients who could be evaluated ) and 9.8 % in the placebo group ( 210 of 2139 ) ; the time to the onset of microalbuminuria was increased by 23 % with olmesartan ( hazard ratio for onset of microalbuminuria , 0.77 ; 95 % confidence interval , 0.63 to 0.94 ; P=0.01 ) . The serum creatinine level doubled in 1 % of the patients in each group . Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events--81 of 2232 patients ( 3.6 % ) as compared with 91 of 2215 patients ( 4.1 % ) (P=0.37)--but a greater number had fatal cardiovascular events--15 patients ( 0.7 % ) as compared with 3 patients ( 0.1 % ) ( P=0.01 ) , a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease ( 11 of 564 patients [ 2.0 % ] vs. 1 of 540 [ 0.2 % ] , P=0.02 ) . CONCLUSIONS Olmesartan was associated with a delayed onset of microalbuminuria , even though blood-pressure control in both groups was excellent according to current st and ards . The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern . ( Funded by Daiichi Sankyo ; Clinical Trials.gov number , NCT00185159 . )", "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", "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 .", "BACKGROUND It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance . METHODS In this double-blind , r and omized clinical trial with a 2-by-2 factorial design , we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan ( up to 160 mg daily ) or placebo ( and nateglinide or placebo ) in addition to lifestyle modification . We then followed the patients for a median of 5.0 years for the development of diabetes ( 6.5 years for vital status ) . We studied the effects of valsartan on the occurrence of three co primary outcomes : the development of diabetes ; an extended composite outcome of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , hospitalization for heart failure , arterial revascularization , or hospitalization for unstable angina ; and a core composite outcome that excluded unstable angina and revascularization . RESULTS The cumulative incidence of diabetes was 33.1 % in the valsartan group , as compared with 36.8 % in the placebo group ( hazard ratio in the valsartan group , 0.86 ; 95 % confidence interval [ CI ] , 0.80 to 0.92 ; P Valsartan , as compared with placebo , did not significantly reduce the incidence of either the extended cardiovascular outcome ( 14.5 % vs. 14.8 % ; hazard ratio , 0.96 ; 95 % CI , 0.86 to 1.07 ; P=0.43 ) or the core cardiovascular outcome ( 8.1 % vs. 8.1 % ; hazard ratio , 0.99 ; 95 % CI , 0.86 to 1.14 ; P=0.85 ) . CONCLUSIONS Among patients with impaired glucose tolerance and cardiovascular disease or risk factors , the use of valsartan for 5 years , along with lifestyle modification , led to a relative reduction of 14 % in the incidence of diabetes but did not reduce the rate of cardiovascular events . ( Clinical Trials.gov number , NCT00097786 .", "The influence of risk factors on CHD and all-cause mortality rates in 35- to 57-year-old men is examined by means of data on 325,348 white men who were screened for the MRFIT . This large data set permits an unusually detailed analysis of factors associated with the 6968 deaths , including 2426 ascribed to CHD , that were detected in the Social Security Administration data set during 6 years of follow-up . Simple cross classification of the data confirms the independent effect of serum cholesterol concentration , diastolic blood pressure , and cigarette smoking as risk factors for CHD and all-cause mortality rates . A distinct escalation of risk is noted for combinations of these risk factors . The strength of the association of each of the risk factors with CHD and all-cause mortality rates diminished with increasing age , although the number of excess deaths attributable to the risk factors increased because of the higher death rates in older men . Comparison of these findings with those observed in the five population s studied in the Pooling Project revealed an overall similarity in the risk relationships . It is estimated that elimination of these risk factors has the potential for reducing the CHD mortality rate by two thirds in 35- to 45-year old men , and by one half in 46- to 57-year-old men", "Objective To compare the incidence of stroke and other cardiovascular events in hypertensive patients receiving a low-dose diuretic and low-dose calcium antagonist combination with those receiving low-dose diuretic monotherapy , and assess the effects of a small blood pressure difference at achieved levels lower than those achieved in previous placebo-controlled trials . Methods The Felodipine Event Reduction ( FEVER ) trial was an investigator- design ed , prospect i ve , multicentre , double-blind , r and omized , placebo-controlled , parallel group trial . It enrolled 9800 Chinese patients , of either sex , aged 50–79 years , with one or two additional cardiovascular risk factors or disease , whose blood pressure , 6 weeks after switching from previous antihypertensive therapy to low-dose ( 12.5 mg a day ) hydrochlorothiazide , was in the range 140–180 mmHg ( systolic ) or 90–100 mmHg ( diastolic ) . These patients were r and omly assigned either to low-dose felodipine extended release or placebo , and followed at 3-month intervals for an average of 40 months . Results The intention-to-treat analysis included 9711 r and omly selected patients with only 30 ( 0.3 % ) lost to follow-up . A total of 31 842 patient-years of follow-up were accumulated , with 85.9 % of patients remaining on blinded r and omized treatment . Add-on therapy was given to 33.9 % of the hydrochlorothiazide – felodipine patients and to 42.3 % of the hydrochlorothiazide – placebo patients . In the felodipine group , systolic blood pressure (SBP)/diastolic blood pressure ( DBP ) decreased ( from r and omization to study end ) from 154.2/91.0 to 137.3/82.5 mmHg , and in the placebo group from 154.4/91.3 to 142.5/85.0 mmHg , with an average difference throughout the trial of 4.2/2.1 mmHg . In the felodipine group , the primary endpoint ( fatal and non-fatal stroke ) was reduced by 27 % ( P = 0.001 ) . Among secondary endpoints , all cardiovascular events were reduced by 27 % ( P by 35 % ( P = 0.012 ) , death by any cause by 31 % ( P = 0.006 ) , coronary events by 32 % ( P = 0.024 ) , heart failure by 30 % ( P = 0.239 ) , cardiovascular death by 33 % ( P = 0.019 ) , cancer by 36 % ( P = 0.017 ) in the felodipine group . No significant differences were found in new-onset diabetes . Both treatments were very well tolerated . Conclusions In moderately complicated hypertensive patients from China even a difference in SBP/DBP as small as 4/2 mmHg , such as that induced by adding low-dose felodipine to low-dose hydrochlorothiazide , is associated with very substantial reductions in the incidence of most types of cardiovascular events . As the SBP achieved in the felodipine group was below the recommended goal of less than 140 mmHg , and SBP in the placebo group was slightly above that level , FEVER provides the required evidence in support of the guidelines recommended goal , even for a hypertensive population not entirely consisting of patients with diabetes or previous cardiovascular events ", "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 Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke . In addition , inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events , including stroke . However , the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established . We evaluated the effects of therapy with an angiotensin-receptor blocker , telmisartan , initiated early after a stroke . METHODS In a multicenter trial involving 20,332 patients who recently had an ischemic stroke , we r and omly assigned 10,146 to receive telmisartan ( 80 mg daily ) and 10,186 to receive placebo . The primary outcome was recurrent stroke . Secondary outcomes were major cardiovascular events ( death from cardiovascular causes , recurrent stroke , myocardial infa rct ion , or new or worsening heart failure ) and new-onset diabetes . RESULTS The median interval from stroke to r and omization was 15 days . During a mean follow-up of 2.5 years , the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group . A total of 880 patients ( 8.7 % ) in the telmisartan group and 934 patients ( 9.2 % ) in the placebo group had a subsequent stroke ( hazard ratio in the telmisartan group , 0.95 ; 95 % confidence interval [ CI ] , 0.86 to 1.04 ; P=0.23 ) . Major cardiovascular events occurred in 1367 patients ( 13.5 % ) in the telmisartan group and 1463 patients ( 14.4 % ) in the placebo group ( hazard ratio , 0.94 ; 95 % CI , 0.87 to 1.01 ; P=0.11 ) . New-onset diabetes occurred in 1.7 % of the telmisartan group and 2.1 % of the placebo group ( hazard ratio , 0.82 ; 95 % CI , 0.65 to 1.04 ; P=0.10 ) . CONCLUSIONS Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke , major cardiovascular events , or diabetes . ( Clinical Trials.gov number , NCT00153062 .", "Background The prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago , but are less clear in those with mildly to moderately elevated blood pressure . Objective To assess whether c and esartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events , cognitive decline and dementia . Design Prospect i ve , double-blind , r and omized , parallel-group study conducted in 1997–2002 . Setting and participants The study was of 4964 patients aged 70–89 years , with systolic blood pressure 160–179 mmHg , and /or diastolic blood pressure 90–99 mmHg , and a Mini Mental State Examination ( MMSE ) test score ⩾ 24 . A total of 527 centres in 15 countries participated in the study . Intervention Patients were assigned r and omly to receive the angiotensin receptor blocker c and esartan or placebo , with open-label active antihypertensive therapy added as needed . As a consequence , active antihypertensive therapy was extensively used in the control group ( 84 % of patients ) . Mean follow-up was 3.7 years . Main outcome measures The primary outcome measure was major cardiovascular events , a composite of cardiovascular death , non-fatal stroke and non-fatal myocardial infa rct ion . Secondary outcome measures included cardiovascular death , non-fatal and fatal stroke and myocardial infa rct ion , cognitive function measured by the MMSE and dementia . Results Blood pressure fell by 21.7/10.8 mmHg in the c and esartan group and by 18.5/9.2 mmHg in the control group . A first major cardiovascular event occurred in 242 c and esartan patients and in 268 control patients ; risk reduction with c and esartan was 10.9 % [ 95 % confidence interval ( CI ) , −6.0 to 25.1 , P = 0.19 ] . C and esartan-based treatment reduced non-fatal stroke by 27.8 % ( 95 % CI , 1.3 to 47.2 , P = 0.04 ) , and all stroke by 23.6 % ( 95 % CI , −0.7 to 42.1 , P = 0.056 ) . There were no significant differences in myocardial infa rct ion and cardiovascular mortality . Mean MMSE score fell from 28.5 to 28.0 in the c and esartan group and from 28.5 to 27.9 in the control group ( P = 0.20 ) . The proportions of patients who had a significant cognitive decline or developed dementia were not different in the two treatment groups . Conclusions In elderly hypertensive patients , a slightly more effective blood pressure reduction during c and esartan-based therapy , compared with control therapy , was associated with a modest , statistically non-significant , reduction in major cardiovascular events and with a marked reduction in non-fatal stroke . Cognitive function was well maintained in both treatment groups in the presence of substantial blood pressure reductions . Both treatment regimens were generally well tolerated", "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", "Most patients with type 2 diabetes mellitus develop cardiovascular disease ( CVD ) , with substantial loss of life expectancy . Nonfatal CVD contributes greatly to excess healthcare costs and decreased quality of life in patients with diabetes . The current epidemic of obesity has raised expectations that CVD associated with type 2 diabetes will become an even greater public health challenge . Despite the importance of this health problem , there is a lack of definitive data on the effects of the intensive control of glycemia and other CVD risk factors on CVD event rates in patients with type 2 diabetes . The Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial is a r and omized , multicenter , double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type 2 diabetes who are at high risk for CVD events because of existing CVD or additional risk factors . ACCORD is testing the effects of 3 medical treatment strategies to reduce CVD morbidity and mortality . All participants are in the glycemia trial , which is testing the hypothesis that a therapeutic strategy that targets a glycosylated hemoglobin ( HbA1c ) level of rate of CVD events more than a strategy that targets an HbA1c level of 7.0%-7.9 % . The lipid trial includes 5,518 of the participants , who receive either fenofibrate or placebo in a double-masked fashion to test the hypothesis of whether , in the context of good glycemic control , a therapeutic strategy that uses a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels together with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ( statin ) to lower low-density lipoprotein cholesterol will reduce the rate of CVD events compared with a strategy that uses a statin plus a placebo . The blood pressure trial includes the remaining 4,733 participants and tests the hypothesis that a therapeutic strategy that targets a systolic blood pressure of rate of CVD events compared with a strategy that targets a systolic blood pressure of the first occurrence of a major CVD event , specifically nonfatal myocardial infa rct ion , nonfatal stroke , or cardiovascular death . Upon the expected completion of participant follow-up in 2009 , the ACCORD trial should document for the first time the benefits and risks of intensive glucose control , intensive blood pressure control , and the combination of fibrate and statin drugs in managing blood lipids in high-risk patients with type 2 diabetes", "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", "BACKGROUND Despite treatment , there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals . Inadequate reduction of their blood pressure is a likely cause , but the optimum target blood pressure is not known . The impact of acetylsalicylic acid ( aspirin ) has never been investigated in patients with hypertension . We aim ed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension . METHODS 18790 patients , from 26 countries , aged 50 - 80 years ( mean 61.5 years ) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg ( mean 105 mm Hg ) were r and omly assigned a target diastolic blood pressure . 6264 patients were allocated to the target pressure Felodipine was given as baseline therapy with the addition of other agents , according to a five-step regimen . In addition , 9399 patients were r and omly assigned 75 mg/day acetylsalicylic acid ( Bamycor , Astra ) and 9391 patients were assigned placebo . FINDINGS Diastolic blood pressure was reduced by 20.3 mm Hg , 22.3 mm Hg , and 24.3 mm Hg , in the major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg ; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg . Further reduction below these blood pressures was safe . In patients with diabetes mellitus there was a 51 % reduction in major cardiovascular events in target group Acetylsalicylic acid reduced major cardiovascular events by 15 % ( p=0.03 ) and all myocardial infa rct ion by 36 % ( p=0.002 ) , with no effect on stroke . There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group , and 129 versus 70 non-fatal major bleeds in the two groups , respectively ( p patients with hypertension was associated with a low rate of cardiovascular events . The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg . Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infa rct ion . There was no effect on the incidence of stroke or fatal bleeds , but non-fatal major bleeds were twice as common", "This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . \" Quality \" as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence", "BACKGROUND Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease . Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons . It is unclear whether the benefits of statins can be extended to an intermediate-risk , ethnically diverse population without cardiovascular disease . METHODS In one comparison from a 2-by-2 factorial trial , we r and omly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo . The first co primary outcome was the composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke , and the second co primary outcome additionally included revascularization , heart failure , and resuscitated cardiac arrest . The median follow-up was 5.6 years . RESULTS The overall mean low-density lipoprotein cholesterol level was 26.5 % lower in the rosuvastatin group than in the placebo group . The first co primary outcome occurred in 235 participants ( 3.7 % ) in the rosuvastatin group and in 304 participants ( 4.8 % ) in the placebo group ( hazard ratio , 0.76 ; 95 % confidence interval [ CI ] , 0.64 to 0.91 ; P=0.002 ) . The results for the second co primary outcome were consistent with the results for the first ( occurring in 277 participants [ 4.4 % ] in the rosuvastatin group and in 363 participants [ 5.7 % ] in the placebo group ; hazard ratio , 0.75 ; 95 % CI , 0.64 to 0.88 ; P cardiovascular risk at baseline , lipid level , C-reactive protein level , blood pressure , and race or ethnic group . In the rosuvastatin group , there was no excess of diabetes or cancers , but there was an excess of cataract surgery ( in 3.8 % of the participants , vs. 3.1 % in the placebo group ; P=0.02 ) and muscle symptoms ( in 5.8 % of the participants , vs. 4.7 % in the placebo group ; P=0.005 ) . CONCLUSIONS Treatment with rosuvastatin at a dose of 10 mg per day result ed in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk , ethnically diverse population without cardiovascular disease . ( Funded by the Canadian Institutes of Health Research and AstraZeneca ; HOPE-3 Clinical Trials.gov number , NCT00468923 . )", "Angiotensin-converting enzyme inhibitors improve endothelial function , inhibit experimental atherogenesis , and decrease ischemic events . The Quinapril Ischemic Event Trial was design ed to test the hypothesis that quinapril 20 mg/day would reduce ischemic events ( the occurrence of cardiac death , resuscitated cardiac arrest , nonfatal myocardial infa rct ion , coronary artery bypass grafting , coronary angioplasty , or hospitalization for angina pectoris ) and the angiographic progression of coronary artery disease in patients without systolic left ventricular dysfunction . A total of 1,750 patients were r and omized to quinapril 20 mg/day or placebo and followed a mean of 27 + /- 0.3 months . The 38 % incidence of ischemic events was similar for both groups ( RR 1.04 ; 95 % confidence interval 0.89 to 1.22 ; p = 0.6 ) . There was also no significant difference in the incidence of patients having angiographic progression of coronary disease ( p = 0.71 ) . The rate of development of new coronary lesions was also similar in both groups ( p = 0.35 ) . However , there was a difference in the incidence of angioplasty for new ( previously unintervened ) vessels ( p = 0.018 ) . Quinapril was well tolerated in patients after angioplasty with normal left ventricular function . Quinapril 20 mg did not significantly affect the overall frequency of clinical outcomes or the progression of coronary atherosclerosis . However , the absence of the demonstrable effect of quinapril may be due to several limitations in study design", "BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events . We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure . METHODS We recruited patients from October , 1997 , to June , 2000 . 13655 patients were registered with previous myocardial infa rct ion ( 64 % ) , angiographic evidence of coronary artery disease ( 61 % ) , coronary revascularisation ( 55 % ) , or a positive stress test only ( 5 % ) . After a run-in period of 4 weeks , in which all patients received perindopril , 12218 patients were r and omly assigned perindopril 8 mg once daily ( n=6110 ) , or matching placebo ( n=6108 ) . The mean follow-up was 4.2 years , and the primary endpoint was cardiovascular death , myocardial infa rct ion , or cardiac arrest . Analysis was by intention to treat . FINDINGS Mean age of patients was 60 years ( SD 9 ) , 85 % were male , 92 % were taking platelet inhibitors , 62 % beta blockers , and 58 % lipid-lowering therapy . 603 ( 10 % ) placebo and 488 ( 8 % ) perindopril patients experienced the primary endpoint , which yields a 20 % relative risk reduction ( 95 % CI 9 - 29 , p=0.0003 ) with perindopril . These benefits were consistent in all predefined subgroups and secondary endpoints . Perindopril was well tolerated . INTERPRETATION Among patients with stable coronary heart disease without apparent heart failure , perindopril can significantly improve outcome . About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event . Treatment with perindopril , on top of other preventive medications , should be considered in all patients with coronary heart disease", "BACKGROUND Diabetes is the most common cause of renal failure in the United States , and data regarding the effects of aggressive blood pressure ( BP ) therapy in normotensive patients with type 2 diabetes are inadequate . METHODS A total of 129 type 2 diabetic patients with a BP of were r and omized to either intensive BP control ( diastolic BP goal 75 mm Hg ) using an angiotensin II receptor blocker , valsartan , versus moderate BP control ( diastolic BP 80 to 90 mm Hg with placebo initially ) to evaluate the effect on the change in urinary albumin excretion ( UAE ) from baseline . RESULTS The mean entrance BP was 126 + /- 8.8/84 + /- 2.4 mm Hg . The mean follow-up period was 1.9 + /- 1.0 years . During the follow-up period , the mean BP was 118 + /- 10.9/75 + /- 5.7 for the intensive v 124 10.9/80 6.5 mm Hg for the moderate BP groups ( P change in creatinine clearance or serum creatinine from baseline between the two groups . An analysis of covariance model for change in log ( UAE + 1 ) , adjusting for age , HBA(1c ) , duration of diabetes , baseline log ( UAE + 1 ) , sex , and ethnicity result ed in a significant treatment difference at 2 years ( P = .007 ) with intensive BP control reducing log ( UAE+1 ) compared with moderate BP control . CONCLUSION Intensive BP control with valsartan to normotensive patients with type 2 diabetes and normo- or microalbuminuria significantly decreased the progression of UAE and in some cases caused regression of UAE", "The associations of diastolic blood pressure ( DBP ) with stroke and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any \" threshold \" below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at \" baseline \" with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this \" regression dilution \" bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrected analyses . ( This regression dilution bias is quite general , so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths . ) The DBP results suggest that for the large majority of individuals , whether conventionally \" hypertensive \" or \" normotensive \" , a lower blood pressure should eventually confer a lower risk of vascular disease", "BACKGROUND Microalbuminuria and hypertension are risk factors for diabetic nephropathy . Blockade of the renin-angiotensin system slows the progression to diabetic nephropathy in patients with type 1 diabetes , but similar data are lacking for hypertensive patients with type 2 diabetes . We evaluated the renoprotective effect of the angiotensin-II-receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria . METHODS A total of 590 hypertensive patients with type 2 diabetes and microalbuminuria were enrolled in this multinational , r and omized , double-blind , placebo-controlled study of irbesartan , at a dose of either 150 mg daily or 300 mg daily , and were followed for two years . The primary outcome was the time to the onset of diabetic nephropathy , defined by persistent albuminuria in overnight specimens , with a urinary albumin excretion rate that was greater than 200 microg per minute and at least 30 percent higher than the base-line level . RESULTS The base-line characteristics in the three groups were similar . Ten of the 194 patients in the 300-mg group ( 5.2 percent ) and 19 of the 195 patients in the 150-mg group ( 9.7 percent ) reached the primary end point , as compared with 30 of the 201 patients in the placebo group ( 14.9 percent ) ( hazard ratios , 0.30 [ 95 percent confidence interval , 0.14 to 0.61 ; P average blood pressure during the course of the study was 144/83 mm Hg in the placebo group , 143/83 mm Hg in the 150-mg group , and 141/83 mm Hg in the 300-mg group ( P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups ) . Serious adverse events were less frequent among the patients treated with irbesartan ( P=0.02 ) . CONCLUSIONS Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria", "BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors are effective in reducing the risk of heart failure , myocardial infa rct ion , and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure . ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure . METHODS In the Prevention of Events with Angiotensin Converting Enzyme Inhibition ( PEACE ) Trial , we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy . The trial was a double-blind , placebo-controlled study in which 8290 patients were r and omly assigned to receive either tr and olapril at a target dose of 4 mg per day ( 4158 patients ) or matching placebo ( 4132 patients ) . RESULTS The mean ( + /-SD ) age of the patients was 64+/-8 years , the mean blood pressure 133+/-17/78+/-10 mm Hg , and the mean left ventricular ejection fraction 58+/-9 percent . The patients received intensive treatment , with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs . The incidence of the primary end point -- death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization -- was 21.9 percent in the tr and olapril group , as compared with 22.5 percent in the placebo group ( hazard ratio in the tr and olapril group , 0.96 ; 95 percent confidence interval , 0.88 to 1.06 ; P=0.43 ) over a median follow-up period of 4.8 years . CONCLUSIONS In patients with stable coronary heart disease and preserved left ventricular function who are receiving \" current st and ard \" therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease , there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization", "The benefits of lowering a systolic blood pressure below 140 mmHg in elderly hypertension remain controversial . This study is a prospect i ve , r and omized , open-label study with blinded assessment of endpoints to compare the 2-year effect of strict treatment to maintain systolic blood pressure below 140 mmHg with that of mild treatment to maintain systolic blood pressure below 160 but at or above 140 mmHg in elderly hypertensive patients . Patients with essential hypertension ( 65–85 years old , with a pretreatment systolic blood pressure of above 160 mmHg ) were r and omly assigned to receive strict treatment ( n=2,212 ) or mild treatment ( n=2,206 ) . The baseline drug was efonidipine hydrochloride , a long-acting calcium antagonist . The primary endpoint was the combined incidence of cardiovascular disease and renal failure , and the secondary endpoints were total deaths and any safety problems . Although final blood pressures ( systolic/diastolic ) were significantly lower in the strict-treatment group compared with the mild-treatment group ( 135.9/74.8 vs. 145.6/78.1 mmHg ; p ) . Total deaths were 54 in the strict-treatment group vs. 42 in the mild-treatment group ( p=0.22 ) , and treatment was withdrawn because of adverse events in 36 patients in each group ( p=0.99 ) . An interaction between age and treatment for the primary endpoints ( p=0.03 ) was seen . Complex clinical features associated with aging seem to have obscured the difference in effect between the two treatments . Further studies are needed to assess the optimal treatment strategy for hypertension in the elderly", "In 1972 - -1973 , 785 symptom-free men , aged 40 to 49 years , without target organ damage , with systolic blood pressures between 150 and 179 mm Hg and diastolic blood pressure below 110 mm Hg , were assigned at r and om to one of two groups : ( 406 to a drug treatment group and 379 to a control group ) for a five-year controlled drug treatment trial to evaluate the effect of therapy on cardiovascular complications . Drug treatment started with hydrochlorothiazide . If systolic blood pressure remained above 140 mm Hg and /or diastolic blood pressure above 90 mm Hg , alphamethyldopa was added . If there were side effects , methyldopa was replaced with propranolol . The control group was not given a placebo . The mean observation time was 66 months ( range 60 to 78 months ) . A difference in blood pressure between groups of about 17 mm Hg systolic and 10 mm Hg diastolic was maintained throughout the study . The study protocol had a rather low \" ethical \" blood pressure roof , 180 mm Hg systolic and /or 110 mm Hg diastolic . Seventeen percent of the control group had an increase in blood pressure above this level during the trial , and drug treatment was started . There was no effect on major cardiovascular morbidity comparing groups as established by r and omization , with 18 events in the treatment group and 20 events in the control group . There was no difference between the groups in total mortality and mortality from cardiovascular events . However , in the subgroups with diastolic blood pressure greater than or equal to 100 mm Hg before r and omization , there was a probable reduction in total morbidity from cardiovascular events in favor or the group receiving drug therapy , 7.6 and 16.4 percent events in the treated and control groups , respectively . Cerebrovascular events occurred only in the control group , 7 versus 0 . Two cases of fatal aortic aneurysms also occurred in the control group . Other \" pressure \" complications , such as marked left ventricular hypertrophy in the electrocardiogram and left ventricular failure , occurred only in the control group . However , regarding coronary heart disease , including sudden death , the incidence tended to be higher in the treated group , although it was not statistically significant . Only 13 men ( 1.7 percent ) failed to meet for regular examinations . At the end of the study these men were also followed up with regard to possible cardiovascular events", "Abstract Blood pressure treatment has shown great efficacy in reducing cardiovascular events in r and omized controlled trials . If this is effective in reducing cardiovascular disease in the general population , is less studied . Between 2001 and 2009 we performed an intervention to improve blood pressure control in the county of Västerbotten , using Södermanl and County as a control . The intervention was directed towards primary care physicians and included lectures on blood pressure treatment , a computerized decision support system with treatment recommendations , and yearly feed back on hypertension control . Each county had approximately 255 000 inhabitants . Differences in age and incidence of cardiovascular disease were small . During follow-up , more than 400 000 patients had their blood pressure recorded . The mean number of measurements was eight per patient , yielding a total of 3.4 million blood pressure recordings . The effect of the intervention will be estimated combining the blood pressure data collected from the electronic medical records , with data on stroke , myocardial infa rct ion and mortality from Swedish health registers . Additional variables , from health registers and Statistics Sweden , will be collected to address for confounders . The blood pressure data collected within this study will be an important asset for future epidemiological studies within the field of hypertension", "BP is an important determinant of kidney disease among patients with diabetes . The recommended thresholds to initiate treatment to lower BP are 130/80 and 125/75 mmHg for people with diabetes and nephropathy , respectively . We sought to determine the effects of lowering BP below these currently recommended thresholds on renal outcomes among 11,140 patients who had type 2 diabetes and participated in the Action in Diabetes and Vascular disease : preterAx and diamicroN-MR Controlled Evaluation ( ADVANCE ) study . Patients were r and omly assigned to fixed combination perindopril-indapamide or placebo , regardless of their BP at entry . During a mean follow-up of 4.3 yr , active treatment reduced the risk for renal events by 21 % ( P developing microalbuminuria and macroalbuminuria ( both P baseline systolic or diastolic BP . Lower systolic BP levels during follow-up , even to rates of renal events . In conclusion , BP-lowering treatment with perindopril-indapamide administered routinely to individuals with type 2 diabetes provides important renoprotection , even among those with initial BP < 120/70 mmHg . We could not identify a BP threshold below which renal benefit is lost", "Background Hypertension guidelines advise aggressive blood pressure ( BP ) lowering in patients with diabetes or high cardiovascular risk , but supporting evidence is limited . We analysed the impact of BP on cardiovascular events in well treated high-risk patients enrolled in a large clinical trial ( Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial ) . Methods Twenty-five thous and five hundred and eighty-eight patients with atherosclerotic disease or diabetes with organ damage , tolerant to angiotensin-converting enzyme inhibitors , were r and omized to ramipril , telmisartan or both . We related the primary composite outcome and its components to : baseline SBP ; SBP changes from baseline to event ; and average in-trial SBP . Results The risk of myocardial infa rct ion did not increase with baseline SBP and was unaffected by subsequent SBP change . In contrast , stroke risk progressively increased with baseline SBP ( P for trend baseline SBP less than 130 mmHg , adjusted for several covariates , cardiovascular mortality increased with further SBP reduction ( P SBP and all outcomes except stroke . Conclusion In high-risk patients , the benefits from SBP lowering below 130 mmHg are driven mostly by a reduction of stroke ; myocardial infa rct ion is unaffected and cardiovascular mortality is unchanged or increased . Future trials should be design ed to test the value of SBP lowering in high-risk patients with SBP in the range of 130–150 mmHg", "Abstract Aims /hypothesisThe renal and cardiovascular protective effects of angiotensin receptor blocker ( ARB ) remain controversial in type 2 diabetic patients treated with a contemporary regimen including an angiotensin converting enzyme inhibitor ( ACEI ) . Methods We examined the effects of olmesartan , an ARB , on primary composite outcome of doubling of serum creatinine , endstage renal disease and death in type 2 diabetic patients with overt nephropathy . Secondary outcome included composite cardiovascular outcomes , changes in renal function and proteinuria . R and omisation and allocation to trial group were carried out by a central computer system . Participants , caregivers , the people carrying out examinations and people assessing the outcomes were blinded to group assignment . Results Five hundred and seventy-seven ( 377 Japanese , 200 Chinese ) patients treated with antihypertensive therapy ( 73.5 % [ n = 424 ] received concomitant ACEI ) , were given either once-daily olmesartan ( 10–40 mg ) ( n = 288 ) or placebo ( n = 289 ) over 3.2 ± 0.6 years ( mean±SD ) . In the olmesartan group , 116 developed the primary outcome ( 41.1 % ) compared with 129 ( 45.4 % ) in the placebo group ( HR 0.97 , 95 % CI 0.75 , 1.24 ; p = 0.791 ) . Olmesartan significantly decreased blood pressure , proteinuria and rate of change of reciprocal serum creatinine . Cardiovascular death was higher in the olmesartan group than the placebo group ( ten vs three cases ) , whereas major adverse cardiovascular events ( cardiovascular death plus non-fatal stroke and myocardial infa rct ion ) and all-cause death were similar between the two groups ( major adverse cardiovascular events 18 vs 21 cases , all-cause deaths ; 19 vs 20 cases ) . Hyperkalaemia was more frequent in the olmesartan group than the placebo group ( 9.2 % vs 5.3 % ) . Conclusions /interpretationOlmesartan was well tolerated but did not improve renal outcome on top of ACEI . Trial registration : Clinical Trials.gov NCT00141453 Funding : The ORIENT study was supported by a research grant from Daiichi Sankyo", "The concept of microalbuminuria has had a major impact on diabetes research and clinical care of patients with diabetes [ 1 - 5 ] . Initial albuminuria is regarded by most research ers as an independent predictor of subsequent progression of nephropathy and risk for cardiovascular morbidity and mortality [ 6 - 8 ] . Angiotensin-converting enzyme ( ACE ) inhibitors have been found to attenuate progression of nephropathy in both types of diabetes in hypertensive [ 9 - 12 ] and normotensive patients [ 13 - 15 ] with microalbuminuria . They were also found to lower urinary albumin excretion in normotensive and normoalbuminuric patients with type 1 diabetes [ 16 ] . The relation between albuminuria and later progression of nephropathy in these patients has not been established , possibly because of short follow-up periods . No data are available on the effect of early introduction of ACE inhibitors in normotensive and normoalbuminuric patients with type 2 diabetes mellitus . We design ed a r and omized , double-blind , placebo-controlled trial of the effect of ACE inhibition on the course of nephropathy in 156 patients with type 2 diabetes . These patients had normal blood pressure and normal urinary albumin excretion at baseline . Methods Patients Potential c and i date s were identified through the computerized records of the central regional laboratory for the northern part of the greater Tel-Aviv area . Persons with hyperglycemia and normal urinalysis results were located through their family physicians . Consent was sought once eligibility was established . Inclusion criteria were age younger than 60 years ; age 40 years or older at diagnosis ; duration of diabetes mellitus less than 10 years with no clinical evidence of malignant , autoimmune , hepatic , cardiovascular , or renal disease ; body mass index less than 30 kg/m2 ; normal blood pressure on at least two consecutive visits ( systolic pressure 140 mm Hg and diastolic pressure 90 mm Hg ; mean pressure 107 mm Hg ) ; serum creatinine concentration of 123 mol/L or less ; and urinary albumin excretion of 30 mg/24 h or less . All baseline data were obtained twice during the run-in prer and omization period . Patients were eligible only if values within the predetermined range were found on both examinations . The average of the values was used as the baseline value . A total of 255 patients who had type 2 diabetes according to World Health Organization criteria [ 17 ] and attended one of eight clinics in the greater Tel-Aviv area were found to be eligible and were contacted during 1990 and 1991 . Of these patients , 214 gave informed consent to participate . Twenty patients were excluded during the observation period : Six had blood pressure values above normal , 5 had microalbuminuria , 3 had serum creatinine concentrations above the trial criterion , 1 patient developed unstable angina pectoris , and 5 withdrew consent . Of the 194 patients included in the study , 102 were women and 92 were men ( mean age SD , 54.9 3.2 years [ range , 37 to 59 years ] ) . The known duration of diabetes was 0 to 9 years ( mean duration , 5.75 2.8 years ) . Patients were instructed to use the st and ard isocaloric diet recommended by the Israeli Diabetic Association , and 69 study patients used diet alone to control their hyperglycemia . Pharmacologic therapy for diabetes was insulin in 34 patients and oral hypoglycemic agents in 91 patients . Protocol The protocol was approved by the hospital review board . After a 2-month observation period , patients were r and omly assigned in a double-blind manner to receive enalapril ( Assia-Riezel Ltd. , Ramat-Gan , Israel ) , 10 mg/d , or placebo . Ninety-seven patients were assigned to receive enalapril , and 97 were assigned to receive placebo . R and omization was done central ly by telephone with a r and om number table [ 18 ] . Patient allocation to placebo or enalapril was recorded and kept by one of the authors . The placebo tablets were similar in appearance to the enalapril tablets . The medications , which came in sealed , numbered packages , were central ly prepared and were given to the patients at each visit by one nurse who was otherwise not involved in the study . Patients were followed by their family physicians , who were unaware of allocation . Two semiannual prescheduled visits took place each year , and interim visits were scheduled as clinical ly indicated . At the semiannual visits , hemoglobin A1c values , serum creatinine concentrations , serum electrolyte levels , and 24-hour albumin excretion and urinary creatinine concentrations were measured . Blood pressure was measured by the physicians twice at each visit by using mercury sphygmomanometers with the patients seated after a 5-minute rest ; physicians recorded the average of the two values . The diastolic pressure was determined at Korotkoff phase V. If a systolic blood pressure of 145 mm Hg or more or a diastolic blood pressure of 95 mm Hg or more was found , measurements were repeated weekly . If elevated values persisted on two consecutive visits , a long-acting calcium-channel blocker ( diltiazem or verapamil ) , hydrochlorothiazide , or both were administered . If systolic blood pressure values of 100 mm Hg or less were repeatedly found , the enalapril dosage was reduced to 5 mg/d ( half of a 10-mg enalapril tablet or half of a placebo tablet ) . Fundoscopy was done yearly by an ophthalmologist , and the presence of retinopathy was recorded . For each patient , follow-up was terminated 6 years after r and omization . Measurements All blood and urine sample s were examined by a central laboratory . Assays were not changed during the study period . Glycosylated hemoglobin values were measured by affinity chromatography with a commercial kit ( Isolab , Biochemical Methodology , Akron , Ohio ) . The normal range of this assay is a hemoglobin A1c value of 3.5 % to 5.6 % and an intra-assay and interassay coefficient of variability of less than 3 % . Urinary albumin concentration was measured twice in 24-hour urine sample s by an automated immunoturbidimetric method [ 19 ] . This procedure has intra-assay and interassay coefficients of variability of 5.9 % and 7.6 % , respectively . Creatinine concentrations were determined by using the automated method of Bartels and colleagues [ 20 ] . Creatinine clearance , normalized for 1.73 m2 of body surface area , was calculated for each visit by using the st and ard formula ( urine creatinine x urine volume/plasma creatinine ) . The mean blood pressure ( defined as the diastolic pressure plus one third of the pulse pressure ) was calculated at each visit . Statistical Analysis Data are expressed as the mean ( SD ) with ranges . A P value less than 0.05 was considered significant . On the basis of the assumptions that 15 % of normotensive , normoalbuminuric patients with type 2 diabetes will develop microalbuminuria during 6 years and that treatment with enalapril will reduce the risk for microalbuminuria by 12 % , we calculated that 69 patients were required in each group for a type 1 error of 0.05 and a power of 0.80 [ 21 ] . To test for adequate r and omization and to compare the patients who completed the trial with those who did not complete the trial , the enalapril and placebo groups and the 38 patients who dropped out were compared for mean age ; mean duration of diabetes ; and mean baseline albumin excretion , creatinine clearance , glycosylated hemoglobin value , and blood pressure by using pooled-variance Student t-tests for independent groups and one-way analysis of variance . To compare the annual means of the various measurements between the two groups and within each group , one between-group factor and one repeated- measures factor were used in analysis of variance . For variables shown to be different by analysis of variance , unpaired t-tests were used for between-group parallel annual means and paired t-tests were used for comparison of intragroup sequential annual means . The rate of decrease of creatinine clearance and the rate of increase of albumin excretion were computed by doing linear regression analysis with all of the semiannual values included in the equation . Urinary albumin values were logarithmically transformed before analysis . The degree of albuminuria at baseline was used as a covariate . The funding source had no involvement in the design , conduct , or reporting of the trial . Results Figure 1 shows the flow of participants during the trial . Thirty-eight patients did not complete the trial . Five patients died ( 3 in the enalapril group and 2 in the placebo group ) ; death was related to coronary heart disease in 3 patients , stroke in 1 patient , and ovarian carcinoma in 1 patient . Six patients violated the protocol ( 2 patients in the enalapril group stopped taking their medication for more than 6 months , and 4 patients in the placebo group took an ACE inhibitor prescribed by consultant physicians for more than 6 months ) . Ten patients were lost to follow-up ( 6 in the enalapril group and 4 in the placebo group ) . The trial medication was discontinued in 12 patients : Six developed a disturbing cough ( 4 in the enalapril group and 2 in the placebo group ) , 4 had an allergic skin reaction ( 2 in the enalapril group and 2 in the placebo group ) , 1 patient in the enalapril group developed leukopenia , and 1 patient in the placebo group developed hyperkalemia . Finally , 5 patients developed severe urinary tract infections that had a detectable influence on renal function ( 2 in the enalapril group and 3 in the placebo group ) . A total of 156 patients completed the trial , of whom 77 received enalapril and 79 received placebo . Figure 1 . Flow of participants through the trial . Baseline data for the two groups and for patients who did not complete the trial are shown in Table 1 . The baseline characteristics of patients in the study groups and those who dropped out did not differ significantly . A modest but steady decrease in hemoglobin A1c values was seen in the enalapril and the placebo groups and may reflect the change in attitude toward glucose control among family physicians in the early 1990s . However ,", "Review articles are an important element of most medical journals and a popular source of information for clinicians ( 1 ) . Given the increasing volume of medical literature and the limited time for reading that busy clinicians have , reliance on review articles is likely to increase . However , concerns have been raised that narrative , non systematic review articles may produce biased conclusions ( 2 , 3 ) . Mulrow ( 4 ) examined 50 review articles published in four major medical journals ( The New Engl and Journal of Medicine , Annals of Internal Medicine , JAMA , and Archives of Internal Medicine ) in 1985 - 1986 and found that none fulfilled 8 explicit criteria for scientifically sound summaries of the evidence . As a result , she and others ( 5 , 6 ) proposed criteria for conducting and evaluating review articles that would improve their quality ; these criteria are the first 10 listed in the Appendix Table . In a study of 36 review articles done by nine content experts and method ologists , these criteria were shown to yield reliable and valid estimates of the scientific quality of review s ( 7 , 8) . We sought to describe the methods used in recently published review articles and determine whether the attention paid to the method ologic shortcomings of review articles has led to improvements in their scientific quality . Methods By using the Science Citation Index ( 9 ) , we stratified the 12 general medicine journals that are considered core journals for ACP Journal Club ( 10 ) into those with high impact factors ( scores 5 ) and those with lower impact factors . We r and omly selected 3 ( The New Engl and Journal of Medicine , Annals of Internal Medicine , and JAMA ) of the 4 high-impact core journals and 3 ( British Medical Journal , American Journal of Medicine , and Journal of Internal Medicine ) of the 8 core journals with lower impact factors . The sampling frame included 3 of the 4 journals examined in Mulrow 's original study ( 4 ) . All 6 journals were h and - search ed by two of the investigators independently , and review articles published between January and December 1996 were retrieved . Review articles were defined as full-text articles published under the banner review that dealt with disease states ; had the words review , overview , or meta- analysis in the title or abstract ; or indicated in the text that the intention was to review or summarize the literature about a clinical topic . Editorials , correspondence , and conference summaries were excluded . Disagreements on article eligibility ( which occurred in five cases ) were resolved by consensus . After training with a test set of articles , five of the authors used explicit criteria ( Appendix Table ) to rate the identified review articles . So that the raters ' assessment s would be blinded , the articles ' authors , author affiliations , and sources of articles were masked . The first 10 criteria in the Appendix Table ( hereafter referred to as method ologic criteria ) have been previously vali date d ( 7 ) and assess method ologic rigor , whereas the last five criteria were developed for this study to evaluate the scientific basis of treatment recommendations . Because inter-rater agreement was excellent on the test set ( overall agreement , 94 % ) , each rater was assigned a r and om sample of 20 % of the articles . One rater independently evaluated a r and om sample of five articles from each rater to assess inter-rater reliability for the criteria . The mean value was 0.79 , indicating substantial agreement ; overall agreement was 95 % and ranged from 84 % for criteria 1 and 6 to 100 % for criteria 2 , 3 , and 5 . After we determined the number of criteria fulfilled by each article , the number of articles meeting each criterion was ascertained . The proportion of review s from high-impact journals and from lower-impact journals that met each criterion were compared . Only the subset of review s containing treatment recommendations were used for the comparisons for criteria 7 to 15 . The chi-square test was used and 95 % CIs for the observed differences were calculated for all comparisons . In addition , articles identified as meta-analyses , systematic review s , or overviews in their title , abstract , or text were compared with the remaining review articles for each criterion ( again by using the chi-square test and by limiting analysis to those that included treatment recommendations for criteria 7 to 15 ) . Logistic regression analysis was used to adjust for journal of publication . The funding organizations were not involved in the design , conduct , analysis , or reporting of this study . Results A total of 158 review articles were identified : 60 from The New Engl and Journal of Medicine , 33 from Annals of Internal Medicine , 24 from British Medical Journal , 18 from American Journal of Medicine , 13 from JAMA , and 10 from Journal of Internal Medicine . ( A full list of the included articles is available from Dr. McAlister on request . ) Most review s were written by more than one author ( median number of authors , 2 [ range , 1 to 10 authors ] ) , and 111 review s ( 70 % ) made treatment recommendations . Although most articles had sections review ing the relevant pathophysiology and pharmacodynamics , 19 articles ( 12 % ) were largely basic science review s. Only 2 review s met all 10 method ologic criteria ; the median number of criteria fulfilled was one ( Figure ) . Nineteen ( 12 % ) of the review articles were described as meta- analysis , systematic review , or overview in the title or abstract ; 12 of these 19 articles were published in high-impact journals . A higher proportion of these articles met the method ologic criteria ( Appendix Table ) ; the comparisons for all but criterion 6 were statistically significant , even after adjustment for journal of publication ( P Percentage of 158 review articles published in 1996 that fulfilled specific method ologic criteria . Table . Comparison of Methods Used in 1996 Review Articles , by Journal Impact Factor The 44 articles that described how evidence was located used the following sources ( which were not mutually exclusive ) : MEDLINE ( 42 articles ) , h and search of reference lists from published studies or review articles ( 30 articles ) , other electronic data bases ( 14 articles ) , contact with experts in the field ( 10 articles ) , h and search of relevant journals ( 7 articles ) , and contact with the pharmaceutical industry ( 5 articles ) . Of the 22 review s that included a description of the electronic search strategy , the search was restricted to English- language publications in 11 . Of the 111 review s in which treatment recommendations were made , a median of 3 therapies ( range , 1 to 23 therapies ) were discussed . The 16 meta-analyses that included treatment recommendations were more focused , examining a median of 1 therapy ( range , 1 to 6 therapies ) . The scientific basis of these recommendations is outlined in the last five criteria of the Appendix Table . Discussion In summary , only a minority of the review articles published in six widely read general medical journals specified rigorous , systematic methods of identifying , evaluating , and synthesizing the evidence , thereby raising concerns about the validity of their conclusions and recommendations ( 11 ) . Furthermore , although most review articles made recommendations for therapeutic options , their clinical relevance may be limited : Only one third discussed benefits and harms of the treatment options , only 6 % mentioned the relative or absolute costs of the various options , less than half provided an estimate of the anticipated treatment effect , and very few presented the results in clinical ly relevant formats that would be easily understood by clinicians . Although there is still substantial room for improvement , these results do represent progress from the situation in 1985 - 1986 ( Appendix Table ) . A higher proportion of recently published review s specify how the evidence was identified and synthesized . This same pattern was observed in a recent study of oncology review articles published in a single journal between 1983 and 1995 ( 12 ) . Similarly , our findings for meta-analyses published in these journals in 1996 are consistent with contemporaneous investigations in other fields and represent substantial improvement over the state of affairs in the mid-1980s ( 13 , 14 ) . Our study had several potential limitations . First , the authors of articles in which systematic methods were not specified may have used such methods but not reported them ( or the journal may have removed the details of the methods in prepublication ) . However , preliminary evidence suggests that there is little difference between the conduct of studies and their published methods ( 7 , 15 ) . In other words , if what was done is not reported , there is a good chance that it was not done rigorously ( 7 ) . Second , our finding that meta-analyses are more scientifically rigorous than other review s may be seen as tautological because the criteria used in this study may be used by meta-analysts in performing their studies . However , meta-analysts disagree over some issues of methodology , and published meta-analyses often vary in the quality of their reports ( 13 ) . Third , the practical importance of the method ologic flaws identified in these review s is difficult to ascertain . We lack empirical evidence that review s with explicit , systematic methods yield results closer to the truth , but it is known that non systematic review s are more prone to r and om and", "Objectives To address whether nondihydropyridine calcium-channel blocker added-on angiotensin-converting-enzyme inhibitor therapy ameliorates albuminuria and cardiovascular outcomes in type 2 diabetes patients . Design The Bergamo Nephrologic Diabetes Complications Trial-B was a multicentre , prospect i ve , double-blind , parallel-group trial comparing renal and cardiovascular outcomes in 281 hypertensive type 2 diabetes patients with microalbuminuria r and omized to at least 2-year VeraTran ( verapamil/tr and olapril 180 mg/2 mg daily ) or tr and olapril ( 2 mg daily , identical image ) treatment . Main outcome was persistent macroalbuminuria ( albuminuria > 200 μg/min in two consecutive visits ) . Treatment targets were SBP/DBP less than 120/80 mmHg and HbA1C less than 7 % . Results Over a median follow-up of 4.5 years , 18 patients ( 13 % ) on VeraTran vs. 15 ( 10.5 % ) on tr and olapril [ unadjusted hazard ratio ( 95 % confidence interval [ CI ] ) 1.07 ( 0.54–2.12 ) , P = 0.852 ] progressed to macroalbuminuria , respectively ; 62 ( 44.9 % ) vs. 71 ( 49.7 % ) [ 0.80 ( 0.57–1.12 ) , P = 0.198 ] regressed to normoalbuminuria ( urinary albumin excretion had major cardiovascular events . BP and metabolic control were similar between groups . Patients with cardiovascular events were significantly less [ 13 ( 9.8 % ) vs. 28 ( 18.9 % ) , hazard ratio : 0.37 ( 0.19–0.71 ) , P = 0.003 ] among those regressing to normoalbuminuria than those without regression . Difference was independent of treatment allocation and was significant also after adjusting for baseline characteristics [ 0.40 ( 0.20–0.79 ) , P = 0.009 ] , follow-up SBP [ 0.40 ( 0.20–0.80 ) , P = 0.010 ] or DBP [ 0.36 ( 0.18–0.73 ) , P = 0.004 ] BP or HbA1C [ 0.43 ( 0.21–0.88 ) , P = 0.021 ] . Conclusion In hypertensive type 2 diabetes patients with microalbuminuria , verapamil added-on tr and olapril did not improve renal or cardiovascular outcomes . Independent of verapamil , tr and olapril normalized albuminuria in half of patients and this translated into significant cardioprotection ", "AIMS The aim of this study was to assess the effect of the angiotensin converting enzyme inhibitor perindopril on cardiovascular events in diabetic patients with coronary artery disease . METHODS AND RESULTS A total of 1502 diabetic patients with known coronary artery disease and without heart failure of 12 218 overall in the EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery ( EUROPA ) disease were r and omized in a double-blinded manner to perindopril 8 mg once daily or placebo . Follow-up was for a median of 4.3 years . The primary end point was cardiovascular death , non-fatal myocardial infa rct ion , and resuscitated cardiac arrest . Perindopril treatment was associated with a non-significant reduction in the primary endpoint in the diabetic population , 12.6 vs. 15.5 % , relative risk reduction 19 % [ ( 95 % CI , -7 to 38 % ) , P=0.13 ] . This was of similar relative magnitude to the 20 % risk reduction observed in the main EUROPA population . CONCLUSION Perindopril tends to reduce major cardiovascular events in diabetic patients with coronary disease in addition to other preventive treatments and the trend towards reduction was of a similar relative magnitude to that observed the general population with coronary artery disease", "BACKGROUND Although several important studies have been performed in hypertensive type 2 diabetic patients , it is not known whether lowering blood pressure in normotensive ( BP offers any beneficial results on vascular complications . The current study evaluated the effect of intensive versus moderate diastolic blood pressure ( DBP ) control on diabetic vascular complications in 480 normotensive type 2 diabetic patients . METHODS The current study was a prospect i ve , r and omized controlled trial in normotensive type 2 diabetic subjects . The subjects were r and omized to intensive ( 10 mm Hg below the baseline DBP ) versus moderate ( 80 to 89 mm Hg ) DBP control . Patients in the moderate therapy group were given placebo , while the patients r and omized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication . The primary end point evaluated was the change in creatinine clearance with the secondary endpoints consisting of change in urinary albumin excretion , progression of retinopathy and neuropathy and the incidence of cardiovascular disease . RESULTS The mean follow-up was 5.3 years . Mean BP in the intensive group was 128 + /- 0.8/75 + /- 0.3 mm Hg versus 137 + /- 0.7/81 + /- 0.3 mm Hg in the moderate group , P creatinine clearance ( P = 0.43 ) , a lower percentage of patients in the intensive group progressed from normoalbuminuria to microalbuminuria ( P = 0.012 ) and microalbuminuria to overt albuminuria ( P = 0.028 ) . The intensive BP control group also demonstrated less progression of diabetic retinopathy ( P = 0.019 ) and a lower incidence of strokes ( P = 0.03 ) . The results were the same whether enalapril or nisoldipine was used as the initial antihypertensive agent . CONCLUSION Over a five-year follow-up period , intensive ( approximately 128/75 mm Hg ) BP control in normotensive type 2 diabetic patients : ( 1 ) slowed the progression to incipient and overt diabetic nephropathy ; ( 2 ) decreased the progression of diabetic retinopathy ; and ( 3 ) diminished the incidence of stroke", "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 Recent trials question previously accepted low blood pressure targets in type 2 diabetes to reduce complication risk . We explored this question in the DIabetic REtinopathy C and esartan Trials-Protect 2 clinical trial . Methods A total of 1905 normoalbuminuric participants with type 2 diabetes and mild-moderate retinopathy were r and omized to c and esartan or placebo . Participants were normotensive [ untreated , blood pressure ( BP ) The effects of c and esartan on microvascular and macrovascular endpoints alone and in combination were analysed , including subgroup analyses by baseline hypertension status . Results Mean age was 57 ± 8 years , 50 % were men , mean diabetes duration was 9 ± 5 years and baseline HbA1c was 8.2 ± 1.6 % . Mean r and omization BP was 123/75 mmHg in the normotensive , and 139/79 mmHg in the treated hypertensive subgroups . During the median 4.7-year follow-up , achieved systolic pressure on c and esartan was 128 mmHg in baseline normotensive individuals , and 136 mmHg in treated hypertensive patients . C and esartan reduced combined macrovascular and microvascular complication risk ; the age and baseline SBP overall adjusted hazard ratio for c and esartan vs. placebo was 0.85 [ 95 % confidence interval ( CI ) 0.72–0.99 ] , P = 0.040 , reflecting hazard ratios of 0.86 ( 0.66–1.13 ) for baseline normotensive individuals and 0.83 ( 0.68–1.02 ) for hypertensive patients . Hazard ratios were 0.87 ( 0.74–1.04 ) for microvascular and 0.84 ( 0.57–1.25 ) for macrovascular complications , when analysed separately . However , an interaction ( P = 0.06 ) between hypertensive [ hazard ratio 0.67 ( 0.42–1.07 ) ] and normotensive ( 1.45 , 0.71–2.94 ) subgroups was observed for macrovascular events . Conclusion C and esartan modestly reduces vascular complication risk in treated hypertensive diabetic individuals at low risk of cardiovascular disease . Separate analyses of microvascular and macrovascular events suggest that c and esartan may not reduce macrovascular events in normotensive persons with type 2 diabetes . Clinical trial registration : http:// clinical trials.gov/ct2/show/NCT00252694", "BACKGROUND There is no evidence from r and omized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus . We investigated whether therapy targeting normal systolic pressure ( i.e. , participants with type 2 diabetes at high risk for cardiovascular events . METHODS A total of 4733 participants with type 2 diabetes were r and omly assigned to intensive therapy , targeting a systolic pressure of less than 120 mm Hg , or st and ard therapy , targeting a systolic pressure of less than 140 mm Hg . The primary composite outcome was nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The mean follow-up was 4.7 years . RESULTS After 1 year , the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the st and ard-therapy group . The annual rate of the primary outcome was 1.87 % in the intensive-therapy group and 2.09 % in the st and ard-therapy group ( hazard ratio with intensive therapy , 0.88 ; 95 % confidence interval [ CI ] , 0.73 to 1.06 ; P=0.20 ) . The annual rates of death from any cause were 1.28 % and 1.19 % in the two groups , respectively ( hazard ratio , 1.07 ; 95 % CI , 0.85 to 1.35 ; P=0.55 ) . The annual rates of stroke , a prespecified secondary outcome , were 0.32 % and 0.53 % in the two groups , respectively ( hazard ratio , 0.59 ; 95 % CI , 0.39 to 0.89 ; P=0.01 ) . Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group ( 3.3 % ) and 30 of the 2371 participants in the st and ard-therapy group ( 1.3 % ) ( P patients with type 2 diabetes at high risk for cardiovascular events , targeting a systolic blood pressure of less than 120 mm Hg , as compared with less than 140 mm Hg , did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events . ( Clinical Trials.gov number , NCT00000620 .", "is well recognized that hypertensives are especially prone to clinical manifestations of atherosclerosis in general and to coronary heart disease ( CHD ) in particular . Prospect i ve epidemiologic investigation of the circumstances under which CHD evolves in hypertensives compared to their more normotensive cohorts has revealed a number of misconceptions concerning the nature of the relationship of blood pressure to atherosclerotic vascular disease . This report is concerned with a detailed examination of the relationship of blood pressure to the development of the various clinical manifestations of CHD in each sex at varying ages . The", "IMPORTANCE Hypertension is the most important preventable cause of morbidity and mortality globally , yet there are relatively few data collected using st and ardized methods . OBJECTIVE To examine hypertension prevalence , awareness , treatment , and control in participants at baseline in the Prospect i ve Urban Rural Epidemiology ( PURE ) study . DESIGN , SETTING , AND PARTICIPANTS A cross-sectional study of 153,996 adults ( complete data for this analysis on 142,042 ) aged 35 to 70 years , recruited between January 2003 and December 2009 . Participants were from 628 communities in 3 high-income countries ( HIC ) , 10 upper-middle-income and low-middle-income countries ( UMIC and LMIC ) , and 4 low-income countries ( LIC ) . MAIN OUTCOMES AND MEASURES Hypertension was defined as individuals with self-reported treated hypertension or with an average of 2 blood pressure measurements of at least 140/90 mm Hg using an automated digital device . Awareness was based on self-reports , treatment was based on the regular use of blood pressure-lowering medications , and control was defined as individuals with blood pressure lower than 140/90 mm Hg . RESULTS Among the 142,042 participants , 57,840 ( 40.8 % ; 95 % CI , 40.5%-41.0 % ) had hypertension and 26,877 ( 46.5 % ; 95 % CI , 46.1%-46.9 % ) were aware of the diagnosis . Of those who were aware of the diagnosis , the majority ( 23,510 [ 87.5 % ; 95 % CI , 87.1%-87.9 % ] of those who were aware ) were receiving pharmacological treatments , but only a minority of those receiving treatment were controlled ( 7634 [ 32.5 % ; 95 % CI , 31.9%-33.1 % ] ) . Overall , 30.8 % , 95 % CI , 30.2%-31.4 % of treated patients were taking 2 or more types of blood pressure-lowering medications . The percentages aware ( 49.0 % [ 95 % CI , 47.8%-50.3 % ] in HICs , 52.5 % [ 95 % CI , 51.8%-53.2 % ] in UMICs , 43.6 % [ 95 % CI , 42.9%-44.2 % ] in LMICs , and 40.8 % [ 95 % CI , 39.9%-41.8 % ] in LICs ) and treated ( 46.7 % [ 95 % CI , 45.5%-47.9 % ] in HICs , 48.3 % , [ 95 % CI , 47.6%-49.1 % ] in UMICs , 36.9 % , [ 95 % CI , 36.3%-37.6 % ] in LMICs , and 31.7 % [ 95 % CI , 30.8%-32.6 % ] in LICs ) were lower in LICs compared with all other countries for awareness ( P Awareness , treatment , and control of hypertension were higher in urban communities compared with rural ones in LICs ( urban vs rural , P awareness , treatment , and control in LICs , but not in other countries . CONCLUSIONS AND RELEVANCE Among a multinational study population , 46.5 % of participants with hypertension were aware of the diagnosis , with blood pressure control among 32.5 % of those being treated . These findings suggest substantial room for improvement in hypertension diagnosis and treatment", "The Study on COgnition and Prognosis in the Elderly ( SCOPE ) assessed the effect of c and esartan on cardiovascular outcomes in elderly patients with mild to moderate hypertension . Patients were r and omized to c and esartan 8–16 mg daily ( n = 2477 ) or placebo ( n = 2460 ) . Due to extensive add‐on therapy , blood pressure reduction was only about 3/2 mmHg greater in the c and esartan group than in the control group . Nevertheless , non‐fatal stroke was reduced by 28 % ( p = 0.04 ) in the c and esartan group compared to the control group , and there was a non‐significant 11 % reduction in major cardiovascular events ( p = 0.19 ) . This report provides results in pre‐specified subgroups of patients ( age , gender , diabetes , history of stroke , smoking and cardiovascular risk at r and omization ) . Reductions in major cardiovascular events and stroke with c and esartan‐based therapy were indicated in all subgroups . A significant interaction between treatment and subgroups was found for one pair of subgroups only ; the reduction in major cardiovascular events with c and esartan was greater in patients with a previous stroke ( 64 % reduction , p = 0.004 ) than in those without ( 5 % reduction , p>0.20 ) . In conclusion , this analysis indicates consistent favourable effects of c and esartan‐based therapy on major cardiovascular events and stroke across the different subgroups of patients . However , the benefit was particularly pronounced in patients who entered the study with a previous stroke", "OBJECTIVE To assess if low ( 1.25 mg ) and /or st and ard ( 5 mg ) doses of the ACE inhibitor ramipril could prevent progression of microalbuminuria ( incipient diabetic nephropathy ) in normotensive type 1 diabetic patients . RESEARCH DESIGN AND METHODS This study , using a multicenter r and omized placebo-controlled double-blind parallel group , was conducted over 2 years in 28 outpatient diabetic clinics in the U.K. and Irel and . We screened 334 type 1 diabetic patients with suspected microalbuminuria and normal blood pressure ; of these , 140 patients 18 - 65 years of age with a diagnosis of type 1 diabetes and persistent microalbuminuria , defined as urinary albumin excretion rate ( AER ) of 20 - 200 microg/min , were enrolled in the study . RESULTS The proportion of patients progressing to macroalbuminuria was reduced in the ramipril groups but did not reach statistical significance over 2 years . AER was significantly lower at year 2 in the combined ramipril-treated patients versus placebo ( P = 0.013 ) . More patients on ramipril regressed to normoalbuminuria ( ramipril , 20 % for 5 mg ramipril , and 4 % for placebo ( P = 0.053 ) . Blood pressure was significantly reduced to a similar extent with both 1.25 and 5 mg ramipril . Supine systolic blood pressure increased from 130 to 134 mmHg in the placebo group and fell in the 1.25 mg ramipril group ( from 132 to 129 mmHg ) and in the 5 mg ramipril group ( from 134 to 130 mmHg ) ( P = 0.003 , compared with placebo ) . No statistically significant changes were observed in glomerular filtration rate ( GFR ) between the placebo- and ramipril-treated groups during the 2-year period . CONCLUSIONS Microalbuminuria is reduced significantly by ramipril treatment in type 1 diabetic patients without hypertension . Although the magnitude of the response was greater , there is no significant difference between responses to 1.25 or 5 mg ramipril . Small but highly significant reductions in systolic and mean arterial pressures occur in ramipril-treated patients . GFR is stable at this stage of the evolution of diabetic nephropathy and is unaffected by ramipril treatment for 2 years", "Summary The latter was due to a reduction in cardiac mortality ( −38 % , p=0.036 ) and a nonsignificant decrease in cerebrovascular mortality ( −32 % , p=0.16 ) . In the double-blind part of the trial , the total mortality rate was not significantly reduced ( −26 % , p=0.077 ) . However , cardiovascular mortality was reduced in the actively treated group ( −38 % , p=0.023 ) , owing to a reduction in cardiac deaths ( −47 % , p=0.048 ) and a non-significant decrease in cerebrovascular mortality ( −43 % , p=0.15 ) . Deaths from myocardial infa rct ion were reduced ( −60 % , p=0.043 ) , and study -terminating morbid cardiovascular events were significantly reduced by active treatment ( −60 % , p=0.0064 ) . Non-terminating cerebrovascular events were reduced ( −52 % , p=0.026 ) , but the non-terminating cardiac events were not ( + 3 % , p=0.98 ) . In the patients r and omised to active treatment there were 29 fewer cardiovascular events and 14 fewer cardiovascular deaths per 1000 patient years during the double-blind part of the trial . A double-blind r and omised placebo-controlled trial of antihypertensive treatment was conducted in patients over the age of 60 . Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range 90 to 119 mm Hg and a systolic pressure in the range 160 to 239 mm Eg . 840 patients were r and omised either to active treatment ( hydrochlorothiazide and triamterene ) or to matching placebo . If the blood pressure remained raised , methyldopa was added to the active regimen and matching placebo in the placebo group . An overall intention-to-treat analysis , combining the double-blind part of the trial and all subsequent follow-up , revealed a non-significant change in total mortality rate ( −9 % , p=0.41 ) but a significant reduction in cardiovascular mortality rate ( −27 % , p=0.037 )", "BACKGROUND Left ventricular dilatation and dysfunction after myocardial infa rct ion are major predictors of death . In experimental and clinical studies , longterm therapy with the angiotensin-converting -- enzyme inhibitor captopril attenuated ventricular dilatation and remodeling . We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infa rct ion . METHODS Within 3 to 16 days after myocardial infa rct ion , 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were r and omly assigned to receive doubleblind treatment with either placebo ( 1116 patients ) or captopril ( 1115 patients ) and were followed for an average of 42 months . RESULTS Mortality from all causes was significantly reduced in the captopril group ( 228 deaths , or 20 percent ) as compared with the placebo group ( 275 deaths , or 25 percent ) ; the reduction in risk was 19 percent ( 95 percent confidence interval , 3 to 32 percent ; P = 0.019 ) . In addition , the incidence of both fatal and nonfatal major cardiovascular events was consistently reduced in the captopril group . The reduction in risk was 21 percent ( 95 percent confidence interval , 5 to 35 percent ; P = 0.014 ) for death from cardiovascular causes , 37 percent ( 95 percent confidence interval , 20 to 50 percent ; P less than 0.001 ) for the development of severe heart failure , 22 percent ( 95 percent confidence interval , 4 to 37 percent ; P = 0.019 ) for congestive heart failure requiring hospitalization , and 25 percent ( 95 percent confidence interval , 5 to 40 percent ; P = 0.015 ) for recurrent myocardial infa rct ion . CONCLUSIONS In patients with asymptomatic left ventricular dysfunction after myocardial infa rct ion , long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events . These benefits were observed in patients who received thrombolytic therapy , aspirin , or beta-blockers , as well as those who did not , suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infa rct ion", "Background : The Reduction in ENdpoints with the Angiotensin Antagonist Losartan ( RENAAL ) study reported that losartan delayed the progression of renal disease in patients with type 2 diabetes and nephropathy . Diabetic or renally impaired patients are at high cardiovascular risk , a risk potentially increased in patients with both conditions", "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", "BACKGROUND The aim of this study is to compare the long-term effect of amlodipine and fosinopril in monotherapy or in combination on urinary albumin excretion ( UAE ) in hypertensive diabetic patients . METHODS We selected 453 hypertensive patients with type 2 diabetes and microalbuminuria and r and omized them to amlodipine ( 5 to 15 mg/day ) , fosinopril ( 10 to 30 mg/day ) , or amlodipine plus fosinopril ( 5/10 to 15/30 mg/day ) for a 3-month titration period . The nonresponder patients or those complaining of side effects during the titration period were discontinued ( n = 144 ) ; the remaining 309 patients were enrolled in the trial and treated with the same therapy for 4 years . Every 6 months , blood pressure ( BP ) , heart rate ( HR ) , UAE , creatinine clearance , and glycosylated hemoglobin ( HbA1c ) were evaluated . RESULTS The combination therapy was more effective in reducing BP than either drug alone at any time of the study without affecting glucose homeostasis . All three treatments provided a significant decrease in UAE during the 48-month study period . However , this effect was more pronounced and became evident earlier with fosinopril than with amlodipine monotherapy ( after 3 v 18 months of therapy ) . In addition , the combination therapy provided a greater antialbuminuric effect than the single drugs . This could be due to the greater antihypertensive effects , although other drug-specific effects can not be excluded . The cardiovascular outcomes were similar in the amlodipine and in the fosinopril group , but they were lower in the combination group . CONCLUSIONS These results strengthen the rationale to use a calcium-antagonist/angiotensin converting enzyme inhibitor combination in the treatment of hypertensive patients with type 2 diabetes", "BACKGROUND The objective of the current study was to examine the efficacy and tolerability of the beta-blocker metoprolol succinate controlled release/extended release ( CR/XL ) in patients with diabetes in the Metoprolol CR/XL R and omized Intervention Trial in Chronic Heart Failure ( MERIT-HF ) . METHODS The Cox proportional hazards model was used to calculate hazard ratios ( HR ) for convenience expressed as relative risks ( risk reduction = 1-HR ) , and 95 % confidence intervals ( CI ) . RESULTS The risk of hospitalization for heart failure was 76 % higher in diabetics compared to non-diabetics ( 95 % CI 38 % to 123 % ) . Metoprolol CR/XL was well tolerated and reduced the risk of hospitalization for heart failure by 37 % in the diabetic group ( 95 % CI 53 % to 15 % ) , and by 35 % in the non-diabetic group ( 95 % CI 48 % to 19 % ) . Pooling of mortality data from the Cardiac Insufficiency Bisoprolol Study II ( CIBIS II ) , MERIT-HF , and the Carvedilol Prospect i ve R and omized Cumulative Survival Study ( COPERNICUS ) showed similar survival benefits in patients with diabetes ( 25 % ; 95 % CI 40 % to 4 % ) and without diabetes ( 36 % ; 95 % CI 44 % to 27 % ) ; test of diabetes by treatment interaction was non-significant . Adverse events were reported more often on placebo than on metoprolol CR/XL . CONCLUSIONS Patients with heart failure and diabetes have a much higher risk of hospitalization than patients without diabetes . Regardless of diabetic status , a highly significant reduction in hospitalizations for heart failure was observed with metoprolol CR/XL therapy , which was very well tolerated also by patients with diabetes . Furthermore , the pooled data showed a statistically significant survival benefit in patients with diabetes", "BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease . Interruption of the renin-angiotensin system slows the progression of renal disease in patients with type 1 diabetes , but similar data are not available for patients with type 2 , the most common form of diabetes . We assessed the role of the angiotensin-II-receptor antagonist losartan in patients with type 2 diabetes and nephropathy . METHODS A total of 1513 patients were enrolled in this r and omized , double-blind study comparing losartan ( 50 to 100 mg once daily ) with placebo , both taken in addition to conventional antihypertensive treatment ( calcium-channel antagonists , diuretics , alpha-blockers , beta-blockers , and central ly acting agents ) , for a mean of 3.4 years . The primary outcome was the composite of a doubling of the base-line serum creatinine concentration , end-stage renal disease , or death . Secondary end points included a composite of morbidity and mortality from cardiovascular causes , proteinuria , and the rate of progression of renal disease . RESULTS A total of 327 patients in the losartan group reached the primary end point , as compared with 359 in the placebo group ( risk reduction , 16 percent ; P=0.02 ) . Losartan reduced the incidence of a doubling of the serum creatinine concentration ( risk reduction , 25 percent ; P=0.006 ) and end-stage renal disease ( risk reduction , 28 percent ; P=0.002 ) but had no effect on the rate of death . The benefit exceeded that attributable to changes in blood pressure . The composite of morbidity and mortality from cardiovascular causes was similar in the two groups , although the rate of first hospitalization for heart failure was significantly lower with losartan ( risk reduction , 32 percent ; P=0.005 ) . The level of proteinuria declined by 35 percent with losartan ( P patients with type 2 diabetes and nephropathy , and it was generally well tolerated", "Blood-pressure and cholesterol lowering in persons without cardiovascular disease Elevated blood pressure and elevated low-density lipoprotein ( LDL ) cholesterol increase the risk of cardiovascular disease . Lowering both should reduce the risk of cardiovascular events substantially . This proposition is examined in this r and omised trial in which patients without cardiovascular disease were r and omised to receive such treatments compared with placebos . The combination of rosuvastatin ( 10 mg per day ) , c and esartan ( 16 mg per day ) , and hydrochlorothiazide ( 12.5 mg per day ) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease . Muscle weakness and dizziness were more common in the combined therapy group , but the rate of discontinuation was similar in the two groups", "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", "BACKGROUND Combination therapy with angiotensin-converting-enzyme ( ACE ) inhibitors and angiotensin-receptor blockers ( ARBs ) decreases proteinuria ; however , its safety and effect on the progression of kidney disease are uncertain . Methods We provided losartan ( at a dose of 100 mg per day ) to patients with type 2 diabetes , a urinary albumin-to-creatinine ratio ( with albumin measured in milligrams and creatinine measured in grams ) of at least 300 , and an estimated glomerular filtration rate ( GFR ) of 30.0 to 89.9 ml per minute per 1.73 m(2 ) of body-surface area and then r and omly assigned them to receive lisinopril ( at a dose of 10 to 40 mg per day ) or placebo . The primary end point was the first occurrence of a change in the estimated GFR ( a decline of ≥ 30 ml per minute per 1.73 m(2 ) if the initial estimated GFR was ≥ 60 ml per minute per 1.73 m(2 ) or a decline of ≥ 50 % if the initial estimated GFR was end-stage renal disease ( ESRD ) , or death . The secondary renal end point was the first occurrence of a decline in the estimated GFR or ESRD . Safety outcomes included mortality , hyperkalemia , and acute kidney injury . Results The study was stopped early owing to safety concerns . Among 1448 r and omly assigned patients with a median follow-up of 2.2 years , there were 152 primary end-point events in the monotherapy group and 132 in the combination-therapy group ( hazard ratio with combination therapy , 0.88 ; 95 % confidence interval [ CI ] , 0.70 to 1.12 ; P=0.30 ) . A trend toward a benefit from combination therapy with respect to the secondary end point ( hazard ratio , 0.78 ; 95 % CI , 0.58 to 1.05 ; P=0.10 ) decreased with time ( P=0.02 for nonproportionality ) . There was no benefit with respect to mortality ( hazard ratio for death , 1.04 ; 95 % CI , 0.73 to 1.49 ; P=0.75 ) or cardiovascular events . Combination therapy increased the risk of hyperkalemia ( 6.3 events per 100 person-years , vs. 2.6 events per 100 person-years with monotherapy ; P ) and acute kidney injury ( 12.2 vs. 6.7 events per 100 person-years , P ACE inhibitor and an ARB was associated with an increased risk of adverse events among patients with diabetic nephropathy . ( Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development ; VA NEPHRON-D Clinical Trials.gov number , NCT00555217 . )", "BACKGROUND Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher , but its role in persons at intermediate risk and with lower blood pressure is unclear . METHODS In one comparison from a 2-by-2 factorial trial , we r and omly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either c and esartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo . The first co primary outcome was the composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke ; the second co primary outcome additionally included resuscitated cardiac arrest , heart failure , and revascularization . The median follow-up was 5.6 years . RESULTS The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg ; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group . The first co primary outcome occurred in 260 participants ( 4.1 % ) in the active-treatment group and in 279 ( 4.4 % ) in the placebo group ( hazard ratio , 0.93 ; 95 % confidence interval [ CI ] , 0.79 to 1.10 ; P=0.40 ) ; the second co primary outcome occurred in 312 participants ( 4.9 % ) and 328 participants ( 5.2 % ) , respectively ( hazard ratio , 0.95 ; 95 % CI , 0.81 to 1.11 ; P=0.51 ) . In one of the three prespecified hypothesis-based subgroups , participants in the subgroup for the upper third of systolic blood pressure ( > 143.5 mm Hg ) who were in the active-treatment group had significantly lower rates of the first and second co primary outcomes than those in the placebo group ; effects were neutral in the middle and lower thirds ( P=0.02 and P=0.009 , respectively , for trend in the two outcomes ) . CONCLUSIONS Therapy with c and esartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease . ( Funded by the Canadian Institutes of Health Research and AstraZeneca ; Clinical Trials.gov number , NCT00468923 . )", "BACKGROUND The optimal systolic blood pressure ( SBP ) treatment goal is in question , with SPRINT ( Systolic Blood Pressure Intervention Trial ) suggesting benefit for 120 mm Hg . However , achieving an SBP this low may reduce diastolic blood pressure ( DBP ) to levels that could compromise myocardial perfusion . OBJECTIVES This study sought to examine the independent association of DBP with myocardial damage ( using high-sensitivity cardiac troponin-T [ hs-cTnT ] ) and with coronary heart disease ( CHD ) , stroke , or death over 21 years . METHODS The authors studied 11,565 adults from the ARIC ( Atherosclerosis Risk In Communities ) cohort , analyzing DBP and hs-cTnT associations as well as prospect i ve associations between DBP and events . RESULTS Mean baseline age was 57 years , 57 % of patients were female , and 25 % were black . Compared with persons who had DBP between 80 to 89 mm Hg at baseline ( ARIC visit 2 ) , the adjusted odds ratio of having hs-cTnT ≥14 ng/l at that visit was 2.2 and 1.5 in those with DBP DBP at baseline was also independently associated with progressive myocardial damage on the basis of estimated annual change in hs-cTnT over the 6 years between ARIC visits 2 and 4 . In addition , compared with a DBP of 80 to 89 mm Hg , a DBP with incident CHD and mortality , but not with stroke . The DBP and incident CHD association was strongest with baseline hs-cTnT ≥14 ng/l ( p value for interaction low DBP with prevalent hs-cTnT and incident CHD were most pronounced among patients with baseline SBP ≥120 mm Hg . CONCLUSIONS Particularly among adults with an SBP ≥120 mm Hg , and thus elevated pulse pressure , low DBP was associated with sub clinical myocardial damage and CHD events . When titrating treatment to SBP < 140 mm Hg , it may be prudent to ensure that DBP levels do not fall below 70 mm Hg , and particularly not below 60 mm Hg", "To appreciate the importance of the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial,1 one needs to remember that the systolic blood pressure ( BP ) target currently recommended by major guidelines for diabetic patients , that is , 130 mm Hg , except in the Appropriate Blood Pressure Control in Diabetes Study ( ABCD ) normotensive trial,7 which consisted of only a few hundred patients and had changes in creatinine clearance as the primary end point . Thus , ACCORD represents the only large-scale r and omized trial that provides information on what happens to the cardiovascular risk of diabetic patients when SBP is reduced to 130 mm Hg as a result of r and omization to the usual ( rather than the tight ) BP control treatment strategy . Thus , the message from ACCORD to guidelines and clinical practice is that in diabetic patients it is not necessary to adopt" ]

[ "OBJECTIVE : To examine whether cycled lighting ( CL ) conditions during neonatal care in very preterm infants ( decrease crying and fussing behavior , improve the consolidation of sleep , and influence activity behavior at 5 and 11 weeks ’ postterm corrected age ( CA ) compared with preterm infants cared for in dim lighting ( DL ) conditions . METHODS : Thirty-seven preterm infants were r and omly assigned to CL ( 7 am–7 pm lights on , 7 pm–7 am lights off [ n = 17 ; mean GA : 30.6 ± 0.95 weeks ; 9 girls ] ) or DL ( lights off whenever the child is asleep [ n = 20 ; GA : 29.5 ± 2.1 weeks ; 8 girls ] ) conditions . Sleeping , crying , and activity behavior was recorded by using parental diaries and actigraphy at 5 and 11 weeks ’ CA . RESULTS : A significant reduction of fussing ( 59.4 minutes/24 hours [ ±25.8 minutes ] ) and crying ( 31.2 minutes/24 hours [ ±14.4 minutes ] ) behavior and a trend to higher motor activity during daytime was found in CL-exposed infants at 5 and 11 weeks ’ CA compared with infants cared for in DL conditions . No significant difference between groups was observed for sleep behavior at 5 and 11 weeks ’ CA . Infants in CL conditions showed a trend to improved daily weight gain ( average : 3.6 g/d ) during neonatal care compared with DL conditions . CONCLUSIONS : CL conditions in neonatal care have beneficial effects on infant ’s fussing and crying behavior and growth in the first weeks of life . This study supports the introduction of CL care in clinical neonatal practice", "Day-night cycled light improves health outcomes in preterm infants , yet the best time to institute cycled light is unclear . The hypothesis of this study was that extremely preterm infants receiving early cycled light would have better health and developmental outcomes than infants receiving late cycled light . Infants born at ≤28 weeks gestation were r and omly assigned to early cycled light ( ECL ) starting at 28 weeks postmenstrual age [ PMA ] or late cycled light ( LCL ) , starting at 36 weeks PMA . Daylight was 200 - 600 lux and night was 5 - 30 lux . Primary outcomes were weight over time and length of hospitalization . Secondary outcomes were hospital costs , sleep development , and neurodevelopment at 9 , 18 , and 24 months corrected age . Of 121 infants r and omized , 118 were included in analysis . Weight gain in the two groups did not differ significantly but increased across time in both groups . In PMA weeks 36 - 44 , the mean weight gain was 193.8 grams in the ECL group compared to 176.3 grams in the LCL group . Effect sizes for weight were Cohen d = 0.26 and 0.36 for 36 and 44 weeks PMA . Infants in the ECL group went home an average of 5.5 days earlier than the LCL group , but this difference was not statistically significant . There were no group differences on neurodevelopmental outcomes . Although statistically non-significant , clinical ly important differences of improved weight gain and decreased hospital stay were observed with ECL . The small observed effect sizes on weight during hospitalization should be considered in future cycled light research with extremely preterm infants . © 2017 Wiley Periodicals ,", "PURPOSE Premature infants lack the tactile stimulation they would have otherwise experienced in the womb . Infant massage is a developmentally supportive intervention that has been documented for several decades to have a positive effect on both full term and preterm infants . The purpose of this study was to assess the short and long term benefits of massage on stable preterm infants . METHODS A quasi experimental design was used , 66 infants were recruited from two university hospitals with tertiary level NICUs ; 32 infants received the massage therapy by their mothers . Data collection by a research er blind to the infants ' group assignments included weight at discharge , pain responses on the PIPP scale at discharge , length of stay in hospital , neuro-developmental outcome ( Bayley scores ) and breastfeeding duration at 12 months corrected age . RESULTS Infants who were massaged had significantly lower scores on the PIPP after a heel-stick compared to before the massage and had lower PIPP scores at discharge compared to the control group . Massaged infants had higher cognitive scores at 12 months corrected age . Weight gain , length of stay , breastfeeding duration and motor scores did not differ between groups . CONCLUSION Stable preterm infants benefit from massage therapy given by their mothers and may be a culturally acceptable form of intervention to improve the outcomes of preterm infants", "Objective : To investigate in a r and omised controlled trial the effect of basic elements of developmental care ( incubator covers and positioning aids ) on growth and neurodevelopment in infants born at Method : Infants were r and omised within 48 h of birth to a developmental care ( DC ) or st and ard care ( C ) group . Outcome measures at 1 and 2 years corrected age were growth , st and ardised neurological examinations , and mental ( MDI ) and psychomotor ( PDI ) development ( Dutch version of the Bayley Scales of Infant Development II ) . Results : 192 infants were recruited ( DC = 98 ; C = 94 ) . Thirteen infants ( DC = 7 , C = 6 ) were excluded because they were admitted for In total , 179 infants met the inclusion criteria . In-hospital mortality was 12/91 ( 13.2 % ) in the DC group and 8/88 ( 9.1 % ) in the C group . Assessment s were carried out on 147 children ( DC = 74 , C = 73 ) at 1 year and 142 children ( DC = 72 , C = 70 ) at 2 years . No significant difference in growth , neurological outcomes or MDI was found . A positive trend in PDI at 1 year ( p = 0.05 ) did not continue once the children reached 2 years . There was no difference found when neurological and developmental scores were combined . Conclusions : Basic developmental care has no positive effect on neurological and mental development or growth at 1 and 2 years of age in infants born at A positive effect on psychomotor development at 1 year did not continue at 2 years of age . Trial registration number : IS RCT N84995192", "OBJECTIVE To evaluate associations between neonatal intensive care unit ( NICU ) room type ( open ward and private room ) and medical outcomes ; neurobehavior , electrophysiology , and brain structure at hospital discharge ; and developmental outcomes at 2 years of age . STUDY DESIGN In this prospect i ve longitudinal cohort study , we enrolled 136 preterm infants born Upon admission , each participant was assigned to a bedspace in an open ward or private room within the same hospital , based on space and staffing availability , where they remained for the duration of hospitalization . The primary outcome was developmental performance at 2 years of age ( n = 86 infants returned for testing , which was 83 % of survivors ) measured using the Bayley Scales of Infant and Toddler Development , 3rd Edition . Secondary outcomes were : ( 1 ) medical factors throughout the hospitalization ; ( 2 ) neurobehavior ; and ( 3 ) cerebral injury and maturation ( determined by magnetic resonance imaging and electroencephalography ) . RESULTS At term equivalent age , infants in private rooms were characterized by a diminution of normal hemispheric asymmetry and a trend toward having lower amplitude integrated electroencephalography cerebral maturation scores ( P = .02 ; β = -0.52 [ CI -0.95 , -0.10 ] ) . At age 2 years , infants from private rooms had lower language scores ( P = .006 ; β = -8.3 [ CI -14.2 , -2.4 ] ) and a trend toward lower motor scores ( P = .02 ; β = -6.3 [ CI -11.7 , -0.99 ] ) , which persisted after adjustment for potential confounders . CONCLUSION These findings raise concerns that highlight the need for further research into the potential adverse effects of different amounts of sensory exposure in the NICU environment", "The Infant Health and Development Program is a r and omized clinical trial to test the efficacy of educational and family support services and pediatric follow-up , offered during the first 3 years of life , in reducing the incidence of developmental delay in low birth weight preterm infants at eight clinical sites ( N = 985 ) . It was hypothesized that larger intervention effects would be found for the domains in which low birth weight preterm infants are known to have problems , specifically visual-motor and spatial skills and receptive language skills . These analyses explore the effects of the Infant Health and Development Program on different domains of cognitive functioning . Cognitive domains are identified by means of factor analysis of the intelligence tests used at 12 , 24 , and 36 months ( Bayley Scales of Infant Development ( including the Mental and Motor scales ) at 12 and 24 months ; the Stanford-Binet , Peabody Picture Vocabulary Test , and Beery Test of Visual Motor Intergration at 36 months ) . Our results reveal that , although intervention benefits accrue across cognitive domains at 24 and 36 months , gains are most pronounced for receptive language and visual-motor and spatial skills", "How should health care professionals choose among the many therapies cl aim ed to be efficacious for treating specific disorders ? The practice of evidence -based medicine provides an answer . Advocates of this approach urge health care professionals to base treatment choices on the best evidence from systematic research on both the efficacy and adverse effects of various therapeutic alternatives . Ideally , health care professionals would compare different treatments by referring to r and omized , double-blind , head-to-head trials that compared the treatment options . Although individual medications are typically well research ed when these placebo-controlled studies are performed , studies that directly compare treatments are rare . In the absence of direct head-to-head trials , other evidence comes from indirect comparisons of two or more therapies by examining individual studies involving each treatment . This article provides an introductory review of methods of such indirect comparisons of therapies across studies , provides examples of how these methods can be used to make treatment decisions , and presents a general overview of relevant issues and statistics for readers interested in underst and ing these methods more thoroughly", "OBJECTIVE . This was a r and omized , controlled trial to investigate the effect of Newborn Individualized Developmental Care and Assessment Program on growth , cognitive , psychomotor , and neuromotor development at 1 and 2 years in infants born at METHODS . Infants were r and omly assigned within 48 hours of birth to the newborn individualized developmental care and assessment program group ( intervention ) or basic developmental care group ( control group [ ie , incubator covers and nests ] ) . At 1 and 2 years ’ corrected age , growth was measured and st and ardized neurologic examinations were administered . Mental and psychomotor development was assessed by using the Dutch version of the Bayley Scales of Infant Development II . Neurologic outcome , Psychomotor Developmental Index , and Mental Developmental Index scores were combined a total outcome measure . RESULTS . One hundred sixty-eight infants were recruited ( intervention : 84 ; control : 84 ) . Four infants ( newborn intervention : 3 ; control : 1 ) were excluded because they were admitted less than or died within the first 5 days , leaving a total of 164 infants who met inclusion criteria . In-hospital mortality was 8 of 81 in the intervention group and 3 of 83 in the control group . At 1 year of age 148 children ( intervention : 70 ; control : 78 ) and at 2 years of age 146 children ( intervention : 68 ; control : 78 ) were assessed . There was no significant difference in growth at 1 and 2 years of age . There was no significant difference found in neurologic outcomes or mental and psychomotor development at 1 and 2 years of age . When neurologic outcome , Mental Developmental Index and Psychomotor Developmental Index scores were combined , there still remained no significant difference . CONCLUSIONS . Newborn individualized developmental care and assessment program developmental care showed no effect on growth or neurologic , mental , or psychomotor development at 1 and 2 years of age in infants born at Duration of the intervention was not associated with neurologic and developmental outcome", "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 To determine the effect of developmental care on neurodevelopmental outcome in formerly preterm infants at a corrected age of 2 years . METHODS A prospect i ve phase-lag study was performed at an Austrian neonatal intensive care unit ( NICU ) . From January 2003 to December 2005 ( study period of conventional care ) and January 2007 to December 2009 ( study period of developmental care ) , we enrolled all infants born in Tyrol at less than 32 weeks of gestation . During this period a total of 261 of 359 preterm infants ( participation rate 72.7 % ) completed the follow-up visit at 2 years of age ; there were 124 children in the conventional and 137 in the developmental care group . The association between developmental care and delayed motor or mental development ( Bayley Scales of Infant Development II ; psychomotor or mental developmental index developmental care group showed less psychomotor delay than did those in the control group ( developmental care group : 16.1 % , conventional care group 27.4 % ; adjusted odds ratio 0.37 [ 95 % confidence interval : 0.19 - 0.74 ] , P=0.005 ) . Not smoking in pregnancy and higher gestational age were also significant predictors for a better psychomotor outcome at 2 years of age . Regarding cognitive outcome , no significant difference was observed between these two groups . CONCLUSION Our data implicate that developmental care may result in an improved 2-year psychomotor outcome in formerly preterm infants", "OBJECTIVE The Neonatal Individualized Developmental Care Program ( NIDCAP ) for very low birth weight ( VLBW ) preterm infants has been suggested by Als et al to improve several medical outcome variables such as time on ventilator , time to nipple feed , the duration of hospital stay , better behavioral performance on Assessment of Preterm Infants ' Behavior ( APIB ) , and improved neurodevelopmental outcomes . We have tested the hypothesis of whether the infants who had received NIDCAP would show advanced sleep-wake pattern , behavioral , and neurodevelopmental outcome . METHODS Thirty-five VLBW infants were r and omly assigned to receive NIDCAP or routine infant care . The goals for NIDCAP intervention were to enhance comfort and stability and to reduce stress and agitation for the preterm infants by : a ) altering the environment by decreasing excess light and noise in the neonatal intensive care unit ( NICU ) and by using covers over the incubators and cribs ; b ) use of positioning aids such as boundary supports , nests , and buntings to promote a balance of flexion and extension postures ; c ) modification of direct h and s-on caregiving to maximize preparation of infants for , tolerance of , and facilitation of recovery from interventions ; d ) promotion of self-regulatory behaviors such as holding on , grasping , and sucking ; e ) attention to the readiness for and the ability to take oral feedings ; and f ) involving parents in the care of their infants as much as possible . The infants ' sleep was recorded at 36 weeks postconceptional age ( PCA ) and at 3 months corrected age ( CA ) using the Motility Monitoring System ( MMS ) , an automated , nonintrusive procedure for determining sleep state from movement and respiration patterns . Behavioral and developmental outcome was assessed by the Neurobehavioral Assessment of the Preterm Infant ( NAPI ) at 36 weeks PCA , the APIB at 42 weeks PCA , and by the Bayley Scales of Infant Development ( BSID ) at 4 , 12 , and 24 months CA . RESULTS Sleep developmental measures at 3 months CA showed a clear developmental change compared with 36 weeks PCA . These include : increased amount of quiet sleep , reduced active sleep and indeterminate sleep , decreased arousal , and transitions during sleep . Longest sleep period at night showed a clear developmental effect ( increased ) when comparing nighttime sleep pattern of infants at 3 months with those at 36 weeks of age . Day-night rhythm of sleep-wake increased significantly from 36 weeks PCA to 3 months CA . However , neither of these sleep developmental changes showed any significant effects of NIDCAP intervention . Although all APIB measures showed better organized behavior in NIDCAP patients , neither NAPI nor Bayley showed any developmental advantages for the intervention group . The neurodevelopmental outcome measured by the Bayley at 4 , 12 , and 24 months CA showed 64 % of the NIDCAP intervention group at the lowest possible score compared with 33 % of the control group . These findings could not be explained by the occurrence of intraventricular hemorrhage or the socioeconomic status of the parents , which showed no significant group effect . CONCLUSION The results of this study , including measures of sleep maturation and neurodevelopmental outcome up to 2 years of age did not demonstrate that the NIDCAP intervention results in increased maturity or development . Buehler et al ( Pediatrics . 1995;96:923 - 932 ) have reported that premature infants ( N = 12 ; mean gestational age 32 weeks , mean birth weight 1700 g ) who received developmental care compared with a similar group of infants who received routine care showed better organized behavioral performance on an APIB assessment at 42 weeks PCA . None of the medical outcome measures were significantly different in this study . Although our APIB results are in agreement , the results of the NAPI , the Bayley and sleep measures do not show an increase in neurodevelopmental maturation . In the earlier report by Als et al ( Journal of the American Medical", "Objective : To determine whether very low birth weight ( VLBW ) newborns ( wearing silicone earplugs grow larger and perform better on developmental exams than controls . Study Design : VLBW newborns ( n=34 ) were r and omized to wearing earplugs or not . Hospital outcomes were abstract ed from medical charts by research staff masked to intervention status . Fourteen extremely low birth weight ( ELBW ) newborns ( were also evaluated at 18 to 22 months . Result : After adjusting for birth weight , 11 surviving newborns in the earplug group were 225 g ( 95 % CI : 45 , 405 ) heavier at 34 weeks post menstrual age than the 13 controls . Six ELBW earplug infants scored 15.53 points ( 95 % CI : 3.03 , 28.02 ) higher than six controls on the Bayley Mental Development Index . Their head circumferences were 2.59 cm ( 95 % CI : 0.97 , 4.21 ) larger . Conclusion : Earplugs may facilitate weight gain in VLBW newborns . Better outcomes may persist at 18 to 22 months at least in ELBW infants", "Objective : The effect of NIDCAP ( Newborn Individualized Developmental Care and Assessment Program ) was examined on the neurobehavioral , electrophysiological and neurostructural development of preterm infants with severe intrauterine growth restriction ( IUGR ) . Study Design : A total of 30 infants , 27–33 weeks gestation , were r and omized to control ( C ; N=17 ) or NIDCAP/experimental ( E ; N=13 ) care . Baseline health and demographics were assessed at intake ; electroencephalography ( EEG ) and magnetic resonance imaging ( MRI ) at 35 and 42 weeks postmenstrual age ; and health , growth and neurobehavior at 42 weeks and 9 months corrected age ( 9 months ) . Results : C and E infants were comparable in health and demographics at baseline . At follow-up , E infants were healthier , showed significantly improved brain development and better neurobehavior . Neurobehavior , EEG and MRI discriminated between C and E infants . Neurobehavior at 42 weeks correlated with EEG and MRI at 42 weeks and neurobehavior at 9 months . Conclusion : NIDCAP significantly improved IUGR preterm infants ' neurobehavior , electrophysiology and brain structure . Longer-term outcome assessment and larger sample s are recommended", "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", "OBJECTIVE : Our objective was to determine the impact of Newborn Individualized Developmental Care and Assessment Program (NIDCAP)-based care on length of stay of very low birth weight ( VLBW ) infants . Secondary outcome measures were days of ventilation , incidence of chronic lung disease , and 18-month neurodevelopmental outcomes . METHODS : This cluster-r and omized , controlled trial took place in a large NICU in Canada , with follow-up evaluation at 18 months of age , from September 1999 to September 2004 . One hundred VLBW singleton infants and 10 VLBW twin sets were assigned r and omly to NIDCAP-based or control care , and 90 % participated in follow-up assessment s. The intervention was NIDCAP-based care ( N = 56 ) , that is , care by NIDCAP-educated staff members and behavioral observations . The control group ( N = 55 ) received st and ard NICU care . Statistical analyses were adjusted for cluster r and omization . Although the intervention was not blinded , the pediatricians making the decisions to discharge the infants were not involved in the study , and the follow-up staff members were blinded with respect to group . RESULTS : NIDCAP group infants had reduced length of stay ( median : NIDCAP : 74 days ; control : 84 days ; P = .003 ) and incidence of chronic lung disease ( NIDCAP : 29 % ; control : 49 % ; odds ratio : 0.42 [ 95 % confidence interval : 0.18–0.95 ] ; P = .035 ) . At 18 months of adjusted age , NIDCAP group infants had less disability , specifically mental delay ( NIDCAP : 10 % ; control : 30 % ; odds ratio : 0.25 [ 95 % confidence interval : 0.08–0.82 ] ; P = .017 ) . CONCLUSION : NIDCAP-based care for VLBW infants improved short- and long-term outcomes significantly", "BACKGROUND Preterm infants are at increased risk of cognitive , motor and behavioral problems . Different intervention programs have been design ed in an attempt to improve outcome , but the results are conflicting . OBJECTIVE To examine the effects of an early intervention program on cognitive , motor and behavioral problems and parenting stress among low birth weight children at 2 years corrected age . METHODS A r and omized controlled trial was conducted including infants with a birth weight to examine the effects of a modified version of the Mother-Infant Transaction Program on cognitive , motor and behavioral outcomes and parenting stress . The children were assessed with the Bayley Scales of Infant Development and the Child Behavior Checklist/2 - 3 ( CBCL ) and the Parenting Stress Index were administered to the parents at 2 years corrected age . RESULTS Sixty-nine children in the intervention group and 67 in the control group were assessed at 2 years . There were no differences between the groups in cognitive or motor outcomes . The intervention group scored consistently lower on all CBCL syndrome scales , but no difference was significant . The mothers in the intervention group reported significantly lower parental stress in both child and parent domain , whereas the fathers reported lower stress in child domain compared to the control group . CONCLUSION This early intervention program does not improve cognitive , motor or behavioral outcomes at 2 years . There was a significant reduction in parenting stress reported by both mothers and fathers in the intervention group", "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 effects of nursery-based intervention with healthy , prematurely born babies and their socially disadvantaged mothers were evaluated . Mother-infant dyads were r and omly assigned to one of three intervention groups : In group one , the babies received special stimulation design ed to make them more active contributors to the interactions with their mothers ; in group two , mothers received special training to help them become more responsive to cues from their babies ; in group three , infants received stimulation and mothers received training . In addition , a fourth group of preterm babies who received regular hospital care served as a comparison group to assess the short-term effects of the stimulation program . Outcome measures design ed to evaluate various aspects of mother-infant interaction and infant development failed to reflect any effects of the interventions , either at the time the babies were discharged from the hospital or one year later . We attribute the lack of positive findings to the fact that the mothers faced numerous crises in their social environments . We conclude , therefore , that nothing short of massive social change is likely to result in measurable effects", "OBJECTIVE : The goal was to examine the effectiveness of an early intervention on cognitive and motor outcomes at corrected ages of 3 and 5 years for children with birth weights ( BWs ) of METHODS : A r and omized controlled trial of a modified version of the Mother-Infant Transaction Program was performed . Outcomes were assessed with the Bayley Scales of Infant Development II and the Wechsler Preschool and Primary Scale of Intelligence-Revised at 3 and 5 years , respectively . McCarthy Scales of Children 's Abilities and the grooved pegboard test were used to test motor outcomes at 5 years . RESULTS : A total of 146 infants were assigned r and omly ( intervention group : 72 infants ; control group : 74 infants ) . The mean BWs were 1396 ± 429 g for the intervention group and 1381 ± 436 g for the control group . After adjustment for maternal education , a nonsignificant difference in Mental Developmental Index scores at 3 years of 4.5 points ( 95 % confidence interval : −0.3 to 9.3 points ) in favor of the intervention group was found , whereas the intervention effect on full-scale IQ scores at 5 years was 6.4 points ( 95 % confidence interval : 0.6–12.2 points ) . Significantly more children in the intervention group had IQ scores of ≥85 at 3 and 5 years . There were no differences between the groups with respect to motor outcomes . CONCLUSION : This modified version of the Mother-Infant Transaction Program improved cognitive outcomes at corrected age of 5 years for children with BWs of < 2000", "BACKGROUND Long term effects of massage therapy in very preterm newborns infants are still to be described . Few studies evaluated neurodevelopment just at six months , and included late preterm infants . OBJECTIVE To study the effect of massage therapy on neurodevelopment of very low birth weight infants at two years corrected age . STUDY DESIGN Newborns with birth weight between > or= 750 and r and omly assigned to massage therapy by mothers plus skin-to-skin care ( Intervention Group ) or just skin-to-skin care ( Control Group ) during their hospital stay . Growth and neurodevelopment outcome were evaluated at 2 years corrected age . RESULTS We followed 73 newborns ( 35 in Intervention Group , and 38 in Control Group ) . Both groups were similar in neonatal data . Growth at 2 years corrected age was similar in both groups . Intervention Group had borderline higher Psychomotor Development Index and significantly higher Mental Development Index scores than Control Group . CONCLUSIONS We suggest that massage therapy by mothers combined to skin-to-skin care during neonatal hospital stay improves neurodevelopment outcome at 2 years corrected age", "Objective : This study investigates the effectiveness of the Newborn Individualized Developmental Care and Assessment Program ( NIDCAP ) on neurobehavioral and electrophysiological functioning of preterm infants with severe intrauterine growth restriction ( IUGR ) . Study Design : Thirty IUGR infants , 28 to 33 weeks gestational age , r and omized to st and ard care ( control/C=18 ) , or NIDCAP ( experimental/E=12 ) , were assessed at 2 weeks corrected age ( 2wCA ) and 9 months corrected age ( 9mCA ) in regard to health , anthropometrics , and neurobehavior , and additionally at 2wCA in regard to electrophysiology ( EEG ) . Result : The two groups were comparable in health and anthropometrics at 2wCA and 9mCA . The E-group at 2wCA showed significantly better autonomic , motor , and self-regulation functioning , improved motility , intensity and response thresholds , and reduced EEG connectivity among several adjacent brain regions . At 9mCA , the E-group showed significantly better mental performance . Conclusion : This is the first study to show NIDCAP effectiveness for IUGR preterm infants" ]

[ "PURPOSE / OBJECTIVES To evaluate self-reports of fatigue by young cancer survivors ( aged 11 - 18 years ) , to compare young survivors ' fatigue scores with the scores of a healthy control group and of the parent proxy evaluation , and to analyze whether demographic or disease-related factors are associated with young survivors ' fatigue . DESIGN Cross-sectional quantitative study . SETTING An urban hospital in southwestern Finl and . SAMPLE 384 survivors diagnosed with an extracranial malignancy at age 16 or younger , who have survived four or more years postdiagnosis , and who are free of cancer . General matched population controls were r and omly selected from the Finnish Population Registry . METHODS Demographic data and a self-report written fatigue question naire . MAIN RESEARCH VARIABLES Total fatigue ( TF ) , general fatigue ( GF ) , sleep or rest fatigue ( SF ) , and cognitive fatigue . FINDINGS The control population s reported significantly more issues with TF , GF , and SF than did the survivor population . In survivors , older age , the need for remedial education at school , and a sarcoma diagnosis were associated with increasing fatigue , whereas female gender , better school grade s , and greater health-related quality -of-life ( HRQOL ) scores were associated with lower fatigue . The study variables explained 49%-65 % of the variation in fatigue scores . CONCLUSIONS Although survivors and their matched controls seem to have similar fatigue , subgroups of survivors do experience excessive fatigue , which may have an impact on their HRQOL . IMPLICATION S FOR NURSING This study increases the knowledge about fatigue levels of young survivors of extracranial malignancies and identifies the need for instruments specifically design ed to assess fatigue in this population . The healthcare team should pay attention to the fatigue level of young survivors , particularly SF", "OBJECTIVE : Cognitive behavioral therapy ( CBT ) is known to be an effective treatment of adolescents with chronic fatigue syndrome ( CFS ) , but its availability is limited . Fatigue in Teenagers on the Internet ( FITNET ) , an Internet-based CBT program for adolescents with CFS , has been developed as an alternative to face-to-face CBT . Recently , its short-term effectiveness has been proven in a r and omized clinical trial . Here we aim ed to assess the long-term outcome of CFS in adolescents after FITNET treatment and after usual care . In addition , factors related to recovery at long-term follow-up ( LTFU ) for adolescents treated with the FITNET program were investigated . METHODS : The study was an LTFU of participants of the FITNET trial . Data were completed for 112 ( 88.2 % ) of 127 approached FITNET study participants . Primary outcomes were fatigue severity ( Checklist Individual Strength–20 ) , physical functioning ( 87-item Child Health Question naire ) , and school/work attendance . RESULTS : After a mean follow-up of 2.7 years , 66 ( 58.9 % ) adolescents had recovered from CFS . Most adolescents who recovered directly after treatment with FITNET were still recovered at LTFU . At LTFU there was no difference between the recovery rates for the different treatment strategies ( original r and omization : FITNET [ 64 % ] versus any form of usual care [ 52.8 % ] ) . Per additional month of “ pretreatment disease duration , ” the odds for recovery were 4 % lower ( odds ratio : 0.96 ; 95 % confidence interval : 0.93–0.99 ; P = .016 ) , and per added point on “ focus on bodily symptoms ” ( Body Consciousness Scale ) of the mother ( 0–20 points ) the odds for recovery were 11 % lower ( odds ratio : 0.89 ; 95 % confidence interval : 0.80–0.99 ; P = .029 ) . CONCLUSIONS : The short-term effectiveness of Internet-based CBT on adolescent CFS is maintained at LTFU . At LTFU , usual care led to similar recovery rates , although these rates were achieved at a slower pace", "Neuropsychologic data are presented from a r and omized , double-blind , placebo-controlled , multicenter study with placebo , topiramate 50 mg/day , and topiramate 100 mg/day . The Cambridge Neuropsychological Test Automated Battery ( CANTAB ) and cognitive adverse events were used to evaluate neurocognitive effects of topiramate . Topiramate 100 mg/day vs placebo was associated with slight statistically significant score increases , indicating slowing , from baseline vs placebo in three CANTAB measures : five-choice reaction time ( P = 0.028 ) , pattern recognition memory mean correct latency ( P = 0.027 ) , and rapid visual information processing mean latency ( P = 0.040 ) . No other patterns related to topiramate treatment were observed in measurements of learning , memory , and visual information processing , except for potential improvement with topiramate 100 mg/day vs placebo in spatial span total errors ( accuracy test ) ( P = 0.040 ) . The most common cognitive and neuropsychiatric adverse events with a higher incidence in the topiramate 50 and 100 mg/day groups vs placebo were anorexia ( 9 % and 11 % vs 3 % ) , insomnia ( 9 % and 3 % vs 3 % ) , fatigue ( 6 % and 9 % vs 6 % ) , and dizziness ( 6 % and 9 % vs 0 % ) . Thus , topiramate 100 mg/day was associated with modest increases in psychomotor reaction times . Learning , memory , and executive function were unchanged . The tolerability profile , including cognitive adverse events , appeared to be acceptable", "The aim of this research is to examine the experience and impact of chemotherapy-related fatigue in recently diagnosed pediatric oncology patients . A repeated- measures , within-subjects , mixed ( quantitative plus qualitative ) design was used to prospect ively assess fatigue during early chemotherapy cycles and to compare fatigue to depressive symptoms . Parental interviews collected concurrently were analyzed for descriptions of the child 's fatigue and mood states and for strategies to cope with fatigue . Results indicated a significant correlation between fatigue and depression , but qualitative analyses suggested that the 2 phenomena may be unique and distinguishable . Qualitative analyses of parent interviews also identified specific strategies that were frequently used in response to high levels of fatigue . The findings illustrate the significant impact of chemotherapy-related fatigue in children being treated for cancer . The study also provides guidance for the assessment of fatigue and related symptoms and identifies specific strategies for coping with fatigue", "OBJECTIVE : To determine nationwide general practitioner (GP)-diagnosed prevalence and pediatrician – diagnosed incidence rates of adolescent chronic fatigue syndrome ( CFS ) , and to assess CFS morbidity . DESIGN AND SETTING : We collected data from a cross-sectional national sample among GPs and prospect i ve registration of new patients with CFS in all pediatric hospital departments in the Netherl and s. PATIENTS AND METHODS : Study participants were adolescents aged 10 to 18 years . A representative sample of GPs completed question naires on the prevalence of CFS in their adolescent patients . Pediatric hospital departments prospect ively reported new cases of CFS in adolescent patients . For every new reported case , a question naire was sent to the reporting pediatrician and the reported patient to assess CFS morbidity . Prevalence was estimated through the data from GP question naires and incidence was estimated on the basis of cases newly reported by pediatricians from January to December 2008 . RESULTS : Prevalence was calculated as 111 per 100 000 adolescents and incidence as 12 per 100 000 adolescents per year . Of newly reported patients with CFS , 91 % scored at or above cutoff points for severe fatigue and 93 % at or above the cutoff points for physical impairment . Forty-five percent of patients with CFS reported > 50 % school absence during the previous 6 months . CONCLUSIONS : Clinical ly diagnosed incidence and prevalence rates show that adolescent CFS is uncommon compared with chronic fatigue . The primary adverse impact of CFS is extreme disability associated with considerable school absence", "Anxiety symptoms are commonly described in children with chronic fatigue syndrome or myalgic encephalopathy ( CFS/ME ) but to date there has been little information on the type of anxiety children experience or the relationship between anxiety and school attendance , disability or fatigue . The aim of this study was to first describe the prevalence and type of anxiety symptoms in children with CFS/ME compared with a normal European population , and secondly to investigate the association of anxiety symptoms with age , gender , school attendance , fatigue , and physical function in paediatric CFS/ME . Data were prospect ively collected on children and young people with CFS/ME referred to a large specialist CFS/ME service . One hundred and sixty-four children with CFS/ME had complete data for the Spence Children ’s Anxiety Scale . Teenage girls had the highest rates of total anxiety symptoms with 38 % ( 95 % CI 27–49 ) over the cut off ( top 10 % of normal European population ) and significantly higher rates of symptoms in each subscale . Younger girls were more likely to score over the cut off in separation anxiety ( 37 % , 19–40 ) and social phobia ( 39 % , 25–47 ) . There was no evidence of association between total anxiety symptoms and : time at school , time to assessment , pain or age . Associations with fatigue and physical function were attenuated when adjusted for other variables . Although anxiety symptoms are high in CFS/ME , particularly in teenage girls , it does not appear to be associated with school attendance or other measures of disability . Separation anxiety and social phobia were the most clearly elevated in paediatric CFS/ME", "Background Childhood obesity is a growing health concern known to adversely affect quality of life in children and adolescents . The Patient Reported Outcomes Measurement Information System ( PROMIS ) pediatric measures were developed to capture child self-reports across a variety of health conditions experienced by children and adolescents . The purpose of this study is to begin the process of validation of the PROMIS pediatric measures in children and adolescents affected by obesity . Methods The pediatric PROMIS instruments were administered to 138 children and adolescents in a cross-sectional study of patient reported outcomes in children aged 8–17 years with age-adjusted body mass index ( BMI ) greater than the 85th percentile in a design to establish known-group validity . The children completed the depressive symptoms , anxiety , anger , peer relationships , pain interference , fatigue , upper extremity , and mobility PROMIS domains utilizing a computer interface . PROMIS domains and individual items were administered in r and om order and included a total of 95 items . Patient responses were compared between patients with BMI 85 to 136 participants were recruited and had all necessary clinical data for analysis . Of the 136 participants , 5 % ended the survey early result ing in missing domain scores at the end of survey administration . In multivariate analysis , patients with BMI ≥ 99th percentile had worse scores for depressive symptoms , anger , fatigue , and mobility ( p for depressive symptoms , anxiety , and fatigue ( p Children and adolescents ranging from overweight to severely obese can complete multiple PROMIS pediatric measures using a computer interface in the outpatient setting . In the 5 % with missing domain scores , the missing scores were consistently found in the domains administered last , suggesting the length of the assessment is important . The differences in domain scores found in this study are consistent with previous reports investigating the quality of life in children and adolescents with obesity . We show that the PROMIS instrument represents a feasible and potentially valuable instrument for the future study of the effect of pediatric obesity on quality of life", "Background Health-related quality of life ( HRQOL ) is an essential subject for children with end-stage renal disease ( ESRD ) and their families . Methods We performed a cross-sectional investigation of HRQOL in children undergoing renal replacement therapies , such as dialysis and renal transplantation , using the 34-item Pediatric Quality of Life Inventory 3.0 End-Stage Renal Disease ( PedsQL 3.0 ESRD ) module . We assessed 92 ESRD patients aged 2–18 from four Korean university hospitals . Results The male : female ratio was 44:48 , and the most common cause of ESRD was chronic glomerulonephritis . Fifty-five children were treated by dialysis , and 37 received renal transplantation . Transplant patients had better HRQOL than dialysis patients in two domains in parent proxy reports : “ About my kidney disease ” and “ Worry . ” In child self-reports , transplant patients had better HRQOL than dialysis patients in one domain : Treatment problems . However , there were no significant differences in total QOL scores between peritoneal dialysis ( PD ) and transplant patients in child self-reports . In addition , there were differences in the ESRD module scores between child self- and parent proxy reports . Children usually reported better QOL than their parents . Child self-reports showed significantly higher QOL scores than parent proxy reports in the domains of General fatigue , Family & peer interaction , and Worry . Children on PD self-reported a significantly higher QOL than children on hemodialysis ( HD ) . Conclusions The PedsQL 3.0 ESRD module may be useful as an ESRD-specific instrument to evaluate HRQOL in children ; however , a larger , longitudinal prospect i ve study is warranted", "PURPOSE / OBJECTIVES To determine the feasibility of collecting symptom data at home from school-age children with acute lymphoblastic leukemia ( ALL ) and from their fathers and mothers and to obtain initial descriptions of pain , sleep disturbance , and fatigue experienced by the family members at home . DESIGN Prospect i ve and descriptive . SETTING Children 's homes in Oregon and southwestern Washington . SAMPLE 9 children with ALL ( aged 8 - 16 years ) , 6 fathers , and 7 mothers . The children received vincristine during the maintenance phase of their outpatient chemotherapy treatments . METHODS With age-appropriate , paper- and -pencil diaries and wrist actigraphy , data were collected for three days in the families ' homes . Families were reminded by telephone to complete their sleep and activity diaries . MAIN RESEARCH VARIABLES Pain , sleep disturbance , and fatigue in school-age children and their fathers and mothers . FINDINGS Most of the families who were approached indicated willingness to participate in the study . After receiving outpatient chemotherapy , the children reported pain , sleep disturbance , and fatigue data over three days . Fathers and mothers also reported symptoms . Actigraphy showed children waking more often during the night than mothers or fathers . CONCLUSIONS Children 's pain , sleep disturbance , and fatigue suggest that the symptoms are influencing families ' quality of life . Larger studies are needed to examine the symptom patterns and health outcomes of children , fathers , and mothers over the course of chemotherapy . IMPLICATION S FOR NURSING Improving sleep and managing pain and fatigue after chemotherapy treatment for children with ALL may improve health outcomes for children and parents", "BACKGROUND Chronic fatigue syndrome is characterised by persistent fatigue and severe disability . Cognitive behavioural therapy seems to be a promising treatment , but its availability is restricted . We developed Fatigue In Teenagers on the interNET ( FITNET ) , the first dedicated internet-based therapeutic program for adolescents with this disorder , and compared its effectiveness with that of usual care . METHODS Adolescents aged 12 - 18 years with chronic fatigue syndrome were assigned to FITNET or usual care in a 1:1 ratio at one tertiary treatment centre in the Netherl and s by use of a computer-generated blocked r and omisation allocation schedule . The study was open label . Primary outcomes were school attendance , fatigue severity , and physical functioning , and were assessed at 6 months with computerised question naires . Analysis was by intention to treat . Thereafter , all patients were offered FITNET if needed . This trial is registered , number IS RCT N59878666 . FINDINGS 68 of 135 adolescents were assigned to FITNET and 67 to usual care , and 67 and 64 , respectively , were analysed . FITNET was significantly more effective than was usual care for all dichotomised primary outcomes at 6 months-full school attendance ( 50 [ 75 % ] vs 10 [ 16 % ] , relative risk 4·8 , 95 % CI 2·7 - 8·9 ; p ( 57 [ 85 % ] vs 17 [ 27 % ] , 3·2 , 2·1 - 4·9 ; p , and normal physical functioning ( 52 [ 78 % ] vs 13 [ 20 % ] , 3·8 , 2·3 - 6·3 ; p ) . No serious adverse events were reported . INTERPRETATION FITNET offers a readily accessible and highly effective treatment for adolescents with chronic fatigue syndrome . The results of this study justify implementation on a broader scale . FUNDING Netherl and s Organisation for Health Research and Development", "OBJECTIVES To determine and compare the prevalence of disturbed sleep in JIA and JDM and the relationship of sleep disturbance to pain , function , disease activity and medications . METHODS One hundred fifty-five patients ( 115 JIA , 40 JDM ) were r and omly sample d and were mailed question naires . Sleep disturbance was assessed by the sleep self-report ( SSR ) and the children 's sleep habits question naire ( CSHQ ) . Fatigue , pain and function were assessed by the paediatric quality of life inventory ( PedsQL ) and disease activity by visual analogue scales ( VASs ) . Joint counts were self-reported . RESULTS Eighty-one per cent responded , of whom 44 % reported disturbed sleep ( CSHQ > 41 ) ; there were no differences between disease groups . Poor reported sleep ( SSR ) was highly correlated with PedsQL fatigue ( r = 0.56 , P Fatigue was highly negatively correlated with quality of life ( r = -0.77 , P worst pain intensity in the last week was correlated to sleep disturbance ( r = 0.32 , P = 0.0005 ) . Fatigue was associated with prednisone and DMARD use . CONCLUSIONS Sleep disturbance and fatigue are prevalent among children with different rheumatic diseases . Sleep disturbance and fatigue are strongly associated with increased pain and decreased quality of life . Strategies aim ed at improving sleep and reducing fatigue should be studied as possible ways of improving quality of life for children with rheumatic illness", "PURPOSE / OBJECTIVES To examine the relationship between physical performance and fatigue in child and adolescent cohorts during the first three cycles of chemotherapy . DESIGN Prospect i ve , observational design . SETTING Two pediatric cancer centers in the upper Midwest region of the United States . SAMPLE 16 children and 14 adolescents newly diagnosed with cancer . METHODS St and ardized instruments were administered during the first and third cycles of chemotherapy . Instruments included physical performance tests ( Timed Up and Down Stairs [ TUDS ] and the 6-Minute Walk Test [ 6MWT ] ) and a self-report fatigue scale . MAIN RESEARCH VARIABLES Fatigue and physical performance . FINDINGS In the child cohort , physical performance appeared to improve and fatigue diminished from cycle 1 to 3 of chemotherapy . When time on TUDS decreased , fatigue tended to decrease ; when 6MWT distance increased , fatigue decreased . In the adolescent cohort , fatigue seemed to decrease but physical performance measures evidence d little change . Correlations between changes in the physical performance variables and fatigue were not significant . CONCLUSIONS Fatigue may decrease early in treatment as disease symptoms resolve . Fatigue in the child cohort was related to physical performance , which is consistent with previous studies that defined fatigue in children as primarily a physical sensation . Findings in the adolescent cohort support research that defined adolescent fatigue as more complex with mental , emotional , and physical components . IMPLICATION S FOR NURSING Knowing how fatigue relates to physical performance in children and adolescents informs the nurse in educating patients and families about symptom management", "OBJECTIVE A small-scale intervention study into narrative self-investigation in adolescent chronic fatigue syndrome ( CFS ) . METHOD The self-confrontation method ( SCM ) is an instrument to assess and change personal life stories . Forty-two adolescents diagnosed with CFS were included and r and omly assigned to either 6 or 12 sessions with the SCM . Twenty-five healthy adolescents were assigned to 6 sessions . Outcome was measured directly after the self-investigation procedure at 4 months . Follow-up measurements were made 10 months later . The Checklist Individual Strength and the Child Health Question naire were used to measure changes in fatigue , physical and psychosocial functioning . RESULTS Self-investigation result ed in significant changes in participants ' narratives . Moreover , after self-investigation there was a significant improvement in fatigue , physical and psychosocial functioning for the adolescents with CFS . The patients who completed 12 sessions improved most . At follow-up , the positive effects were maintained . CONCLUSION Self-investigation enables a move beyond the symptoms of CFS in an individualized , patient centered way . Narrative transformation seems to contribute to improved physical and psychosocial outcome in adolescent CFS . PRACTICE IMPLICATION S The SCM allows adolescents to discover ( for themselves ) factors that might cause or perpetuate their fatigue . The results suggest that self-investigation is a useful instrument in the management of adolescent CFS", "The French incidence study has registered all new cases of Type 1 diabetic children under 20 years of age , from a population of 2.32 million , in an exhaustive and prospect i ve manner . Three hundred and forty cases were identified between 1 January 1988 and 31 December 1989 , yielding a mean annual incidence rate 7.3 per 10(5 ) . The lowest rate was observed in the youngest age group ( 0 - 4 yr : 4.1 per 10(5 ) ) and the highest around pubertal development ( 10 - 14 yr : 11.5 per 10(5 ) ) . Details of the previous personal and family history , and the clinical and biological pictures of the disease at diagnosis were recorded . Almost 8 per cent of the children had a first-degree relative with Type 1 diabetes . Polyuria , weight loss , fatigue and abdominal pain were the most frequently reported symptoms , which were of median duration 4.4 months . Mean weight loss before diagnosis was 9.4 + /- 6.8 ( + /- SD)% of body weight and was not significantly related to age . Ketonuria was detected in 83.8 per cent and acidosis ( total CO2 less than or equal to 18 mmol l-1 , if measured ) in 48 per cent of the cases . Ketonuria and acidosis were significantly more frequent in the younger age group than in the rest of the group ( p less than 0.001 )", "OBJECTIVE To compare adolescents who do and do not recover from acute infectious mononucleosis in terms of fatigue severity and activity levels before , during , and in the 2 years following infection . DESIGN Prospect i ve case-control study . SETTING The baseline and 12- and 24-month evaluations occurred in the subjects ' homes . The 6-month outpatient visit occurred at Children 's Memorial Hospital in Chicago , Illinois . PARTICIPANTS Three hundred one adolescents ( aged 12 - 18 years ) with acute infectious mononucleosis . MAIN EXPOSURES All participants were evaluated at baseline ( during active infection ) . Six months following infection , 39 of them met criteria for chronic fatigue syndrome . These subjects were matched by sex and Tanner stage to 39 r and omly selected screened-negative subjects . Both groups were reevaluated at 12- and 24-month follow-ups . OUTCOME MEASURES Scores from the Fatigue Severity Scale and the Modifiable Activity Question naire . RESULTS For both groups , physical activity levels declined and sleep increased as a result of having mononucleosis . Compared with their matched controls , adolescents with chronic fatigue syndrome reported significantly higher levels of fatigue at all points and spent significantly more time sleeping during the day 6 and 12 months following infection . The 2 groups did not differ significantly in terms of physical activity levels before , during , or after infection . There was a consistent trend for decreased physical activity in the chronic fatigue syndrome group . CONCLUSIONS Adolescents with chronic fatigue syndrome appear to be pushing themselves in an attempt to maintain similar activity levels as their peers , but paying for it in terms of fatigue severity and an increased need for sleep , particularly during the day", "This prospect i ve , two-site , r and omized , controlled pilot study assessed the feasibility of an enhanced physical activity ( EPA ) intervention in hospitalized children and adolescents receiving treatment for a solid tumor or for acute myeloid leukemia ( AML ) , and assessed different statistical techniques to detect the intervention 's sleep and fatigue outcomes . Twenty-nine patients ( 25 with a solid tumor and 4 with AML ) participated . Data were collected from actigraph ; patient , parent , and staff nurse reports of patient fatigue ; parent sleep diaries ; and patient charts . The intervention was successfully implemented 85.4 % of the scheduled times . We used two different statistical methods to analyze the longitudinal data . Using an ANOVA model , sleep was significantly more efficient in the experimental arm than in the control arm when daily differences from baseline sleep efficiency values were averaged and compared ( F=4.17 , P=0.053 ) . However , in a mixed model ( repeated measures ) analysis , sleep duration ( F=0.54 , P=0.47 ) and sleep efficiency ( F=0.04 , P=0.85 ) were not seen to differ between study arms . We conclude that an inpatient intervention of EPA can be delivered to children and adolescents receiving chemotherapy . Our findings identify design and statistical considerations for a future effectiveness study of the EPA intervention in hospitalized pediatric oncology patients", "This experimental , r and omized controlled study was conducted for children with cancer who are 7 to 12 years of age and receiving chemotherapy treatment to detect the impact of appropriate nursing interventions on decreasing the fatigue syndrome . The research sample is composed of a total of 60 children with cancer , with 30 children being included in the experimental group and 30 children included in the control group with their mothers . In the experimental group , after the 7th to 10th day of the chemotherapy treatment , throughout a week , the research er conducted the effective nursing interventions every day for 45 to 60 minutes . In the control group , routine nursing interventions were carried out . The experimental and control group children 's mean scores for the Fatigue Scale-Child and those of mothers for Fatigue Scale-Parent were compared . A statistically significant difference was found between the Fatigue Scale-Child and Fatigue Scale-Parent mean scores of the experimental and the control group children ( P fatigue of children with cancer can be reduced by implementing appropriate nursing interventions", "BACKGROUND Fatigue is described as one of the most distressing symptoms of cancer therapy ; yet it has received limited clinical attention . Children are suffering from a symptom that is under-diagnosed during their treatment . AIM The aim of this study is : ( a ) to assess the change in fatigue scores during cancer treatment according to children 's perspectives , and ( b ) to describe the possible causes of fatigue from children 's points of view . SAMPLE AND METHODS The present study is part of an ongoing prospect i ve study . The research group consisted of 40 ( n = 40 ) children aged 7 - 12 years with cancer who are being followed up in the oncology clinic of a Greek children 's hospital . After parental consent was obtained , data were collected using the Child Fatigue Scale and a sociodemographic data form . RESULTS The children with cancer reported a statistically significant increase in fatigue scores during their treatment ( F = 6.846 , P = 0.003 ) . Gender was the only demographic factor associated with a significant increase in the fatigue scores ( F = 4.857 , P = 0.034 ) . CONCLUSIONS Cancer treatment was found significantly to increase children 's fatigue levels . Medical procedures and the hospital environment seemed to be major causative factors of the fatigue experienced by children with cancer during their treatment", "PURPOSE / OBJECTIVES To examine the influence of the proposed symptom cluster of fatigue , nausea and vomiting , and sleep disturbances on clinical outcomes defined as behavior changes , depression , and performance status in children and adolescents before and after receiving cisplatin , doxorubicin , or ifosfamide chemotherapy . DESIGN A prospect i ve , descriptive , within-group , before- and -after-chemotherapy design was used . SETTING Two major childhood cancer treatment hospitals in the United States . SAMPLE 67 patients aged 7 - 18 years who were receiving chemotherapy courses of cisplatin , doxorubicin , or ifosfamide . METHODS Fatigue , depression , behavior , and performance assessment s were completed on the first day of cisplatin , doxorubicin , or ifosfamide therapy and one week later . Patients wore a wrist actigraph on the nondominant h and during the course of therapy and for 48 hours after discharge from the hospital . Nausea and vomiting were measured every 24 hours during the course of therapy and for 48 hours after discharge . A linear mixed model was used to evaluate the influence of the symptom cluster . Regression analysis was used to examine the associations between performance status and the symptom cluster . Principal component analysis with varimax rotation was used to produce the correlation of sleep symptoms . MAIN RESEARCH VARIABLES Fatigue , nausea and vomiting , sleep disturbances , behavior , depression , and performance . FINDINGS Adolescents with the cluster of increased fatigue and sleep disturbances experienced more depressive symptoms and behavior changes . Children with higher levels of fatigue had increased depressive symptoms . The more fatigue parents perceived in their children or adolescents , the more behavior and emotional difficulties were reported . CONCLUSIONS Fatigue , sleep disturbance , and nausea and vomiting , when clustered , impacted depressive symptoms and behavior changes in adolescents after chemotherapy . In children , fatigue alone impacted depressive symptoms and behavior changes . IMPLICATION S FOR NURSING Symptom clusters can have a significant impact on children 's and adolescents ' quality of life during cancer treatment . Early recognition and intervention for these symptoms are an important nursing role" ]

[ "Background Nonalcoholic fatty liver disease ( NAFLD ) is one of the most common reasons of enzyme increase in liver . In About 10 percent of patients with NAFLD , the disease progresses toward Non Alcoholic Steatohepatitis ( NASH ) and about one third of them may progress toward cirrhosis , liver dysfunction , and even hepatocellular carcinoma . Objectives According to high prevalence of NAFLD and the fact that there is no consensus on treatment of this disease , the aim of this study was to assess the effects of metformin , pioglitazone , and silymarin on treatment of NAFLD . Patients and Methods Sixty six patients with NAFLD who were presented in the Endocrinology and Metabolism clinic of Boo’ali Hospital , Qazvin , Iran , were assigned r and omly into three groups ( n = 22 ) . First group was treated by pioglitazone 15 mg/d , second group by metformin 500 mg/d , and third group by silymarin 140 mg/d . All patients underwent clinical and biochemical evaluations including weight , fasting blood sugar ( FBS ) , lipid profiles , body mass index ( BMI ) , aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , and serum insulin levels in pre- and post-intervention after eight-week follow up . Results Before the treatment there was no significant difference between three groups with respect to average age , BMI and gender , FBS , lipid profile , AST , ALT , serum insulin level , and Homeostasis Model Assessment ( HOMA ) index for insulin resistance . After the intervention , a significant reduction was observed in average amount of FBS , lipid profile , ALT , AST , serum insulin level and HOMA index in three groups ( P FBS , TG , serum insulin level , and HOMA index was observed in pioglitazone group , the most reduction in average amount of cholesterol was seen in metformin group , and the most decrease in average amount of AST and ALT occurred in silymarin group . Conclusions These results suggest that all drugs are beneficial in improving biochemical indices in patients with NAFLD . Changes in AST and ALT in silymarin group were demonstrated more than that in other groups and the average difference between changes was significant between silymarin and metformin groups", "This prospect i ve study was carried out in order to evaluate the influence on liver morphology and function of a very-low-calorie formula diet . Fourty-one morbidly obese , non-alcoholic subjects had liver biopsy performed before and after a median weight loss of 34 kg . Fatty change improved ( p less than 0.001 ) , but 24 % of the patients developed slight portal inflammation ( p = 0.039 ) or slight portal fibrosis ( p = 0.063 ) . Patients developing portal fibrosis had a higher degree of fatty change at entry ( p = 0.029 ) , a more pronounced reduction of fatty change ( p = 0.014 ) and a faster weight loss ( p = 0.026 ) . Liver biochemistry , which was of no individual diagnostic value , improved . It is concluded that morbidly obese subjects with a high degree of hepatic fatty change are at risk of developing portal inflammation and fibrosis when undergoing very fast dietary weight reductions ", "OBJECTIVE Non-alcoholic fatty liver disease ( NAFLD ) is an increasingly recognized health problem . Various treatment strategies such as thiazolidinediones , metformin , lipid-lowering agents and antioxidants have been evaluated . So far , no single intervention has convincingly improved liver histology . Experience of using silymarin alone or in combination with other agents in patients with NAFLD is limited in the medical literature . The present study was conducted to evaluate the efficacy of silymarin plus vitamin E in the treatment of NAFLD . PATIENTS AND METHODS A sample of 36 patients was enrolled . The diagnosis of NAFLD was confirmed by percutaneous liver biopsy . All patients were r and omized to one of the following intervention groups : group I : treated with 2 tablets per day of silymarin plus vitamin E ( Eurosil 85 ® , MEDAS SL ) and a lifestyle modification program consisting of hypocaloric diet ( 1520 kcal , 52 % of carbohydrates , 25 % of lipids and 23 % of proteins ) and exercise for 3 months and group II ( only with the hypocaloric diet ) . Anthropometric variables as waist circumference , weight , body mass index ( BMI ) were measured . Biochemical parameters : Glucose , triglycerides , AST , ALT , GGt levels and insulin resistance ( HOMA-IR ) were determined under fasting conditions . Non-invasive NAFLD-index were applied before and after the treatments : Fatty liver index ( FLI ) , liver accumulation product ( LAP ) and NAFLD-Fibrosis score ( FS ) . RESULTS The mean age was 47.4 ± 11.2 years old ( range 18 - 67 ) ; 22 men and 14 women . In group I , 11 patients ( 61 % ) have a NAS-score > 5 and 10 ( 55.5 % ) in the group II ( NS ) . Anthropometric parameters decreased after treatment in both groups . Patients in both groups showed a decrease in GGt levels after treatment ( group I : 68 IU/L vs. 46.2 ± 27 IU/L ; p decrease in AST and ALT levels . In both groups , we observed a decrease in : FLI index ( group I : 86.2 ± 19 vs. 76.9 + 20 ; p ) , and NAFLD-FS index ( group I : -1.6 ± 1.8 vs. -2.1 ± 1.5 ; p decreased GGt levels , and in the FLI and NAFLD-FS indexes ; whereas patients in group II without decrease of 5 % by weight showed no improvement in any of the analyzed parameters . CONCLUSIONS Treatment with silymarin plus vitamin E and a hypocaloric diet ameliorate function hepatic test , and non-invasive NAFLD index . Silymarin can be an alternative valid therapeutic option particularly when other drugs are not indicated or have failed or as a complementary treatment associated with other therapeutic programs", "Silymarin , used by 30 to 40 % of liver disease patients , is composed of six major flavonolignans , each of which may contribute to silymarin 's hepatoprotective properties . Previous studies have only described the pharmacokinetics for two flavonolignans , silybin A and silybin B , in healthy volunteers . The aim of this study was to determine the pharmacokinetics of the major silymarin flavonolignans in liver disease patients . Healthy volunteers and three patient cohorts were administered a single , 600-mg p.o . dose of milk thistle extract , and 14 blood sample s were obtained over 24 h. Silybin A and B accounted for 43 % of the exposure to the sum of total silymarin flavonolignans in healthy volunteers and only 31 to 38 % in liver disease cohorts as a result of accumulation of silychristin ( 20–36 % ) . Area under the curve ( AUC0–24h ) for the sum of total silymarin flavonolignans was 2.4- , 3.3- , and 4.7-fold higher for hepatitis C virus ( HCV ) noncirrhosis , nonalcoholic fatty liver disease ( p ≤ 0.03 ) , and HCV cirrhosis cohorts ( p ≤ 0.03 ) , respectively , compared with healthy volunteers ( AUC0–24h = 2021 ng · h/ml ) . Caspase-3/7 activity correlated with the AUC0–24h for the sum of all silymarin conjugates among all subjects ( R2 = 0.52 ) and was 5-fold higher in the HCV cirrhosis cohort ( p ≤ 0.005 versus healthy ) . No correlation was observed with other measures of disease activity , including plasma alanine aminotransferase , interleukin 6 , and 8-isoprostane F2α , a measure of oxidative stress . These findings suggest that the pharmacokinetics of silymarin is altered in patients with liver disease . Patients with cirrhosis had the highest plasma caspase-3/7 activity and also achieved the highest exposures for the major silymarin flavonolignans", "BACKGROUND AND AIM Hepatoprotectants are routinely prescribed in China to prevent anti-tuberculosis drug-induced liver injury ( ATLI ) . However , their biological mechanisms have not yet been clearly demonstrated . This study aims to evaluate the preventive effects of Silybum marianum against drug-induced liver injury among tuberculosis patients and to provide clinical guidelines for tuberculosis management in China . METHODS A r and omized controlled trial was performed in Jiangsu , China . Tuberculosis patients were r and omly allocated to the experimental group ( anti-tuberculosis therapy plus S. marianum capsule ) or the control group ( anti-tuberculosis therapy plus vitamin C tablet ) . The primary outcomes were the occurrence of probable and possible ATLI , the peak aspartate aminotransferase/alanine aminotransferase ratio and the maximum altered alkaline phosphatase or gamma-glutamyl transferase . RESULTS The final analysis comprised 183 cases in the experiment group and 187 cases in the control group . The risk of developing probable ATLI was not significantly different between the two groups . During the follow-up period , 43.72 % of cases in the experiment group and 35.83 % of cases in the control group were determined to have possible ATLI ( relative risk = 1.23 , 95 % confidence interval : 0.94 - 1.54 ) . When using a more strict definition of possible ATLI , the adjusted relative risk ( 95 % confidence interval ) was 1.76 ( 1.14 - 2.56 ) . The risks of adverse drug reactions , prolonged treatment length , taking second-line tuberculosis drugs , and the clearance of tuberculosis bacteria were similar between the two groups . CONCLUSIONS No significant preventive effect of silymarin was found for either lowering the risk of liver injury or boosting the positive outcomes . Worse , we even found a potential risk of liver damage caused by the hepatoprotectant", "Liver steatosis can evolve to steatohepatitis ( NASH ) through a series of biochemical steps related to oxidative stress in hepatocytes . Antioxidants , such as silybin , have been proposed as a treatment of patients with nonalcoholic fatty liver disease ( NAFLD ) and NASH . In this study , we evaluated , in patients with histologically documented NASH , the oxidant/antioxidant status and lipid “ fingerprint ” in the serum of NASH patients , both in basal conditions and after 12 months of treatment with silybin-based food integrator Realsil ( RA ) . The oxidant/antioxidant status analysis showed the presence of a group of patients with higher basal severity of disease ( NAS scores 4.67 ± 2.5 ) and a second group corresponding to borderline NASH ( NAS scores = 3.8 ± 1.5 ) . The chronic treatment with RA changed the NAS score in both groups that reached the statistical significance only in group 2 , in which there was also a significant decrease of serum lipid peroxidation . The lipidomic profile showed a lipid composition similar to that of healthy subjects with a restoration of the values of free cholesterol , lysoPC , SM , and PC only in group 2 of patients after treatment with RA . Conclusion . These data suggest that lipidomic and /or oxidative status of serum from patients with NASH could be useful as prognostic markers of response to an antioxidant treatment", "Background Spirulina platensis , a cynobacterium used frequently as a dietary supplement had been found to exhibit many immune-stimulating and antiviral activities . It had been found to activate macrophages , NK cells , T cells , B cells , and to stimulate the production of Interferon gamma ( IFN-γ ) and other cytokines . Natural substances isolated from Spirulina platensis had been found to be potent inhibitors against several enveloped viruses by blocking viral absorption/penetration and some replication stages of progeny viruses after penetration into cells . We aim ed to study whether this dietary supplement possesses any therapeutically feasible activity worthy of further larger controlled clinical evaluation . Methods Sixty six patients with chronic hepatitis C virus infection and eligible for inclusion had been r and omized to either Spirulina or Silymarin treated groups for a period of six months treatment . The two groups were followed up and blindly compared for early ( after 3 months ) and end of 6 months treatment virological response . The effects of both treatments on each of alanine aminotransferase ( ALT ) , Chronic Liver Disease Question naire scores ( CLDQ ) , Arizona Sexual Experience Scale scores ( ASEX ) and the occurrence of any attributable adverse events were also compared . Results Among the 30 patients who had been treated with Spirulina and completed the 6 months protocol , 4 patients ( 13.3 % ) had a complete end of treatment virological response and 2 patients ( 6.7 % ) had a partial end of treatment response defined as significant decrease of virus load of at least 2-logs10 . Though the proportion of responders in Spirulina group was greater than in the Silymarin group , the difference was not statistically significant at the end of both 6 months ( p = 0.12 ) and 3 months treatment ( p = 0.22 ) by Exact test . Alanine aminotransferase as well as CLDQ and ASEX scores were found to be more significantly improved in Spirulina than in Silymarin treated group . Conclusions Our results could suggest a therapeutically feasible potential for Spirulina platensis in chronic HCV patients , worthy to conduct a larger sized and longer study to confirm these safety and efficacy encouraging results .Trial Registration WHO Clinical Trial Registration ID : ACTRN12610000958088http://apps.who.int/trial search /trial.aspx?trialid =", "Background Hepatitis is a common adverse effect of antituberculosis drugs . Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown . We aim ed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury ( antiTB-DILI ) in patients with tuberculosis . Methods A double-blind r and omized placebo-controlled trial was performed . Tuberculosis patients were r and omly allocated to receive placebo or silymarin . The outcomes of interests were antiTB-DILI and the maximum liver enzymes at week 4 . Antioxidative enzymes ( i.e. , superoxide dismutase ( SOD ) , glutathione and malondialdehyde assays ) were assessed . The risks of antiTB-DILI between the two groups were compared . A number need to treat was estimated . Results A total of 55 out of 70 expected numbers of patients were enrolled . There were 1/27 ( 3.7 % ) and 9/28 ( 32.1 % ) patients who developed antiTB-DILI in the silymarin and the placebo groups . Risk reduction was 0.28 ( 0.10 , 0.47 ) , i.e. , receiving silymarin was 28 % at lower risk for antiTB-DILI than placebo . This led to prevention of 28 patients from being antiTB-DILI among 100 treated patients . Median ( IQR ) of ALT levels at week 4 in the placebo and the silymarin group were 35.0 ( 15 , 415 ) IU/L and 31.5 ( 20 , 184 ) IU/L ( p = 0.455 ) . The decline of SOD level at week 4 in the silymarin group was less than the placebo group ( p Silymarin reduced the incidence of antiTB-DILI . The benefit of silymarin may be explained from superoxide dismutase restoration . Larger clinical trials are required to confirm the result of our small study [ Clinical trials . Gov Identifier Nct01800487 ]", "CONTEXT The botanical product silymarin , an extract of milk thistle , is commonly used by patients to treat chronic liver disease , despite scant and conflicting evidence of its efficacy . OBJECTIVE To determine the effect of silymarin on liver disease activity in patients with chronic hepatitis C virus ( HCV ) infection unsuccessfully treated with interferon-based therapy . DESIGN , SETTING , AND PARTICIPANTS Multicenter , double-blind , placebo-controlled trial conducted at 4 medical centers in the United States . Participants included 154 persons with chronic HCV infection and serum alanine aminotransferase ( ALT ) levels of 65 U/L or greater who were previously unsuccessfully treated with interferon-based therapy . Enrollment began in May 2008 and was completed in May 2010 , with the last follow-up visit completed in March 2011 . INTERVENTION Participants were r and omly assigned to receive 420-mg silymarin , 700-mg silymarin , or matching placebo administered 3 times per day for 24 weeks . MAIN OUTCOME MEASURES The primary outcome measure was serum ALT level of 45 U/L or less ( considered within the normal range ) or less than 65 U/L , provided this was at least a 50 % decline from baseline values . Secondary outcomes included changes in ALT levels , HCV RNA levels , and quality -of-life measures . RESULTS After 24 weeks of treatment , only 2 participants in each treatment group ( P ≥ .99 ) met the primary outcome measure ( 3.8 % [ 95 % CI , 0.5 % to 13.2 % ] for placebo , 4.0 % [ 95 % CI , 0.5 % to 13.7 % ] for 420-mg silymarin , and 3.8 % [ 95 % CI , 0.5 % to 13.2 % ] for 700-mg silymarin ) . The mean decline in serum ALT activity at the end of treatment did not differ significantly ( P = .75 ) across the 3 treatment groups ( mean decline , -4.3 [ 95 % CI , -17.3 to 8.7 ] U/L for placebo , -14.4 [ 95 % CI , -41.6 to 12.7 ] U/L for 420-mg silymarin , -11.3 [ 95 % CI , -27.9 to 5.4 ] U/L for 700-mg silymarin ) ; there likewise were no significant differences in HCV RNA levels ( mean change , 0.07 [ 95 % CI , -0.05 to 0.18 ] log10 IU/mL for placebo , -0.03 [ 95 % CI , -0.18 to 0.12 ] log10 IU/mL for 420-mg silymarin , 0.04 [ 95 % CI , -0.08 to 0.16 ] log10 IU/mL for 700-mg silymarin ; P = .54 ) or quality -of-life measures . The adverse event profile of silymarin was comparable with that of placebo . CONCLUSION Higher than customary doses of silymarin did not significantly reduce serum ALT levels more than placebo in participants with chronic HCV infection unsuccessfully treated with interferon-based therapy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00680342", "BACKGROUND No pharmacologic agents have been approved for the treatment of non-alcoholic steatohepatitis ( NASH ) that is common in our region . The present study was design ed to evaluate the efficacy of silymarin , a known herbal drug , in the treatment of NASH . METHODS This clinical -trial study was conducted on 64 patients with NASH who were r and omly divided as case group ( 33 ) and control group ( 31 ) . Abdominal sonography and persistent elevation in levels of aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) more than 1.2 times of the upper normal limit within the last six months were selected as inclusion criteria . They were advised to take low-fat , low carbohydrate diet , do regular sport activity to lose weight up to 4 Kg . Patients in the case group received 210 mg/day silymarin orally for 8 weeks and those in the control group received placebo . After 8 weeks , the patients were reevaluated and their AST and ALT levels were measured . This study was registered in the Iranian Registry of Clinical Trial ( www.i rct .ir ) with registration number ID : I RCT 201202159018N1 . RESULTS The mean age of patients in case and control groups was 43.6±8.3 and 39.4±10.5 years , respectively . Their BMI were 27.4±1.7 and 27.5±1.9 , respectively . Their weights were also 79±9.2 and 76.9±9.5 kg , respectively . Serum concentrations of ALT were 91.3±21.3 and 38.4±11.8 in case group before and after the study respectively , whiles the figures were 84.6±23.3 and 52.3±29 in the control group ( P=0.026 ) . The same trend was seen for AST ( P=0.038 ) . CONCLUSION The patients who had taken silymarin experienced more notable fall in hepatic enzymes", "The only currently recommended treatment for nonalcoholic fatty liver disease ( NAFLD ) is lifestyle modification . Preliminary studies of silybin showed beneficial effects on liver function . Realsil ( RA ) comprises the silybin phytosome complex ( silybin plus phosphatidylcholine ) coformulated with vitamin E. We report on a multicenter , phase III , double-blind clinical trial to assess RA in patients with histologically documented NAFLD . Patients were r and omized 1:1 to RA or placebo ( P ) orally twice daily for 12 months . Prespecified primary outcomes were improvement over time in clinical condition , normalization of liver enzyme plasma levels , and improvement of ultrasonographic liver steatosis , homeostatic model assessment ( HOMA ) , and quality of life . Secondary outcomes were improvement in liver histologic score and /or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines , ferritin , and liver fibrosis markers . We treated 179 patients with NAFLD ; 36 were also HCV positive . Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol ( 69 per group ) . Baseline patient characteristics were generally well balanced between groups , except for steatosis , portal infiltration , and fibrosis . Adverse events ( AEs ) were generally transient and included diarrhea , dysgeusia , and pruritus ; no serious AEs were recorded . Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels , HOMA , and liver histology . Body mass index normalized in 15 % of RA patients ( 2.1 % with P ) . HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers . This is the first study to systematic ally assess silybin in NAFLD patients . Treatment with RA but not P for 12 months was associated with improvement in liver enzymes , insulin resistance , and liver histology , without increases in body weight . These findings warrant further investigation", "BACKGROUND / AIMS The incidence of obese patients with fatty liver has recently increased in Japan as well as in the United States and Europe . Fatty liver may occasionally progress to liver cirrhosis . In this study , we have compared the effects of restricted diet and exercise versus no treatment in obese patients with fatty liver . METHODS Twenty-five obese patients with fatty liver were divided into treated and control groups . Fifteen obese patients followed a program of restricted diet ( ideal weight x 25 Cal x kg(-1 ) ) and exercise ( walking or jogging ) for a trial period of 3 months . No changes in diet or lifestyle were made by the other 10 patients during the same trial period . Blood biochemical tests and liver histology were compared in all patients before and after the trial . RESULTS In the treated group , weight , blood biochemical data such as aminotransferase , albumin , cholinesterase , total cholesterol and fasting blood glucose values , and steatosis were significantly decreased after the trial . In the control group , there were no significant differences in the clinical and histological findings before and after the trial . CONCLUSIONS These results indicate that restricted diet and exercise therapy , such as walking and jogging , are useful means of improving blood biochemical data and histological findings in liver tissues related to fatty liver", "BACKGROUND / AIMS Silymarin has protective effects in different experimental conditions , but its efficacy in human liver cirrhosis has not been completely established . Therefore , this study was carried out to determine the effect of silymarin in alcoholics with liver cirrhosis with respect to survival and clinical and laboratory changes . METHODS From February 1986 to June 1989 , we enrolled 200 alcoholics with histologically or laparoscopically proven liver cirrhosis in a r and omized , double-blind multicenter trial comparing 450 mg of silymarin ( 150 mg/ three times per day ) with placebo . The primary outcome was time to death , and the secondary outcome was the progression of liver failure . Additional analyses were also performed in 75 patients in whom anti-hepatitis C virus antibodies were measured after completion of the trial . RESULTS One hundred and three patients were assigned to receive silymarin and 97 to receive placebo . The two groups were well matched for demographic and baseline clinical and laboratory features . A 2-year study period was completed in 125 patients ( 57 receiving silymarin and 68 receiving placebo ) . Twenty-nine patients ( 15 receiving silymarin , and 14 receiving placebo ) died during the trial . Survival was similar in patients receiving silymarin or placebo . The effect of silymarin on survival was not influenced by sex , the persistence of alcohol intake , the severity of liver dysfunction or by the presence of alcoholic hepatitis in the liver biopsy . Silymarin did not have any significant effect on the course of the disease . No relevant side-effects were observed in any group . CONCLUSIONS The results of this study indicate that silymarin has no effect on survival and the clinical course in alcoholics with liver cirrhosis", "BACKGROUND / AIMS Several studies have demonstrated that diabetic patients with cirrhosis require insulin treatment because of insulin resistance . As chronic alcoholic liver damage is partly due to the lipoperoxidation of hepatic cell membranes , anti-oxidizing agents may be useful in treating or preventing damage due to free radicals . The aim of this study was to ascertain whether long-term treatment with silymarin is effective in reducing lipoperoxidation and insulin resistance in diabetic patients with cirrhosis . METHODS A 12-month open , controlled study was conducted in two well-matched groups of insulin-treated diabetics with alcoholic cirrhosis . One group ( n=30 ) received 600 mg silymarin per day plus st and ard therapy , while the control group ( n=30 ) received st and ard therapy alone . The efficacy parameters , measured regularly during the study , included fasting blood glucose levels , mean daily blood glucose levels , daily glucosuria levels , glycosylated hemoglobin ( HbA1c ) and malondialdehyde levels . RESULTS There was a significant decrease ( p fasting blood glucose levels , mean daily blood glucose levels , daily glucosuria and HbA1c levels already after 4 months of treatment in the silymarin group . In addition , there was a significant decrease ( p fasting insulin levels and mean exogenous insulin requirements in the treated group , while the untreated group showed a significant increase ( p fasting insulin levels and a stabilized insulin need . These findings are consistent with the significant decrease ( p basal and glucagon-stimulated C-peptide levels in the treated group and the significant increase in both parameters in the control group . Another interesting finding was the significant decrease ( p malondialdehyde/levels observed in the treated group . CONCLUSIONS These results show that treatment with silymarin may reduce the lipoperoxidation of cell membranes and insulin resistance , significantly decreasing endogenous insulin overproduction and the need for exogenous insulin administration", "BACKGROUND / AIMS Silybum marianum is a herbal preparation commonly used by subjects with chronic hepatitis C ( CHC ) . The aims of this pilot study were to assess the efficacy and safety of S. marianum on serum hepatitis C virus ( HCV ) RNA , alanine aminotransferase levels and well-being in patients with CHC . METHODS Twenty-four subjects with CHC were enrolled into a r and omized , double-blind , placebo-controlled , crossover study . Subjects received 12 weeks of S. marianum ( either 600 mg or 1200 mg/day ) and placebo separated by a 4-week washout interval . Baseline biochemical , virological , psychological and quality -of-life tests were performed , with biochemical tests repeated monthly , and HCV RNA titer and quality -of-life and psychological assessment s repeated at the end of both treatment periods . RESULTS Seventeen patients completed the trial . Mean changes in HCV RNA titers , serum ALT levels and Short Form-36 scores were not significantly different for subjects on S. marianum compared to those on placebo . There was no significant change in mean State-Trait Anxiety Inventory State-Anxiety scores on S. marianum from baseline . Adverse events were similar with S. marianum and placebo . CONCLUSIONS S. marianum is well tolerated in subjects with CHC , but does significantly affect serum HCV RNA , alanine aminotransferase levels , quality of life or psychological well-being in subjects with this condition", "The Romanian product Silimarina ( synonym Legalon ) was administered in a r and omized double-blind trial , to a group of 180 patients with chronic persistent hepatitis ( CPH ) , chronic active hepatitis ( CAH ) and hepatic cirrhosis ( HC ) . The trial lasted for 40 days . The results showed favourable effects similar with those obtained with other preparations produced by foreign drug industries . The Romanian product proved to have no toxic effect . The authors discuss the present possibilities of estimating the evolution of chronic liver disease", "BACKGROUND / AIMS A double-blinded trial evaluating silymarin , an herbal supplement for liver disease , to prevent complications of chronic hepatitis C virus infection has not been done . SUBJECTS One hundred and seventy-seven consenting residents of an Egyptian village with chronic hepatitis C virus were r and omly assigned to receive either silymarin or multivitamin supplements . METHODS Participants had baseline and follow-up clinical , ultrasound , blood tests and quality -of-life assessment s. Community nurses visited weekly to ascertain compliance , distribute supplements and record adverse effects . RESULTS At 12 months almost all of 141 remaining subjects reported feeling better , although symptoms and quality -of-life scores did not differ between the silymarin and multivitamin groups . Both the silymarin and vitamins were tolerated equally well ; and > 95 % of supplements were taken by > 95 % of subjects . One in each group had no detectable hepatitis C virus antibodies while two in the silymarin group and three receiving multivitamins had undetectable hepatitis C virus RNA . Serum alanine aminotransferase elevations did not differ between groups . Serum hepatic fibrosis marker , hyaluronic acid and YKL-40 , and abdominal ultrasound results were similar in both groups and may have progressed slightly at 12 months . CONCLUSIONS The recommended dose of silymarin can be safely taken for 1 year and improves symptoms and general well-being , but has no effect upon hepatitis C virus viremia , serum ALT , or serum and ultrasound markers for hepatic fibrosis . More prolonged evaluation and a higher dose may be required to ascertain whether milk thistle supplements prevent complications of chronic hepatitis C virus", "BACKGROUND : Silymarin derived from silybum marianum ( milk thistle ) , a flowering member of the daisy family , may benefit liver function in people infected with the hepatitis C virus . The aims of this pilot study were to assess the efficacy and safety of silymarin on serum hepatitis C virus ( HCV ) RNA , serum aminotransferases ( ALT , AST ) levels , liver fibrosis and well-being in patients with chronic hepatitis C ( CHC ) . METHODS : This prospect i ve self-controlled trial study was conducted from March to September 2006 at Department of Gastroenterology , Isfahan University of Medical Sciences , Isfahan , Iran . 55 patients with HCV ( 10 female and 45 male ) with a mean age of 31.8 ± 6.4 years ( 10 - 67 years ) were participated in the study . Patients received 24 weeks of silymarin ( 630 mg/day ) . Baseline virological biochemical , liver fibrosis ( by a serum fibrosis markers , including YKL–40 and Hyaluronic acid ) , and SF-36 question naire were performed with biochemical tests repeated at the end of the treatment period . RESULTS : There was statistically difference in mean of ALT ( 108.7 ± 86.6 vs 70.3 ± 57.7 ) before and after the treatment ( p means of AST were 99.4 ± 139.7 and 59.7 ± 64.32 before and after the treatment with statistically differences ( p = 0.004 ) . After the treatment , nine patients were found with negative HCV-RNA ( p = 0.004 ) and statistically significant improvement in results of liver fibrosis markers were found only in fibrosis group ( p = 0.015 ) . Quality of life was improved significantly ( p patients with CHC performing silymarin ( 650 mg/day ) for 6 months , improved serum HCV-RNA titer , serum aminotransferases ( ALT , AST ) , hepatic fibrosis and patient 's quality of life . More future studies are warranted", "PURPOSE Milk thistle or its purified extract , silymarin ( Silybum marianum ) , is widely used in treating acute or chronic hepatitis . Although silymarin is hepatoprotective in animal experiments and some human hepatotoxic exposures , its efficacy in ameliorating the symptoms of acute clinical hepatitis remains inconclusive . In this study , our purpose was to determine whether silymarin improves symptoms , signs and laboratory test results in patients with acute clinical hepatitis , regardless of etiology . METHODS This is a r and omized , placebo-controlled trial in which participants , treating physicians and data management staff were blinded to treatment group . The study was conducted at two fever hospitals in Tanta and Banha , Egypt where patients with symptoms compatible with acute clinical hepatitis and serum alanine aminotransferase ( ALT ) levels > 2.5 times the upper limit of normal were enrolled . The intervention consisted of three times daily ingestion of either a st and ard recommended dose of 140 mg of silymarin ( Legalon , MADAUS GmbH , Cologne , Germany ) , or a vitamin placebo for four weeks with an additional four-week follow-up . The primary outcomes were symptoms and signs of acute hepatitis and results of liver function tests on days 2 , 4 and 7 and weeks 2 , 4 , and 8 . Side-effects and adverse events were ascertained by self-report . RESULTS From July 2003 through October 2005 , 105 eligible patients were enrolled after providing informed consent . No adverse events were noted and both silymarin and placebo were well tolerated . Patients r and omized to the silymarin group had quicker resolution of symptoms related to biliary retention : dark urine ( p=0.013 ) , jaundice ( p=0.02 ) and scleral icterus ( p=0.043 ) . There was a reduction in indirect bilirubin among those assigned to silymarin ( p=0.012 ) , but other variables including direct bilirubin , ALT and aspartate aminotransferase ( AST ) were not significantly reduced . CONCLUSIONS Patients receiving silymarin had earlier improvement in subjective and clinical markers of biliary excretion . Despite a modest sample size and multiple etiologies for acute clinical hepatitis , our results suggest that st and ard recommended doses of silymarin are safe and may be potentially effective in improving symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process", "Background : Non-alcoholic fatty liver disease is the most common liver disease worldwide . Aim : The aim of this study is to compare the metabolic effects of the Mediterranean diet versus the diet associated with silybin , phosphatidylcholine and vitamin E complex in overweight patients with non-alcoholic fatty liver disease . Methods : Thirty Caucasian overweight patients were r and omized into three groups of 10 ( Groups A , B and C ) . A personalized Mediterranean diet was started in Group A and B patients . In association with the diet , Group B patients were given Realsil complex , daily , for 6 months . Group C patients refused any treatment . Results : We showed that the Mediterranean diet alone , or in association with the Realsil complex , led to the significant variation in BMI , waist circumference , total cholesterol and triglycerides . We also observed a statistically significant decrease in homeostasis model assessment technique in Group B patients", "The study was undertaken to determine the long-term effect of misoprostol , on hepatitis B virus ( HBV ) elimination in patients treated during acute phase of viral hepatitis B. Forty male patients were evaluated 12 months after treatment with misoprostol ( M-group ) or sylimarin ( S-group ) . HBsAg clearance , as an indicator of HBV elimination , and serum bilirubin concentration , prothrombin index , and activities of alanine transaminase , aspartate transaminase , alkaline phosphatase as well as gamma glutamyltranspeptidase were analysed . At the end of treatment phase , improvement of liver function demonstrated through these biochemical indices was faster in M-group . After 12 months of follow-up HBsAg was cleared in all misoprostol treated patients and in 85 % among S-group . Moreover misoprostol treatment result ed with normalization of bilirubin concentration and enzymes activity in all patients . Two among sylimarin treated patients ( both HBsAg positive ) , had transaminases activities elevated over 100 U/l , that result ed with significantly higher values than in M-group . These results confirm beneficial effect of misoprostol treatment in patients with liver injury , but promising effect on HBV clearance should be confirmed in a study involving more patients", "Goals The goal of this study was to examine the effect of a st and ardized silybin and soy phosphatidylcholine complex ( IdB 1016 ) on serum markers of iron status . Background Milk thistle and its components are widely used as an alternative therapy for liver disease because of purported antioxidant , anti-inflammatory , and iron chelating properties . Study Thirty-seven patients with chronic hepatitis C and Batts-Ludwig fibrosis stage II , III , or IV were r and omized to 1 of 3 doses of IdB 1016 for 12 weeks . Serum ferritin , serum iron , total iron binding capacity , and transferrin-iron saturation were measured at baseline , during treatment , and 4 weeks thereafter . Wilcoxon signed rank tests were used to compare baseline and posttreatment values . Results There was a significant decrease in serum ferritin from baseline to end of treatment ( mean , 244 vs. 215 μg/L ; median , 178 vs. 148 μg/L ; P=0.0005 ) ; 78 % of subjects had a decrease in serum ferritin level . There was no significant change in serum iron or transferrin-iron saturation . Multivariate logistic regression analysis in a model that included dose , age , sex , HFE genotype , history of alcohol use , and elevated baseline ferritin levels demonstrated that stage III or IV fibrosis was independently associated with decreased posttreatment serum ferritin level . Conclusions Treatment with IdB 1016 is associated with reduced body iron stores , especially among patients with advanced fibrosis stage", "Although nonalcoholic steatohepatitis ( NASH ) has generally been considered a benign condition , the increasing prevalence and severity of obesity has heightened concerns about the frequency with which NASH progresses to end-stage liver disease . The aim of this study is to determine the frequency , clinical features , and posttransplantation history of decompensated liver disease secondary to NASH . The frequency of NASH as a cause of end-stage liver disease was prospect ively determined in patients evaluated for liver transplantation . NASH was considered to be the primary cause of liver disease in patients who had histological evidence of steatohepatitis and in whom chronic liver diseases other than NASH were excluded . Posttransplantation histological characteristics were also determined in patients with NASH and compared with those of patients with pretransplantation diagnoses of cholestatic liver diseases , alcoholic disease , and hepatitis C. Of 1,207 patients evaluated for liver transplantation during the study period , 31 patients ( 2.6 % ) had NASH as the primary cause of liver disease . In the same period , 546 liver transplantations were performed , 16 of which ( 2.9 % ) were for end-stage disease secondary to NASH . Posttransplantation steatosis was seen in 60 % of transplant recipients with NASH versus 5 % of those with cholestatic disease , 15 % of those with alcoholic disease , and 15 % of those with hepatitis C. Steatohepatitis recurred in 33 % of transplant recipients with NASH , with progression to cirrhosis in 12.5 % . NASH can progress to end-stage liver disease in a minority of affected patients and was the primary cause of liver disease in 2.9 % of patients evaluated for liver transplantation at our center . Recurrence of steatosis and NASH is frequent and can be severe after liver transplantation" ]

[ "Cancer patients are commonly associated with various physical and psychological symptoms . In palliative setting , the aims are to relieve those symptoms , improve quality of life , and increase medication adherence among cancer patients . Antidepressants are generally accepted for the treatment of depression among patients with or without cancer . Some other potential benefits of the antidepressants have been reported in cancer patients . OBJECTIVE This study aims to review the use of antidepressants for physical and psychological symptoms in cancer patients . RESULTS Our findings showed the mixed result of positive and negative findings in various symptoms associated with cancer patients . These studies are categorised according to the hierarchy of evidence from high to low level , namely r and omised controlled trials , cohort studies , case-control studies , case series , case reports , as well as other type of publications . The majority of antidepressants used in cancer patients seem to be beneficial for the treatment of depression , anxiety , hot flashes and other symptoms such as sexual dysfunction , fatigue , nicotine dependence , vasomotor symptoms , executive functions , sleep problems , pruritus , as well as for hypochondriasis . While fluoxetine was found to be associated with the reduction of antiemetic property in ondansetron , mirtazapine was identified to be a good alternative in treating nausea and cachexia among cancer patients . CONCLUSION More research studies with adequate statistical power are warranted to vali date the use of antidepressants among cancer patients in treating these physical and psychological symptoms", "& NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies", "Goals of the workThis study aim ed to compare the effectiveness of mirtazapine and imipramine on not only the distressing symptoms of cancer patients such as pain , nausea , vomiting , appetite loss , and sleep disturbances but also depressive and anxiety symptoms . Material s and methods Fifty-three patients with cancer who were diagnosed with major depressive disorder , anxiety disorder , or adjustment disorder were included . Twenty patients on mirtazapine , 13 patients on imipramine , and 20 patients in the control group without medication were interviewed during three visits ( baseline , third week , and sixth week ) . Pain , nausea , vomiting , appetite loss , and sleep disturbances were evaluated with self- assessment single-symptom scales during each visit . The patients were also asked to complete the Hospital Anxiety Depression Scale ( HADS ) during each visit . Main results There were no significant differences among the three visits in the mirtazapine , imipramine , or control groups in terms of pain , nausea , vomiting , or appetite loss . For the initial , middle , and late insomnia , only the mirtazapine group showed improvements ( p = 0.001 , p = 0.001 , p = 0.003 ) . There were also significant differences in the mean total ( p = 0.03 ) , anxiety ( p = 0.003 ) , and depression ( p = 0.025 ) scores of HADS among the three visits for patients taking mirtazapine . There were no significant differences for HADS scores from the baseline to the end point for patients taking imipramine or control group patients . Conclusion Our findings suggest that mirtazapine is effective for resolving insomnia as well as anxiety and depressive symptoms in cancer patients . However , more systematic research , such as placebo-controlled studies , is needed", "Objective We examine the reliability and validity of the Patient Health Question naire Anxiety and Depression Scale (PHQ-ADS)—which combines the nine-item Patient Health Question naire depression scale and seven-item Generalized Anxiety Disorder scale — as a composite measure of depression and anxiety . Methods Baseline data from 896 patients enrolled in two primary -care based trials of chronic pain and one oncology- practice –based trial of depression and pain were analyzed . The internal reliability , st and ard error of measurement , and convergent , construct , and factor structure validity , as well as sensitivity to change of the PHQ-ADS were examined . Results The PHQ-ADS demonstrated high internal reliability ( Cronbach & agr ; values of .8 to .9 ) in all three trials . PHQ-ADS scores can range from 0 to 48 ( with higher scores indicating more severe depression/anxiety ) , and the estimated st and ard error of measurement was approximately 3 to 4 points . The PHQ-ADS showed strong convergent ( most correlations , 0.7–0.8 range ) and construct ( most correlations , 0.4–0.6 range ) validity when examining its association with other mental health , quality of life , and disability measures . PHQ-ADS cutpoints of 10 , 20 , and 30 indicated mild , moderate , and severe levels of depression/anxiety , respectively . Bifactor analysis showed sufficient unidimensionality of the PHQ-ADS score . PHQ-ADS change scores at 3 months differentiated ( p reliable and valid composite measure of depression and anxiety which , if vali date d in other population s , could be useful as a single measure for jointly assessing two of the most common psychological conditions in clinical practice and research . Trial Registration : Clinical trials.gov Identifier : NCT00926588 ( SCOPE ) ; NCT00386243 ( ESCAPE ) ; NCT00313573 ( INCPAD )", "BACKGROUND Major depressive disorder ( MDD ) is a common and debilitating illness in patients with cancer . However , the optimal treatment of depression in these patients remains uncertain , with limited evidence to support the use of pharmacologic therapy . We conducted a pilot study to evaluate the feasibility of an antidepressant clinical trial in the oncology population and the process of symptom-oriented selection of antidepressants ( citalopram or mirtazapine ) in patients with cancer and MDD . METHODS This was a single center , two-arm , nonr and omized , open-label , nine-week pilot study of mirtazapine or citalopram in cancer patients with MDD . The primary endpoint was the feasibility to recruit and to retain patients . Secondary outcomes included changes in Patient Health Question naire-9 ( PHQ-9 ) ( depression ) , Functional Assessment of Cancer Therapy-General ( FACT-G ) ( quality of life ) , Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-Fatigue ) ( fatigue ) , and Pittsburgh Sleep Quality Index ( PSQI ) ( sleep ) . We conducted descriptive statistics and responder analyses . RESULTS Of 21 patients , 18 ( 86 % ) successfully completed the study . An average of 2.8 subjects were enrolled per month . Mean scores on the PHQ-9 improved overall by 6.4 points ( 95 % confidence interval [ CI ] 3.6 - 9.2 ) . Additionally , mean FACT-G , FACIT-Fatigue , and PSQI scores improved in both study arms . CONCLUSION Conducting antidepressant clinical trials is challenging in the oncology population . We approached but did not meet our feasibility goals . Depression and quality of life ( QOL ) scores improved with both mirtazapine and citalopram , but evidence -based pharmacologic treatments for depression in cancer patients are needed", "This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . \" Quality \" as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence", "We performed a pilot open-label , crossover trial of mirtazapine ( 15 and 30 mg at night ) in advanced cancer patients with pain and other distressing symptoms . Twenty patients completed the trial and sixteen dropped out . Following a baseline assessment , patients completed a one-week observation period and were then r and omized to a starting dose of either 15 mg or 30 mg of mirtazapine given at bedtime . After three weeks , subjects were switched to the alternate dose and followed by an additional three-week period , completing the treatment . The average age of the completers was 60.2 years and consisted of 7 women and 13 men . The majority were Caucasian ( n = 18 , 90 % ) and married ( n = 18 , 90 % ) . The drop-out group did not significantly differ from the completers based on age , gender , race , marital status , or tumor type . We examined the impact of mirtazapine therapy on patients ' levels of depression , pain intensity , appetite , insomnia , weight , and overall quality of life . A series of repeated measures ANOVAs were conducted to compare the completers ' status at Weeks 1 , 4 , and 7 compared to baseline and to examine the interaction with starting dose and baseline observations . Scores on the Zung self-rating Depression Scale ( F = 8.20 , P Functional Assessment of Cancer Therapy - General Measure ( F = 5.73 , P mirtazapine dosage . Patients ' weights were significantly higher at both Week 4 and Week 7 , independent of dosage . Trend level differences were found on Memorial Pain Assessment Card items for pain , pain relief , and mood and on numeric rating scales measuring nausea , anxiety , insomnia , and appetite . This open-label pilot study suggests that mirtazapine may be effective for improving multiple symptoms , depression and quality of life in patients with advanced cancer . A controlled trial of this drug would be valuable", "& NA ; The purpose of this study was to determine the levels of change on st and ard pain scales that represent clinical ly important differences to patients . Data from analgesic studies are often difficult to interpret because the clinical importance of the results is not obvious . Differences between groups , as summarized by a change in mean values over time , can be difficult to apply to clinical care . Baseline scores vary widely and group mean differences could reflect large changes in a few patients , small changes in many patients , or any combination of these outcomes . Determination of the proportion of patients who have a clinical ly important improvement in their pain would provide a more interpretable result with direct clinical implication s. However , determining a clinical ly important outcome requires information about the degree of change over time that is clinical ly important . Data from the titration phase of a multiple cross‐over r and omized clinical trial of oral transmucosal fentanyl citrate ( OTFC ) for the treatment of cancer‐related breakthrough pain were re‐analyzed to examine the differences in pain scores between treatment episodes that did and did not yield adequate pain relief . The scales evaluated were absolute pain intensity difference ( PID , 0–10 scale ) , percentage pain intensity difference ( PID% , 0–100 % scale ) , pain relief ( PR , 0 ( none ) , 1 ( slight ) , 2 ( moderate ) , 3 ( lots ) , 4 ( complete ) ) , sum of the pain intensity difference ( SPID over 60 min ) , percentage of maximum total pain relief ( % Max TOTPAR over 60 min ) , and global medication performance ( 0 ( poor ) , 1 ( fair ) , 2 ( good ) , 3 ( very good ) , 4 ( excellent ) ) . Adequate relief was defined by the patient 's decision not to use another dose of opioid medication as a rescue , in addition to the study medication , to treat each painful episode . One hundred thirty OTFC naive patients contributed data on 1268 episodes of breakthrough pain . The scales that were converted to a percentage change yielded the best accuracy in predicting adequate relief , with balanced sensitivity and specificity . The best cut‐off point for both the % Max TOTPAR and the PID% was 33 % . The best cut‐off points for the absolute scales were absolute pain intensity difference of 2 , pain relief of 2 ( moderate ) , and SPID of 2 . The global medication performance of 2 ( good ) had excellent values as well . This study presents data ‐derived cut‐off points for the changes in several pain scales , each reflecting the clinical ly important improvement for patients treating breakthrough cancer pain episodes with OTFC . Confirmation in other patient population s and different pain syndromes will be needed . The use of consistent clinical ly important cut‐off points as the primary outcome in future pain therapy clinical trials will enhance their validity , comparability , and clinical applicability", "Abstract Background : Depression is quite common among cancer patients . It has yet to be determined which antidepressant is the most effective in cancer patients with depression . Methods : The present study included 21 consecutive depressed oncology patients of whom 19 were followed up for 6 months . All patients initially received mirtazapine 15 mg/day and the dose was increased in the absence of significant treatment response and adverse effects . Results : Depressive symptoms diminished at the end of month 1 and this improvement was maintained for the remaining 23 weeks of the study . Mean 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) scores fell significantly from 21.4 ± 4.9 at baseline to 6.5 ± 3.2 at the end of the first month of treatment ( p adverse effect during treatment ; however , the vast majority of these adverse effects were described as mild to moderate . Conclusion : This prospect i ve , open-label study provides preliminary evidence regarding the efficacy , safety and tolerability of mirtazapine treatment in cancer patients with depression . Relatively low doses of mirtazapine appeared to be safe and effective for treating cancer patients undergoing radiotherapy and /or chemotherapy , and the reduction in the severity of depressive symptoms was maintained until the end of the 24-week treatment period", "We performed an open-label single-institution phase II trial of mirtazapine ( 15 - 30 mg by mouth [ po ] every day [ qd ] ) , a tetracyclic antidepressant that may lead to weight gain , for 8 weeks in nondepressed patients with cancer-related cachexia/anorexia ( CRCA ) . The primary end point was the proportion of patients who gained ≥1 kg at week 4 . Secondary end points were quality of life and appetite . From June 2006 to July 2007 , 17 of 58 eligible patients were enrolled . On intention-to-treat analysis at week 4 , 4 of 17 patients ( 24 % ) gained 1 kg or more , 1 patient maintained weight ( gain of 400 g ) and 2 patients lost weight ( 800 g and 1.2 kg ) ; 24 % and 6 % improved appetite and health-related quality of life ( HQOL ) , respectively . Mirtazapine is a promising agent for the treatment of CRCA", "AIMS The purpose of the present paper was to evaluate the effectiveness of mirtazapine orally disintegrating tablets for nausea and sleep disturbance , which are common and distressing symptoms of cancer . METHODS This was a 4-week , prospect i ve , open-labeled study of cancer patients . Assessment s were performed at baseline and on days 1 , 3 , 5 , 7 , 14 , and 28 . Primary outcome measures were the Clinical Global Impression scale for nausea/vomiting and the Chonnam National University Hospital-Leeds Sleep Evaluation Question naire ( C-LSEQ ) including total amount of night sleep time . The secondary outcome measures consisted of pain items in the 36-item Short Form Health Survey , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the EuroQoL (EQ)-5D . Forty-two cancer patients were enrolled . RESULTS Those with nausea ( n = 28 ) improved significantly from day 1 . The total night sleep time and each item on the C-LSEQ improved from days 1 - 5 . The scores on the MADRS and the depression/anxiety dimension and visual analog scale of EQ-5D improved significantly from the first week . Pain measures also improved from day 1 . Exacerbation of sleepiness developed in approximately one-third of subjects during the initial few days , but disappeared gradually . CONCLUSION In the present study mirtazapine rapidly improved nausea , sleep disturbance , pain and quality of life , as well as depression in cancer patients . Mirtazapine may be an effective treatment option in managing cancer patients with multiple distressing symptoms , including nausea and sleep disturbance", "ABSTRACT Introduction : Chronic breathlessness is a common and distressing symptom of advanced disease with few effective treatments . Central nervous system mechanisms are important in respiratory sensation and control . Consequently , drugs which may modify processing and perception of afferent information in the brain may have a role . Antidepressants have been proposed ; however , current evidence is limited . Of potentially suitable antidepressants , mirtazapine is an attractive option given its tolerability profile , low cost , and wide availability , along with additional potential benefits . Areas covered : The paper provides an overview of the physiology of breathlessness , with an emphasis on central mechanisms , particularly the role of fear circuits and the associated neurotransmitters . It provides a potential rationale for how mirtazapine may improve chronic breathlessness and quality of life in patients with advanced disease . The evidence was identified by a literature search performed in PubMed through to October 2018 . Expert opinion : Currently , there is insufficient evidence to support the routine use of antidepressants for chronic breathlessness in advanced disease . Mirtazapine is a promising c and i date to pursue , with definitive r and omized controlled trials required to determine its efficacy and safety in this setting" ]

[ "Positive psychotic symptoms , such as threat/\"control-override \" delusions or comm and hallucinations , have been related to aggression in patients with schizophrenia . However , retrospective data collection has hampered evaluation of the direct influence of psychopathology on aggressive behavior . In this study , we monitored aggressive behavior and psychopathology prospect ively and in close temporal proximity in 157 treatment-resistant in patients diagnosed with chronic schizophrenia or schizoaffective disorder participating in a 14-week double-blind clinical trial . Aggressive behavior was rated with the overt aggression scale ( OAS ) . Psychopathology was assessed using the positive and negative syndrome scale ( PANSS ) . At baseline , subjects who would be aggressive during the study had higher scores on only two PANSS items : hostility and poor impulse control . During the study PANSS positive subscale scores were significantly higher in aggressive subjects . Total PANSS scores were higher within 3 days of an aggressive incident , as were positive and general psychopathology subscale scores . However , in a smaller sub sample for whom PANSS ratings were available within 3 days before aggressive incidents , only scores on the PANSS positive subscale were significantly higher . These findings in chronic , treatment resistant in patients support the view that positive symptoms may lead to aggression", "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", "OBJECTIVE Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia , but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents , particularly in patients who have had suboptimal response to prior treatments . METHOD The authors examined the effects of clozapine , olanzapine , risperidone , and haloperidol on 16 measures of neurocognitive functioning in a double-blind , 14-week trial involving 101 patients . A global score was computed along with scores in four neurocognitive domains : memory , attention , motor function , and general executive and perceptual organization . RESULTS Global neurocognitive function improved with olanzapine and risperidone treatment , and these improvements were superior to those seen with haloperidol . Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments . Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol . Clozapine yielded improvement in motor function but not more than in other groups . Average effect sizes for change were in the small to medium range . More than half of the patients treated with olanzapine and risperidone experienced \" clinical ly significant \" improvement ( changes in score of at least one-half st and ard deviation relative to baseline ) . These findings did not appear to be mediated by changes in symptoms , side effects , or blood levels of medications . CONCLUSIONS Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs , and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects", "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 Acute psychotic illness , especially when associated with agitated or violent behaviour , can require urgent pharmacological tranquillisation or sedation . In several countries , clinicians often use benzodiazepines ( either alone or in combination with antipsychotics ) for this outcome . OBJECTIVES To estimate the effects of benzodiazepines , alone or in combination with antipsychotics , when compared with placebo or antipsychotics , alone or in combination with antihistamines , to control disturbed behaviour and reduce psychotic symptoms . SEARCH METHODS We search ed the Cochrane Schizophrenia Group 's register ( January 2012 ) , inspected reference lists of included and excluded studies and contacted authors of relevant studies . SELECTION CRITERIA We included all r and omised clinical trials ( RCTs ) comparing benzodiazepines alone or in combination with any antipsychotics , versus antipsychotics alone or in combination with any other antipsychotics , benzodiazepines or antihistamines , for people with acute psychotic illnesses . DATA COLLECTION AND ANALYSIS We reliably selected studies , quality assessed them and extracted data . For binary outcomes , we calculated st and ard estimates of relative risk ( RR ) and their 95 % confidence intervals ( CI ) using a fixed-effect model . For continuous outcomes , we calculated the mean difference ( MD ) between groups . If heterogeneity was identified , this was explored using a r and om-effects model . MAIN RESULTS We included 21 trials with a total of n = 1968 participants . There was no significant difference for most outcomes in the one trial that compared benzodiazepines with placebo , although there was a higher risk of no improvement in people receiving placebo in the medium term ( one to 48 hours ) ( n = 102 , 1 RCT , RR 0.62 , 95 % CI 0.40 to 0.97 , very low quality evidence ) . There was no difference in the number of participants who had not improved in the medium term when benzodiazepines were compared with antipsychotics ( n = 308 , 5 RCTs , RR 1.10 , 95 % CI 0.85 to 1.42 , low quality evidence ) ; however , people receiving benzodiazepines were less likely to experience extrapyramidal effects ( EPS ) in the medium term ( n = 536 , 8 RCTs , RR 0.15 , 95 % CI 0.06 to 0.39 , moderate quality of evidence ) . Data comparing combined benzodiazepines and antipsychotics versus benzodiazepines alone did not yield any significant results . When comparing combined benzodiazepines/antipsychotics ( all studies compared haloperidol ) with the same antipsychotics alone ( haloperidol ) , there was no difference between groups in improvement in the medium term ( n = 155 , 3 RCTs , RR 1.27 , 95 % CI 0.94 to 1.70 , very low quality evidence ) but sedation was more likely in people who received the combination therapy ( n = 172 , 3 RCTs , RR 1.75 , 95 % CI 1.14 to 2.67 , very low quality evidence ) . However , more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine ( n = 60,1 RCT , RR 25.00 , 95 % CI 1.55 to 403.99 , very low quality evidence ) or ziprasidone ( n = 60 , 1 RCT , RR 4.00 , 95 % CI 1.25 to 12.75very low quality evidence ) . When haloperidol and midazolam were compared with olanzapine , there was some evidence the combination was superior in terms of improvement , sedation and behaviour . AUTHORS ' CONCLUSIONS The evidence from trials for the use of benzodiazepines alone is not good . There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects . Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects . Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify . Much more high quality research is needed in this area", "BACKGROUND Difficulties with affect regulation and impulse control have a strong influence on violence . The objective of this study was to determine whether baseline depression and impulsivity predict aggression and whether they predict differential response to antiaggressive treatment . This is important , as we lack knowledge as to the selection of antipsychotics for the treatment of aggression . METHODS Physically aggressive in patients with schizophrenia who received an evaluation of depression and impulsivity at baseline were r and omly assigned in a double-blind , parallel group , 12-week trial to clozapine , olanzapine , or haloperidol . Trait impulsivity was measured by the Barratt Impulsiveness Scale ; depression by the Positive and Negative Syndrome Scale Depression factor . The number and severity of aggressive events , as measured by the Modified Overt Aggression Scale ( MOAS ) , were the outcome measures . RESULTS Baseline depression and impulsivity predicted higher levels of aggression , as measured by the MOAS total score , over the 12-week treatment period across all 3 medication groups . In addition , there was a strong interaction effect between baseline depression/impulsivity and medication grouping in predicting MOAS score . In particular , when higher depression and impulsivity were present at baseline , patients on haloperidol presented with more aggression than patients on the other 3 medications . CONCLUSIONS Depression and impulsivity are important predictors of aggression and of differential response to antiaggressive treatment . This is most likely due to the medications ' dissimilar neurotransmitter profiles . By identifying patients who will respond better to a given medication , we will be able to develop individualized strategies for the treatment of violent behavior", "BACKGROUND There has been considerable support for the observation that atypical antipsychotics have a broader range of therapeutic effects than traditional antipsychotics . We are exploring whether this exp and ed clinical efficacy can also be seen in patients with treatment-resistant schizophrenia . METHOD The subjects were 157 treatment-resistant in patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder . They were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol in a 14-week double-blind trial and rated with a st and ard measure of clinical antipsychotic efficacy ( Positive and Negative Syndrome Scale [ PANSS ] ) . Factor analysis at baseline and endpoint together with changes in 5 PANSS-derived factors were examined . Data were gathered from June 1996 to December 1999 . RESULTS The underlying PANSS factor structure , as indicated by the factor loadings , was essentially identical at baseline and endpoint . At baseline , the excitement factor was followed by the positive , negative , cognitive , and depression/anxiety factors , explaining 49.4 % of the total variance . At endpoint , the positive factor was followed by the negative , excitement , cognitive , and depression/anxiety factors , explaining 55.5 % of the total variance . The endpoint data indicated statistically significant ( p haloperidol . The negative factor showed significant improvement for clozapine and olanzapine , with significant worsening for haloperidol . Clozapine , olanzapine , and risperidone were superior to haloperidol on the negative factor , while clozapine was also superior to risperidone . The cognitive factor showed significant improvement for all atypicals , as did the depression/anxiety factor . Only clozapine showed improvement on the excitement factor and was superior to both haloperidol and risperidone . CONCLUSIONS Treatment with atypical antipsychotics did not substantially change the underlying PANSS 5-factor structure . However , antipsychotic treatment with all 3 atypical medications was associated with significant improvements on 3 of 5 syndromal domains ( positive , cognitive , and depression/anxiety ) of schizophrenia . Clozapine and olanzapine also showed improvement on the negative factor . Only clozapine was associated with improvement on the excitement domain . This finding confirms that atypicals are associated with improvement of an exp and ed spectrum of symptoms in treatment-resistant patients", "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 ", "CONTEXT Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community . Finding appropriate treatment of violent behaviors is of primary importance . OBJECTIVE To compare the efficacy of 2 atypical antipsychotic agents , clozapine and olanzapine , with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder . DESIGN AND SETTING R and omized , double-blind , parallel-group , 12-week trial . Physically assaultive subjects with schizophrenia or schizoaffective disorder who were in patients in state psychiatric facilities were r and omly assigned to treatment with clozapine ( n = 37 ) , olanzapine ( n = 37 ) , or haloperidol ( n = 36 ) . MAIN OUTCOME MEASURES Number and severity of physical assaults as measured by the Modified Overt Aggression Scale ( MOAS ) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score . Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale ( PANSS ) . RESULTS Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score . Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures . There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales . CONCLUSIONS Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior . This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications", "The purpose of this study was to compare the effects of olanzapine , clozapine , and haloperidol on neurocognitive function in schizophrenic patients who present with documented episodes of physical aggression and to determine whether change in cognitive function is related to aggression . One hundred physically aggressive schizophrenic in patients were assigned to a r and omized , double-blind , parallel-group , 12-week treatment , and received cognitive evaluations at baseline . There were 33 , 34 , and 33 subjects in the clozapine , olanzapine , and haloperidol groups , respectively . They were administered a battery of tests assessing psychomotor function , general executive function , visual and verbal memory , and visuospatial ability . A general cognitive index was derived from the above battery . The overall score on the Modified Overt Aggression Scale was used to measure the number and severity of the aggressive events . Psychiatric symptoms and side effects were also assessed . The improvement in the general cognitive index differed significantly among the 3 treatment groups , with olanzapine being superior to both haloperidol and clozapine . Further analyses revealed significantly greater improvement with olanzapine in several cognitive domains . Furthermore , improvement in the general cognitive index was significantly associated with a decrease in aggression in the olanzapine group but not in the other 2 medication groups . In violent schizophrenic patients , olanzapine treatment is associated with better cognitive functioning relative to haloperidol and clozapine . This improvement in neurocognitive function is associated with a decrease in aggressive behavior . As clozapine markedly reduced aggression , there may be different pathways for the antiaggressive effect of olanzapine and that of clozapine", "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", "Abstract : The subjects were 157 treatment-resistant in patients diagnosed with chronic schizophrenia or schizoaffective disorder . They were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol in a 14-week , double-blind trial . Incidents of overt aggression were recorded and their severity was scored . The Positive and Negative Syndrome Scale was administered . Atypical antipsychotics showed an overall superiority over haloperidol , particularly after the first 24 days of the study when the dose escalation of clozapine was completed . Once an adequate therapeutic dose of clozapine was reached , it was superior to haloperidol in reducing the number and severity of aggressive incidents . Patients exhibiting persistent aggressive behavior showed less improvement of psychotic symptoms than the other patients . There was an interaction between aggressiveness , medication type , and antipsychotic response : risperidone and olanzapine showed better antipsychotic efficacy in patients exhibiting less aggressive behavior ; the opposite was true for clozapine . Clozapine appears to have superior antiaggresive effects in treatment-resistant patients ; this superiority develops after the patient has been exposed to an adequate dose regimen", "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", "OBJECTIVE Despite extensive experience with antipsychotic medications , we have limited capacity to predict which patients will benefit from which medications and for what symptoms . Such prediction is of particular importance for the proper treatment of violence . Our goal was to determine whether executive function predicts outcome of treatment for aggressive behavior and whether such prediction varies across medication groups . METHOD Ninety-nine physically aggressive in patients ( aged 18 - 60 years ) with schizophrenia or schizoaffective disorder ( diagnosed according to DSM-IV ) who completed tests of executive function were r and omly assigned in a double-blind , parallel-group , 12-week trial to clozapine ( n = 32 ) , olanzapine ( n = 32 ) , or haloperidol ( n = 35 ) . The number and severity of aggressive events as measured by the Modified Overt Aggression Scale ( MOAS ) were the outcome measures . Psychopathology and medication side effects were also assessed . The study was conducted from 1999 to 2004 . RESULTS Poor executive function predicted higher levels of aggression , as measured by MOAS scores over the 12-week period , in all 3 medication groups ( F(1,98 ) = 222.2 , P antiaggression effect even in the presence of executive dysfunction . CONCLUSIONS Executive function was a strong predictor of response to antiaggression treatment in all medication groups , but clozapine still retained clinical efficacy in the presence of poor executive functioning . Olanzapine was particularly efficacious in the absence of executive dysfunction . These findings have important implication s for a targeted approach to the treatment of aggression in patients with schizophrenia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01123408" ]

[ "BACKGROUND Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events . Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol , we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment . METHODS We r and omly assigned 17,802 apparently healthy men and women with low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin , 20 mg daily , or placebo and followed them for the occurrence of the combined primary end point of myocardial infa rct ion , stroke , arterial revascularization , hospitalization for unstable angina , or death from cardiovascular causes . RESULTS The trial was stopped after a median follow-up of 1.9 years ( maximum , 5.0 ) . Rosuvastatin reduced LDL cholesterol levels by 50 % and high-sensitivity C-reactive protein levels by 37 % . The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio for rosuvastatin , 0.56 ; 95 % confidence interval [ CI ] , 0.46 to 0.69 ; P myocardial infa rct ion ( hazard ratio , 0.46 ; 95 % CI , 0.30 to 0.70 ; P=0.0002 ) , 0.18 and 0.34 for stroke ( hazard ratio , 0.52 ; 95 % CI , 0.34 to 0.79 ; P=0.002 ) , 0.41 and 0.77 for revascularization or unstable angina ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.70 ; P combined end point of myocardial infa rct ion , stroke , or death from cardiovascular causes ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.69 ; P death from any cause ( hazard ratio , 0.80 ; 95 % CI , 0.67 to 0.97 ; P=0.02 ) . Consistent effects were observed in all subgroups evaluated . The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes . CONCLUSIONS In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels , rosuvastatin significantly reduced the incidence of major cardiovascular events . ( Clinical Trials.gov number , NCT00239681 .", "BACKGROUND The objective of this study was to assess the cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels . METHODS We performed a cost-effectiveness analysis based on actual clinical , cost , and health-related quality -of-life data from the Cholesterol and Recurrent Events ( CARE ) trial . Survival and recurrent coronary heart disease events were modeled from trial data in Markov models , with the use of different assumptions regarding the long-term benefit of therapy . RESULTS Pravastatin therapy increased quality -adjusted life expectancy at an incremental cost of $ 16,000 to $ 32,000 per quality -adjusted life-year gained . In subgroup analyses , the cost-effectiveness of pravastatin therapy was more favorable for patients > 60 years of age and for patients with pretreatment low-density lipoprotein cholesterol levels > 125 mg/dL. Results were sensitive to the cost of pravastatin and to assumptions about long-term survival benefits from pravastatin therapy . CONCLUSIONS The cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels compares favorably with other interventions", "BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD", "Objectives To evaluate the cost effectiveness of 40 mg simvastatin daily continued for life in people of different ages with differing risks of vascular disease . Design A model developed from a r and omised trial was used to estimate lifetime risks of vascular events and costs of treatment and hospital admissions in the United Kingdom . Setting 69 hospitals in the UK . Participants 20 536 men and women ( aged 40 - 80 ) with coronary disease , other occlusive arterial disease , or diabetes . Interventions 40 mg simvastatin daily versus placebo for an average of 5 years . Main outcome measures Cost effectiveness of 40 mg simvastatin daily expressed as additional cost per life year gained . Major vascular event defined as non-fatal myocardial infa rct ion or death from coronary disease , any stroke , or revascularisation procedure . Results were extrapolated to younger and older age groups at lower risk of vascular disease than were studied directly , as well as to lifetime treatment . Results At the April 2005 UK price of � 4.87 ( € 7 ; $ 9 ) per 28 day pack of generic 40 mg simvastatin , lifetime treatment was cost saving in most age groups and vascular disease risk groups studied directly . Gains in life expectancy and cost savings decreased with increasing age and with decreasing risk of vascular disease . People aged 40 - 49 with 5 year risks of major vascular events of 42 % and 12 % at start of treatment gained 2.49 and 1.67 life years , respectively . Treatment with statins remained cost saving or cost less than � 2500 per life year gained in people as young as 35 years or as old as 85 with 5 year risks of a major vascular event as low as 5 % at the start of treatment . Conclusions Treatment with statins is cost effective in a wider population than is routinely treated at present", "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", "Aims /hypothesisWe estimated the cost-effectiveness of atorvastatin treatment in the primary prevention of cardiovascular disease in patients with type 2 diabetes using data from the Collaborative Atorvastatin Diabetes Study (CARDS).Subjects and methods A total of 2,838 patients , who were aged 40 to 75 years and had type 2 diabetes without a documented history of cardiovascular disease and without elevated LDL-cholesterol , were recruited from 32 centres in the UK and Irel and and r and omly allocated to atorvastatin 10 mg daily ( n = 1,428 ) or placebo ( n = 1,410 ) . These subjects were followed-up for a median period of 3.9 years . Direct treatment costs and effectiveness were analysed to provide estimates of cost per endpoint-free year over the trial period for alternative definitions of endpoint , and of cost per life-year gained and cost per quality -adjusted life-year ( QALY ) gained over a patient ’s lifetime . Results Over the trial period , the incremental cost-effectiveness ratio ( ICER ) was estimated to be £ 7,608 per year free of any CARDS primary endpoint ; the ICER was calculated to be £ 4,896 per year free of any cardiovascular endpoint and £ 4,120 per year free of any study endpoint . Over lifetime , the incremental cost per life-year gained was £ 5,107 and the cost per QALY was £ 6,471 ( costs and benefits both discounted at 3.5 % ) . Conclusions /interpretation Primary prevention of cardiovascular disease with atorvastatin is a cost-effective intervention in patients with type 2 diabetes , with the ICER for this intervention falling within the current acceptance threshold ( £ 20,000 per QALY ) specified by the National Institute for Health and Clinical Excellence ( NICE )", "Abstract Objective : To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia . Design : Economic benefit analysis based on data from the West of Scotl and coronary prevention study . Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated . Scottish record linkage data provided disease specific survival . Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotl and coronary prevention study . Subjects : Men with hypercholesterolaemia similar to the subjects in the West of Scotl and coronary prevention study . Main outcome : Cost consequences , the number of transitions from health to cardiovascular disease prevented , the number needed to start treatment , and cost per life year gained . Results : If 10 000 of these men started taking pravastatin , 318 of them would not make the transition from health to cardiovascular disease ( number needed to treat , 31.4 ) , at a net discounted cost of £ 20 m over 5 years . These benefits imply an undiscounted gain of 2460 years of life , and thus £ 8121 per life year gained , or £ 20 375 per life year gained if benefits are discounted . Restriction to the 40 % of men at highest risk reduces the number needed to treat to 22.5 ( £ 5601 per life year gained ( undiscounted ) and £ 13 995 per life year gained ( discounted ) ) . Conclusions : In subjects without evidence of prior myocardial infa rct ion but who have hypercholesterolaemia , the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups . Key messages The West of Scotl and coronary prevention study showed that pravastatin can prevent cardiovascular disease in men with hypercholesterolaemia So far , reports have deemed this prevention unjustified due to adverse economic implication s This analysis , based on data from the West of Scotl and coronary prevention study and extensive data from the Scottish record linkage system , shows that using pravastatin in this way is worth considering because of its substantial clinical benefit at a reasonable cost Practitioners must now consider using pravastatin to prevent cardiovascular disease in men with hypercholesterolaemia Increased economic efficiency may be obtained by restricting prevention to patients with additional risk", "Purpose Normative data for WHOQOL-bref are scarce in the literature and unavailable in Latin American countries . The main objective of this study was to provide normative scores of WHOQOL-bref in a general population sample in Brazil and to describe differences in mean scores according to some socio-demographic characteristics . Methods WHOQOL-bref was applied to a r and omly selected sample of the general population of Porto Alegre . Participants were literate people aged 20 to 64 years . The question naires were self-administered in the presence of an interviewer in the respondent ’s home . Results The response rate was 68 % , and the final sample contained 751 respondents ( 38 % men , 62 % women ) . Low quality of life was observed in the following subgroups : female gender , lower economic class , lower educational level , and the subgroup reporting a chronic medical condition . The mean scores of the WHOQOL-bref and percentiles of scores are reported as normative data for the general population . Conclusion Our results can be useful to research ers using the WHOQOL-bref to compare their results with normative data from a r and omly selected sample of general population . Additionally , the ability of WHOQOL-bref to discriminate different population subgroups makes it an important tool to identify vulnerable groups in epidemiological surveys", "OBJECTIVE To assess the cost-effectiveness of rosuvastatin in the treatment of hypercholesterolemia and the prevention of ischemic heart disease ( IHD ) in Portugal . METHODS A probabilistic Markov model was constructed to analyze the costs and consequences of lifetime treatment with rosuvastatin , atorvastatin , pravastatin , and simvastatin . For this purpose , the results from r and omized head-to-head trials evaluating low-density lipoprotein ( LDL ) changes were combined with the results from a meta- analysis defining the relationship between LDL levels and fatal and nonfatal IHD events . The incidence of myocardial infa rct ion ( MI ) was derived from a 9-year Portuguese observational study . The eligible population was defined as untreated individuals aged more than 35 years with LDL levels above 115 mg/dl . Death rates due to IHD and other causes were obtained from official data . Re source use in the treatment of MI was estimated by a Delphi panel of eight Portuguese cardiologists with at least 15 years of clinical practice . Costs were calculated from the payers ' perspective . RESULTS Rosuvastatin increases life expectancy between 5.5 and 12.1 days per patient . It is cost-saving when compared to atorvastatin , but it increases costs when assessed against pravastatin and simvastatin ( euro1,004 and euro684 per patient , respectively ) . Therefore , rosuvastatin is a dominant alternative compared to atorvastatin , having an incremental cost-effectiveness ratio of euro30,350 to pravastatin and euro39,340 to simvastatin . In the probabilistic sensitivity analysis , performed rosuvastatin always dominates atorvastatin and is associated with a cost per life-year gained inferior to euro50,000 in 95.7 % of the cases when compared to pravastatin and in 67.0 % simulations when assessed against simvastatin . CONCLUSIONS Rosuvastatin is a cost-effective alternative in the prevention of IHD in Portugal", "Recent large-scale r and omized , controlled trials of 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors ( statins ) have shown statistically significant reductions in cardiovascular events , strokes , and total mortality among selected groups , including patients with risk factors for vascular disease or a history of vascular disease ( 1 - 5 ) . In addition , cost-effectiveness analyses of the Sc and inavian Simvastatin Survival Study and the West of Scotl and Coronary Prevention Study have shown favorable cost-effectiveness ratios ( 6 , 7 ) . A limitation of the r and omized , controlled trials of statin therapy published to date , however , has been their failure to enroll patients older than 75 years of age . Ongoing r and omized , controlled trials are including patients in this age category , but results will not be available for some time ( 8 , 9 ) . Meanwhile , analyses of data from two secondary prevention trials , the Sc and inavian Simvastatin Survival Study and the Cholesterol and Recurrent Events ( CARE ) trial , have found that participants 65 to 70 years of age and those 65 to 75 years of age , respectively , experienced statistically significant reductions in cardiac end points similar to those seen in trial participants as a whole ( 10 , 11 ) . These results raise the prospect of extending the use of statins to patients older than 75 years of age with established coronary heart disease ( 12 ) . Although the issue of efficacy in patients older than 75 years of age will not be resolved definitively until trials of patients in this age group are published , decision-analytic models can test various assumptions about efficacy to gauge the potential cost-effectiveness of statins in this context . We modeled the cost-effectiveness of statin therapy in a hypothetical cohort of patients 75 to 84 years of age with a history of myocardial infa rct ion by extrapolating results from published r and omized , controlled trials and epidemiologic data . Methods Model We compared two strategies for patients 75 to 84 years of age with previous myocardial infa rct ion : usual care and initiation of HMG-CoA reductase inhibitor therapy . We developed a Markov model ( 13 ) and conducted a cohort simulation to track costs and health outcomes for hypothetical patients r and omly assigned to one of these strategies . In this model , patients can occupy one of six health states : baseline ( history of at least one myocardial infa rct ion ) , recurrent myocardial infa rct ion , postrecurrent myocardial infa rct ion , stroke , post-stroke , or dead ( Figure 1 ) . The model was not configured to deal with multiple events ( such as recurrent myocardial infa rct ion after stroke ) because such sequences of events occur infrequently enough to have a small effect on the overall analysis . Other health states , such as congestive heart failure , were not modeled explicitly but were averaged into the mortality estimates and quality -of-life weights . The model was constructed by using DATA 3.5 software ( TreeAge Software , Williamstown , Massachusetts ) . We adopted the societal perspective in all analyses . Figure 1 . Markov model . MI Transition Probabilities Each state of the model has an associated mortality rate that specifies the probability of dying in any given cycle ( Table 1 ) . These mortality rates were determined by using mortality risk ratios relative to all-cause mortality for an age-matched unselected population ; all-cause mortality rates were obtained from vital statistics data ( 14 ) . We chose to use mortality risk ratios ( multiplicative model ) rather than excess mortality ( additive model ) because a multiplicative model better captures how the risk for death from coronary heart disease changes with age ( 15 , 16 ) . Table 1 . Variables Governing Transition Probabilities for the Markov Model For purpose s of calibration , we initially created a two-state ( alive or dead ) Markov model , with mortality rates based on the 10-year survival curve after acute myocardial infa rct ion for patients 75 to 84 years of age ( 17 ) . The life expectancy of patients in the calibration model was then used as a benchmark to calibrate life expectancy for patients in the usual care strategy of the full six-state model . In the six-state model , we differentiated between death after recurrent myocardial infa rct ion or stroke and death from nonmyocardial infa rct ion or nonstroke causes because statins , by preventing both myocardial infa rct ion and stroke ( 2 ) , also prevent death after these events . Because patients with a history of myocardial infa rct ion have a higher chance of dying of coronary heart disease that is unrelated to recurrent myocardial infa rct ion ( for example , arrhythmia ) , this cohort has a higher risk for death from causes other than myocardial infa rct ion or stroke than does an unselected population . Long-term mortality after recurrent myocardial infa rct ion was adjusted upward to account for the additional risk for death after a recurrent event , on the basis of hazard ratios for coronary heart disease death as a function of nonfatal reinfa rct ion ( 18 ) . We converted these ratios into a hazard ratio for total mortality on the basis of data from the same trial indicating that coronary heart disease caused 76 % of deaths ( 19 ) and on the assumption of no excess risk for noncoronary heart disease death in patients with reinfa rct ion . Mortality rates after stroke were based on published data from the Oxfordshire Community Stroke Project ( 20 ) . Transition probabilities to recurrent myocardial infa rct ion or stroke from the baseline state are based on data describing reinfa rct ion rates ( 21 ) and stroke rates ( 22 , 23 ) . All of the data used to determine transition probabilities are population -based and specific to patients older than 75 years of age , with the exception of data from a clinical trial of patients up to 75 years of age ( 18 , 19 ) . We used data from a follow-up study of patients 65 to 75 years of age in the CARE trial to estimate the relative risk reduction conferred by statin therapy for the end points of myocardial infa rct ion ( fatal and nonfatal combined ) and stroke ( 11 ) . This study stratified patients in the CARE trial into those younger than 65 years of age and those 65 to 75 years of age and found that the latter group experienced statistically significant and clinical ly important reductions in cardiac and cerebrovascular events . Our base-case analysis used the mean estimates of relative risk reduction published in this study for patients 65 to 75 years of age , and the sensitivity analysis used the 95 % confidence limits . We applied risk reductions due to statin therapy to only two transitions out of the baseline state : recurrent myocardial infa rct ion and stroke . Because we did not explicitly model multiple strokes or recurrent myocardial infa rct ion , the model is based on the assumption that patients discontinue statin therapy after their first stroke or recurrent myocardial infa rct ion and no longer experience any additional costs or benefits of statin therapy . We also assumed that patients in the baseline state who are receiving statin therapy continue to accrue the benefits and costs associated with this therapy for the duration of their time in the baseline state . In a sensitivity analysis , we limited benefits of statin therapy to the first 5 years in the baseline state ; this time frame is similar to the duration of follow-up for the large r and omized , controlled trials of statin therapy ( 1 - 5 ) . Under this scenario , after 5 years , patients experience the same event rates and mortality rates as those not using statin therapy but continue to accrue the costs of drug while in the baseline state . This conservative analysis was conducted to examine the consequences of continuing to take a drug that in fact provides no additional benefit beyond the period for which it has been studied . Health-Related Quality of Life The model measured health effects in terms of quality -adjusted life expectancy . The health-related quality -of-life weights for the health states ( Table 2 ) were derived from time-tradeoff scores collected from patients with myocardial infa rct ion in the quality -of-life sub study of Global Use of Strategies to Open Occluded Coronary Arteries ( GUSTO-I ) ( 24 ) , which included patients older than 75 years of age . That study reported quality -of-life scores in patients who experienced various levels of disability from in-hospital stroke after myocardial infa rct ion and in patients who did not have a stroke . The quality -of-life weight ( utility ) for stroke was derived from the mean time-tradeoff utility for patients with ischemic stroke in GUSTO-I because these represent most nonfatal strokes . Bounds for sensitivity analysis were based on quality -of-life estimates approximately 1 SD from the mean . We also conducted a sensitivity analysis in which health states were not adjusted for quality -of-life differences . Table 2 . Utilities , Costs , and Discount Rate The base-case model assumed no disutility associated with statin use . This assumption was based on two studies of pravastatin that included patients older than 75 years of age and showed that pravastatin was well tolerated , with an incidence of adverse events similar to that of placebo ( 25 , 26 ) . However , because we know of no published studies of utilities in patients receiving statins , we performed a sensitivity analysis using a utility decrement of 0.013 in patients taking statins . This number represents the utility decrement related to taking warfarin , a drug associated with considerably more inconvenience ( monthly laboratory monitoring ) , lifestyle modification , and risk than statins ( 27 ) . Costs In the base-case model , we included the following direct medical costs for both strategies : hospitalizations for nonfatal and fatal myocardial infa rct ion , hospitalizations for stroke , and post-stroke institutional care ( nursing home and rehabilitation ) . Patients in the statin group also experienced yearly drug costs and the cost of two additional office visits and two hepatic function" ]

[ "Background —Arterial distensibility measures , generally from pulse-wave velocity ( PWV ) , are widely used with little knowledge of relationships to patient outcome . We tested whether aortic PWV predicts cardiovascular and all-cause mortality in type 2 diabetes and glucose-tolerance – tested ( GTT ) multiethnic population sample s. Methods and Results — Participants were r and omly sample d from ( 1 ) a type 2 diabetes outpatient clinic and ( 2 ) primary care population registers , from which nondiabetic control subjects were given a GTT . Brachial blood pressures and Doppler-derived aortic PWV were measured . Mortality data over 10 years ’ follow-up were obtained . At any level of systolic blood pressure ( SBP ) , aortic PWV was greater in subjects with diabetes than in controls . Mortality risk doubled in subjects with diabetes ( hazard ratio 2.34 , 95 % CI 1.5 to 3.74 ) and in those with glucose intolerance ( 2.12 , 95 % CI 1.11 to 4.0 ) compared with controls . For all groups combined , age , sex , and SBP predicted mortality ; the addition of PWV independently predicted all-cause and cardiovascular mortality ( hazard ratio 1.08 , 95 % CI 1.03 to 1.14 for each 1 m/s increase ) but displaced SBP . Glucose tolerance status and smoking were other independent contributors , with African-Caribbeans experiencing reduced mortality risk ( hazard ratio 0.41 , 95 % CI 0.25 to 0.69 ) . Conclusions —Aortic PWV is a powerful independent predictor of mortality in both diabetes and GTT population sample s. In displacing SBP as a prognostic factor , aortic PWV is probably further along the causal pathway for arterial disease and may represent a useful integrated index of vascular status and hence cardiovascular risk", "BACKGROUND There are limited data describing the presenting characteristics , management , and outcomes of diabetic and nondiabetic patients with an acute coronary syndrome ( ACS ) . OBJECTIVE To examine differences in these factors , patients with ST-segment elevation acute myocardial infa rct ion , non-ST-segment elevation acute myocardial infa rct ion , and unstable angina were enrolled in a large multinational coronary disease registry . METHODS The Global Registry of Acute Coronary Events is a prospect i ve observational study of patients hospitalized with an ACS at 94 hospitals in 14 countries . The study sample consisted of 5403 patients with ST-segment elevation acute myocardial infa rct ion , 4725 with non-ST-segment elevation acute myocardial infa rct ion , and 5988 with unstable angina . RESULTS Approximately 1 in 4 patients presented to participating hospitals with a history of diabetes . Patients with diabetes were older , more often women , with a greater prevalence of comorbidities , and they were less likely to be treated with effective cardiac therapies than nondiabetic patients . Patients with diabetes who developed an ACS were at increased risk for each hospital outcome examined including heart failure , renal failure , cardiogenic shock , and death . These differences remained after adjustment for potentially confounding prognostic factors . CONCLUSIONS A considerable proportion of patients with an ACS has diabetes and is at increased risk for adverse outcomes compared with patients without diabetes . There are certain proven therapeutic strategies that remain underused in the diabetic population . A more widespread awareness of this increased risk and a more diligent use of proven cardiac treatment approaches are indicated for patients with diabetes who develop an ACS", "Background Individuals with type 1 diabetes mellitus are at high risk for the development of hypertension , contributing to cardiovascular complications . Hyperglycaemia-mediated neurohormonal activation increases arterial stiffness , and is an important contributing factor for hypertension . Since the sodium glucose cotransport-2 ( SGLT2 ) inhibitor empagliflozin lowers blood pressure and HbA1c in type 1 diabetes mellitus , we hypothesized that this agent would also reduce arterial stiffness and markers of sympathetic nervous system activity . Methods Blood pressure , arterial stiffness , heart rate variability ( HRV ) and circulating adrenergic mediators were measured during clamped euglycaemia ( blood glucose 4–6 mmol/L ) and hyperglycaemia ( blood glucose 9–11 mmol/L ) in 40 normotensive type 1 diabetes mellitus patients . Studies were repeated after 8 weeks of empagliflozin ( 25 mg once daily ) . Results In response to empagliflozin during clamped euglycaemia , systolic blood pressure ( 111 ± 9 to 109 ± 9 mmHg , p = 0.02 ) and augmentation indices at the radial ( -52 % ± 16 to -57 % ± 17 , p = 0.0001 ) , carotid ( + 1.3 ± 1 7.0 to -5.7 ± 17.0 % , p 14.3 % , p 0.0001 ) declined . Similar effects on arterial stiffness were observed during clamped hyperglycaemia without changing blood pressure under this condition . Carotid-radial pulse wave velocity decreased significantly under both glycemic conditions ( p ≤ 0.0001 ) , while declines in carotid-femoral pulse wave velocity were only significant during clamped hyperglycaemia ( 5.7 ± 1.1 to 5.2 ± 0.9 m/s , p = 0.0017 ) . HRV , plasma noradrenalin and adrenaline remained unchanged under both clamped euglycemic and hyperglycemic conditions . Conclusions Empagliflozin is associated with a decline in arterial stiffness in young type 1 diabetes mellitus subjects . The underlying mechanisms may relate to pleiotropic actions of SGLT2 inhibition , including glucose lowering , antihypertensive and weight reduction effects . Trial registration Clinical trial registration :", "Background — The primary objective of this mechanistic open-label , stratified clinical trial was to determine the effect of 8 weeks ’ sodium glucose cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration in subjects with type 1 diabetes mellitus ( T1D ) . Methods and Results — Inulin ( glomerular filtration rate ; GFR ) and paraaminohippurate ( effective renal plasma flow ) clearances were measured in individuals stratified based on having hyperfiltration ( T1D-H , GFR ≥ 135 mL/min/1.73m2 , n=27 ) or normal GFR ( T1D-N , GFR 90–134 mL/min/1.73m2 , n=13 ) at baseline . Renal function and circulating levels of renin-angiotensin-aldosterone system mediators and NO were measured under clamped euglycemic ( 4–6 mmol/L ) and hyperglycemic ( 9–11 mmol/L ) conditions at baseline and end of treatment . During clamped euglycemia , hyperfiltration was attenuated by −33 mL/min/1.73m2 with empagliflozin in T1D-H , ( GFR 172±23–139±25 mL/min/1.73 m2 , P declines in plasma NO and effective renal plasma flow and an increase in renal vascular resistance ( all P on GFR and renal function parameters were observed during clamped hyperglycemia . In T1D-N , GFR , other renal function parameters , and plasma NO were not altered by empagliflozin . Empagliflozin reduced hemoglobin A1c significantly in both groups , despite lower insulin doses in each group ( P⩽0.04 ) . Conclusions — In conclusion , short-term treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin attenuated renal hyperfiltration in subjects with T1D , likely by affecting tubular-glomerular feedback mechanisms . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01392560", "BACKGROUND There is controversy over the usefulness of prediabetes as a diagnostic label . Using data from US National Health and Nutrition Examination Surveys ( NHANES ) between 1988 and 2014 , we examined the cardiovascular and renal burdens in adults with prediabetes over time and compared patterns with other glycaemic status groups . METHODS We analysed cross-sectional survey data from non-pregnant adults aged 20 years and older from the NHANES survey periods 1988 - 94 , 1999 - 2004 , 2005 - 10 , and 2011 - 14 . We defined diagnosed diabetes as patients ' self-report that they had been previously diagnosed by a physician or health professional ; among those with no self-reported diabetes , prediabetes was defined as a fasting plasma glucose ( FPG ) concentration of 100 - 125 mg/dL ( 5·6 - 6·9 mmol/L ) or an HbA1c of 5·7 - 6·4 % ( 39 - 47 mmol/mol ) ; undiagnosed diabetes as an FPG of 126 mg/dL ( 7·0 mmol/L ) or higher or an HbA1c of 6·5 % ( 48 mmol/mol ) or higher ; and normal glycaemic status as an FPG of less than 100 mg/dL ( 5·6 mmol/L ) and an HbA1c of less than 5·7 % ( 39 mmol/mol ) . We repeated the analyses using varying definitions of prediabetes ( FPG 110 - 125 mg/dL [ 6·1 - 6·9 mmol/L ] or HbA1c 5·7 - 6·4 % [ 39 - 47 mmol/mol ] , FPG 110 - 125 mg/dL [ 6·1 - 6·9 mmol/L ] or HbA1c 6·0 - 6·4 % [ 42 - 47 mmol/mol ] , and FPG 100 - 125 mg/dL [ 5·6 - 6·9 mmol/L ] and HbA1c 5·7 - 6·4 % [ 39 - 47 mmol/mol ] ) . For each group over time , we estimated the prevalences of hypertension and dyslipidaemia ; and among individuals with those conditions , we estimated the proportions who had been treated and who were achieving care goals . By glycaemic group , we estimated those who were current , former , and never smokers ; mean 10-year risk of cardiovascular disease ( using estimators from the Framingham Heart Study , the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) , and the ACC/AHA ASCVD guidelines ) ; albuminuria ( median and albumin-to-creatinine ratio ≥30 mg/g ) , estimated glomerular filtration rate ( eGFR ; mean and ; and prevalence of myocardial infa rct ion and stroke . For all estimates , we calculated predicted changes between 1988 - 94 and 2011 - 14 using logistic regression models adjusted for age , sex , and race or ethnic group . FINDINGS We obtained data for 27 971 eligible individuals . In 2011 - 14 , in the population of adults with prediabetes , 36·6 % ( 95 % CI 32·8 - 40·5 ) had hypertension , 51·2 % ( 47·0 - 55·3 ) had dyslipidaemia , 24·3 % ( 21·7 - 27·3 ) smoked ; 7·7 % ( 6·8 - 8·8 ) had albuminuria ; 4·6 % ( 3·7 - 5·9 ) had reduced eGFR ; and 10-year cardiovascular event risk ranged from 5 % to 7 % . From 1988 - 94 to 2011 - 14 , adults with prediabetes showed significant increases in hypertension ( + 9·7 percentage points [ 95 % CI 5·4 - 14·0 ] ) ; no change in dyslipidaemia ; decreases in smoking ( -6·4 percentage points [ -10·7 to -2·1 ] ) ; increased use of treatment to lower blood pressure ( 54·2 % [ 49·0 - 59·3 ] to 81·4 % [ 76·7 - 85·3 ] , + 27·2 percentage points [ 20·5 - 33·8 ] p ( 6·6 % to 40·2 % , + 33·6 percentage points [ 30·2 - 37·0 ] , p blood pressure ( 25·8 % to 62·0 % , + 36·2 percentage points [ 30·7 - 41·8 ] , p lipids ( 1·0 % to 32·8 % , + 31·8 percentage points [ 29·1 - 34·4 , p showed decreases in cardiovascular risk ( ASCVD -1·9 percentage points [ -2·5 to -1·3 ] to UKPDS -2·7 [ -3·5 to -1·9 ] , p in prevalence of albuminuria , reduced eGFR , myocardial infa rct ion , or stroke . Prevalence and patterns were consistent across all prediabetes definitions examined . Compared with adults with prediabetes , adults with diagnosed diabetes showed much larger improvements in cardiovascular and renal risk treatments , apart from smoking , which did not decline . INTERPRETATION Over 25 years , cardiovascular and renal risks and disease have become highly prevalent in adults with prediabetes , irrespective of the definitions used . Identification of people with prediabetes might increase the opportunity for cardiovascular and renal risk reduction . FUNDING None", "Background Although unstable coronary artery disease is the most common reason for admission to a coronary care unit , the long-term prognosis of patients with this diagnosis is unknown . This is particularly true for patients with diabetes mellitus , who are known to have a high morbidity and mortality after an acute myocardial infa rct ion . Methods and Results Prospect ively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes ( OASIS ) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non – Q-wave myocardial infa rct ion . Overall , 1718 of 8013 registry patients ( 21 % ) had diabetes . Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients ( 23 % versus 20 % , P rates of catheterization and angioplasty . Diabetes independently predicted mortality ( relative risk [ RR ] , 1.57 ; 95 % CI , 1.38 to 1.81;P cardiovascular death , new myocardial infa rct ion , stroke , and new congestive heart failure . Moreover , compared with their nondiabetic counterparts , women had a significantly higher risk than men ( RR , 1.98 ; 95 % CI , 1.60 to 2.44 ; and RR , 1.28 ; 95 % CI , 1.06 to 1.56 , respectively ) . Interestingly , diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease . Conclusions Hospitalization for unstable angina or non – Q-wave myocardial infa rct ion predicts a high 2-year morbidity and mortality ; this is especially evident for patients with diabetes . Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease", "BACKGROUND Information and behaviour can spread through interpersonal ties . By targeting influential individuals , health interventions that harness the distributive properties of social networks could be made more effective and efficient than those that do not . Our aim was to assess which targeting methods produce the greatest cascades or spillover effects and hence maximise population -level behaviour change . METHODS In this cluster r and omised trial , participants were recruited from villages of the Department of Lempira , Honduras . We blocked villages on the basis of network size , socioeconomic status , and baseline rates of water purification , for delivery of two public health interventions : chlorine for water purification and multivitamins for micronutrient deficiencies . We then r and omised villages , separately for each intervention , to one of three targeting methods , introducing the interventions to 5 % sample s composed of either : r and omly selected villagers ( n=9 villages for each intervention ) ; villagers with the most social ties ( n=9 ) ; or nominated friends of r and om villagers ( n=9 ; the last strategy exploiting the so-called friendship paradox of social networks ) . Participants and data collectors were not aware of the targeting methods . Primary endpoints were the proportions of available products redeemed by the entire population under each targeting method . This trial is registered with Clinical Trials.gov , number NCT01672580 . FINDINGS Between Aug 4 , and Aug 14 , 2012 , 32 villages in rural Honduras ( 25 - 541 participants each ; total study population of 5773 ) received public health interventions . For each intervention , nine villages ( each with 1 - 20 initial target individuals ) were r and omised , using a blocked design , to each of the three targeting methods . In nomination-targeted villages , 951 ( 74·3 % ) of 1280 available multivitamin tickets were redeemed compared with 940 ( 66·2 % ) of 1420 in r and omly targeted villages and 744 ( 61·0 % ) of 1220 in indegree-targeted villages . All pairwise differences in redemption rates were significant ( p increased adoption of the nutritional intervention by 12·2 % compared with r and om targeting ( 95 % CI 6·9 - 17·9 ) . Targeting the most highly connected individuals , by contrast , produced no greater adoption of either intervention , compared with r and om targeting . INTERPRETATION Introduction of a health intervention to the nominated friends of r and om individuals can enhance that intervention 's diffusion by exploiting intrinsic properties of human social networks . This method has the additional advantage of scalability because it can be implemented without mapping the network . Deployment of certain types of health interventions via network targeting , without increasing the number of individuals targeted or the re sources used , could enhance the adoption and efficiency of those interventions , thereby improving population health . FUNDING National Institutes of Health , The Bill & Melinda Gates Foundation , Star Family Foundation , and the Canadian Institutes of Health Research", "The diabetes and obesity epidemics are closely intertwined . International r and omized controlled trials demonstrate that , in high-risk individuals , type 2 diabetes can be prevented or at least delayed through lifestyle modification and , to a lesser degree , medication . We explored the relative roles of science , surgery , service delivery , and social policy in preventing diabetes . Although it is clear that there is a role for all , diabetes is a complex problem that dem and s commitment across a range of government and nongovernment agencies to be effectively controlled . Accordingly , we argue that social policy is the key to achieving and sustaining social and physical environments required to achieve widespread reductions in both the incidence and prevalence of diabetes", "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", "Care pathways are a prominent feature of efforts to improve healthcare quality , outcomes and accountability , but sociological studies of pathways often find professional resistance to st and ardisation . This qualitative study examined the adoption and adaptation of a novel pathway as part of a r and omised controlled trial in an unusually complex , non-linear field - emergency general surgery - by teams of surgeons and physicians in six theoretically sample d sites in the UK . We find near-universal receptivity to the concept of a pathway as a means of improving peri-operative processes and outcomes , but concern about the impact on appropriate professional judgement . However , this concern translated not into resistance and implementation failure , but into a nuancing of the pathways-as-realised in each site , and their use as a means of enhancing professional decision-making and inter-professional collaboration . We discuss our findings in the context of recent literature on the interplay between managerialism and professionalism in healthcare , and highlight practical and theoretical implication", "Some medical scientists argue that only data from r and omized controlled trials ( RCTs ) are trustworthy . They cl aim data from natural experiments and administrative data sets are always spurious and can not be used to evaluate health policies and other population -wide phenomena in the real world . While many acknowledge biases caused by poor study design s , in this article we argue that several valid design s using administrative data can produce strong findings , particularly the interrupted time series ( ITS ) design . Many policy studies neither permit nor require an RCT for cause- and -effect inference . Framing our arguments using Campbell and Stanley ’s classic research design monograph , we show that several “ quasi-experimental ” design s , especially interrupted time series ( ITS ) , can estimate valid effects ( or non-effects ) of health interventions and policies as diverse as public insurance coverage , speed limits , hospital safety programs , drug abuse regulation and withdrawal of drugs from the market . We further note the recent rapid uptake of ITS and argue for exp and ed training in quasi-experimental design s in medical and graduate schools and in post-doctoral curricula", "Aims : With the increase in the number of systematic review s available , a logical next step to provide decision makers in healthcare with the evidence they require has been the conduct of review s of existing systematic review s. Syntheses of existing systematic review s are referred to by many different names , one of which is an umbrella review . An umbrella review allows the findings of review s relevant to a review question to be compared and contrasted . An umbrella review 's most characteristic feature is that this type of evidence synthesis only considers for inclusion the highest level of evidence , namely other systematic review s and meta-analyses . A methodology working group was formed by the Joanna Briggs Institute to develop method ological guidance for the conduct of an umbrella review , including diverse types of evidence , both quantitative and qualitative . The aim of this study is to describe the development and guidance for the conduct of an umbrella review . Methods : Discussion and testing of the elements of methods for the conduct of an umbrella review were held over a 6-month period by members of a methodology working group . The working group comprised six participants who corresponded via teleconference , e-mail and face-to-face meeting during this development period . In October 2013 , the methodology was presented in a workshop at the Joanna Briggs Institute Convention . Workshop participants , review authors and method ologists provided further testing , critique and feedback on the proposed methodology . Results : This study describes the methodology and methods developed for the conduct of an umbrella review that includes published systematic review s and meta-analyses as the analytical unit of the review . Details are provided regarding the essential elements of an umbrella review , including presentation of the review question in a Population , Intervention , Comparator , Outcome format , nuances of the inclusion criteria and search strategy . A critical appraisal tool with 10 questions to help assess risk of bias in systematic review s and meta-analyses was also developed and tested . Relevant details to extract from included review s and how to best present the findings of both quantitative and qualitative systematic review s in a reader friendly format are provided . Conclusions : Umbrella review s provide a ready means for decision makers in healthcare to gain a clear underst and ing of a broad topic area . The umbrella review methodology described here is the first to consider review s that report other than quantitative evidence derived from r and omized controlled trials . The methodology includes an easy to use and informative summary of evidence table to readily provide decision makers with the available , highest level of evidence relevant to the question posed", "Atrial fibrillation ( AF ) is prevalent in patients with type 2 diabetes mellitus ( DM ) and is associated with markers of poor glycemic control ; however , the impact of glycemic control on incident AF and outcomes is unknown . The aims of this study were to prospect ively evaluate if intensive glycemic control in patients with DM affects incident AF and to evaluate morbidity and mortality in patients with DM and incident AF . A total of 10,082 patients with DM from the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) cohort were studied in a r and omized , double-blind fashion . Participants were r and omized to an intensive therapeutic strategy targeting a glycated hemoglobin level of or a st and ard strategy targeting a glycated hemoglobin level of 7.0 % to 7.9 % . Incident AF occurred in 159 patients ( 1.58 % ) over the follow-up period , at a rate of 5.9 per 1,000 patient-years in the intensive-therapy group and a rate of 6.37 per 1,000 patient-years in the st and ard-therapy group ( p = 0.52 ) . In a multivariate model , predictors of incident AF were age , weight , diastolic blood pressure , heart rate , and heart failure history . Patients with DM and new-onset AF had a hazard ratio of 2.65 for all-cause mortality ( 95 % confidence interval 1.8 to 3.86 , p myocardial infa rct ion ( 95 % confidence interval 1.33 to 3.31 , p = 0.0015 ) , and a hazard ratio of 3.80 for the development of heart failure ( 95 % confidence interval 2.48 to 5.84 , p rate of new-onset AF . Patients with DM and incident AF had an increased risk for morbidity and mortality compared with those without AF", "BACKGROUND In patients with acute myocardial infa rct ion ( MI ) , increased plasma glucose levels at hospital admission are associated with worse outcome . We aim ed to assess the predictive value of admission glucose concentrations on short- and long-term mortality in patients with acute MI undergoing primary or rescue percutaneous coronary intervention ( PCI ) . METHODS We analyzed the 30-day and long-term ( mean follow-up 3.7 years ) outcome of 978 patients prospect ively included in a single-center registry of patients with acute MI treated with PCI within 24 hours after onset of symptoms . Patients were classified according to plasma glucose levels at admission : 11.0 mmol/L ( group III , n = 308 ) . RESULTS Mortality at 30 days was 1.2 % in group I , 6.3 % in group II , and 16.6 % in group III ( P relative risk of death at 30 days for group III versus group I was 3.9 ( 95 % CI 1.2 - 13.2 ) . During long-term follow-up , mortality was similar in groups I and II . However , in group III adjusted mortality remained significantly increased compared with group I ( relative risk 1.76 , CI 1.01 - 3.08 ) . CONCLUSIONS In patients undergoing emergency PCI for acute MI , glucose levels at hospital admission are predictive for short- and long-term survival . Knowledge of admission glucose levels may improve initial bedside risk stratification", "IMPORTANCE The value of measuring levels of glycated hemoglobin ( HbA1c ) for the prediction of first cardiovascular events is uncertain . OBJECTIVE To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease ( CVD ) risk . DESIGN , SETTING , AND PARTICIPANTS Analysis of individual-participant data available from 73 prospect i ve studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment . MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes ( eg , C-index ) and reclassification ( eg , net reclassification improvement ) of participants across predicted 10-year risk categories of low ( incident fatal and nonfatal CVD outcomes ( 13,237 coronary heart disease and 7603 stroke outcomes ) were recorded . In analyses adjusted for several conventional cardiovascular risk factors , there was an approximately J-shaped association between HbA1c values and CVD risk . The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate , but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein . The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 ( 95 % CI , 0.7350 to 0.7517 ) . The addition of information on HbA1c was associated with a C-index change of 0.0018 ( 0.0003 to 0.0033 ) and a net reclassification improvement of 0.42 ( -0.63 to 1.48 ) for the categories of predicted 10-year CVD risk . The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting , r and om , or postload plasma glucose levels . CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes , additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk", "Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P deaths related to diabetes ( 15 % to 27 % , P myocardial infa rct ion ( 8 % to 21 % , P microvascular complications ( 33 % to 41 % , P patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % )", "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", "BACKGROUND Diabetes mellitus is a major health problem that is growing rapidly worldwide . A collaborative and integrated team approach in which pharmacists can play a pivotal role should be sought when managing patients with diabetes . OBJECTIVE To identify and summarize the main outcomes of pharmacist interventions in the management of type 2 diabetes . METHODS PubMed , Cochrane Central Register of Controlled Trials , and Web of Science were search ed for r and omized controlled trials evaluating the effectiveness of any pharmacist intervention directed at patients with type 2 diabetes in comparison with usual care . Outcome measures of interest included glycosylated hemoglobin ( Alc ) , blood glucose , blood pressure , lipid profile , body mass index ( BMI ) , 10-year coronary heart disease ( CHD ) risk , medication adherence , health-related quality of life ( HRQoL ) , and economic outcomes . The risk of bias in included studies was assessed using the Cochrane risk of bias tool . RESULTS Thirty-six studies were included in this systematic review , involving 5,761 participants . The studies evaluated the effects of several pharmacist interventions carried out in various countries and in different health care facilities , such as community pharmacies , primary care clinics , and hospitals . The number of studies reporting each outcome of interest varied . Alc was evaluated in 26 studies , of which 24 reported a greater reduction in this outcome in the intervention group compared with the control group , with the difference in change between groups ranging from -0.18 % to -2.1 % . Eighteen studies assessed change in systolic blood pressure , of which 17 studies reported a greater improvement in this outcome in the intervention group , with the difference in change between groups varying between -3.3 mmHg and -23.05 mmHg . For diastolic blood pressure , a greater effect was also observed in the intervention group in 14 out of 15 studies , with the difference in change between groups varying between -0.21 mmHg and -9.1 mmHg . Thirteen studies described total cholesterol as an outcome measure , of which 10 reported a greater improvement in this outcome in the intervention group , with the difference in change between groups ranging from + 18.95 mg dL(-1 ) to -32.48 mg dL(-1 ) . With regard to low-density lipoprotein cholesterol , a greater reduction in this parameter in the intervention group was documented in 12 out of 15 studies , with the difference in change between groups varying between + 7.35 mg dL(-1 ) and -30 mg dL(-1 ) . Similarly , favorable data were reported on high-density lipoprotein cholesterol in the intervention group in 9 out of 12 studies that assessed this outcome , with the difference in change between groups ranging from -5.8 mg dL(-1 ) to + 11 mg dL(-1 ) . Data on triglycerides were also reported in 12 studies , of which 9 reported a greater reduction in triglycerides levels in the intervention group , with the difference in change between groups varying between + 12 mg dL(-1 ) and -62 mg dL(-1 ) . Overall , a beneficial effect on BMI was also described in the intervention group in 12 out of 14 studies . Of note , in all 6 studies that estimated the 10-year CHD risk among study patients , a greater improvement in the intervention group versus the control group was found . In addition , pharmacist interventions also had a positive impact on medication adherence and HRQoL in most studies that ascertained these outcomes . Finally , although only 3 studies conducted a cost-effectiveness analysis , pharmacist interventions proved to be cost-effective . CONCLUSIONS The findings from this review clearly support the involvement of pharmacists as members of health care teams in the management of patients with type 2 diabetes . DISCLOSURES This systematic review was not funded . The authors declare that they have no conflicts of interest . Concept and study design were created by Pousinho , Morgado , and Alves . Pousinho took the lead in data collection , along with Alves , and data interpretation was performed by Pousinho , Falcão , and Alves . The manuscript was primarily written by Pousinho , along with Alves , and revised by Alves , Morgado , and Falcão", "AIM To evaluate the effects of canagliflozin on plasma volume , urinary glucose excretion ( UGE ) , fasting plasma glucose ( FPG ) , glycated haemoglobin ( HbA1c ) and additional measures of fluid/electrolyte balance in patients with type 2 diabetes on background therapy with metformin and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers . METHODS Patients ( N = 36 ) were r and omized ( 1:1 ) to receive canagliflozin 300 mg or placebo for 12 weeks . Pharmacodynamic parameters were assessed at baseline and at weeks 1 and 12 . RESULTS Increased 24-h UGE was seen in the canagliflozin group compared with a reduction in the placebo group at both week 1 ( 91.8 vs. -2.4 g ) and week 12 ( 82.6 vs. -0.4 g ) . Canagliflozin also reduced both FPG and HbA1c . Reductions in body weight and blood pressure were observed at weeks 1 and 12 . Canagliflozin decreased plasma volume compared with an increase with placebo at week 1 ( -5.4 vs. 4.3 % ; p = 0.02 ) , but this was largely attenuated at week 12 ( 4.6 vs. 5.8 % ; p = 0.76 ) . A modest numerical increase in urine volume was observed with canagliflozin at week 1 that was attenuated at week 12 ; other measures of volume status ( i.e. blood urea nitrogen , serum creatinine and haematocrit ) remained modestly increased with canagliflozin at week 12 . CONCLUSION Canagliflozin provided sustained effects on UGE and FPG over 12 weeks and a transient reduction in plasma volume that was largely attenuated by week 12", "BACKGROUND Cardiovascular morbidity is a major burden in patients with type 2 diabetes . In the Steno-2 Study , we compared the effect of a targeted , intensified , multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria . METHODS The primary end point of this open , parallel trial was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , revascularization , and amputation . Eighty patients were r and omly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment , with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia , hypertension , dyslipidemia , and microalbuminuria , along with secondary prevention of cardiovascular disease with aspirin . RESULTS The mean age of the patients was 55.1 years , and the mean follow-up was 7.8 years . The decline in glycosylated hemoglobin values , systolic and diastolic blood pressure , serum cholesterol and triglyceride levels measured after an overnight fast , and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group . Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease ( hazard ratio , 0.47 ; 95 percent confidence interval , 0.24 to 0.73 ) , nephropathy ( hazard ratio , 0.39 ; 95 percent confidence interval , 0.17 to 0.87 ) , retinopathy ( hazard ratio , 0.42 ; 95 percent confidence interval , 0.21 to 0.86 ) , and autonomic neuropathy ( hazard ratio , 0.37 ; 95 percent confidence interval , 0.18 to 0.79 ) . CONCLUSIONS A target-driven , long-term , intensified intervention aim ed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent", "Aims /hypothesisThe cost-effectiveness of screening for diabetes is unknown but has been modelled previously . None of these models has taken account of uncertainty . We aim ed to describe these uncertainties in a model where the outcome was CHD risk . Subjects and methods Our model used population data from the Danish Inter99 study , and simulations were run in a theoretical population of 1,000,000 individuals . CHD risk was estimated using the UK Prospect i ve Diabetes Study ( UKPDS ) risk engine , and risk reduction from published r and omised clinical trials . Probabilistic sensitivity analysis was used to provide confidence intervals for modelled outputs . Uncertain parameter values were independently simulated from distributions derived from existing literature and deterministic sensitivity analysis performed using multiple model runs under different strategy choices and using extreme parameter estimates . Results In the least conservative model ( low costs and multiplicative risk reduction for combined treatments ) , the 95 % confidence interval of the incremental cost-effectiveness ratio varied from £ 23,300–82,000 . The major contributors to this uncertainty were treatment risk reduction model parameters : the risk reduction for hypertension treatment and UKPDS risk model intercept . Overall cost-effectiveness ratio was not sensitive to decisions about which groups to screen , nor the costs of screening or treatment . It was strongly affected by assumptions about how treatments combine to reduce risk . Conclusions /interpretationOur model suggests that there is considerable uncertainty about whether or not screening for diabetes would be cost-effective . The most important but uncertain parameter is the effect of treatment . In addition to directly influencing current policy decisions , health care modelling can identify important unknown or uncertain parameters that may be the target of future research", "BACKGROUND Among patients with coronary artery disease ( CAD ) , improvement of lifestyle-related risk factors ( LRFs ) reduces cardiovascular morbidity and mortality . However , modification of LRFs is highly challenging . OBJECTIVES This study sought to evaluate the impact of combining community-based lifestyle programs with regular hospital-based secondary prevention . METHODS The authors performed a r and omized controlled trial of nurse-coordinated referral of patients and their partners to 3 widely available community-based lifestyle programs , in 15 hospitals in the Netherl and s. Patients admitted for acute coronary syndrome and /or revascularization , with ≥1 LRF ( body mass index > 27 kg/m2 , self-reported physical inactivity , and /or smoking ) were included . All patients received guideline -based usual care . The intervention was based on 3 lifestyle programs for weight reduction , increasing physical activity , and smoking cessation . The primary outcome was the proportion of success at 12 months , defined as improvement in ≥1 qualifying LRF using weight ( ≥5 % reduction ) , 6-min-walking distance ( ≥10 % improvement ) , and urinary cotinine ( 200 ng/ml detection limit ) without deterioration in the other 2 . RESULTS The authors r and omized 824 patients . Complete data on the primary outcome were available in 711 patients . The proportion of successful patients in the intervention group was 37 % ( 133 of 360 ) compared with 26 % ( 91 of 351 ) in the control group ( p = 0.002 ; risk ratio : 1.43 ; 95 % confidence interval : 1.14 to 1.78 ) . In the intervention group , partner participation was associated with a significantly greater success rate ( 46 % vs. 34 % ; p = 0.03 ) . CONCLUSIONS Among patients with coronary artery disease , nurse-coordinated referral to a comprehensive set of community-based , widely available lifestyle interventions , with optional partner participation , leads to significant improvements in LRFs . ( RESPONSE-2 : R and omised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists 2 ; NTR3937 )", "Over the past decades , we have observed an increase of prevalence of diabetes in many countries along with significant differences in prevalence trends between countries worldwide ( 1 ) . In Europe and other Western countries , the prevalence rate reaches a plateau or has slowed down on the level of ∼8–10 % . In Asia , a continuous rise in prevalence has been monitored , similar to that in Africa , and an explosion of diabetes prevalence can be observed in the Arabic region . Surprisingly , in each of the countries , there is a significant number of people who do not develop diabetes during their lives despite living unhealthy lifestyles in similar environments — in Europe , an estimated 10 % of the population ( 2 ) . These people might be the secret answer to successful individual diabetes prevention , but we still do not underst and the detailed mechanisms of why some people develop diabetes— and why others do not . What we can do is observe individual lifestyle and environment as determinants for the development or prevention of diabetes and the respective risk factors including genetic susceptibility . The interplay between these determinants , influencing the probability of the individual staying healthy or how a person learns or chooses a healthy lifestyle , will define success in diabetes prevention ( 3 ) . Innovative actions are needed to slow down the progression of type 2 diabetes . The purpose of this article is to offer innovative policy and environmental strategic activities design ed to enable sustainable diabetes prevention with scalability on national level . # # # Why Do We Need Environmental and Policy Changes in Diabetes Prevention ? Diabetes prevention is a success story , but it generates new challenges . Throughout the past 15 years , a number of r and omized controlled trials have sought to test various interventions to prevent diabetes ( 4 ) . The results are overwhelmingly positive on an individual level , with a significant relative diabetes risk reduction attributed to lifestyle and pharmacological intervention ( 5" ]

[ "This study was design ed to evaluate the effects of enriching an essential amino acid ( EAA ) mixture with leucine on muscle protein metabolism in elderly and young individuals . Four ( 2 elderly and 2 young ) groups were studied before and after ingestion of 6.7 g of EAAs . EAAs were based on the composition of whey protein [ 26 % leucine ( 26 % Leu ) ] or were enriched in leucine [ 41 % leucine ( 41 % Leu ) ] . A primed , continuous infusion of L-[ring-2H5]phenylalanine was used together with vastus lateralis muscle biopsies and leg arteriovenous blood sample s for the determinations of fractional synthetic rate ( FSR ) and balance of muscle protein . FSR increased following amino acid ingestion in both the 26 % ( basal : 0.048 + /- 0.005%/h ; post-EAA : 0.063 + /- 0.007%/h ) and the 41 % ( basal : 0.036 + /- 0.004%/h ; post-EAA : 0.051 + /- 0.007%/h ) Leu young groups ( P FSR did not increase following ingestion of 26 % Leu EAA ( basal : 0.044 + /- 0.003%/h ; post-EAA : 0.049 + /- 0.006%/h ; P > 0.05 ) but did increase following ingestion of 41 % Leu EAA ( basal : 0.038 + /- 0.007%/h ; post-EAA : 0.056 + /- 0.008%/h ; P FSR responses , the mean response of muscle phenylalanine net balance , a reflection of muscle protein balance , was improved ( P EAA can reverse an attenuated response of muscle protein synthesis in elderly but does not result in further stimulation of muscle protein synthesis in young subjects", "Background Age-related muscle wasting has been strongly implicated with falls and fractures in the elderly , but it has also been associated with cognitive decline and dementia . Progressive resistance training ( PRT ) and adequate dietary protein are recognised as important contributors to the maintenance of muscle health and function in older adults . However , both factors also have the potential to improve brain function and prevent cognitive decline via several pathways , including the regulation of various growth and neurotrophic factors [ insulin-like growth factor-1 ( IGF-1 ) ] ; brain-derived growth factor ( BDNF ) ] and /or the modulation of systemic inflammation . The primary aim of this study is to investigate whether a modest increase in dietary protein achieved through the consumption of lean red meat three days per week , when combined with PRT , can enhance muscle mass , size and strength and cognitive function in community-dwelling older people . Methods / Design The study design is a 48-week r and omised controlled trial consisting of a 24-week intervention with a 24-week follow-up . Men and women ( n=152 ) aged 65 years and over residing in the community will be r and omly allocated to : 1 ) PRT and provided with 220 g ( raw weight ) of lean red meat to be cooked and divided into two 80 g servings on each of the three days that they complete their exercise session , or 2 ) control PRT in which participants will be provided with and advised to consume ≥1 serving ( ~1/2 cup ) of rice and /or pasta or 1 medium potato on each of the three training days . The primary outcome measures will be muscle mass , size and strength and cognitive function . Secondary outcomes will include changes in : muscle function , neural health ( corticospinal excitability and inhibition and voluntary activation ) , serum IGF-1 and BDNF , adipokines and inflammatory markers , fat mass and inter-/intra-muscular fat , blood pressure , lipids and health-related quality of life . All outcome measures will be assessed at baseline and 24 weeks , with the exception of cognitive function and the various neurobiological and inflammatory markers which will also be assessed at week 12 . Discussion The findings from this study will provide important new information on whether a modest increase in dietary protein achieved through the ingestion of lean red meat can enhance the effects of PRT on muscle mass , size and strength as well as cognitive function in community-dwelling older adults . If successful , the findings will form the basis for more precise exercise and nutrition guidelines for the management and prevention of age-related changes in muscle and neural health and cognitive function in the elderly . Trial registration Australian New Zeal and Clinical Trials Registry : ACTRN12613001153707 . Date registered 16th October , 2013", "Purpose Polyphenolic curcumin is known to have potent anti-inflammatory effects ; thus the present study investigated the hypothesis that curcumin ingestion would attenuate muscle damage after eccentric exercise . Methods Fourteen untrained young men ( 24 ± 1 years ) performed 50 maximal isokinetic ( 120 ° /s ) eccentric contractions of the elbow flexors of one arm on an isokinetic dynamometer and the same exercise with the other arm 4 weeks later . They took 150 mg of curcumin ( theracurmin ) or placebo ( starch ) orally before and 12 h after each eccentric exercise bout in a r and omised , crossover design . Maximal voluntary contraction ( MVC ) torque of the elbow flexors , range of motion of the elbow joint , upper-arm circumference , muscle soreness , serum creatine kinase ( CK ) activity , and plasma interleukin-6 ( IL-6 ) and tumor necrosis factor-α ( TNF-α ) concentration were measured before , immediately after , and 24 , 48 , 72 and 96 h after each eccentric exercise . Changes in these variables over time were compared between curcumin and placebo conditions by two-way repeated measures ANOVA . Results MVC torque decreased smaller and recovered faster ( e.g. , 4 days post-exercise : −31 ± 13 % vs. −15 ± 15 % ) , and peak serum CK activity was smaller ( peak : 7684 ± 8959 IU/L vs. 3398 ± 3562 IU/L ) for curcumin than placebo condition ( P changes in IL-6 and TNF-α were evident after exercise . Conclusion It is concluded that theracurmin ingestion attenuates some aspects of muscle damage such as MVC loss and CK activity increase", "We decided to test the hypothesis that possibly by combining a narcotic antagonist and amino-acid therapy consisting of an enkephalinase inhibitor ( D-phenylalanine ) and neurotransmitter precursors ( L-amino- acids ) to promote neuronal dopamine release might enhance compliance in methadone patients rapidly detoxified with the narcotic antagonist Trexan ( Dupont , Delaware ) . In this regard , Thanos et al. [ J. Neurochem . 78 ( 2001 ) 1094 ] and associates found increases in the dopamine D2 receptors ( DRD2 ) via adenoviral vector delivery of the DRD2 gene into the nucleus accumbens , significantly reduced both ethanol preference ( 43 % ) and alcohol intake ( 64 % ) of ethanol preferring rats , which recovered as the DRD2 , returned to baseline levels . This DRD2 overexpression similarly produced significant reductions in ethanol non-preferring rats , in both alcohol preference ( 16 % ) and alcohol intake ( 75 % ) . This work further suggests that high levels of DRD2 may be protective against alcohol abuse [ JAMA 263 ( 1990 ) 2055 ; Arch , Gen. Psychiatr . 48 ( 1991 ) 648 ] . The DRD2 A1 allele has also been shown to associate with heroin addicts in a number of studies . In addition , other dopaminergic receptor gene polymorphisms have also associated with opioid dependence . For example , Kotler et al. [ Mol . Phychiatr . 3 ( 1997 ) 251 ] showed that the 7 repeat allele of the DRD4 receptor is significantly overpresented in the opioid-dependent cohort and confers a relative risk of 2.46 . This has been confirmed by Li et al. [ Mol . Psychiatry 2 ( 1997 ) 413 ] for both the 5 and 7 repeat alleles in Han Chinese case control sample of heroin addicts . Similarly Duaux et al. [ Mol . Psychiatry 3 ( 1998 ) 333 ] in French Heroin addicts , found a significant association with homozygotes alleles of the DRD3-Bal 1 . A study from NIAAA , provided evidence which strongly suggests that DRD2 is a susceptibility gene for substance abusers across multiple population s ( 2003 ) . Moreover , there are a number of studies utilizing amino-acid and enkephalinase inhibition therapy showing reduction of alcohol , opiate , cocaine and sugar craving behavior in human trials ( see Table 1 ) . Over the last decade , a new rapid method to detoxify either methadone or heroin addicts utilizing Trexan sparked interest in many treatment centers throughout the United States , Canada , as well as many countries on a worldwide basis . In using the combination of Trexan and amino-acids , results were dramatic in terms of significantly enhancing compliance to continue taking Trexan . The average number of days of compliance calculated on 1000 patients , without amino-acid therapy , using this rapid detoxification method is only 37 days . In contrast , the 12 subjects tested , receiving both the Trexan and amino-acid therapy was relapse-free or reported taking the combination for an average of 262 days ( p amino-acid therapy and enkephalinase inhibition while blocking the delta-receptors with a pure narcotic antagonist may be quite promising as a novel method to induce rapid detox in chronic methadone patients . This may also have important ramifications in the treatment of both opiate and alcohol-dependent individuals , especially as a relapse prevention tool . It may also be interesting too further test this hypothesis with the sublingual combination of the partial opiate mu receptor agonist buprenorphrine", "BACKGROUND Nutritional supplementation may be used to treat muscle loss with aging ( sarcopenia ) . However , if physical activity does not increase , the elderly tend to compensate for the increased energy delivered by the supplements with reduced food intake , which results in a calorie substitution rather than supplementation . Thus , an effective supplement should stimulate muscle anabolism more efficiently than food or common protein supplements . We have shown that balanced amino acids stimulate muscle protein anabolism in the elderly , but it is unknown whether all amino acids are necessary to achieve this effect . OBJECTIVE We assessed whether nonessential amino acids are required in a nutritional supplement to stimulate muscle protein anabolism in the elderly . DESIGN We compared the response of muscle protein metabolism to either 18 g essential amino acids ( EAA group : n = 6 , age 69 + /- 2 y ; + /- SD ) or 40 g balanced amino acids ( 18 g essential amino acids + 22 g nonessential amino acids , BAA group ; n = 8 , age 71 + /- 2 y ) given orally in small boluses every 10 min for 3 h to healthy elderly volunteers . Muscle protein metabolism was measured in the basal state and during amino acid administration via L-[ring-(2)H(5)]phenylalanine infusion , femoral arterial and venous catheterization , and muscle biopsies . RESULTS Phenylalanine net balance ( in nmol x min(-1 ) . 100 mL leg volume(-1 ) ) increased from the basal state ( P muscle protein synthesis and no change in breakdown . CONCLUSION Essential amino acids are primarily responsible for the amino acid-induced stimulation of muscle protein anabolism in the elderly", "Background Delayed onset muscle soreness ( DOMS ) due to eccentric muscle activity is associated with inflammatory responses and production of reactive oxygen species ( ROS ) that sustain both inflammation and oxidative stress . Curcumin , a powerful promoter of anti-oxidant response , is one of the best-investigated natural products , and is now commercially available as a lecithin delivery system ( Meriva ® , Indena SpA , Milan ) with improved bio-availability . The aim of this study was to test whether curcumin could attenuate damage from oxidative stress and inflammation related to acute muscle injury induced by eccentric continuous exercise Methods This was a r and omised , placebo-controlled , single-blind pilot trial . Twenty male healthy , moderately active volunteers were r and omised to curcumin given as the Phytosome ® delivery system 1 g twice daily ( 200 mg curcumin b.i.d . ) or matching placebo . Supplementation was initiated 48 hours prior to a downhill running test and was continued for 24 hours after the test ( 4 days in total ) . Muscle damage was quantified by magnetic resonance imaging , laboratory tests and histological analyses on muscle sample s obtained 48 hours after the test . Patient-reported pain intensity was also recorded . Results Subjects in the curcumin group reported less pain in the lower limb as compared with subjects in the placebo group , although significant differences were observed only for the right and left anterior thighs . Significantly fewer subjects in the curcumin group had MRI evidence of muscle injury in the posterior or medial compartment of both thighs . Increases in markers of muscle damage and inflammation tended to be lower in the curcumin group , but significant differences were only observed for interleukin-8 at 2 h after exercise . No differences in markers of oxidative stress and muscle histology were observed Conclusions Curcumin has the potential for preventing DOMS , as suggested by its effects on pain intensity and muscle injury . Larger studies are needed to confirm these results and further clarify the mechanism of action of curcumin ", "CONTEXT A clear underst and ing of what patients , families , and health care practitioners view as important at the end of life is integral to the success of improving care of dying patients . Empirical evidence defining such factors , however , is lacking . OBJECTIVE To determine the factors considered important at the end of life by patients , their families , physicians , and other care providers . DESIGN AND SETTING Cross-sectional , stratified r and om national survey conducted in March-August 1999 . PARTICIPANTS Seriously ill patients ( n = 340 ) , recently bereaved family ( n = 332 ) , physicians ( n = 361 ) , and other care providers ( nurses , social workers , chaplains , and hospice volunteers ; n = 429 ) . MAIN OUTCOME MEASURES Importance of 44 attributes of quality at the end of life ( 5-point scale ) and rankings of 9 major attributes , compared in the 4 groups . RESULTS Twenty-six items consistently were rated as being important ( > 70 % responding that item is important ) across all 4 groups , including pain and symptom management , preparation for death , achieving a sense of completion , decisions about treatment preferences , and being treated as a \" whole person . \" Eight items received strong importance ratings from patients but less from physicians ( P mentally aware , having funeral arrangements planned , not being a burden , helping others , and coming to peace with God . Ten items had broad variation within as well as among the 4 groups , including decisions about life-sustaining treatments , dying at home , and talking about the meaning of death . Participants ranked freedom from pain most important and dying at home least important among 9 major attributes . CONCLUSIONS Although pain and symptom management , communication with one 's physician , preparation for death , and the opportunity to achieve a sense of completion are important to most , other factors important to quality at the end of life differ by role and by individual . Efforts to evaluate and improve patients ' and families ' experiences at the end of life must account for diverse perceptions of quality . JAMA . 2000;284:2476 - 2482", "Limited data have suggested that the consumption of fluid milk after resistance training ( RT ) may promote skeletal muscle hypertrophy . The aim of this study was to assess whether a milk-based nutritional supplement could enhance the effects of RT on muscle mass , size , strength , and function in middle-aged and older men . This was an 18-mo factorial design ( r and omized control trial ) in which 180 healthy men aged 50 - 79 yr were allocated to the following groups : 1 ) exercise + fortified milk , 2 ) exercise , 3 ) fortified milk , or 4 ) control . Exercise consisted of progressive RT with weight-bearing impact exercise . Men assigned to the fortified milk consumed 400 ml/day of low-fat milk , providing an additional 836 kJ , 1000 mg calcium , 800 IU vitamin D(3 ) , and 13.2 g protein per day . Total body lean mass ( LM ) and fat mass ( FM ) ( dual-energy X-ray absorptiometry ) , midfemur muscle cross-sectional area ( CSA ) ( quantitative computed tomography ) , muscle strength , and physical function were assessed . After 18 mo , there was no significant exercise by fortified milk interaction for total body LM , muscle CSA , or any functional measure . However , main effect analyses revealed that exercise significantly improved muscle strength ( approximately 20 - 52 % , P LM ( 0.6 kg , P FM ( -1.1 kg , P muscle CSA ( 1.8 % , P gait speed ( 11 % , P muscle size , strength , or function . In conclusion , the daily consumption of low-fat fortified milk does not enhance the effects of RT on skeletal muscle size , strength , or function in healthy middle-aged and older men with adequate energy and nutrient intakes", "Introduction Oral curcumin decreases inflammatory cytokines and increases muscle regeneration in mice . Purpose To determine effects of curcumin on muscle damage , inflammation and delayed onset muscle soreness ( DOMS ) in humans . MethodS eventeen men completed a double-blind r and omized-controlled crossover trial to estimate the effects of oral curcumin supplementation ( 2.5 g twice daily ) versus placebo on single-leg jump performance and DOMS following unaccustomed heavy eccentric exercise . Curcumin or placebo was taken 2 d before to 3 d after eccentric single-leg press exercise , separated by 14-d washout . Measurements were made at baseline , and 0 , 24 and 48-h post-exercise comprising : ( a ) limb pain ( 1–10 cm visual analogue scale ; VAS ) , ( b ) muscle swelling , ( c ) single-leg jump height , and ( d ) serum markers of muscle damage and inflammation . St and ardized magnitude-based inference was used to define outcomes . Results At 24 and 48-h post-exercise , curcumin caused moderate-large reductions in pain during single-leg squat ( VAS scale −1.4 to −1.7 ; 90 % CL : ±1.0 ) , gluteal stretch ( −1.0 to −1.9 ; ±0.9 ) , squat jump ( −1.5 to −1.1 ; ± 1.2 ) and small reductions in creatine kinase activity ( −22–29 % ; ±21–22 % ) . Associated with the pain reduction was a small increase in single-leg jump performance ( 15 % ; 90 % CL ± 12 % ) . Curcumin increased interleukin-6 concentrations at 0-h ( 31 % ; ±29 % ) and 48-h ( 32 % ; ±29 % ) relative to baseline , but decreased IL-6 at 24-h relative to post-exercise ( −20 % ; ±18 % ) . Conclusions Oral curcumin likely reduces pain associated with DOMS with some evidence for enhanced recovery of muscle performance . Further study is required on mechanisms and translational effects on sport or vocational performance", "In the World Health Organization ’s International Classification of Functioning , Disability and Health , participation restriction — the social and personal consequences of health conditions and their environment — is an important component of the concept of disability . The cross-sectional associations between perceived participation restriction and health , demographic and socio-economic factors were examined in 7,878 community-dwelling adults aged 50 years and over in North Staffordshire , UK who responded to a postal survey . All health conditions , impairments , activity limitations , demographic and socio-economic factors were associated with participation restriction , after adjusting for age and gender in a logistic regression analysis . Health and disability factors most strongly and independently associated with participation restriction in a multivariate analysis were the number of peripheral joint pains , the number of health conditions , cognitive impairment , anxiety , depression , and activity limitation . Perceived adequacy of income , employment status and occupational class were also significantly associated with participation restriction after adjusting for health and disability factors . In conclusion , perceived participation restriction is associated with a range of health and socio-economic factors . Although further prospect i ve research is needed to identify the direction of causal association , these factors represent potential targets for intervention to prevent or reduce participation restriction in older adults in the community", "Age-related loss of skeletal muscle mass and strength are risk factors for sarcopenia , osteoporosis , falls , fractures , frailty , and mortality . Dietary magnesium ( Mg ) could play a role in prevention of age-related loss of skeletal muscle mass , power , and strength directly through physiological mechanisms or indirectly through an impact on chronic low- grade inflammation , itself a risk factor for loss of skeletal muscle mass and strength . In a cross-sectional study of 2570 women aged 18 to 79 years , we examined associations between intakes of Mg , estimated using a food-frequency question naire ( FFQ ) , dual-energy X-ray absorptiometry (DXA)-derived measures of muscle mass ( fat-free mass as a percentage of body weight [ FFM% ] , fat-free mass index [ FFMI , kg/m(2 ) ] ) , leg explosive power ( LEP ) , and grip strength ( n = 949 only ) . We also examined associations between circulating hs-CRP ( C-reactive protein ) and muscle mass and LEP , and explored the potential attenuation of these relationships by Mg . We compared our findings with those of age and protein intake . Endpoints were calculated by quintile of Mg and adjusted for relevant confounders . Significant positive associations were found between a higher Mg and indices of skeletal muscle mass and LEP , and also with hs-CRP , after adjustment for covariates . Contrasting extreme quintiles of Mg intake showed differences of 2.6 % for FFM% ( p trend for LEP . We also found that higher hs-CRP was negatively associated with skeletal muscle mass and , in statistical modeling , that a higher dietary Mg attenuated this negative relationship by 6.5 % , with greater attenuation in women older than 50 years . No association was found between Mg and grip strength . Our results suggest that dietary magnesium may aid conservation of age-related loss of skeletal muscle mass and power in women of all ages", "Enkephalins are a biochemical pathway for endogenous analgesia . A number of compounds inhibit degradation of enkephalins within the body . One of these compounds , D-phenylalanine ( DPA ) , has been shown to increase the pain threshold in animals . It is hypothesized that this naloxone reversible analgesia is induced by DPA blockage of enkephalin degradation by the enzyme carboxypeptidase A. Preliminary studies of chronic pain patients have shown a response rate to DPA from 32 % to 75 % . This study was a double-blind crossover evaluation of a r and omized parallel design to determine the efficacy of DPA in 30 subjects with chronic pain from varied etiology which was unrelieved by multiple therapeutic interventions . Each patient received a stabilized therapeutic regimen during this study consisting of four weeks of either DPA 250 mg or lactose ( placebo ) orally four times a day . After four weeks the DPA and placebo groups were crossed over for an additional four weeks of treatment . Pain was quantified using a visual analog pain scale and a cold pressor test . Data from the pain question naires revealed more pain relief on DPA reported by 25 % of the patients , more pain relief on placebo reported by 22 % of the patients , and no difference in pain relief reported by 53 % of the patients . Lowest pain level of the visual analog scale was reported by 47 % of the patients on DPA and 53 % on placebo . There appears to be no significant analgesic effect from D-phenylalanine in chronic pain patients when compared to placebo", "UNLABELLED Ginger has been shown to exert anti-inflammatory effects in rodents , but its effect on human muscle pain is uncertain . Heat treatment of ginger has been suggested to enhance its hypoalgesic effects . The purpose of this study was to examine the effects of 11 days of raw ( study 1 ) and heat-treated ( study 2 ) ginger supplementation on muscle pain . Study 1 and 2 were identical double-blind , placebo controlled , r and omized experiments with 34 and 40 volunteers , respectively . Participants consumed 2 grams of either raw ( study 1 ) or heated ( study 2 ) ginger or placebo for 11 consecutive days . Participants performed 18 eccentric actions of the elbow flexors to induce pain and inflammation . Pain intensity , perceived effort , plasma prostagl and in E(2 ) , arm volume , range-of-motion and isometric strength were assessed prior to and for 3 days after exercise . Results Raw ( 25 % , -.78 SD , P = .041 ) and heat-treated ( 23 % , -.57 SD , P = .049 ) ginger result ed in similar pain reductions 24 hours after eccentric exercise compared to placebo . Smaller effects were noted between both types of ginger and placebo on other measures . Daily supplementation with ginger reduced muscle pain caused by eccentric exercise , and this effect was not enhanced by heat treating the ginger . PERSPECTIVE This study demonstrates that daily consumption of raw and heat-treated ginger result ed in moderate-to-large reductions in muscle pain following exercise-induced muscle injury . Our findings agree with those showing hypoalgesic effects of ginger in osteoarthritis patients and further demonstrate ginger 's effectiveness as a pain reliever", "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" ]

[ "Reports in the surgical literature are conflicting as to whether appendectomy \" in passing \" during laparotomy for trauma or for some other disease state does or does not significantly increase patient morbidity or mortality . A chart survey of all appendectomies ( 342 for acute appendicitis and 146 as incidental procedures ) performed on the trauma service of Grady Memorial Hospital over a 40 month period appeared to indicate that the wound infection rate ( 6.8 percent ) was the same as that for acute simple or suppurative appendicitis ( 6.7 percent ) , whereas the intraabdominal sepsis rate ( 17.5 percent ) paralleled that for more advanced gangrenous or perforative appendicitis ( 18.6 percent ) . Since the validity of a retrospective review is always open to question , a prospect i ve , r and omized trial was carried out only on patients with a negative abdominal exploration for trauma over a 22 month interval at the same trauma service . An odd second from the last digit hospital number dictated appendectomy , provided the appendix was readily accessible ; an even digit in the same locus dictated retention of the appendix . In no patient did intraperitoneal sepsis develop , regardless of the procedure chosen . Wound infection rates were 1.8 percent for appendectomy ( 1 of 56 ) , if local anatomic considerations precluded an easy appendectomy ( 0 of 45 ) , and 3.6 percent for the control subjects without appendectomy ( 3 of 83 ) . There were no deaths . These data cast considerable doubt on the reliability of retrospective review s and support the generally accepted dictum that incidental appendectomy , especially in the trauma patient , can be a relatively innocuous procedure", "We undertook a prospect i ve study of the effect of incidental appendectomy on the safety of cholecystectomy in patients under the age of 50 years . One hundred twenty patients were r and omized to have either cholecystectomy alone or cholecystectomy and appendectomy . All patients received preoperative antibiotic cover . Both groups were well matched for age , sex , obesity , and length of hospital stay . Twelve patients were withdrawn from the trial . Wound infections occurred in three of the 56 patients in the cholecystectomy group ( 5.3 % ) and in two of the 52 patients in the cholecystectomy plus appendectomy group ( 3.8 % ) . Incidental appendectomy is a safe addition to elective cholecystectomy", "Abstract Background : The aggressive surgical approach to patients suspected of having acute appendicitis for fear of perforation , and the inaccuracy of available diagnostic methods lead to an unacceptably high negative appendicectomy rate , especially in young women , in whom gynecological disorders frequently mimic appendicitis . Our objectives were to determine the value of diagnostic laparoscopy in women of child-bearing age to reduce the number of negative laparotomies and establish the correct diagnosis to allow prompt and appropriate treatment . Methods : 161 consecutive adult female patients under 50 years of age with a clinical diagnosis of acute appendicitis underwent diagnostic laparoscopy prior to the planned appendicectomy . If an inflamed appendix was found , appendicectomy was usually done through a muscle-splitting McBurney incision . Other diagnoses were treated accordingly . A normal appendix was not removed . Results were compared to a group of 42 similar patients in whom the laparoscopy was omitted for various reasons , to 23 postmenopausal women , and to all 137 male adults , directly operated by the McBurney approach . Results : After laparoscopy , 55 % of the patients required appendicectomy for appendicitis while in 23 % a gynecological diagnosis was made in spite of previous examination by a gynecologist . Fourteen percent had a negative laparoscopy . There were no false-negative results . The negative appendicectomy rate after laparoscopy was 5 % due to two false positives and eight laparoscopy failures . In the group of fertile females who escaped laparoscopy the negative appendicectomy rate was 38 % . The respective rates for postmenopausal women and men were 4 % and 8 % . Conclusions : All women of child-bearing age suspected of having acute appendicitis should undergo diagnostic laparoscopy prior to the planned appendicectomy , regardless of the certainty of the preoperative diagnosis . This is currently the only way to reduce the negative appendicectomy rate and establish a correct diagnosis allowing prompt and appropriate treatment . In male patients and postmenopausal women one may proceed directly to emergency appendicectomy" ]

[ "Study design : Follow-up study of seven individuals with spinal cord injury ( SCI ) who completed a 9-month r and omized control trial ( RCT ) of exercise training . Objective : In a 9-month RCT conducted in our lab , individuals with SCI who participated in a twice-weekly supervised exercise training reported greater perceived quality of life ( PQOL ) , and less stress and pain than a nonexercising control cohort . The present follow-up study examined the voluntary continuation of exercise training after the study ended and the persistence of the accrued psychosocial benefits . Setting : Centre for Health Promotion and Rehabilitation , McMaster University , Hamilton , Ontario , Canada . Methods : Five men and two women ( age 42.3±3.6 years ) with SCI ( C5–T12 ; ASIA A – D 12.7±8.2 years postinjury ) were invited to continue supervised exercise training twice weekly at the completion of the 9-month RCT . Exercise adherence , PQOL , stress and bodily pain were measured at a 3-month follow-up and were compared to values obtained at baseline , and at 3 , 6 and 9 months during the intervention . Results : There was a significant decrease in adherence at the 3-month follow-up compared to the overall 9-month adherence rate ( 42.7 versus 80.6 % , respectively ; P decrease in PQOL ( P for increased pain ( P=0.07 ) and stress ( P=0.12 ) , at follow-up compared to the end of the 9-month trial . Finally , there was a significant negative correlation between pain at the conclusion of the RCT and exercise adherence over the 3-month follow-up period ( r=−0.91 ; P exercise adherence to the maintenance of exercise-related increases in psychological well-being among individuals with SCI", "The purpose of this study is to assess satisfaction with life domains in people with spinal cord injuries ( SCI ) and investigate whether participation in sports and physical recreation is associated with life satisfaction in SCI . 1,748 r and omly selected participants with SCI who fulfilled the criteria : SCI at level C5 or below , wheelchair dependent ; aged 18 - 50 at the time of injury ; at least 1 year post-injury , were approached to take part in this study . Completed replies were received from 985 individuals with SCI ( 198 women , 798 men ) . The measures used included the Sports Participation Question naire , the Life Satisfaction Question naire and the Hospital Anxiety and Depression Scale . The numbers of hours participating in sports decreased significantly after injury . There was a greater decrease in numbers participating in team sports in comparison to the decrease seen in numbers participating in individual sports . The highest level of satisfaction existed within social domains such as : family life and contacts with friends . The lowest level of satisfaction was found in regard to the participant 's sexual life and vocational situation . Higher satisfaction with life in general was demonstrated in respondents with SCI involved in sports or physical recreation compared to those not participating in physical activities", "Study design : R and omized controlled trial of exercise training in persons with spinal cord injury . Objective : The purpose of this study was to examine the effects of 9 months of twice-weekly exercise training on strength , arm ergometry performance , and indices of psychological well-being and quality of life . Setting : Centre for Health Promotion and Rehabilitation , McMaster University , Hamilton , Ontario , Canada . Methods : Thirty-four men and women ( aged 19–65 years ) with traumatic spinal cord injury ( C4–L1 ; ASIA A – D ) of 1–24 years duration volunteered to participate , and were r and omized into exercise ( EX ; n=21 ) and control ( CON ; n=13 ) groups . Twenty-three subjects ( 11 EX ; 12 CON ) successfully completed the 9-month study . Subjects were assessed for one repetition maximum ( 1RM ) strength , arm ergometry performance , and several indices of quality of life and psychological well-being at baseline , 3 , 6 , and 9 months . Results : At baseline , there were no significant differences between groups in age , submaximal arm ergometry performance , muscle strength , or psychological well-being . Following training , the EX group had significant increases in submaximal arm ergometry power output ( 81 % ; P significant increases in upper body muscle strength ( 19–34 % ; P less pain , stress and depression after training , and scored higher than CON in indices of satisfaction with physical function , level of perceived health and overall quality of life ( P ) . Exercise adherence ( per cent of prescribed sessions attended ) in those subjects who completed the 9 months of training was 82.5 % . Conclusions : These results demonstrate that long-term twice-weekly exercise training in this population is feasible , and results in significant gains in both physical and psychological well-being ", "The purpose of the present investigation was to study the effects of an arm ergometer training programme on several physiological variables of recreational wheelchair subjects . Ten paraplegics ( 5 experimental , 5 control ) were tested prior to and immediately after a 2 month exercise regimen at 80 % of peak heart rate ( 30 min per day , 5 days per week , for 8 consecutive weeks at 50 rev/min ) . The results demonstrated significant increases ( P VO2max ( 1 min-1 & ml kg-1 min-1 ) and workload but only mild improvements in maximal heart rate and post exercise blood lactates . Body fat , vital capacity and forced expiratory volume did not change with training . Triceps lateralis fibre distribution and fast twitch ( FT ) fibre area were unaffected by the endurance training programme . However , slow twitch ( ST ) fibre area increased ( P paraplegic subjects following an arm ergometer endurance training programme react similarly to changes previously observed in non-h and icapped subjects . The values when compared with normals are low as a result of the relative inactivity of the subjects due to the lack of available exercise programmes for wheelchair people", "Although considered the gold-st and ard research design , r and omized controlled trials ( RCT ) create a series of method ological , ethical , and practical challenges when applied to exercise training studies of people with spinal cord injury ( SCI ) . These challenges are discussed , and some pragmatic alternatives are suggested to advance SCI research while maintaining scientific integrity", "Objectives : To assess pain relieving effects of an intensive exercise programme on a seated double-poling ergometer in individuals with spinal cord injury ( SCI ) . Setting : Stockholm , Sweden . Methods : A total of 13 wheelchair-dependent individuals with a thoracic or lumbar SCI were recruited to a 10-week training period ( three times weekly ) assessing the effects of regular training on upper-body strength , aerobic and mechanical power , and crossover effects on functional performance , as well as cardiovascular risk factors . Eight of the participants reported pain and were included in this exploratory pain protocol and assessed using the International SCI Basic Pain Data set , the Wheelchair Users ’ Shoulder Pain Index and International SCI Quality of Life Basic Data set . Results : For those with neuropathic pain , median pain intensity ratings decreased from 5 on a 0–10 numerical rating scale at base-line to 3 at the end of study , and four of seven participants reported an improvement on the Patient Global Impression of Change scale . For those with musculoskeletal pain ( n=5 ) , median pain intensity ratings improved from 4 at baseline to 0 at the end of study . All but one rated no musculoskeletal pain at all at the end of study and number of days with pain per week decreased from 5.5 to 0.7 . None of the participants developed pain , because of overuse during the training period and few reported unwanted side effects . Conclusion : Considering its promising effects and safety , an intensive exercise programme can be tried for treating musculoskeletal pain and also neuropathic pain following SCI", "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 ." ]

[ " We analysed self-reported cold data for 95 pairs of identical twins who took part in a double-blind trial of vitamin C tablets . One member of each twin pair took vitamin C and the other took a well matched placebo each day for 100 days . Vitamin C had no significant effect except for shortening the average duration of cold episodes by 19 %", "Three hundred eleven employees of the National Institutes of Health volunteered to take 1 gm of ascorbic acid or lactose placebo in capsules three times a day for nine months . At the onset of a cold , the volunteers were given an additional 3 gm daily of either a placebo or ascorbic acid . One hundred ninety volunteers completed the study . Dropouts were defined as those who missed at least one month of drug ingestion . They represented 44 % of the placebo group and 34 % of those taking ascorbic acid . Analysis of these data showed that ascorbic acid had at best only a minor influence on the duration and severity of colds , and that the effects demonstrated might be explained equally well by a break in the double blind", "During 7 weeks in the spring of 1973 a double-blind pilot study on 172 children in the age group 8 - 9 was carried out to test the possible effect of 1000 mg vitamin C daily as a prophylactic agent against common colds . During the autumn of 1973 , a main study was carried out on 642 children of the same age . The investigations had the same pattern and lasted for 3 months . Both studies have been processed on the same principles . The results were somewhat divergent but , like previously published studies on children , seemed to indicate that the duration and severity of the cold were reduced while , on the other h and , the incidence remained unaltered or indeed increased . The total number of days of upper respiratory tract infection was smaller for the vitamin C group only in the pilot study ( not in the main study ) . No proven biochemical effects were obtained . Preventive treatment of healthy children with vitamin C in large doses this had no definitely proved effect against colds", "METHOD A large number of women living in two towns in South Wales , and their husb and s , were asked to cooperate in the trial . These women had been identified several years previously in a study of child growth and nutrition and had already cooperated in a prophylactic trial of vitamin C ( Elwood et al. , 1975 ) . The subjects were visited in September and October and those who agreed were given ten effervescent tablets of either vitamin C ( 1 G ) or an inert ; placebo . Allocation of households to vitamin C or placebo was r and om , but each husb and received the same tablets as his wife . This was done to avoid confusion if tablets were shared . The smoking habit of each subject was recorded . Instructions were given that , when symptoms suggestive of a cold commenced , the tablets were to be started , three tablets per day until the 10 tablets had been taken . Symptoms were to be recorded each day for the duration of the cold . Sufficient detail was requested to enable colds to be classed as ‘ simple ’ , that is nasal symptoms with or without general symptoms such as fever or malaise but without any symptom referable to the chest such as cough . ‘ Chest ’ colds were recorded as any symptom-complex which included cough , wheezing , or other chest symptoms . A stamped addressed envelope was given to each subject for the return of the record card . An arbitrary date was chosen approximately six months after the trial commenced , and any subject who had not returned a", "A concentration of 15 pig/ml was arbitrarily taken as a level read.ly obtainable in h blood wiLh bo.h antibiotics . Th19 strains resistant to penicillin and tetracycline only were resis : ant to tetracycline in concentrations above 20 Ag/lml . This resis ance pattern occurs quite frequently in strains of S. aph . aureus isolated both from hospital patients and from the general comnnunity . It would appear therefore that any microbiological advantage which minocycline may exert over other tetracyclines is due to its sup rior activity against strains of Staph . aureus which are resistant to tetracycline . ' -I am , etc . , ARTHUR A. B. MITCHELL Bacteriology Department , Law Hospital , Carluke ,", "Three different dosages of vitamin C , dependent on body weight , were administered to 44 school-aged monozygotic twins for five months using a double-blind , co-twin control study design . The mothers recorded daily observations of cold symptoms , and multiple biochemical , anthropometric , and psychological measurements were made at the beginning and end of the study . Paired comparisons showed no significant overall treatment effect on cold symptoms , but the response was not uniform in all sub-groups . Treated girls in the youngest two groups had significantly shorter and less severe illness episodes , and an effect on severity was also observed in the youngest group of boys . The seven treated twins in the latter group also grew an average of 1.3 cm more than their untreated co-twins during the five-minth period of the study", "A r and omized controlled trial of the effect of 1 g ascorbic acid per day in the prevention of the common cold was conducted on 688 adult women . There is evidence of a small reduction by vitamin C in the mean number of chest colds , but no evidence of any effect on simple colds . The existence of a subgroup of vulnerable women in the community who benefit from vitamin C was considered but further examination of the data gives no support to this conclusion", "A prospect i ve , r and omized , double-blind study was carried out to determine whether vitamin C prophylaxis , 2.0 g/day , vs placebo prophylaxis would reduce the incidence or morbidity of the common cold and other respiratory illnesses in 674 marine recruits during an eight-week period . Whole-blood ascorbic acid levels measured six weeks after initiation of the study were significantly higher in the vitamin C group . There was no difference between the two groups in the incidence or duration of colds . The vitamin C group rated their colds as being less severe , but this was not reflected in different symptom complexes or in fewer sick-call visits or training days lost . This study and the literature do not support the prophylactic use of vitamin C to prevent the common cold", "OBJECTIVE To determine the effect of large doses of vitamin C in the treatment of the common cold . STUDY DESIGN Double-blind , r and omised clinical trial with four intervention arms : vitamin C at daily doses of 0.03 g ( \" placebo \" ) , 1 g , 3 g , or 3 g with additives ( \" Bio-C \" ) taken at onset of a cold and for the following two days . PARTICIPANTS AND SETTING 400 healthy volunteers were recruited from staff and students of the Australian National University , Canberra , ACT , between May 1998 and November 1999 . The trial continued for 18 months . INTERVENTIONS Participants were instructed to commence medication when they had experienced early symptoms of a cold for four hours , and to record daily their symptoms , severity , doctor visits and use of other medications . MAIN OUTCOME MEASURES Duration of symptoms and cold episodes ; cumulative symptom severity scores after 7 , 14 and 28 days ; doctor visits ; and whether participants guessed which medication they were taking . RESULTS 149 participants returned records for 184 cold episodes . No significant differences were observed in any measure of cold duration or severity between the four medication groups . Although differences were not significant , the placebo group had the shortest duration of nasal , systemic and overall symptoms , and the lowest mean severity score at 14 days , and the second lowest at 7 and 28 days . CONCLUSIONS Doses of vitamin C in excess of 1 g daily taken shortly after onset of a cold did not reduce the duration or severity of cold symptoms in healthy adult volunteers when compared with a vitamin C dose less than the minimum recommended daily intake", "A controlled study was made of the effects of natural orange juice , synthetic orange juice , and placebo in the prevention of the common cold ; both natural and synthetic orange juices contained 80 mg of ascorbic acid daily . Three-hundred sixty-two healthy normal young adult volunteers , ages 17 to 25 years , were studied for 72 days with 97 % of participants completing the trial . There was a 14 to 21 % reduction in total symptoms due to the common cold in the supplemented groups that was statistically significant ( P less than 0.05 ) . Ascorbic acid supplementation also increased the number of \" episode-free \" subjects . However , the clinical usefulness of the results does not support prophylactic ascorbic acid supplements in the well-nourished adult . The results in this study with both natural and synthetic orange juice of physiological content of ascorbic acid , are similar to those obtained using a \" megadose \" of ascorbic acid", "This study determined whether daily supplementation with 600 mg vitamin C would reduce the incidence of symptoms of upper-respiratory-tract ( URT ) infections after participation in a competitive ultramarathon race ( > 42 km ) . Ultramarathon runners with age-matched controls were r and omly divided into placebo and experimental ( vitamin C-supplemented ) groups . Symptoms of URT infections were monitored for 14 d after the race . Sixty-eight percent of the runners in the placebo group reported the development of symptoms of URT infection after the race ; this was significantly more ( P duration and severity of symptoms of URT infections reported in the vitamin C-supplemented nonrunning control group was also significantly less than in the nonrunning control group receiving the placebo ( P vitamin C supplementation may enhance resistance to the postrace URT infections that occur commonly in competitive ultramarathon runners and may reduce the severity of such infections in those who are sedentary", "In a survey of double-bind design , 3 groups of approximately 70 student volunteers took 1 g L-ascorbic acid , 1 g D-isoascorbic acid , or placebo tablets every day for 15 weeks and the incidence and duration of colds were recorded . The group taking D-isoascrobic acid suffered 34 % fewer colds than the other two groups ; the results were also analyzed in relation to the sex and smoking habits of the volunteers . The rationale for investigating D-isoascorbic acid , an isomer of L-ascorbic acid which has limited antiscorbutic activity , is discussed", "Ascorbic acid is widely used as a prophylactic and therapeutic agent against the common cold , and is in fact often recommended for this purpose by medical practitioners . It may be administered as a large dose as soon as possible after the first symptoms are felt , and this dosage is then continued for a few days in order to \" abort \" the cold . Though many people use this treatment on themselves and believe it is effective , it is impossible to assess its efficacy . Untreated subjects may experience symptoms such as sneezing or a mild sore throat , which then disappear without going on to a full cold , and patients ' assessment s of their colds are much influenced by any treatment owing to the placebo effect ( Diehl et a/. , 1938 ) . In these studies we attempted to show by in-vitro experiments that exposure of cells to ascorbic acid increased their resistance to infection with viruses . Though there was no activity in vitro , we also attempted to demonstrate a protective effect in ftnmy»1 « or man , since it was thought that host resistance might be enhanced indirectly", "Self-reported cold data have been analyzed for 95 pairs of identical twins aged 14 - 64 who took part in a double-blind trial of vitamin C tablets . One member of each twin pair took a tablet containing 1 g vitamin C and the other took a well-matched placebo each day for 100 days . In the total sample there was no effect of vitamin C in preventing colds . However , subdivision of the data showed a significant preventive effect of the placebo in the 51 pairs living together and an equal and opposite preventive effect of the vitamin C in the 44 pairs living apart . The placebo effect in the pairs living together may be attributed to the large proportion who wrongly perceived which treatment they were taking . The reduction of colds in the vitamin C group of the pairs living apart was about 20 % . There were significant correlations between cold symptoms reported and the personality trait of neuroticism . No side effects of substantive changes in serum biochemistry could be attributed to the vitamin C dose", "Abstract A double-blind study to evaluate vitamin C supplements for respiratory-Infection prophylaxis was conducted among 641 children at a Navajo boarding school over a 14-week period . Supplements", "The combination of a regular daily supplement of vitamin C with extra dosage at the time of illness has been shown to reduce the disability due to common colds and other winter illness , but we have seen little effect on frequency of infections , sense of ( well-being ) , or levels of serum cholesterol . The variable results that have been obtained from some other trials of vitamin C may be due in part to variation in the initial nutritional state of the subjects , with the greatest effects to be expected where there is most room for improvement . Because of the great variation in individual susceptibility to infection large numbers of subjects are required in these trials and they must be strictly double-blind . Although we have seen no clear evidence of harmful side-effects , occasional sensitivity to large doses of vitamin C can not be ruled out , and the withdrawal depression of blood levels could conceivably interfere with a patient 's ability to h and le stress", "A r and omised double-blind trial involving vitamin C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections ( bronchitis and bronchopneumonia ) . Patients were assessed clinical ly and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg vitamin C per day , or placebo . This relatively modest oral dose led to a significant increase in plasma and white cell vitamin C concentration even in the presence of acute respiratory infection . Using a clinical scoring system based on major symptoms of the respiratory condition , patients supplemented with the vitamin fared significantly better than those on placebo . This was particularly the case for those commencing the trial most severely ill , many of whom had very low plasma and white cell vitamin C concentrations on admission . Various mechanisms by which vitamin C could assist this type of patient are discussed", "Beginning at about the age of seven and following a tonsillectomy I began to be plagued with otitis media of which I suffered from 50 to 60 bouts over the next 20 years . These recurrent infections were treated by a series of different methods including Cubeb cigarette smoke blown into the ear by my mother , the local application of heat , sulfadiazine in nasal sprays and the earlier and later forms of injected penicillin which was useful as soon as I suffered from a sore throat if taken at the first signs of infection , but only for the secondary bacterial component of my double infection which began with a vims which appeared to pass the sentence which was executed by the bacteria . I stumbled upon the employment of ascorbic acid because of the advertisements for the bioflavonoids and vitamin C as beneficial in the prevention - and treatment of the common cold . It was apparent that the mixture diminished the symptoms of the common cold for me and for my wife , but not enough for us to continue with its employment , Would larger doses perhaps be more effective ? The doses were increased as each increment proved itself as giving better results until I reached a maximum and satisfactory effect . I did not permit myself to be dissuaded by the gloomy conclusions of others , whose work I continued to recognize had shown only that vitamin C had not been helpful against colds at the dosage used in their studies , and not the unmeasured generality that this drug had been proven utterly useless against colds . I was then able to suppress colds , at will , in five subjects . There is no doubt that we really suffered from colds during these suppressed versions of the disease , because we continued to be aware — but just aware — of whatever symptoms had been characteristic of our formerly unmodified colds . Although running of the nose would be practically non-existent , on rare occasions a single drop might appear at the nares ; however , not -a trace of \" itchiness \" had accompanied it in its roll down the turbinates . The thickened stage of nasal discharge was never reached . Sneezing and coughing were quite unusual . A throat did not proceed to \" soreness \" but , in some cases , there was a slight sensation of its presence . Hoarseness was uncommon . Headache was inconsequential . Malaise , if at all recognizable was usually so minor as to be undeserving of the name . Secondary bacterial invasions did not occur . I learned that the treatment had to be initiated early enough and needed to be continued at a high level for some time and then withdrawn or", " One hundred forty-six volunteers were r and omized to receive a placebo or an allicin-containing garlic supplement , one capsule daily , over a 12-week period between November and February . They used a five-point scale to assess their health and recorded any common cold infections and symptoms in a daily diary . The active-treatment group had significantly fewer colds than the placebo group ( 24 vs 65,P challenged virally ( 366 vs 111,P longer duration of symptoms ( 5.01 vs 1.52 days , P get a cold and recovered faster if infected . Volunteers taking placebo were much more likely to get more than one cold over the treatment period . An allicin-containing supplement can prevent attack by the common cold virus", "A r and omised controlled trial was carried out to study the effect of 10 g of ascorbic acid taken during the first 2 1/2 days on the symptoms of the common cold . Altogether 1524 volunteers were recruited from a number of working groups in different parts of the country ; 482 developed colds . There was no evidence that upper respiratory or general constitutional symptoms were alleviated by ascorbic acid . Among the men who had any colds at all , significantly fewer on active than on placebo treatment had two or more colds ; however , this effect was not seen in women . Ascorbic acid is of no value in the treatment of the common cold ; its preventive effect , if any , is not such as to justify advising its general use as a prophylactic measure", "We have initiated a population ‐based , double‐blind , r and omized controlled trial to examine the effects of supplementation of beta‐carotene and vitamin C on the incidence of gastric cancer . The subjects were participants in an annual health screening program conducted by four municipalities in Akita prefecture , one of the regions with the highest mortality from gastric cancer in Japan . We measured their serum levels of pepsinogens ( PGs ) I and II , and asked persons diagnosed with chronic atrophic gastritis ( defined as PGI to take diet supplements containing 0 or 15 mg/day beta‐carotene and 50 or 500 mg/day vitamin C for 5 years . During the first year of recruitment conducted in one village from June through September , 1995 , 52 % ( 635/1214 ) of screening participants had chronic atrophic gastritis and 73 % ( 439/602 ) of eligible persons responded . However , in response to a National Cancer Institute press report released on January 18 , 1996 , indicating that two beta‐carotene trials had shown no benefit and potential harm from the supplement , we discontinued the beta‐carotene and continued with the trial using only vitamin C. Of 397 participants remaining at this point , 77 % ( 305 ) consented to stay in the study . The results indicate that a r and omized controlled trial for cancer prevention is feasible in the Japanese asymptomatic population", "A large scale double-blind trial was conducted to test the cl aim that the intake of one gram of vitamin C per day substantially reduces the frequency and duration of \" colds \" . It was found that in terms of the average number of colds and days of sickness per subject the vitamin group experienced less illness than the placebo group , but the differences were smaller than have been cl aim ed and were statistically not significant . However , there was a statistically significant difference ( P vitamin experienced approximately 30 % fewer total days of disability ( confined to the house or off work ) than those receiving the placebo , and this difference was statistically highly significant ( P reduction in disability appeared to be due to a lower incidence of constitutional symptoms such as chills and severe malaise , and was seen in all types of acute illness , including those which did not involve the upper respiratory tract", "In a large double-blind study among Navaho school children , we evaluated the effects of vitamin C in 1- and 2-gram daily doses on acute respiratory illness during a 14-week period . ' We found no evidence of significant prophylaxis , but our findings did suggest a modest therapeutic benefit in that children taking vitamin Chad from 28 % to 34 % fewer days of morbidity caused by respiratory episodes than those taking placebo . Likewise , in classroom surveillance , younger children on vitamin C had 26 % fewer symptom-days of cough and nasal discharge recorded . These observations were consistent with other recent trials using 1 gram daily ( 4 grams during illness ) in Canadian adults L ' and 250 - 500 milligrams daily in Irish schoolchildren.3 The clinical significance of this modest therapeutic result in minor , selflimited illness was , in itself , question able . However , further study was indicated to determine : ( a ) if use of vitamin C could prevent complications of the common cold in children , such as superinfections or otitis media ; ( b ) if certain symptoms or symptom complexes responded specifically to vitamin C therapy ; and ( c ) if indeed , as our data had suggested , l higher blood ascorbic acid levels were correlated with fewer days of illness . A second investigation was design ed to confirm , if possible , and exp and our previous findings . The second trial was conducted in two Navaho boarding schools during January through May 1974 , using doses of 1 gram vitamin C daily versus placebo tablets . This report presents preliminary routine surveillance findings from the second study", "Twenty-one healthy , susceptible adult male volunteers were enrolled in a doubleblind study design ed for evaluation of the prophylactic efficacy of ascorbic acid ( 3 g daily ) in induced rhinovirus 44 infection of the upper respiratory tract . While in continuous isolation , 11 men received 1 g of ascorbic acid three times daily , and 10 men received a placebo for two weeks , after which an intranasal inoculum containing 100 TCID50 of rhinovirus 44 was administered . Each man continued to receive the same dose of medication for one week after the viral challenge . All participants subsequently developed typical illness due to rhinovirus . Similar levels of antibody in serum , nasal washings , and sputum developed in all subjects . Nasal shedding of virus and the flow of the nasal mucociliary blanket were unaffected by the ingestion of ascorbic acid . No prophylactic benefit was demonstrated from the daily ingestion of 3 g of ascorbic acid in induced rhinovirus 44 infection in man . Viral infections of the respiratory tract are the most common illness affecting mankind . The mortality from these afflictions is low , but the morbidity , when assessed as discomfort and time lost from gainful employment and leisure pursuits , is high . Therefore , it is critical to assess the controversial cl aims for the efficacy of ascorbic acid ( vitamin C ) for the prevention and relief of colds [ 1 - 5 ] . The need for a further study of the possible role of ascorbic acid in the prophylaxis and therapy of viral infections of the respiratory tract under carefully controlled circumstances was evident", "In recent years , a number of benefits of prophylactic pharmacologic doses of vitamin C have been suggested . In addition to cl aims by Linus Pauling [ 1971 ] and others of a reduction in the morbidity due to the common cold and upper respiratory infections , other authors have subsequently suggested that serum cholesterol levels may be lowered [ Spittle , 1971 ] . Some investigations have suggested that this effect may be observed only in hypercholesterolemic individuals and not those with normal cholesterol levels [ Sokoloff et al , 1966 ; Ginter et al , 1970 ] . It has also been suggested that exogenous vitamin C might improve mental alertness as measured by IQ test performance [ Kubala and Katz , 1960 ] . The present study was design ed to test these hypotheses by means of a double-blind co-twin control study", "We performed a double blind r and omized study in order to assess the efficacy of a multivitamin supplement for the prevention of common infections in healthy elderly subjects . Non-institutionalized , independent subjects over 60 years of age , living in the Nevers area ( central France ) were recruited by announcements and r and omly assigned to a treatment or a placebo group . The treatment or placebo tablets were to be taken daily for 4 months . The principal criterion of response was the incidence of infections , as recorded from a detailed question naire presented at entrance , in the middle ( 2 months ) and at the end ( 4 months ) of the study . Blood sample s were taken at the entrance in the study and after two and four months in order to monitor vitamin status . No significant difference was found between the two groups for the incidence of infections . In fact the observed incidences during the two two-month periods were higher in the treatment ( 0.38 and 0.21 ) than in the placebo group ( 0.29 and 0.13 ) . After two months and after four months of supplementation , blood vitamin indicators of the subjects were significantly higher in the treatment than in the placebo group for vitamins B1 , B2 , B6 , E and folates ( p vitamin C status was slightly higher in the treatment than in the placebo group . For vitamin A status , the evolution was similar in the two groups . In conclusion , short-term supplementation of healthy elderly subjects with the investigated supplement is not likely to afford a meaningful protection against common infections", " Between December 1972 and February 1973 , 2349 volunteers participated in a double-blind trial to assess the effect of large doses of vitamin C on the incidence and severity of winter illness . In addition , records were kept but no tablets taken during March . Subjects were r and omly allocated to eight treatment regimens : three prophylactic-only ( daily dose 0.25 , 1 or 2 g ) , two therapeutic-only ( 4 or 8 g on the first day of illness ) , one combination ( 1 g daily and 4 g on the first day of illness ) , and two all-placebo . None of the groups receiving vitamin C showed a difference in sickness experience that was statistically significant from that of the placebo groups , but the results obtained were compatible with an effect of small magnitude from both the prophylactic and therapeutic regimens , and an effect of somewhat greater magnitude from the combination regimen . The combination regimen was associated more with a reduction in severity than frequency of illness , although the extra dosage was limited to the first day of illness . In spite of the eightfold range in daily dose , the three prophylactic-only regimens showed no evidence of a dose-related effect , but the 8 g therapeutic dose was associated with less illness than the 4 g therapeutic dose . There was no evidence of side effects from the 1 and 2 g prophylactic doses of vitamin C , and no evidence of a rebound increase in illness during the month following withdrawal of the daily vitamin supplements . On the basis of this and other studies it is suggested that the optimum daily dose of vitamin C is less than 250 mg , except possibly at the time of acute illness , when a larger daily intake may be beneficial", "After their r and om -llocation to one of three treatment aroups , 622 volunteers received either vitamin C or placebo in a maintenance dose of 500 mg once weekly and a therapeutic dose of 1500 mg daily on the 1st day and 1000 mg on the next 4 days of any illness . Two forms of vitamin C were employed : a sustained-release capsule containing ascorbic acid and a regular tabet containing a mixture of sodium and calcium ascorbate . In the 448 subjects who completed an average of 15 weeks in the study of total of 635 episodes of illness were recroded . Respiratory symptoms were recorded on at least 1 day in 92 per cent of these episodes . There were no consistent or significant differences in the sickness experience of the subjects receiving the sustained-release vitamin capsules compared to those receiving the vitamin tablets , but subjects in both vitamin groups experienced less severe illness than subjects in the placebo group , with approximately 25 per cent fewer days spent indoors because of the illness ( P smaller than 0.05 ) . These results are compatible with the belief that supplementary vitamin C can reduce the burden of winter illness , but the intake need not be as high as has sometimes been cl aim ed", "Jtending to make one pair different from another , so providing a more efficient test of the treatment effect . The increase in efficiency of the matched pair over the r and om group design is dependent upon the extent to which the matching has removed extraneous factors influencing the effect of the drug . The ultimate matched pair in human experimentation is a pair of monozygotic ( MZ ) twins who have been reared together . Not only is there a perfect match for age , sex , and family background but , perhaps most importantly , genetic constitution is identical , at least for nuclear genes . The paired and unpaired design s are shown in Table I and have been compared extensively by Christian and Kang [ 1972 ] . The paired analysis allows the partition of variance between individuals ( 0111 ) into that between pairs ( oip ) and that within pairs ( a2 wp ) . For sufficiently large N , if oip > 0 ( ie , if the between-pairs mean square is significantly greater than the pairs x treatments mean square ) , then the paired design will give a more powerful test of the between-treatments effect than the unpaired design . For the num­ bers we have here , it may be shown that oi1/a2 wp is the multiplier to estimate how many more pairs of unrelated individuals would be needed to provide a test of the between-treatments effect of the same power as is provided by a given number of pairs of twins", "Summary The occurrence of common cold symptoms was recorded daily for a period of nine months by children from two male and two female boarding schools . All the children in one male and one female school received tablets containing 200 mg Vitamin C , or placebo tablets , daily on a double blind basis . Children in the other two schools received 200 or 500 mg tablets of Vitamin C. Leucocyte ascorbic acid concentrations were significantly raised in those children receiving active tablets . Comparisons of incidence , duration , severity and total intensity of cold characteristics , and of cold frequencies , were made between the different treatment groups . Cold symptoms were grouped into those characteristic of Catarrhal ( C-colds ) , and those of Toxic ( T-colds ) , colds . Whole ( W-colds ) consisted of at least one C-symptom in combination with one or more T-symptoms . 200 mg of Vitamin C had a beneficial effect on severity and total intensity of C- and W-colds , but did not affect T-colds , in girls . 500 mg produced further slight beneficial effects . With 200 mg the cold categories in boys tended to show a deterioration , and the deterioration continued in the group receiving 500 mg . Analysis of cold frequency indicated that T-colds are commoner in girls . Their C-cold frequency diminished with the smaller dose , and their T-cold frequency was reduced by the larger dose of Vitamin C. In boys C-cold frequency diminished with 500 mg of Vitamin C daily . These data suggest that there is a sexual difference in the effects of Vitamin C on the characteristics of the common cold . Evaluation of the effects of Vitamin C on toxic and catarrhal symptoms in relation to administered doses is of more importance than examination of its prophylactic or therapeutic actions . 500 mg had some beneficial effect in girls : any beneficial effect of Vitamin C on the common cold in boys will probably be associated with administration of a higher daily dose", "Summary The occurrence and severity of nine symptoms of the common cold were recorded daily for 35 weeks by girls and boys in four Dublin boarding schools . Half the children in each school received placebo or 200 mg tablets , or 200 mg or 500 mg tablets , of Vitamin C daily on a double blind basis . Diets or environmental conditions did not differ between the schools . A score for the severity of each symptom was obtained daily for all the subjects throughout the trial in the different treatment groups . The degree of association between pairs of symptoms was calculated . The symptoms of the common cold syndrome ( the W-complex ) tended to exist in two groups defined as Toxic and Catarrhal complexes ( T- and C-complexes ) . The intensity and quality of W-complex symptoms were assessed in terms of the correlation value above which the constituent T- and C-complexes became manifest , the average correlation values of the constituent complexes , and the linkage of the symptoms in these complexes . The values for , and quality of , the complexes were dependent on the sex of the sample s and the dose of Vitamin C administered . Boys tended to have more complicated W-complexes which broke down into T- and C-complexes with the lower dose of Vitamin C. These became more complicated when increasing doses of Vitamin C were administered . Girls had less complicated W-complexes , but more complicated T- and C-complexes , than boys . Increasing doses of Vitamin C made the girls ' T- and C-complexes less complicated . Administration of Vitamin C appeared to benefit the common cold syndrome more in girls than in boys", "Abstract The effect of daily administration of placebo or 200 or 500 mg . tablets of vitamin C on symptom association and on the incidence , duration , severity , and total intensity of the symptoms in the common cold has been studied . The metabolism of ascorbic acid during the common cold , and after disappearance of all the symptoms , has been investigated by examining the plasma and leucocyte ascorbic-acid concentrations after a loading dose of 500 mg . vitamin C. Cold symptoms tend to dissociate into toxic and catarrhal complexes , the complexity and frequency of which differ between boys and girls . Vitamin C reduces symptom association and alters the frequency of toxic and catarrhal complexes . It significantly reduces the severity and total intensity of colds in girls , but does not benefit cold symptoms in boys at a daily dose of 500 mg . During colds , especially of the catarrhal variety , ascorbic acid is transferred out of the leucocytes into the plasma , where it is rapidly metabolised in both sexes , but this effect is more pronounced in females . There is a significant positive correlation between metabolic utilisation of ascorbic acid during colds and intensity of cold symptoms", "BACKGROUND An ever increasing dem and to evaluate the effect of dietary supplements on specific health conditions by use of a \" significant scientific \" st and ard has prompted the publication of this study . OBJECTIVE To study the effect of megadose Vitamin C in preventing and relieving cold and flu symptoms in a test group compared with a control group . DESIGN Prospect i ve , controlled study of students in a technical training facility . SUBJECTS A total of 463 students ranging in age from 18 to 32 years made up the control group . A total of 252 students ranging in age from 18 to 30 years made up the experimental or test group . METHOD Investigators tracked the number of reports of cold and flu symptoms among the 1991 test population of the facility compared with the reports of like symptoms among the 1990 control population . Those in the control population reporting symptoms were treated with pain relievers and decongestants , whereas those in the test population reporting symptoms were treated with hourly doses of 1000 mg of Vitamin C for the first 6 hours and then 3 times daily thereafter . Those not reporting symptoms in the test group were also administered 1000-mg doses 3 times daily . RESULTS Overall , reported flu and cold symptoms in the test group decreased 85 % compared with the control group after the administration of megadose Vitamin C. CONCLUSION Vitamin C in megadoses administered before or after the appearance of cold and flu symptoms relieved and prevented the symptoms in the test population compared with the control group", "Vitamin C has been a popular medication for preventing the common cold and reducing the severity of cold symptoms for many years . - ' Professor Pauling 's recent book on the subject has led to even further use of vitamin C in even larger doses . This study was performed to look for a difference in the frequency and severity of colds in a generally healthy , middle-class , medically aware population of employees at the National Institutes of Health . High doses of vitamin C were used for both prevention and treatment ; virus isolations were attempted in an effort to relate viral types to vitamin C response ; and the study was continued for a nine-month period in an attempt to examine seasonal variations of viruses and colds . The study was conducted so that nurses , physicians , and volunteers did not know who received placebo and who received ascorbic acid . Only the consulting statistician and the pharmacist could relate patient code numbers to medication received . Progress was monitored by a research committee not connected with the day-to-day activities", "Among the many cl aims made about the value of large doses of vitamin C , those relating to the prevention and treatment of \" colds \" have aroused most interest , and the first question to be answered is whether there is any real evidence that such an effect exists , or whether the cl aims are based entirely on wishful thinking . If there is no good evidence of an effect , then there is little point in pursuing the matter . If , on the other h and , the evidence suggests that there is some sort of effect , a host of secondary questions present themselves : ( 1 ) Is the effect specific for the common-cold group of viruses , or is it a more general anti-infective ( or even antistress ) effect ? ( 2 ) Is it a reflection of an increased metabolic need in certain individuals or at certain times , or is it a pharmacological action unrelated to the normal metabolic function of ascorbic acid ? ( 3 ) Is the beneficial effect related to a regular daily intake ( \" prophylactic \" ) or to extra intake during the course of an illness ( \" therapeutic \" ) or to a com bination of both ? ( 4 ) Are large doses really necessary , or could equally good results be ob tained with a more moderate supplementation of normal dietary intake ? ( 5 ) If large doses are necessary , does the risk of side effects outweigh the possible benefits ? From a practical point of view it is this last question that most urgently needs to be answered . Further , since it seems reasonable to suppose that side effects are more likely to appear with higher doses and with prolonged intake , the first point to establish is whether there is any value to the regular \" prophylactic \" use of large doses of vitamin C , and whether in fact the size of the daily dose is as important as has been cl aim ed . In passing , it may be noted that although we have seen no symptomatic evidence of toxicity result ing from doses of up to 2000 mg daily over three or four months in healthy persons , this does not mean that this dose level is necessarily safe for longer periods , particularly in individuals with preexisting disease , or that the occasional individual might not show some unusual and undesirable reaction . Furthermore , while perhaps not a side effect in the ordinary sense of the word , the depression in blood ascorbate levels that occurs on sudden withdrawal of a chronic high intake should be recognized as a potentially harmful reaction . For example , an individual admitted to the hospital with an acute medical or surgical condition might be at a physiological disadvantage if this period of unusual stress coincided with an acute hypoascorbemia due to sudden withdrawal of a regular high intake . What then , is the evidence regarding the prophylactic use of large doses of vitamin C ? There is , of course , a great deal of anecdotal evidence , but this is of dubious value because of the well-recognized interaction between mental", "We review ed the clinical data relating to the efficacy and safety of pharmacologic doses of ascorbic acid in the prevention and treatment of the common cold . Although one study tentatively supports the hypothesis that such doses of ascorbic acid may be efficacious , a second study by the same group did not confirm the significant findings , and no clear , reproducible pattern of efficacy has emerged from the review of all the evidence . Similarly , there is currently little adequate evidence on either the presence or the absence of serious adverse reactions to such doses of ascorbic acid , although many such reactions have been hypothesized . The unrestricted use of ascorbic acid for these purpose s can not be advocated on the basis of the evidence currently available" ]

[ "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 ( enrolment , 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", "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", "Summary In a double-blind study of the comparative effectiveness of eight phenothiazines , 322 newly-admitted state psychiatric hospital patients requiring tranquilizing drug therapy were r and omly assigned to treatment with one of the following drugs : chlorpromazine , thioridazine , triflupromazine , prochlorperazine , perphenazine , thiopropazate , trifluoperazine , and fluphenazine . The design of the study permitted flexible dosages , and treatment , unless prematurely terminated , lasted 30 days . Psychological and /or psychiatric assessment s were made prior to treatment and at the end of 5 , 15 , and 30 days . Although results again substantiated the effectiveness of the phenothiazine compounds as a whole , evidence of differential drug effectiveness was equivocal using raw scores derived from st and ard rating scales and traditional methods of statistical analysis . Such analyses suggested negligible treatment differences in terms of means . Non-constant , non-additive treatment effects were greatly in evidence , however ; and the high incidence of heterogeneity of variance and of regression indicated that the drugs were neither equivalent nor interchangeable . Subsequent analyses of MSRPP Total Morbidity , involving the more severely ill patients and using a scale transformation to achieve homogeneity of variance , yielded significant treatment differences at every evaluation period . In these analyses , the drugs found to be consistently effective over the 30-day treatment period were prochlorperazine , perphenazine , and fluphenazine . Those found to be less effective were thioridazine , triflupromazine , and thiopropazate . For the less severely ill patients , significant mean differences among the eight drugs were not obtained ; however , there was a tendency for the rank order of drug efficacy in this group to be the reverse of that obtained with the severely ill patients", "In a controlled study , inpatient violence was measured during placebo , high-potency ( haloperidol ) and low-potency ( chlorpromazine or clozapine ) neuroleptics . Some patients had a marked increase in violent behavior with the moderately high-dose haloperidol , but not with low-potency neuroleptics . The authors discuss reasons for the increased violence with haloperidol , including akathisia and drug-induced behavioral toxicity", "Objective To compare the effect of intramuscular olanzapine with intramuscular haloperidol plus promethazine on rapid tranquillisation of agitated or violent people with mental illness . Design Pragmatic , allocation concealed , r and omised controlled trial . Setting Emergency services of a general hospital psychiatry department in Vellore , south India . Participants 300 adults with agitated or violent behaviour as a result of mental illness ; 150 r and omised to intramuscular olanzapine and 150 r and omised to intramuscular haloperidol plus promethazine . Interventions Open treatment with intramuscular olanzapine or intramuscular haloperidol plus promethazine . Main outcome measures Primary outcome was proportion of patients who were tranquil or asleep at 15 minutes and 240 minutes . Secondary outcomes were proportion of patients who were tranquil , asleep , restrained , absconding , or clinical ly improved at 15 , 30 , 60 , 120 , and 240 minutes ; additional medical interventions and adverse effects over four hours ; and compliance with oral drugs and adverse effects over two weeks . Results Of 300 people r and omised to receive either intramuscular olanzapine or intramuscular haloperidol plus promethazine , follow-up data were available for primary outcomes for 298 ( 99 % ) . Both treatments result ed in similar proportions of people being tranquil or asleep at 15 minutes ( olanzapine 131/150 ( 87 % ) , haloperidol plus promethazine 136/150 ( 91 % ) ; relative risk 0.96 , 95 % confidence interval 0.34 to 1.47 ) and 240 minutes ( olanzapine 144/150 ( 96 % ) , haloperidol plus promethazine 145/150 ( 97 % ) ; relative risk 0.99 , 0.95 to 1.03 ) . However , more people given olanzapine than those given haloperidol plus promethazine required additional drugs over four hours ( 65/150 ( 43 % ) v 31/150 ( 21 % ) ; relative risk 2.07 , 1.43 to 2.97 ) . Adverse effects were uncommon with both treatments . Conclusions Intramuscular olanzapine and intramuscular haloperidol plus promethazine were effective at rapidly tranquillising or sedating agitated or violent patients with mental illness but the combination result ed in fewer additional medical interventions within four hours of intervention . Trial registration Clinical trials NCT00455234", "Objective To determine whether haloperidol alone results in swifter and safer tranquillisation and sedation than haloperidol plus promethazine . Design Pragmatic r and omised open trial ( January-July 2004 ) . Setting Psychiatric emergency room , Rio de Janeiro , Brazil . Participants 316 patients who needed urgent intramuscular sedation because of agitation , dangerous behaviour , or both . Interventions Open treatment with intramuscular haloperidol 5 - 10 mg or intramuscular haloperidol 5 - 10 mg plus intramuscular promethazine up to 50 mg ; doses were at the discretion of the prescribing clinician . Main outcome measures The primary outcome was proportion tranquil or asleep by 20 minutes . Secondary outcomes were asleep by 20 minutes ; tranquil or asleep by 40 , 60 , and 120 minutes ; physically restrained or given additional drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; additional visit from the doctor during the subsequent 24 hours ; overall antipsychotic load in the first 24 hours ; and still in hospital after 2 weeks . Results Primary outcome data were available for 311 ( 98.4 % ) people , 77 % of whom were thought to have a psychotic illness . Patients allocated haloperidol plus promethazine were more likely to be tranquil or asleep by 20 minutes than those who received intramuscular haloperidol alone ( relative risk 1.30 , 95 % confidence interval 1.10 to 1.55 ; number needed to treat 6 , 95 % confidence interval 4 to 16 ; P=0.002 ) . No differences were found after 20 minutes . However , 10 cases of acute dystonia occurred , all in the haloperidol alone group . Conclusions Haloperidol plus promethazine is a better option than haloperidol alone in terms of speed of onset of action and safety . Enough data are now available to change guidelines that continue to recommend treatments that leave people exposed to longer periods of aggression than necessary and patients vulnerable to distressing and unsafe adverse effects . Trial registration Current Controlled Trials IS RCT N83261243", "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", "BACKGROUND The pharmacological management of violence in people with psychiatric disorders is under- research ed . AIMS To compare interventions commonly used for controlling agitation or violence in people with serious psychiatric disorders . METHOD We r and omised 200 people to receive intramuscular lorazepam ( 4 mg ) or intramuscular haloperidol ( 10 mg ) plus promethazine ( 25 - 50 mg mix ) . RESULTS At blinded assessment s 4 h later ( 99.5 % follow-up ) , equal numbers in both groups ( 96 % ) were tranquil or asleep . However , 76 % given the haloperidol-promethazine mix were asleep compared with 45 % of those allocated lorazepam ( RR=2.29,95 % CI 1.59 - 3.39 ; NNT=3.2,95 % CI 2.3 - 5.4 ) . The haloperidol-promethazine mix produced a faster onset of tranquillisation/sedation and more clinical improvement over the first 2 h. Neither intervention differed significantly in the need for additional intervention or physical restraints , numbers absconding , or adverse effects . CONCLUSIONS Both interventions are effective for controlling violent/agitated behaviour . If speed of sedation is required , the haloperidol-promethazine combination has advantages over lorazepam", "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 " ]

[ "OBJECTIVE This study evaluated the effect of a atorvastatin-fenofibrate combination on lipid profile , in comparison to each drug alone , in patients with type 2 diabetes and combined hyperlipidemia ( CHL ) . RESEARCH DESIGN AND METHODS A total of 120 consecutive patients , who were free of coronary artery disease ( CAD ) at entry , were studied for a period of 24 weeks . These patients were r and omly assigned to atorvastatin ( 20 mg/day , n = 40 ) , micronized fenofibrate ( 200 mg/day , n = 40 ) , or a combination of both ( atorvastatin 20 mg/day plus fenofibrate 200 mg/day , n = 40 ) . The effect of treatment on LDL cholesterol , triglycerides ( TGs ) , HDL cholesterol , apolipoprotein A-I and B , lipoprotein(a ) , and plasma fibrinogen ( PF ) was recorded . Moreover , the percentage of patients that reached the American Diabetes Association treatment goals and the estimated CAD risk status were calculated . RESULTS No patient was withdrawn from the study because of side effects . The atorvastatin-fenofibrate combination reduced total cholesterol by 37 % , LDL cholesterol by 46 % , TGs by 50 % , and PF by 20 % , whereas it increased HDL cholesterol by 22 % ( P LDL cholesterol treatment goal of TG levels of optimal HDL cholesterol levels of > 45 mg/dl . These rates were significantly higher than those of both monotherapies . Combined treatment reduced the 10-year probability for myocardial infa rct ion from 21.6 to 4.2 % . CONCLUSIONS The atorvastatin-fenofibrate combination has a highly beneficial effect on all lipid parameters and PF in patients with type 2 diabetes and CHL . It improved patients ' CAD risk status significantly more than each drug alone", "Abstract —Interindividual variability in low density lipoprotein ( LDL ) cholesterol ( LDL-C ) response during treatment with statins is well documented but poorly understood . To investigate potential metabolic and genetic determinants of statin responsiveness , 19 patients with refractory heterozygous familial hypercholesterolemia were sequentially treated with placebo , atorvastatin ( 10 mg/d ) , bile acid sequestrant , and the 2 combined , each for 4 weeks . Levels of LDL-C , mevalonic acid ( MVA ) , 7-&agr;-OH-4-cholesten-3-one , and leukocyte LDL receptor and hydroxymethylglutaryl coenzyme A reductase mRNA were determined after each treatment period . Atorvastatin ( 10 mg/d ) reduced LDL-C by an overall mean of 32.5 % . Above-average responders ( & Dgr;LDL-C −39.5 % ) had higher basal MVA levels ( 34.4±6.1 & mgr;mol/L ) than did below-average responders ( & Dgr;LDL-C −23.6 % , P ; basal MVA 26.3±6.1 & mgr;mol/L , P an apolipoprotein E4 allele ( 3 of 11 versus 6 of 8 , respectively;P in 7-&agr;-OH-4-cholesten-3-one , hydroxymethylglutaryl coenzyme A reductase mRNA , or LDL receptor mRNA , but the latter increased in the good responders on combination therapy ( P Severe mutations were not more common in poor than in good responders . We conclude that poor responders to statins have a low basal rate of cholesterol synthesis that may be secondary to a genetically determined increase in cholesterol absorption , possibly mediated by apolipoprotein E4 . If so , statin responsiveness could be enhanced by reducing dietary cholesterol intake or inhibiting absorption", "OBJECTIVE It has been repeatedly proven that statins improve endothelial function in isolated hypercholesterolaemia but there is far less evidence in the case of combined hyperlipidaemia . Studies assessing the effects of fibrates on endothelium have been neglected . Therefore , we conducted a trial in which the effects of fenofibrate and atorvastatin monotherapy on both endothelium-dependent vascular reactivity and biochemical parameters were compared in patients with combined hyperlipidaemia . METHODS 29 otherwise healthy males ( aged 47.4+/-7.8 years ) with combined hyperlipidaemia ( total cholesterol 7.55+/-1.20 mmol/l , triglycerides 5.41+/-4.54 mmol/l ) were included into the r and omised , single-blind , cross-over study to receive either 200 mg of micronised fenofibrate or 10 mg of atorvastatin daily -- each of the drugs for a period of 10 weeks . Analysed biochemical parameters were as follows : serum total- , LDL- and HDL-cholesterol , apolipoproteins A-I and B , triglycerides , fibrinogen , uric acid , C-reactive protein ( CRP ) , insulin , and homocysteine . Endothelial function was investigated by duplex Doppler ultrasonography at the brachial artery . Two indices of endothelial-dependent postischaemic changes were used - the recently introduced index of peak blood flow ( PBF ) representing the level of reactive hyperaemia and traditional flow-mediated dilatation ( FMD ) . RESULTS We observed a small improvement in FMD after both fenofibrate and atorvastatin ( from 2.26 % to 2.98 % and 2.87 % , respectively ; NS ) . PBF increased from 448 ml/min to 536 ml/min after fenofibrate ( P=0.04 ) and to 570 ml/min after atorvastatin ( P=0.03 ) . The effects of both fenofibrate and atorvastatin on endothelial function did not differ significantly ( P-values of 0.82 and 0.47 for FMD and PBF , respectively ) . Significant correlations ( P vascular reactivity and biochemical indices were found between FMD and CRP ( r=-0.60 ) and between both FMD and PBF , and insulinaemia ( r=-0.48 and -0.56 , respectively ) only during treatment with fenofibrate . CONCLUSIONS Both fenofibrate and atorvastatin significantly improved endothelium-dependent vascular reactivity without mutual difference . The PBF was superior to FMD for the detection of this improvement . The beneficial effect of both drugs did not correlate with the change of lipid profile during therapy . The improvement of vascular reactivity during treatment with fenofibrate ( opposed to atorvastatin ) was related to the reduction of indirect marker of chronic vessel wall inflammation and of insulin resistance . The PBF was more reproducible than FMD because of considerably lower intra-subject variability", "Abstract . Objectives : In patients with mixed lipid disorders , monotherapy may not effectively control all lipid abnormalities . We undertook this study to assess the efficacy of fenofibrate in combination with atorvastatin in patients with severe mixed dyslipidemia . Methods : This was an 18-week , open-label study conducted in our lipid clinic . After a 6-week dietary baseline phase , patients received 200 mg/day micronised fenofibrate for 6 weeks . At the end of this period the subjects discontinued this treatment and received 40 mg/day atorvastatin for 6 weeks . Finally 200 mg/day of micronised fenofibrate was added to the statin therapy . Results : Administration of micronised fenofibrate reduced serum triglycerides ( P total cholesterol and low-density lipoprotein ( LDL ) cholesterol ( P serum high-density lipoprotein ( HDL ) cholesterol levels ( P Atorvastatin monotherapy induced a more pronounced decrease of total and LDL cholesterol . However , plasma triglycerides , although significantly lower than baseline values ( P serum HDL cholesterol concentrations were higher during fibrate therapy than during the statin one . During the combination therapy , the decrease in triglycerides was greater than that observed with fenofibrate alone , while the decrease in LDL cholesterol was more pronounced than that observed with atorvastatin alone . Conclusion : The combination of atorvastatin with micronised fenofibrate in patients with severe mixed dyslipidemia may have a favourable effect on some major coronary artery disease risk factors", "An elevated plasma fibrinogen level is increasingly accepted as an independent risk indicator of cardiovascular disease . This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels . One group of agents with this capacity are the fibric acid derivatives , e.g. ciprofibrate and gemfibrozil . We studied fibrinogen levels after 12 weeks of treatment with ciprofibrate ( n = 48 ) and gemfibrozil ( n = 51 ) in hypercholesterolenic patients . The correlation of the decrease in fibrinogen with lipid lowering and the contribution of the acute phase and genetic polymorphisms to this decrease were also evaluated . After 12 weeks of treatment , the fibrinogen levels were significantly decreased ( p ciprofibrate group ( mean 3.4 g/l pre-treatment to 2.4 g/l after 12 weeks ) was larger than in the gemfibrozil group ( mean 3.4 g/l to 3.0 g/l ) . The lipid lowering effect was comparable for the two drugs but there was no correlation for either ciprofibrate or gemfibrozil between the lipid lowering and the magnitude or the velocity of the fibrinogen lowering effect . An attenuation of the major regulatory mechanism of plasma fibrinogen levels , the acute phase reaction , was invoked as the underlying mechanism . However , pre-treatment C-reactive protein levels were not increased and did not change after treatment . Moreover , no effects of the polymorphisms of the fibrinogen beta-gene on the decrease of the plasma fibrinogen levels were observed . This suggests that a new , as yet unknown , mechanism is involved in fibrinogen lowering by fibrates", "OBJECTIVE To determine the efficacy and safety of a statin-fibrate combination in diabetes patients . DESIGN . : An open 21-month trial in which each patient first received the single drug for 6 months and then a combination of the two for 1 year . SETTING Three lipid clinics in university-based tertiary care hospitals . PATIENTS One hundred and forty-eight patients with type 2 ( non-insulin-dependent , NIDDM ) diabetes mellitus under stable control for 3 months by means of diet and oral hypoglycaemic medication . INTERVENTION Patients from one clinic ( n = 48 ) received bezafibrate slow release ( 400 mg day-1 ) , and patients from the other two clinics ( n = 100 ) received simvastatin 20 mg day-1 . Six months later , all patients were switched to a daily combination of 400 mg bezafibrate slow release and 20 mg simvastatin for 1 year . RESULTS The combination of statin and fibrate led to a 23 % reduction in total cholesterol , 42 % reduction in triglycerides , 29 % reduction in LDL-c , 25 % increase in HDL-c , 10 % decrease in fibrinogen and 19 % reduction of Lp(a ) levels , and a decrease in the cholesterol/HDL-c ratio ( from 8.9 to 5.4 ) in all 148 patients . Cardiovascular ( CV ) event rate was significantly reduced from 9.5 % during the first 6 months of the study to less than 2 % during the last year of the study ( whilst on combination Rx ) . Side-effects with all treatments included only two patients who developed myopathy when on the combined regimen and one on the single statin regimen . However , plasma creatinine phosphokinase ( CPK ) levels doubled ( but remained within the normal range ) in most of the patients on combination therapy , compared with only a mild increase in patients receiving a single medication . CONCLUSIONS The statin and fibrate combination was found to be more efficacious than a single medication for treatment of diabetic dyslipidaemia , as evidence d by improvement in the lipoprotein profile , reductions in Lp(a ) , fibrinogen and CV event rate , and almost no clinical ly significant side-effects", "OBJECTIVES We compared vascular and metabolic responses ( and adverse responses ) to statin and fibrate therapies alone or in combination in patients with combined hyperlipidemia . BACKGROUND The mechanisms of action for statins and fibrates are distinct . METHODS Fifty-six patients were given atorvastatin 10 mg and placebo , atorvastatin 10 mg and fenofibrate 200 mg , or fenofibrate 200 mg and placebo daily during each two-month treatment period of a r and omized , double-blind , placebo-controlled crossover trial with two washout periods of two months ' each . RESULTS Lipoproteins were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone . Flow-mediated dilator response to hyperemia and plasma high-sensitivity C-reactive protein and fibrinogen levels were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone ( p plasma adiponectin levels and insulin sensitivity ( determined by the Quantitative Insulin-Sensitivity Check Index [ QUICKI ] ) were significantly greater than those of atorvastatin alone ( p = 0.022 for adiponectin and p = 0.049 for QUICKI by ANOVA ) . No patients were withdrawn from the study as the result of serious adverse effects . CONCLUSIONS Combination therapy is safe and has beneficial additive effects on endothelial function in patients with combined hyperlipidemia", "The effects on the coagulative and rheologic pattern of two lipid-lowering drugs , bezafibrate and simvastatin , were studied in 36 hypercholesterolemic subjects . Patients were r and omly divided into two groups ( 18 subjects each ) and received bezafibrate R 400 mg/day or simvastatin 10 - 40 mg/day over a twelve week period . Besides a decrease in plasma fibrinogen and fibrinopeptide A ( p bezafibrate induced a reduction of factor VIIc and VIIIc activity ( p antithrombin 3 activity was increased ( p hemorheologic pattern was greatly improved ( p Simvastatin caused a slight decrease in factor VIIIc activity and a moderate reduction of beta thromboglobulin . The efficacy of bezafibrate in reducing the activation of the coagulative cascade and improving the hemorheologic pattern has been con firmed ; the peculiar triglycerides- and fibrinogen-lowering effect of the drug , not observed with simvastatin , could be responsible for these modifications", "BACKGROUND HMG-CoA reductase inhibitors ( statins ) reduce the risk of venous thromboembolism ( VTE ) in healthy people . Statins reduce levels of inflammation biomarkers ; however , the mechanism for the reduction in VTE risk is unknown . AIM In a large cohort of healthy people , we studied associations of statin use with plasma hemostatic factors related to VTE risk . METHODS Cross-sectional analyses were performed in the Multi-Ethnic Study of Atherosclerosis ( MESA ) , a cohort study of 6814 healthy men and women aged 45 - 84 years , free of clinical cardiovascular disease at baseline ; 1001 were using statins at baseline . Twenty-three warfarin users were excluded . Age , race and sex-adjusted mean hemostatic factor levels were compared between statin users and non-users , and multivariable linear regression models were used to assess associations of statin use with hemostatic factors , adjusted for age , race/ethnicity , education , income , aspirin use , hormone replacement therapy ( in women ) , and major cardiovascular risk factors . RESULTS Participants using statins had lower adjusted levels of D-dimer ( - 9 % ) , C-reactive protein ( - 21 % ) and factor VIII ( - 3 % ) than non-users ( P Homocysteine and von Willebr and factor levels were non-significantly lower with statin use . Higher fibrinogen ( 2 % ) and plasminogen activator inhibitor-1 ( 22 % ) levels were observed among statin users than among non-users ( P LDL and triglyceride levels did not attenuate the observed differences in these factors with statin use . CONCLUSIONS Findings of lower D-dimer , FVIII and C-reactive protein levels with statin use suggest hypotheses for mechanisms whereby statins might lower VTE risk . A prospect i ve study or clinical trial linking these biochemical differences to VTE outcomes in statin users and non-users is warranted", "BACKGROUND Elevated plasma low-density lipoprotein cholesterol ( LDL-C ) concentrations are highly atherogenic , especially the small , dense LDL ( sdLDL ) species . Fenofibrate has been reported to shift the LDL profile by decreasing the sdLDL subfraction and increasing larger LDL subclasses . Atorvastatin , anantihyperlipidemic agent , has been reported to reduce plasma total cholesterol ( TC ) and triglyceride ( TG ) concentrations and thus could modify the LDL profile . OBJECTIVE The aim of this study was to compare the effects of fenofi brate and atorvastatin on st and ard lipid concentrations and the LDL profile . METHODS In this r and omized , open-label , parallel-group study , men and women aged 18 to 79 years with type II primary dyslipidemia , defined as LDL-C ≥160 and TG 150 to 400 mg/dL , after a 4- to 6-week washout period while eating an appropriate diet , were r and omized to receive either atorvastatin 10 mg once daily or fenofi-brate 200 mg once daily . Plasma lipid concentrations and cholesterol and apolipoprotein ( apo ) B ( reflecting the LDL particle number ) in each LDL subfraction prepared by ultracentrifiigation were determined at baseline and after 12 weeks of treatment . Tolerability was assessed using adverse events ( AEs ) obtained on laboratory analysis and vital sign measurement . Adherence was assessed by counting unused drug supplies . RESULTS A total of 165 patients ( 117 men , 48 women ; mean [ SD ] age , 50.1 [ 10.7 ] years ; mean TC concentration , 289 mg/dL ) were r and omized to receive atorvastatin ( n = 81 ) or fenofibrate ( n = 84 ) . Compared with fenofibrate , atorvastatin was associated with a significantly greater mean ( SD ) percentage decrease in TC ( 27.0 % [ 12.3 % ] vs 16.5 % [ 12.9 % ] ; P ( 35.4 % [ 15.8 % ] vs 17.3 % [ 17.2 % ] ; P ratio ( 29.1 % [ 16.3 % ] vs 22.9 % [ 15.9 % ] ; P = 0.001 ) , and apoB ( 30.3 % [ 12.7 % ] vs 19.6 % [ 15.5 % ] ; P atorvastatin , fenofibrate was associated with a significantly greater decrease in TG ( 37.2 % [ 25.9 % ] vs 20.2 % [ 27.3 % ] ; P 0.001 ) and a significantly greater increase in HDL-C concentration ( 10.4 % [ 15.7 % ] vs 4.6 % [ 12.1 % ] ; P = 0.017 ) . Fibrinogen concentration was significantly different between the 2 groups ( P = 0.002 ) ; it was decreased with fenofibrate use ( 4.6 % [ 23.7 % ] ) and was increased with atorvastatin use ( 5.7 % [ 23.5 % ] ) . Atorvastatin did not markedly affect the LDL distribution ; it was associated with a homogeneous decrease in cholesterol and apoB concentrations in all subfractions , whereas fenofibrate was associated with a marked movement toward a normalized LDL profile , shifting the sdLDL subfractions toward larger and less atherogenic particles , particularly in those patients with baseline TG ≥200 mg/dL. No serious AEs related to the study treatments were reported . A total of 5 AEs were observed in 8 patients , including : abdominal pain , 3 patients ( 2 in the atorvastatin group and 1 in the fenofibrate group ) ; abnormal liver function test results , 1 ( fenofibrate ) ; increased creatine Phosphokinase activity , 2 ( atorvastatin ) ; gastrointestinal disorders , 1 ( fenofibrate ) ; and vertigo , 1 ( fenofibrate ) . CONCLUSION In these dyslipidemic patients , fenofibrate treatment was associated with an improved LDL subfraction profile beyond reduction in LDL-C , particularly in patients with elevated TG concentration , whereas atorvastatin was associated with equally reduced concentrations of cholesterol and apoB in all LDL subfractions independent of TG concentrations", "Low-density lipoprotein ( LDL ) apheresis is a treatment option in patients with coronary artery disease and elevated LDL cholesterol concentrations if maximal drug therapy fails to achieve adequate LDL cholesterol reduction . This therapy is more effective when combined with strong lipid-lowering drugs , such as atorvastatin . However , conflicting data have been published concerning the effect of atorvastatin on fibrinogen concentration . Therefore , we investigated the effect of atorvastatin compared to simvastatin on fibrinogen concentration and other hemorheological parameters in patients treated by weekly LDL apheresis . Hemorheological parameters were , studied twice in 9 patients ( 4 female , 5 male , 54.0+/-8.9 years ) with coronary artery disease treated by weekly LDL immunoadsorption , once during concomitant simvastatin therapy ( 40 mg daily ) and once during atorvastatin therapy ( 40 mg daily ) . Fibrinogen concentration , plasma and blood viscosity at different shear rates , parameters of red cell aggregation at stasis and shear rate 3/s , and erythrocyte filterability were determined 7 days after the last LDL apheresis after each drug had been given for a minimum for 8 weeks . Fibrinogen concentration did not show any statistically significant difference during therapy with atorvastatin ( 3.09+/-0.36 g/L ) compared to simvastatin ( 3.13+/-0.77 g/L ) . Plasma and blood viscosity as well as erythrocyte filterability were also unchanged . The increase in red cell aggregation at stasis during atorvastatin treatment ( 5.82+/-1.00 U versus 4.89+/-0.48 U during simvastatin ; p high-density liprotein ( HDL ) cholesterol concentration ( 1.17+/-0.21 mmol/L versus 1.31+/-0.30 mmol/L during simvastatin ; p LDL cholesterol showed a strong trend to lower concentrations during atorvastatin ( 4.14+/-0.61 mmol/L versus 4.56+/-0.66 mmol/L during simvastatin ; p = 0.07 ) , despite a reduced plasma volume treated ( 3,547+/-1,239 ml during atorvastatin versus 3,888+/-1,206 mL during simvastatin ; p fibrinogen concentration and other hemorheological parameters were unchanged during atorvastatin compared to simvastatin therapy with the exception of a higher red cell aggregation at stasis . Therefore , with respect to hemorheology , we conclude that atorvastatin should not be withheld from hypercholesterolemic patients regularly treated with LDL immunoadsorption", "Summary We conducted an open-label study to test the effects of atorvastatin on serum lipids , lipoprotein(a ) [ Lp(a ) ] and plasma fibrinogen levels . A total of 90 dyslipidaemic , nonsmoking patients ( 45 patients with primary hypercholesterolaemia and 45 patients with primary mixed hyperlipidaemia ) aged 48 ± 11 years were studied . The patients were treated with 20 mg of atorvastatin for 24 weeks , in a single nocturnal dose . At baseline and every eight weeks , the fasting lipid profile , together with serum Lp(a ) and plasma fibrinogen levels ( Clauss method ) , were measured . Atorvastatin was highly effective in normalising the serum lipid profile . No significant change in median serum Lp(a ) levels was observed in the whole group of patients ( 0.14 g/l before , vs. 0.16 g/l after , treatment ) as well as in patients with raised ( > 0.30 g/l ) baseline levels ( n = 32 ) . A small non-significant increase of plasma fibrinogen was found ( 3.04 g/l vs. 3.14 g/l ) after 24 weeks of atorvastatin administration . The effects of atorvastatin on both these variables did not differ in patients with hypercholesterolaemia or mixed hyperlipidaemia . In conclusion , our findings suggest that the effect of atorvastatin on plasma fibrinogen levels in dyslipidaemic patients without evident vascular disease is not clinical ly relevant . Furthermore , any rise in fibrinogen levels that may occur is likely to be transient in nature . Further studies are necessary to clarify this issue . There was no evidence that atorvastatin influences serum Lp(a ) levels ", "Fibrates and HMG CoA reductase inhibitors are commonly used in the treatment of diabetic dyslipidaemia . However , these two groups of drugs have not been compared in diabetic patients in a r and omized controlled trial . Therefore , a multicentre study was performed in 73 subjects with non-insulin-dependent ( Type 2 ) diabetes mellitus ( NIDDM ) and combined hyperlipidaemia ( serum cholesterol 6.2 - 10.0 mmol l(-1 ) , serum triglycerides 2.3 - 10.0 mmol l(-1 ) ) , comparing the efficacy of 400 mg bezafibrate with 10 mg simvastatin in a double-blind fashion . Treatment with bezafibrate during 12 weeks reduced serum triglycerides significantly more than simvastatin ( -41 % vs -22 % , p HDL cholesterol more ( bezafibrate : + 17 % vs simvastatin : + 9 % , p LDL cholesterol levels decreased by 14 % ( p simvastatin and increased by 21 % ( p bezafibrate . This increase in LDL cholesterol was positively correlated with fasting serum triglycerides ( p serum apolipoprotein B concentration , suggesting an increase in LDL particle size . Metabolic control of diabetes ( fasting glycaemia ; HbA1c ) and insulin secretion ( C-peptide levels ) were unaffected by both treatments . The incidence of side-effects during treatment was similar for both drugs . Thus , 400 mg bezafibrate mainly increases HDL cholesterol and lowers serum triglycerides but at the expense of an increase in LDL cholesterol ; 10 mg simvastatin lowers LDL cholesterin more effectively but has a smaller effect on HDL cholesterol and triglycerides", "Previous studies suggested that certain lipid-lowering drugs such as statins suppress ubiquinone , affect mitochondrial function , and may have deleterious effect on skeletal or cardiac muscles with potentially serious clinical consequences , especially in patients with established coronary heart disease and left ventricular dysfunction . In this double-blind study , we assessed the effects of 20 mg simvastatin ( S , n = 32 ) or 200 mg micronized fenofibrate ( F , n = 32 , control group ) on rest and exercise left ventricular function in hypercholesterolemic survivors of a previous Q-wave acute myocardial infa rct ion . Left ventricular radionuclide imaging was performed at rest and during submaximal exercise and global and segmental ( nine segment regional wall-motion score ) ejection fractions were measured before treatment and 12 weeks later . Serum ubiquinone was reduced after treatment ( p = 0.03 ) in the S but not the F group , whereas total and low-density lipoprotein ( LDL ) cholesterol were significantly reduced in both groups . Before treatment , mean global ejection fraction was 52.1+/-12.2 % and 49.3+/-11.8 % at rest in F and S patients , respectively , and increased ( 56.0+/-13.7 % in F and 52.1+/-12.9 % in S ) at peak exercise ( no difference between groups ) . After treatment , the increase in ejection fraction tended to be lower in S ( 0 ) than in F ( + 3.8 % ) but not significantly . However , ejection fraction at rest increased after treatment in S ( p = 0.009 ) but not in F. Subgroup analyses indicated that the improvement in rest ejection fraction in S was essentially observed in patients with ejection fraction 40 % ( + 1.8 % ) . Finally , the numbers of akinetic or hypokinetic segments at rest and during exercise were not different in the two groups before and after treatment . Mean maximal exercise load ( 113+/-23 watts in F vs. 104+/-27 W in S before treatment ) was not modified by the treatment ( 111+/-21 and 104+/-27 W ) . Thus a 12-week lipid-lowering treatment with either S or F did not negatively alter left ventricular function during exercise in dyslipidemic patients with established coronary heart disease and did not affect their ability to exercise . The improvement in left ventricular function at rest after simvastatin in patients with left ventricular dysfunction warrants confirmation in further studies with large sample size", "Vein graft atherosclerosis is a common and serious complication of coronary artery bypass grafting ( CABG ) . There is mounting evidence that lipoprotein abnormalities play an equally important role in the development of lesions in saphenous vein grafts after CABG as in native coronary vessel disease . The potential benefit of low‐dose lipid lowering combination therapy in these patients has not been investigated . In a r and omized , double‐blind , placebo‐controlled study , we compared the efficacy and safety of a low‐dose combination of colestipol 10 g and simvastatin 10 mg/day ( CS ) to colestipol 10 mg and bezafibrate 400 mg/day ( CB ) for 2 months in 33 patients with serum total cholesterol > 6.5 mmol/l and triglyceride In the CS group , total cholesterol decreased by 29 % and low‐density lipoprotein ( LDL ) cholesterol by 42 % ; similarly , CB reduced total cholesterol by 17 % , LDL cholesterol by 23 % , triglyceride by 19 % , and increased high‐density lipoprotein ( HDL ) cholesterol by 14 % . Lipoprotein ( a ) and hemostatic factors were unaffected by either therapy in this study . Both combination therapies were well tolerated with no significant clinical or biochemical side effects . We conclude that low‐dose combinations of colestipol and simvastatin or colestipol and bezafibrate are effective and well tolerated in the management of moderate hyperlipidemia in patients who had undergone CABG", "OBJECTIVE To examine the atherogenic risk-reducing effect of bezafibrate and lovastatin . DESIGN , SETTING , PATIENTS , INTERVENTIONS Double-blind , r and omized clinical trial of male and female patients with moderate hypercholesterolaemia with or without hypertriglyceridaemia . Two months dietary treatment followed by 400 mg sustained release bezafibrate every day or 20 mg lovastatin every day for 6 months . Patients recruited ( n = 561 ) and treated ( n = 524 ) by primary care physicians throughout Austria . MAIN OUTCOME MEASURES Multifactorial assessment of atherogenic risk profile . RESULTS Bezafibrate increased high density lipoprotein cholesterol by 16 % , lovastatin by 10 % ( P Bezafibrate decreased low density lipoprotein cholesterol by 20 % , lovastatin by 27 % ( P Bezafibrate decreased total cholesterol by 15 % , lovastatin by 18 % ( P Bezafibrate reduced triglycerides by 29 % , lovastatin by 13 % ( P fibrinogen by 9.4 % and 3.0 % , respectively . Fibrinogen reduction as a result of bezafibrate administration was dependent on starting levels . The risk ratio cholesterol : high density lipoprotein cholesterol ( baseline both 6.1 ) reduction was 27 % in both groups . The low : high density lipoprotein ratio ( baseline : 4.1/4.2 ) reduction reached 31 % and 34 % respectively . Coronary events ' probability ( calculated from multifactorial risk functions ) were greatly reduced by both agents ( 41%/33 % ) . Hypertriglyceridaemic patients had a higher initial global coronary risk and profited more from treatment . Bezafibrate was significantly better tolerated ( P lovastatin ; most events were gastrointestinal ( 6 vs 14 , ns ) or as a result of creatine phosphokinase elevations ( 3 vs 12 , P risk parameters for developing coronary heart disease , and calculated multifactorial coronary risk was similarly decreased . When selecting a drug for moderate dyslipidaemia and if haemostatic regulation is disturbed , the additional effect of bezafibrate on elevated fibrinogen levels should be considered", "In order to assess the efficacy of gemfibrozil on lipid and haemostatic parameters in patients with plurimetabolic syndrome , a multicenter double-blind placebo controlled , parallel study was carried out in 56 patients with primary hypertriglyceridemia and glucose intolerance . These patients had elevated PAI activity and antigen and t-PA antigen levels at rest and after venous occlusion . Gemfibrozil reduced plasma triglyceride levels ( P free fatty acids ( P high density lipoprotein cholesterol levels ( P plasma triglyceride levels ( triglyceride reduction > or = 50 % ) ( n=15 ) , insulin levels ( P insulin resistance index were reduced by gemfibrozil treatment , suggesting an improvement of the insulin resistance index in this patient subgroup . Gemfibrozil treatment did not affect plasma fibrinolysis or fibrinogen levels , despite marked reduction of plasma triglycerides and improvement of the insulin sensitivity associated with triglyceride normalization", "AIM OF THE STUDY We studied the effects of fluvastatin and bezafibrate in monotherapy and in combination on plasma fibrinogen , t-plasminogen activator inhibitor ( PAI-1 ) and C reactive protein ( CRP ) in patients with coronary artery disease ( CAD ) and mixed hyperlipidaemia . DESIGN In this r and omised , double blind , multicentre trial 333 patients with stable angina pectoris or previous myocardial infa rct ion or coronary revascularisation and mixed hyperlipidaemia ( LDL-cholesterol 135 - 250 mg/dl and triglycerides ( TG ) 180 - 400 mg/dl ) were r and omised to fluvastatin 40 mg , bezafibrate 400 mg , fluvastatin 20 mg + bezafibrate 400 mg or fluvastatin 40 mg + bezafibrate 400 mg treatments for 24 weeks . RESULTS Plasma fibrinogen significantly decreased after treatment with the combinations fluvastatin+bezafibrate ( -14 and -16 % ) and with bezafibrate monotherapy ( -9 % ) . No significant reduction was observed after fluvastatin monotherapy ( -4 % ) . No significant changes were observed in PAI-1 and CRP plasma levels . Combination therapy significantly decreased both LDL-C and TG , and significantly increased HDL-C. CONCLUSIONS The combined effects on fibrinogen and plasma lipids achieved by fluvastatin and bezafibrate combination treatment might be more useful than the simple reduction of cholesterol in preventing ischaemic cardiovascular disease", "Diabetic dyslipoproteinemia characterized by hypertriglyceridemia , low high-density lipoprotein ( HDL ) cholesterol , and often elevated low-density lipoprotein ( LDL ) cholesterol with predominance of small , dense LDL is a strong risk factor for atherosclerosis . It is unclear whether fibrate or statin therapy is more effective in these patients . We compared atorvastatin ( 10 mg/day ) with fenofibrate ( 200 mg/day ) , each for 6 weeks separated by a 6-week washout period in 13 patients ( 5 men and 8 women ; mean age 60.0+/-6.8 years ; body mass index 30.0+/-3.0 kg/m2 ) with type 2 diabetes mellitus ( hemoglobin A1c 7.3+/-1.1 % ) and mixed hyperlipoproteinemia ( LDL cholesterol 164.0+/-37.8 mg/dl , triglycerides 259.7+/-107 mg/dl , HDL cholesterol 48.7+/-11.0 mg/dl ) using a r and omized , crossover design . Lipid profiles , LDL subfraction distribution , fasting plasma viscosity , red cell aggregation , and fibrinogen concentrations were determined before and after each drug . Atorvastatin decreased all LDL subfractions ( LDL cholesterol , -29 % ; p small , dense LDL . Fenofibrate predominantly decreased triglyceride concentrations ( triglycerides , -39 % ; p LDL subtype distribution from small , dense LDL ( -31 % ) to intermediate-dense LDL ( + 36 % ) . The concentration of small , dense LDL was comparable during therapy to both drugs ( atorvastatin 62.8+/-19.5 mg/dl , fenofibrate 63.0+/-18.1 mg/dl ) . Both drugs induced an increase in HDL cholesterol ( atorvastatin + 10 % , p fibrinogen concentration ( -15 % , p plasma viscosity by 3 % ( p red cell aggregation by 15 % ( p atorvastatin and fenofibrate can improve lipoprotein metabolism in type 2 diabetes . However , the medications affect different aspects of lipoprotein metabolism", "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", "BACKGROUND Coadministration of statin and fenofibrate monotherapies is frequently used to treat patients with dyslipidemia ; however , a fixed-dose combination ( FDC ) tablet is not currently marketed . OBJECTIVE This study evaluates a new FDC tablet of atorvastatin 40 mg and fenofibrate 100 mg . METHODS This was a 12-week , multicenter , double-blind , r and omized , parallel-group Phase IIb study . Adults with dyslipidemia ( non-HDL-C > 130 mg/dL and triglycerides [ TG ] > or = 150 but were r and omly assigned in a 1:1:1 ratio to receive the FDC , atorvastatin 40 mg , or fenofibrate 145 mg for 12 weeks . Study medication was taken once daily in the evening , without regard to meals . Patients attended follow-up visits after 4 , 8 , and 12 weeks of the double-blind treatment . The primary efficacy end points were the mean percentage changes from baseline to the final visit ( week 12 ) in non-HDL-C , HDL-C , and TG . Secondary variables were LDL-C , VLDL-C particle concentration , total cholesterol , apolipoprotein B , lipoprotein ( a ) , high-sensitivity C-reactive protein , fibrinogen , homocysteine , creatinine , myeloperoxidase , and lipoprotein-associated phospholipase A2 . Tolerability was assessed by adverse events , laboratory parameters , vital signs , physical examinations , and ECGs . RESULTS Patients ( n = 220 ) were aged 26 to 87 years ; 115 ( 52.3 % ) were men and 105 ( 47.7 % ) were women ; 189 ( 85.9 % ) were white , 17 ( 7.7 % ) were black , and 15 ( 6.8 % ) were Hispanic or Latino ; and mean ( SD ) weight was 200.5 ( 40.85 ) lb ( range , 103.5 - 367.4 lb ) . Previous treatments were statins ( 25.9 % [ 57/220 ] ) , fibrates ( 1.8 % [ 4/220 ] ) , and dietary supplements ( 25.5 % [ 56/220 ] ) ; 57.7 % ( 127/220 ) of patients were treatment naive . Use of the FDC was associated with an improvement in non-HDL-C ( -44.8 % ) that was significantly greater than with fenofibrate monotherapy ( -16.1 % ; P P = NS ) . HDL-C increased significantly more in the FDC group ( 19.7 % ) than with atorvastatin ( 6.5 % ; P NS ) . TG lowering in the FDC group ( -49.1 % ) was significantly greater than with both atorvastatin ( -28.9 % ; P 0.001 ) . LDL-C lowering in the FDC group ( -42.3 % ) was significantly greater than with fenofibrate ( -13.9 % ; P other lipid variables and multiple secondary variables . The FDC was generally well tolerated ; the tolerability profile was consistent with those of atorvastatin and fenofibrate monotherapies . Treatment-emergent adverse events ( ie , those occurring after the first dose of study medication ) were recorded in 43 of 73 patients ( 58.9 % ) for the FDC , 49 of 74 ( 66.2 % ) for atorvastatin , and 48 of 73 ( 65.8 % ) for fenofibrate . CONCLUSIONS In this 12-week study , patients with dyslipidemia treated with the 40/100-mg atorvastatin/ fenofibrate FDC had a significantly greater reduction in TG than those treated with atorvastatin 40 mg or higher-dose fenofibrate 145 mg . Treatment with the FDC was also associated with a significantly greater reduction in non-HDL-C compared with fenofibrate alone and a greater increase in HDL-C compared with atorvastatin alone . All treatments were generally well tolerated", "The safety and efficacy of combined bezafibrate-simvastatin therapy was evaluated in 49 patients with diet-resistant mixed hyperlipidaemia ( type IIb ) . After a two-month placebo phase , patients were r and omized to receive either Bezafibrate Slow Release ( SR ) 400 mg mane or simvastatin 20 mg nocte followed by three months combination therapy . Total cholesterol , triglycerides and high-density lipoprotein ( HDL ) cholesterol were measured at monthly intervals . Apolipoproteins ( apo ) A1 and B , lipoprotein ( a ) [ Lp(a ) ] and fibrinogen were measured before and after each treatment . Simvastatin was more effective than Bezafibrate SR in reducing total cholesterol ( 2.0 vs. 1.1 mmol/l , p = 0.003 ) and lowering LDL cholesterol ( 1.7 vs. 0.4 mmol/l , p = 0.0001 ) whereas Bezafibrate SR was more effective in reducing triglycerides ( by 41 % vs. 17 % , p = 0.001 ) and fibrinogen ( by 23 % vs. 3 % , p = 0.004 ) . Compared with simvastatin monotherapy , combined drug therapy induced further reductions in triglycerides ( by 26 % , p = 0.0003 ) and apoB ( by 11 mg/dl , p = 0.03 ) and an increase in apoA1 ( by 21 mg/dl , p = 0.0008 ) . Symptomatic and biochemical adverse events did not occur more frequently on combined drug therapy than on monotherapy . The combination of bezafibrate and simvastatin was more effective in controlling mixed hyperlipidaemia than either drug alone and did not provoke more adverse events", "Accelerated coronary artery disease is the most serious obstacle to long-term survival in heart transplant recipients . Hyperlipemia , hyperinsulinism , and changes in endothelial cell hemostatic function have been implicated in cardiac allograft vascular disease . Both lovastatin and bezafibrate are safe , effective , and well tolerated therapies for hyperlipidemia . Our study compares the effect of these lipid-lowering drugs in 21 patients with post-heart transplantation hyperlipidemia on different risk factors related to insulin resistance syndrome . Patients were given the same diet for 3 months , then r and omized to lovastatin or bezafibrate for a period of 8 weeks , and crossed over to an additional 8 weeks of either bezafibrate or lovastatin . Baseline parameters were also compared with those of a control group of healthy subjects and after both periods of pharmacologic treatment . Transplant patients had higher insulin ( 35 + /- 3 vs 24 + /- 3 microIU/L ) , fibrinogen ( 298 + /- 15 vs 261 + /- 14 mg/dl ) , and plasminogen activator inhibitor-1 ( PAI-1 ) ( 17 + /- 2 vs 11.7 + /- 2 arbitrary units/ml ) plasma levels than controls . Significant decreases in insulin ( -37 + /- 3 % ) , fibrinogen ( -12 + /- 4 % ) , and PAI-1 plasma levels ( -18 + /- 12 % ) were only observed after bezafibrate treatment . In conclusion , bezafibrate decreases plasma insulin , fibrinogen , and PAI-1 in hyperlipidemic heart transplant recipients", "Hyperlipidemia is an important risk factor for atherosclerosis . Hemorheological factors contribute to morbidity and mortality in patients with dyslipidemia . We evaluated the effects of 3 antihyperlipidemic drugs ( pravastatin , atorvastatin , and fenofibrate ) , which have different mechanisms of action and different patterns of action on lipid profiles , on erythrocyte deformability and fibrinogen levels in patients with type IIa and type IIb hyperlipidemia . Twenty-one patients ( 4 men and 17 women ) with type IIa and IIb hyperlipidemia were r and omized to 3 drugs ( pravastatin 20 mg/d , atorvastatin 10 mg/d , fenofibrate 250 mg/d ) for 8 weeks . Plasma glucose , total cholesterol , triglyceride , high-density lipoprotein cholesterol ( HDL-C ) , and low-density lipoprotein cholesterol ( LDL-C ) analysis were performed on a BM-Hitachi 747 - 200 autoanalyzer ( Hitachi-Roche , Tokyo , Japan ) . Fibrinogen analysis was performed according to Clauss method . Erythrocyte deformability was assessed with cell transit analysis device . There was no significant difference in body mass index , lipid profile , fibrinogen level , and erythrocyte deformability index values among the groups before treatment ( P > .05 ) . In all groups , there were statistically significant reductions in total LDL-C levels ( P triglyceride levels were significantly reduced in the atorvastatin and fenofibrate groups ( P .05 ) . There was no significant change in HDL-C levels during the treatment with statins ( P > .05 ) , but there was a significant increase in the fenofibrate group ( P Mean erythrocyte deformability index was improved in all the groups ( P fibrinogen levels during the treatment of pravastatin and atorvastatin ( P > .05 ) , but in fenofibrate group , fibrinogen levels were significantly decreased ( P erythrocyte deformability index . Only fenofibrate has significant beneficial effects on the fibrinogen levels", "Evaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects . A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent . We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator ( t-PA ) , plasminogen activator inhibitor-1 ( PAI-1 ) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen . Although both fibrates effectively lowered triglyceride and cholesterol levels , no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment . However , both fibrates influenced plasma fibrinogen levels , albeit in a different way . Fibrinogen antigen levels were elevated by 17.6 % ( p gemfibrozil after six and twelve weeks , respectively , whereas with ciprofibrate there was no effect . Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point , no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment . However , after twelve weeks , gemfibrozil enhanced functional fibrinogen levels by 7.2 % ( p functional fibrinogen levels by 12.5 % ( p ciprofibrate treatment , functional fibrinogen levels were decreased by 10.1 % ( p functionality of fibrinogen as assessed by the ratio of functional fibrinogen ( determined by either of the two Clauss assays ) to fibrinogen antigen . Taken together , our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates , by differences in treatment period and /or by the different outcomes of various assay systems . Interestingly , the two fibrates tested both reduced the functionality of fibrinogen", "A double-blind , placebo-controlled , cross-over study was conducted in 21 men with combined hyperlipoproteinaemia to examine if lipid-lowering treatment with gemfibrozil ( 10 - 12 weeks ) affects blood coagulation and fibrin gel structure at rest or during mental stress . Gemfibrozil lowered plasma triglycerides by 57 + /- 4 % , whereas high density lipoprotein ( HDL ) cholesterol increased by 22 + /- 5 % . Gemfibrozil lowered the triglyceride content of low density lipoprotein ( LDL ) . Gemfibrozil reduced the plasma concentrations of thrombin-antithrombin complex ( TAT ) and prothrombin fragment F1 + 2 ( F1 + 2 ) , both at rest and during mental stress . However , there were no effects of gemfibrozil treatment on the plasma concentrations of fibrinogen , factor VII antigen , activated factor VII ( VIIa ) or activated factor XII ( XIIa ) , or on fibrin gel structure . Acute mental stress per se did not influence coagulation factors , reaction products or fibrin gel structure , or their responses to the study drug . Thus , gemfibrozil reduced thrombin generation in men with combined hyperlipoproteinaemia , without influencing the plasma levels of fibrinogen , VIIa and XIIa , or fibrin gel structure . Attenuation of thrombin generation may contribute to the primary -preventive effects of gemfibrozil on coronary heart disease", "Background Hypolipidaemic agents do not usually normalize all of the multiple lipoprotein abnormalities in patients with familial combined hyperlipidaemia ( FCHL ) . The effect of the simvastatin-ciprofibrate combination in comparison with each drug alone on the lipoprotein abnormality patterns was studied in patients with FCHL and coronary artery disease ( CAD ) . Methods Sixty patients ( 53 men and seven women ) , mean age 52 years ( range 36–60 years ) , were studied . After a 4-week placebo period , patients were r and omly assigned to three groups . The first group ( n = 20 ) received simvastatin ( 20 mg daily ) , the second group ( n = 20 ) ciprofibrate ( 100 mg daily ) and the third group ( n = 20 ) the combination of both drugs for a 1 2-week period . Parameters measured were as follows : plasma fibrinogen , total cholesterol , triglycerides , low density lipoprotein ( LDL ) , very low density lipoprotein , intermediate density lipoprotein , and high density lipoprotein cholesterol , as well as LDL subfraction distribution and structure by density gradient ultracentrifugation . Apoproteins ( apo ) B and Al were assessed by immunoturbidometry . Results At baseline , apoB , LDL cholesterol and triglycerides were increased , whereas LDL particles were small and dense . ApoB was significantly reduced by all three interventions . Drug combination and ciprofibrate significantly reduced plasma fibrinogen ( -24 and −25 % , respectively ; P and triglycerides ( -51 and −49 % , respectively ; P combination and simvastatin significantly reduced LDL cholesterol ( -25 and −22 % , respectively ; P with ciprofibrate ( -10 % ; P ) . Ciprofibrate and drug combination increased LDL particle size ( parameter K −0.24 versus −0.61 and −0.30 versus −0.62 , respectively ; P whereas simvastatin had no significant effect on LDL particle size . The cholesterol content of LDL particles was reduced with ciprofibrate and the drug combination only in the dense LDL particles ( LDL3–5 ) and increased in the light ( LDL1–2 ) subfractions , whereas simvastatin reduced the cholesterol content of all LDL subfractions except LDL2 . Ciprofibrate and drug combination reduced the triglyceride content of al ! LDL subfractions . Conclusion Combined treatment with simvastatin and ciprofibrate effectively reduced plasma fibrinogen , triglycerides , total and LDL cholesterol and increased LDL particle size in patients with FCHL and CAD . These effects might induce a clinical benefit for these patients", "In 12 weeks of active treatment , we compared the efficacy and safety of a new ( micronized ) formulation of fenofibrate ( F ) ( 200 mg/day ) with that of simvastatin ( S ) ( 20 mg/day ) , an inhibitor of hydroxy-methyl-glutaryl coenzyme A (HMG-CoA)-reductase . Men and women with primary hyperlipoproteinemia ( HLP ) with low-density lipoprotein ( LDL ) cholesterol level 180 - 300 mg/dl and triglyceride level The decrease in total cholesterol differed between type IIa patients ( F - 17.9 vs. S - 25.8 % ) , the decrease in triglyceride levels between the type II b groups ( F - 52.8 vs. S - 14 % ) , whereas the degree of decrease in LDL cholesterol ( F - 20.9 vs. S - 34.9 % ) differed among all patients . Despite the difference in LDL cholesterol decrease , no difference was noted in total apolipoprotein ( apo ) B lowering ( F - 20.8 and S - 26.5 % ) . Increases in high-density lipoprotein ( HDL ) cholesterol ( F + 18.5 vs. S + 15 % ) differed specifically in type IIb patients ( F + 33.6 vs. S + 11.4 % ) , accompanied by a more pronounced increase in apo AI with fenofibrate ( F + 10.5 % vs. S no change ) . Improvement in the ratios of total cholesterol/HDL cholesterol and apo AI/apo B occurred similarly with both drugs . Only fenofibrate , not simvastatin , decreased both fibrinogen ( -10.3 vs. + 3.6 % ) and uric acid ( -25 % vs. no change ) in type IIa and type IIb patients . Safety parameters reflected drug-specific known side effects , underscoring the safety of both drugs in addition to their efficacy in lipid lowering . Besides its advantages in type IIb hyperlipidemia , micronized fenofibrate proved a potent drug in decreasing total and LDL cholesterol and in very effectively decreasing apo B-containing lipoproteins , which is a recommendation for its use in primary hypercholesterolemia", "AIMS Assess insulin sensitivity after treatment with a selective PPAR-alpha agonist compared to an HMG CoA reductase inhibitor in human subjects with type 2 diabetes mellitus . METHODS Thirteen subjects with Type 2 diabetes mellitus were studied in a double-blind crossover design with 4-week placebo run-in and washout and 12-week treatment periods , r and omised to micronised fenofibrate 267 mg or atorvastatin 10 mg daily followed by the alternate drug in the second period . Insulin resistance was measured using the isoglycaemic hyperinsulinaemic clamp method with isotope dilution . RESULTS Weight , physical activity and other medications did not change . Total cholesterol ( mean + /- st and ard error ) was 4.60+/-0.21 versus 3.9+/-0.22 mmol/L after fenofibrate and atorvastatin respectively , p LDL was 2.70+/-0.19 versus 1.95+/-0.23 mmol/L , p triglyceride 1.64+/-0.23 versus 1.84+/-0.26 mmol/L , p Insulin-stimulated whole-body glucose disposal ( 35.4+/-3.1 versus 33.2+/-3.0 μmol/kg/min ) and nadir endogenous glucose production ( 6.2+/-1.4 versus 7.0+/-1.1 μmol/kg/min ) revealed no significant differences in effects of the treatments . CONCLUSIONS In human subjects with Type 2 diabetes mellitus there were characteristic differences in lipid profile changes but no difference in insulin sensitivity after treatment with micronised fenofibrate compared to atorvastatin . This study finds no evidence of increased insulin sensitivity using this selective PPAR-alpha agonist over a commonly used statin at these doses" ]

[ "Background Both low back pain ( LBP ) and neck pain ( NP ) are major occupational health problems . In the workplace , participatory ergonomics ( PE ) is frequently used on musculoskeletal disorders . However , evidence on the effectiveness of PE to prevent LBP and NP obtained from r and omised controlled trials ( RCTs ) is scarce . This study evaluates the process of the Stay@Work participatory ergonomics programme , including the perceived implementation of the prioritised ergonomic measures . Methods This cluster- RCT was conducted at the departments of four Dutch companies ( a railway transportation company , an airline company , a steel company , and a university including its university medical hospital ) . Directly after the r and omisation outcome , intervention departments formed a working group that followed the steps of PE during a six-hour working group meeting . Guided by an ergonomist , working groups identified and prioritised risk factors for LBP and NP , and composed and prioritised ergonomic measures . Within three months after the meeting , working groups had to implement the prioritised ergonomic measures at their department . Data on various process components ( recruitment , reach , fidelity , satisfaction , and implementation components , i.e. , dose delivered and dose received ) were collected and analysed on two levels : department ( i.e. , working group members from intervention departments ) and participant ( i.e. , workers from intervention departments ) . Results A total of 19 intervention departments ( n = 10 with mental workloads , n = 1 with a light physical workload , n = 4 departments with physical and mental workloads , and n = 4 with heavy physical workloads ) were recruited for participation , and the reach among working group members who participated was high ( 87 % ) . Fidelity and satisfaction towards the PE programme rated by the working group members was good ( 7.3 or higher ) . The same was found for the Stay@Work ergocoach training ( 7.5 or higher ) . In total , 66 ergonomic measures were prioritised by the working groups . Altogether , 34 % of all prioritised ergonomic measures were perceived as implemented ( dose delivered ) , while the workers at the intervention departments perceived 26 % as implemented ( dose received ) . Conclusions PE can be a successful method to develop and to prioritise ergonomic measures to prevent LBP and NP . Despite the positive rating of the PE programme the implementation of the prioritised ergonomic measures was lower than expected . Trial registration Current Controlled Trials IS RCT", "Background Effective interventions to influence workplace sitting are needed , as office-based workers demonstrate high levels of continued sitting , and sitting too much is associated with adverse health effects . Therefore , we developed a theory-driven , Web-based , interactive , computer-tailored intervention aim ed at reducing and interrupting sitting at work . Objective The objective of our study was to investigate the effects of this intervention on objective ly measured sitting time , st and ing time , and breaks from sitting , as well as self-reported context -specific sitting among Flemish employees in a field-based approach . Methods Employees ( n=213 ) participated in a 3-group r and omized controlled trial that assessed outcomes at baseline , 1-month follow-up , and 3-month follow-up through self-reports . A sub sample ( n=122 ) were willing to wear an activity monitor ( activPAL ) from Monday to Friday . The tailored group received an automated Web-based , computer-tailored intervention including personalized feedback and tips on how to reduce or interrupt workplace sitting . The generic group received an automated Web-based generic advice with tips . The control group was a wait-list control condition , initially receiving no intervention . Intervention effects were tested with repeated- measures multivariate analysis of variance . Results The tailored intervention was successful in decreasing self-reported total workday sitting ( time × group : P sitting at work ( time × group : P and leisure time sitting ( time × group : P=.03 ) , and in increasing objective ly measured breaks at work ( time × group : P=.07 ) ; this was not the case in the other conditions . The changes in self-reported total nonworkday sitting , sitting during transport , television viewing , and personal computer use , objective ly measured total sitting time , and sitting and st and ing time at work did not differ between conditions . Conclusions Our results point out the significance of computer tailoring for sedentary behavior and its potential use in public health promotion , as the effects of the tailored condition were superior to the generic and control conditions . Trial Registration Clinical trials.gov NCT02672215 ; http:// clinical trials.gov/ct2/show/NCT02672215 ( Archived by WebCite at http://www.webcitation.org/6glPFBLWv", "Background Arm , shoulder and neck symptoms are very prevalent among computer workers . In an attempt to reduce these symptoms , a large occupational health service in the Netherl and s developed a preventive programme on exposure to risk factors , prevalence of arm , shoulder and neck symptoms , and sick leave in computer workers . The purpose of this study was to assess the effectiveness of this intervention programme . Methods The study was a r and omised controlled trial . The participants were assigned to either the intervention group or the usual care group by means of cluster r and omisation . At baseline and after 12 months of follow-up , the participants completed the RSI QuickScan question naire on exposure to the risk factors and on the prevalence of arm , shoulder and neck symptoms . A tailor-made intervention programme was proposed to participants with a high risk profile at baseline . Examples of implemented interventions are an individual workstation check , a visit to the occupational health physician and an education programme on the prevention of arm , shoulder and neck symptoms . The primary outcome measure was the prevalence of arm , shoulder and neck symptoms . Secondary outcome measures were the scores on risk factors for arm , shoulder and neck symptoms and the number of days of sick leave . Sick leave data was obtained from the companies . Multilevel analyses were used to test the effectiveness . Results Of the 1,673 persons invited to participate in the study , 1,183 persons ( 71 % ) completed the baseline question naire and 741 persons participated at baseline as well as at 12-month follow-up . At 12-month follow-up , the intervention group showed a significant positive change ( OR = 0.48 ) in receiving information on healthy computer use , as well as a significant positive change regarding risk indicators for work posture and movement , compared to the usual care group . There were no significant differences in changes in the prevalence of arm , shoulder and neck symptoms or sick leave between the intervention and usual care group . Conclusions The effects of the RSI QuickScan intervention programme were small , possibly as a result of difficulties with the implementation process of the proposed interventions . However , some significant positive effects were found as to an increase in receiving education and a decrease in exposure to adverse postures and movements . With regard to symptoms and sick leave , only small and non-significant effects were found . Trial registration Netherl and s National Trial Register", "BACKGROUND This study exp and ed previous NIOSH-IRS research examining the effects of rest breaks and stretching exercises on symptoms and performance in data -entry workers . METHODS All workers spent 4 weeks with conventional breaks ( two 15 min breaks per day ) and 4 weeks with supplementary breaks ( two 15 min breaks plus four 5 min breaks per day ) . One-half were assigned at r and om to a group instructed to perform brief stretching exercises during breaks . The remainder comprised the \" no stretching \" ( control ) group . RESULTS 51 workers ( stretch group n = 21 ; no stretch group n = 30 ) completed the study symptom question naires . Discomfort and eyestrain were significantly lower with supplementary breaks , and supplementary breaks attenuated accumulation of discomfort and eyestrain during work sessions . Data -entry speed was significantly faster with supplementary breaks so that work output was maintained , despite replacing 20 min of work time with break time . In the stretch group , workers reported stretching during only 25 % of conventional breaks and 39 % of supplementary breaks , and no significant effects of stretching on discomfort or performance were observed . CONCLUSIONS These results provide further converging evidence that supplementary breaks reliably minimize discomfort and eyestrain without impairing productivity . Low compliance in performing stretches prevented valid assessment of stretching effects . Further research on stretching exercises and exercise compliance is warranted", "Background Low back pain ( LBP ) and neck pain ( NP ) are a major public health problem with considerable costs for individuals , companies and society . Therefore , prevention is imperative . The Stay@Work study investigates the (cost-)effectiveness of Participatory Ergonomics ( PE ) to prevent LBP and NP among workers . Methods In a r and omised controlled trial ( RCT ) , a total of 5,759 workers working at 36 departments of four companies is expected to participate in the study at baseline . The departments consisting of about 150 workers are pre-stratified and r and omised . The control departments receive usual practice and the intervention departments receive PE . Within each intervention department a working group is formed including eight workers , a representative of the management , and an occupational health and safety coordinator . During a one day meeting , the working group follows the steps of PE in which the most important risk factors for LBP and NP , and the most adequate ergonomic measures are identified on the basis of group consensus . The implementation of ergonomic measures at the department is performed by the working group . To improve the implementation process , so-called ' ergocoaches ' are trained . The primary outcome measure is an episode of LBP and NP . Secondary outcome measures are actual use of ergonomic measures , physical workload , psychosocial workload , intensity of pain , general health status , sick leave , and work productivity . The cost-effectiveness analysis is performed from the societal and company perspective . Outcome measures are assessed using question naires at baseline and after 6 and 12 months . Data on the primary outcome as well as on intensity of pain , sick leave , work productivity , and health care costs are collected every 3 months . Discussion Prevention of LBP and NP is beneficial for workers , employers , and society . If the intervention is proven (cost-)effective , the intervention can have a major impact on LBP and NP prevention and , thereby , on work disability prevention . Results are expected in 2010.Trial registration IS RCT", "Background Excessive sitting time is a risk factor for cardiovascular disease mortality and morbidity independent of physical activity . This aim of this study was to evaluate the impact of a sit-st and workstation on sitting time , and vascular , metabolic and musculoskeletal outcomes in office workers , and to investigate workstation acceptability and feasibility . Methods A two-arm , parallel-group , individually r and omised controlled trial was conducted in one organisation . Participants were asymptomatic full-time office workers aged ≥18 years . Each participant in the intervention arm had a sit-st and workstation installed on their workplace desk for 8 weeks . Participants in the control arm received no intervention . The primary outcome was workplace sitting time , assessed at 0 , 4 and 8 weeks by an ecological momentary assessment diary . Secondary behavioural , cardiometabolic and musculoskeletal outcomes were assessed . Acceptability and feasibility were assessed via question naire and interview . ANCOVA and magnitude-based inferences examined intervention effects relative to controls at 4 and 8 weeks . Participants and research ers were not blind to group allocation . Results Forty-seven participants were r and omised ( intervention n = 26 ; control n = 21 ) . Relative to the control group at 8 weeks , the intervention group had a beneficial decrease in sitting time ( −80.2 min/8-h workday ( 95 % CI = −129.0 , −31.4 ) ; p = 0.002 ) , increase in st and ing time ( 72.9 min/8-h workday ( 21.2 , 124.6 ) ; p = 0.007 ) and decrease in total cholesterol ( −0.40 mmol/L ( −0.79 , −0.003 ) ; p = 0.049 ) . No harmful changes in musculoskeletal discomfort/pain were observed relative to controls , and beneficial changes in flow-mediated dilation and diastolic blood pressure were observed . Most participants self-reported that the workstation was easy to use and their work-related productivity did not decrease when using the device . Factors that negatively influenced workstation use were workstation design , the social environment , work tasks and habits . ConclusionS hort-term use of a feasible sit-st and workstation reduced daily sitting time and led to beneficial improvements in cardiometabolic risk parameters in asymptomatic office workers . These findings imply that if the observed use of the sit-st and workstations continued over a longer duration , sit-st and workstations may have important ramifications for the prevention and reduction of cardiometabolic risk in a large proportion of the working population .Trial registration Clinical Trials.gov NCT02496507", "Objectives Prolonged sitting at work has been found to increase risk for musculoskeletal pain . The office-based intervention \" Take a St and ! \" was effective in reducing sitting time at work . We aim ed to study the effect of the intervention on a secondary outcome : musculoskeletal pain . Methods Take a St and ! included 19 offices ( 317 workers ) at four workplaces cluster r and omized to intervention or control . The multicomponent intervention lasted three months and included management support , environmental changes , and local adaptation . Control participants behaved as usual . Musculoskeletal pain was measured by self-report question naire assessing pain in neck-shoulders , back and extremities in three categories at baseline , and one and three months follow-up . Results At one month , there was no difference in odds ratio ( OR ) for pain in neck-shoulders between the two groups . However , after three months , the OR was 0.52 [ 95 % confidence interval ( 95 % CI ) 0.30 - 0.92 ] for pain in neck-shoulders in the intervention compared to the control group . No differences were found between the intervention and control group for pain in back and extremities over the three months . For total pain score a slight reduction was found in the intervention compared to the control group at one and three months [ -0.13 ( 95 % CI -0.23- -0.03 ) and -0.17 ( 95 % CI -0.32- -0.01 ) ] . Conclusions The secondary analyses showed that the office-based intervention Take a St and ! reduced neck-shoulder pain after three months and total pain score after one and three months among office workers , but not neck-shoulder pain after one month or pain in the back and extremities", "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", "Health and safety literature stresses the value of programs aim ed at preventing musculoskeletal injuries . The concepts of empowerment learning are often recommended as guidelines for worker education yet these approaches are largely untested . The present study compares the traditional approach involving lecture and discussion with a participatory method . A sample of 102 participants employed at a central ized reservation facility was used . Participants were r and omly assigned to either the traditional education group or the participatory education group . Data collection utilized surveys completed by study participants and observational checklists completed by a trained observer . Data were collected prior to intervention and at approximately 3 , 6 , and 12 months post intervention . Results of data analysis provide no evidence that participatory methods are more effective than traditional methods in encouraging workers to position their work equipment correctly or to maintain good working postures to prevent musculoskeletal injuries", "OBJECTIVE The literature on psychosocial job factors and musculoskeletal pain is inconclusive in part due to insufficient control for confounding by biomechanical factors . The aim of this study was to investigate prospect ively the independent effects of effort-reward imbalance ( ERI ) at work on regional musculoskeletal pain of the neck and upper extremities of call center operators after controlling for ( i ) duration of computer use both at work and at home , ( ii ) ergonomic workstation design , ( iii ) physical activities during leisure time , and ( iv ) other individual worker characteristics . METHODS This was a one-year prospect i ve study among 165 call center operators who participated in a r and omized ergonomic intervention trial that has been described previously . Over an approximate four-week period , we measured ERI and 28 potential confounders via a question naire at baseline . Regional upper-body pain and computer use was measured by weekly surveys for up to 12 months following the implementation of ergonomic interventions . Regional pain change scores were calculated as the difference between average weekly pain scores pre- and post intervention . RESULTS A significant relationship was found between high average ERI ratios and one-year increases in right upper-extremity pain after adjustment for pre-intervention regional mean pain score , current and past physical workload , ergonomic workstation design , and anthropometric , sociodemographic , and behavioral risk factors . No significant associations were found with change in neck-shoulder or left upper-extremity pain . CONCLUSIONS This study suggests that ERI predicts regional upper-extremity pain in -computer operators working > or=20 hours per week . Control for physical workload and ergonomic workstation design was essential for identifying ERI as a risk factor", "Introduction : Lateral and medial epicondylitis associated with work activity is a common upper extremity musculoskeletal disorder with a prevalence of 4–30 % depending upon the work setting and diagnostic criteria . The influence of treatment , ergonomic factors , medical history , psychosocial variables , and aging on the improvement of symptoms has not been well defined . Methods : This was a prospect i ve cohort study of a cohort of 45 workers with active elbow tendonitis for an average of 13 months . Complete resolution of symptoms was the defined outcome measure . Results : The predictive factors for persistent elbow tendonitis included older age ( OR = 1.1 , 95 % CI : 0.99 , 1.33 ) , higher h and repetition level for their job(s ) ( OR = 2.5 , 95 % CI : 1.00 , 6.25 ) , more deviation from a neutral wrist position during the work activity ( OR = 2.0 , 95 % CI : 0.80 , 5.56 ) , and lower perceived decision authority on the job ( OR = 0.9 , 95 % CI : 0.79 , 0.98 ) . Other ergonomic , psychosocial , and electrophysiologic measures were not predictive . The models had relatively high sensitivity and specificity . Treatment effects could not be evaluated due to incomplete data available . Conclusions : Older workers with jobs requiring more repetition and awkward wrist postures , and less decision authority were less likely to have resolution of their elbow tendonitis . Implication s : Workers at highest risk for persistent elbow tendonitis should be placed at jobs with lower repetition levels and that use more neutral wrist postures . Effective interventions must address both the ergonomic and psychosocial risk factors in a multifaceted approach to this problem", "Objectives : To study the effectiveness of using a computer mouse with a feedback signal for upper extremity musculoskeletal symptoms in office workers . Methods : A r and omised controlled trial with 8 months of follow-up was carried out . The intervention consisted of a computer mouse with a feedback signal . In total , 354 subjects were allocated to the intervention group or the control group . Measurements were performed with electronic question naires at baseline , after 4 months and after 8 months . Outcome variables were the prevalence and incidence of upper extremity musculoskeletal symptoms and disability in the upper extremities . The intervention process was evaluated by software registration . Results : The use of the mouse with a feedback signal result ed in a significant decrease in duration of mouse usage over time . No differences were found in the number of mouse usage rest breaks . No differences were found in the prevalence ( p = 0.29 ) or incidence ( p = 0.832 ) of upper extremity musculoskeletal symptoms between the groups 8 months after baseline . The prevalence decreased from 49 % at baseline to 44 % after 8 months in the control group , while it remained at 36 % in the intervention group . The incidence was 21 % in the control group and 22 % in the intervention group . Among the population with upper extremity musculoskeletal symptoms at baseline , the risk of experiencing symptoms after 8 months did not differ between the groups ( p = 0.49 ) . Minor disability was found in both groups . In the intervention group , a lower level of physical disability over time was reported than in the control group ( p = 0.02 ) . Conclusions : A feedback signal computer mouse does not affect the prevalence and incidence of upper extremity musculoskeletal symptoms , but it does lower disability scores . Given the high prevalence , study ing preventive interventions for upper extremity musculoskeletal symptoms is of high importance . Trial registration number : IS RCT N13222474", "Objectives This study investigated the effectiveness of the Stay@Work participatory ergonomics programme to reduce workers′ exposure to psychosocial and physical risk factors . Methods 37 departments ( n=3047 workers ) from four Dutch companies participated in this cluster r and omised controlled trial ; 19 ( n=1472 workers ) were r and omised to an intervention group ( participatory ergonomics ) and 18 ( n=1575 workers ) to a control group ( no participatory ergonomics ) . During a 6 h meeting guided by an ergonomist , working groups devised ergonomic measures to reduce psychosocial and physical workload and implemented them within 3 months in their departments . Data on psychosocial and physical risk factors for low back pain and neck pain were collected at baseline and after 6 months . Psychosocial risk factors were measured using the Job Content Question naire and physical risk factors using the Dutch Musculoskeletal Question naire . Intervention effects were studied using multilevel analysis . Results Intervention group workers significantly increased on decision latitude ( 0.29 points ; 95 % CI 0.07 to 0.52 ) and decision authority ( 0.16 points ; 95 % CI 0.04 to 0.28 ) compared to control workers . However , exposure to awkward trunk working postures significantly increased in the intervention group ( OR 1.86 ; 95 % CI 1.15 to 3.01 ) compared to the control group . No significant differences between the intervention and control group were found for the remaining risk factors . After 6 months , loss to follow-up was 35 % in the intervention group and 29 % in the control group . Conclusion Participatory ergonomics was not effective in reducing exposure to psychosocial and physical risk factors for low back pain and neck pain among a large group of workers . Trial registration IS RCT N27472278", "Background : Call centre work with computers is associated with increased rates of upper body pain and musculoskeletal disorders . Methods : This one year , r and omised controlled intervention trial evaluated the effects of a wide forearm support surface and a trackball on upper body pain severity and incident musculoskeletal disorders among 182 call centre operators at a large healthcare company . Participants were r and omised to receive ( 1 ) ergonomics training only , ( 2 ) training plus a trackball , ( 3 ) training plus a forearm support , or ( 4 ) training plus a trackball and forearm support . Outcome measures were weekly pain severity scores and diagnosis of incident musculoskeletal disorder in the upper extremities or the neck/shoulder region based on physical examination performed by a physician blinded to intervention . Analyses using Cox proportional hazard models and linear regression models adjusted for demographic factors , baseline pain levels , and psychosocial job factors . Results : Post-intervention , 63 participants were diagnosed with one or more incident musculoskeletal disorders . Hazard rate ratios showed a protective effect of the armboard for neck/shoulder disorders ( HR = 0.49 , 95 % CI 0.24 to 0.97 ) after adjusting for baseline pain levels and demographic and psychosocial factors . The armboard also significantly reduced neck/shoulder pain ( p = 0.01 ) and right upper extremity pain ( p = 0.002 ) in comparison to the control group . A return-on-investment model predicted a full return of armboard and installation costs within 10.6 months . Conclusion : Providing a large forearm support combined with ergonomic training is an effective intervention to prevent upper body musculoskeletal disorders and reduce upper body pain associated with computer work among call centre employees", "Purpose The aim of the study was to determine effects of ergonomic intervention on work-related upper extremity musculoskeletal disorders ( WUEMSDs ) among computer workers . Methods Four hundred computer workers answered a question naire on work-related upper extremity musculoskeletal symptoms ( WUEMSS ) . Ninety-four subjects with WUEMSS using computers at least 3 h a day participated in a prospect i ve , r and omized controlled 6-month intervention . Body posture and workstation layouts were assessed by the Ergonomic Question naire . We used the Visual Analogue Scale to assess the intensity of WUEMSS . The Upper Extremity Function Scale was used to evaluate functional limitations at the neck and upper extremities . Health-related quality of life was assessed with the Short Form-36 . After baseline assessment , those in the intervention group participated in a multicomponent ergonomic intervention program including a comprehensive ergonomic training consisting of two interactive sessions , an ergonomic training brochure , and workplace visits with workstation adjustments . Follow-up assessment was conducted after 6 months . Results In the intervention group , body posture ( p workstation layout ( p = 0.002 ) improved over 6 months ; furthermore , intensity ( p duration ( p frequency ( p = 0.009 ) of WUEMSS decreased significantly in the intervention group compared with the control group . Additionally , the functional status ( p = 0.001 ) , and physical ( p and mental ( p = 0.035 ) health-related quality of life improved significantly compared with the controls . There was no improvement of work day loss due to WUEMSS ( p > 0.05 ) . Conclusions Ergonomic intervention programs may be effective in reducing ergonomic risk factors among computer workers and consequently in the secondary prevention of WUEMSDs", "This study was an economic evaluation conducted alongside a cluster r and omised controlled trial with a follow-up of 12 months . The aim was to evaluate the cost-effectiveness and cost-benefit of the Stay@Work Participatory Ergonomics programme ( PE ) compared to a control group ( no PE ) . In total , 37 departments ( n=3047 workers ) were r and omised into either the intervention ( PE ) or control group ( no PE ) . During a meeting , working groups followed the steps of PE , and composed and prioritized ergonomic measures aim ed to prevent low back pain ( LBP ) and neck pain ( NP ) . Working groups had to implement the ergonomic measures within three months in their department . Cost data included those directly related to LBP and NP . Cost-effectiveness analyses ( CEA ) and cost-benefit analyses ( CBA ) were performed . After 12 months , health care costs and costs of productivity losses were higher in the intervention group than in the control group ( the mean total cost difference was $ /euro$127 ; 95 % CI $ /euro$-164 - $ /euro$418 ) . From a societal perspective , the CEA showed that PE was not cost-effective compared to control for LBP and NP prevalence , work performance , and sick leave . The CBA from a company perspective showed a monetary loss of $ /euro$78 per worker . The PE programme was neither cost-effective nor cost-beneficial on any of the effect measures", "OBJECTIVE Examine the effect of a multi-component office ergonomics intervention on visual symptom reductions . METHODS Office workers were assigned to either a group receiving a highly adjustable chair with office ergonomics training ( CWT ) , a training-only group ( TO ) or a control group ( C ) . A work environment and health question naire was administered 2 and 1 month(s ) pre-intervention and 3 , 6 , and 12 months post-intervention . Multi-level statistical models tested hypotheses . RESULTS The CWT intervention lowered daily visual symptoms ( p CWT group differed significantly from the TO group ( p = 0.01 ) post-intervention . CONCLUSION Workers who received a highly adjustable chair and office ergonomics training had reduced visual symptoms and the effect was maintained through twelve months post-intervention . The lack of a training-only group effect supports implementing training in conjunction with the highly adjustable chair to reduce visual symptoms", "Background Prolonged sitting time is detrimental for health . Individuals with desk-based occupations tend to sit a great deal and sit-st and workstations have been identified as a potential strategy to reduce sitting time . Hence , the objective of the current study was to examine the effects of using sit-st and workstations on office workers ’ sitting time at work and over the whole day . Methods We conducted a r and omized controlled trial pilot with crossover design and waiting list control in Sydney , Australia from September 2011 to July 2012 ( n = 42 ; 86 % female ; mean age 38 ± 11 years ) . Participants used a sit-st and workstation for four weeks in the intervention condition . In the time-matched control condition , participants received nothing and crossed over to the intervention condition after four weeks . The primary outcomes , sitting , st and ing and walking time at work , were assessed before and after using the workstations with ActivPALs and self-report question naires . Secondary outcomes , domain-specific sitting over the whole day , were assessed by self-report . Linear mixed models estimated changes in outcomes adjusting for measurement time , study grouping and covariates . Results Intervention participants significantly reduced objective ly assessed time spent sitting at work by 73 min/workday ( 95 % CI : -106,-39 ) and increased st and ing time at work by 65 min/workday ( 95 % CI : 47 , 83 ) ; these changes were significant relative to controls ( p = 0.004 and p respectively ) . Total sitting time significantly declined in intervention participants ( -80 min/workday ; 95 % CI : -155 , -4 ) . Conclusions This study shows that introducing sit-st and workstations in the office can reduce desk-based workers ’ sitting time at work in the short term . Larger scale studies on more representative sample s are needed to determine the public health impact of sit-st and workstations . Trial registration", "Objective : To evaluate the participatory ergonomic method on the development of upper extremity musculoskeletal disorders and disability in office employees . Methods : This study is a r and omized controlled intervention study . It comprised 116 office workers using computers . Those in the intervention group were taught office ergonomics and the risk assessment method . Cox proportional hazards model and generalized estimating equations ( GEEs ) were used . Results : In the 10-month postintervention follow-up , the possibility of developing symptoms was 50.9 % . According to multivariate analysis results , the possibility of developing symptoms on the right side of the neck and in the right wrist and h and was significantly less in the intervention group than in the control group ( p Neck disability/symptom scores over time were significantly lower in the intervention group compared with the control group ( p participatory ergonomic intervention decreases the possibility of musculoskeletal complaints and disability/symptom level in office workers", "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", "OBJECTIVE The aim of this r and omized controlled trial ( RCT ) was to investigate the effectiveness of the Stay@Work participatory ergonomics ( PE ) program to prevent low-back and neck pain . METHODS A total of 37 departments were r and omly allocated to either the intervention ( PE ) or control group ( no PE ) . During a six-hour meeting , working groups followed the PE steps and composed and prioritized ergonomic measures aim ed at preventing low-back and neck pain . Subsequently , working groups were requested to implement the ergonomic measures in the departments . The primary outcomes were low-back and neck pain prevalence and secondary outcomes were pain intensity and duration . Data were collected by question naires at baseline , and after 3- , 6- , 9- , and 12-months follow-up . Additionally , the course of low-back and neck pain ( transitions from no symptoms to symptoms and from symptoms to no symptoms ) was modeled . RESULTS The r and omization procedure result ed in 19 intervention departments ( N=1472 workers ) and 18 control departments ( N=1575 workers ) . After 12 months , the intervention was not more effective than the control group in reducing the prevalence of low-back and neck pain or reducing pain intensity and duration . PE did not increase the probability of preventing low-back pain [ odds ratio ( OR ) 1.23 , 95 % confidence interval ( 95 % CI ) 0.97 - 1.57 ) or neck pain ( OR 1.01 , 95 % CI 0.74 - 1.40 ) . However , PE increased the probability of recovering from low-back pain ( OR 1.41 , 95 % CI 1.01 - 1.96 ) , but not from neck pain ( OR 0.95 , 95 % CI 0.72 - 1.26 ) . CONCLUSION PE neither reduced low-back and neck pain prevalence nor pain intensity and duration nor was it effective in the prevention of low-back and neck pain or the recovery from neck pain . However , PE was more effective in the recovery from low-back pain", "Work Related Musculoskeletal Disorders ( WMSDs ) among office workers with intensive computer use is widespread and the prevalence of symptoms is growing . This r and omized controlled trial investigated the effects of an office ergonomics training combined with a sit-st and workstation on musculoskeletal and visual discomfort , behaviors and performance . Participants performed a lab-based customer service job for 8 h per day , over 15 days and were assigned to : Ergonomics Trained ( n = 11 ) or Minimally Trained ( n = 11 ) . The training consisted of : a 1.5-h interactive instruction , a sit/st and practice period , and ergonomic reminders . Ergonomics Trained participants experienced minimal musculoskeletal and visual discomfort across the 15 days , varied their postures , with significantly higher performance compared to the Minimally Trained group who had a significantly higher number of symptoms , suggesting that training plays a critical role . The ability to mitigate symptoms , change behaviors and enhance performance through training combined with a sit-st and workstation has implication s for preventing discomforts in office workers", "We investigated , on behalf of a large electronics manufacturer , two types of worker training interventions for their efficacy in preventing unnecessary muscle tension and the symptoms of work-related musculoskeletal disorders . The first intervention , Muscle Learning Therapy ( MLT ) , used electromyographic ( sEMG ) feedback and operant conditioning to decrease muscle tension during complex work tasks . The second intervention used adult learning and cognitive behavioral techniques in small group discussion to advance the worker 's capabilities for symptom and stress management and problem-solving . Workers were r and omly assigned to a control group or one of the two treatment conditions . Prior to training , baseline data were collected using symptom diaries and sEMG recordings of the trapezius and forearm muscles of the left and right arms . The training interventions were conducted for 6 weeks with reinforcement training provided at 18 and 32 weeks post-baseline . Follow-up data were collected after the initial 6-week training period and at 32 weeks , prior to the reinforcement training . Symptom outcomes demonstrated significant differences at 6 weeks , increasing in severity for the control group and declining modestly for the educational group , with little change for the MLT group . These differences were not maintained at further follow-up . The MLT group was consistently effective in reducing muscle tension in the trapezius areas after 6 and 32 weeks , and was partially effective for the forearms . Further testing is recommended of these training interventions , especially with the inclusion of strategic , periodic reinforcement of the worker 's learning", "Study Design . A prospect i ve r and omized control trial . Objective . To determine the degree to which a new behavior-based lift training program ( LiftTrainer ™ ; Ascension Technology , Burlington , VT ) could reduce the incidence of low back disorder in distribution center jobs that require repetitive lifting . Summary of Background Data . Most studies show programs aim ed at training lifting techniques to be ineffective in preventing low back disorders , which may be due to their conceptual rather than behavioral learning approach . Methods . A total of 2144 employees in 19 distribution centers were r and omized into either the LiftTrainer ™ program or a video control group . In the LiftTrainer ™ program , participants were individually trained in up to 5 , 30-minute sessions while instrumented with motion capture sensors to quantify the L5/S1 moments . Twelve months following the initial training , injury data were obtained from company records . Results . Survival analyses ( Kaplan-Meier ) indicated that there was no difference in injury rates between the 2 training groups . Likewise , there was no difference in the turnover rates . However , those with a low ( average twisting moment at the end of the first session experienced a significantly ( P lower rate of low back disorder than controls . Conclusions . While overall the LiftTrainer ™ program was not effective , those with twisting moments below 30 Nm reported fewer injuries , suggesting a shift in focus for “ safe ” lifting programs", "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", "BACKGROUND Low back injuries are common and costly , accounting for 15 to 25 percent of injuries covered by workers ' compensation and 30 to 40 percent of the payments made under that program . The high costs of injury , the lack of effective treatment . and the evidence that there are behavioral risk factors have led to widespread use of employee education programs that teach safe lifting and h and ling . The effectiveness of those programs , however , has received little rigorous evaluation . METHODS We evaluated an educational program design ed to prevent low back injury in a r and omized , controlled trial involving about 4000 postal workers . The program , similar to that in wide use in so-called back schools , was taught by experienced physical therapists . Work units of workers and supervisors were trained in a two-session back school ( three hours of training ) , followed by three to four reinforcement sessions over the succeeding few years . Injured subjects ( from both the intervention and the control groups ) were r and omized a second time to receive either training or no training after their return to work . RESULTS Physical therapists trained 2534 postal workers and 134 supervisors . Over 5.5 years of follow-up , 360 workers reported low back injuries , for a rate of 21.2 injuries per 1000 worker-years of risk . The median time off from work per injury was 14 days ( range , 0 to 1717 ) ; the median cost was $ 204 ( range , zero to $ 190,380 ) . After their return to work , 75 workers were injured again . Our comparison of the intervention and control groups found that the education program did not reduce the rate of low back injury , the median cost per injury , the time off from work per injury , the rate of related musculoskeletal injuries , or the rate of repeated injury after return to work ; only the subjects ' knowledge of safe behavior was increased by the training . CONCLUSIONS A large-scale , r and omized , controlled trial of an educational program to prevent work-associated low back injury found no long-term benefits associated with training", "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", "Objectives : The aim of this intervention study was to determine the effects of an alternative mouse and /or a forearm support board on the change in upper body discomfort scores and the development of incident musculoskeletal disorders . Methods : This r and omised controlled intervention trial followed 206 engineers for one year . Participants were r and omised to receive ( 1 ) a conventional mouse only , ( 2 ) an alternative mouse only , ( 3 ) a forearm support board , or ( 4 ) an alternative mouse plus forearm support board . Outcome measures included weekly upper body discomfort scores and incident musculoskeletal disorders . Results : During the study , 42 participants were diagnosed with an incident musculoskeletal disorder . The group that received the forearm support board experienced a reduction in their right upper extremity discomfort ( beta-coefficient −0.35 , 95 % CI −0.67 to −0.03 ) in comparison to those who did not receive a forearm board . The group that received the alternative mouse had a protective , but non-significant ( p = 0.20 ) , effect on incident cases of right upper extremity musculoskeletal disorders ( HR 0.57 , 95 % CI 0.24 to 1.34 ) and a non-significant reduction in neck/shoulder discomfort ( beta-coefficient −0.23 , 95 % CI −0.056 to 0.10 ) in comparison to those who received a conventional mouse . Conclusions : In engineers who use a computer for more than 20 h per week , a forearm support board may reduce right upper extremity discomfort attributed to computer use", "A pilot study examined the effectiveness of a biofeedback mouse in reducing upper extremity pain and discomfort in office workers ; in addition , relative mouse use ( RMU ) , satisfaction and the feasibility of running a r and omised controlled trial ( RCT ) in a workplace setting were evaluated . The mouse would gently vibrate if the h and was idle for more than 12 s. The feedback reminded users to rest the arm in neutral , supported postures . Analysis showed a statistically significant reduction in shoulder pain and discomfort for the intervention group at T2 ( 38.7 % lower than controls ) . Statistically significant differences in RMU time between groups were seen post intervention ( −7 % at T1 and + 15 % at T2 for the intervention group ) . Fifty-five percent of the intervention group was willing to continue using the mouse . It appears feasible to perform an RCT for this type of intervention in a workplace setting . Further study including more participants is suggested . Practitioner Summary : The study findings support the feasibility of conducting r and omised control trials in office setting s to evaluate ergonomics interventions . The intervention result ed in reduced pain and discomfort in the shoulder . The intervention could be a relevant tool in the reduction of upper extremity musculoskeletal disorder . Further research will better explain the study 's preliminary findings", "OBJECTIVES A cross-sectional study was conducted to assess the association of upper extremity musculoskeletal disorders and work-related factors among employees using video display terminals at a large metropolitan newspaper . METHODS The study included 1050 r and omly selected workers from four departments . The workers were asked to complete question naires on symptoms , job tasks , and psychosocial and work organization conditions . Musculoskeletal disorders of the upper extremities were defined by frequency , duration , and intensity of symptoms not attributable to acute injury . Data were analyzed with the use of logistic regression . RESULTS A total of 973 workers completed the survey . The one-year period prevalence rate for any musculoskeletal disorder of the upper extremities was 41 % . Neck symptoms ( 26 % ) were the most frequently reported , followed by h and or wrist ( 22 % ) , shoulder ( 17 % ) , and elbow ( 10 % ) symptoms . Greater time working at the video display station was associated with increased h and or wrist symptoms in a dose-response relationship . In addition , variables corresponding to increased work-load dem and s ( eg , increased time working under deadline and increased job pressure ) were associated with increased neck , shoulder , and h and or wrist disorders . Women were more likely to report symptoms in several areas , but this finding may reflect the concentration of women in jobs involving more risk factors . CONCLUSIONS The results suggest a high prevalence of musculoskeletal disorders of the upper extremities among newspaper employees , and they provide additional evidence that increased work load , time pressure , and greater hours of computer use are related to the occurrence of work-related musculoskeletal disorders among these workers , particularly for disorders in the h and or wrist area", "Study Design . R and omized controlled trial ( RCT ) . Objectives . To compare the effectiveness of training and equipment to reduce musculoskeletal injuries , increase comfort , and reduce physical dem and s on staff performing patient lifts and transfers at a large acute care hospital . Summary of Background Data . Back injury to nursing staff during patient h and ling tasks is a major issue in health care . The value of mechanical assistive devices in reducing injuries to these workers is unclear . Methods . This three-armed RCT consisted of a “ control arm , ” a “ safe lifting ” arm , and a “ no strenuous lifting ” arm . A medical , surgical , and rehabilitation ward were each r and omly assigned to each arm . Both intervention arms received intensive training in back care , patient assessment , and h and ling techniques . Hence , the “ safe lifting ” arm used improved patient h and ling techniques using manual equipment , whereas the “ no strenuous lifting ” arm aim ed to eliminate manual patient h and ling through use of additional mechanical and other assistive equipment . Results . Frequency of manual patient h and ling tasks was significantly decreased on the “ no strenuous lifting ” arm . Self-perceived work fatigue , back and shoulder pain , safety , and frequency and intensity of physical discomfort associated with patient h and ling tasks were improved on both intervention arms , but staff on the mechanical equipment arm showed greater improvements . Musculoskeletal injury rates were not significantly altered . Conclusions . The “ no strenuous lifting ” program , which combined training with assured availability of mechanical and other assistive patient h and ling equipment , most effectively improved comfort with patient h and ling , decreased staff fatigue , and decreased physical dem and s. The fact that injury rates were not statistically significantly reduced may reflect the less sensitive nature of this indicator compared with the subjective indicators", "There is evidence that performing job tasks involving repetition , vibration , sustained posture or forceful movement may contribute to symptoms of work related upper extremity disorders . Typing is one such activity ; symptoms that develop as a result of this activity can affect performance of work , self-care and leisure occupations . Studies investigating the impact of ergonomic keyboards on symptom reduction are limited , and little research exists regarding the reduction of key activation force as an intervention . Methods : This r and omized , prospect i ve study used a sample of 68 symptomatic workers employed by a single company . One group received a commercially available ergonomic keyboard , a second group used a modified version of the same keyboard design ed to reduce activation force , vibration and key travel . We measured symptoms and clinical signs , functional status , and device satisfaction in both groups over a six-month study period . Results : Between-groups analyses indicated that the groups performed similarly on the outcomes of interest . Repeated-measure analysis identified a reduction of symptoms , an improvement in functional status , preference for and increased satisfaction with the intervention keyboards , and maintenance of typing speed and accuracy for both groups . Conclusions", "Objectives To examine whether the introduction of intermittent st and ing bouts during the workday using a height-adjustable workstation can improve subjective levels of fatigue , musculoskeletal discomfort and work productivity relative to seated work . Methods Overweight/obese office workers ( n=23 ; age 48.2±7.9 years , body mass index 29.6±4 kg/m2 ) undertook two , 5-day experimental conditions in an equal , r and omised ( 1:1 ) order . In a simulated office environment , participants performed their usual occupational tasks for 8 h/day in a : seated work posture ( SIT condition ) ; or interchanging between a st and ing and seated work posture every 30 min using an electric , height-adjustable workstation ( ST AND -SIT condition ) . Self-administered question naires measuring fatigue , musculoskeletal discomfort and work productivity were performed on day 5 of each experimental condition . Results Participants ’ total fatigue score was significantly higher during the SIT condition ( mean 67.8 ( 95 % CI 58.8 to 76.7 ) ) compared with the ST AND -SIT condition ( 52.7 ( 43.8 to 61.5 ) ; p was significantly reduced during the ST AND -SIT condition compared with the SIT condition ( 31.8 % reduction ; p=0.03 ) . Despite concentration/focus being significantly higher during the SIT condition ( p=0.006 ) , there was a trend towards improved overall work productivity in favour of the ST AND -SIT condition ( p=0.053 ) . Conclusions Transitioning from a seated to a st and ing work posture every 30 min across the workday , relative to seated work , led to a significant reduction in fatigue levels and lower back discomfort in overweight/obese office workers , while maintaining work productivity . Future investigations should be directed at underst and ing whether sustained use of height-adjustable workstations promote concentration and productivity at work . Trial Registration Number ACTRN12611000632998", "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 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", "PURPOSE This study aim ed to examine whether reductions in sitting time through alternating 30-min bouts of sitting and st and ing can reduce postpr and ial glucose , insulin , and triglyceride responses . METHODS Twenty-three overweight/obese sedentary office workers ( 17 males and six females ; mean ± SD : age , 48.2 ± 7.9 yr ; body mass index , 29.6 ± 4.0 kg · m(-2 ) ) undertook two short-term ( 5 d ) experimental conditions in an equal , r and omized ( 1:1 ) order . In a simulated office environment , participants performed typical occupational tasks for 8 h · d(-1 ) while in a 1 ) seated work posture ( control condition ) or 2 ) interchanging between a seated and st and ing work posture every 30 min using an electric , height-adjustable workstation ( intervention condition ) . Fasting and postpr and ial blood sample s after a mixed test drink were collected hourly for 4 h on days 1 and 5 of each condition to assess serum insulin , plasma glucose , and triglycerides . Dietary intake ( kJ · d(-1 ) ) and physical activity were st and ardized during each condition . The trial was registered with the Australian New Zeal and Clinical Trials Registry ( ACTRN12611000632998 ) . RESULTS After adjustment for time ( days 1 and 5 ) , incremental area under the analyte time curve differed significantly between conditions for plasma glucose ( P = 0.007 ) but not for serum insulin or plasma triglycerides . Adjusted mean glucose incremental area under the analyte time curve was lowered by 11.1 % after the intervention condition ( 6.38 mM · h(-1 ) ( confidence interval , 5.04 - 7.71 ) ) relative to the control condition ( 7.18 mM · h(-1 ) ( confidence interval , 5.85 - 8.52 ) ) . No temporal changes ( days 1 vs 5 ) between conditions were observed . CONCLUSIONS Alternating st and ing and sitting in 30-min bouts results in modest beneficial effects on postpr and ial glucose responses in overweight/obese office workers", "OBJECTIVES This study examined the health-related effects of two worksite interventions , physical exercise and reduced workhours , on women employed in dentistry . METHODS Six workplaces were r and omized to one of the following three conditions : ( i ) 2.5 hours of weekly , m and atory physical exercise of middle-to-high intensity to be performed during workhours ( N=62 ) , ( ii ) a reduction of full-time weekly workhours from 40 to 37.5 hours ( N=50 ) , and ( iii ) reference . In all , 177 women participated . Biomarkers and self-ratings in question naires were obtained before the intervention ( T ( 1 ) ) , and six ( T ( 2 ) ) and 12 months ( T ( 3 ) ) after the intervention . RESULTS The results showed increased levels of physical activity and exercise in all of the groups , the level of physical exercise being significantly greater in the physical exercise group . Repeated- measures analyses of variance using data from T ( 1 ) and T (3)for biological measures and all three time points for self-ratings produced significant interaction effects for glucose , waist-to-hip ratio , and work ability and clear trends for general symptoms and upper-extremity disorders . Posthoc analyses showed that the results of the health-related measures differed between the interventions , decreased glucose and upper-extremity disorders in the exercise group , and increased high-density lipoprotein and waist-to-hip ratio among those working reduced hours . CONCLUSIONS These results show that the two interventions had small and varied effects on biomarkers and self-reports of different aspects of health among women . It is suggested that interventions involving a modest reduction in workhours seem to be more effective if these hours are used for physical exercise", "BACKGROUND The purpose of this study was to determine the effects of an alternative mouse and /or a forearm support board on nerve function at the wrist among engineers . METHODS This r and omized controlled intervention trial followed 206 engineers for 1 year . Distal motor latency ( DML ) at baseline and follow-up was conducted for the median and ulnar nerves at the right wrist . RESULTS One hundred fifty-four subjects agreed to a nerve conduction study at the beginning and end of the study period . Those who received the alternative mouse had a protective effect ( OR = 0.47 , 95 % CI 0.22 - 0.98 ) on change in the right ulnar DML . There was no significant effect on the median nerve DML . The forearm support board had no significant effect on the median or ulnar nerve DML . CONCLUSIONS In engineers who use a computer for more than 20 hr per week , an alternative mouse may have a protective effect for ulnar nerve function at the wrist . No protective effect of a forearm support board was found for the median nerve", "INTRODUCTION Non-specific neck pain is a major burden to industry , yet the impact of introducing a workplace ergonomics and exercise intervention on work productivity and severity of neck pain in a population of office personnel is unknown . RESEARCH QUESTION Does a combined workplace-based best practice ergonomic and neck exercise program reduce productivity losses and risk of developing neck pain in asymptomatic workers , or decrease severity of neck pain in symptomatic workers , compared to a best practice ergonomic and general health promotion program ? DESIGN Prospect i ve cluster r and omised controlled trial . PARTICIPANTS AND SETTING Office personnel aged over 18 years , and who work>30 hours/week . INTERVENTION Individualised best practice ergonomic intervention plus 3 × 20 minute weekly , progressive neck/shoulder girdle exercise group sessions for 12 weeks . CONTROL Individualised best practice ergonomic intervention plus 1-hour weekly health information sessions for 12 weeks . MEASUREMENTS Primary ( productivity loss ) and secondary ( neck pain and disability , muscle performance , and quality of life ) outcome measures will be collected using vali date d scales at baseline , immediate post-intervention and 12 months after commencement . PROCEDURE 640 volunteering office personnel will be r and omly allocated to either an intervention or control arm in work group clusters . ANALYSIS Analysis will be on an ' intent-to-treat ' basis and per protocol . Multilevel , generalised linear models will be used to examine the effect of the intervention on reducing the productivity loss in dollar units ( AUD ) , and severity of neck pain and disability . DISCUSSION The findings of this study will have a direct impact on policies that underpin the prevention and management of neck pain in office personnel", "Typing is associated with musculoskeletal complaints ( MSCs ) , caused by multiple risk factors . Although a wide variety of ergonomic intervention programs were conducted to reduce risk factors and MSC 's , only few of them were found evidence based . This study aim ed to test the efficacy of a workplace intervention in reducing MSC 's among computer workers . 66 computer workers were assigned r and omly to one of three intervention programs : ergonomic intervention including biofeedback , intervention without biofeedback and control group without intervention . The efficacy was tested by advanced assessment including ; pain location and severity , posture at work , upper extremity 3D kinematics , muscle activity and psychosocial status . Working hypothesis ; significant score differences will be found between the study groups which underwent ergonomic intervention and the control group on the following measures : pain complaints , upper extremity kinematics , muscle activity and psychosocial status . Significant differences were found between pre and post intervention and between research groups and the control group in pain , posture and motion . The ergonomic intervention with biofeedback had no unique contribution in comparison to other interventions . In conclusion ; the proposed intervention program was found efficient for reducing pain among computer workers" ]

[ "The efficacy and safety of 4-g 5-aminosalicylic acid enemas were assessed in 153 patients with ulcerative colitis involving up to 50 cm of distal colon . Seventy-six patients received active medication and 77 received a placebo . There were 20 dropouts ( 6 in the active group and 14 in the placebo group ) during the study because of insufficient efficacy . After 6 wk of therapy , 48 of the 76 patients ( 63 % ) receiving 5-aminosalicylic acid were considered to be \" much improved \" by the study physician compared to 22 of the 77 patients ( 29 % ) on placebo ( p = 0.001 ) . A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy . Mean disease activity index declined 55 % for patients on 5-aminosalicylic acid and 24 % for patients on placebo ( p = 0.0001 ) . Analysis of subgroups indicated that patients most likely to respond were those with disease confined to the 20 - 40 cm from the anus . Response was not affected by concurrent sulfasalazine , but patients requiring concurrent oral steroids had a diminished response . Rapid onset of efficacy was shown by a significant reduction in rectal bleeding within 3 days of treatment initiation . 5-Aminosalicylic acid enemas are well tolerated and are of benefit in the treatment of ulcerative colitis confined to the distal colon", "Purpose Ulcerative colitis ( UC ) is associated with impaired health-related quality of life ( HRQL ) and work-related outcomes ( WRO ) . This analysis examined correspondences among measures of HRQL and WRO in patients with UC , as well as the magnitude of each measure ’s responsiveness to disease activity and treatment . Methods An open-label , prospect i ve trial of delayed-release mesalamine tablets formulated with MMX ® technology included 8 weeks of treatment for patients with active mild-to-moderate UC ( n = 137 ) and 12 months of maintenance treatment for patients with quiescent UC ( n = 206 ) . Spearman correlations ( ρ ) measured inter-domain associations across measures of generic HRQL [ 12-item Short-Form Health Survey ( SF-12v2 ) ] , disease-specific HRQL [ Short Inflammatory Bowel Disease Question naire ( SIBDQ ) ] , and disease-specific WRO [ Work Productivity and Activity Impairment for Specific Health Problems ( WPAI : SHP ) ] . Responsiveness to disease activity and treatment was assessed for each instrument . Results Changes in scores from baseline to week 8 were moderately correlated across all instrument domains : 65 of 80 ( 81 % ) between-instrument inter-domain correlations were of moderate magnitude ( 0.30 < ρ < 0.70 ) , with an average magnitude of 0.42 [ 95 % confidence interval ( CI ) 0.38–0.46 ] . Associations between symptom measures were stronger for SIBDQ ( |average ρ| = 0.41 ; 95 % CI 0.34–0.48 ) and WPAI : SHP ( 0.40 ; 0.30–0.47 ) than SF-12v2 ( 0.30 ; 0.27–0.34 ) . SIBDQ was most sensitive to treatment [ effect size ( dz ) for change from baseline to week 8 = 0.62 ; 95 % CI 0.35–0.89 ] , followed by WPAI : SHP ( dz = 0.43 ; 0.32–0.54 ) and SF-12v2 ( dz = 0.33 ; 0.27–0.39 ) . Conclusion While the SIBDQ showed the greatest overall responsiveness to disease activity and treatment , all three patient-reported outcomes instruments provided complementary interpretive information regarding the impact of UC treatment", "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", "Abstract Background and Aims R and omised trials have described the benefits of adalimumab [ ADA ] for ulcerative colitis [ UC ] ; however , few data are available on health-related quality of life [ HRQL ] and health care costs in clinical practice . Methods InspirADA , a multicentre , prospect i ve study , evaluated the effect of ADA in patients with moderate to severe UC treated according to usual clinical practice . Outcomes assessed were : Simple Clinical Colitis Activity Index [ SCCAI ] response/remission rates ; changes in HRQL ; all-cause direct costs ; and UC-related direct and indirect costs from baseline to Week 26 . Results Data from 463 patients were analysed . At Week 26 , 67 % ( 95 % confidence interval [ CI ] : 62 % , 71 % ) of patients achieved response ; 48 % [ 95 % CI : 44 % , 53 % ] were in remission . For the overall population , significant [ all p the Short Inflammatory Bowel Disease Question naire [ SIBDQ ] ( mean change ± st and ard deviation [ SD ] : 17.4 ± 14.5 ) and the European Quality of Life—5 Dimensions—5 Level [ EQ-5D-5L ] ( index : 0.1 ± 0.2 ; visual analogue scale [ VAS ] : 19.5 ± 25.8 ) . Parallel improvements were seen in work productivity [ 11 % absolute decrease in absenteeism ; 25 % absolute decrease in impairment while working ; and 27 % absolute decrease in impairment of ability to perform daily activities , all p , cumulative all-cause medical costs and UC-related medical costs were significantly [ both p The safety profile of ADA was consistent with that observed in previous clinical trials . Conclusions ADA therapy in usual clinical practice is effective at improving and maintaining symptomatic control , improving HRQL , and decreasing costs of medical care among patients with UC", "Background and Aims : This study assessed the efficacy of maintenance treatment with multimatrix mesalazine following achievement of complete or partial remission after induction treatment with high-dose multimatrix mesalazine . Methods : In this phase 3b/4 , open-label , multicentre , prospect i ve , single-arm study , patients with mild-to-moderate ulcerative colitis were treated with multimatrix mesalazine 4.8g/day once daily for 8 weeks [ induction phase ] . At Week 8 , those who achieved complete or partial remission , based on predefined clinical and endoscopic criteria , were eligible to receive 12 months of multimatrix mesalazine 2.4g/day once daily maintenance therapy . The primary endpoint was the proportion of patients in complete remission at Month 12 . Results : A total of 717 patients received induction treatment ; 25.9 % and 39.3 % of patients achieved complete and partial remission , respectively , at Week 8 . A total of 461 patients entered the maintenance phase . The likelihood of remaining in/achieving complete remission at Month 12 was higher for patients who entered the maintenance phase in complete remission compared with those who began maintenance in partial remission [ 47.8 % vs 26.0 % ; p Month 12 , mucosal healing [ endoscopy score ≤ 1 ] was demonstrated in 76.4 % [ 139/182 ] and 63.5 % [ 176/277 ] of those who were in complete and partial remission , respectively , at the end of induction . Conclusion : Patients achieving complete remission before dose reduction were more likely to remain in remission at Month 12", "BACKGROUND Crohn 's disease ( CD ) is a chronic inflammatory bowel disease usually diagnosed in early adult life and characterized by unpredictable flares and debilitating symptoms such as diarrhea , abdominal pain , and fever , which can interfere with a patient 's ability to work and perform daily activities . OBJECTIVE The aim of this study was to assess the validity , reliability , and responsiveness of the Work Productivity and Activity Impairment question naire in CD ( WPAI : CD ) . METHODS The WPAI : CD was tested in CD patients enrolled in a 26-week r and omized clinical trial of cer-tolizumab pegol versus placebo . Discriminative validity of WPAI : CD absenteeism , presenteeism(reduced on-the-job effectiveness ) , overall work productivity loss ( absenteeism + presenteeism ) , and activity impairment scores was assessed relative to 5 measures of disease severity and health status : CD Activity Index ( CDAI ) , Short Form-36 physical component summary ( PCS ) and mental health component summary ( MCS ) scores , Inflammatory Bowel Disease Question naire ( IBDQ ) , and the 5-dimensional EuroQoL health-related quality -of-life visual analog scale ( EQ-VAS ) . Responsiveness was assessed by comparing changes in WPAI : CD scores from baseline to week 26 for patients in remission ( CDAI A total of 662 patients ( mean [ range ] age , 37.4 [ 18 - 77 ] years ; male , 288 [ 43.5 % ] ; white , 629 [ 95.0 % ] ) were enrolled in the study . Patients with CD of the worst severity ( CDAI > median ) showed significantly higher impairment in work ( + 10.5 % ) and activities ( + 10.4 % ) versus patients with \" best health \" ( no problems ) ( both , P worst \" IBDQ , PCS , MCS , and EQ-VAS scores also showed significantly higher impairments in work ( IBDQ , VAS -24.2 % ; PCS , -24.1 % ; MCS , -15.9 % ; EQ-VAS , -16.5 % ) and activities ( IBDQ , -23.3 % ; PCS , -21.8 % ; MCS , -16.5 % ; EQ-VAS , -17.2 % ) versus \" best \" scores ( all , P WPAI : CD impairment scores for patients in remission versus patients failing to achieve remission ( P SRMs were small ( ie , 0.5 ) for patients in remission . CONCLUSIONS The discriminative validity , reliability , and responsiveness of the WPAI : CD were demonstrated . The WPAI : CD may be useful for evaluating drug impact on CD", "OBJECTIVE Health-related quality of life ( HRQOL ) affects outcome in chronic diseases such as inflammatory bowel disease ( IBD ) . The inflammatory bowel disease question naire ( IBDQ ) , a disease-specific HRQOL question naire , can define changes in health status in IBD , but simple instruments are needed for daily application . The present study proposed to develop a short version of the IBDQ , the SIBDQ , for community physicians . METHODS Using data from a clinical trial in 149 patients with Crohn 's disease , 10 items were selected ( by forward stepwise regression ) that best explained the variance of the IBDQ or dimensional scores ( bowel , systemic , social , emotional ) . The validity , reliability , and responsiveness of the SIBDQ were then assessed in 150 different patients with Crohn 's disease and 45 with ulcerative colitis . All scores were reported with a 7-point scale ( 1 = poor HRQOL , 7 = optimum HRQOL ) . RESULTS Mean SIBDQ scores were similar ( p = 0.22 ) in Crohn 's patients among 14 participating centers at study entry . Mean scores were lower in active Crohn 's disease ( range 4.00 - 4.92 ) than inactive disease ( range 4.67 - 5.83 ; p = 0.0015 ) . In active ulcerative colitis , the mean SIBDQ was 4.79 + /- 1.17 compared to 5.90 + /- 0.80 ( p = 0.0006 ) in inactive disease . The SIBDQ explained 92 % and 90 % of the IBDQ variance in Crohn 's disease and ulcerative colitis , respectively . In patients with stable Crohn 's disease , the test-retest reliability coefficient was 0.65 and Crohnbach 's alpha was 0.78 , indicating good reliability . In patients with Crohn 's disease who relapsed during follow-up , the mean SIBDQ decreased by -0.93 + 0.55 ( p = 0.001 ) . CONCLUSION The SIBDQ is valid , reliable , and able to detect meaningful clinical changes in HRQOL that might occur in the office setting", "OBJECTIVES The Work Productivity and Activity Impairment Question naire ( WPAI ) is an instrument that measures work impairment in the setting of different diseases . One previous study validating the WPAI in Crohn 's disease ( CD ) patients suggested that its reproducibility may be unsatisfactory . This study evaluated the validity and reproducibility of the Spain Spanish version of the WPAI question naire in CD patients . METHODS In a prospect i ve study , convergent validity was tested comparing WPAI with quality of life and CD activity indices . Known-groups validity was assessed by comparing WPAI scores in CD patients with active versus inactive disease . Reproducibility of repeated tests was evaluated by comparing two WPAI measures obtained two to four weeks apart in stable patients . RESULTS One hundred eight patients were included in the various steps of the analysis . The WPAI showed adequate known groups validity and convergent validity . The reproducibility of the test and , specifically , that of the evaluation of presenteeism ( the impairment of productivity while working ) were good . CONCLUSIONS This study confirms the validity of WPAI for measuring work impairment in CD patients . In contrast to previous studies , the test reproducibility was adequate", "Summary The construct validity of a quantitative work productivity and activity impairment ( WPAI ) measure of health outcomes was tested for use in clinical trials , along with its reproducibility when administered by 2 different methods . 106 employed individuals affected by a health problem were r and omised to receive either 2 self-administered question naires ( self administration ) or one self-administered question naire followed by a telephone interview ( interviewer administration ) . Construct validity of the WPAI measures of time missed from work , impairment of work and regular activities due to overall health and symptoms , were assessed relative to measures of general health perceptions , role ( physical ) , role ( emotional ) , pain , symptom severity and global measures of work and interference with regular activity . Multivariate linear regression models were used to explain the variance in work productivity and regular activity by validation measures . Data generated by interviewer-administration of the WPAI had higher construct validity and fewer omissions than that obtained by self-administration of the instrument . All measures of work productivity and activity impairment were positively correlated with measures which had proven construct validity . These validation measures explained 54 to 64 % of variance ( p productivity and activity impairment variables of the WPAI . Overall work productivity ( health and symptom ) was significantly related to general health perceptions and the global measures of interference with regular activity . The self-administered question naire had adequate reproducibility but less construct validity than interviewer administration . Both administration methods of the WPAI warrant further evaluation as a measure of morbidity", "Background : Impairment of health‐related quality of life , employment , and productivity has been documented in patients with moderate to severe ulcerative colitis . Methods : Using prospect ively collected data from the Active Ulcerative Colitis Trials 1 and 2 , we examined the impact of clinical response or remission , as defined using the Mayo score , on health‐related quality of life , employment , disability , productivity , and hours worked per week . These analyses were based on observed data and included all 728 patients , regardless of their r and omized treatment group ( i.e. , placebo and infliximab patients were grouped for analysis ) . Changes in Inflammatory Bowel Disease Question naire ( IBDQ ) and Medical Outcomes Study 36‐Item Short Form ( SF‐36 ) scores among nonresponders , responders , and patients in remission were compared . In addition , changes in employment , disability status , productivity , and hours worked per week of patients in clinical remission and patients not in clinical remission were compared . Results : Ulcerative colitis patients in clinical response or remission had significantly improved IBDQ and SF‐36 scores at week 30 compared with those of nonresponders ( P receiving disability compensation ( 58.8 % ) than were those not in remission ( 8.3 % and 20.0 % , respectively ; P improvements from baseline in productivity and both actual and fully productive hours worked per week were greater for patients in remission compared with those not in remission ( P < 0.05 for all three comparisons ) . Conclusions : These results confirm the validity of response and remission as defined using the Mayo score", "We assessed oral 5-aminosalicylic acid ( 5-ASA ) prepared with a pH-sensitive polymer coating in 87 patients with mildly to moderately active ulcerative colitis in a double-blind , placebo-controlled trial . Patients were r and omly assigned to receive 5-ASA at a dosage of either 4.8 or 1.6 g per day or placebo for six weeks . The outcome was monitored by flexible proctosigmoidoscopic examinations and physicians ' assessment s at three-week intervals and by patients ' recordings of daily symptoms . Results showed 24 percent complete and 50 percent partial responses in those receiving 4.8 g of 5-ASA per day as compared with 5 percent complete and 13 percent partial responses in those receiving placebo ( P less than 0.0001 , rank-sum test ) . At a dosage of 1.6 g per day , the response was twice as good as with placebo , but the difference did not reach statistical significance ( P = 0.51 ) . Age , sex , duration of disease , duration of active symptoms , or extent of disease did not affect the clinical outcome . We conclude that oral 5-ASA administered in a dosage of 4.8 g per day is effective therapy , at least in the short term , for mildly to moderately active ulcerative colitis", "Needing a single index of degree of illness in Crohn 's disease , the National Cooperative Crohn 's Disease Study group collected data prospect ively from 187 visits of 112 patients with Crohn 's disease of the small bowel , colon , or both . Information on 18 predictor variables was gathered at each visit . In addition , the attending physician rated his over-all evaluation of how well the patient was doing and compared the patient 's status with that at the previous visit . A multiple regression computer program was utilized to derive an equation for prediction of the physician 's over-all ratings from a subset of the predictor variables fulfilling a combination of constraints . This equation , numerically simplified and utilizing eight selected variables , is the Crohn 's Disease Activity Index . Index values of 150 and below are associated with quiescent disease ; values above that indicate active disease , and values above 450 are seen with extremely severe disease" ]

[ "OBJECTIVE Only a few prospect i ve studies have examined the relationship between the frequency of cigarette smoking and the incidence of diabetes mellitus . The purpose of this study was to determine whether greater frequency of cigarette smoking accelerated the development of diabetes mellitus , and whether quitting reversed the effect . METHODS Data were collected in the Cancer Prevention Study I , a prospect i ve cohort study conducted from 1959 through 1972 by the American Cancer Society where volunteers recruited more than one million acquaintances in 25 US states . From these over one million original participants , 275,190 men and 434,637 women aged > or = 30 years were selected for the primary analysis using predetermined criteria . RESULTS As smoking increased , the rate of diabetes increased for both men and women . Among those who smoked > or = 2 packs per day at baseline , men had a 45 % higher diabetes rate than men who had never smoked ; the comparable increase for women was 74 % . Quitting smoking reduced the rate of diabetes to that of non-smokers after 5 years in women and after 10 years in men . CONCLUSIONS A dose-response relationship seems likely between smoking and incidence of diabetes . Smokers who quit may derive substantial benefit from doing so . Confirmation of these observations is needed through additional epidemiological and biological research", "Puerto Ricans living in the United States mainl and present multiple disparities in prevalence of chronic diseases , relative to other racial and ethnic groups . Allostatic load ( AL ) , or the cumulative wear and tear of physiological responses to stressors such as major life events , social and environmental burden , has been proposed as a possible mechanism for the inequalities observed in minority groups , but has not been studied in Puerto Ricans . The aim of this study was to determine the association of AL to six chronic diseases ( abdominal obesity , hypertension , diabetes , and self-reported cardiovascular disease ( CVD ) , arthritis and cancer ) in Puerto Ricans , and to contrast AL to metabolic syndrome ( MetS ) . Participants of the Boston Puerto Rican Health Study ( n=1116 , ages 45 - 75 years ) underwent a home-based interview , where question naires were completed and biological sample s collected . A summary definition of AL was constructed using clinical ly-defined cutoffs and medication use for 10 physiological parameters in different body systems . Logistic regression models were run to determine associations between AL score and disease status , controlling for age , sex , smoking , alcohol use , physical activity , total fat intake and energy intake . Parallel models were also run with MetS score replacing AL . We found that increasing categories of AL score were significantly associated with abdominal obesity , hypertension , diabetes and self-reported cardiovascular disease ( CVD ) and arthritis , but not with self-reported cancer . The strength of associations of AL with all conditions , except diabetes and cancer , was similar to or larger than those of MetS score . In conclusion , Puerto Rican older adults experienced physiological dysregulation that was associated with increased odds of chronic conditions . AL was more strongly associated with most conditions , compared to MetS , suggesting that this cumulative measure may be a better predictor of disease . These results have prospect i ve research implication s for Puerto Ricans and other ethnic groups", "Background Discrimination promotes multisystem physiological dysregulation termed allostatic load , which predicts morbidity and mortality . It remains unclear whether weight-related discrimination influences allostatic load . Purpose The aim of this study was to prospect ively examine 10-year associations between weight discrimination , allostatic load , and its components among adults 25–75 years in the Midlife Development in the US Biomarker Sub study . Methods Participants with information on weight discrimination were analyzed ( n=986 ) . At both timepoints , participants self-reported the frequency of perceived weight discrimination across nine scenarios as “ never/rarely ” ( scored as 0 ) , “ sometimes ” ( 1 ) , or “ often ” ( 2 ) . The two scores were averaged and then dichotomized as “ experienced ” versus “ not experienced ” discrimination . High allostatic load was defined as having ≥3 out of 7 dysregulated systems ( cardiovascular , sympathetic/parasympathetic nervous systems , hypothalamic pituitary axis , inflammatory , lipid/metabolic , and glucose metabolism ) , which collectively included 24 biomarkers . Relative risks ( RR ) were estimated from multivariate models adjusted for sociodemographic and health characteristics , other forms of discrimination , and BMI . Results Over 41 % of the sample had obesity , and 6 % reported weight discrimination at follow-up . In multivariable-adjusted analyses , individuals who experienced ( versus did not experience ) weight discrimination had twice the risk of high allostatic load ( RR , 2.07 ; 95 % CI , 1.21 ; 3.55 for baseline discrimination ; 2.16 , 95 % CI , 1.39 ; 3.36 for long-term discrimination ) . Weight discrimination was associated with lipid/metabolic dysregulation ( 1.56 ; 95 % CI 1.02 , 2.40 ) , glucose metabolism ( 1.99 ; 95 % CI 1.34 , 2.95 ) , and inflammation ( 1.76 ; 95 % CI 1.22 , 2.54 ) , but no other systems . Conclusions Perceived weight discrimination doubles the 10-year risk of high allostatic load . Eliminating weight stigma may reduce physiological dysregulation , improving obesity-related morbidity and mortality ", "Chronically stressed rodents who are allowed to eat calorie-dense \" comfort \" food develop greater mesenteric fat , which in turn dampens hypothalamic-pituitary-adrenocortical ( HPA ) axis activity . We tested whether similar relations exist in humans , at least cross-sectionally . Fifty-nine healthy premenopausal women were exposed to a st and ard laboratory stressor to examine HPA response to acute stress and underwent diurnal saliva sampling for basal cortisol and response to dexamethasone administration . Based on perceived stress scores , women were divided into extreme quartiles of low versus high stress categories . We found as hypothesized that the high stress group had significantly greater BMI and sagittal diameter , and reported greater emotional eating . In response to acute lab stressor , the high stress group showed a blunted cortisol response , lower diurnal cortisol levels , and greater suppression in response to dexamethasone . These cross-sectional findings support the animal model , which suggests that long-term adaptation to chronic stress in the face of dense calories result in greater visceral fat accumulation ( via ingestion of calorie-dense food ) , which in turn modulates HPA axis response , result ing in lower cortisol levels", "Background — The impact of overall dietary patterns that reflect actual eating behaviors on mortality caused by cardiovascular or other chronic diseases is largely unknown . Methods and Results — We prospect ively evaluated the relation between dietary patterns and risk of cardiovascular , cancer , and all-cause mortality among 72 113 women who were free of myocardial infa rct ion , angina , coronary artery surgery , stroke , diabetes mellitus , or cancer and were followed up from 1984 to 2002 . Dietary patterns were derived by factor analysis based on vali date d food frequency question naires administered every 2 to 4 years . Two major dietary patterns were identified : High prudent pattern scores represented high intakes of vegetables , fruit , legumes , fish , poultry , and whole grains , whereas high Western pattern scores reflected high intakes of red meat , processed meat , refined grains , french fries , and sweets/desserts . During 18 years of follow-up , 6011 deaths occurred , including 1154 cardiovascular deaths and 3139 cancer deaths . After multivariable adjustment , the prudent diet was associated with a 28 % lower risk of cardiovascular mortality ( 95 % confidence interval [ CI ] , 13 to 40 ) and a 17 % lower risk of all-cause mortality ( 95 % CI , 10 to 24 ) when the highest quintile was compared with the lowest quintile . In contrast , the Western pattern was associated with a higher risk of mortality from cardiovascular disease ( 22 % ; 95 % CI , 1 to 48 ) , cancer ( 16 % ; 95 % CI , 3 to 30 ) , and all causes ( 21 % ; 95 % CI , 12 to 32 ) . Conclusion — Greater adherence to the prudent pattern may reduce the risk of cardiovascular and total mortality , whereas greater adherence to the Western pattern may increase the risk among initially healthy women", "OBJECTIVE The present study investigated the long-term impact of exposure to poverty-related stressors during childhood on allostatic load , an index of physiological dysregulation , and the potential mediating role of substance use . METHOD Participants ( n = 162 ) were rural children from New York State , followed for 8 years ( between the ages 9 and 17 ) . Poverty- related stress was computed using the cumulative risk approach , assessing stressors across 9 domains , including environmental , psychosocial , and demographic factors . Allostatic load captured a range of physiological responses , including cardiovascular , hypothalamic pituitary adrenal axis , sympathetic adrenal medullary system , and metabolic activity . Smoking and alcohol/drug use were tested as mediators of the hypothesized childhood risk-adolescent allostatic load relationship . RESULTS Cumulative risk exposure at age 9 predicted increases in allostatic load 8 years later . Smoking , but not alcohol and drug use , was a significant mediator of the prospect i ve , longitudinal relationship between childhood cumulative risk and adolescent allostatic load . CONCLUSIONS The present paper contributes to the underst and ing of the role of early life stress in health across the life span and of the mechanisms by which adverse childhood environments impact health as children emerge into early adulthood . This knowledge will have implication s for early intervention efforts", "Objective : The purpose of this study was to assess , in borderline hypertensive subjects , the homeostatic and allostatic responses of serum electrolytes , proteins , lipids , hematocrit and renal function to an extreme dietary sodium challenge , and to evaluate whether the responses in these clinical parameters were associated with a concomitant response in blood pressure . Subjects and methods : Data from middle-aged adults with a diagnosis of mild , uncomplicated borderline hypertension were collected at the end of 1-month r and omized trials of low ( 24 ± 13 mmol/day ) and high ( 309 ± 88 mmol/day ) dietary sodium intake . A total of 48 subjects ( 38 men and 10 women ) were examined . Results : Serum sodium increased ( p low to high sodium diets . Serum proteins ( p and hematocit ( p a high sodium diet . However , creatinine clearance ( an indicator of glomerular filtration ) increased with sodium intake ( p = 0.004 ) . None of these biochemical or renal functional responses was associated with a change in blood pressure . Conclusion : There are modest yet significant changes in serum electrolytes associated with changes in dietary sodium intake , suggesting that these ions are under an allostatic control mechanism . Serum proteins also appear to function as allostatic compensatory mechanisms , off setting the net effect of increased serum salinity . It is speculated that the adaptive allostatic renal response to a high sodium diet ( an increase in GFR ) may result in loss of the ability to appropriately vary renal filtration if that diet is chronically maintained", "BACKGROUND The extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain . METHODS We calculated hazard ratios for cause-specific death , according to baseline diabetes status or fasting glucose level , from individual-participant data on 123,205 deaths among 820,900 people in 97 prospect i ve studies . RESULTS After adjustment for age , sex , smoking status , and body-mass index , hazard ratios among persons with diabetes as compared with persons without diabetes were as follows : 1.80 ( 95 % confidence interval [ CI ] , 1.71 to 1.90 ) for death from any cause , 1.25 ( 95 % CI , 1.19 to 1.31 ) for death from cancer , 2.32 ( 95 % CI , 2.11 to 2.56 ) for death from vascular causes , and 1.73 ( 95 % CI , 1.62 to 1.85 ) for death from other causes . Diabetes ( vs. no diabetes ) was moderately associated with death from cancers of the liver , pancreas , ovary , colorectum , lung , bladder , and breast . Aside from cancer and vascular disease , diabetes ( vs. no diabetes ) was also associated with death from renal disease , liver disease , pneumonia and other infectious diseases , mental disorders , nonhepatic digestive diseases , external causes , intentional self-harm , nervous-system disorders , and chronic obstructive pulmonary disease . Hazard ratios were appreciably reduced after further adjustment for glycemia measures , but not after adjustment for systolic blood pressure , lipid levels , inflammation or renal markers . Fasting glucose levels exceeding 100 mg per deciliter ( 5.6 mmol per liter ) , but not levels of 70 to 100 mg per deciliter ( 3.9 to 5.6 mmol per liter ) , were associated with death . A 50-year-old with diabetes died , on average , 6 years earlier than a counterpart without diabetes , with about 40 % of the difference in survival attributable to excess nonvascular deaths . CONCLUSIONS In addition to vascular disease , diabetes is associated with substantial premature death from several cancers , infectious diseases , external causes , intentional self-harm , and degenerative disorders , independent of several major risk factors . ( Funded by the British Heart Foundation and others . )" ]

[ "Objective : Despite evidence demonstrating that risk-factor management is effective in reducing recurrent cerebrovascular disease , there are very few structured care programmes for stroke survivors . The aim was to implement and evaluate an integrated care programme in stroke . Methods : 186 patients with stroke were r and omised to either the treatment ( integrated care ) or control ( usual care ) group and were followed up over 12 months . The Integrated Care for the Reduction of Secondary Stroke ( ICARUSS ) model of integrated care involved collaboration between a specialist stroke service , a hospital coordinator and a patient ’s general practitioner . The primary aim was to promote the management of vascular risk factors through ongoing patient contact and education . Results : In the 12 months poststroke , systolic blood pressure ( sBP ) decreased in the treatment group but increased in controls . The group difference was significant , and remained so when age , sex , disability and sBP at discharge were accounted for ( p = 0.04 ) . Treatment patients also exhibited better modification of body mass index ( p = 0.007 ) and number of walks taken ( p controls . Rankin scores indicated significantly reduced disability in treatment patients relative to controls in the year poststroke ( p = 0.003 ) . Conclusions : Through an integrated system of education , advice and support to both patient and GP , the ICARUSS model was effective in modifying a variety of vascular risk factors and therefore should decrease the likelihood or recurrent stroke or vascular event", "BACKGROUND AND PURPOSE Limited evidence exists on the benefits of organized care for improving risk factor control in patients with stroke or transient ischaemic attack . The effectiveness of an individualized management programme in reducing absolute cardiovascular disease risk in this high-risk population was determined . METHODS This was a prospect i ve , multicentre , cluster-r and omized controlled trial with blinded assessment of outcomes and intention-to-treat analysis . Patients hospitalized for stroke/transient ischaemic attack and aged ≥18 years were recruited from four hospitals . General practice s treating recruited patients were r and omized to provide either usual care or an individualized management programme comprising nurse-led education and review of care plans by stroke specialists in addition to usual care . The primary outcome was a change in cardiovascular Framingham Risk Score between baseline and 12 months . RESULTS From January 2010 to November 2013 , 156 general practice s ( 280 patients ) were r and omly assigned to usual care ( control ) and 159 ( 283 patients ) to the intervention . The median age was 70.1 years ; 65 % were male . Overall , > 80 % of participants were prescribed recommended secondary prevention therapies at baseline . The primary efficacy analysis comprised 533 participants , with 30 either dying or lost to follow-up . In adjusted analyses , no significant between-group difference was found in the cardiovascular risk score at 12 months ( 0.04 , 95 % confidence interval -1.7 , 1.8 ) . CONCLUSIONS The effectiveness of an organized secondary prevention programme for stroke may be limited in patients from high-performing hospitals with regular post-discharge follow-up and communication with general practice", "Background and aim Behavioral and lifestyle interventions in stroke patients need to be intense enough to result in sustainable treatment differences among groups of a r and omized trial . Therefore , we report the effects of multidomain interventions on lifestyle and laboratory parameters after 12 and 24 months from a trial that examined whether intensive risk factor management can prevent cognitive decline in ischemic stroke patients . Methods This prospect i ve r and omized , open-label , blinded endpoint trial recruited patients within three months after acute stroke in five Austrian neurological clinics during June 2010 and November 2012 . One hundred and one patients were r and omized into multidomain intervention and 101 into st and ard care . Lifestyle interventions were individualized to match predefined targets of regular physical activity , healthy diet , and adequate physiological risk factor control . Results A total of 167 participants ( 80 intervention , 87 control ) completed the 12-month visit and 155 ( 76 intervention , 79 control ) the 24-month visit . During the first 12 months , adherence to healthy lifestyle and adequately controlled physiological parameters ( measured by summary scores ) improved significantly in the intervention group compared to controls ( p consumption of reduced-fat milk ( p = 0.031 ) , reduced-fat spreads ( p = 0.007 ) , and fish ( p = 0.021 ) increased in the intervention group from baseline to 12 months but not in controls . After 24 months , the group difference was significant for the lifestyle summary score but no longer for the combined laboratory lifestyle score . Conclusions These results demonstrate that intensified individualized multidomain lifestyle interventions in stroke patients are effective in promoting healthy lifestyle in stroke care", "BACKGROUND hypertension is a common risk factor for stroke/transient ischaemic attack ( TIA ) and there is good evidence that blood pressure ( BP ) control prevents recurrent stroke . We investigated whether telephone follow-up ( TFU ) improved risk factor management in hypertensive patients after stroke/TIA . METHODS we conducted a r and omised controlled trial and assigned hypertensive patients within 1 month of stroke or TIA to receive usual care ( n = 27 ) or usual care plus regular TFU ( n = 29 ) . Primary outcome was the difference in 12 h ambulatory systolic BP change from baseline to 6 months ( DeltaSBP ) in both groups . TFU at 7 days , 1 , 2 and 4 months included patient-focussed education and goal setting . RESULTS mean baseline BP was 145/83 mm Hg ( st and ard deviation ( SD ) 21/14 ) . There was no significant difference in DeltaSBP over 6 months with TFU . Median DeltaSBP was 0 mm Hg ( interquartile range 19.5 ) in the TFU group and 3.0 mm Hg ( 20 ) fall in the usual care group ( P = 0.29 ) . Post hoc analysis showed that statin use increased from baseline to 6 months ( P = 0.02 ) and cholesterol was significantly lower at 6 months in all patients ( mean reduction 0.95 mmol/l ; P BP control over 6-month follow-up in primary care after stroke/TIA", "Objective : To examine the effect of an early exercise and education programme on psychosocial health of transient ischaemic attack ( TIA ) and mild , non-disabling stroke patients . Design : R and omized , parallel-group , clinical trial . Setting : Hospital and academic institution . Participants : A total of 55 newly diagnosed transient ischaemic attack/mild stroke patients ( Mean[SD ] ; 69[11]y ) . Intervention : Participants were r and omized to either an eight-week , twice weekly , 90-minute exercise and education programme ( experimental group ) or to a usual care control group . Main measures : Psychosocial measures ( SF-36 , Hospital Anxiety and Depression Scale , Profile of Mood States , International Physical Activity Question naire , Stroke Awareness Question naire ) were assessed at baseline and eight-week and 12-month follow-up . Results : The experimental group demonstrated improvements in the Physical Component Score ( Mean[SD ] ; 44.1[11.7 ] to 47.4[11.3]% ) , Vitality ( 46.5[12.4 ] to 54.2[14.2]% ) , Physical Functioning ( 45.6[10.7 ] to 51.9[14.7]% ) , Role Physical ( 38.7[10.8 ] to 43.1[13.6]% ) and Global Health ( 49.1[10.3 ] to 54.4[13.6]% ) from the SF-36 , at the eight-week follow-up assessment ( P 0.05 ) . The experimental group demonstrated a greater awareness of the signs and symptoms associated with stroke ( P Mental Component Score ( SF-36 ) , the Hospital Anxiety and Depression Scale or the International Physical Activity Question naire between treatment groups ( P > 0.05 ) . Conclusion : Early engagement in an exercise and education programme may improve physical health perceptions in transient ischaemic attack/mild stroke patients . However , secondary prevention exercise and education programmes warrant further research with regards to their effects on perceptions of mental health in this population group", "Objective : To evaluate whether enhanced secondary prevention more significantly influences readiness to change health behaviour after minor stroke/transient ischaemic attack , compared with conventional stroke secondary prevention . Design : Single-blind r and omized control trial . Setting : Rural district general hospital outpatient clinic . Subjects : Fifteen women and 37 men with a mean age of 68.3 years with first minor stroke or transient ischaemic attack . Interventions : The intervention group received ‘ enhanced secondary prevention ’ ( additional advice , motivational interviewing and telephone support ) to change health behaviour . Both groups received ‘ conventional care ’ which included advice given during routine care . Main measures : The primary outcome was ‘ readiness to change behaviour ’ measured using a vali date d stroke specific score based on the transtheoretical model . Secondary outcomes were the Hospital Anxiety and Depression Scale , and self-reported alcohol consumption , smoking behaviour , exercise frequency , and fruit and vegetable consumption . Results : Analysis of the data for the 52 participants showed no statistical difference in the groups for the primary outcome of readiness to change behaviour . Statistically significant improvements for change in self-reported exercise were demonstrated ( P = 0.007 ) ; to 2—3 times per week in the intervention group compared to 0—1 times per week in the control group , and in fruit and vegetable consumption ( P = 0.033 ) ; to 10 portions of fruit and vegetables consumed per week in the intervention group compared to 1 or 2 portions a week for the control group . No evidence of a difference between groups was seen for alcohol consumption or Hospital Anxiety and Depression Scale . Conclusions : While no difference was demonstrated between the groups for readiness to change behaviour , a clinical ly significant effect in reported exercise behaviour and diet were demonstrated in the intervention group . This interesting finding indicates a dissonance between the behaviour scale and actual behaviour change , potentially indicating a lack of sensitivity of the scale to detect a change in this patient group", "Background : Lifestyle modification is associated with a substantially decreased risk of cardiovascular events . However , the role of lifestyle intervention for secondary prevention in patients with noncardioembolic ischemic stroke is inadequately defined . We assessed the hypothesis that lifestyle intervention can reduce the onset of new vascular events in patients with noncardioembolic mild ischemic stroke . Methods : We conducted an observer-blind r and omized controlled trial that enrolled 70 patients ( 48 men , mean age 63.5 years ) with acute noncardioembolic mild ischemic stroke . The patients were allocated in equal numbers to a lifestyle intervention group or a control group . We performed lifestyle interventions , which comprised exercise training , salt restriction and nutrition advice for 24 weeks . Then all patients were prospect ively followed up for occurrence of the primary endpoints , including hospitalization due to stroke recurrence and the onset of other vascular events . We also evaluated systolic blood pressure ( SBP ) at the clinic and at home , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , hemoglobin A1c ( HbA1c ) and high-sensitivity C-reactive protein ( hs-CRP ) to compare the efficacy of the lifestyle interventions . Results : This trial was terminated earlier than expected because of the prespecified early stopping rule for efficacy . After the 24-week intervention period , the intervention group showed a significant increase in daily physical activity and a significant decrease in salt intake ( physical activity , p = 0.012 ; salt intake , p blood pressure was decreased and the HDL-C levels were increased in the intervention group ( SBP , p LDL-C , HbA1c and hs-CRP tended to decrease in the intervention group , but this decrease did not achieve significance . After a median follow-up period of 2.9 years , 12 patients allocated to the control group and 1 patient in the lifestyle intervention group experienced at least 1 vascular event . A sequential plans analysis indicated the superiority of the lifestyle intervention in interim analysis . Kaplan-Meier survival curves after the log-rank test showed a significant prognostic difference between the r and omized groups ( p = 0.005 ) . Conclusions : Lifestyle intervention with appropriate medication is beneficial for reducing the incidence of new vascular events and improving vascular risk factors in patients with noncardioembolic mild ischemic stroke", "OBJECTIVE We sought to evaluate whether comprehensive postdischarge care management for stroke survivors is superior to organized acute stroke department care with enhanced discharge planning in improving a profile of health and well-being . METHODS This was a r and omized trial of a comprehensive postdischarge care management intervention for patients with ischemic stroke and National Institutes of Health Stroke Scale scores greater than or equal to 1 discharged from an acute stroke department . An advanced practice nurse performed an in-home assessment for the intervention group from which an interdisciplinary team developed patient-specific care plans . The advanced practice nurse worked with the primary care physician and patient to implement the plan during the next 6 months . The intervention and usual care groups were compared using a global and closed hypothesis testing strategy . Outcomes fell into 5 domains : ( 1 ) neuromotor function , ( 2 ) institution time or death , ( 3 ) quality of life , ( 4 ) management of risk , and ( 5 ) stroke knowledge and lifestyle . RESULTS Treatment effect was near 0 SD for all except the stroke knowledge and lifestyle domain , which showed a significant effect of the intervention ( P = .0003 ) . CONCLUSIONS Postdischarge care management was not more effective than organized stroke department care with enhanced discharge planning in most domains in this population . The intervention did , however , fill a postdischarge knowledge gap", "Abstract Goal : Evidence -based guidelines exist for the prevention and treatment of patients with cerebral ischemia . Despite these guidelines , there are gaps in clinical practice . Our study aim ed to determine if a physician-directed , nurse-case-management program could reduce individual patient vascular risk factors . Methods : Patients hospitalized with atherosclerotic cerebral ischemia with ≥ 1 major uncontrolled risk factor for stroke ( hypertension , tobacco use , dyslipidemia , diabetes ) were eligible to enroll in our study . Patients were r and omized to management by the nurse-prevention program or usual care . Patients in the usual-care group received their initial risk-factor assessment and a scheduled follow-up at 1 year . Patients in the usual-care group underwent further follow-up by primary care and /or neurology as recommended during their hospitalization or outpatient visit . Patients assigned to the prevention group received individualized education , motivational interviewing , and were aided in setting up their risk-factor modification goal plan . Additional education was tailored to each patient based on individualized risk factors . Prevention-group patients also underwent consultation with a registered dietitian and an exercise physiologist . The primary endpoint of the study was improvement of ≥ 1 major patient risk factor for occurrence of stroke to goal at 1 year . Results : At 1-year post-hospitalization , patients in the nurse-care-management group were 42 % more likely to have met the primary endpoint ( n = 18 ; 61 % nurse-managed patients ) compared with 33 % ( n = 18 ) of patients undergoing usual care ( P = 0.09 ) . There was no significant reduction in minor risk factors for either patient group . Patients in the prevention group had greater reductions in low-density lipoprotein cholesterol levels ( −38 vs −4 ; P = 0.0083 ) , changes in cardiovascular risk score ( −5.2 vs 1.3 ; P = 0.0033 ) , and had a greater reductions in systolic blood pressure ( −12.2 vs −0.105 ; P = 0.07 ) than their usual-care counterparts ( changes shown respectively ) . Patients in the prevention group were more likely to follow a prescribed diet than those in the usual-care group ( 50 % ) vs 7 % , respectively ; P = 0.0070 ) and maintain an exercise program ( 83 % vs 33 % , respectively ; P = 0.0018 ) . Summary : A physician-directed , nurse case-management system for patients post-hospitalization for cerebral ischemia is feasible and may help improve long-term control of major patient risk factors for stroke . A larger trial is needed to verify trends noted in our study", "Background : Disparities of care among stroke survivors are well documented . Effective interventions to improve recurrent stroke preventative care in vulnerable population s are lacking . Methods and Results : In a r and omized controlled trial , we tested the efficacy of components of a chronic care model – based intervention versus usual care among 404 subjects having an ischemic stroke or transient ischemic attack within 90 days of enrollment and receiving care within the Los Angeles public healthcare system . Subjects had baseline systolic blood pressure ( SBP ) ≥120 mm Hg . The intervention included a nurse practitioner/physician assistant care manager , group clinics , self-management support , report cards , decision support , and ongoing care coordination . Outcomes were collected at 3 , 8 , and 12 months , analyzed as intention-to-treat , and used repeated- measures mixed-effects models . Change in SBP was the primary outcome . Low-density lipoprotein reduction , antithrombotic medication use , smoking cessation , and physical activity were secondary outcomes . Average age was 57 years ; 18 % were of black race ; 69 % were of Hispanic ethnicity . Mean baseline SBP was 150 mm Hg in both arms . SBP decreased to 17 mm Hg in the intervention arm and 14 mm Hg in the usual care arm ; the between-arm difference was not significant ( −3.6 mm Hg ; 95 % confidence interval , −9.2 to 2.2 ) . Among secondary outcomes , the only significant difference was that persons in the intervention arm were more likely to lower their low-density lipoprotein not improve SBP control beyond that attained in usual care among vulnerable stroke survivors . A community-centered component could strengthen the intervention impact . Clinical Trial Registration : URL : https:// clinical trials.gov . Unique identifier : NCT00861081" ]

[ "Background For total hip arthroplasty ( THA ) , minimally invasive surgery ( MIS ) uses a smaller incision and less muscle dissection than the classic approach ( CLASS ) , and may lead to faster rehabilitation . Questions / purpose sDoes minimally invasive hip arthroplasty result in superior clinical outcomes ? Patients and Methods In this double-blind r and omized controlled trial , 120 consecutive primary noncemented THAs in 120 patients were assigned to one of two groups ( MIS or CLASS ) . The r and omization sequence was stratified for two groups of surgeons , ie , those using a posterolateral approach ( PL-CLASS or PL-MIS ) and those using an anterolateral approach ( AL-CLASS or AL-MIS ) . Length of the incisions was 18 cm for the CLASS procedures . MIS incisions were extended at the skin level to 18 cm at the end of the procedure . The primary end point was the Harris hip score ( HHS ) at 6 weeks postoperatively . Patient-centered question naires were obtained preoperatively and after 6 weeks and 1 year . Results For the patients in the MIS group ( average 7.8 cm incision length ) , statistically significant increased mean HHSs were seen compared with the CLASS group at 6 weeks and 1 year . This difference was small and mainly caused by the favorable results of the PL-MIS . In the MIS group , surgical time was longer . A learning curve was observed based on operation time and complication rate . Although not statistically significant , the perioperative complication rate was rather high in the ( anterolateral ) MIS group . Conclusions The minimal invasive approach in THA did not show a clinical ly relevant superior outcome in the first postoperative year . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence", "Background There has been increasing interest in performing total hip arthroplasty ( THA ) with minimally invasive surgery ( MIS ) . This study was conducted to examine the effectiveness of MIS-THA using the new two-incision technique versus the one-incision technique . Methods A consecutive series of 113 patients who underwent MIS-THAs ( 63 one-incision cases , 50 two-incision cases ) were studied . One-incision THA was performed with a posterolateral approach . For the two-incision , the first incision for cup insertion was made over the anterolateral side of the hip . Intermuscular dissection was performed between the gluteus medius and the tensor fascia lata . The second incision , for stem insertion , was made on the posterolateral side of the hip along the fiber of the gluteus maximus . Intermuscular dissection was made between the gluteus medius and the piriformis . Results Postoperative rehabilitation was significantly more rapid in the new two-incision group compared to the group with one incision . Postoperatively , the Harris Hip Score and the Western Ontario and the McMaster Universities Osteoarthritis Index score were significantly different between the two groups , especially the functional sections . Conclusions The findings of this study show that our new two-incision MIS-THA is an excellent surgical modality that allows early rehabilitation", "PURPOSE OF THE STUDY There have been few prospect i ve studies comparing minimally invasive approaches for total hip replacement . We wanted to ascertain the contribution of the minimally invasive posterior approach in comparison with the st and ard posterolateral approach in terms of early outcome . MATERIAL S AND METHODS This was prospect i ve comparative consecutive series of patients . Patients with major architectural problems or undergoing revision arthroplasty were excluded . One hundred ten patients ( 116 hips ) were divided into two groups which were comparable for number of patients , gender , age , body mass index , indication for surgery , and preoperative function scores . The preoperative ASA score was lower in the minimally invasive group ( p=0.04 ) . The patients were in the lateral reclining position for the two approaches and classical instrumentation using the same implants ( stems and cemented or non-cemented cups ) were used . We noted operative time and blood loss ( using the Brecher method based on the hematocrit at day 1 and 5 and the number of blood transfusions ) , postoperative pain , and implant position . Functional outcome was assessed with the modified Harris score and the WOMAC index ( at 6 weeks and 3 and 6 months ) . Statview(R ) was used to search for statistical significance considering p Mean blood loss was significantly less in the minimally invasive group ( p=0.027 ) as was the level of postoperative pain as confirmed by the lesser consumption of morphine analgesics ( p=0.006 ) . Other operative variables as well as implant position were comparable . There were no major complications in the minimally invasive group . In the st and ard group , there was one case of common peroneal nerve palsy , two dislocations , and two fractures related to falls after prosthesis implantation . The WOMAC index was better after the minimally invasive approach at six weeks and at three months ( p modified Harris score was better only at six weeks . Functional outcome and pain became comparable thereafter . DISCUSSION AND CONCLUSION The minimally invasive posterior approach does not require an orthopedic table nor specific instrumentation . A minute procedure is required with ligature of the posteromedial circumflex artery of the thigh to improve exposure and limit intraoperative bleeding . It enables satisfactory reproducible implant positioning . Conversion to an open posterolateral approach is possible if needed . The minimally invasive posterior approach enables a reduction in intraoperative bleeding and in postoperative pain while allowing earlier more rapid rehabilitation . Early clinical outcome is better but beyond six weeks , the functional results are comparable for the two approaches . The minimally invasive posterior approach is a reliable reproducible approach with a progressive learning curve", "BACKGROUND AND PURPOSE Systematic review s and meta-analyses often include an evaluation of the method ological quality of the individual studies that have been included , and are usually conducted by at least 2 individuals . The objective of this study was to assess the method ological quality and reliability of a series of r and omized controlled trials ( RCTs ) of both pharmacological and nonpharmacological interventions by use of the 10-item Physiotherapy Evidence -Based Data base ( PEDro ) Scale . METHODS Two abstract ors independently review ed 81 RCTs assessing a variety of interventions . The Cohen kappa statistic and the intraclass correlation coefficient ( ICC ) were used to assess agreement between abstract ors . RESULTS The average total PEDro scores were 5.94 ( SD=1.43 ) for all studies combined , 6.88 ( SD=1.2 ) for pharmacological studies , and 5.29 ( SD=1.26 ) for nonpharmacological studies . The median score for pharmacological studies was significantly higher than that for nonpharmacological studies ( 7 versus 5 ) . Pair-wise kappa scores ranged from a low of .452 for concealed allocation among drug trials to perfect agreement ( 1.00 ) for r and omization and reporting of results from between-group comparisons . The ICCs associated with the cumulative PEDro score were .91 ( 95 % confidence interval [CI]=.83-.94 ) for all studies , .89 ( 95 % CI=.78-.95 ) for pharmacological studies , and .91 ( 95 % CI=.84-.952 ) for nonpharmacological studies . DISCUSSION AND CONCLUSION The method ological quality for pharmacological interventions was significantly higher than that for nonpharmacological interventions . There was good agreement between raters at an individual item level and in total PEDro scores . A lack of reporting clarity , poor organization of the report , or the failure to include salient details contributed to less-than-perfect agreement between raters", "Minimally invasive total hip arthroplasty using a short skin incision is a subject of much debate in the literature . The present study estimates the possible minimal length of the exposure in an unselected patient cohort and compares the lateral mini-incision technique and traditional total hip arthroplasty ( THA ) . One hundred and two patients were divided into three groups according to the type of surgery and length of incision : mini-incision ( less than 10 cm ) was performed in 38 patients ; midi-incision ( 10–14 cm ) in 43 ; and st and ard-incision ( longer than 14 cm ) in 21 patients . No statistical difference was found with regard to intraoperative and total blood loss , the rate of complications , and postoperative recovery . Significantly decreased body mass index ( BMI ) , shorter operative time , and higher number of hips with malpositioning of the acetabular cup were found in the mini-incision group . These patients , however , experienced less pain in the early postoperative period and were highly satisfied with the cosmetic results . The length of incision was shortened and optimized ( less than 14 cm ) in 82 % of patients , and mini-incision was performed in 38 patients of this unselected cohort . Because of the underst and able dem and of the patients for less invasive intervention , the surgeon should use a smaller but not necessarily mini-incision with minimal soft tissue trauma that still allows him to perform the procedure well , without compromising the type of implants and the otherwise excellent long-term results . R and omized prospect i ve studies are needed to explore the real value of the minimally invasive total hip arthroplasty . RésuméLa chirurgie arthroplastie de la hanche par voie mini invasive est un sujet de débat et de controverse dans la littérature . Cette étude a pour but d’estimer la longueur minimale de la voie d’abord sur une suite de patients non sélectionnés et de comparer la technique de mini incision avec la technique d’incision traditionnelle antérolatérale . Cent deux patients ont été divisés en trois groupes , en fonction du type de chirurgie et en fonction de la longueur d’incision . Premier groupe : mini incision moins de 10 cm chez 38 patients , deuxième groupe : incision moyenne 10 à 14 cm chez 43 patients et troisième groupe : incision st and ard , supérieure à 14 cm chez 21 patients . Aucune différence statistique n’a été trouvée pour la perte sanguine et sur le taux des complications post-opératoires . Dans le groupe des mini incisions peu de sujets avaient une surcharge pondérale , par contre , il existait un gr and nombre de hanches avec une mal position de la cupule . Ces patients ont cependant présenté moins de douleur dans la période post-opératoire et ont été très satisfaits du résultat cosmétique . La longueur de l’incision dans la chirurgie prothétique de la hanche peut être raccourcie et la longueur optimum peut être de moins de 14 cm chez 82 % des patients . Une mini incision a été réalisé dans cette série , chez 38 patients du fait de la dem and e des patients pour une chirurgie mini invasive , les chirurgiens ont utilisé une petite incision avec un minimum de traumatisme des tissus mous . Cette mini incision doit donc permettre au chirurgien de réaliser son intervention correctement sans compromission sur le type d ’ implants , ni sur la qualité des résultats à long terme . Il n’y a pas besoin pour cela nécessairement d’une mini incision néanmoins des études prospect ives r and omisées doivent être réalisées pour explorer le vrai résultat de la chirurgie arthroplastie par voie mini invasive", "Patients are inquiring about mini-incision primary total hip arthroplasty with increasing frequency . There are no published r and omized controlled trials to substantiate cl aims that the mini-incision direct lateral approach is better than a st and ard approach . The purpose of our study was to review our initial experience with the mini-incision technique through the direct lateral approach , with the intent of implementing a r and omized controlled trial if the approach could be shown as safe and effective . Of importance was determining if there is any difference in component positioning and if there is any difference in intraoperative or postoperative complications between the two groups . We retrospectively compared a consecutive series of 87 primary total hip arthroplasties . Thirty-four total hip arthroplasties were done using a mini-incision direct lateral approach . The mean abduction angle was 45 ° for both groups . The femoral stem alignment was within five degrees of neutral in 97 % of the mini group and 94 % of the st and ard group . There were no dislocations , infections , neurologic or wound complications . There were no differences in medical complications or blood transfusions . A significant decrease was found regarding body mass index , which reflects the bias in patient selection and lack of r and omization . We conclude that it is safe to continue further study with this approach because as there was no increase in complications or component malpositioning . Level of Evidence : Therapeutic study , Level III ( retrospective comparative study ) . See the Guidelines for Authors for a complete description of levels of evidence", "BACKGROUND Minimally invasive total hip arthroplasty has stirred substantial controversy with regard to whether it provides superior outcomes compared with total hip arthroplasty performed through longer incisions . The orthopaedic literature is deficient in well- design ed scientific studies to support the clinical superiority of this approach . The objective of this study was to compare the results of a single mini-incision approach with those of a st and ard-incision total hip arthroplasty in the early postoperative period . METHODS Two hundred and nineteen patients ( 219 hips ) admitted for unilateral total hip arthroplasty between December 2003 and June 2004 were r and omized to undergo surgery through a short incision of All patients were blinded to the size of the incision for the duration of the hospital stay . The anesthetic , analgesic , and postoperative physiotherapy protocol s were st and ardized , with the staff also blinded to the technique used . A single surgeon , who had performed more than 300 short-incision hip replacements prior to the start of this study and who performs an average of 415 primary total hip replacements a year , performed all procedures through a single-incision posterior approach using a cementless cup and cemented stem . RESULTS The two groups were matched for age , grade according to the system of the American Society of Anesthesiologists , and body mass index . No significant difference was detected with respect to postoperative hematocrit , blood transfusion requirements , pain scores , or analgesic use . We found no difference in early walking ability or length of hospital stay and no difference in component placement , cement-mantle quality , or functional outcome scores at six weeks . The patient variables significantly associated with a probability of early discharge independent of incision length were patient age and preoperative hemoglobin levels ( p surgical scars contracted significantly over six weeks ( p single-incision posterior approach by a high-volume hip surgeon with extensive experience in less invasive approaches to the hip is safe and reproducible . However , it offers no significant benefit in the early postoperative period compared with a st and ard incision of 16 cm . As it is not known whether lower-volume and less-experienced surgeons can achieve similar results , the mini-incision technique merits further study before wide dissemination and implementation of this family of surgical approaches can be recommended", "AIM Benefits of less damage of soft tissues and muscles in minimally invasive hip replacement lead to expectations of better results in gait rehabilitation . The aim of the study is to evaluate post-operative walking ability in terms of different surgical approaches . METHOD 16 patients underwent a minimally invasive total hip replacement ( MIS group ) and 16 other patients got a THA using a transgluteal approach ( st and ard group ) . Differences in functional indices of ground reaction forces and symmetry indices were measured one day pre-operatively as well as 8 , 14 and 28 weeks post-operatively . The results were compared between the surgical approaches and to an age-matched healthy control group . RESULTS There are significantly reduced pain symptoms and a higher functional ability in both surgical groups 8 weeks post-operatively . There are no differences in gait parameters between the surgical groups after 28 weeks . Trends in gait velocity , temporal parameters and in functional indices of ground reaction forces show advantages for the minimally invasive group 8 and 14 weeks post-operatively . Patients do not reach the age-matched control group . CONCLUSION Obviously the immediate post-operative advantages of minimally invasive hip replacement provide better chances for gait rehabilitation compared to the transgluteal approach . Due to the complexity of the problem clinical and gait analysis studies should be linked more closely", "Total hip arthroplasty through minimally invasive procedures potentially reduces operative trauma , which is expected to result in improved recovery and rehabilitation . We presently perform total hip arthroplasty using minimally invasive techniques via an anterolateral modification of the Watson-Jones approach . This approach is performed in the supine position and requires sterile draping of both legs . It also involves a modified operative technique which preserves the pelvitrochanteric muscles and extends the release of the hip capsule . In order to employ a proven implant system ( BICON-PLUS ® threaded cup , SL-PLUS ® stem ) , it was necessary to modify the stem rasps and use manipulation rasps as trial stems . In this report , we compare 50 conventional total hip replacements with 50 procedures performed using the minimally invasive procedure in terms of blood loss and the duration of the operation . The length of the skin incision varied between 7 and 12 cm with the minimally invasive technique , compared to 15 to 22 cm with the conventional procedure . Both groups were virtually identical with respect to average blood loss ( haemoglobin on 10th post-operative day : minimally invasive group , 108.0 g/L ; conventional group , 112.0 g/L ) and the duration of the procedure ( minimally invasive group , 60 minutes ; conventional group , 58 minutes ) . The position of the implanted components correlated with the pre-operative planning with regard to medial head offset , centre of rotation of the hip , and leg length , and was as satisfactory as that observed with the conventional procedure . The complication rate was low ( 2.9 % ) . Shaft fissures occurred in the first months of use of the minimally invasive procedure before adaptation of the shaft rasps . Dislocations were attributable to improper patient behaviour . Minimally invasive surgery via the anterolateral approach in the supine position was equivalent to the conventional procedure , had a low rate of complications , and did not adversely impact the technical success of the procedure", "In this study , interleukin-6 ( IL-6 ) , C-reactive protein ( CRP ) , and haemoglobin levels were evaluated to compare the degree of surgical invasion between mini and st and ard incisions in total hip arthroplasty ( THA ) . Sixty-two patients admitted for primary cementless THA were enrolled in this r and omised study . The patients were allocated to have surgery through either a mini incision of In each group , inflammatory responses were evaluated by IL-6 , CRP , and haemoglobin levels before operation and one day after operation . Significant differences were not found in IL-6 , CRP , and haemoglobin levels between both groups . At six months after surgery , there were no significant differences in postoperative Harris hip scores or radiographic evaluations between both groups . In conclusion , a 5.0 cm difference in the skin incision to the hip joint seemed to have no influence on the degree of surgical invasion during THA.RésuméAfin de mesurer l ’ importance de l’agression chirurgicale tissulaire dans les prothèses totales de hanche , incision st and ard , versus mini-invasifs , les niveaux d’Interleukin 6 ( IL-6 ) de protéine C-réactive ( CRP ) et d’hémoglobine doivent être appréciés . 62 patients devant bénéficier d’une prothèse totale de hanche primaire sans ciment ont été enrôlés dans cette étude r and omisée . Ces patients devaient bénéficier soit d’une mini-incision inférieure à 10 cm , soit d’une incision st and ard supérieure à 15 cm . Chaque groupe a été évalué avec ces différents facteurs biologiques avant l’intervention et un jour après intervention . Il n’a été trouvé aucune différence significative dans les deux groupes avec ces différents marqueurs Inteleukin , CRP et hémoglobine . Six mois après la chirurgie pas de différence significative non plus au niveau des scores de Harris ou au niveau de l’évaluation radiographique . En conclusion , la différence d’incision cutanée de 5 cm ne semble pas avoir d’influence sur l ’ importance des lésions des parties molles au cours d’une prothèse totale de hanche", "AIMS Our primary aim was to evaluate whether there is really less bleeding in patients for whom the minimally invasive posterior approach is used in comparison with the direct lateral approach for primary total hip arthroplasty . Our secondary aim was to evaluate the clinical functional results after six months as well as the postoperative radiographic result . METHODS In a comparative non-r and om prospect i ve study , 76 adult patients underwent elective total hip arthroplasty using one of two approaches . The minimally invasive posterior approach ( 34 cases ; mini-incision group ) was compared with the st and ard direct lateral approach ( 42 cases ; control group ) . RESULTS Lower total estimated bleeding ( means of 1083.5 ml versus 1682.3 ml ; p lower intraoperative bleeding ( means of 745.6 ml versus 1282.8 ml ; p volume of blood drained after the operation ( means of 340 ml and 399 ml ; p = 0.77 ) . There was also a difference between the two groups regarding the need for allogenic transfusion ( 8.8 % in the mini-incision group versus 28.6 % , p = 0.02 ) . We observed a better clinical result in the mini-incision group ( p = 0.002 ) despite the lack of difference between the two groups in relation to the radiographic result . DISCUSSION Our results draw attention to the possibility that other authors may have underestimated blood losses when using minimally invasive approaches . CONCLUSION The minimally invasive approach gave rise to a positive final impression with regard to lower blood loss", "Scar cosmesis is one of the proposed benefits of mini-incision total hip replacement as opposed to st and ard-incision procedures ; however , there has been no scientific proof of this clinical outcome . The cosmetic appearances of healed incisions of 34 primary total hip replacement procedures done by one surgeon using either a mini-incision ( 20 procedures ) or a st and ard-length incision ( 14 procedures ) were compared at an average of 2 years postoperatively . Each scar ’s appearance was grade d independently by two plastic surgeons using a st and ardized rating system . Patients answered a question naire regarding their subjective assessment of their scar . The blinded observers found that more mini-scars ( six of 20 ) were rated poor than st and ard scars ( one of 14 ) and that more st and ard-incision patients had scars that were rated good . More mini-incision patients ( two of 20 versus zero of 14 ) had wound-healing problems . All the patients thought that their hip scar was acceptable in appearance , but 30 of 31 patients rated the relief of pain and total hip replacement longevity as higher priorities than scar cosmesis . The cosmesis of mini-incision total hip replacement scars may be inferior to st and ard-incision scars because of skin and soft tissue damage produced by high retractor pressures needed for exposure using a limited skin incision . Level of Evidence : Therapeutic study , Level II-2 ( prospect i ve comparative study ) . See the Guidelines for Authors for a complete description of levels of evidence", "Some surgeons have suggested that a minimally invasive two-incision approach allows total hip arthroplasty to be done without cutting or damaging any muscle or tendon . To our knowledge that cl aim has not been supported by any published clinical or basic science data . Our purpose in doing this study was to quantify the extent and location of damage to the abductor and external rotator muscles and tendons after two-incision and mini-posterior total hip arthroplasty . Ten cadavers ( 20 hips ) were studied . In each cadaver one hip r and omly was assigned to the two-incision group and the contralateral hip was assigned to the mini-posterior group . After inserting the total hip arthroplasty components the muscle damage was assessed using a technique described previously . Damage to the muscle of the gluteus medius and gluteus minimus was substantially greater with the two-incision technique than with the mini-posterior technique . Every two-incision total hip replacement caused measurable damage to the abductors , the external rotators , or both . Every mini-posterior hip replacement caused the external rotators to detach during the exposure and had additional measurable damage to the abductor muscles and tendon . We do not support the contention that a two-incision total hip arthroplasty is done without cutting muscle or tendon . None of the two-incision hip replacements were done without cutting , reaming , or damaging the gluteus medius or gluteus minimus muscle or external rotators", "BACKGROUND Minimally invasive total hip arthroplasty is purported to allow an improved and faster rehabilitation in the immediate postoperative period because of reduced soft-tissue damage compared with total hip arthroplasty performed with use of a st and ard approach . In the present study , a minimally invasive approach was compared with a traditional st and ard approach in terms of the effect on gait kinematics as demonstrated with gait analysis and electromyography . METHODS Twenty r and omized patients who underwent a primary total hip replacement with use of a minimally invasive modified Watson-Jones approach ( minimally invasive group ) were compared with a group of twenty patients who underwent a total hip arthroplasty with use of a st and ard transgluteal Hardinge approach ( st and ard group ) . All patients received the same cementless implant , inserted with use of st and ard instruments , and all operations were performed by a single , experienced surgeon . The patients were evaluated with use of three-dimensional gait analysis and dynamic electromyograms at three time points : preoperatively , ten days postoperatively , and twelve weeks postoperatively . Temporospatial and joint-kinematic parameters were evaluated . RESULTS There were no significant differences between the two groups with regard to the temporospatial variables of velocity , cadence , step length , and stride length at any tested time point . With regard to the range of motion of the operatively treated hip , the minimally invasive group had a smaller decrease at the ten-day time point in comparison with the st and ard group . However , this finding was not significant . The reduction in the range of motion was mainly caused by reduced hip extension . A compensatory increase in the pelvic tilt was observed in both groups . One patient in the st and ard group showed a positive Trendelenburg gait ten days postoperatively ; it had disappeared completely at the twelve-week time point . CONCLUSIONS With regard to gait kinematics in the early postoperative period ( three months ) , the present study showed no significant benefit for patients who underwent a total hip arthroplasty through a minimally invasive Watson-Jones approach in comparison with those who were managed with a st and ard transgluteal approach", "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 .", "To assess the potential recovery rate of a minimally invasive total hip replacement technique with minimal soft tissue disruption , an accelerated rehabilitation protocol was implemented with weightbearing as tolerated on the day of surgery . One hundred consecutive patients were enrolled in this prospect i ve study . Ninety-seven patients ( 97 % ) met all the inpatient physical therapy goals required for discharge to home on the day of surgery ; 100 % of patients achieved these goals within 23 hours of surgery . Outpatient therapy was initiated in 9 % of patients immediately , 62 % of patients by 1 week , and all patients by 2 weeks . The mean time to discontinued use of crutches , discontinued use of narcotic pain medications , and resumed driving was 6 days postoperatively . The mean time to return to work was 8 days , discontinued use of any assistive device was 9 days , and resumption of all activities of daily living was 10 days . The mean time to walk ½ mile was 16 days . Furthermore , there were no readmissions , no dislocations , and no reoperations . Therefore , a rapid rehabilitation protocol is safe and fulfills the potential benefits of a rapid recovery with minimally invasive total hip arthroplasty", "Minimally invasive hip arthroplasty is thought to result in less soft tissue damage , earlier ambulation , and improved rehabilitation . This prospect i ve blinded cohort study objective ly analyzed early functional walking ability by stride analysis 2 days postoperatively . Ninety-five patients were analyzed , 43 of who received the minimal incision and 52 the traditional incision . Patients , physiotherapists , and assessors were blinded to the incision used . Velocity , cadence , stride length , operated and nonoperated limb step-length , and the ratio of step length of the operated to nonoperated limbs were recorded . No significant differences in any of these variables were shown between the minimal-incision and traditional-incision groups . This study demonstrates no functional benefits of the minimally invasive incision over the st and ard one in terms of early walking ability", "The interest in minimally invasive approaches for total hip replacement ( THR ) has not waned in any way . We carried out a prospect i ve and comparative study in order to analyse the interest of the anterolateral minimal invasive ( ALMI ) approach in comparison with a minimally invasive posterior ( MIP ) approach . A group of 35 primary THRs with a large head using the ALMI approach was compared with a group of 43 THR performed through a MIP approach . The groups were not significantly different with respect to age , sex , bony mass index , ASA score , Charnley class , diagnoses and preoperative Womac index and PMA score . The preoperative Harris Hip Score was significantly lower in the ALMI group . The duration of surgical procedure was longer and the calculated blood loss more substantial in the ALMI group . The perioperative complications were significantly more frequent in this group , with four greater trochanter fractures , three false routes , one calcar fracture , and two metal back bascules versus one femoral fracture in MIP group . Other postoperative data ( implant positioning , morphine consumption , length of hospital stay , type of discharge ) are comparable , such as the early functional results . No other complication has been noted during the first 6 months . The ALMI approach uses the intermuscular interval between the tensor fascia lata and the gluteus medius . It leaves intact the abductor muscles , the posterior capsule and the short external rotators . The early clinical results are excellent , despite the initial complications related to the initial learning curve for this approach and the use of a large head . The stability and the absence of muscular damage should permit acceleration of the postoperative rehabilitation in parallel with less perioperative complications after the initial learning curve . RésuméNous rapportons une étude prospect i ve et comparative de l’abord antéro-latéral mini invasif de la hanche ( AMLI ) pour 35 arthroplasties totales primaires avec tête de gr and diamètre avec l’abord mini invasif postérieur ( MIP ) pour 43 arthroplasties . Les deux groupes n’étaient pas différents selon l’âge , le sexe , l’indice de masse osseuse , le score ASA , la classe de Charnley , le diagnostic , l’index WOMAC et le score de Merle d’Aubigné et Postel . Le score de Harris était plus faible dans le groupe AMLI . La durée opératoire et la perte sanguine calculée étaient plus importantes dans le groupe AMLI . Dans ce même groupe les complications per-opératoires étaient plus fréquentes , avec quatre fractures du gr and trochanter , trois fausses routes , une fracture du calcar , et deux bascules du composant acétabulaire alors qu’il n’y avait qu’une fracture fémorale dans le groupe MIP . Les autres données post-opératoires étaient identiques notamment le résultat fonctionnel précoce . Il n’y avait pas d’autre complication pendant les 6 premiers mois . L’abord antéro-latéral utilise l’intervalle entre le tenseur et le gluteus medius laissant intact les abducteurs , la capsule postérieure et les pelvi-trochantériens . Les résultats cliniques précoces étaient excellents en dépit des complications initiales liées à la courbe d’apprentissage et l’utilisation d’une tête de gr and diamètre . La stabilité et l’absence de dommage musculaire permettaient une récupération post-opératoire plus précoce", " A group of 42 primary total hip arthroplasties performed through an abridged surgical incision ( group 1 ) was prospect ively compared to a cohort of 42 primary total hip arthroplasties performed through a st and ard surgical incision ( group 2 ) . The length of the incision was 8.8 + /- 1.5 cm for group 1 and 23.0 + /- 2.1 cm for group 2 . The groups were not significantly different with respect to age , height , preoperative Harris Hip scores ( HHS ) , estimated blood loss , or length of hospital stay ( P>.05 ) . Group 1 patients had a lower body mass index than group 2 patients ( P Length of surgery was slightly less for group I ( P = .02 ) . A 0 % incidence was found of infection , nerve palsy , component malposition , and aseptic loosening in both groups . No dislocations occurred in group 1 , and one dislocation occurred in group 2 . Patients in group 1 have expressed considerable enthusiasm regarding the cosmetic appearance of the surgical incisions , and their postoperative HHS are slightly higher than those of group 2 ( P = .042 ) . Total hip arthroplasty can be performed safely and effectively through an abridged surgical incision , but this investigation confirms no dramatic clinical benefit other than cosmetic appeal", "UNLABELLED In arthroplasty the term \" minimal invasive \" not only refers to the length of the skin incision but more so to its soft tissue and thereby muscle-protecting features . STUDY AIM The aim of this study is to compare the early postoperative mobilisation and rehabilitation of the different surgical approaches in cementless total hip arthroplasty . METHODS 27 patients underwent a total hip replacement ( Trilogy cup , MAYO stem ) via a ventral minimal invasive approach ( one incision technique ) ( MIS group ) . 23 patients underwent a total hip replacement with the same implant via a anterolateral transgluteal approach ( st and ard group ) . We evaluated the Harris Hip Score ( HHS ) , the visual analogue scale ( VAS ) for pain and patient satisfaction preoperatively as well as 3 days , 10 days , 6 weeks and 3 months postoperatively . RESULTS After 3 and 10 days the MIS group showed better scores for pain , gait and mobilisation as well as for the overall HHS compared to the st and ard group . These differences could not be shown 6 weeks postoperatively . The MIS group had a significantly higher rate of complications with 22 % transient impairment of the lateral cutaneous nerve . CONCLUSION The patients of the MIS group showed a better mobilisation and rehabilitation during the early postoperative period . This can be attributed to the lessened intraoperative damage of to soft tissue and especially muscle damage . Due to the increased rate of nerve irritations , we modified our surgical approach . The minimal invasive approach to modern hip joint arthroplasty remains a non-st and ard technique . Compared to the st and ard approach it carries additional risks ( like nerve damage and malpositioning of the implants and thus should remain in the h and s of the experienced orthopaedic surgeon in specialised orthopaedic centres", "Objective : To compare the results of single-incision minimally invasive total hip replacement ( ≤ 10 cm ) to st and ard-incision ( 16 cm ) total hip replacement in the early postoperative period with respect to functional and mobilizing ability ( transfers , mobilizing , walking and stair assessment ) . Setting : Orthopaedic wards of a regional orthopaedic centre . Subjects : Two hundred and nineteen total hip replacement patients were tested between December 2003 and June 2004 . Interventions : Patients were r and omized to either total hip replacement through a minimally invasive ( ≤ 10 cm ) or st and ard incision ( 16 cm ) . A single surgeon performed all procedures using the same type of component fixation . Postoperative physiotherapy assessment and treatment was st and ardized . Analgesia was also st and ardized . All patients , physiotherapy staff and assessors were blinded to the incision used . Main outcome measures : Patients were tested two days post operatively and were assessed for the following activities : transfer from supine to sit , transfer from sitting to st and ing , mobilizing , ascending and descending stairs and weight-bearing . Results : The shorter incision offered no significant improvement in patient ability in relation to transfer from lying to sitting , transfer from sitting to st and ing , mobilizing or weight-bearing . Ascending/descending stairs gave a total time for the minimal incision of 38.7 s against 40.8 s for a st and ard incision . There was no difference in walking velocity between the st and ard incision and minimal incision groups two days post operatively ( minimal incision = 0.26 m/s versus st and ard incision = 0.26 m/s ) or six weeks post operatively ( minimal incision = 0.90 m/s versus st and ard incision = 0.93 m/s ) . There was no difference between groups with respect to walking aids at six-week review . The mean length of stay for the minimally invasive approach was 3.65 days ( SD 2.04 ) against 3.68 days ( SD 2.45 ) for the st and ard approach . This was not significantly different . Conclusion : Total hip replacement performed through a minimally invasive incision of ≤ 10 cm compared with a st and ard incision of 16 cm offers no significant benefit in terms of the rate or ability of patients to mobilize and perform functional tasks necessary for safe discharge ", "Background The rehabilitation of patients for total hip arthroplasty is unsatisfactory , especially the prolonged rehabilitation . Aims To explore indications and key points of anterolateral minimally-invasive total hip arthroplasty . Methods 110 patients admitted for unilateral total hip arthroplasty were r and omly selected for surgery with either anterolateral minimally-invasive incision or st and ard posterolateral incision . Demographic data , perioperative index and postoperative function index were recorded and statistically analyzed . Results No significant difference was detected in operation time , abduction angle , anteversion angle , stem alignment and stem fixation . The incision length , blood loss , perioperative transfusion and 100-mm VAS score at the first 24 h in minimally-invasive group were significantly lower . The Harris hip score and Barthel index were significantly higher in minimally-invasive group at 3 months ’ follow-up , but not significantly different 3 years after operation . Conclusions There are fewer traumas , fewer blood losses and more rapid recovery in this approach", "The purpose of this prospect i ve r and omized study was to compare the early results of primary total hip arthroplasties performed with a minimally invasive technique or a st and ard technique . A consecutive series of 70 patients who underwent primary bilateral simultaneous total hip arthroplasties was studied . All procedures were performed through a posterolateral approach . Operative times and duration of hemovac drains were significantly shorter in the group with a minimally invasive technique ( P risk of infection when using this technique . There were no any late transfusions in any of our patients postdischarge . This minimally invasive technique did not offer any advantages because the results were not different , and in our h and s , it increased our infection rate", "Introduction : Minimally invasive surgery represents one of the most recent techniques to have emerged within THA . In conventional THA , the incision typically measures 15–20 cm . Minimal invasive approach defined as less invasive to the skin , muscles , or bone may reduce complications and improve recovery time . A number of different approaches and methods have been described in literature . Purpose : This is a prospect i ve study describing the technique and early results of the modified antero-lateral minimal invasive ( ALMI ) approach and comparing our results to the results of other investigators interested in minimal invasive THA . Material s and methods : Seventy-five consecutive primary total hip arthroplasties ( cemented and cementless ) were done through a modified ALMI approach ( 6–8 cm ) , in which we kept the hip abductors intact . Neither special instruments nor specially design ed prostheses were needed . Minimum follow-up was 12 months . Results : The mean Harris hip score for patients after 12-month follow-up was 90 while the mean Merle d’Abugine mean score was 16.5 . Both scores reached almost the maximum values within 3 months after surgery . The cup abduction angle for 70 % patients was between 35 ° and 45 ° . No femoral stem mal-alignment was recorded . The mean operative time of cemented prosthesis was 65 min while that of the cementless prosthesis was 55 min . No wound complications or dislocations were recorded . All the patients were allowed to weight bear in the second post-operative day and involved in an early rehabilitation program . Conclusion : ALMI hip approach with sparing of hip abductors is safe and gives excellent orientation for positioning of prosthesis components . It also allows early and smooth post-operative rehabilitation with fast recovery of the patient in terms of weight bearing", "BACKGROUND Few prospect i ve r and omized studies have demonstrated benefits of minimally invasive total hip arthroplasty when compared with conventional total hip arthroplasty . We hypothesized that patients treated with a posterior mini-incision would have better results than those treated with a posterior long incision with regard to the achievement of established goals for pain relief and functional recovery permitting hospital discharge by the second postoperative day . METHODS Sixty of 231 eligible patients were r and omized ( with thirty in each group ) to have a total hip arthroplasty performed through either a posterior mini-incision ( 10 + /- 2 cm ) or a traditional long incision ( 20 + /- 2 cm ) . After completion of the total hip arthroplasty , the mini-incision group underwent extension of the skin incision to 20 cm . Patients were evaluated on the basis of self-determined pain scores , requirements for pain medicine , need for assistive gait devices , and time until discharge . Gait analysis provided objective functional assessment . RESULTS The average hospital stay was 63.2 + /- 13.3 hours in the mini-incision group and 73.6 + /- 23.5 hours in the long-incision group ( p = 0.04 ) . More patients with a mini-incision were discharged by the second postoperative day ( p = 0.003 ) and more were using just a single assistive device at the time of discharge ( p = 0.005 ) . As scored on a verbal analog scale of 0 to 10 points , patients with a mini-incision had less pain on each postoperative day and the pain score remained significantly lower at the time of discharge ( mean , 2.2 + /- 1.0 points compared with 3.1 + /- 0.9 points in the long-incision group ; p = 0.002 ) . After hospital discharge , there were no clinical differences in pain or function between the two groups of patients . CONCLUSIONS Compared with conventional total hip arthroplasty performed through a posterior incision , posterior minimally invasive total hip arthroplasty result ed in better early pain control , earlier discharge to home , and less use of assistive devices . Subsequent evaluations at six weeks and three months showed equivalency between the clinical results in the two groups . LEVEL OF EVIDENCE Therapeutic Level", "Technical and patient care improvements have occurred with the posterior mini-incision total hip arthroplasty . We hypothesized that these changes would provide better results for patients . The clinical and radiographic results of 100 total hip arthroplasties done with the posterior mini incision between January 2004 and October 2004 were compared with 100 mini-incision total hip arthroplasties done between December 2001 and September 2002 . There were no differences in diagnosis , age , and body mass index of the patients in each group . Component positions were not compromised in either group . There were improvements in the 2004 group with decreased hospital stay , reduction of postoperative pain and opioid analgesic use , reduced use of assistive devices , and earlier muscle recovery . In the 2004 group there were no complications of infection , dislocation , or sciatic palsy . The posterior mini-incision operation has shown improved results with experience and changes in technique and patient care treatment . Level of Evidence : Therapeutic study , Level IV ( case series ) . See the Guidelines for Authors for a complete description of levels of evidence" ]

[ "Context Daily injections are required for growth hormone ( GH ) replacement therapy , which may cause low compliance as a result of inconvenience and distress in patients . Objective C-terminal peptide-modified human GH ( MOD-4023 ) is developed for once-a-week dosing regimen in GH-deficient ( GHD ) adults and children . The present trial was a safety and dose-finding study for weekly MOD-4023 in GHD children . Design A multicenter , open-label , r and omized , controlled phase 2 study in children with GHD , evaluating the safety , tolerability , pharmacokinetics/pharmacodynamics , and efficacy of three different weekly MOD-4023 doses , compared with daily recombinant human GH ( r-hGH ) . Setting The trial was conducted in 14 endocrinology centers in Europe . Patients Fifty-three prepubertal children with GHD completed 12 months of treatment with either MOD-4023 ( N = 42 ) or r-hGH ( N = 11 ) . Interventions C-terminal peptide-modified hGH ( MOD-4023 ) was administered weekly at a dose of either 0.25 , 0.48 , or 0.66 mg/kg/wk and compared with daily hGH at a dose of 0.24 mg/kg/wk . Results MOD-4023 showed an estimated half-life approximately fivefold to 10-fold longer when compared with daily r-hGH . Insulin-like growth factor (IGF)-I and IGF-binding peptide 3 showed a dose-dependent increase during MOD-4023 treatment . IGF-I st and ard deviation score for MOD-4023 did not exceed + 2 . All MOD-4023 cohorts demonstrated adequate catch-up growth . The 0.66 mg/kg/wk dose demonstrated efficacy closest to daily r-hGH . No serious adverse events were observed during MOD-4023 treatment , and its tolerability was consistent with known properties of r-hGH . Conclusions This study confirms the long-acting properties of MOD-4023 and shows a promising safety and tolerability profile . This provides support for initiation of a phase 3 study in GHD children using a single weekly injection of MOD-4023", "Context TransCon Growth Hormone ( GH ) ( Ascendis Pharma ) is a long-acting recombinant sustained-release human GH prodrug in development for children with GH deficiency ( GHD ) . Objective To compare the pharmacokinetics , pharmacodynamics , safety , and efficacy of weekly TransCon GH to that of daily GH in prepubertal children with GHD . Design R and omized , open-label , active-controlled study of three doses of weekly TransCon GH versus daily Genotropin ( Pfizer ) . Setting Thirty-eight centers in 14 European countries and Egypt . Patients Prepubertal male and female treatment-naïve children with GHD ( n = 53 ) . Interventions Subjects received one of three TransCon GH doses ( 0.14 , 0.21 , or 0.30 mg GH/kg/wk ) or Genotropin 0.03 mg GH/kg/d for 26 weeks . Main Outcome Measures GH and insulinlike growth factor-1 ( IGF-1 ) levels , growth , adverse events , and immunogenicity . Results Both GH maximum concentration and area under the curve were similar following TransCon GH or Genotropin administration at comparable doses . A dose response was observed , with IGF-1 st and ard deviation scores increasing into the normal range for all three TransCon GH doses . Annualized mean height velocity for the three TransCon GH doses ranged from 11.9 cm to 13.9 cm , which was not statistically different from 11.6 cm for Genotropin . Adverse events were mild to moderate , and most were unrelated to the study drug . Injection site tolerance was good . One TransCon GH subject developed a low-titer , nonneutralizing antibody response to GH . Conclusions The results suggest that long-acting TransCon GH is comparable to daily Genotropin for GH ( pharmacokinetics ) and IGF-1 ( pharmacodynamics ) levels , safety , and efficacy and support advancement into phase 3 development", "Background / Aims : MOD-4023 is a long-acting human growth hormone ( hGH ) in clinical trials for the treatment of growth hormone deficiency ( GHD ) . A key goal is maintenance of serum concentrations of insulin-like growth factor ( IGF ) 1 within normal range throughout GH dosing . The study aim ed to develop a pharmacokinetic model for MOD-4023 and a pharmacodynamic model for the effect of MOD-4023 on IGF-1 to allow estimation of peak and mean IGF-1 and to identify the optimal IGF-1 sampling day . Methods : MOD-4023 ( 0.25 , 0.48 , or 0.66 mg/kg ) was administered weekly for 12 months to 41 GH-naive GHD children ( age 3–11 years ) . The control group ( n = 11 , age 4–9 years ) received daily recombinant human growth hormone ( r-hGH ; 34 µg/kg ) . Sparse sample s ( 4/subject ) were obtained to determine serum concentrations of MOD-4023 or r-hGH and IGF-1 . Results : A 2-compartment pharmacokinetic model with first-order absorption fit MOD-4023 data well ; a 1-compartment model was appropriate for r-hGH . For both , weight-normalized systemic parameters were preferred over allometric scaling . For MOD-4023 , an indirect model fit IGF-1 SDS data well ; baseline IGF-1 increased over time . At steady state , sample s obtained 4 days following dose administration predicted mean IGF-1 SDS during the dosing interval well . Conclusion : The IGF-1 profile is consistent with the weekly dosing interval . Sampling 4 days following dose administration allows estimation of mean IGF-1 SDS during the dosing interval in GHD patients ", "CONTEXT LB03002 is a novel sustained-release GH preparation administered once weekly . OBJECTIVE Our objective was to examine the pharmacokinetics , pharmacodynamics , and safety of LB03002 vs. daily GH . DESIGN AND SETTING This open-label , crossover study compared the pharmacokinetics and pharmacodynamics of LB03002 and daily GH . PATIENTS AND OTHER PARTICIPANTS Six male and three female patients with adult GH deficiency participated in the single-center study . INTERVENTION Subjects were on stable daily GH treatment before the study . After a 4-wk washout with no GH , five weekly doses of LB03002 were given . MAIN OUTCOME MEASURE GH and IGF-I concentrations were measured during the last dose of daily GH and during the first and fifth weekly doses of LB03002 . RESULTS The observed maximal serum GH concentration was approximately doubled after LB03002 ( 6.1 + /- 3.2 and 4.5 + /- 2.2 microg/liter at first and fifth doses ) compared with daily GH ( 2.7 + /- 2.2 microg/liter ) . A sustained increase in GH concentration for more than 48 h was observed with LB03002 , such that dose-normalized area under the curve ( AUC ) was not significantly different between daily GH and LB03002 . Mean maximal serum IGF-I concentration was 34 - 41 % greater with LB03002 than with daily GH , and AUC was 7-fold greater . However , normalized to GH dose , AUC for IGF-I was comparable . Adverse events and local reactions were acceptable , and there were no evident safety concerns with LB03002 . CONCLUSIONS Multiple weekly doses of LB03002 appeared safe and well tolerated . Comparable GH bioavailability and sustained IGF-I elevations support the use of once-weekly LB03002 to replace daily GH therapy", "Objective We assessed the efficacy and safety of a weekly pegylated human growth hormone ( PEG-rhGH ) ( Jintrolong ) vs daily rhGH for children with growth hormone deficiency ( GHD ) . Design Phase II and III , multicenter , open-label , r and omized controlled trials . Methods 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively . Patients in the phase II study were r and omized 1:1:1 to weekly Jintrolong ( 0.1 mg/kg/week PEG-rhGH complex ) , weekly Jintrolong ( 0.2 mg/kg/week PEG-rhGH complex ) or daily rhGH ( 0.25 mg/kg/week ) for 25 weeks . Patients in the phase III study were r and omized in a 2:1 ratio to weekly Jintrolong ( 0.2 mg/kg/week ) or daily rhGH ( 0.25 mg/kg/week ) for 25 weeks . The primary endpoint for both studies was height velocity ( HV ) increase at the end of treatment . Other growth-related parameters , safety and compliance were also monitored . Results The phase II study established the preliminary efficacy , safety and recommended dose of Jintrolong PEG-rhGH . In the phase III study , we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment ( from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year ) vs daily rhGH ( from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year ) at the end of treatment ( P the height st and ard deviation scores was associated with Jintrolong throughout the treatment ( P compliance were comparable between the two groups . Conclusion Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH", "Objective Growth hormone ( GH ) replacement therapy currently requires daily injections , which may cause distress and low compliance . C-terminal peptide (CTP)-modified growth hormone ( MOD-4023 ) is being developed as a once-weekly dosing regimen in patients with GH deficiency ( GHD ) . This study ’s objective is to evaluate the safety , pharmacokinetics ( PK ) , pharmacodynamics ( PD ) and efficacy of MOD-4023 administered once-weekly in GHD adults . Design 54 adults with GHD currently treated with daily GH were normalized and r and omized into 4 weekly dosing cohorts of MOD-4023 at 18.5 % , 37 % , 55.5 % or 123.4 % of individual cumulative weekly molar hGH dose . The study included 2 stages : Stage A assessed the effectiveness and PK/PD profiles of the 4 dosing regimens of MOD-4023 . Stage B was an extension period of once-weekly MOD-4023 administration ( 61.7 % molar hGH content ) to collect further safety data and confirm the results from Stage A. Results Dose-dependent response was observed for both PK and PD data of weekly MOD-4023 treatment . Insulin-like growth factor I ( IGF-I ) SDS levels were maintained within normal range . The 18.5 % cohort was discontinued due to low efficacy . MOD-4023 was well tolerated and exhibited favorable safety profile in all dose cohorts . The reported adverse events were consistent with known GH-related side effects . Conclusions Once-weekly MOD-4023 administration in GHD adults was found to be clinical ly effective while maintaining a favorable safety profile and may obviate the need for daily injections . Weekly GH injections may improve compliance and overall outcome . The promising results achieved in this Phase 2 study led to a pivotal Phase 3 trial , which is currently ongoing", "BACKGROUND Insulin-like growth factor-I ( IGF-I ) is a potent mitogen for normal and neoplastic cells , whereas IGF-binding protein-3 ( IGFBP-3 ) inhibits cell growth in many experimental systems . Acromegalics , who have abnormally high levels of growth hormone and IGF-I , have higher rates of colorectal cancer . We therefore examined associations of plasma levels of IGF-I and IGFBP-3 with the risk of colorectal cancer in a prospect i ve case-control study nested in the Physicians ' Health Study . METHODS Plasma sample s were collected at baseline from 14916 men without diagnosed cancer . IGF-I , IGF-II , and IGFBP-3 were assayed among 193 men later diagnosed with colorectal cancer during 14 years of follow-up and among 318 age- and smoking-matched control subjects . All P values are two-sided . RESULTS IGFBP-3 levels correlated with IGF-I levels ( r=.64 ) and with IGF-II levels ( r=.90 ) . After controlling for IGFBP-3 , age , smoking , body mass index ( weight in kg/[height in m]2 ) , and alcohol intake , men in the highest quintile for IGF-I had an increased risk of colorectal cancer compared with men in the lowest quintile ( relative risk [RR]=2.51 ; 95 % confidence interval [CI]=1.15 - 5.46 ; P for trend = .02 ) . After controlling for IGF-I and other covariates , men with higher IGFBP-3 had a lower risk ( RR=0.28 ; 95 % CI=0.12 - 0.66 ; P for trend = .005 , comparing extreme quintiles ) . The associations were consistent during the first and the second 7-year follow-up intervals and among younger and older men . IGF-II was not associated with risk . CONCLUSIONS Our findings suggest that circulating IGF-I and IGFBP-3 are related to future risk of colorectal cancer", "BACKGROUND Insulin-like growth factor (IGF)-I , a mitogenic and antiapoptotic peptide , can affect the proliferation of breast epithelial cells , and is thought to have a role in breast cancer . We hypothesised that high circulating IGF-I concentrations would be associated with an increased risk of breast cancer . METHODS We carried out a nested case-control study within the prospect i ve Nurses ' Health Study cohort . Plasma concentrations of IGF-I and IGF binding protein 3 ( IGFBP-3 ) were measured in blood sample s collected in 1989 - 90 . We identified 397 women who had a diagnosis of breast cancer after this date and 620 age-matched controls . IGF-I concentrations were compared by logistic regression with adjustment for other breast-cancer risk factors . FINDINGS There was no association between IGF-I concentrations and breast-cancer risk among the whole study group . In postmenopausal women there was no association between IGF-I concentrations and breast-cancer risk ( top vs bottom quintile of IGF-I , relative risk 0.85 [ 95 % CI 0.53 - 1.39 ] ) . The relative risk of breast cancer among premenopausal women by IGF-I concentration ( top vs bottom tertile ) was 2.33 ( 1.06 - 5.16 ; p for trend 0.08 ) . Among premenopausal women less than 50 years old at the time of blood collection , the relative risk was 4.58 ( 1.75 - 12.0 ; p for trend 0.02 ) . After further adjustment for plasma IGFBP-3 concentrations these relative risks were 2.88 and 7.28 , respectively . INTERPRETATION A positive relation between circulating IGF-I concentration and risk of breast cancer was found among premenopausal but not postmenopausal women . Plasma IGF-I concentrations may be useful in the identification of women at high risk of breast cancer and in the development of risk reduction strategies . Additional larger studies of this association among premenopausal women are needed to provide more precise estimates of effect", "BACKGROUND GH treatment currently requires daily sc injections , result ing in suboptimal compliance . A GH regimen with fewer injections may offer patients and caregivers a less arduous option . LB03002 is a novel sustained-release GH formulation for once-weekly dosing . PATIENTS AND METHODS GH-deficient , GH-naive prepubertal children were r and omized to four groups who received 0.2 mg/kg/wk LB03002 for 12 months , followed by 0.5 mg/kg/wk for another 24 months ( n=13 ) ; 0.5 mg/kg/wk LB03002 for 36 months ( n=13 ) ; 0.7 mg/kg/wk LB03002 for 12 months , followed by 0.5 mg/kg/wk for another 24 months ( n=13 ) ; or daily GH 0.03 mg/kg/d for 24 months , switched to 0.5 mg/kg/wk LB03002 for 12 months ( n = 12 ) . RESULTS Height velocity increased in all groups ; the increase was less for the 0.2 mg/kg/wk LB03002 group at 12 ( P = 0.008 ) and 24 months ( P = 0.030 ) , with no statistically significant differences at any time for the 0.5 mg/kg/wk and 0.7 mg/kg/wk LB03002 groups , vs. daily GH . Height sd score gain at 12 months was significantly ( P = 0.023 ) less for the 0.2 mg/kg/wk group ( 1.05 ± 0.38 ) than daily GH ( 1.47 ± 0.29 ) , but with no statistically significant difference for the 0.5 mg/kg/wk ( 1.37 ± 0.39 ) and 0.7 mg/kg/wk ( 1.50 ± 0.44 ) LB03002 groups vs. daily GH . There were no significant differences in height sd score gain between any groups at 24 and 36 months . Bone maturation did not differ for any LB03002 dose compared with daily GH . Serum IGF-I concentrations increased as expected , with no long-term differences between groups . Mean fasting glucose and glycosylated hemoglobin concentrations did not exceed normal ranges for any treatment group at any time . CONCLUSION LB03002 at doses of 0.5 mg/kg/wk and 0.7 mg/kg/wk was shown to be effective and safe with once-weekly dosing in GH-deficient children , and 0.5 mg/kg/wk LB03002 was chosen as the optimal dose for long-term assessment", "To evaluate the safety , local tolerability , pharmacodynamics and pharmacokinetics of escalating single doses of once‐weekly somapacitan , a reversible , albumin‐binding GH derivative , vs once‐daily GH in children with GH deficiency ( GHD )", "Background / Aims : To determine the optimal dose of LB03002 , a sustained-release , once-weekly formulation of recombinant human growth hormone ( rhGH ) , and to compare its efficacy and safety with daily rhGH in children with idiopathic short stature ( ISS ) . Methods : This multicenter , r and omized , open-label , phase II study included GH-naïve , prepubertal children with ISS , r and omized to receive daily rhGH 0.37 mg/kg/week ( control , n = 16 ) , LB03002 0.5 mg/kg/week ( n = 14 ) , or LB03002 0.7 mg/kg/week ( n = 16 ) . The primary endpoint was height velocity ( HV ) change at week 26 . Results : At week 26 , the least square ( LS ) means for HV change ( cm/year ) with control , LB03002 0.5 mg/kg/week , and LB03002 0.7 mg/kg/week were 5.08 , 3.65 , and 4.38 , and the LS means for the change in height st and ard deviation score were 0.65 , 0.49 , and 0.58 , respectively . The lower bound of the 90 % confidence interval for the difference between LB03002 0.7 mg/kg/week and the control in the LS mean for HV change ( –1.72 ) satisfied the noninferiority margin ( –1.75 ) . Adverse events were generally mild and short-lived . Conclusion : A once-weekly regimen of LB03002 0.7 mg/kg demonstrated noninferiority to the daily regimen of rhGH 0.37 mg/kg/week in terms of HV increments . LB03002 was well tolerated and its safety profile was comparable with that of daily rhGH", "BACKGROUND Sustained-release GH formulations may provide a strategy for improving treatment compliance and persistence in GH-deficient patients . OBJECTIVE The aim of the study was to examine efficacy and safety of LB03002 , a sustained-release GH formulation for once-weekly administration . DESIGN We conducted a phase III , 12-month , multinational , r and omized , open-label , comparator-controlled trial with a 12-month uncontrolled extension . PATIENTS Prepubertal GH treatment-naive GH-deficient children ( mean age , 7.8 y ) participated in the study . INTERVENTION We administered once-weekly LB03002 ( n=91 ) or daily GH ( n=87 ) for 1 year , followed by once-weekly LB03002 for all patients for another year ( LB03002 throughout , n=87 ; switched to LB03002 , n=80 ) . OUTCOME MEASURES Height , height velocity ( HV ) , IGF-1 , GH antibodies , and adverse events were determined throughout . Primary analysis was noninferiority of LB03002 vs daily GH at 1 year by analysis of covariance . RESULTS Mean±SD HV during year 1 was 11.63±2.60 cm/y with LB03002 , and 11.97±3.09 cm/y with daily GH , with increases from baseline of 8.94±2.91 and 9.04±3.19 cm/y , respectively . The least square mean HV difference for LB03002 - daily GH was -0.43 cm/y ( 99 % confidence interval , -1.45 to 0.60 cm/y ) . Mean HV also remained above baseline in year 2 ( 8.33±1.92 cm/y in the LB03002 throughout group , and 7.28±2.34 cm/y in the switched to LB03002 group ) . Injection site reactions occurred more frequently in LB03002-treated patients but were considered mild to moderate in > 90 % of cases . CONCLUSIONS Growth response with once-weekly LB03002 in GH-deficient children is comparable to that with daily GH , achieving expected growth rates for 24 months . Once-weekly LB03002 is a strong c and i date for long-term GH replacement in GH-deficient children" ]

[ " A series of 80 patients with cervical , trochanteric or subtrochanteric hip fractures were r and omized to either treatment without traction , skin traction , or skeletal traction during the 1883 h between admission and operation . The institution of skin or skeletal traction was not particularly painful for the patient , but we found no indication that either was of discernible benefit . The number of analgesic medications needed was no higher in patients without traction . We conclude that traction should not be administered routinely to patients awaiting operation for hip fracture", "We r and omised 50 patients with extracapsular fractures of the femoral neck to receive either a bupivacaine femoral nerve block or systemic analgesia alone . A femoral nerve block was found to be an easy and effective procedure which significantly reduced perioperative analgesic requirements and postoperative morbidity", "Background : Hip fracture surgery usually carries a high dem and for rehabilitation and a significant risk of perioperative morbidity and mortality . Postoperative epidural analgesia may reduce morbidity and has been shown to facilitate rehabilitation in elective orthopedic procedures . No studies exist on the effect of postoperative epidural analgesia on pain and rehabilitation after hip fracture surgery . Methods : Sixty elderly patients were included in a r and omized , double-blind study comparing 4 days of continuous postoperative epidural infusion of 4 ml/h bupivacaine , 0.125 % , and 50 & mgr;g/ml morphine versus placebo . Both patient groups received balanced analgesia and intravenous nurse-controlled analgesia with morphine . All patients followed a well-defined multimodal rehabilitation program . Pain , ability to participate in four basic physical functions , and any factors restricting participation were assessed on the first 4 postoperative days during physiotherapy . Results : Epidural analgesia provided superior dynamic analgesia during all basic physical functions , and patients were significantly less restricted by pain , which was the dominating restricting factor in the placebo group . Motor blockade was not a restricting factor during epidural analgesia . Despite improved pain relief , scores for recovery of physical independence were not different between groups . Conclusion : Postoperative epidural analgesia after hip fracture surgery provides superior analgesia attenuating pain as a restricting factor during rehabilitation without motor dysfunction . However , superior analgesia did not translate into enhanced rehabilitation . Future studies with multimodal rehabilitation are required to establish whether superior analgesia can be translated into enhanced rehabilitation and reduced morbidity in hip fracture patients", "Background Recent studies have indicated that unmanaged pain , both acute and chronic , can affect mental status and might precipitate delirium , especially in elderly patients with hip fractures . The aim of this study was to assess the effectiveness of fascia iliaca compartment block ( FICB ) for prevention of perioperative delirium in hip surgery patients who were at intermediate or high risk for this complication . Material s and methods On admission , all included patients were divided into three groups according to low , intermediate or high risk for perioperative delirium . Eligible patients ( those classified as at intermediate or high risk for developing delirium ) were sequentially r and omly assigned to study treatment ( FICB prophylaxis or placebo ) according to a computer-generated r and omization code . The primary outcome was perioperative delirium . Diagnosis of the syndrome was defined using the Diagnostic and Statistical Manual of Mental Disorders , 4th edition ( DSM-IV ) and Confusion Assessment Method ( CAM ) criteria . Secondary outcome variables were severity of delirium and delirium duration . Results Delirium occurred in 33 ( 15.94 % ) out of 207 patients r and omized to FICB prophylaxis or the placebo group . Incidence of delirium in the FICB prophylaxis group was 10.78 % ( 11/102 ) , significantly different from the incidence ( 23.8 % , 25/105 ) in the placebo group [ relative risk 0.45 , 95 % confidence interval ( CI ) 0.23–0.87 ] . Nine of 17 patients with high risk for delirium and included in the FICB prophylaxis group developed delirium , whereas 10 of 16 high-risk patients included in the placebo group became delirious ( relative risk 0.84 , CI 0.47–1.52 ) . Two of 85 patients with intermediate risk for delirium and included in the FICB prophylaxis group developed delirium , whereas 15 of 89 intermediate-risk patients included in the placebo group became delirious ( relative risk 0.13 , CI 0.03–0.53 ) . Severity of delirium according to the highest value of the DRSR-98 during an episode with delirium in patients in the FICB prophylaxis group was on average 14.34 , versus 18.61 in the placebo group ( mean difference 4.27 , 95 % CI 1.8–5.64 , P 0.001 ) . Mean duration of delirium in the FICB prophylaxis group was significantly shorter than in the placebo group ( FICB 5.22 days versus placebo 10.97 days , 95 % CI 3.87–7.62 , P high-risk patients between FICB prophylaxis and placebo groups in terms of delirium incidence . However , FICB prophylaxis significantly prevented delirium occurrence in intermediate-risk patients . Thus FICB prophylaxis could be beneficial , particularly for intermediate-risk patients ", "The purpose of this prospect i ve , r and omized , double-blinded study was to evaluate the sensory onset time and the quality of sensory block of ropivacaine , a new long-acting local anesthetic , compared with bupivacaine , for 3-in-1 blocks . Fifty ASA physical status I – III patients undergoing hip surgery after trauma were r and omly assigned to two study groups of 25 patients each . The two study groups received a 3-in-1 block with either 20 mL of ropivacaine 0.5 % or 20 mL of bupivacaine 0.5 % . Blocks in both groups were performed using a nerve stimulator . The sensory onset time and the quality of sensory block was assessed by pinprick test in the central sensory region of each of the three nerves and compared with the same stimulation in the contralateral leg . We used a scale from 100 % ( normal sensation ) to 0 % ( no sensory sensation ) . We did not find significant differences in sensory onset times between the ropivacaine group and the bupivacaine group ( 30 ± 11 vs 32 ± 10 min ) . The quality of sensory blocks was also comparable between the study groups ( 19 % ± 20 % vs 21 % ± 15 % ) . We conclude that the sensory onset time and quality of sensory block during 3-in-1 blocks performed with ropivacaine are comparable to those with bupivacaine . Ropivacaine is described as being less potent than bupivacaine , making this local anesthetic promising for 3-in-1 blocks because of its reportedly lower incidence of cardiovascular and central nervous system complications . Implication s Ropivacaine 0.5 % has a sensory onset time and quality of sensory block during 3-in-1 blocks similar to that of bupivacaine 0.5 % . Ropivacaine is described as being less potent than bupivacaine , making it a promising local anesthetic for 3-in-1 blocks because of its reportedly lower cardiovascular and central nervous system toxicity", "OBJECTIVES Auricular acupressure is known to decrease the level of anxiety in patients during ambulance transport . The purpose of this r and omized , double-blind , sham control study was to determine whether auricular acupressure can decrease not only the level of anxiety but also the level of pain in a group of elder patients with acute hip fracture . METHODS With the assistance of the Vienna Red Cross , 38 patients with acute hip fracture were enrolled into this study . Patients were r and omized into two study groups : the true intervention group and the sham control group . Subjects in the true intervention group ( n = 18 ) received bilateral auricular acupressure at three auricular acupressure points for hip pain . Patients in the sham group ( n = 20 ) received bilateral auricular acupressure at sham points . Baseline demographic information , anxiety level , pain level , blood pressure , and heart rate were obtained before the administration of the appropriate acupressure intervention . The level of anxiety , level of pain , hemodynamic profiles , and level of satisfaction were reassessed once the patients arrived at the hospital . RESULTS Patients in the true intervention groups had less pain ( F = 28 , p = 0.0001 ) and anxiety ( F = 4.3 , p = 0.018 ) and lower heart rate ( F = 18 , p = 0.0001 ) on arrival at the hospital than did patients in the sham control group . As a result , the patients in the true intervention group reported higher satisfaction in the care they received during the ride to the hospital . CONCLUSIONS The authors encourage physicians , health care providers , and emergency rescuers to learn this easy , noninvasive , and inexpensive technique for its effects in decreasing anxiety and pain during emergency transportation", "A consecutive series of 100 patients with femoral neck fractures were assessed by a mental test score on admission . The 67 scoring within the normal range were r and omly assigned to skin traction or no traction between admission and operation . Using pain assessment scales and records of analgesic consumption , there was found to be little difference between the two groups . The conclusion was that skin traction offered no benefits in pain control for the patient and therefore should not be used routinely", "OBJECTIVES To evaluate the rate of postoperative complications , length of stay , and 1-year mortality before and after introduction of a comprehensive multidisciplinary fast-track treatment and care program for hip fracture patients ( the optimized program ) . DESIGN Retrospective chart review with historical control . SETTING Orthopedic ward ( 110 beds ) at a university hospital ( 700 beds ) . PARTICIPANTS Five hundred thirty-five consecutive patients aged 40 and older ( 94%>or=60 ) hospitalized for hip fracture between January 1 , 2003 , and March 31 , 2004 . Three hundred and thirty-six patients ( 70.3 % ) were community dwellers before the fracture and 159 ( 29.7 % ) were admitted from nursing homes . INTERVENTION The fast-track treatment and care program included a switch from systemic opiates to a local femoral nerve catheter block ; an earlier assessment by the anesthesiologist ; and a more- systematic approach to nutrition , fluid and oxygen therapy , and urinary retention . RESULTS In the intervention group , the rate of any in-hospital postoperative complication was reduced from 33 % to 20 % ( odds ratio=0.61 , 95 % confidence interval=0.4 - 0.9 ; P=.002 ) . Rates of confusion ( P=.02 ) , pneumonia ( P=.03 ) , and urinary tract infection ( P length of stay was 15.8 days in the control group , versus 9.7 days in the intervention group ( P 12-month mortality was 23 % in the control group versus 12 % in the intervention group ( P=.02 ) . Overall 12-month mortality was 29 % in the control group and 23 % in the intervention group ( P=.2 ) . CONCLUSION The optimized hip fracture program reduced the rate of in-hospital postoperative complications and mortality . R and omized clinical trials are needed to confirm these results and eluci date the elements of the program that have the greatest effect on clinical outcomes and mortality", "OBJECTIVES To compare the intraoperative hemodynamic effects and ephedrine requirements in elderly patients undergoing orthopedic surgery under subarachnoid anesthesia with hyperbaric bupivacaine with or without fentanyl . MATERIAL AND METHODS Sixty patients over 75 years of age and scheduled for semi-urgent surgical repair of a fractured femur were r and omized to two groups . Group F received subarachnoid surgery with 5 mg of bupivacaine and 15 micrograms of fentanyl . Group B received 7.5 mg bupivacaine . We recorded blood pressure , heart rate and oxygen saturation every 5 minutes and extension of anesthesia . Hemodynamic changes and ephedrine required by each patient were analyzed , along with side effects . RESULTS Group F patients were more hemodynamically stable 10 and 20 minutes after infusion of the anesthetic , and more hypotensive episodes occurred in group B. Group B consumed significantly more ephedrine ( p total dose of ephedrine administered was greater in group B ( 190 mg ) than in group F ( 40 mg ) . The extension of anesthetic block was sufficient for surgery in all cases . No side effects from fentanyl administration were observed . CONCLUSION Adding fentanyl to the local anesthetic used for subarachnoid anesthesia in elderly patients is effective for maintaining greater hemodynamic stability , allowing use of a lower dose of hyperbaric bupivacaine and reducing the need for intravenous ephedrine during surgery", "STUDY OBJECTIVE We determine whether 3-in-1 femoral nerve block is effective as analgesia for fractured neck of femur when administered by emergency physicians . METHODS This was a prospect i ve , r and omized controlled trial with blinded assessors conducted in a district general hospital emergency department in the United Kingdom . Over a 6-month period , all patients with fractured neck of femur were considered for study . Patients were r and omly assigned to receive 3-in-1 nerve block with bupivacaine plus intravenous morphine or intravenous morphine . An accreditation package for all ED medical staff was devised to ensure competence in the technique of 3-in-1 nerve block . Pain scores were recorded on arrival and at intervals up to 24 hours after admission . Morphine consumption in the first 24 hours was recorded . RESULTS Ninety-four patients sustained fractured neck of femur during the study period ; 50 were studied . Of 44 not studied , 42 were confused , 1 did not consent , and 1 was overlooked . Patients receiving 3-in-1 nerve blocks recorded a faster time to reach the lowest pain score : 2.88 hours for patients with nerve block and 5.81 hours for control patients ( mean difference -2.93 h ; 95 % confidence interval [ CI ] -5.48 to -0.38 h ) . Nerve block recipients required significantly less morphine per hour than control patients ( mean of 0.49 mg/h versus 1.17 mg/h ; mean difference -0.68 mg/h ; 95 % CI -1.23 to -0.12 mg/h ) . CONCLUSION Three-in-one femoral nerve block is an effective method of providing analgesia to patients with fractured neck of femur in the ED . All grade s of medical staff were able to apply and consoli date this skill", "Purpose : Levobupivacaine has been extensively evaluated for spinal anesthesia . Its pharmacologic properties are similar to those of bupivacaine , but differences in density between two commercially-available preparations of plain levobupivacaine might lead to different block profiles . We examined the characteristics of spinal anesthesia using the same dose of 0.5 % and 0.75 % plain levobupivacaine . Methods : In this r and omized , controlled , double-blind clinical trial , 60 ASA I-III patients , scheduled for hip fracture surgery , were r and omly allocated to receive spinal anesthesia with 15 mg of either 0.5 % ( group Levo-0.5 ) , or 0.75 % ( group Levo-0.75 ) plain levobupivacaine . Onset time ( primary outcome ) , sensory block height level by pinprick , motor block using a modified Bromage scale , and hemodynamic variables were recorded . Results : In group Levo-0.5 ( n=29 ) , surgical anesthesia was obtained within 15 ( 10–20 ) min , compared to 12 ( 7–21 ) min in group Levo-0.75 ( n=31 ) ( p=0.409 ) . The highest sensory block level was T11 ( T6–T12 ) in group Levo-0.5 , and T10 ( T8–T12 ) in group Levo-0.75 ( p=0.759 ) . Mean duration of anesthesia was 285 ( 224–303 ) min in group Levo-0.5 , and 318 ( 243–375 ) min in group Levo-0.75 ( p=0.117 ) . The groups were similar in regards to the number of failed blocks requiring general anesthesia , and the number of patients requiring vasopressors . Conclusions : In this population of elderly patients , spinal anesthesia with 15 mg of either 0.5 % or 0.75 % plain levobupivacaine result ed in similar onset of pharmacological actions , and outcomes . Potential differences in baricity did not appear to be clinical ly relevant in this setting .RésuméObjectif : La lévobupivacaïne en rachianesthésie a fait l’objet de nombreuses évaluations . Ses propriétés pharmacologiques sont semblables à celles de la bupivacaïne , mais les densités différentes de deux préparations de lévobupivacaïne simple disponibles sur le marché pourraient avoir pour conséquences des profils de blocs différents . Nous avons examiné les caractéristiques d’une rachianesthésie réalisée à l’aide d’une même dose de lévobupivacaïne simple à 0,5 % ou à 0,75 % .Méthode : Dans cette étude clinique r and omisée , contrôlée et en double aveugle , 60 patients ASA I-III devant subir une chirurgie pour une fracture de la hanche ont été r and omisés à recevoir une rachianesthésie avec 15 mg de lévobupivacaïne simple , soit à 0,5 % ( groupe Levo-0.5 ) , soit à 0,75 % ( groupe Levo-0.75 ) . Le délai d’installation ( résultat principal ) , le niveau du bloc sensitif mesuré à la piqûre , le bloc moteur mesuré par une échelle de Bromage modifiée et les variables hémodynamiques ont été enregistrés . Résultats : Dans le groupe Levo-0.5 ( n=29 ) , l’anesthésie chirurgicale a été réalisée en 15 ( 10–20 ) min , par rapport à 12 ( 7–21 ) min dans le groupe Levo-0.75 ( n=31 ) ( P=0,409 ) . Le niveau de bloc sensitif le plus élevé était T11 ( T6–T12 ) dans le groupe Levo-0.5 , et T10 ( T8–T12 ) dans le groupe Levo-0.75 ( P=0,759 ) . La durée moyenne de l’anesthésie était de 285 ( 224–303 ) min dans le groupe Levo-0.5 , et de 318 ( 243–375 ) min dans le groupe Levo-0.75 ( P=0,117 ) . Le nombre de blocs non réussis ayant nécessité une anesthésie générale et le nombre de patients nécessitant des vasopresseurs étaient semblables dans les deux groupes . Conclusion : La rachianesthésie réalisée avec 15 mg de lévobupivacaïne simple à 0,5 % ou 0,75 % chez une population de patients âgés provoque des réactions pharmacologiques semblables et donne des résultats similaires . Les différences possibles de baricité ne semblent pas avoir été pertinentes dans ce context", "Objective To compare the analgesic benefit of preoperative skin traction with the placement of a pillow under the injured extremity in patients with hip fractures . Design Prospect i ve , r and omized clinical study . Setting University-affiliated teaching institution . Patients and Participants One hundred consecutive patients with hip fractures admitted to the authors ' institution who met inclusion criteria were enrolled . Fifty-five patients had femoral neck fractures , and forty-five patients had intertrochanteric fractures . The average patient age was seventy-eight years . Intervention All patients were preoperatively r and omized into two intervention groups . One group underwent placement of five pounds of skin traction on the injured extremity , whereas the second underwent placement of a pillow under the injured extremity . Fifty patients were enrolled in each intervention group . Results With respect to immediate postintervention pain levels , patients treated with a pillow showed a trend toward better pain relief , as compared with patients treated with skin traction ; however , this was not statistically significant . On the morning after admission , patients treated with a pillow had a statistically significant greater reduction in pain ( p = 0.04 ) . These patients also requested a statistically significant lower amount of pain medication ( p preoperative skin traction in patients with hip fractures does not provide significant pain relief , as compared with pillow placement under the injured extremity , and thus should not be routinely performed in this patient population for analgesia", "This prospect i ve , r and omised , double blind study examined the efficacy of intrathecal morphine for post-operative analgesia in Chinese patients undergoing surgery to repair fractured hips . There were a total of 40 American Society of Anesthesiologists physical status grade I to IV patients scheduled for surgery following a fractured neck of the femur . Patients were r and omised to a control group in which they received subarachnoid plain 0.5 % bupivacaine , 2.2 mL , and normal saline , 0.4 mL , giving a total volume of 2.6 mL , or to a study group in which they received plain 0.5 % bupivacaine , 2.2 mL , and preservative-free morphine , 0.2 mg , diluted with normal saline to a total volume of 2.6 mL. Patients were monitored for up to 24 hours by staff blinded to group allocation . The level of pain was assessed by a visual analogue pain score and the time of first request for analgesia was noted . The results show the median pain-free period in the control group was nine hours ( range , 2 - 24 hours ) , while it was 24 hours ( range , 16 - 24 hours ) in the morphine group , a significant difference ( P major complications were reported . Intrathecal morphine is a useful technique for giving post-operative pain relief , especially in the elderly , in whom many other techniques can not be safely used", "BACKGROUND AND OBJECTIVES This prospect i ve r and omized study was design ed to determine the hemodynamic effects and quality of combined lumbar and sacral plexus block compared with plain bupivacaine spinal anesthesia in the elderly for repair of proximal femoral fractures . METHODS Twenty-nine elderly patients ranging in age from 68 to 97 years were r and omly assigned to 2 groups : a spinal anesthesia group with single-shot 3 mL 0.5 % plain bupivacaine , and a combined block group with 30 mL lidocaine 1.33 % with epinephrine for the posterior lumbar plexus block and 10 mL same mixture for the parasacral block and an iliac crest block with 5 mL lidocaine 1 % . RESULTS No need for general anesthesia was encountered in either group . Anesthesia was judged unsatisfactory in 1 of 15 patients in the combined block group . The initial decrease of mean arterial pressure was 38 % in the spinal group and 27 % in the block group and was not significantly different . A more prolonged hemodynamic effect was found in the spinal group , indicated by the more frequent use of ephedrine to stabilize blood pressure ( P Patients over 85 years had a significantly larger decrease in blood pressure than younger patients ( P Plain bupivacaine spinal anesthesia and combined lumbar/sacral plexus block provided adequate anesthesia for repair of hip fracture in the elderly . Hypotension was induced by both the combined peripheral nerve block and plain bupivacaine spinal anesthesia in aged patients ; hypotension was found to be longer lasting after spinal anesthesia and of a larger magnitude in patients over 85 years of age ", "OBJECTIVES To examine the relationship between early physical therapy ( PT ) , later therapy , and mobility 2 and 6 months after hip fracture . DESIGN Prospect i ve , multisite observational study . SETTING Four hospitals in the New York City area . PARTICIPANTS Four hundred forty-three hospitalized older patients discharged after surgery for hip fracture in 1997 - 98 . MEASUREMENTS Patient demographics , fracture type , comorbidities , dementia , number of new impairments at discharge , amount of PT between day of surgery and postoperative day ( POD ) 3 , amount of therapy between POD4 and 8 weeks later , and prefracture , 2- , and 6-month mobility measured using the Functional Independence Measure . RESULTS More PT immediately after hip fracture surgery was associated with significantly better locomotion 2 months later . Each additional session from the day of surgery through POD3 was associated with an increase of 0.4 points ( P=.032 ) on the 14-point locomotion scale , but the positive relationship between early PT and mobility was attenuated by 6 months postfracture . There was no association between later therapy and 2- or 6-month mobility . CONCLUSION PT immediately after hip fracture surgery is beneficial . The effects of later therapy on mobility were difficult to assess because of limitations of the data . Well- design ed r and omized , controlled trials of the effect of varying schedules and amounts of therapy on functional status after hip fracture would be informative", "INTRODUCTION The usefulness of peripheral femoral nerve block for pain management after hip fracture has been established . This prospect i ve and r and omised study compared the analgesia effect of a continuous femoral nerve block ( CF ) versus two conventional analgesia procedures after hip fracture . PATIENTS AND METHODS Patients . ( n=62 ) scheduled for surgery under spinal anaesthesia were prospect ively included . After surgery , analgesia ( 48 hours ) was r and omised : group FC ( femoral catheter , anterior paravascular approach , initial bolus followed by continuous infusion of ropivacaine 0.2 % ) , group P ( iv 2 g propacetamol/6 hours ) , group M ( sc morphine , 0.05 mg/kg per 4 hour ) . Intravenous morphine titration was performed , followed by subcutaneous ( sc ) morphine every 4 hours according to the VAS score . The primary end-point was the morphine requirements . Secondary end-points were VAS score , side effects , and mortality . RESULTS Demographic data and surgical procedures were similar between groups . After morphine titration , the VAS pain score did not differ between groups . All patients in-group M received additional morphine . Morphine mean consumption was increased in CF group : 26 mg ( 5 - 42 ) versus P : 8 mg ( 3 - 12 ) ( p=0.0001 ) or M : 19 mg ( 8 - 33 ) ( p constipation was decreased in P group vs CF . Percentage of patients requiring no morphine was similar between P ( n=6 ; 28 % ) and CF ( n=6 ; 28 % ) and greater than M ( n=0 ; 0 % ) . Hospital discharge , cardiovascular or pulmonary complications and mortality after 6 months showed no statistical difference . CONCLUSION Continuous femoral nerve block provided limited pain relief after hip fracture did not reduced side effects and induced an expensive cost", "Background This prospect i ve , r and omized double-blind study , conducted over 19 months in a tertiary care ED , sought to determine if a fascia-iliaca regional anesthetic block provides better and safer pain relief than does parenteral analgesia . Aims This study also aim ed to determine the effectiveness of parenteral NSAID analgesia for acute hip fractures . Methods Patients > 65 years old presenting at an adult ED with acute hip fractures were r and omized upon presentation to the ED into two groups ( A and B ) using numbers generated by the EPI-INFO ™ ( Atlanta , GA : Centers for Disease Control and Prevention ) program . The r and omization list was kept by one of the authors who did not interact with the patients . Two groups of patients were to receive either ( A ) a fascia-iliaca block with bupivacaine and parenteral saline injection , or ( B ) the same block with saline and an IV NSAID injection . Upon admission to the study , vital signs such as blood pressure , mean blood pressure ( MAP ) , heart rate ( HR ) , respiratory rate ( RR ) and pain-intensity measurements [ using the Visual Analogue Scale ( VAS ) ] were obtained and repeated at 15 min , 2 h and at8 h. The occurrence of complications was registered . Results One hundred seventy-five patients were r and omized , and 21 were excluded from participation . The remaining 154 patients were grouped as : group A ( n = 62 ) or group B ( n = 92 ) . The mean pain level on admission to the ED for all patients , assessed with the VAS , was 8.21 ± 0.91 ( CI 95 % : 6.43–9.99 ) ; in group A the VAS was 7.6 ± 0.22 and in group B 8.5 ± 0.72 ( p = 0.411 ) . At 15-min evaluation , values were : group A 6.24 ± 0.17 and group B 2.9 ± 0.16 ( p h the VAS for group A was 2.03 ± 0.12 and for group B 4.4 ± 0.91 ( p = 0.083 ) . Conclusion This study demonstrates that : ( 1 ) parenteral NSAIDs are very effective as analgesics after hip fractures in elderly patients , ( 2 ) fascia-iliaca regional blocks are nearly as effective for up to about 8 h after administration and ( 3 ) regional fascia-iliaca blocks effectively control post-hip fracture pain . ( 4 ) Fascia iliaca regional block has a rapid onset", "Background : Hip fracture patients are in severe pain upon arrival at the emergency department . Pain treatment is traditionally based on systemic opioids . No study has examined the effect of fascia iliaca compartment blockade ( FICB ) in acute hip fracture pain management within a double-blind , r and omized setup . Methods : Forty-eight patients with suspected hip fracture were included immediately after arrival in the emergency department , before x-ray confirmation of their fracture . Included patients were r and omly assigned to two groups of 24 . In the FICB group , the patients received an FICB with 1.0 % mepivacaine and a placebo intramuscular injection of isotonic saline . In the morphine group , the patients received a placebo FICB with 0.9 % saline and an intramuscular injection of 0.1 mg/kg morphine . Patients received intravenous rescue morphine when necessary . Results : Maximum pain relief was superior in the FICB group both at rest ( P median total morphine consumption was 0 mg ( interquartile range , 0–0 mg ) in the FICB group and 6 mg ( interquartile range , 5–7 mg ) in the morphine group ( P Pain relief was superior at all times and at all measurements in the FICB group . The study supports the use of FICB in acute management of hip fracture pain because it is an effective , easily learned procedure that also may reduce opioid side effects in this fragile , elderly group of patients", "Background : Perioperative myocardial ischaemia is an important risk factor for cardiac morbidity and mortality after noncardiac surgery . The impact of analgesic management on the incidence and severity of cardiac ischemia was studied in 77 elderly patients undergoing surgical treatment of traumatic hip fracture", "Background : Hip fracture is common in the geriatric population . Patients in this group are often at high risk for perioperative complications from concurrent diseases . Conventional spinal anesthesia can be associated with hypotension but has a better postoperative outcome compared to general anesthesia . We judged that a reduced dose of bupivacaine in combination with sufentanil could give reliable blocks with minimal hypotension", "AIM This study compares the efficacy of a walking recovery rehabilitation program with or without specific back exercises in patients affected by unstable extracapsular hip fractures and secondary back pain . Further , it reports data and images about analysed tomographic changes of the psoas muscle ipsilateral to fractures . METHODS A prospect i ve , r and omized , parallel treatment trial was carried out . Patients admitted for rehabilitation after fractures were evaluated for secondary back pain . If clinical ly indicated , patients were further scheduled for a computed tomography ( CT ) scan of the lumbar spine by which we evaluated cross-sectional changes in density and fibroadipose degeneration of the body of the psoas muscle . When back pain matched cross-sectional changes in psoas density , the patient was eligible for our study , enrolled and r and omly assigned to 1 of 2 study groups . Both groups were scheduled for hip rehabilitation and walking training plus a back protocol for the study group only . Pain was evaluated subjectively with a visual analog scale to calculate treatment effectiveness and Harris hip score was used to assess the outcome after surgery . RESULTS Thirty-seven patients out of about hundred were enrolled . In all cases CT scans showed age-related changes commonly seen in the lumbar spine and significant fibroadipose degeneration and altered density in the ipsilateral psoas muscles . With back exercises added to the st and ard rehabilitation protocol , all study patients recovered significantly better than control group patients ( P psoas changes that can be of relevance for a more rational choice of physical exercises . Causes of back pain may be more complex than described by the textbooks and prognosis is more favourable following specific back training", "The use of ultrasound reduces the onset time , improves the quality of sensory block , and minimizes the risks associated with the supraclavicular approach for brachial plexus and stellate ganglion blockade . The present study was design ed to evaluate whether ultrasound also facilitates the approach for 3-in-1 blocks . Forty patients ( ASA physical status II or III ) undergoing hip surgery after trauma were r and omly assigned to two groups . In the ultrasound ( US ) group , 20 mL bupivacaine 0.5 % was administered under US guidance , whereas in the control group , the same amount and concentration of local anesthetic was administered with the assistance of a nerve stimulator ( NS ) . After US- or NS-based identification of the femoral nerve , the local anesthetic solution was administered , and the distribution of the local anesthetic solution was visualized and recorded on videotape in the US group . The quality and the onset of the sensory block was assessed by using the pinprick test in the central sensory region of each of the three nerves and compared with the same stimulation on the contralateral leg every 10 min for 60 min . The rating was performed using a scale from 100 % ( uncompromised sensibility ) to 0 % ( no sensory sensation ) . Heart rate , noninvasive blood pressure , and oxygen saturation were measured at short intervals for 60 min . The onset of sensory blockade was significantly shorter in Group US compared with Group NS ( US 16 + /- 14 min , NS 27 + /- 16 min , P quality of the sensory block after injection of the local anesthetic was also significantly better in Group US compared with Group NS ( US 15 % + /- 10 % of initial value , NS 27 % + /- 14 % of initial value , P analgesic effect was achieved in 95 % of the patients in the US group and in 85 % of the patients in the NS group . In the US group , visualization of the cannula tip , the femoral nerve , the major vessels , and the local anesthetic spread was possible in 85 % of patients . Incidental arterial puncture ( n = 3 ) was observed only in the NS group . We conclude that an US-guided approach for 3-in-1 block reduces the onset time , improves the quality of the sensory block and minimizes the risks associated with this regional anesthetic technique . Implication s : The onset time and the quality of a regional anesthetic technique for the lower extremity is improved by ultrasonographic nerve identification compared with older techniques . ( Anesth Analg 1997;85:854 - 7", "Intrathecal ( IT ) clonidine is an effective analgesic , but it also produces hemodynamic depression and sedation which are likely to be related to IT clonidine ’s cephalad spread within the cerebrospinal fluid . We hypothesized that IT clonidine ’s side effects could be reduced without compromising the duration and quality of analgesia by injecting clonidine IT in a hyperbaric solution and elevating the patient ’s trunk . We prospect ively r and omized 30 elderly patients to receive IT150μ gofeitherisobaric(ISO ) or hyperbaric ( HYPER ) clonidine for postoperative analgesia after surgical repair of traumatichip fracture . Hemodynamics , IV fluid administration , visual analog pain scores , sedation scores , and clonidine cerebrospinal fluid levels were recorded at fixed intervals . Patients in the ISO group required significantly more crystalloid fluid administration ( median , 2500 mL ; range , 1500–3000 mL ) than those in the HYPER group ( median , 1500 ; range , 500–3000 mL ) to maintain adequate arterial blood pressure ( P the decrease in heart rate was significantly more pronounced in the ISO than in the HYPER group ( P The duration of analgesia was significantly larger in the ISO ( median , 400 min ; range , 115–400 min ) than in the HYPER ( median , 265 min ; range , 205–400 min ) group ( P 0.05 ) . Sedation scores did not differ between groups . We conclude that increasing the baricity of IT clonidine solution in the conditions of our experiment reduces hemodynamic side effects but also analgesia from IT administered clonidine", "Background and objective : This prospect i ve , r and omized study was conducted to compare unilateral spinal block using small doses of hyperbaric bupivacaine and single-agent anaesthesia with sevoflurane in elderly patients undergoing hip surgery . Methods : Thirty patients ( > 65 yr ) undergoing hip fracture repair were r and omly allocated to receive unilateral spinal anaesthesia with hyperbaric bupivacaine 7.5 mg 0.5 % ( Group Spinal , n = 15 ) or volatile induction and maintenance anaesthesia with sevoflurane ( Group SEVO , n = 15 ) . General anaesthesia was induced by increasing the inspired concentration to 5 % . A laryngeal mask airway was placed without muscle relaxants , and the end-tidal concentrations of sevoflurane were adjusted to maintain cardiovascular stability . Hypotension ( decrease in systolic arterial pressure > 20 % from baseline ) , hypertension or bradycardia ( heart rate ) requiring treatment , and the length of stay in the postanaesthesia care unit was recorded . Cognitive functions were evaluated the previous day , and 1 and 7 days after surgery with the Mini Mental State Examination test . Results : Hypotension occurred in seven patients of Group Spinal ( 46 % ) and in 12 patients of Group SEVO ( 80 % ) ( P = 0.05 ) . Phenylephrine was required to control hypotension in three spinal patients ( 21 % ) and four SEVO patients ( 26 % ) ( n.s . ) . SEVO patients had lower heart rates than spinal patients from 15 to 60 min after anaesthesia induction ( P = 0.01 ) . Bradycardia was observed in three SEVO patients ( 22 % ) . Discharge from the postanaesthesia care unit required 15 ( range 5 - 30 ) min in Group Spinal and 55 ( 15 - 80 ) min in Group SEVO ( P = 0.0005 ) . Eight patients in Group Spinal ( 53 % ) and nine patients in Group SEVO ( 60 % ) showed cognitive decline ( Mini Mental State Examination test decreased ⩾ 2 points from baseline ) 24 h after surgery ( n.s . ) . Seven days after surgery , confusion was still present in one patient of Group Spinal ( 6 % ) and in three patients of Group SEVO ( 20 % ) ( n.s . ) . Conclusions : In elderly patients undergoing hemiarthroplasty of the hip , induction and maintenance with sevoflurane provide a rapid emergence from anaesthesia without more depression of postoperative cognitive function compared with unilateral spinal anaesthesia . This technique represents an attractive option when patient refusal , lack of adequate co-operation or concomitant anticoagulant therapy contraindicate the use of spinal anaesthesia", " 153 consecutive patients with displaced cervical and trochanteric hip fractures were considered for inclusion in this study . 75 were excluded because of senile confusion and the remaining 78 were r and omized to skeletal or skin traction preoperatively . The effect on pain alleviation was evaluated with a Visual Analogue Scale ( VAS ) and by the number of doses of analgesics administered . The processing time through the emergency department , radiographic department and to the ward , as well as time to operation , was registered . No significant difference in the VAS pain evaluation was found . There was a small significant increase in consumption of analgesics of no clinical importance in patients with skin traction , and no effect of traction type on the processing time or time to operation . Fracture type did not affect the outcome . Since half of the patients found the application of skeletal traction painful , compared to one fifth with skin traction , skeletal traction should not be routinely used to alleviate pain preoperatively in these patients", "Summary Objective The aim of the study was to assess the effect of low ejection fraction ( EF ) on hypotension during lateral or supine position of spinal anaesthesia in patients older than 75 years old . Methods We analyzed 41 patients who had undergone hip surgery between August 2000 and October 2001 in the Aydin SSK State Hospital retrospectively . Patients older than 75 years of age and an EF less than 50 % were selected and spinal anaesthesia was performed with hyperbaric bupivacaine 0.5 % , lateral decubitus or supine position . The patients were divided into two groups : Group I ( unilateral group , n = 23 ) and Group II ( supine group , n = 18 ) . History of hypertension , diabetes mellitus , and ASA status , preoperative value of EF and cardiac index , and intraoperative hypotension , bradycardia , ephedrine use , and maximal sensorial block levels were recorded . Results The age range of patients was between 75 and 103 . The maximal sensorial block level was evaluated due to lower or higher than thoracic sixth segment for each patient in intraoperative period . The sensorial block level higher than thoracic sixth segment were determined 2 patient in Group I and 14 patients in Group II ( p = 0.001 ) . Hypotension was observed in five patients in Group I and 10 patients in Group II ( p = 0.015 ) . In Group I , the number of ephedrine used patient was lower than Group II ( p = 0.015 ) . Conclusions Elderly patients with low EF were more likely to predispose to higher sensorial block level and hypotension was more common during spinal anaesthesia with supine position compared to lateral decubitus position", "BACKGROUND AND OBJECTIVES The perioperative use of continuous psoas compartment block ( CPCB ) was compared with traditional pain management for patients with fracture of the femur . The anatomy of CPCB was also tested in cadavers . METHODS Forty consecutive patients ( range , 67 - 96 years old ) were prospect ively r and omized either to group A ( given local anesthetics using a CPCB ) or group B ( given perioperative analgesia with meperidine ) . In another part of the study , CPCB was performed in 15 fresh cadavers , and dissection of the lumbar region was performed after dye injection . RESULTS Continuous psoas compartment block was performed successfully in all patients in group A and was used in the pre- ( 16 - 48 hours ) and postoperative ( 72 hours ) periods . Visual analog scale score in group A was lower than in group B in 5/7 preoperative and 9/9 postoperative 8 hourly assessment s. Differences reached statistical significance ( P Patient satisfaction was higher in group A in the pre- ( P to achieve surgical anesthesia in 85 % ( 17/20 ) of the patients , and additional anesthesia was needed . The anatomic study failed to support the existence of a defined \" psoas compartment \" previously described , and supported the clinical findings . Injected dye was found in the region of the origin of the sciatic nerve ( essential for the production of anesthesia for hip surgery ) in only 26 % ( 4/15 ) of cadavers . CONCLUSIONS The CPCB seems to be an appropriate technique for efficient and safe perioperative pain control . However , in our dissections , the psoas compartment was not well defined in all patients , thus , using this route for anesthesia may result in only partial success", "OBJECTIVES The treatment of pain after surgery to repair a hip fracture is essential for an early start of rehabilitation and for reducing morbidity and mortality . Given that patients are elderly and have multiple medical conditions , local-regional analgesia can be an effective approach . Our aim was to compare the efficacy of obturator and femoral cutaneous nerve blocks and total intravenous analgesia in terms of level of patient satisfaction , complications , start of rehabilitation , and cost . PATIENTS AND METHODS Prospect i ve study of 75 patients undergoing surgery to repair hip fractures . Patients were r and omized to receive intravenous analgesia only , blockade of both nerves , or blockade of only the obturator nerve . In each group we recorded visual analog scale ( VAS ) pain scores , satisfaction with postoperative analgesia , time elapsed until start of rehabilitation , need for postoperative analgesics , side effects , and the cost of drugs . RESULTS Analgesia was significantly more effective in patients with nerve blocks than in those who received only intravenous analgesia ( mean [ SD ] VAS scores , 2.6 [ 1.4 ] and 5.6 [ 0.7 ] , respectively ) . Patients with nerve blocks also had a pain-free period of more than 24 hours ( P doses of supplementary analgesics or other drugs , had fewer side effects ( P expenditure ( 2.6 Euros [ 1.5 Euros]/patient vs 7.0 Euros [ 0.4 Euros]/patient ) . The tested techniques had no complications . CONCLUSIONS The nerve blocks were effective , easy to perform , and safe . They afforded numerous advantages : extended period of postoperative analgesia , fast recovery , lower costs , and no complications", "Intraoperative hypotension is a common and potentially deleterious event in elderly patients undergoing spinal anaesthesia for repair of hip fractures . The synergism between intrathecal opioids and local anaesthetics may allow a reduction in the dose of local anaesthetic and cause less sympathetic block and hypotension , while still maintaining adequate anaesthesia . We studied 40 elderly patients having either an insertion of a dynamic hip screw or a hemi-arthroplasty and compared 9.0 mg glucose-free bupivacaine with added fentanyl 20 μg ( group BF ) with 11.0 m glucose-free bupivacaine alone ( group B ) . Hypotension was defined as a fall in systolic blood pressure to less than 75 % baseline or less than 90 mmHg . The incidence and frequency of hypotension in group BF were less than in group B. Similarly , falls in systolic , diastolic and mean blood pressures were all less in group BF than in group B. However , there were four failed blocks in group BF and one in group", "Background and Objectives . Recently it has been demonstrated that the use of ultrasound ( US ) improves the onset time and the quality of sensory block for 3‐in‐1 blocks compared with conventional nerve stimulator ( NS ) techniques . The present study was design ed to evaluate if US guidance for 3‐in‐1 blocks reduces the amount of local anesthetic compared to NS guidance . Methods . After institutional approval and informed consent , 60 patients undergoing hip surgery following trauma were r and omly assigned to three groups of 20 patients each . In group A , the 3‐in‐1 block was performed using US guidance with 20 mL 0.5 % bupivacaine . Group B received 20 mL 0.5 % bupivacaine , and group C received 30 mL 0.5 % bupivacaine during NS guidance . The quality and the onset time was assessed by pinprick test in the central sensory region of each of the three targeted nerves and compared with the contralateral leg every 10 minutes for 1 hour by a blinded observer . The rating was undertaken using a scale from 100 % ( uncompromised sensibility ) to 0 % ( no sensation ) . Results . Overall success for the 3‐in‐1 block in group A was 95 % and in groups B and C 80 % . Onset time was significantly shorter in the US‐guided group compared with both NS‐guided groups ( group A 13 ± 6 minutes ; group B 27 ± 12 minutes ; and group C 26 ± 13 minutes ; P C ) . Quality of sensory block was significantly better in group A ( 4 % ± 5 % of initial value ) compared with groups B and C ( group B 21 % ± 11 % of initial value , P < .01 to group A ; group C 22 % ± 19 % , P < .01 to group A ) . Conclusion . The amount of local anesthetic for 3‐in‐1 blocks can be reduced by using US guidance compared with the conventional NS‐guided technique", "We undertook a trial on 60 patients with AO 31A2 fractures of the hip who were r and omised after stabilisation of the fracture into two equal groups , one of which received post-operative treatment using a non-invasive interactive neurostimulation device and the other with a sham device . All other aspects of their rehabilitation were the same . The treatment was continued for ten days after operation . Outcome measurements included the use of a visual analogue scale for pain , the brief pain inventory and Ketorolac for post-operative control of pain , and an overall assessment of outcome by the surgeon . There were significantly better results for the patients receiving treatment by active electrical stimulation ( repeated measures analysis of variance , p < 0.001 ) . The findings of this pilot trial justify a larger study to determine if these results are more generally applicable", "OBJECTIVE To determine the optimal dose of bupivacaine in providing adequate surgical anaesthesia with minimal haemodynamic disturbances . METHODS Three different doses of spinal bupivacaine in combination with or without fentanyl for surgical repair of hip fracture were used . Sixty patients were r and omly divided into three groups ( A , B and C ) to receive a spinal anaesthetic of bupivacaine 10 mg , 8 mg and 6 mg respectively . In addition to bupivacaine , group B and C also received fentanyl 20 microg in spinal mixture . RESULTS Intra operative heart rate was statistically insignificant in all three groups . Statistically significant drop in systolic blood pressure was found in group A & B at different study timings while statistically significant drop in diastolic blood pressure was only found in group A. Sensory block characteristics were similar among all three groups . Motor block pattern was found marginally significant in group C with highest time to achieve desired block . All patients had satisfactory level of surgical anaesthesia . CONCLUSION This study concluded that low dose , 6 mg bupivacaine with 20 microg fentanyl provide adequate anaesthesia for surgical repair of hip fracture with stable haemodynamics", "Aging and disease may make elderly patients particularly susceptible to hypotension during spinal anesthesia . We compared the hemodynamic effect of continuous spinal anesthesia ( CSA ) and small dose single injection spinal anesthesia ( SA ) regarding the incidence of hypotension . Seventy-four patients aged > 75 yr undergoing surgical repair of hip fracture were r and omized into 2 groups of 37 patients each . Group CSA received a continuous spinal anesthetic with a titration of 2.5 mg boluses every 15 min of isobaric bupivacaine , while group SA received a single injection spinal anesthetic with 7.5 mg of isobaric bupivacaine . The overall variations in noninvasive automated arterial blood pressure were not statistically significantly different in the 2 groups at baseline and after CSA or SA ( not significant ) . In the SA group , 68 % of patients experienced at least one episode of hypotension ( decrease in systolic arterial blood pressure greater than 20 % of baseline value ) versus 31 % of patients in the CSA group ( P = 0.005 ) . In the SA group , 51 % of patients experienced at least one episode of severe hypotension ( decrease in systolic arterial blood pressure more than 30 % of baseline value ) versus 8 % of patients in the CSA group ( P elderly patients undergoing hip fracture repair , CSA provides fewer episodes of hypotension and severe hypotension compared with a single intrathecal injection of 7.5 mg bupivacaine", "Clonidine in spinal and epidural blocks prolongs anesthesia , but can cause hypotension and bradycardia . The aim of our study was to compare hemodynamic and analgesic effects of spinal versus epidural clonidine alone and after repetitive dosing . In a prospect i ve , r and omized , double-blind study , we evaluated 40 patients scheduled for lower extremity orthopedic surgery under continuous spinal or epidural anesthesia with bupivacaine 0.5 % ( initial dose 5 mg and 50 mg , respectively ) . In either spinal or epidural technique one-half of patients received clonidine ( 150 micro gram ) in addition to bupivacaine . Repeat doses of the same anesthetic mixture were allowed in cases of subsequent pain . Mean arterial pressure ( MAP ) and heart rate were recorded for 6 h after each injection . Duration of clinical ly useful anesthesia was defined as the time from drug administration to first sensation of pain . Intrathecal , but not epidural , clonidine decreased MAP significantly compared with bupivacaine alone . MAP after intrathecal clonidine with bupivacaine was lower than epidural clonidine with bupivacaine 5 and 6 h after injection . Repetitive administration caused no further decrease in MAP . Onset time required to surgical anesthesia ( sensory block of T11 ) did not differ among the four groups . Duration of spinal and epidural anesthesia was increased more than two fold by clonidine . In summary , the addition of clonidine prolongs analgesia by either route . These results may be explained by clonidine 's sites of action in hemodynamic control and the density of bupivacaine-induced block . ( Anesth Analg 1995;80:322 - 7", "OBJECTIVES To develop and test the effect of a nurse-led interdisciplinary intervention program for delirium on the incidence and course ( severity and duration ) of delirium , cognitive functioning , functional rehabilitation , mortality , and length of stay in older hip-fracture patients . DESIGN Longitudinal prospect i ve before/after design ( sequential design ) . SETTING The emergency room and two traumatological units of an academic medical center located in an urban area in Belgium . PARTICIPANTS 60 patients in an intervention cohort ( 81.7 % females , median age = 82 , interquartile range ( IQR ) = 13 ) and another 60 patients in a usual care/nonintervention cohort ( 80 % females , median age = 80 , IQR = 12 ) . INTERVENTION ( 1 ) Education of nursing staff , ( 2 ) systematic cognitive screening , ( 3 ) consultative services by a delirium re source nurse , a geriatric nurse specialist , or a psychogeriatrician , and ( 4 ) use of a scheduled pain protocol . MEASUREMENTS All patients were monitored for signs of delirium , as measured by the Confusion Assessment Method ( CAM ) . Severity of delirium was assessed using a variant of the CAM . Cognitive and functional status were measured by the Mini-Mental State Examination ( MMSE ) ( including subscales of memory , linguistic ability , concentration , and psychomotor executive skills ) and the Katz Index of activities of daily living ( ADLs ) , respectively . RESULTS Although there was no significant effect on the incidence of delirium ( 23.3 % in the control vs 20.0 % in the intervention cohort ; P = .82 ) , duration of delirium was shorter ( P = .03 ) and severity of delirium was less ( P = .0049 ) in the intervention cohort . Further , clinical ly higher cognitive functioning was observed for the delirious patients in the intervention cohort compared with the nonintervention cohort . Additionally , a trend toward decreased length of stay postoperatively was noted for the delirious patients in the intervention cohort . Despite these positive intervention effects , no effect on ADL rehabilitation was found . Results for risk of mortality were inconclusive . CONCLUSIONS This study demonstrated the beneficial effects of an intervention program focusing on early recognition and treatment of delirium in older hip-fracture patients and confirms the reversibility of the syndrome in view of the delirium 's duration and severity", "Background : In this prospect i ve r and omized study , the authors compared the analgesic effect of a fascia iliaca compartment ( FIC ) block with that of intravenous ( i.v . ) alfentanil when administered to facilitate positioning for spinal anaesthesia in elderly patients undergoing surgery for a femoral neck fracture", "BACKGROUND Proximal femur fractures are one of the most common injuries necessitating operative treatment . The aim of this prospect i ve study was to evaluate and compare the possible effects of the preoperative application of a skin traction device , with or without weights , on pain relief in patients with acute proximal femur fracture . MATERIAL S AND METHODS This study included 108 pre-operative patients with hip fractures . The subjects were r and omly divided into three groups , and the following treatments were administered : Group 1 , skin traction with 2 kg of weights ; Group 2 , skin traction without weights ; and Group 3 , pillow placement under the affected limb . RESULTS Pain was assessed using the visual analog scale ( VAS ) . No significant differences were observed in the scores of the three groups before the pain relief treatment . All three modes of treatment result ed in significant pain reduction in subjects . Patients treated without a weight-loaded skin traction kit had better pain relief compared to the other two groups ; this outcome was statistically significant . CONCLUSION This study indicates that pillow placement under an injured limb can be safely used instead of traction , which has no significant benefit . However , an external device , such as a skin traction kit without weight , may be used in patients with persistent pain ; this external device may have an additive placebo effect , as was proven in this study", "One thous and , three hundred and thirty three patients who underwent anaesthesia for surgical fixation of a hip fracture were studied prospect ively to assess the effects on outcome of general and spinal anaesthesia . There were no significant differences between the groups in risk factors , length of hospital stay or mortality rates after 30 days or one year . The data presented may be useful for those wishing to audit anaesthetic services provided to patients with hip fracture", "BACKGROUND Delirium and pain are common following hip fracture . Untreated pain has been shown to increase the risk of delirium in older adults undergoing elective surgery . This study was performed to examine the relationship among pain , analgesics , and other factors on delirium in hip fracture patients . METHODS We conducted a prospect i ve cohort study at four New York hospitals that enrolled 541 patients with hip fracture and without delirium . Delirium was identified prospect ively by patient interview supplemented by medical record review . Multiple logistic regression was used to identify risk factors . RESULTS Eighty-seven of 541 patients ( 16 % ) became delirious . Among all subjects , risk factors for delirium were cognitive impairment ( relative risk , or RR , 3.6 ; 95 % confidence interval , or CI , 1.8 - 7.2 ) , abnormal blood pressure ( RR 2.3 , 95 % CI 1.2 - 4.7 ) , and heart failure ( RR 2.9 , 95 % CI 1.6 - 5.3 ) . Patients who received less than 10 mg of parenteral morphine sulfate equivalents per day were more likely to develop delirium than patients who received more analgesia ( RR 5.4 , 95 % CI 2.4 - 12.3 ) . Patients who received meperidine were at increased risk of developing delirium as compared with patients who received other opioid analgesics ( RR 2.4 , 95 % CI 1.3 - 4.5 ) . In cognitively intact patients , severe pain significantly increased the risk of delirium ( RR 9.0 , 95 % CI 1.8 - 45.2 ) . CONCLUSIONS Using admission data , clinicians can identify patients at high risk for delirium following hip fracture . Avoiding opioids or using very low doses of opioids increased the risk of delirium . Cognitively intact patients with undertreated pain were nine times more likely to develop delirium than patients whose pain was adequately treated . Undertreated pain and inadequate analgesia appear to be risk factors for delirium in frail older adults", " Seven hundred forty-nine community-dwelling , previously ambulatory , elderly patients who sustained a femoral neck or intertrochanteric fracture underwent prospect i ve follow-up to determine whether anesthetic technique ( spinal or general ) had an effect on inpatient morbidity and mortality , or 1-year mortality . One hundred seven patients were excluded from the study as the anesthetic technique was \" predetermined \" based on a underlying medical condition . Of the remaining 642 patients , 362 ( 56.4 % ) received general and 280 ( 43.6 % ) received spinal anesthesia . Twenty ( 3.1 % ) patients died during hospitalization ; 73 ( 11.4 % ) patients developed one or more postoperative medical complications . The 1-year mortality rate was 12.1 % . There was no difference in inpatient morbidity and mortality , or 1-year mortality rates between patients receiving general or spinal anesthesia", "In a r and omized , double-blind investigation the analgesic effect of continuous blockade of the lumbar plexus as an adjunct to acetylsalicyclic acid by suppository after surgery for femoral neck fractures under spinal anaesthesia was examined in 20 patients . Before surgery , a catheter was inserted into the femoral nerve sheath . The patients were allocated r and omly to receive bupivacaine or saline by bolus and then continuous infusion , started immediately after the operation . No statistically significant differences in additional morphine requirements , visual analogue pain scores or adverse effects were observed between the two treatment groups . It is concluded that continuous blockade of the lumbar plexus as an adjunct to rectal acetylsalicyclic acid offers no major additional pain relief after surgery for femoral neck fractures under spinal anaesthesia", "Abstract . We performed a prospect i ve r and omised trial to evaluate the efficacy of pre-operative skin traction for proximal femoral fractures in 311 patients . We found a significant difference in pain score on the evening of admission and the first morning after admission between the groups with traction compared the group without . However , there was no corresponding increase in analgesic requirement during this period . The peak pain score pattern also was different in our population . No other objective benefit can be shown from using skin traction , and its routine use should be ab and oned . Résumé . Nous avons mené une étude prospect i ve et r and omisée pour évaluer l'efficacité de la traction cutanée préopératoire pour les fractures fémorales proximales chez 311 malades . Nous avons trouvé une différence notable dans le score de la douleur le soir de l'admission et le premier matin après l'admission entre le groupe avec traction comparé au groupe sans traction . Cependant , il n'y avait pas d'augmentation correspondante de la nécessité d'analgésiques pendant cette période ou la douleur était cotée au plus haut . Aucun autre avantage objectif d'utiliser la traction cutanée n'a été montré et son usage habituel devrait être ab and onné", "Background : The aim of this study was to compare the intra‐ and postoperative analgesia provided by the catheter‐technique psoas compartment block and the epidural block in hip‐fractured patients . We also compared hemodynamic stability , motor blockade , ease of performing the technique , and complications", "BACKGROUND In Central Europe , ambulances for patients suffering from pain caused by nonlife-threatening trauma , such as hip fractures are staffed by medical personnel ( medics ) without physicians . Thus , there is an urgent need for nonpharmacological interventions that can be applied during the transport by basic life-support ( BLS ) medical personnel . METHODS In all , 101 patients were screened for participation in this r and omized placebo-controlled double-blind study , and r and omly assigned to two groups ( verum and sham transcutaneous electrical nerve stimulation [ TENS ] ) . First , medic A recorded all baseline parameters and measurements , then medic B performed TENS in absence of medic A. At the end of transportation , medic A performed data collection . Each patient was asked to grade his/her pain and anxiety level on visual analog scales ( VAS , 0 to 100 mm ) . RESULTS From 101 screened patients fulfilling the entry criteria , 29 declined consent and 9 had to be excluded from the analysis because of their final diagnosis . Therefore , the data from 30 patients ( group 1 , verum TENS ) as well as from 33 patients ( group 2 [ control ] , sham TENS ) were analyzed . No significant differences in potentially influencing factors were found before treatment . Pain scores upon arrival at the hospital differed significantly between group 1 and group 2 ( p pain reduction was observed between departure from the site of emergency and arrival at the hospital ( VAS : 89 + /- 9 to 59 + /- 6 mm ) , whereas pain scores remained nearly unchanged in group 2 ( VAS : 86 + /- 12 to 79 + /- 11 mm ) . CONCLUSION Our findings show that TENS is a valuable and fast-acting pain treatment under the difficult circumstances of \" out-of-hospital rescue \" . Because of its lack of side effects , it could also be a valuable tool in the hospital", "We report the results of a r and omised trial to determine the effects of skin traction on 252 patients awaiting surgery for fractures of the proximal femur . They were allocated r and omly to be nursed free in bed or to receive Hamilton-Russell skin traction . No differences were found between the groups in terms of pain suffered , analgesia required , frequency of pressure sores or ease of operation . The application of skin traction to patients with fractures of the upper femur is time-consuming and we recommend therefore that its routine use should be discontinued", "Background and Objectives . Experimental investigations have demonstrated a synergistic interaction between opioids and local anesthetics . This study aims to assess the effective benefit-risk ratio of continuous spinal anesthesia ( CSA ) induced with either 1.6 % lidocaine alone or in combination with 1 % meperidine . Methods . Thirty-four elderly patients ( 80.7 ± 7.3 years ) operated on for fracture of the neck of the femur were r and omly allocated to two groups . In the first group ( n = 15 ) , CSA was induced with lidocaine 1.6 % plain , whereas in the second group ( n = 19 ) 1 % meperidine was added . Reinjections were performed in both groups using lidocaine 1.6 % alone . Results . In the lidocaine group , 43 ± 13 mg was used for induction whereas in the other group the addition of 18 ± 5 mg of meperidine significantly reduced the dose of lidocaine required to 28 ± 8 mg ( p 0.001 ) . Delay between two reinjections was increased to 51 ± 7 minutes in the lidocaine plus meperidine group , compared to 35 ± 6 minutes in the lidocaine group ( p 0.001 ) . Ephedrine was required for 9 out of the 19 patients in the lidocaine plus meperidine group , whereas it was required for only two patients in the other group ( p = 0.05 ) . Mean plasma concentrations of meperidine 1 hour and 3 hours after induction was 45.5 ± 12 ng/ml and 59 ± 22 ng/ml , respectively , and drowsiness was observed in 95 % of the patients in the second group . Delay before requirement for pain medication was 2.2 ± 2 hours in the lidocaine group and 14.1 ± 8 hours in the lidocaine plus meperidine group ( p % meperidine with 1.6 % lidocaine during the induction of CSA decreases the initial induction dose , prolongs analgesia , produces initial drowsiness , and provides long-lasting pain relief . However , such benefits are offset by some impairment of hemodynamic stability that is likely to make this combination of drugs unacceptable as an enhanced analgesic technique", "Sixty elderly patients ( > 70 yr old ) undergoing surgery for hip fracture were prospect ively studied in order to compare hemodynamic tolerance of titrated doses of hyperbaric bupivacaine using continuous spinal anesthesia ( CSA ) versus single-dose spinal anesthesia ( SDSA ) . Patients were r and omized into two groups ( CSA group : n = 30 ; SDSA group : n = 30 ) . The SDSA patients received 10 - 15 mg of 0.5 % hyperbaric bupivacaine ( based on age and height ) , and the CSA patients received a starting dose of 5 mg of 0.5 % hyperbaric bupivacaine , followed after 15 min by optional reinjection of 2.5 mg every 5 min until a T10 level sensory block was reached . Onset of anesthesia , noninvasive hemodynamic variables and the need for ephedrine were studied for 4 h after induction of anesthesia . Spinal anesthesia was successful in all patients . Decreases in mean arterial pressure were significantly less frequent and less pronounced in the CSA group ( 19.9 % + /- 1.6 % of the baseline value ) than in the SDSA group ( 40.2 % + /- 1.9 % , P mean dose of ephedrine was significantly less in the CSA group ( 1.8 + /- 0.7 mg , administered to only 37 % of patients ) than in the SDSA group ( 19.4 + /- 3.3 mg administered to all patients , P late complications related to the spinal anesthesia technique were observed in either group . We concluded that CSA , using small titrated doses of 0.5 % hyperbaric bupivacaine , is safe , efficient , and provides better hemodynamic stability than SDSA in elderly patients . ( Anesth Analg 1996;82:312 - 6", "We evaluated the systemic and local effects of clonidine as an analgesic adjunct to psoas compartment block ( PCB ) with levobupivacaine . In a r and omized , prospect i ve , double-blind trial , 36 patients requiring hip fracture surgery received PCB and general anesthesia . Patients were r and omized into three groups . Each patient received PCB with 0.4 mL/kg of levobupivacaine 0.5 % . The control group ( group L ) received IV saline , the systemic clonidine group ( group IC ) received IV clonidine 1 & mgr;g/kg , and the peripheral clonidine group ( group C ) received IV saline and PCB with clonidine 1 & mgr;g/kg . The interval from time of completion of block injection to first supplementary analgesic administration was longer in group IC compared with group L ( mean ± sd , 13.4 ± 6.1 versus 7.3 ± 3.6 h ; P = 0.03 ) . There was no difference between group C and group L ( 10.3 ± 5.9 versus 7.3 ± 3.6 h ; P > 0.05 ) . The groups were similar in terms of 24 h cumulative morphine and acetaminophen consumption . There were no significant differences among groups regarding postoperative adverse effects ( bradycardia , hypotension , sedation , and nausea ) . We conclude that IV but not perineural clonidine ( 1 & mgr;g/kg ) prolongs analgesia after PCB without increasing the incidence of adverse effects ", "During a period of one year , all patients above the age of 60 with surgical repair of fractured neck of femur were investigated in a prospect ively r and omized design . A follow-up study included a total number of 56 patients , 32 were allocated to halothane anaesthesia with intubation , 24 received spinal anaesthesia . In addition , 15 patients of the halothane group and 17 patients with spinal anaesthesia were investigated with regard to endocrine stress response . Total mortality was 12.5 % , and different anaesthetic management had no influence on the postoperative course . During the operation , adrenaline and ADH increased in both groups . This increase was attenuated by spinal anaesthesia . Noradrenaline was markedly increased even before the operation , and concentrations increased in the halothane group in the course of the operation . There was a linear correlation to time between accident and the beginning of the operation . With regard to endocrine parameters , prompt surgical treatment is beneficial", "& NA ; Untreated pain is a major health care issue and very little is known about the treatment of pain and the effect of pain on post‐operative outcomes in older adults . This study was performed to identify the impact of pain on outcomes following hip fracture in older adults . Four hundred and eleven consecutive cognitively intact patients admitted with hip fracture to four New York hospitals were enrolled in a prospect i ve cohort study . Patients were interviewed daily using st and ardized pain assessment s. We used multiple logistic regression and ordinary least squares linear regression to examine the association of post‐operative pain on immediate post‐operative outcomes ( duration of stay , physical therapy sessions missed or shortened , ambulation following surgery , and post‐operative complications ) and outcomes 6 months following fracture ( locomotion , mortality , return to the community , residual pain ) . Patients with higher pain scores at rest had significantly longer hospital lengths of stay ( P=0.03 ) , were significantly more likely to have physical therapy sessions missed or shortened ( P=0.002 ) , were significantly less likely to be ambulating by post‐operative day 3 ( P ambulate past a bedside chair ( P=0.01 ) , and had significantly lower locomotion scores at 6 months ( P=0.02 ) . Pain at rest was not significantly associated with post‐operative complications , nursing home placement , survival at 6 months , or residual pain at 6 months . Post‐operative pain is associated with increased hospital length of stay , delayed ambulation , and long‐term functional impairment . Whereas appropriate caution is warranted in administering opioid analgesics to older adults , these data suggest that improved pain control may decrease length of stay , enhance functional recovery , and improve long‐term functional outcomes", "One hundred twenty patients with cervical or trochanteric hip fractures were allocated r and omly to groups receiving either skin traction or no special treatment while awaiting surgery . No differences were found between the groups in terms of pain experienced , the need for supplementary analgesics , or complications during the hospital stay . In addition , the repositioning and percentage of united fractures after 4 months did not differ significantly between the groups . The application of skin traction offered no benefits , and thus routine use of preoperative skin traction in patients with hip fractures is not recommended", "A prospect i ve study was performed over a period of 2 years to identify the cause of peroneal palsy following hip fracture treatment . Sixty-eight patients in Group I had their injured leg placed in traction in a splint with a metal frame . In Group II ( 66 patients ) elevation only of the fractured extremity was maintained with a few pillows . There were five cases of peroneal palsy in Group I and none in Group II . The difference is significant . Direct pressure on the nerve in the area of the fibular head during the preoperative traction period seems to be the cause of this transient dysfunction", " Fifty patients with fractured neck of femur that required surgical correction with either a compression screw or pin and plate device were r and omly allocated to receive one of two anaesthetic techniques , general anaesthesia combined with either opioid supplementation or triple nerve block ( three in one block ) with subcostal nerve block . The nerve blocks significantly reduced the quantity of opioid administered after operation ; 48 % of these patients required no additional analgesia in the first 24 hours . Plasma prilocaine levels in these patients were well below the toxic threshold , and peak absorption occurred 20 minutes after the injection . No untoward sequelae were associated with the nerve blocks", "Background Spinal anesthesia for surgical repair of hip fracture in the elderly is associated with a high incidence of hypotension . The synergism between intrathecal opioids and local anesthetics may make it possible to achieve reliable spinal anesthesia with minimal hypotension using a minidose of local anesthetic . Methods Twenty patients aged ≥ 70 yr undergoing surgical repair of hip fracture were r and omized into two groups of 10 patients each . Group A received a spinal anesthetic of bupivacaine 4 mg plus fentanyl 20 & mgr;g , and group B received 10 mg bupivacaine . Hypotension was defined as a systolic pressure of ephedrine boluses 5–10 mg up to a maximum 50 mg , and thereafter by phenylephrine boluses of 100–200 & mgr;g . Results All patients had satisfactory anesthesia . One of 10 patients in group A required ephedrine , a single dose of 5 mg . Nine of 10 patients in group B required vasopressor support of blood pressure . Group B patients required an average of 35 mg ephedrine , and two patients required phenylephrine . The lowest recorded systolic , diastolic , and mean blood pressures as fractions of the baseline pressures were , respectively , 81 % , 84 % , and 85%versus 64 % , 69 % , and 64 % for group A versus group B. Conclusions A “ minidose ” of 4 mg bupivacaine in combination with 20 & mgr;g fentanyl provides spinal anesthesia for surgical repair of hip fracture in the elderly . The minidose combination caused dramatically less hypotension than 10 mg bupivacaine and nearly eliminated the need for vasopressor support of blood pressure", "Intraoperative hypotension is a common and sometimes deleterious event in elderly patients undergoing spinal anaesthesia for repair of hip fractures . The synergism between intrathecal opioids and local anaesthetics may allow a reduction in the dose of local anaesthetic and reduce hypotension , while still maintaining adequate anaesthesia . We studied 42 elderly patients having insertion of a Richards pin and plate and compared 7.5 mg hyperbanic bupivacaine with added fentanyl 20 microg ( group BF ) to 12.5 mg hyperbaric bupivacaine alone ( group B ) . Hypotension was defined as a fall in systolic blood pressure to less than 75 % baseline or less than 90 mmHg and occurred with an overall incidence of 59.5 % . There was no difference in the incidence or severity of hypotension between the two groups . Two patients from group B and one from group BF experienced mild discomfort . Pruritus was more common in group BF", "BACKGROUND The aim of this study was to compare safety and efficacy of catheter-mediated femoral nerve block analgesia with systemic pain therapy in patients with proximal femoral fractures in the pre-operative and post-operative setting using a protocol for coordinating pain management . METHODS In a prospect i ve r and omised trial of patients attending the emergency department , 100 individuals were selected with a clinical ly diagnosed proximal femoral fracture . Patients were divided into two equal groups A and B. Group A ( n=50 ) received a catheter-mediated femoral nerve block with 1 % prilocaine ( 40 ml ) and post-operatively 0.2 % ropivacaine ( 30 ml ) 6 hourly . Group B ( n=50 ) initially received intravenous metamizol ( 1 g ) and a fixed combination of oral tilidine ( 100 mg ) + naloxone ( 8 mg ) . Patients aged 90 years or more received a reduced dose ( tilidine 75 mg + naloxone 6 mg ) . In the post-operative period regular oral ibuprofen ( 400 mg , 8 hourly ) in addition to oral tilidine ( 50 mg ) + naloxone ( 4 mg ) was given as required for break through pain . Pain intensity was measured using a verbal rating scale ( VRS ) from 1 to 5 : pain free ( = 1 ) , mild pain ( = 2 ) , moderate pain ( =3 ) , severe pain ( = 4 ) , excruciating pain ( = 5 ) . Pain scores were recorded at rest ( R ) , during passive anteflection ( 30 degrees ) of the hip ( PA ) on arrival and at 15 and 30 min after initial administration of analgesia . Thereafter , recordings were made 4 times a day up to the third post-operative day . RESULTS Pain scores were comparable for both groups on admission ( VRS in R 2.50 vs. 2.46 ; VRS during PA 4.30 vs. 4.34 ) . Significant pain relief was achieved in both groups following initial administration of analgesia , but the total pain scores in group A were significantly lower than in group B ( VRS in R 1.22 vs. 1.58 , p No difference was noted between the two groups during the first 3 post-operative days . No severe complications occurred as a result of analgesia , however , the catheter was dislodged in 20 % of patients in group A result ing in the need for systemically administered analgesia . CONCLUSION All patients presenting with proximal femoral fractures should receive adequate analgesia within the emergency department even prior to radiographic imaging . Femoral nerve block should be considered as the method of choice . The insertion of a femoral nerve block catheter has the dual advantage of early analgesia permitting repeated clinical examination in addition to continued post-operative pain management . The cumbersome logistics inherent in this technique within the clinical setting limits its practical application . An initial single-shot regional nerve block followed by a systemic post-operative analgesia protocol was considered an appropriate alternative . The execution of safe , consistent and appropriate regional nerve block anaesthesia is reliant on formal guidelines and protocol s as agreed by the multidisciplinary teams involved with patient-directed pain management and good clinical practice", "Quantitative assessment of myocardial ischaemia during incremental spinal , single-dose spinal and general anaesthesia may provide guidelines for the choice of anaesthetic technique for osteo synthesis of hip fractures in the elderly atherosclerotic individual . Forty-three patients with coronary artery disease were allocated to receive either incremental spinal anaesthesia ( bupivacaine 0.5 % plain ) ( A ) , single-dose spinal anaesthesia ( 2.5 mL of bupivacaine 0.5 % plain ) ( B ) or general anaesthesia ( fentanyl , thiopentone , atracurium , enflurane , N2O/O2 ) ( C ) for hip surgery . ST segment monitoring was performed from the induction of anaesthesia and for the following 48 h , and perioperative hypotension , blood loss and fluid therapy were recorded . ST depression developed in two out of 14 ( A ) , seven out of 15 ( B ) and six out of 14 ( C ) patients ( P = 0.14 ) . In ( A ) , a total of seven ST depressions occurred in the observation period as opposed to 125 in ( B ) and 16 in ( C ) ( P ST depression only occurred in ( B ) . Three ( A ) , 33 ( B ) and 40 ( C ) hypotensive events were recorded ( P ST depression compared with 10 % of normotensive patients ( P bupivacaine were used as opposed to the fixed 2.5 mL dose in ( B ) ( P mortality was higher in ( B ) ( P mortality between the three groups . The incidence of hypotension and myocardial ischaemia was lowest in the group receiving incremental spinal anaesthesia", "Purpose : To study the influence on pain and h and ling of different preoperative immobilization procedures for hip fractures . Method : 123 consecutive patients with displaced cervical and trochanteric hip fractures were r and omized to skin traction , placement in a special foam pillow ( Lasse pillow ) , and comfortable placement with an ordinary pillow under the hip from admission to operation . The effect on pain alleviation was evaluated with a Visual Analogue Scale and by the number of doses of analgesics administered . The processing time through the emergency department , X-ray department and to the ward as well as time to operation was registered . Results : No clinical ly significant difference in the VAS pain evaluation was found . There was no difference in the total consumption of analgesics in the emergency department or on the ward and no effect of immobilization type on the processing time or time to operation . Fracture type did not affect the outcome . Approximately one third of the patients found placement on a regular pillow or the application of skin traction uncomfortable as opposed to only one of 19 of the patients lying in the special Lasse pillow . There was no other difference in processing time with regard to different forms of pillow nursing and skin traction . Conclusion : The most convenient immobilization should be chosen as there is no significant difference concerning pain and h and ling time . Increased attention to analgesic medication and rapid h and ling to be operated are of importance to promote the rehabilitation process", "Postoperative hypothermia initiates an increased oxygen dem and in the postoperative period and may endanger patients with restricted cardiopulmonary reserves . In order to compare net heat losses and gains , we studied 28 women undergoing hip fracture surgery , using either general anaesthesia or spinal analgesia . The superficial and central temperatures were followed in the per‐ and postoperative period . Total body heat was calculated from temperature measurements . Temperature changes were unrelated to the type of anaesthesia . Large net heat losses occurred on transfer to the recovery room" ]

[ "BACKGROUND According to previous studies , probiotic and prebiotic supplementation have desirable effects on glycemic parameters . Thus far , the effect of supplementation on the glycemic parameters and adipokines in non-alcoholic fatty liver disease ( NAFLD ) has not been assessed . Therefore , the aim of this study was to determine the effects of supplementation with probiotic and prebiotic on adiokines and glycemic parameters in the patients with NAFLD . METHODS In the present r and omized , double-blind , placebo-controlled trial , 89 patients with NAFLD were r and omly divided into three groups to receive one probiotic capsule + 16 g/d maltodextrin ( probiotic group ) or 16 g/d oligofructose powder + one placebo capsule ( prebiotic group ) , and one placebo capsule + 16 g/d maltodextrin ( control group ) for 12 weeks . All the subjects in the study were advised to follow the weight loss diet and physical activity recommendations during the intervention . Fasting blood sample s were taken at baseline and after the intervention to measure leptin , adiponectin , insulin , and fasting blood sugar . RESULTS At the end of the study , serum concentrations of leptin , insulin , and HOMA-IR decreased significantly in the probiotic and prebiotic groups compared with the control group . Despite the changes within the groups , serum concentrations of adiponectin did not change significantly between the three groups . Also , fasting blood sugar did not change between the groups , but decreased in the prebiotic group . Quantitative insulin-sensitivity check index ( QUICKI ) increased significantly in probiotic and prebiotic groups compared with the control group . CONCLUSION Probiotic and prebiotic supplementation along with lifestyle intervention has a favorable impact on glycemic parameters and leptin levels compared with lifestyle intervention alone", "Objective : To study the clinical effect of probiotics in the treatment of non-alcoholic fatty liver disease ( NAFLD ) . Methods : A total of 200 patients with NAFLD were r and omly divided into 4 groups : control group ( routine treatment group ) and combined treatment group A , B and C. Each group had equal patients . The control group received orally polyene phosphatidylcholine capsules ; whereas combined group A , B and C were given orally the live \" combined Bifidobacterium Lactobacillus and Enterococcus powder \" , \" two live combined Bacillus subtilis and Enterococcus \" , and the both probiotics respectively . The duration of treatment was 1 month . Laboratory parameters were evaluated before treatment and thirtieth day after treatment , including cholesterol ( TC ) , triglyceride ( TG ) , high density lipoprotein cholesterol ( HDL-C ) , low density lipoprotein cholesterol(LDL-C ) , alanine aminotransferase(ALT ) , aspartate aminotransferase ( AST ) , fasting blood glucose ( FPG ) , serum high molecular weight adiponectin ( HMW-APN ) and serum TNFα . Meanwhile the faece sample was collected for routine test and bacterial culture . Liver ultrasound scan was done in all patients . Results : In terms of blood lipids and blood glucose , each group improved after treatment with significant differences ( P for liver function , serum ALT and AST decreased after treatment in each group ; especially in combined group C which were lower than those of control group [ ( 33.7±7.6 ) U/L vs. ( 45.0±8.5 ) U/L ; ( 22.0±1.6 ) U/L vs. ( 29.4±3.7 ) U/L ; P decreased after treatment in each group , in addition the values in combined group C was significantly lower than that of control group[(0.51±0.27 ) µg/L vs. ( 0.82±0.28 ) µg/L , P increased after treatment in each group , and the HMW-APN in combined C group was significantly higher than that of control group[(9.28±3.72 ) µg/L vs. (7.87±3.96)µg/L , P of fatty liver by ultrasound , but the difference between groups was not statistically significant . ( 6 ) Compared with before treatment , fecal flora in combined groups was all reduced ( P improve intestinal microecological system in NAFLD patients via inhibiting TNFα and enhancing adiponectin , possibly result ing in regulating blood glucose , lipid metabolism , and protecting liver injury from NAFLD", "BACKGROUND Probiotics have a beneficial effect on nonalcoholic fatty liver disease ( NAFLD ) in animal models . R and omized placebo-controlled trials ( RCTs ) in NAFLD are still lacking in humans despite a large number of data from animal research . AIM We performed a double-blind single center RCT of live multi-strain probiotic vs. placebo in type 2 diabetes patients with NAFLD . METHODS A total of 58 patients met the criteria for inclusion . They were r and omly assigned to receive the multi-probiotic \" Symbiter \" ( concentrated biomass of 14 probiotic bacteria genera Bifidobacterium , Lactobacillus , Lactococcus , Propionibacterium ) or placebo for 8-weeks administered as a sachet formulation in double-blind treatment . The primary main outcomes were the changes in fatty liver index ( FLI ) and liver stiffness ( LS ) measured by Shear Wave Elastography ( SWE ) . Secondary outcomes were the changes in aminotransferase activity , serum lipids and cytokines ( TNF-α , IL-1β , IL-6 , IL-8 , and IFN-γ ) levels . Analysis of covariance was used to assess the difference between groups . RESULTS In the probiotic group , FLI significantly decreased from 84.33+/-2.23 to 78.73+/-2.58 ( p reduction of LS measured by SWE was detected . Analysis of the secondary outcomes showed that probiotics reduced the level of serum AST and GGT . Among the markers of chronic systemic inflammatory state , only TNF-α and IL-6 levels changed significantly after the treatment with the probiotic . CONCLUSION The probiotic \" Symbiter \" reduces liver fat , aminotransferase activity , and the TNF-α and IL-6 levels in NAFLD patients . Modulation of the gut microbiota might represent a new therapy for NAFLD , which should be tested in larger studies", "BACKGROUND Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Oral administration of synbiotic has been proposed as an effective treatment of NAFLD because of its modulating effect on the gut flora , which can influence the gut-liver axis . OBJECTIVE The objective was to evaluate the effects of supplementation with synbiotic on hepatic fibrosis , liver enzymes , and inflammatory markers in patients with NAFLD . DESIGN In a r and omized , double-blind , placebo-controlled clinical trial conducted as a pilot study , 52 patients with NAFLD were supplemented twice daily for 28 wk with either a synbiotic or a placebo capsule . Both groups were advised to follow an energy-balanced diet and physical activity recommendations . RESULTS At the end of the study , the alanine aminotransferase ( ALT ) concentration decreased in both groups ; this reduction was significantly greater in the synbiotic group . At the end of the study , the following significant differences [ means ( 95 % CIs ) ] were seen between the synbiotic and placebo groups , respectively : ALT [ -25.1 ( -26.2 , -24 ) compared with -7.29 ( -9.5 , -5.1 ) IU/L ; P 0.001 ] , aspartate aminotransferase [ -31.33 ( -32.1 , -30.5 ) compared with -7.94 ( -11.1 , -4.8 ) IU/L ; P ] , γ-glutamyltransferase [ -15.08 ( -15.5 , -14.7 ) compared with -5.21 ( -6.6 , -3.9 ) IU/L ; P protein [ -2.3 ( -3 , -1.5 ) compared with -1.04 ( -1.5 , -0.6 ) mmol/L ; P 0.05 ] , tumor necrosis factor-α [ -1.4 ( -1.7 , -1.1 ) compared with -0.59 ( -0.8 , -0.3 ) mmol/L ; P p65 [ -0.016 ( -0.022 , -0.011 ) compared with 0.001 ( -0.004 , -0.007 ) mmol/L ; P score as determined by transient elastography [ - 2.98 ( -3.6 , -2.37 ) compared with -0.77 ( -1.32 , -0.22 ) kPa ; P CONCLUSIONS Synbiotic supplementation in addition to lifestyle modification is superior to lifestyle modification alone for the treatment of NAFLD , at least partially through attenuation of inflammatory markers in the body . Whether these effects will be sustained with longer treatment duration s remains to be determined", "Non-alcoholic fatty liver disease ( NAFLD ) has been suggested to be well correlated with altered blood pressure . This study was conducted to determine the effects of symbiotic and vitamin E supplementation on blood pressure and inflammatory indices of patients with NAFLD . This r and omized , double-blind , placebo-controlled trial was performed among 60 NAFLD patients aged 25 to 64 years old . Participants were r and omly divided into four groups to receive a 400 IU alpha-tocopherol and 2 × 108 CFU/g symbiotic supplement for 8 weeks . The anthropometric parameters , systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) , serum malondialdehyde ( MDA ) , nitric oxide ( NO ) and tumor necrosis factor α ( TNFα ) were assessed at baseline and after 8 weeks of intervention . After 8 weeks of intervention , combined symbiotic and alpha-tocopherol , symbiotic and alpha-tocopherol alone administration , compared with the placebo , result ed in significant decreases in SBP ( -17.07±2.1 , -16.07±3.56 , -1.73±2.25 and -1.55±3.01 mmHg , P=0.01 ) , serum MDA ( -1.19±0.5 , -0.12±0.65 , 0.14 ± 0.64 and 0.16±0.34 nmol/mL , P ) , serum TNFα ( -15.62±13.93 , -9.24±7.12 , -11.44 ± 15.47 and 3.01±1.71 pg/ml , P concentrations . A significant decrease in serum AST ( -11.36±4.52 , -7.43±8.58 , -5.93±6.61 and 2.5±5.75 μmol/L , P , ALT ( -12.79±3.65 , -3.66±6.81 , -6.54±7.66 and 4.16±3.43 μmol/L , P ALP ( -26.8±11.1 , -4.56±9.22 , -14.48±12.22 and 5.19±2.64 μmol/L , P NO concentration were not significant . Alpha-tocopherol and symbiotic supplementation among patients with NAFLD result ed in decreased SBP , serum MDA , TNFα levels and enzymes liver ; however , they did not affect DBP and serum NO concentration ", "Background It is generally believed that exhaustive search es of bibliographic data bases are needed for systematic review s of health care interventions . The CENTRAL data base of controlled trials ( RCTs ) has been built up by exhaustive search ing . The CONSORT statement aims to encourage better reporting , and hence indexing , of RCTs . Our aim was to assess whether developments in the CENTRAL data base , and the CONSORT statement , mean that a simplified RCT search strategy for identifying RCTs now suffices for systematic review s of health care interventions . Methods RCTs used in the Cochrane review s were identified . A brief RCT search strategy ( BRSS ) , consisting of a search of CENTRAL , and then for variants of the word r and om across all fields ( r and om$.af . ) in MEDLINE and EMBASE , was devised and run . Any trials included in the meta-analyses , but missed by the BRSS , were identified . The meta-analyses were then re-run , with and without the missed RCTs , and the differences quantified . The proportion of trials with variants of the word r and om in the title or abstract was calculated for each year . The number of RCTs retrieved by search ing with \" r and om$.af . \" was compared to the highly sensitive search strategy ( HSSS ) . Results The BRSS had a sensitivity of 94 % . It found all journal RCTs in 47 of the 57 review s. The missing RCTs made some significant differences to a small proportion of the total outcomes in only five review s , but no important differences in conclusions result ed . In the post-CONSORT years , 1997–2003 , the percentage of RCTs with r and om in the title or abstract was 85 % , a mean increase of 17 % compared to the seven years pre-CONSORT ( 95 % CI , 8.3 % to 25.9 % ) . The search using r and om$.af . reduced the MEDLINE retrieval by 84 % , compared to the HSSS , thereby reducing the workload of checking retrievals . Conclusion A brief RCT search strategy is now sufficient to locate RCTs for systematic review s in most cases . Exhaustive search ing is no longer cost-effective , because in effect it has already been done for CENTRAL", "Background : Non-alcoholic steatohepatitis ( NASH ) is a clinicopathological entity that is being recognized more frequently in recent years . This study aim ed to evaluate the effects of Metformin , with and without a probiotic supplement on liver aminotransferases in patients with NASH . Methods : Sixty four patients 18 - 75 years with NASH confirmed by biopsy and histological assessment were enrolled to study . Patients were r and omized to one of the following treatments for 6 months : Group I , probiotic ( Protexin two tablets per day ) plus Metformin 500 mg two tablets per day ( Met/Pro ) , or group II , Metformin 500 mg two tablets per day plus two placebo tablet ( Met/P ) . After 6 month alanine aminotransferase ( ALT ) , aspartate aminotransferase , and ultrasound grading of NASH were assessed . Results : In group I , serum alanine aminotransferase ( ALT : 133.7 ± 70 vs. 45.2 ± 32.5 ; P 0.00 ) , and aspartate aminotransferase activity ( AST : 123.1 ± 72 vs. 44.2 ± 33.9 ; P and ultrasound grading of NASH ( P while serum alanine aminotransferase ( ALT ) was not significantly reduced ( 118.4 ± 67.9 vs. 112.5 ± 68.7 ; P ( AST : 125.3 ± 71 vs. 113.4 ± 71 ; P did fall significantly ( P fell significantly in both groups . Conclusions : Probiotic combination with Metformin improves liver aminotransferases better than metformin alone in patients with NASH", "Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries ; it can progress to nonalcoholic steatohepatitis ( NASH ) , cirrhosis and hepatocarcinoma . The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients . In a r and omized , controlled clinical trial , involving 50 biopsy-proven NASH patients , we investigated the effects of synbiotic supplementation on metabolic parameters , hepatic steatosis , intestinal permeability , small intestinal bacterial overgrowth ( SIBO ) and lipopolysaccharide ( LPS ) serum levels . Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone . Before and after the intervention we assessed steatosis by magnetic resonance imaging , intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing . NASH patients presented high gut permeability , but low prevalence of SIBO . After the intervention , only the synbiotic group presented a reduction in steatosis , lost weight , diminished BMI and waist circumference measurement . Synbiotic did not improve intestinal permeability or LPS levels . We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss", "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 : Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Oral administration of symbiotic and Vitamin E has been proposed as an effective treatment in NAFLD patients . This study was carried out to assess the effects of symbiotic and /or Vitamin E supplementation on liver enzymes , leptin , lipid profile , and some parameters of insulin resistance ( IR ) in NAFLD patients . Material s and Methods : We r and omly assigned sixty NAFLD adult patients to receive ( 1 ) symbiotic twice daily + Vitamin E-like placebo capsule ; ( 2 ) 400 IU/d Vitamin E + symbiotic-like placebo ; ( 3 ) symbiotic twice daily + 400 IU/d Vitamin E ; and ( 4 ) symbiotic-like placebo + Vitamin E-like placebo for 8 weeks . Results : Symbiotic plus Vitamin E supplementation led to a significant decrease in concentrations of liver transaminase ( P ≤ 0.05 ) . Mean difference of apolipoprotein A-1 was more significant in symbiotic group compared to control . However , mean difference of apolipoprotein B100/A-1 was only significant in symbiotic group compared to control . At the end of the study , significant differences in total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) were seen between the symbiotic plus Vitamin E and control groups ( P of symbiotic plus Vitamin E supplements led to a significant decrease in concentrations of triglycerides ( TG ) after the intervention . Significant differences in leptin , fasting blood sugar ( FBS ) , and insulin levels were seen between the symbiotic plus Vitamin E and control groups at the end of the study ( P contrast , symbiotic and /or Vitamin E supplementation did not affect high-density lipoprotein cholesterol and homeostasis model assessment for IR levels . Conclusion : In our study , symbiotic plus Vitamin E supplementation was the most effective treatment in lowering liver enzymes , leptin , FBS , insulin , TG , TC , and LDL-C among NAFLD patients", "Background : Probiotics are commonly used after bariatric surgery ; however , uncertainty remains regarding their efficacy . Our aim was to compare the effect of probiotics vs placebo on hepatic , inflammatory and clinical outcomes following laparoscopic sleeve gastrectomy ( LSG ) . Methods : This r and omized , double-blind , placebo-controlled , trial of 6-month treatment with probiotics ( Bio-25 ; Supherb ) vs placebo and 6 months of additional follow-up was conducted among 100 morbidly obese nonalcoholic fatty liver disease ( NAFLD ) patients who underwent LSG surgery . The primary outcome was a reduction in liver fat content , measured by abdominal ultrasound , and secondary outcomes were improvement of fibrosis , measured by shear-wave elastography , metabolic and inflammatory parameters , anthropometrics and quality of life ( QOL ) . Fecal sample s were collected and analyzed for microbial composition . Results : One hundred patients ( 60 % women , mean age of 41.9±9.8 years and body mass index of 42.3±4.7 kg m−2 ) were r and omized , 80 % attended the 6-month visit and 77 % completed the 12-month follow-up . Fat content and NAFLD remission rate were similarly reduced in the probiotics and placebo groups at 6 months postsurgery ( −0.9±0.5 vs −0.7±0.4 score ; P=0.059 and 52.5 vs 40 % ; P=0.262 , respectively ) and at 12 months postsurgery . Fibrosis , liver-enzymes , C-reactive protein ( CRP ) , leptin and cytokeratin-18 levels were significantly reduced and QOL significantly improved within groups ( P⩽0.014 for all ) , but not between groups ( P⩾0.173 for all ) at 6 and 12 months postsurgery . Within- sample microbiota diversity ( alpha-diversity ) increased at 6-month postsurgery compared with baseline in both study arms ( P⩽0.008 ) and decreased again at 12 months postsurgery compared with 6 months postsurgery ( P⩽0.004 ) but did not reach baseline values . Conclusions : Probiotics administration does not improve hepatic , inflammatory and clinical outcomes 6- and 12 months post-LSG", "BACKGROUND Probiotics have profound effect on nonalcoholic steatohepatitis ( NASH ) in animal models . We aim ed to test the hypothesis that probiotics treatment was superior to usual care in reducing liver fat in NASH patients . MATERIAL AND METHODS Patients with histology-proven NASH were r and omized to receive probiotics ( n = 10 ) or usual care ( n = 10 ) for 6 months . The Lepicol probiotic formula contained Lactobacillus plantarum , Lactobacillus deslbrueckii , Lactobacillus acidophilus , Lactobacillus rhamnosus and Bifidobacterium bifidum . The primary endpoint was change in intrahepatic triglyceride content ( IHTG ) , as measured by proton-magnetic resonance spectroscopy , from baseline to month 6 . Secondary endpoints included changes in liver biochemistry and metabolic profile . RESULTS IHTG decreased from 22.6 ± 8.2 % to 14.9 ± 7.0 % in the probiotic group ( P = 0.034 ) but remained static in the usual care group ( 16.9 ± 6.1 % to 16.0 ± 6.6 % ; P = 0.55 ) . Six subjects in the probiotic group had IHTG reduced by more than 30 % from baseline , compared to 2 subjects in the usual care group ( P = 0.17 ) . The probiotic group also had greater reduction in serum aspartate aminotransferase level ( P = 0.008 ) . On the other h and , the use of probiotics was not associated with changes in body mass index , waist circumference , glucose and lipid levels . CONCLUSIONS Probiotics treatment may reduce liver fat and AST level in NASH patients . The therapeutic potential of probiotics in NASH should be tested in larger studies", "BACKGROUND People search medline for trials of healthcare interventions for clinical decisions , or to produce systematic review s , practice guidelines , or technology assessment s. Finding all relevant r and omized controlled trials ( RCTs ) with little extraneous material is challenging . OBJECTIVE To provide comparative data on the operating characteristics of search filters design ed to retrieve RCTs from medline . METHODS We identified 38 filters . The testing data base comprises h and search ing data from 161 clinical journals indexed in medline . Sensitivity , specificity and precision were calculated . RESULTS The number of terms and operating characteristics varied considerably . Comparing the retrieval against the single term ' r and omized controlled trials.pt . ' ( sensitivity for retrieving RCTs , 93.7 % ) , 24 of 38 filters had statistically higher sensitivity ; 6 had a sensitivity of at least 99.0 % . Four other filters had specificities ( non retrieval of non- RCTs ) that were statistically not different or better than the single term ( 97.6 % ) . Precision was poor : only two filters had precision ( proportion of retrieved articles that were RCTs ) statistically similar to that of the single term (56.4%)-all others were lower . Filters with more search terms often had lower specificity , especially at high sensitivities . CONCLUSION Many RCT filters exist ( n = 38 ) . These comparative data can direct the choice of an RCT filter", "BACKGROUND Cross-sectional studies have identified a high intake of simple sugars as an important dietary factor predicting nonalcoholic fatty liver disease ( NAFLD ) . OBJECTIVE We examined whether overfeeding overweight subjects with simple sugars increases liver fat and de novo lipogenesis ( DNL ) and whether this is reversible by weight loss . DESIGN Sixteen subjects [ BMI ( kg/m² ) : 30.6 ± 1.2 ] were placed on a hypercaloric diet ( > 1000 kcal simple carbohydrates/d ) for 3 wk and , thereafter , on a hypocaloric diet for 6 mo . The subjects were genotyped for rs739409 in the PNPLA3 gene . Before and after overfeeding and after hypocaloric diet , metabolic variables and liver fat ( measured by proton magnetic resonance spectroscopy ) were measured . The ratio of palmitate ( 16:0 ) to linoleate ( 18:2n-6 ) in serum and VLDL triglycerides was used as an index of DNL . RESULTS Carbohydrate overfeeding increased weight ( ±SEM ) by 2 % ( 1.8 ± 0.3 kg ; P by 27 % from 9.2 ± 1.9 % to 11.7 ± 1.9 % ( P = 0.005 ) . DNL increased in proportion to the increase in liver fat and serum triglycerides in subjects with PNPLA3 - 148IIbut not PNPLA3 - 148MM . During the hypocaloric diet , the subjects lost 4 % of their weight ( 3.2 ± 0.6 kg ; P their liver fat content ( from 11.7 ± 1.9 % to 8.8 ± 1.8 % ; P 10-fold greater relative change in liver fat ( 27 % ) than in body weight ( 2 % ) . The increase in liver fat was proportional to that in DNL . Weight loss restores liver fat to normal . These data indicate that the human fatty liver avidly accumulates fat during carbohydrate overfeeding and support a role for DNL in the pathogenesis of NAFLD . This trial was registered at www.hus.fi as 235780", "OBJECTIVE The present pilot trial was carried out to evaluate the effects of an acute treatment with a mixture containing 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus per day in patients with non alcoholic fatty liver disease ( NAFLD ) . RESEARCH METHODS A sample of 30 patients with NAFLD ( diagnosed by liver biopsy ) was enrolled and 28 patients were analyzed in a double blind r and omized clinical trial . Patients were r and omized to one of the following treatments during 3 months : group I , treated with one tablet per day with 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus and group II , treated with one placebo tablet ( 120 mg of starch ) . RESULTS In group I , alanine amino transferase ( ALT : 67.7 + /- 25.1 vs. 60.4 + /- 30.4 UI/L ; p aspartate aminotransferase activity ( AST : 41.3 + /- 15.5 vs. 35.6 + /- 10.4 UI/L ; p gammaglutamine transferase levels ( gammaGT : 118.2 + /- 63.1 vs. 107.7 + /- 60.8 UI/L ; p liver function parameters remained unchanged ( ALT : 60.7 + /- 32.1 vs. 64.8 + /- 35.5 UI/L ; p aspartate aminotransferase activity ( AST : 31.7 + /- 13.1 vs. 36.4 + /- 13.8 UI/L ; ns ) and gammaglutamine transferase levels ( gammaGT : 82.1 + /- 55.1 vs. 83.6 + /- 65.3 UI/L ; ns ) . Anthropometric parameters and cardiovascular risk factors remained unchanged after treatment in both groups . CONCLUSION A tablet of 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus , with a r and omized clinical design , improved liver aminotransferases levels in patients with NAFLD", "Background : Regarding to the growing prevalence of nonalcoholic fatty liver disease ( NAFLD ) , concentrating on various strategies to its prevention and management seems necessary . The aim of this study was to determine the effects of symbiotic on C-reactive protein ( CRP ) , liver enzymes , and ultrasound findings in patients with NAFLD . Methods : Eighty NAFLD patients were enrolled in this r and omized , double-blind , placebo-controlled clinical trial . Participants received symbiotic in form of a 500 mg capsule ( containing seven species of probiotic bacteria and fructooligosaccharides ) or a placebo capsule daily for 8 weeks . Ultrasound grading , CRP , and liver enzymes were evaluated at the baseline and the end of the study . Results : In the symbiotic group , ultrasound grade decreased significantly compared to baseline ( P symbiotic supplementation was not associated with changes in alanine aminotransferase ( ALT ) and aspartate transaminase ( AST ) levels . In the placebo group , there was no significant change in steatosis grade whereas ALT and AST levels were significantly increased ( P = 0.002 , P = 0.02 , respectively ) . CRP values remained static in either group . Conclusions : Symbiotic supplementation improved steatosis in NAFLD patients and might be useful in the management of NAFLD or protective against its progression", "Objective : Nonalcoholic fatty liver disease ( NAFLD ) is a condition defined by exceeding triglycerides accumulation in the liver . The condition can develop into fibrosis , cirrhosis , and hepatocellular carcinoma . Considering the ever-increasing prevalence of NAFLD , the aim of the present study was to investigate the effects of probiotic supplementation on glycemic and inflammatory indices in patients with NAFLD . Methods : This r and omized clinical trial was conducted on 42 patients with NAFLD who had been referred to a gastroenterology clinic . Subjects in the intervention and control groups consumed 2 capsules/day probiotic or placebo , respectively , for 8 weeks . Fasting blood sugar ( FBS ) , insulin , insulin resistance , tumor necrosis factor alpha ( TNF-α ) , and interleukin 6 ( IL-6 ) were measured at baseline and at the end of the study . Results : Means of FBS , insulin , insulin resistance , and IL-6 were significantly different between groups after intervention ( p 0.05 ) . In the probiotic group , insulin , insulin resistance , TNF-α , and IL-6 decreased significantly at the end of the study compared to the beginning of study . Conclusion : Considering the effects of probiotic supplementation on the reduction of glycemic and inflammatory indices in patients with NAFLD , consumption of probiotics is recommended as a complementary therapy in these patients", "Objectives : This study aims to evaluate the effects of some probiotics on sonographic and biochemical nonalcoholic fatty liver disease ( NAFLD ) . Methods : This r and omized triple-blind trial was conducted among 64 obese children with sonographic NAFLD . They were r and omly allocated to receive probiotic capsule ( containing Lactobacillus acidophilus ATCC B3208 , 3 × 109 colony forming units [ CFU ] ; Bifidobacterium lactis DSMZ 32269 , 6 × 109 CFU ; Bifidobacterium bifidum ATCC SD6576 , 2 × 109 CFU ; Lactobacillus rhamnosus DSMZ 21690 , 2 × 109 CFU ) or placebo for 12 weeks . Results : After intervention , in the probiotic group the mean levels of alanine aminotransferase decreased from 32.8 ( 19.6 ) to 23.1 ( 9.9 ) U/L ( P = 0.02 ) and mean aspartate aminotransferase decreased from 32.2 ( 15.7 ) to 24.3 ( 7.7 ) U/L ( P = 0.02 ) . Likewise the mean cholesterol , low-density lipoprotein-C , and triglycerides as well as waist circumference decreased in the intervention group , without significant change in weight , body mass index , and body mass index z score . After the trial , normal liver sonography was reported in 17 ( 53.1 % ) and 5 ( 16.5 % ) of patients in the intervention and placebo groups , respectively . Conclusions : The present findings suggest that a course of the abovementioned probiotic compound can be effective in improving pediatric NAFLD", "BACKGROUND Long-term statin treatment reduces the frequency of cardiovascular events , but safety and efficacy in patients with abnormal liver tests is unclear . We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation ( GREACE ) study population . METHODS GREACE was a prospect i ve , intention-to-treat study that r and omly assigned by a computer-generated r and omisation list 1600 patients with coronary heart disease ( aged 2·6 mmol/L and triglycerides statin or usual care , which could include statins . The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests ( defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal ) compared with patients with abnormal liver tests who did not receive a statin . This risk reduction was compared with that for patients treated ( or not ) with statin and normal liver tests . FINDINGS Of 437 patients with moderately abnormal liver tests at baseline , which were possibly associated with non-alcoholic fatty liver disease , 227 who were treated with a statin ( mainly atorvastatin 24 mg per day ) had substantial improvement in liver tests ( p with a statin had further increases of liver enzyme concentrations . Cardiovascular events occurred in 22 ( 10 % ) of 227 patients with abnormal liver tests who received statin ( 3·2 events per 100 patient-years ) and 63 ( 30 % ) of 210 patients with abnormal liver tests who did not receive statin ( 10·0 events per 100 patient-years ; 68 % relative risk reduction , p ) . This cardiovascular disease benefit was greater ( p=0·0074 ) than it was in patients with normal liver tests ( 90 [ 14 % ] events in 653 patients receiving a statin [ 4·6 per 100 patient-years ] vs 117 [ 23 % ] in 510 patients not receiving a statin [ 7·6 per 100 patient-years ] ; 39 % relative risk reduction , p Seven ( 880 participants who received a statin discontinued statin treatment because of liver-related adverse effects ( transaminase concentrations more than three-times the upper limit of normal ) . INTERPRETATION Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease . FUNDING None", "Gut microbiota modifiers may have beneficial effects of non‐alcoholic fatty liver disease ( NAFLD ) but r and omised controlled trials ( RCT ) are lacking in children ", "BACKGROUND & AIMS : Silymarin is a complex mixture of 6 major flavonolignans and other minor polyphenolic compounds derived from the milk thistle plant Silybum marianum ; it has shown antioxidant , anti‐inflammatory and antifibrotic effects , and may be useful in patients with nonalcoholic fatty liver disease ( NAFLD ) . We aim ed to study the efficacy of silymarin in patients with nonalcoholic steatohepatitis (NASH)—the more severe form of NAFLD . METHODS : We performed a r and omized , double‐blind , placebo‐controlled trial of consecutive adults with biopsy‐proven NASH and a NAFLD activity score ( NAS ) of 4 or more at a tertiary care hospital in Kuala Lumpur , Malaysia , from November 2012 through August 2014 . Patients were r and omly assigned to groups given silymarin ( 700 mg ; n = 49 patients ) or placebo ( n = 50 patients ) 3 times daily for 48 weeks . After this 48‐week period , liver biopsies were repeated . The primary efficacy outcome was a decrease of 30 % or more in NAS ; findings from 48‐week liver biopsies were compared with those from the baseline biopsy . Secondary outcomes included changes in steatosis , lobular inflammation , hepatocyte ballooning , NAS and fibrosis score , and anthropometric measurements , as well as glycemic , lipid , and liver profiles and liver stiffness measurements . RESULTS : The percentage of patients achieving the primary efficacy outcome did not differ significantly between the groups ( 32.7 % in the silymarin group vs 26.0 % in the placebo group ; P = .467 ) . A significantly higher proportion of patients in the silymarin group had reductions in fibrosis based on histology ( reductions of 1 point or more ; 22.4 % ) than did the placebo group ( 6.0 % ; P = .023 ) , and based on liver stiffness measurements ( decrease of 30 % or more ; 24.2 % ) than did the placebo group ( 2.3 % ; P = .002 ) . The silymarin group also had significant reductions in mean aspartate aminotransferase to platelet ratio index ( reduction of 0.14 , P = .011 compared with baseline ) , fibrosis‐4 score ( reduction of 0.20 , P = .041 compared with baseline ) , and NAFLD fibrosis score ( reduction of 0.30 , P number of adverse events ; adverse events that occurred were not attributed to silymarin . CONCLUSIONS : In a r and omized trial of 99 patients , we found that silymarin ( 700 mg , given 3 times daily for 48 weeks ) did not reduce NAS scores by 30 % or more in a significantly larger proportion of patients with NASH than placebo . Silymarin may reduce liver fibrosis but this remains to be confirmed in a larger trial . It appears to be safe and well tolerated . Clinical Trials.gov : NCT02006498", "Objective To explore why reports that seem to describe r and omised controlled trials are sometimes not indexed ( “ tagged ” ) with RCT ( r and omised controlled trial ) [ pt ] ( publication type ) in Medline . Design Cross sectional study . Setting The Cochrane Collaboration and US National Library of Medicine worked together to identify and retag records of r and omised controlled trials with RCT [ pt ] , 1994 to 2006 . Data source Published reports entered into Medline in 2005 . Main outcome measures Type of trial information presented ( for example , main results , design , and methods ) , trial design , and other Medline indexing terms applied . Results 572/591 ( 97 % ) untagged records and 578/594 ( 97 % ) tagged records contained information from r and omised controlled trials . Type of trial information and design differed between untagged and tagged reports . Fewer than half ( 234/572 , 41 % , 95 % confidence interval 37 % to 45 % ) of untagged reports but most tagged reports ( 526/578 , 91 % , 89 % to 93 % ) described the main results of the trial . Untagged reports were more likely than tagged reports to contain information on design and methods , baseline characteristics , long term follow-up , and secondary analyses . Untagged reports of main results were more likely than tagged reports to be from trials using a crossover design ( 36 % v 10 % , difference 25 % , 95 % confidence interval 19 % to 32 % ) . The Medical Subject Heading “ R and omized Controlled Trials ” was the most common clinical trial term applied to untagged reports , although more than half of untagged reports had no indexing related to trials . Conclusion Based on the results for 2005 , at least 3000 records describing r and omised controlled trials but not indexed using RCT [ pt ] may have been entered into Medline between 2006 and 2011 . Research ers and healthcare decision makers relying on using RCT [ pt ] may be missing important evidence in their search es , particularly for design and methods , baseline characteristics , long term follow-up , and secondary data analyses", "Although non-alcoholic fatty liver disease ( NAFLD ) is the leading aetiology of liver disorders in the world , there is no proven treatment for NAFLD patients with normal or low BMI . The aim of this study was to evaluate the efficacy of synbiotics supplementation in NAFLD patients with normal or low BMI . In this r and omised , double-blind , placebo-controlled , clinical trial , fifty patients with NAFLD were assigned to take either a synbiotic supplement or a placebo capsule for 28 weeks . Both groups were advised to follow a healthy lifestyle . At the end of the study , hepatic steatosis and fibrosis reduced in both groups ; however , the mean reduction was significantly greater in the synbiotic group rather than in the placebo group ( P Furthermore , serum levels of fasting blood sugar , TAG and most of the inflammatory mediators reduced in the synbiotic group significantly compared with the placebo group ( P that synbiotic supplementation improves the main features of NAFLD in patients with normal and low BMI , at least partially through reduction in inflammatory indices . Further studies are needed to address the exact mechanism of action of these effects", "Background / Aims Non-alcoholic fatty liver disease ( NAFLD ) is one of the most prevalent chronic liver diseases in recent years . The aim of this study was to evaluate the effects of sitagliptin with and without a synbiotic supplement in the treatment of patients with NAFLD . Methods In total , 138 NAFLD patients aged 18 - 60 years were enrolled in the study . Patients were r and omized to one of the following treatments for 16 weeks : Group I ( n=68 ) , sitagliptin 50 mg daily plus placebo ( one capsule per day ) or group II ( n=70 ) sitagliptin 50 mg daily plus synbiotic ( one capsule per day ) . Changes in fasting blood glucose ( FBS ) , liver enzymes , lipid profile , and body mass index were compared between the groups . Results The mean change in FBS with sitagliptin-placebo from baseline was -10.47±5.77 mg/dL , and that with sitagliptin-synbiotic was -13.52±4.16 mg/dL. There was a significant difference between the groups ( P The mean change in cholesterol ( Chol ) was -8.34±28.83 mg/dL with sitagliptin-placebo and -21.25±15.50 mg/dL with sitagliptinsynbiotic . There was a significant difference between the two groups ( P=0.029 ) . The administration of sitagliptin-placebo induced an increase of 6.13±27.04 mg/dL in low density lipoprotein ( LDL ) , whereas sitagliptin-synbiotic induced a decrease of 14.92±15.85 mg/dL in LDL . A significant difference was observed between the two groups ( P in the sitagliptin-synbiotic group , there was significant improvement in aspartate aminotransferase ( AST ) level compared to the sitagliptin-placebo group ( P=0.018 ) . Conclusions Sitagliptin-synbiotic produced greater improvement in FBS , AST , Chol , and LDL compared to sitagliptin alone in patients with NAFLD", "Background Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in developed and developing countries . The use of synbiotics has been proposed as a probable management strategy for patients with NAFLD . Objective We investigated the effects of synbiotic yogurt on hepatic steatosis and liver enzymes as primary outcomes and on oxidative stress markers , adipokine concentration , and gut peptide concentration as secondary outcomes in patients with NAFLD . Methods In this 24-wk , open-label , r and omized controlled clinical trial , 102 patients [ 50 men and 52 women ; mean age : 40 y ; body mass index ( in kg/m2 ) ( mean ± SD ) : 31.2 ± 4.9 ] were r and omly assigned to 3 groups , including 2 intervention groups and 1 control group . The intervention groups consumed 300 g synbiotic yogurt containing 108 colony-forming units Bifidobacterium animalis/mL and 1.5 g inulin or conventional yogurt daily and were advised to follow a healthy lifestyle ( i.e. , diet and exercise ) . The control group was advised to follow a healthy lifestyle alone . We evaluated differences between groups in liver function measures by using repeated- measures ANOVA , ANCOVA , and logistic regression . Results At the end of the study , the grade s of NAFLD , as determined by ultrasonography , showed a significant decrease in the synbiotic group compared with the conventional and control groups ( P respectively : serum concentration of alanine aminotransferase ( -14.5 ± 15.6 compared with 4.6 ± 15.4 and 3.1 ± 14.4 IU/L ; P = 0.008 ) , aspartate aminotransferase ( -7.5 ± 6.1 compared with 3.0 ± 8.2 and 3.1 ± 5.7 IU/L ; P ) , alkaline phosphatase ( -26.2 ± 16.8 compared with 3.4 ± 30.1 and 1.5 ± 31.9 IU/L ; P = 0.024 ) , and γ-glutamyltransferase ( -6.0 ± 6.0 compared with 1.0 ± 6.4 and 7.6 ± 11.4 IU/L ; P ) . Conclusion Synbiotic yogurt consumption improved hepatic steatosis and liver enzyme concentrations in patients with NAFLD . This trial was registered at the Iranian Registry of Clinical Trials website ( www.i rct .ir ) as I RCT 2017020932417N2", "BACKGROUND The manipulation of gut microbiota via administration of probiotics has been proposed as a potential strategy for the treatment of non-alcoholic fatty liver disease ( NAFLD ) . Hence , we performed a double-blind single center r and omized placebo-controlled trial ( RCT ) to evaluate the efficacy of coadministration of probiotics with omega-3 vs. placebo in type-2 diabetic patients with NAFLD . METHODS A total of 48 patients met the criteria for inclusion . They were r and omly assigned to receive \" Symbiter Omega \" combination of probiotic biomass supplemented with flax and wheat germ oil ( 250 mg of each , concentration of omega-3 fatty acids 1 - 5 % ) or placebo for 8-weeks . The primary main outcomes were the change in fatty liver index ( FLI ) and liver stiffness ( LS ) measured by Shear Wave Elastography ( SWE ) . Secondary outcomes were the changes in transaminases level , serum lipids and cytokines levels . RESULTS In probiotic-omega group , FLI significantly decreased from 83.53±2.60 to 76.26±2.96 ( P the placebo group ( 82.86±2.45 to 81.09±2.84 ; P=0.156 ) . Changes of LS in both groups were insignificant . Analysis of secondary outcomes showed that the coadministration of probiotics with omega-3 lead to significant reduction of serum gamma-glutamyl transpeptidase , triglycerides , and total cholesterol . Chronic systemic inflammatory markers after intervention decrease significantly only in Symbiter Omega group : IL-1β ( P=0.029 ) , TNF-α ( P live multi-strain probiotic mixture with omega-3 fatty acids once daily for 8 weeks to patients with NAFLD can reduce liver fat , improve serum lipids , metabolic profile , and reduce chronic systemic inflammatory state ", "BACKGROUND Non-alcoholic fatty liver disease ( NAFLD ) and its advanced form non-alcoholic steatohepatitis ( NASH ) are the most common causes of elevated liver enzymes in the general population . NASH , and to a lesser extent NAFLD have been associated with increased liver-related , cardiovascular disease ( CVD ) , and allcause mortality . No effective treatment is widely acceptable . OBJECTIVE The purpose of this review is to summarize available data on the impact of statins on NAFLD and NASH . METHOD A comprehensive review of the literature was performed to identify studies assessing the effect of statin use in NAFLD/NASH . RESULTS Recent reports have shown that the use of statins in patients with elevated plasma aminotransferases may be beneficial . Post hoc data from three large prospect i ve r and omized clinical trials ( n>11 , 000 ) suggest that specific statins ( mainly atorvastatin ) ameliorate NAFLD/NASH and reduce CVD events twice as much as in those with normal liver function . Several biopsy studies have found that rosuvastatin use is related with significant histological ameliorating effects in the setting of NASH . Statin treatment may also protect from hepatocellular carcinoma ( HCC ) related to NAFLD/NASH . CONCLUSION Since NAFLD/NASH patients have high CVD risk , they will probably require a statin . Thus , why not select a specific statins ( atorvastatin or rosuvastatin , both generic now ) that offer a substantial liver- and CVDrelated adverse event reduction ? The administration of statins in these patients is as safe as in the general population", "Adiposity is an increasing public health problem in China . We aim ed to examine the associations of adiposity with non-alcoholic fatty liver disease ( NAFLD ) and other chronic liver diseases in Chinese adults . The prospect i ve China Kadoorie Biobank recruited 512,891 adults aged 30–79 years from 10 areas . During 10 years of follow-up , 7,386 incident liver disease cases were recorded among 503,991 participants without prior cancer or chronic liver disease at baseline . The mean body mass index ( BMI ) ( SD ) was 23.7 ( 3.3 ) kg/m2 and mean waist circumference ( WC ) 80.3 ( 9.8 ) cm , with 33 % having BMI ≥25 kg/m2 . Throughout the range examined ( BMI 15–50 ) BMI showed a log-linear positive association with NAFLD ( n = 1,298 ) , with adjusted HR per 5 kg/m2 of 2.81 ( 95 % CI 2.63–3.01 ) , adjusting for regression dilution . There were also positive associations of percent body fat , WC , and waist-to-hip ratio with NAFLD , with HRs per 1-SD of 2.27 ( 2.14–2.41 ) , 2.60 ( 2.44–2.76 ) , and 1.84 ( 1.76–1.92 ) . BMI was unrelated to viral hepatitis ( n = 1,477 ) , and had a U-shaped association with cirrhosis ( n = 2,082 ) and an inverse association with liver cancer ( n = 2,568 ) , which disappeared after excluding the first 5 years of follow-up . Among Chinese adults , adiposity was a major risk factor for NAFLD but not other chronic liver diseases", "The intestinal microbiota is closely associated with the development of obesity and nonalcoholic fatty liver disease ( NAFLD ) . This study investigated the effects of probiotic treatment on visceral fat area ( VFA ) and intrahepatic fat ( IHF ) fraction in NAFLD . Sixty-eight obese NAFLD patients ( > 5 % proton density fat fraction [ PDFF ] on magnetic resonance imaging [ MRI ] ) were r and omized to probiotic and placebo groups for 12 weeks . The probiotic mixture included 6 bacterial species . VFA and IHF were measured using the MRI-PDFF technique . Body weight and total body fat were reduced in the probiotic group but not in the placebo group . The mean IHF fraction was reduced after 12 weeks of treatment in the probiotic group compared to that at baseline ( from 16.3 ± 15.0 % to 14.1 ± 7.7 % , p = 0.032 ) but was not reduced in the placebo group . The decrease in IHF ( mean difference : −2.61 % , p = 0.012 ) was also greater in the probiotic group than in the placebo group . Reduction of triglyceride was greater in the probiotic treatment group than in the placebo group ( mean difference : −34.0 mg/dl , p = 0.0033 ) . However , the changes in IHF percentage and triglyceride levels were not different between placebo and control groups after adjusting for changes in body weight . Treatment with probiotics for 12 weeks result ed in significant reduction in IHF and body weight in obese NAFLD patients" ]

[ "BACKGROUND Sedentary activities , such as watching television , may disrupt habituation to food cues , thereby increasing motivation to eat and energy intake . OBJECTIVE These experiments were design ed to examine the effect of television watching on habituation of ingestive behavior in children . DESIGN In experiment 1 , all children worked for access to cheeseburgers in trials 1 - 7 ( habituating stimulus ) . In trials 8 - 10 , children in the control group continued to work for cheeseburgers without any dishabituating stimuli , whereas children in the other groups received either a novel food ( French fries ) or television as dishabituating stimuli . Responding for food and amount of food eaten were measured . In experiment 2 , all children had access to 1000 kcal of a preferred snack food . One group watched a continuous television show , and the control groups either watched no television or watched a repeated segment of a television show , which controls for the television stimulus but requires reduced allocation of attention . RESULTS In experiment 1 , both the novel food and the television watching groups reinstated responding for food ( P = 0.009 ) and increased the amount of energy earned ( P = 0.018 ) above the level of the control subjects . In experiment 2 , the continuous television group spent more time eating ( P consumed more energy than the no television and the repeated segment groups ( P = 0.007 ) . CONCLUSION These experiments show that television watching can dishabituate eating or disrupt the development of habituation , which may provide a mechanism for increased energy intake associated with watching television", "PURPOSE Although moderate-to-vigorous physical activity is related to premature mortality , the relationship between sedentary behaviors and mortality has not been fully explored and may represent a different paradigm than that associated with lack of exercise . We prospect ively examined sitting time and mortality in a representative sample of 17,013 Canadians 18 - 90 yr of age . METHODS Evaluation of daily sitting time ( almost none of the time , one fourth of the time , half of the time , three fourths of the time , almost all of the time ) , leisure time physical activity , smoking status , and alcohol consumption was conducted at baseline . Participants were followed prospect ively for an average of 12.0 yr for the ascertainment of mortality status . RESULTS There were 1832 deaths ( 759 of cardiovascular disease ( CVD ) and 547 of cancer ) during 204,732 person-yr of follow-up . After adjustment for potential confounders , there was a progressively higher risk of mortality across higher levels of sitting time from all causes ( hazard ratios ( HR ) : 1.00 , 1.00 , 1.11 , 1.36 , 1.54 ; P for trend Age-adjusted all-cause mortality rates per 10,000 person-yr of follow-up were 87 , 86 , 105 , 130 , and 161 ( P for trend sitting time and mortality from all causes and CVD , independent of leisure time physical activity . In addition to the promotion of moderate-to-vigorous physical activity and a healthy weight , physicians should discourage sitting for extended periods", "Background In developed countries , regular breakfast consumption is inversely associated with excess weight and directly associated with better dietary and improved physical activity behaviors . Our objective was to describe the frequency of breakfast consumption among school-going adolescents in Delhi and evaluate its association with overweight and obesity as well as other dietary , physical activity , and sedentary behaviors . Methods Design : Cross-sectional study . Setting : Eight schools ( Private and Government ) of Delhi in the year 2006 . Participants : 1814 students from 8th and 10th grade s ; response rate was 87.2 % ; 55 % were 8th grade rs , 60 % were boys and 52 % attended Private schools . Main outcome measures : Body mass index , self-reported breakfast consumption , diet and physical activity related behaviors , and psychosocial factors . Data analysis : Mixed effects regression models were employed , adjusting for age , gender , grade level and school type ( SES ) . Results Significantly more Government school ( lower SES ) students consumed breakfast daily as compared to Private school ( higher SES ) students ( 73.8 % vs. 66.3 % ; p overall prevalence of overweight and obesity among adolescents who consumed breakfast daily ( 14.6 % ) was significantly lower vs. those who only sometimes ( 15.2 % ) or never ( 22.9 % ) consumed breakfast ( p Intake of dairy products , fruits and vegetables was 5.5 ( 95 % CI 2.4 - 12.5 ) , 1.7 ( 95 % CI 1.1 - 2.5 ) and 2.2 ( 95 % CI 1.3 - 3.5 ) times higher among those who consumed breakfast daily vs. those who never consumed breakfast . Breakfast consumption was associated with greater physical activity vs. those who never consumed breakfast . Positive values and beliefs about healthy eating ; body image satisfaction ; and positive peer and parental influence were positively associated with daily breakfast consumption , while depression was negatively associated . Conclusion Daily breakfast consumption is associated with less overweight and obesity and with healthier dietary- and physical activity-related behaviors among urban Indian students . Although prospect i ve studies should confirm the present results , intervention programs to prevent or treat childhood obesity in India should consider emphasizing regular breakfast consumption", "OBJECTIVE To assess prevailing food patterns among Balearic Isl and s ' adolescents , and socio-economic and lifestyle determinants . DESIGN Cross-sectional nutritional survey carried out ( 2007 - 2008 ) in the Balearic Isl and s , a Mediterranean region . Dietary assessment was based on a 145-item semi-quantitative FFQ and two non-consecutive 24 h recalls . Anthropometric measurements and questions related to socio-economic , lifestyle , physical activity and body image were assessed . SETTING Data obtained from a representative sample of all inhabitants living in the Balearic Isl and s aged 12 - 17 years . SUBJECTS A r and om sample ( n 1231 ) of the adolescent population ( 12 - 17 years old ) was interviewed . RESULTS Factor analysis identified two major dietary food patterns : ' Western ' and ' Mediterranean ' . The ' Western ' dietary pattern was higher among boys than girls , associated with spending ≥4 h/d on media screen time , but less prevalent among those adolescents who desired a thinner body and those girls who desired to remain the same weight . The ' Mediterranean ' dietary pattern was mainly followed by girls , and also boys who spent h/d on media screen time and girls with high parental socio-economic status . CONCLUSIONS The present study shows the existence of two major dietary patterns among Balearic Isl and s ' adolescents : ' Western ' and ' Mediterranean ' , but girls are more ' Mediterranean ' than boys . This evidence supports that the food pattern of Balearic Isl and s ' adolescents is in a transitional state characterised by the loss of the traditional Mediterranean dietary pattern towards a Western dietary pattern . Low parental socio-economic status , much leisure-time on sedentary behaviours such as media screen time and body image are factors associated with the ' Western ' dietary pattern", "The association of television viewing and obesity in data collected during cycles II and III of the National Health Examination Survey was examined . Cycle II examined 6,965 children aged 6 to 11 years and cycle III examined 6,671 children aged 12 to 17 years . Included in the cycle III sample were 2,153 subjects previously studied during cycle II . These surveys , therefore , provided two cross-sectional sample s and one prospect i ve sample . In all three sample s , significant associations of the time spent watching television and the prevalence of obesity were observed . In 12- to 17-year-old adolescents , the prevalence of obesity increased by 2 % for each additional hour of television viewed . The associations persisted when controlled for prior obesity , region , season , population density , race , socioeconomic class , and a variety of other family variables . The consistency , temporal sequence , strength , and specificity of the associations suggest that television viewing may cause obesity in at least some children and adolescents . The potential effects of obesity on activity and the consumption of calorically dense foods are consistent with this hypothesis", "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", "Alarm about the increasing prevalence of childhood obesity has focussed attention on individual lifestyle behaviours that may contribute to unhealthy weight . More distal predictors such as maternal employment may also be implicated since working mothers have less time to supervise children 's daily activities . The research reported here used two waves of data from the Longitudinal Study of Australian Children to investigate whether mothers ' hours in paid work shape young children 's television viewing , snacking and physical activity , and through those lifestyle behaviours , children 's weight at ages 4 - 5 years and 6 - 7 years . At both ages , children 's lifestyle behaviours were interrelated and associated with weight status . Cross-sectional analysis confirmed small , direct associations between longer hours of maternal employment and child weight at age 4 - 5 years , but not with child 's weight measured two years later . In both the cross-sectional and prospect i ve analyses , the children of mothers who worked part-time watched less television and were less likely to be overweight than children of mothers who were not employed or who worked full-time . While associations were small , they remained significant after adjustment for maternal weight , household income and other factors . The combination of direct and indirect relationships between mothers ' work hours and the weight status of their young children provides additional support to calls for family-friendly work policies as an important means for promoting healthy family lifestyles and early childhood wellbeing", "BACKGROUND Underst and ing the inter-relationships between lifestyle factors in youth is important with respect to the development of effective promotional programmes for healthy eating and active living . The present study aim ed to explore the associations of dietary habits ( DH ) with physical activity ( PA ) and screen time ( ST ) among Saudi adolescents aged between 15 and 19 years of age relative to gender . METHODS Data were obtained from the Arab Teens Lifestyle Study , a school-based multicentre lifestyle study conducted in 2009/2010 in three major cities in Saudi Arabia . A multistage stratified cluster r and om sampling technique was used . The number of participants with complete data for DH and PA was 2886 and the respective number for DH and ST was 2822 . Assessment included weight , height , body mass index , total daily ST ( television viewing , video/computer games and Internet use ) , PA and DH using self-reported question naires . RESULTS Females were significantly more sedentary and less active than males ( P gender by PA and gender by ST interactions for several DH . Logistic regression analyses revealed significant associations of higher PA with a higher consumption of fruit , vegetables , milk , French fries/potato chips and energy drinks , whereas higher ST was significantly associated with a higher consumption of sugar-sweetened drinks , fast foods , cake/doughnuts and energy drinks . CONCLUSIONS Healthful dietary habits were associated mostly with PA , whereas sedentary behaviours , independent of PA , negatively impacted upon eating behaviours . The low PA levels and high sedentary levels of Saudi females represent a great concern . The results reported in the present study have important implication s for both youth public health policies and intervention programmes" ]

[ "Almonds , together with other nuts , reduce serum cholesterol levels and may reduce the risk of coronary heart disease . There is much current interest in the relation of coronary heart disease to postpr and ial events . We have therefore assessed the effects of varying amounts of almonds on the postpr and ial blood glucose response to a carbohydrate meal . Our aim was to assess the effect of adding almonds to a bread meal . Nine healthy volunteers ( 2 women , 7 men ; mean age , 27.8 years ; mean body mass index , 22.9 kg/m2 ) were r and omly fed with 3 test meals and 2 white bread control meals on separate days . Subjects were fed the meals after a 10- to 12-hour overnight fast . Each meal contained 50 g of available carbohydrate from white bread eaten alone or with 30 , 60 , or 90 g ( approximately 1 , 2 , or 3 oz ) of almonds . Capillary finger-prick blood sample s for glucose analysis were obtained at 0 , 15 , 30 , 45 , 60 , 90 , and 120 minutes . Glycemic responses were assessed by calculating the incremental area under the 2-hour blood glucose curve . The addition of almonds to white bread result ed in a progressive reduction in the glycemic index of the composite meal in a dose-dependent manner for the 30-g ( 105.8 + /- 23.3 ) , 60-g ( 63.0 + /- 9.0 ) , and 90-g ( 45.2 + /- 5.8 ) doses of almonds ( r = -0.524 , n = 36 , P = .001 ) . We conclude that , in addition to lowering serum cholesterol levels , almonds may also reduce the glycemic impact of carbohydrate foods with which they are eaten", "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 Walnut consumption is associated with reduced risk of coronary heart disease ( CHD ) . OBJECTIVE We assessed the effect of walnuts on lipid and glucose metabolism , adipokines , inflammation and endothelial function in healthy Caucasian men and postmenopausal women ≥50years old . DESIGN Forty subjects ( mean±SEM : age 60±1years , BMI 24.9±0.6kg/m(2 ) ; 30 females ) were included in a controlled , cross-over study and r and omized to receive first a walnut-enriched ( 43g/d ) and then a Western-type ( control ) diet or vice-versa , with each lasting 8weeks and separated by a 2-week wash-out . At the beginning and end of each diet phase , measurements of fasting values , a mixed meal test and an assessment of postpr and ial endothelial function ( determination of microcirculation by peripheral artery tonometry ) were conducted . Area under the curve ( AUC ) , incremental AUC ( iAUC ) and treatment × time interaction ( shape of the curve ) were evaluated for postpr and ial triglycerides , VLDL-triglycerides , chylomicron-triglycerides , glucose and insulin . RESULTS Compared with the control diet , the walnut diet significantly reduced non-HDL-cholesterol ( walnut vs. control : -10±3 vs. -3±2mg/dL ; p=0.025 ) and apolipoprotein-B ( -5.0±1.3 vs. -0.2±1.1mg/dL ; p=0.009 ) after adjusting for age , gender , BMI and diet sequence . Total cholesterol showed a trend toward reduction ( p=0.073 ) . Fasting VLDL-cholesterol , LDL-cholesterol , HDL-cholesterol , triglycerides and glucose , insulin , HOMA-IR , and HbA1c did not change significantly . Similarly , fasting adipokines , C-reactive protein , biomarkers of endothelial dysfunction , postpr and ial lipid and glucose metabolism and endothelial function were unaffected . CONCLUSION Daily consumption of 43 g of walnuts for 8weeks significantly reduced non-HDL-cholesterol and apolipoprotein-B , which may explain in part the epidemiological observation that regular walnut consumption decreases CHD risk ", "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", "Nut consumption has been associated with reduced coronary heart disease ( CHD ) risk . In addition to cholesterol-lowering properties , almonds have been shown to lower oxidized LDL concentrations . However , little is known regarding their effects on other markers of oxidative stress . The dose-response effects of whole almonds , taken as snacks , were compared with low-saturated fat ( in the therapeutic diets of hyperlipidemic subjects . In a r and omized crossover study , 27 hyperlipidemic men and women consumed 3 isoenergetic ( mean 423 kcal/d or 1770 kJ/d ) supplements each for 1 mo . Supplements consisted of full-dose almonds ( 73 + /- 3 g/d ) , half-dose almonds plus half-dose muffins ( half-dose almonds ) , and full-dose muffins ( control ) . Subjects were assessed at wk 0 , 2 and 4 . Mean body weights differed weight loss on the half-dose almond treatment was greater than on the control ( P almonds reduced serum concentrations of malondialdehyde ( MDA ) ( P = 0.040 ) and creatinine-adjusted urinary isoprostane output ( P = 0.026 ) compared with the control . Serum concentrations of alpha- or gamma-tocopherol , adjusted or unadjusted for total cholesterol , were not affected by the treatments . Almond antioxidant activity was demonstrated by their effect on 2 biomarkers of lipid peroxidation , serum MDA and urinary isoprostanes , and supports the previous finding that almonds reduced oxidation of LDL-C. Antioxidant activity provides an additional possible mechanism , in addition to lowering cholesterol , that may account for the reduction in CHD risk with nut consumption", "BACKGROUND 3-Hydroxy-3-methyl-glutaryl-coenzyme A ( HMG-CoA ) reductase inhibitors reduce serum cholesterol and are increasingly advocated in primary prevention to achieve reductions in LDL cholesterol . Newer dietary approaches combining cholesterol-lowering foods may offer another option , but these approaches have not been compared directly with statins in the same persons . OBJECTIVE The objective was to compare , in the same subjects , the cholesterol-lowering potential of a dietary portfolio with that of a statin . DESIGN Thirty-four hyperlipidemic participants underwent all three 1-mo treatments in r and om order as out patients : a very-low-saturated-fat diet ( control diet ) , the same diet plus 20 mg lovastatin ( statin diet ) , and a diet high in plant sterols ( 1.0 g/1000 kcal ) , soy-protein foods ( including soy milks and soy burgers , 21.4 g/1000 kcal ) , almonds ( 14 g/1000 kcal ) , and viscous fibers from oats , barley , psyllium , and the vegetables okra and eggplant ( 10 g/1000 kcal ) ( portfolio diets ) . Fasting blood sample s were obtained at 0 , 2 , and 4 wk . RESULTS LDL-cholesterol concentrations decreased by 8.5+/-1.9 % , 33.3+/-1.9 % , and 29.6+/-1.3 % after 4 wk of the control , statin , and portfolio diets , respectively . Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk ( P=0.013 ) , 9 participants ( 26 % ) achieved their lowest LDL-cholesterol concentrations with the portfolio diet . Moreover , the statin ( n=27 ) and the portfolio ( n=24 ) diets did not differ significantly ( P=0.288 ) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff . CONCLUSIONS Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention . They may , therefore , bridge the treatment gap between current therapeutic diets and newer statins", "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 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 —Although recent studies have indicated that nut consumption may improve levels of blood lipids , nuts are not generally recommended as snacks for hyperlipidemic subjects because of their high fat content . Furthermore , the effective dose is still unknown . Methods and Results —The dose-response effects of whole almonds , taken as snacks , were compared with low-saturated fat ( in the therapeutic diets of hyperlipidemic subjects . In a r and omized crossover study , 27 hyperlipidemic men and women consumed 3 isoenergetic ( mean 423 kcal/d ) supplements each for 1 month . Supplements provided 22.2 % of energy and consisted of full-dose almonds ( 73±3 g/d ) , half-dose almonds plus half-dose muffins , and full-dose muffins . Fasting blood , expired air , blood pressure , and body weight measurements were obtained at weeks 0 , 2 , and 4 . Mean body weights differed reduction in levels of blood lipids . Significant reductions from baseline were seen on both half- and full-dose almonds for LDL cholesterol ( 4.4±1.7 % , P = 0.018 , and 9.4±1.9 % , P and LDL : HDL cholesterol ( 7.8±2.2 % , P = 0.001 , and 12.0±2.1 % , P for lipoprotein(a ) ( 7.8±3.5 % , P = 0.034 ) and oxidized LDL concentrations ( 14.0±3.8 % , P seen in pulmonary nitric oxide between treatments . Conclusions —Almonds used as snacks in the diets of hyperlipidemic subjects significantly reduce coronary heart disease risk factors , probably in part because of the nonfat ( protein and fiber ) and monounsaturated fatty acid components of the nut", "Correction to : International Journal of Obesity ( 2003 ) 27,1365–1372 . doi:10.1038/sj.ijo.0802411 In the abstract of the above paper , the last sentence in the results section was incorrectly published . The sentence should read : Among subjects with type 2 diabetes , diabetes medication reductions were sustained or further reduced in a greater proportion of almond-LCD as compared to CHO-LCD subjects ( 96 vs 50 % , respectively )", "OBJECTIVE To determine the effects of the Dietary Approaches to Stop Hypertension ( DASH ) eating pattern on cardiometabolic risks in type 2 diabetic patients . RESEARCH DESIGN AND METHODS A r and omized crossover clinical trial was undertaken in 31 type 2 diabetic patients . For 8 weeks , participants were r and omly assigned to a control diet or the DASH eating pattern . RESULTS After following the DASH eating pattern , body weight ( P = 0.007 ) and waist circumference ( P = 0.002 ) reduced significantly . Fasting blood glucose levels and A1C decreased after adoption of the DASH diet ( −29.4 ± 6.3 mg/dl ; P = 0.04 and −1.7 ± 0.1 % ; P = 0.04 , respectively ) . After the DASH diet , the mean change for HDL cholesterol levels was higher ( 4.3 ± 0.9 mg/dl ; P = 0.001 ) and LDL cholesterol was reduced ( −17.2 ± 3.5 mg/dl ; P = 0.02 ) . Additionally , DASH had beneficial effects on systolic ( −13.6 ± 3.5 vs. −3.1 ± 2.7 mmHg ; P = 0.02 ) and diastolic blood pressure ( −9.5 ± 2.6 vs. −0.7 ± 3.3 mmHg ; P = 0.04 ) . CONCLUSIONS Among diabetic patients , the DASH diet had beneficial effects on cardiometabolic risks", "OBJECTIVE To determine the effects of daily walnut consumption on endothelial function , cardiovascular biomarkers , and anthropometric measures in type 2 diabetic individuals . RESEARCH DESIGN AND METHODS This study was a r and omized , controlled , single-blind , crossover trial . Twenty-four participants with type 2 diabetes ( mean age 58 years ; 14 women and 10 men ) were r and omly assigned to one of the two possible sequence permutations to receive an ad libitum diet enriched with 56 g ( 366 kcal ) walnuts/day and an ad libitum diet without walnuts for 8 weeks . Subjects underwent endothelial function testing ( measured as flow-mediated dilatation [ FMD ] ) and assessment of cardiovascular biomarkers before and after each 8-week treatment phase . The primary outcome measure was the change in FMD after 8 weeks . Secondary outcome measures included changes in plasma lipids , A1C , fasting glucose , insulin sensitivity , and anthropometric measures . RESULTS Endothelial function significantly improved after consumption of a walnut-enriched ad libitum diet compared with that after consumption of an ad libitum diet without walnuts ( 2.2 ± 1.7 vs. 1.2 ± 1.6 % ; P = 0.04 ) . The walnut-enriched diet increased fasting serum glucose and lowered serum total cholesterol and LDL cholesterol from baseline ( 10.0 ± 20.5 mg/dl , P = 0.04 ; −9.7 ± 14.5 mg/dl , P no significant changes in anthropometric measures , plasma A1C , and insulin sensitivity . CONCLUSIONS A walnut-enriched ad libitum diet improves endothelium-dependent vasodilatation in type 2 diabetic individuals , suggesting a potential reduction in overall cardiac risk", "Background : Previous studies have demonstrated that nuts consumption have beneficial effects on serum lipid profiles in hyperlipidemic or normolipidemic subjects . However , similar studies in diabetes field are quite rare . So , we aim ed to investigate the effects of hazelnut consumption on fasting blood sugar ( FBS ) and lipid profiles in patients with type 2 Diabetes . Material s and Methods : An 8-week controlled r and omized parallel study in patients with type 2 diabetes . Fifty eligible volunteers were assigned to either the control or intervention groups . 10 % of total daily calorie intake was replaced with hazelnuts in intervention group . Blood sample s were collected from fasting patients at the start and at the end of the study . Results : After 8 weeks , there were significant differences in high-density lipoprotein-cholesterol ( HDL-C ) concentrations between two groups , using analyses of covariance ( P = 0.009 ) , which was due to the larger HDL-C reduction in control group ( P = 0.003 ) . Although , Hazelnut group achieved greater reduction in triglyceride ( TG ) concentrations than control group , these changes were not statistically significant . Neither between-group changes nor within-group changes were significant for FBS , total cholesterol ( TC ) , TG , and low-density lipoprotein-cholesterol ( LDL-C ) levels . Conclusion : Results of this study indicated that incorporation of hazelnuts into diet can prevent reduction of HDL-C concentrations in patients with type 2 diabetes , but had no effect on FBS or other lipid profile indices", "OBJECTIVE Fat intake , especially monounsaturated fatty acid ( MUFA ) , has been liberalized in diabetic diets to preserve HDL cholesterol and improve glycemic control , yet the exact sources have not been clearly defined . Therefore , we assessed the effect of mixed nut consumption as a source of vegetable fat on serum lipids and HbA1c in type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 117 type 2 diabetic subjects were r and omized to one of three treatments for 3 months . Supplements were provided at 475 kcal per 2,000-kcal diet as mixed nuts ( 75 g/day ) , muffins , or half portions of both . The primary outcome was change in HbA1c . RESULTS The relative increase in MUFAs was 8.7 % energy on the full-nut dose compared with muffins . Using an intention-to-treat analysis ( n = 117 ) , full-nut dose ( mean intake 73 g/day ) reduced HbA1c ( −0.21 % absolute HbA1c units , 95 % CI −0.30 to −0.11 , P muffins . LDL cholesterol also decreased significantly after full-nut dose compared with muffin . The LDL cholesterol reduction after half-nut dose was intermediate and not significantly different from the other treatments . Apolipoprotein ( apo ) B and the apoB : apoA1 ratio behaved similarly . Nut intake related negatively to changes in HbA1c ( r = −0.20 , P = 0.033 ) and LDL cholesterol ( r = −0.24 , P = 0.011 ) . CONCLUSIONS Two ounces of nuts daily as a replacement for carbohydrate foods improved both glycemic control and serum lipids in type 2 diabetes ", "Context Some experts attribute a low incidence of heart disease in Mediterranean countries to dietary habits . Contribution In this multicenter , 3-group trial , investigators r and omly assigned 772 adults at high risk for cardiovascular disease to a low-fat diet or to a Mediterranean diet supplemented with either virgin olive oil ( 1 L per week ) or nuts ( 30 g per day ) . After 3 months , the Mediterranean diet groups had lower mean plasma glucose level , systolic blood pressure , and total cholesterolhigh-density lipoprotein cholesterol ratio than the low-fat diet group . Caution s The Mediterranean diet groups received more nutritional education than the low-fat diet group . Implication s Mediterranean diets supplemented with olive oil or nuts may improve cardiovascular risk factors . The Editors Cardiovascular disease is the main cause of death in industrialized countries , but incidence rates have marked geographic differences . The low incidence of coronary heart disease ( CHD ) in Mediterranean countries has been partly ascribed to dietary habits ( 1 - 3 ) . Recent findings from large European cohort studies ( 4 - 6 ) suggest that a high degree of adherence to the Mediterranean diet is associated with a reduction in mortality . In small clinical studies , the Mediterranean diet or some of its components have reduced blood pressure ( 7 ) and have improved lipid profiles ( 8 , 9 ) and endothelial function ( 10 ) . Moreover , a recent cross-sectional study ( 11 ) and a 2-year feeding trial ( 12 ) have shown that adherence to the Mediterranean diet is associated with reduced markers of vascular inflammation . These beneficial effects on surrogate markers of cardiovascular risk add biological plausibility to the epidemiologic evidence that supports a protective effect of the Mediterranean diet . Olive oil , a rich source of monounsaturated fatty acids , is a main component of the Mediterranean diet . Virgin olive oil retains all the lipophilic components of the fruit , -tocopherol , and phenolic compounds with strong antioxidant and anti-inflammatory properties ( 13 , 14 ) . Tree nuts , which are also typical in the Mediterranean diet , have a favorable fatty acid profile and are a rich source of nutrients and other bioactive compounds that may beneficially influence the risk for CHD , such as fiber , phytosterols , folic acid , and antioxidants ( 15 ) . Frequent nut intake has been associated with decreased CHD rates in prospect i ve studies ( 15 ) . Walnuts differ from all other nuts through their high content of polyunsaturated fatty acids , particularly -linolenic acid , a plant n-3 fatty acid ( 16 ) , which may confer additional antiatherogenic properties ( 17 ) . Therefore , we design ed a large-scale feeding trial in high-risk participants to assess the effects of 2 Mediterranean diets , one supplemented with virgin olive oil and the other supplemented with mixed nuts , compared with a low-fat diet on cardiovascular outcomes . We report the results of a 3-month intervention on intermediate markers of cardiovascular risk in the first 772 participants who were recruited into the trial . Supplement . Original Version ( PDF ) Methods Study Design The Prevencin con Dieta Mediterrnea ( PREDIMED ) Study is a large , parallel-group , multicenter , r and omized , controlled , 4-year clinical trial that aims to assess the effects of the Mediterranean diet on the primary prevention of cardiovascular disease ( www.predimed.org ) . An estimated 9000 high-risk participants ( > 5000 participants are already recruited ) will be assigned to 3 interventions : Mediterranean diet with virgin olive oil , Mediterranean diet with mixed nuts , or low-fat diet . The main outcome is an aggregate of cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke ) . The anticipated completion date of the trial is December 2010 . We design ed our present study to assess the 3-month effects of the dietary interventions on surrogate markers of cardiovascular risk in participants entering the study during the first 6 months of recruitment . The institutional review boards of the 10 participating centers approved the study protocol . Participants and Recruitment From October 2003 to March 2004 , we selected 930 potential participants in primary care centers affiliated with 10 teaching hospitals across Spain . Eligible participants were community-dwelling men , 55 to 80 years of age , and women , 60 to 80 years of age , who fulfilled at least 1 of 2 criteria : type 2 diabetes or 3 or more CHD risk factors ( current smoking , hypertension [ blood pressure > 140/90 mm Hg or treatment with antihypertensive drugs ] , low-density lipoprotein [ LDL ] cholesterol level 4.14 mmol/L [ 160 mg/dL ] [ or treatment with hypolipidemic drugs ] , high-density lipoprotein [ HDL ] cholesterol level 1.04 mmol/L [ 40 mg/dL ] , body mass index [ BMI ] 25 kg/m2 , or a family history of premature CHD ) . Exclusion criteria were history of cardiovascular disease , any severe chronic illness , drug or alcohol addiction , history of allergy or intolerance to olive oil or nuts , or low predicted likelihood of changing dietary habits according to the stages-of-change model ( 18 ) . The primary care physicians based participants ' eligibility on review of clinical records and a screening visit . They obtained a list of c and i date s from computer-based records of patients who attended each participating center and review ed their clinical records to exclude those who did not meet eligibility criteria . They then invited suitable c and i date s by telephone to attend a screening visit . The visit included an interview with administration of a 26-item question naire to inquire about medical conditions and risk factors related to eligibility . Of the eligible c and i date s who met entry requirements , 95 % agreed to participate and provided informed consent . R and omization and Intervention After the screening visit , each center r and omly assigned eligible participants to 1 of 3 diet groups by using a computer-generated r and om-number sequence . The coordinating center constructed the r and omization table , and participants were r and omly assigned into blocks of 50 participants balanced by center , sex , and age group ( . We concealed allocation into the intervention groups by using closed envelopes with correlative numbers by prespecified subgroups of sex and age . The baseline examination included the administration of a 14-item question naire , an extension of a previously vali date d question naire ( 19 ) , that assessed the degree of adherence to the traditional Mediterranean diet . We assigned values of 0 or 1 to each item ( Appendix Table 1 ) . We also administered a 137-item vali date d food frequency question naire ( 20 ) ; the vali date d Spanish version ( 21 ) of the Minnesota Leisure Time Physical Activity Question naire ; and a 47-item question naire about education , lifestyle , history of illnesses , and medication use . We performed anthropometric and blood pressure measurements and obtained sample s of fasting blood and spot urine . We repeated all examinations at 3 months . The same dietitian delivered the interventions to the 3 r and omized groups in each center . On the basis of the assessment of individual Mediterranean diet scores , the dietitian gave personalized dietary advice during a 30-minute session to each participant , with recommendations on the desired frequency of intake of specific foods . We advised participants who were allocated to the low-fat diet to reduce intake of all types of fat , and we gave them a leaflet with written recommendations according to the American Heart Association guidelines ( 22 ) . For total fat intake , these recommendations were opposite to those given to participants in the 2 Mediterranean diet groups , who received instructions intended to increase the 14-item Mediterranean diet score , including increased consumption of vegetable fats and oils . We did not suggest any energy restriction . While the participants who were allocated to the low-fat diet did not receive further intervention , those assigned the 2 Mediterranean diet groups had access to more intense intervention in 2 ways . First , they were given a free provision of typical Mediterranean fatty foods ( olive oil or nuts ) . Depending on group assignment , participants were given either free virgin olive oil ( 15 L [ 1 L/wk ] for 3 months ) or free sachets of walnuts , hazelnuts , and almonds ( 1350 g of walnuts [ 15 g/d ] , 675 g of hazelnuts [ 7.5 g/d ] , and 675 g of almonds [ 7.5 g/d ] for 3 months ) . To improve adherence and account for family needs , participants in the corresponding Mediterranean diet groups were given excess olive oil or additional 1000-g packets of nuts . We analyzed the nutrient composition of the olive oil and nuts used in the study by st and ard methods in a reference laboratory ( Appendix Table 2 ) ) . Second , 1 week after inclusion , the dietitian delivered a 1-hour group session with up to 20 participants , with separate sessions for each Mediterranean diet group . Each group session consisted of informative talks and provision of written material s with elaborate descriptions of typical Mediterranean foods and seasonal shopping lists , meal plans , and cooking recipes . Throughout the study , all participants had free and continuous access to their center dietitian for advice and consultation . Measurements Trained personnel measured weight and height by using calibrated scales and a wall-mounted stadiometer , respectively ; waist circumference midway between the lowest rib and the iliac crest by using an anthropometric tape ; and blood pressure in triplicate with a vali date d semiautomatic oscillometer ( Omron HEM-705CP , Hoofddorp , the Netherl and s ) . We calculated energy and nutrient intake from Spanish food composition tables ( 23 ) . At the 3-month visit and when consulted by participants , dietitians assessed any adverse effects from the interventions by administering a checklist of symptoms and gave advice on how to remedy them . The checklist included mouth symptoms ; bloating , fullness , or indigestion ; altered bowel", "Background / Objectives : Snacks contribute toward a significant proportion of human total daily energy intake . This study investigated the effects of almonds , a satiating and nutrient-rich , common snack , on postpr and ial glycemia , appetite , short-term body weight and fasting blood parameters when consumed with meals or alone as a snack . Methods : This was a 4-week r and omized , parallel-arm study that entailed consuming almonds ( 43 g/day ) with breakfast ( BF ) or lunch ( LN ) , alone as a morning ( MS ) or afternoon ( AS ) snack or no almonds ( CL ) . Participants ( N=137 ) with increased risk for type 2 diabetes completed an oral glucose tolerance test ( OGTT ) and acute-feeding session at baseline , followed by almond consumption for 4 weeks before repeating the OGTT and acute-feeding trials . Anthropometric , biochemical and appetite responses were assessed . Results : Almonds lowered serum glucose responses postpr and ially . Effects were most prominent in the snack groups . Almonds , consumed as snacks , also reduced hunger and desire to eat during the acute-feeding session . After 4 weeks , anthropometric measurements and fasting blood biochemistries did not differ from the control group or across intervention groups . Without specific guidance , daily energy intake was reduced to compensate for energy from the provided almonds . Dietary monounsaturated fat and α-tocopherol intakes were significantly increased in all almond groups . Conclusion : Almonds provide post-ingestive metabolic and appetitive benefits and did not increase the risk for weight gain . This suggests that almonds may be a healthful snack option", "BACKGROUND It is known that obesity , sodium intake , and alcohol consumption factors influence blood pressure . In this clinical trial , Dietary Approaches to Stop Hypertension , we assessed the effects of dietary patterns on blood pressure . METHODS We enrolled 459 adults with systolic blood pressures of less than 160 mm Hg and diastolic blood pressures of 80 to 95 mm Hg . For three weeks , the subjects were fed a control diet that was low in fruits , vegetables , and dairy products , with a fat content typical of the average diet in the United States . They were then r and omly assigned to receive for eight weeks the control diet , a diet rich in fruits and vegetables , or a \" combination \" diet rich in fruits , vegetables , and low-fat dairy products and with reduced saturated and total fat . Sodium intake and body weight were maintained at constant levels . RESULTS At base line , the mean ( + /-SD ) systolic and diastolic blood pressures were 131.3+/-10.8 mm Hg and 84.7+/-4.7 mm Hg , respectively . The combination diet reduced systolic and diastolic blood pressure by 5.5 and 3.0 mm Hg more , respectively , than the control diet ( P systolic blood pressure by 2.8 mm Hg more ( P diastolic blood pressure by 1.1 mm Hg more than the control diet ( P=0.07 ) . Among the 133 subjects with hypertension ( systolic pressure , > or = 140 mm Hg ; diastolic pressure , > or = 90 mm Hg ; or both ) , the combination diet reduced systolic and diastolic blood pressure by 11.4 and 5.5 mm Hg more , respectively , than the control diet ( P 326 subjects without hypertension , the corresponding reductions were 3.5 mm Hg ( P blood pressure . This diet offers an additional nutritional approach to preventing and treating hypertension", "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", "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 Recent studies have identified potential beneficial effects of eating nuts , most of which have substantial amounts of monounsaturated fats . Macadamia nuts are 75 % fat by weight , 80 % of which is monounsaturated . OBJECTIVE To examine variations in serum lipid levels in response to a high-monounsaturated fat diet based on macadamia nuts . METHODS A r and omized crossover trial of three 30-day diets was conducted in 30 volunteers aged 18 to 53 years from a free-living population . Each was fed a \" typical American \" diet high in saturated fat ( 37 % energy from fat ) ; an American Heart Association Step 1 diet ( 30 % energy from fat ) ; and a macadamia nut-based monounsaturated fat diet ( 37 % energy from fat ) in r and om order . Serum total cholesterol , high-density lipoprotein cholesterol , and triglyceride levels were measured . RESULTS Mean total cholesterol level after the typical American diet was 5.20 mmol/L ( 201 mg/dL ) . After the Step 1 diet and the macadamia nut diet , total cholesterol level was 4.99 mmol/L ( 193 mg/dL ) and 4.95 mmol/L ( 191 mg/dL ) , respectively . Low-density lipoprotein cholesterol level was 3.37 mmol/L ( 130 mg/dL ) ( typical diet ) , 3.21 mmol/L ( 124 mg/dL ) ( Step 1 diet ) , and 3.22 mmol/L ( 125 mg/dL ) ( macadamia nut diet ) . High-density lipoprotein cholesterol level was 1.43 mmol/L ( 55 mg/dL ) ( typical ) , 1.34 mmol/L ( 52 mg/dL ) ( Step 1 ) , and 1.37 mmol/L ( 53 mg/dL ) ( macadamia nut ) . Lipid values after the Step 1 and macadamia nut diets were significantly different from those after the typical diet ( P macadamia nut-based diet high in monounsaturated fat and the moderately low-fat diet both had potentially beneficial effects on cholesterol and low-density lipoprotein cholesterol levels when compared with a typical American diet", "Objectives : Metabolic syndrome is a precursor of diabetes and cardiovascular disease ( CVD ) . Walnut ingestion has been shown to reduce CVD risk indices in diabetes . This r and omized controlled crossover trial was performed to investigate the effects of daily walnut consumption on endothelial function and other biomarkers of cardiac risk in a population of overweight individuals with visceral adiposity . Methods : Forty-six overweight adults ( average age , 57.4 years ; 28 women , 18 men ) with elevated waist circumference and 1 or more additional signs of metabolic syndrome were r and omly assigned to two 8-week sequences of walnut-enriched ad libitum diet and ad libitum diet without walnuts , which were separated by a 4-week washout period . The primary outcome measure was the change in flow-mediated vasodilation ( FMD ) of the brachial artery . Secondary measures included serum lipid panel , fasting glucose and insulin , Homeostasis Model Assessment –Insulin Resistance values , blood pressure , and anthropometric measures . Results : FMD improved significantly from baseline when subjects consumed a walnut-enriched diet as compared with the control diet ( 1.4 % ± 2.4 % versus 0.3 % ± 1.5 % ; p = 0.019 ) . Beneficial trends in systolic blood pressure reduction were seen , and maintenance of the baseline anthropometric values was also observed . Other measures were unaltered . Conclusion : Daily ingestion of 56 g of walnuts improves endothelial function in overweight adults with visceral adiposity . The addition of walnuts to the diet does not lead to weight gain . Further study of the potential role of walnut intake in diabetes and CVD prevention is warranted", "BACKGROUND Low-fat vegetarian and vegan diets are associated with weight loss , increased insulin sensitivity , and improved cardiovascular health . OBJECTIVE We compared the effects of a low-fat vegan diet and conventional diabetes diet recommendations on glycemia , weight , and plasma lipids . DESIGN Free-living individuals with type 2 diabetes were r and omly assigned to a low-fat vegan diet ( n = 49 ) or a diet following 2003 American Diabetes Association guidelines ( conventional , n = 50 ) for 74 wk . Glycated hemoglobin ( Hb A(1c ) ) and plasma lipids were assessed at weeks 0 , 11 , 22 , 35 , 48 , 61 , and 74 . Weight was measured at weeks 0 , 22 , and 74 . RESULTS Weight loss was significant within each diet group but not significantly different between groups ( -4.4 kg in the vegan group and -3.0 kg in the conventional diet group , P = 0.25 ) and related significantly to Hb A(1c ) changes ( r = 0.50 , P = 0.001 ) . Hb A(1c ) changes from baseline to 74 wk or last available values were -0.34 and -0.14 for vegan and conventional diets , respectively ( P = 0.43 ) . Hb A(1c ) changes from baseline to last available value or last value before any medication adjustment were -0.40 and 0.01 for vegan and conventional diets , respectively ( P = 0.03 ) . In analyses before alterations in lipid-lowering medications , total cholesterol decreased by 20.4 and 6.8 mg/dL in the vegan and conventional diet groups , respectively ( P = 0.01 ) ; LDL cholesterol decreased by 13.5 and 3.4 mg/dL in the vegan and conventional groups , respectively ( P = 0.03 ) . CONCLUSIONS Both diets were associated with sustained reductions in weight and plasma lipid concentrations . In an analysis controlling for medication changes , a low-fat vegan diet appeared to improve glycemia and plasma lipids more than did conventional diabetes diet recommendations . Whether the observed differences provide clinical benefit for the macro- or microvascular complications of diabetes remains to be established . This trial was registered at clinical trials.gov as NCT00276939", "We tested the effects of feeding a diet very high in fiber from fruit and vegetables . The levels fed were those , which had originally inspired the dietary fiber hypothesis related to colon cancer and heart disease prevention and also may have been eaten early in human evolution . Ten healthy volunteers each took 3 metabolic diets of 2 weeks duration . The diets were : high-vegetable , fruit , and nut ( very-high-fiber , 55 g/1,000 kcal ) ; starch-based containing cereals and legumes ( early agricultural diet ) ; or low-fat ( contemporary therapeutic diet ) . All diets were intended to be weight-maintaining ( mean intake , 2,577 kcal/d ) . Compared with the starch-based and low-fat diets , the high-fiber vegetable diet result ed in the largest reduction in low-density lipoprotein ( LDL ) cholesterol ( 33 % + /- 4 % , P fecal bile acid output ( 1.13 + /- 0.30 g/d , P = .002 ) , fecal bulk ( 906 + /- 130 g/d , P fecal short-chain fatty acid outputs ( 78 + /- 13 mmol/d , P fecal bulk , the actual concentrations of fecal bile acids were lowest on the vegetable diet ( 1.2 mg/g wet weight , P = .002 ) . Maximum lipid reductions occurred within 1 week . Urinary mevalonic acid excretion increased ( P = .036 ) on the high-vegetable diet reflecting large fecal steroid losses . We conclude that very high-vegetable fiber intakes reduce risk factors for cardiovascular disease and possibly colon cancer . Vegetable and fruit fibers therefore warrant further detailed investigation", "Reductions in low-density lipoprotein-cholesterol ( LDL-C ) result from diets containing almonds , or diets that are either low in saturated fat or high in viscous fibers , soy proteins , or plant sterols . We have therefore combined all of these interventions in a single diet ( portfolio diet ) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events . Twenty-five hyperlipidemic subjects consumed either a portfolio diet ( n=13 ) , very low in saturated fat and high in plant sterols ( 1.2 g/1,000 kcal ) , soy protein ( 16.2 g/1,000 kcal ) , viscous fibers ( 8.3 g/1,000 kcal ) , and almonds ( 16.6 g/1,000 kcal ) , or a low-saturated fat diet ( n=12 ) based on whole-wheat cereals and low-fat dairy foods . Fasting blood , blood pressure , and body weight were obtained at weeks 0 , 2 , and 4 of each phase . LDL-C was reduced by 12.1 % + /- 2.4 % ( P ratio of LDL-C to high-density lipoprotein-cholesterol ( HDL-C ) significantly ( 30.0 % + /- 3.5 % ; P reductions in LDL-C and the LDL : HDL-C ratio were both significantly lower on the portfolio diet than on the control diet ( P Mean weight loss was similar on test and control diets ( 1.0 kg and 0.9 kg , respectively ) . No difference was seen in blood pressure , HDL-C , serum triglycerides , lipoprotein(a ) [ Lp(a ) ] , or homocysteine concentrations between diets . Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy", "BACKGROUND The effect of dietary composition on blood pressure is a subject of public health importance . We studied the effect of different levels of dietary sodium , in conjunction with the Dietary Approaches to Stop Hypertension ( DASH ) diet , which is rich in vegetables , fruits , and low-fat dairy products , in persons with and in those without hypertension . METHODS A total of 412 participants were r and omly assigned to eat either a control diet typical of intake in the United States or the DASH diet . Within the assigned diet , participants ate foods with high , intermediate , and low levels of sodium for 30 consecutive days each , in r and om order . RESULTS Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg ( P reductions of 4.6 mm Hg during the control diet ( P participants with and in those without hypertension , blacks and those of other races , and women and men . The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level ; and the difference was greater with high sodium levels than with low ones . As compared with the control diet with a high sodium level , the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension , and 11.5 mm Hg lower in participants with hypertension . CONCLUSIONS The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially , with greater effects in combination than singly . Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods", "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", "Regular nut consumption may improve markers of inflammation and endothelial dysfunction . The quantity of nuts required to achieve these health benefits without compromising body weight and acceptance is unknown . This study compared the effects of incorporating hazelnuts at 2 different doses with a diet without nuts on inflammatory markers , cell adhesion molecules , and body composition in 107 overweight and obese individuals . This was a r and omized , controlled , parallel 12-wk intervention including 3 treatment arms : no nuts ( control group ) , 30 g/d of hazelnuts , or 60 g/d of hazelnuts . Blood pressure , body composition , plasma high-sensitivity C-reactive protein ( hs-CRP ) , interleukin 6 ( IL-6 ) , intercellular adhesion molecule 1 ( ICAM-1 ) , vascular cell adhesion molecule 1 ( VCAM-1 ) , lipid , and apolipoprotein ( apo ) profiles were assessed at baseline and at 6 and 12 wk . \" Desire \" and \" liking \" for nuts were assessed during the intervention . Results showed no significant differences in follow-up clinical outcomes between groups after adjusting for baseline values , age , sex , and BMI ( all P ≥ 0.10 ) , except for a tendency toward improvement in VCAM-1 concentration in the 60-g/d nut group ( P = 0.07 ) . Hazelnut consumption significantly improved diet quality in a dose-response manner . Desire and liking for nuts remained stable in the 30-g/d group , whereas these ratings decreased significantly over time in the 60-g/d group ( both P of hazelnut consumption appears to have minimal effect on inflammatory markers and cell adhesion molecules in this group of healthy , normocholesterolemic overweight and obese individuals . Nut consumption improves diet quality without adversely affecting body composition . Consuming 30 g/d of nuts regularly is achievable , whereas 60 g/d appears to compromise desire and liking", "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", "CONTEXT Combining foods with recognized cholesterol-lowering properties ( dietary portfolio ) has proven highly effective in lowering serum cholesterol under metabolically controlled conditions . OBJECTIVE To assess the effect of a dietary portfolio administered at 2 levels of intensity on percentage change in low-density lipoprotein cholesterol ( LDL-C ) among participants following self-selected diets . DESIGN , SETTING , AND PARTICIPANTS A parallel- design study of 351 participants with hyperlipidemia from 4 participating academic centers across Canada ( Quebec City , Toronto , Winnipeg , and Vancouver ) r and omized between June 25 , 2007 , and February 19 , 2009 , to 1 of 3 treatments lasting 6 months . INTERVENTION Participants received dietary advice for 6 months on either a low-saturated fat therapeutic diet ( control ) or a dietary portfolio , for which counseling was delivered at different frequencies , that emphasized dietary incorporation of plant sterols , soy protein , viscous fibers , and nuts . Routine dietary portfolio involved 2 clinic visits over 6 months and intensive dietary portfolio involved 7 clinic visits over 6 months . MAIN OUTCOME MEASURES Percentage change in serum LDL-C. RESULTS In the modified intention-to-treat analysis of 345 participants , the overall attrition rate was not significantly different between treatments ( 18 % for intensive dietary portfolio , 23 % for routine dietary portfolio , and 26 % for control ; Fisher exact test , P = .33 ) . The LDL-C reductions from an overall mean of 171 mg/dL ( 95 % confidence interval [ CI ] , 168 - 174 mg/dL ) were -13.8 % ( 95 % CI , -17.2 % to -10.3 % ; P dietary portfolio ; -13.1 % ( 95 % CI , -16.7 % to -9.5 % ; P Percentage LDL-C reductions for each dietary portfolio were significantly more than the control diet ( P 2 dietary portfolio interventions did not differ significantly ( P = .66 ) . Among participants r and omized to one of the dietary portfolio interventions , percentage reduction in LDL-C on the dietary portfolio was associated with dietary adherence ( r = -0.34 , n = 157 , P dietary portfolio compared with the low-saturated fat dietary advice result ed in greater LDL-C lowering during 6 months of follow-up . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00438425", "THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard", "Studies consistently show the beneficial effects of eating nuts , but as high-energy foods , their regular consumption may lead to weight gain . We tested if daily consumption of walnuts ( approximately 12 % energy intake ) for 6 months would modify body weight and body composition in free-living subjects . Ninety participants in a 12-month r and omized cross-over trial were instructed to eat an allotted amount of walnuts ( 28 - 56 g ) during the walnut-supplemented diet and not to eat them during the control diet , with no further instruction . Subjects were unaware that body weight was the main outcome . Dietary compliance was about 95 % and mean daily walnut consumption was 35 g during the walnut-supplemented diet . The walnut-supplemented diet result ed in greater daily energy intake ( 557 kJ ( 133 kcal ) ) , which should theoretically have led to a weight gain of 3.1 kg over the 6-month period . For all participants , walnut supplementation increased weight ( 0.4 ( se 0.1 ) kg ) , BMI ( 0.2 ( se 0.1 ) kg/m(2 ) ) , fat mass ( 0.2 ( se 0.1 ) kg ) and lean mass ( 0.2 ( se 0.1 ) kg ) . But , after adjusting for energy differences between the control and walnut-supplemented diets , no significant differences were observed in body weight or body composition parameters , except for BMI ( 0.1 ( se 0.1 ) kg/m(2 ) ) . The weight gain from incorporating walnuts into the diet ( control-->walnut sequence ) was less than the weight loss from withdrawing walnuts from the diet ( walnut-->control sequence ) . Our findings show that regular walnut intake result ed in weight gain much lower than expected and which became non-significant after controlling for differences in energy intake", "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", "Wound-care journals contain abundant reports of trials , but not all report a satisfactory methodology . Systematic review s of wound-care trials have highlighted many areas for improvement , and the National Institute for Clinical Excellence ( NICE ) guidelines recommend that primary research in the field of pressure ulcer prevention should adhere more closely to current method ological st and ards in terms of conduct and reporting . The CONSORT tool was developed to help achieve these improvements in the design and reporting of r and omised controlled trials ( RCTs )", "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", "Cohort studies are equivocal regarding a relationship between regular nut consumption and reduced risk of type 2 diabetes mellitus . Although acute trials show reductions in postpr and ial glycemia in healthy individuals ingesting 60 to 90 g almonds , trials have not been conducted using a single serving of almonds ( 28 g ) in individuals with type 2 diabetes mellitus . This r and omized crossover trial examined the impact of one serving of almonds at mealtime on postpr and ial glycemia , insulinemia , and plasma glucagon-like peptide-1 in healthy individuals and individuals with type 2 diabetes mellitus . On 2 occasions separated by at least 1 week , 19 adults ( including 7 adults with type 2 diabetes mellitus ) consumed a st and ardized evening meal and fasted overnight before ingesting the test meal ( bagel , juice , and butter ) with or without almonds . A small pilot study ( 6 - 7 subjects per group ) was also conducted to observe whether chronic almond ingestion ( 1 serving 5 d/wk for 12 weeks ) lowered hemoglobin A(1c ) in individuals with type 2 diabetes mellitus . A st and ard serving of almonds reduced postpr and ial glycemia significantly in participants with diabetes ( -30 % , P = .043 ) but did not influence glycemia in participants without diabetes ( -7 % , P = .638 ) . Insulinemia and glucagon-like peptide-1 at 30 minutes postmeal were not impacted by almond ingestion for either group . In the pilot study , regular almond ingestion for 12 weeks reduced hemoglobin A(1c ) by 4 % ( P = .045 for interaction ) but did not influence fasting glucose concentrations . These data show that modest almond consumption favorably improves both short-term and long-term markers of glucose control in individuals with uncomplicated type 2 diabetes mellitus", "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" ]

[ "OBJECTIVES To identify the most responsive method of measuring gait speed , to estimate the responsiveness of other outcome measures , and to determine whether gait speed predicts discharge destination in acute stroke . DESIGN A prospect i ve cohort study . SETTING Five acute-care hospitals . PATIENTS Fifty subjects with residual gait deficits after a first-time stroke . INTERVENTIONS Five- ( 5mWT ) and 10-meter walk tests ( 10mWT ) at comfortable and maximum speeds , with 2 evaluations conducted an average + /- st and ard deviation ( SD ) of 8 + /- 3 and 38 + /- 5 days poststroke . MAIN OUTCOME MEASURE St and ardized response mean ( SRM = mean change/SD of change ) was used to estimate responsiveness for each walk test , the Berg Balance Scale , the Barthel Index , the Stroke Rehabilitation Assessment of Movement ( STREAM ) , and the Timed Up and Go ( TUG ) . RESULTS The SRMs were 1.22 and 1.00 for the 5mWT , and .92 and .83 for the 10mWT performed at a comfortable and maximum pace , respectively . The SRMs for the Berg Balance Scale , the Barthel Index , the STREAM , and the TUG were 1.04,.99,.89 , and .73 , respectively . The probability of discharge to a rehabilitation center for persons walking at 0.6 m/s at the first evaluation was.95 and .22 , respectively . CONCLUSIONS The 5mWT at a comfortable pace is recommended as the measure of choice for clinicians and research ers who need to detect longitudinal change in walking disability in the first 5 weeks poststroke", "Background Frailty is a term commonly used to describe the condition of an older person who has chronic health problems , has lost functional abilities and is likely to deteriorate further . However , despite its common use , only a small number of studies have attempted to define the syndrome of frailty and measure its prevalence . The criteria Fried and colleagues used to define the frailty syndrome will be used in this study ( i.e. weight loss , fatigue , decreased grip strength , slow gait speed , and low physical activity ) . Previous studies have shown that clinical outcomes for frail older people can be improved using multi-factorial interventions such as comprehensive geriatric assessment , and single interventions such as exercise programs or nutritional supplementation , but no interventions have been developed to specifically reverse the syndrome of frailty . We have developed a multidisciplinary intervention that specifically targets frailty as defined by Fried et al. We aim to establish the effects of this intervention on frailty , mobility , hospitalisation and institutionalisation in frail older people . Methods and Design A single centre r and omised controlled trial comparing a multidisciplinary intervention with usual care . The intervention will target identified characteristics of frailty , functional limitations , nutritional status , falls risk , psychological issues and management of chronic health conditions . Two hundred and thirty people aged 70 and over who meet the Fried definition of frailty will be recruited from clients of the aged care service of a metropolitan hospital . Participants will be followed for a 12-month period . Discussion This research is an important step in the examination of specifically targeted frailty interventions . This project will assess whether an intervention specifically targeting frailty can be implemented , and whether it is effective when compared to usual care . If successful , the study will establish a new approach to the treatment of older people at risk of further functional decline and institutionalisation . The strategies to be examined are readily transferable to routine clinical practice and are applicable broadly in the setting of aged care health services . Trial Registration Australian New Zeal and Clinical Trails Registry : ACTRN12608000250336", "OBJECTIVES To define clinical ly relevant cutpoints for usual gait speed and to investigate their predictive value for health-related events in older persons . DESIGN Prospect i ve cohort study . SETTING Health , Aging and Body Composition Study . PARTICIPANTS Three thous and forty-seven well-functioning older persons ( mean age 74.2 ) . MEASUREMENTS Usual gait speed on a 6-m course was assessed at baseline . Participants were r and omly divided into two groups to identify ( Sample A ; n=2,031 ) and then vali date ( Sample B ; n=1,016 ) usual gait-speed cutpoints . Rates of persistent lower extremity limitation events ( mean follow-up 4.9 years ) were calculated according to gait speed in Sample A. A cutpoint ( defining high- ( or = 1 m/s ) groups ) was identified based on persistent lower extremity limitation events . The predictive value of the identified cutpoints for major health-related events ( persistent severe lower extremity limitation , death , and hospitalization ) was evaluated in Sample B using Cox regression analyses . RESULTS A grade d response was seen between risk groups and health-related outcomes . Participants in the high-risk group had a higher risk of persistent lower extremity limitation ( rate ratio (RR)=2.20 , 95 % confidence interval (CI)=1.76 - 2.74 ) , persistent severe lower extremity limitation ( RR=2.29 , 95 % CI=1.63 - 3.20 ) , death ( RR=1.64 , 95 % CI=1.14 - 2.37 ) , and hospitalization ( RR=1.48 , 95 % CI=1.02 - 2.13 ) than those in the low-risk group . CONCLUSION Usual gait speed of less than 1 m/s identifies persons at high risk of health-related outcomes in well-functioning older people . Provision of a clinical ly meaningful cutpoint for usual gait speed may facilitate its use in clinical and research setting", "OBJECTIVE To investigate the influence of the use of a rollator walking aid on assessment of gait and mobility . DESIGN Prospect i ve , longitudinal study . SUBJECTS Geriatric patients during inpatient rehabilitation ( n=109 ; mean age 83.1 years ) . METHODS Assessment at the beginning and prior to discharge from rehabilitation using : gait- analysis ( GAITRite ® , speed , cadence , stride-time , stride-length , base-of-support , double-support ) , Performance-Oriented-Mobility- Assessment ( POMA ) , and Timed-Up- and -Go ( TUG ) . Differences between outcomes obtained without and with rollator use were calculated for baseline assessment and for changes over time for the total group and subgroups according to diagnosis ( hip fracture vs. other ) . Responsiveness was calculated using st and ardized response means . RESULTS Baseline performances were significantly ( p ≤ 0.05 ) higher when assessed with vs. without rollator in the total group and in hip fracture ( except cadence ) and other ( except cadence , stride-time , TUG ) patients . Changes over time were significantly greater when assessed without vs. with rollator in the total group and hip fracture ( except cadence , POMA ) and other patients ( except base-of-support , double-support ) . Tests without rollator showed superior responsiveness ( except TUG ) . CONCLUSION The use of rollator walking aids limits the detection of initial gait and mobility deficits , adversely affects the assessment of changes over time in gait and mobility performance , and reduces the responsiveness of tests . When full weight-bearing is permitted , assessment without a walking aid is recommended", "Examining gait characteristics in older adults who are transitioning to frailty enhances our underst and ing of movement control in this fall-prone population and helps to better target preventive interventions . This work presents data on temporal and spatial gait parameters of a group of older adults who have been operationally defined as \" transitionally frail \" . Gait speed , cadence , stride length , stance , swing , double-support , and horizontal heel velocity at heel contact were measured in 50 transitionally frail older adults while walking at a self-selected pace . These data suggest that the temporal and spatial gait features of these older adults differ substantially from published results from other older adults", "OBJECTIVES To assess the ability of gait speed alone and a three-item lower extremity performance battery to predict 12-month rates of hospitalization , decline in health , and decline in function in primary care setting s serving older adults . DESIGN Prospect i ve cohort study . SETTING Primary care programs of a Medicare health maintenance organization ( HMO ) and Veterans Affairs ( VA ) system . PARTICIPANTS Four hundred eighty-seven persons aged 65 and older . MEASUREMENTS Lower extremity performance Established Population for Epidemiologic Studies of the Elderly ( EPESE ) battery including gait speed , chair st and s , and t and em balance tests ; demographics ; health care use ; health status ; functional status ; probability of repeated admission scale ( Pra ) ; and primary physician 's hospitalization risk estimate . RESULTS Veterans had poorer health and higher use than HMO members . Gait speed alone and the EPESE battery predicted hospitalization ; 41 % ( 21/51 ) of slow walkers ( gait speed hospitalized at least once , compared with 26 % ( 70/266 ) of intermediate walkers ( 0.6 - 1.0 m/s ) and 11 % ( 15/136 ) of fast walkers ( > 1.0 m/s ) ( P decline in function and health status in both health systems . Performance measures , alone or in combination with self-report measures , were more able to predict outcomes than self-report alone . CONCLUSION Gait speed and a physical performance battery are brief , quantitative estimates of future risk for hospitalization and decline in health and function in clinical population s of older adults . Physical performance measures might serve as easily accessible \" vital signs \" to screen older adults in clinical setting " ]

[ "The purpose of this study was to investigate the prevalence , clinical characteristics , and management of functional constipation at pediatric gastroenterology clinics . A prospect i ve survey using the Rome III criteria was distributed to a group of parents of children with a constipation history and its control group in May 2008 . The mean prevalence of constipation was 6.4 % , which was similar to those in other countries . Statistically significant variables for children without constipation were that more children had a body mass index of below the 10th percentile even though they received more mother 's care and ate balanced meals compared to the constipation group . Meanwhile , the constipation group frequently showed a history of constipation in infancy , picky-eating , lack of exercise , and retentive posturing . When analyzed with the Rome III criteria , the children showed greater than 60 % rate of hard stools , painful stools , a history of large fecal mass in rectum , and its disappearance of constipation symptoms after passing a large stool . Our study found different approaches amongst pediatric gastroenterologists like rectal examinations , disimpaction , or drug treatment . Several factors addressed in our study can provide better guidelines for clinicians treating constipation and its future research", "The influence of childhood nutrition on the development of constipation beyond the period of weaning and breastfeeding is relatively understudied . In addition , eating patterns in childhood can be highly correlated with overweight and sedentary behaviour , which may also have an influence on constipation . The aim of this study was to assess whether common dietary patterns , sedentary behaviour and childhood overweight are associated with constipation in childhood . The study was embedded in a population -based prospect i ve birth cohort . Information on dietary intake was obtained by a food frequency question naire at the child 's age of 14 months ( n = 2420 ) . The adherence scores on a ' Health conscious ' and ' Western-like ' diet were extracted from principal component analysis . At the age of 24 , 36 and 48 months , information on constipation and sedentary behaviour , and weight and height was obtained by parental-derived question naires and from the child health centres , respectively . Adherence to a ' Western-like ' dietary pattern was associated with a higher prevalence of constipation up to 48 months [ adjusted odds ratio ( aOR ) ; 95 % confidence interval ( CI ) : 1.39 ; 1.02 - 1.87 ] , which was not mediated by overweight or sedentary behaviour . Adherence to a ' Health Conscious ' dietary pattern was only associated at short term , with a lower prevalence of constipation at 24 months ( aOR ; 95%CI : 0.65 ; 0.44 - 0.96 ) . No association was found between overweight , sedentary behaviour and constipation . Our results suggest that specific dietary patterns in early childhood could be associated with higher or lower risks for constipation , but these effects are time-dependent . Overweight and sedentary behaviour seem to not have a major role on constipation in childhood", "BACKGROUND Experimental studies suggest that gut microbiota deviations predispose toward energy storage and obesity . OBJECTIVE We wanted to establish whether early gut microbiota composition can guide weight development throughout early childhood . DESIGN Overweight and obese children ( n = 25 ) were selected from a prospect i ve follow-up study at the age of 7 y and identified according to the International Obesity Task Force criteria . Normal-weight children ( n = 24 ) were selected from the same cohort and matched for gestational age and body mass index at birth , mode of delivery , probiotic supplementation , duration of breastfeeding , use of antibiotics during infancy , and frequencies of atopic diseases and atopic sensitization . Early fecal microbiota composition was analyzed by fluorescent in situ hybridization ( FISH ) with microscopic and flow cytometry detection and by quantitative real-time polymerase chain reaction ( qRT-PCR ) . RESULTS The bifidobacterial numbers in fecal sample s during infancy , as assessed by the FISH with flow cytometry , were higher in children remaining normal weight , [ median : 2.19 x 10(9 ) cells/g ( interquartile range : 1.10 - 5.28 x 10(9 ) cells/g ) ] than in children becoming overweight [ 1.20 x 10(9 ) cells/g ( 0.48 - 1.59x 10(9 ) cells/g ) ; P = 0.02 ] . A similar tendency was found by FISH with microscopic detection and qRT-PCR . The microbiota aberrancy during infancy in children becoming overweight was also associated with a greater number of Staphylococcus aureus [ 0.64 x 10(6 ) cells/g ( 0.33 - 1.00 x 10(6 ) cells/g ) ] than in children remaining normal weight [ 0.27 x 10(6 ) cells/g ( 0.17 - 0.50 x 10(6 ) cells/g ) ; P = 0.013 ] . CONCLUSION Aberrant compositional development of the gut microbiota precedes overweight , offering new possibilities for preventive and therapeutic applications in weight management", "Objective To examine the association of constipation with exercise , non-exercise physical activity , and sedentary behaviours in Hong Kong adolescents . Methods In 2006–2007 , 42 secondary schools were r and omly selected to participate in the Hong Kong Student Obesity Surveillance ( HKSOS ) project . A total of 33692 Form 1–7 students ( 44.9 % boys ; mean age 14.8 , SD 1.9 years ) completed an anonymous question naire on lifestyle behaviours . Constipation was defined as a frequency of evacuation of less than once every two days . Exercise ( moderate-to-vigorous levels ) and non-exercise physical activity ( NEPA ) were each considered insufficient when less than 1 hour per day , and sedentary behaviours were considered excessive when over 4 hours per day . Logistic regression was used to calculate adjusted odds ratio ( AOR ) for constipation in relation to exercise , NEPA , and sedentary behaviours , adjusting for potential confounders . Results Constipation was identified in 15.6 % ( 95 % CI 15.2 % – 16.0 % ) of adolescents overall , 14.0 % in those with sufficient exercise and 19.6 % in those without . Constipation was associated with insufficient exercise ( AOR 1.26 , 95 % CI 1.16 – 1.36 ) , insufficient NEPA 1.21 ( 1.10 – 1.33 ) and excessive sedentary behaviours ( 1.25 , 1.17 – 1.34 ) . Compared with having none of the above 3 inactive behaviours , increasing AORs of constipation were observed for having 1 ( AOR 1.23 ) , 2 ( AOR 1.57 ) and 3 ( AOR 1.88 ) inactive behaviours ( p for trend Conclusions Constipation was associated with insufficient physical activity and excessive sedentary behaviours among Chinese adolescents with a dose-response relation . If the association is causal , constipation could be prevented by promotion of physical activity", "Objectives : The aim of the study was to determine the frequency of functional constipation according to the Rome III criteria in children with morbid obesity and to evaluate by measuring colonic transit times ( CTTs ) whether decreased colonic motility is present in these children . Patients and Methods : Ninety-one children with morbid obesity ages 8 to 18 years , entering a prospect i ve , r and omized controlled study evaluating the effect of an outpatient versus inpatient treatment program of obesity , participated . All of the children filled out a st and ardized question naire regarding their bowel habits , and CTTs were measured using radioopaque markers . Food diaries were also recorded to evaluate their diet . Results : A total of 19 children ( 21 % ) had functional constipation according to the Rome III criteria , whereas 1 child had functional nonretentive fecal incontinence . Total CTT exceeded 62 hours in only 10.5 % of the children with constipation , and among them , 2 had a total CTT of > 100 hours . In the nonconstipated group 8.3 % had a delayed CTT . Furthermore , no difference was found between the diet of children with or without constipation , specifically not with respect to fiber and fat intake . Conclusions : Our study confirms a high frequency of functional constipation in children with obesity , using the Rome III criteria . However , abnormal colonic motility , as measured by CTT , was delayed in only a minority of patients . No relation was found between constipation in these children and fiber or fat intake", "Background There is no data on diet- and activity-related behaviors associated with overweight and obesity among Pakistani school-aged children . The study aim ed to explore dietary behaviors , physical activity and sedentary lifestyle associated with overweight and obesity , and their socio-demographic correlates , among Pakistani primary school children . Methods A population -based cross-sectional study was conducted with a representative multistage r and om cluster sample of 1860 children aged five to twelve years in Lahore , Pakistan . Overweight ( > + 1 SD ) and obesity ( > + 2 SD ) were defined using the World Health Organization reference 2007 . Chi-square test was used as the test of trend . Linear regression was used to examine the predictive power of independent variables in relation to body mass index ( BMI ) . Logistic regression was used to quantify the independent predictors and adjusted odds ratios ( aOR ) with 95 % confidence intervals ( CI ) were obtained . Statistical significance was considered at P skipping breakfast ( 8 % ) , eating fast food and snacks ≥ once a week ( 43 % ) and being involved in sedentary lifestyle > one hour a day ( 49 % ) were significantly more likely to be overweight and obese while those participating in physical activity > twice a week ( 53 % ) were significantly less likely to be overweight and obese ( all P Skipping breakfast ( P eating fast food and snacks ( P = 0.001 ) and sedentary lifestyle ( P association with BMI while physical activity showed an independent inverse association ( P = 0.001 ) . Skipping breakfast ( aOR 1.82 , 95 % CI 1.22 - 2.71 ) , eating fast food and snacks ≥ once a week ( OR 1.41 , 95 % CI 1.07 - 1.86 ) , physical activity > twice a week ( aOR 0.49 , 95 % CI 0.34 - 0.70 ) and sedentary lifestyle > one hour a day ( aOR 1.56 , 95 % CI 1.19 - 2.03 ) were independent predictors of being overweight . Skipping breakfast had independent inverse association with physical activity ( aOR 0.63 , 95 % CI 0.45 - 0.89 ) and eating fast food and snacks had independent positive association with sedentary lifestyle ( aOR 1.79 , 95 % CI 1.49 - 2.16 ) . Female gender was independently associated with skipping breakfast ( aOR 1.50 , 95 % CI 1.04 - 2.16 ) . Male gender ( aOR 1.64 , 95 % CI 1.33 - 2.02 ) , urban area with high SES ( aOR 5.09 , 95 % CI 3.02 - 8.60 ) and higher parental education ( aOR 1.74 , 95 % CI 1.12 - 2.68 ) were significant independent predictors of eating fast food and snacks ≥ once a week . Living in the rural area was independently associated ( aOR 2.51 , 95 % CI 1.71 - 3.68 ) with physical activity > twice a week . Male gender ( aOR 1.60 , 95 % CI 1.31 - 1.95 ) , urban area with low SES ( aOR 1.46 , 95 % CI 1.02 - 2.09 ) , high-income neighborhoods ( aOR 1.52 , 95 % CI 1.02 - 2.25 ) , higher parental education ( aOR 1.55 , 95 % CI 1.03 - 2.34 ) and fewer siblings ( aOR 1.38 , 95 % CI 1.10 - 1.73 ) were independent predictors of sedentary lifestyle > one hour a day . Conclusions Dietary behaviors , physical activity and sedentary lifestyle are independent predictors of overweight and higher BMI among Pakistani primary school children , and are significantly affected by the child 's socio-demographic characteristics . These findings support the urgent need to develop a National strategy for diet and physical activity and to implement culturally relevant behavioral interventions in the re source -poor developing country setting", "OBJECTIVES : This study examines long-term prognoses for children with constipation in adulthood and identifies prognostic factors associated with clinical outcomes . METHODS : In a Dutch tertiary hospital , children ( 5–18 years of age ) who were diagnosed as having functional constipation were eligible for inclusion . After a 6-week treatment protocol , prospect i ve follow-up evaluations were conducted at 6 and 12 months and annually thereafter . Good clinical outcomes were defined as ≥3 bowel movements per week for ≥4 weeks , with ≤2 fecal incontinence episodes per month , irrespective of laxative use . RESULTS : A total of 401 children ( 260 boys ; median age : 8 years [ interquartile range : 6–9 years ] ) were included , with a median follow-up period of 11 years ( interquartile range : 9–13 years ) . The dropout rate during follow-up was 15 % . Good clinical outcomes were achieved by 80 % of patients at 16 years of age . Thereafter , this proportion remained constant at 75 % . Poor clinical outcomes at adult age were associated with : older age at onset ( odds ratio [ OR ] : 1.15 [ 95 % confidence interval [ CI ] : 1.02–1.30 ] ; P = .04 ) , longer delay between onset and first visit to our outpatient clinic ( OR : 1.24 [ 95 % CI : 1.10–1.40 ] ; P = .001 ) , and lower defecation frequency at study entry ( OR : 0.92 [ 95 % CI : 0.84–1.00 ] ; P = .03 ) . CONCLUSIONS : One-fourth of children with functional constipation continued to experience symptoms at adult age . Certain risk factors for poor clinical outcomes in adulthood were identified . Referral to a specialized clinic should be considered at an early stage for children who are unresponsive to first-line treatment", "Background : Constipation is a pediatric problem commonly encountered by many health care workers in primary , secondary , and tertiary care . To assist medical care providers in the evaluation and management of children with functional constipation , the North American Society for Pediatric Gastroenterology , Hepatology , and Nutrition and the European Society for Pediatric Gastroenterology , Hepatology , and Nutrition were charged with the task of developing a uniform document of evidence -based guidelines . Methods : Nine clinical questions addressing diagnostic , therapeutic , and prognostic topics were formulated . A systematic literature search was performed from inception to October 2011 using Embase , MEDLINE , the Cochrane Data base of Systematic Review s and Cochrane Central Register of Controlled Clinical Trials , and PsychInfo data bases . The approach of the Grading of Recommendations Assessment , Development and Evaluation was applied to evaluate outcomes . For therapeutic questions , quality of evidence was assessed using the Grading of Recommendations , Assessment , Development , and Evaluation system . Grading the quality of evidence for the other questions was performed according to the classification system of the Oxford Centre for Evidence -Based Medicine . During 3 consensus meetings , all recommendations were discussed and finalized . The group members voted on each recommendation , using the nominal voting technique . Expert opinion was used where no r and omized controlled trials were available to support the recommendation . Results : This evidence -based guideline provides recommendations for the evaluation and treatment of children with functional constipation to st and ardize and improve their quality of care . In addition , 2 algorithms were developed , one for the infants and the other for older infants and children . Conclusions : This document is intended to be used in daily practice and as a basis for further clinical research . Large well- design ed clinical trials are necessary with regard to diagnostic evaluation and treatment", "Oatmeal porridge has been consumed for centuries and has several health benefits . We aim ed to investigate the effect of oatmeal porridge on gut microflora functions . A total of ten healthy subjects ingested 60 g oatmeal porridge daily for 1 week . The following microflora-associated characteristics were assessed before and after the intervention : intestinal gas production following lactulose ingestion , faecal excretion of SCFA and faecal levels of urease and β-galactosidase . In addition , rectal levels of PGE2 were measured . Microbial fermentation as evaluated by intestinal gas production and excretion of SCFA did not change significantly following the dietary intervention . However , faecal levels of β-galactosidase and urease decreased after eating oatmeal porridge ( P=0·049 and 0·031 , respectively ) . Host inflammatory state , as measured by rectal levels of PGE2 , also decreased , but the change was not significant ( P=0·168 ) . The results suggest that oatmeal porridge has an effect on gut microbial functions and may possess potential prebiotic properties that deserve to be investigated further", "BACKGROUND Ingestion of a meal stimulates colonic motility . It is unclear whether the nutrient composition of a meal affects colonic motor response . AIMS To investigate and compare the effects of a predominantly fat or carbohydrate meal on colonic motility . METHODS In 18 healthy subjects , ambulatory colonic manometry was performed by placing a six sensor , solid state probe from the mid-transverse colon to the rectum . In a r and omised , crossover design , 10 and 27 hours after probe placement , subjects received 4.18 MJ meals containing 60 % calories from fat or carbohydrate sources . Prepr and ial and postpr and ial pressure activity and motor patterns were evaluated . RESULTS Both meals induced phasic activity with a greater area under the curve ( p Fat induced motor activity persisted longer ( p carbohydrate meal , but the onset of motor response was slower ( p propagating pressure waves , only the fat meal induced more ( p waves . After both meals , 50 % of subjects exhibited high amplitude ( more than 103 mm Hg ) , prolonged duration ( more than 13 seconds ) propagating waves . Both meals induced greater activity ( p Carbohydrate meals induce colonic motor response , but the effects are short lived when compared with fat meals . The prolonged , segmental , and retro grade phasic activity induced by the fat meal may delay colon transit . Thus meal composition influences colonic motor response", "OBJECTIVE The aim was to analyze the prevalence of eating problems and specific associations between overweight , obesity , and eating behavior in children with incontinence . SUBJECTS AND METHODS Forty-three consecutively presented children with incontinence , diagnosed to International Children 's Continence Society st and ards , and 44 matched continent controls were examined prospect ively . All children received a physical examination , sonography , and a one-dimensional intelligence test . Child psychopathology was measured with the Child Behavior Checklist ( CBCL/4 - 18 ) . Eating problems were assessed with the German version of the Dutch Eating Behaviour Question naire for Children ( DEBQ-C ) and a 40-item-parental question naire referring to atypical eating problems . RESULTS Of the 43 children with incontinence , 23.3 % had nocturnal enuresis ( NE ) only , 37.2 % had any form of daytime urinary incontinence ( DUI ) ( isolated or combined with NE ) and 39.5 % had fecal incontinence ( FI ) ( isolated or combined with NE and /or DUI ) . Incontinent children showed significantly more CBCL externalizing symptoms ( 35.7 % vs. 6.8 % ) and total problems ( 46.3 % vs. 6.8 % ) in the clinical range ( > 90th percentile ) , as well as significantly lower mean IQ ( 105.5 vs. 120.6 ) than continent controls . Of the children with incontinence , 16.9 % were affected by obesity ( ≥95th body mass index [ BMI ] percentile ) compared with none of the continent controls . Especially in children with FI , the rate of obesity was significantly increased ( 23.5 % ) . In addition , 46.5 % of incontinent children , but none of the controls , had constipation . Again , children with FI ( 82.4 % ) had the highest rate of constipation ( > DUI : 25 % > NE only : 20 % ) . \" Food refusal \" ( FR ) and \" intense fear of gaining weight \" ( GW ) , but not other eating problems , were significantly more common among incontinent children ( FR mean score 7.3 ; GW mean score 1.4 ) than in controls ( FR mean score 5.6 ; GW mean score 0.7 ) . After controlling for BMI percentiles , FR still was significantly higher in incontinent children . Children with FI had the highest score of FR among all subgroups of incontinence ( mean score 9.1 ) . CONCLUSIONS This study shows that overweight , obesity , behavioral and eating problems are especially associated with disorders of the gastrointestinal tract ( FI and constipation ) , and only to a lesser degree with those of the urinary tract ( DUI and NE ) . These problems should be addressed routinely in the clinical care of children with incontinence", "Objectives : Decreased physical activity levels in children may partly explain the rising prevalence of functional constipation in childhood . The aim of the present study , therefore , was to examine the association between physical activity and functional constipation during the preschool period . Methods : This study was embedded in the Generation R study , a large prospect i ve birth-cohort study in Rotterdam , The Netherl and s. Physical activity was measured by an Actigraph accelerometer in 347 children ( 182 boys , 165 girls ; mean age 25.1 months ) and data were expressed as counts per minute . Data were categorized into light activity ( 302–614 counts/15 seconds ) , moderate activity ( 615–1230 counts/15 seconds ) , and vigorous activity ( ≥1231 counts/15 seconds ) . Functional constipation in the third and fourth year of life was defined according to the Rome II criteria . Results : Children spending time in the highest tertile of light ( adjusted odds ratio [ OR ] 0.34 ; 95 % confidence interval [ CI ] 0.13–0.87 ) , moderate ( adjusted OR 0.37 ; 95 % CI 0.14–0.97 ) , and total activity ( adjusted OR 0.37 ; 95 % CI 0.15–0.92 ) at the age of 2 years had significantly less functional constipation in the fourth year of life . For functional constipation in the third year of life , the results were in similar direction but not statistically significant . Additionally , children with physical activity of more than the WHO recommendation of 60 min/day had significantly less functional constipation in the fourth year of life ( adjusted OR 0.48 ; 95 % CI 0.24–0.97 ) . Conclusions : Physical activity is associated with a decreased risk of functional constipation in the preschool period , but this may be time dependent", "Constipation frequency was investigated among 1897 subjects ( 874 males and 1023 females ) , ranging in age from 6 to 70 years , chosen at r and om between city inhabitants and farmers . Bowel habit was studied in 966 obese patients ( 390 males and 576 females ) . The authors followed for the diagnosis of constipation either the commonest and restrictive criterion of the weekly bowel actions or the clinical one which implies also others parameters , like hard or small stools , difficulties of expulsion or feeling of incomplete evacuation after defecation . The statistical analysis showed that constipation frequency is 8.3 % in obese patients and 1.5 % in normal-weighting , according to weekly bowel actions criterion : the difference is statistically significative ( p less than 0.001 )", "The presence of methane on lactulose breath test among irritable bowel syndrome ( IBS ) subjects is highly associated with the constipation-predominant form . Therefore , we set out to determine whether methane gas can alter small intestinal motor function . In dogs , small intestinal fistulae were created to permit measurement of intestinal transit . Using a radiolabel , we evaluated transit during infusion of room air and subsequently methane . In this model , small intestinal infusion of methane produced a slowing of transit in all dogs by an average of 59 % . In a second experiment , guinea pig ileum was pinned into an organ bath for the study of contractile activity in response to brush strokes applied to the mucosa . The force of contraction was measured both orad and aborad to the stimulus . The experiment was repeated while the bath was gassed with methane . Contractile activities orad and aborad to the stimulus were significantly augmented by methane compared with room air ( P humans with IBS who had undergone a small bowel motility study were compared such that subjects who produced methane on lactulose breath test were compared with those producing hydrogen . The motility index was significantly higher in methane-producing IBS patients ( 1,851 + /- 861 ) compared with hydrogen producers ( 1,199 + /- 301 ) ( P small intestinal transit and appears to do so by augmenting small bowel contractile activity", "Two groups of beneficial bacteria are dominant in the human gut , the Bacteroidetes and the Firmicutes . Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people , and that this proportion increases with weight loss on two types of low-calorie diet . Our findings indicate that obesity has a microbial component , which might have potential therapeutic implication", "BACKGROUND This study was conducted to assess the national prevalence of different grade s of nutritional status ( underweight , normal weight , overweight and obesity ) among Iranian school-students and to compare the prevalence of overweight and obesity using three different sets of criteria . METHODS This cross-sectional national survey was conducted on a representative sample of 21 111 school students including 10 253 boys ( 48.6 % ) and 10 858 girls ( 51.4 % ) aged 6 - 18 years , selected by multistage r and om cluster sampling from urban ( 84.6 % ) and rural ( 15.4 % ) areas of 23 provinces in Iran The percentage of subjects in the corresponding body mass index ( BMI ) categories of the Centers of Disease Control and Prevention ( CDC ) , the International Obesity Task Force ( IOTF ) and the obtained national percentiles were assessed and compared . RESULTS There was no gender differences in BMI , but was higher in boys living in urban than in rural areas ( 18.4 + /- 3.88 vs. 17.86 + /- 3.66 kg/m(2 ) respectively , P prevalence of underweight was 13.9 % ( 8.1 % of boys and 5.7 % of girls ) according to the CDC percentiles , and 5 % ( 2.6 % of boys and 2.4 % of girls ) according to the obtained percentiles . According to the CDC , IOTF and national cut-offs , the prevalence of overweight was 8.82 % , 11.3 % and 10.1 % respectively ; and the prevalence of obesity was 4.5 % , 2.9 % and 4.79 % respectively . The prevalence of overweight was highest ( 10.98 % ) in the 12-year-old group and that of obesity ( 7.81 % ) in the 6-year-old group . The kappa correlation coefficient was 0.71 between the CDC and IOTF criteria , 0.64 between IOTF and national cut-offs , and 0.77 between CDC and national cut-offs . CONCLUSIONS The findings of this study warrant the necessity of paying special attention to monitoring of the time trends in child obesity based on uniform definitions , as well as to design programmes to prevent and control associated factors" ]

[ "Background —Recent clinical trials have demonstrated that aggressive lipid lowering by statins could prevent recurrent events after acute coronary syndrome ( ACS ) . We hypothesized that this efficacy was caused by a significant reduction in plaque volume by aggressive LDL cholesterol ( LCL-C ) lowering . The present study investigated the effect of early statin treatment on plaque volume of a nonculprit lesion by serial volumetric intravascular ultrasound in patients with ACS . Methods and Results —Seventy patients with ACS were enrolled . All patients underwent emergency coronary angiography and percutaneous coronary intervention ( PCI ) . They were r and omized to intensive lipid-lowering therapy ( n=35 ; atorvastatin 20 mg/d ) or control ( n=35 ) groups after PCI . Volumetric intravascular ultrasound analyses were performed at baseline and 6-month follow-up for a non-PCI site in 48 patients ( atorvastatin , n=24 ; control , n=24 ) . LDL-C level was significantly decreased by 41.7 % in the atorvastatin group compared with the control group , in which LDL-C was increased by 0.7 % ( P was significantly reduced in the atorvastatin group ( 13.1±12.8 % decrease ) compared with the control group ( 8.7±14.9 % increase ; P ) . Percent change in plaque volume showed a significant positive correlation with follow-up LDL-C level ( R=0.456 , P=0.0011 ) and percent LDL-C reduction ( R=0.612 , P by atorvastatin for 6 months significantly reduced the plaque volume in patients with ACS . Percent change in plaque volume showed a significant positive correlation with percent LDL-C reduction , even in patients with low baseline", "Gastric bypass leads to the remission of type 2 diabetes independently of weight loss . Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation . We prospect ively studied 12 patients undergoing gastric bypass and six patients undergoing gastric b and ing over a 6-wk period . Plasma fibroblast growth factor (FGF)19 , stimulated by bile acid absorption in the terminal ileum , and plasma bile acids were measured . In canine and rodent models , we investigated changes in the gut hormone response after altered bile flow . FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric b and ing . In the canine model , both food and bile , on their own , stimulated satiety gut hormone responses . However , when combined , the response was doubled . In rats , drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response , reduced food intake , and lower body weight . In conclusion , after gastric bypass , bile flow is altered , leading to increased plasma bile acids , FGF19 , incretin . and satiety gut hormone concentrations . Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes", "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", "Background —Angiography of the coronary arteries reflects only changes in luminal dimensions . With intravascular ultrasound , cross-sectional images can be obtained and area measurements can be added to calculate volumes of the external elastic membrane ( EEM ) , plaque plus media ( P+M ) , and lumen . The aim of this study was to investigate the effect of lipid lowering by simvastatin on coronary atherosclerotic P+M as changes in volumes of EEM , P+M , and lumen . Methods and Results —In 40 male patients with hypercholesterolemia , ischemic heart disease , and a nonsignificant coronary artery lesion in a not previously revascularized coronary artery , serial intravascular ultrasound studies with an ECG-triggered pullback were performed at baseline , after 3 months on a lipid-lowering diet , and after another 12 months on simvastatin 40 mg/d . Mean length of the analyzed atherosclerotic segments was 5.9±3.3 mm . After 12 months on simvastatin , a significant reduction in P+M volume of 6.3 % ( P = 0.002 ) was observed , whereas only a nonsignificant reduction in EEM volume of 1.8 % was seen without any concomitant change in lumen volume . A significant reduction in total cholesterol of 31.0 % ( 6.1±0.8 versus 4.2±0.7 mmol/L , P ) and LDL cholesterol of 42.6 % ( 4.0±0.8 versus 2.2±0.6 mmol/L , P Conclusions —Lipid-lowering therapy with simvastatin for 12 months is associated with a significant P+M regression in coronary arteries measured as reduction in P+M and EEM volumes without any concomitant change in lumen volume ", "Objective The purpose of this study was to learn whether preoperative eating habits can be used to predict outcome after vertical b and ed gastroplasty ( VBG ) and Roux-en-Y gastric bypass ( RYGB ) . Background Summary Several independent r and omized and sequential studies have reported significantly greater weight loss after RYGB in comparison with VBG . Although the mechanism responsible for weight loss after both procedures is restriction of intake rather than malabsorption , the relationships between calorie intake , food preferences , and postoperative weight loss are not well defined . Methods During the past 5 years , 138 patients were prospect ively selected for either VBG or RYGB , based on their preoperative eating habits . All patients were screened by a dietitian who determined total calorie intake and diet composition before recommending VBG or RYGB . Thirty patients were selected for VBG ; the remaining 108 patients were classified as “ sweets eaters ” or “ snackers ” and had RYGB . Detailed recall diet histories also were performed at each postoperative visit . Results Early morbidity rate was zero after VBG versus 3 % after RYGB . There were no deaths . Mean follow-up was 39 ± 11 months after VBG and 38 ± 14 months after RYGB . Mean weight loss peaked at 74 ± 23 lb at 12 months after VBG and 99 ± 24 lb at 16 months after RYGB ( p ≤ 0.001 ) . Twelve of 30 VBG patients lost > 50 % of their excess weight versus 100 of 108 RYGB patients ( p ≤ 0.0001 ) . Milk/ice cream intake was significantly greater postoperatively in patients who underwent VBG versus patients who underwent RYGB after 6 months ( p ≤ 0.003 ) , whereas solid sweets intake was significantly greater after VBG during the first 18 months postoperatively ( p ≤ 0.004 ) . Revision of VBG was performed in 6 of 30 patients ( 20 % ) for complications or poor weight loss , whereas only 2 of 108 patients who underwent RYGB required surgical revisions ( p ≤ 0.001 ) . Conclusions These data show that VBG adversely alters postoperative eating behavior toward soft , high-calorie foods , result ing in problematic postoperative weight loss . Conversely , RYGB patients had significantly greater weight loss despite inferior preoperative eating habits . The high rate", "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", "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 . )", "BACKGROUND Hyperoxaluria and increased calcium oxalate stone formation occur after Roux-en-Y gastric bypass ( RYGB ) surgery for morbid obesity . The etiology of this hyperoxaluria is unknown . We hypothesized that after bariatric surgery , intestinal hyperabsorption of oxalate contributes to increases in plasma oxalate and urinary calcium oxalate supersaturation . METHODS We prospect ively examined oxalate metabolism in 11 morbidly obese subjects before and 6 and 12 months after RYGB ( n = 9 ) and biliopancreatic diversion-duodenal switch ( BPD-DS ) ( n = 2 ) . We measured 24-hour urinary supersaturations for calcium oxalate , apatite , brushite , uric acid , and sodium urate ; fasting plasma oxalate ; 72-hour fecal fat ; and increases in urine oxalate following an oral oxalate load . RESULTS Six and 12 months after RYGB , plasma oxalate and urine calcium oxalate supersaturation increased significantly compared with similar measurements obtained before surgery ( all P ≤ .02 ) . Fecal fat excretion at 6 and 12 months was increased ( P = .026 and .055 , 0 vs 6 and 12 months ) . An increase in urine oxalate excretion after an oral dose of oxalate was observed at 6 and 12 months ( all P ≤ .02 ) . Therefore , after bariatric surgery , increases in fecal fat excretion , urinary oxalate excretion after an oral oxalate load , plasma oxalate , and urinary calcium oxalate supersaturation values were observed . CONCLUSION Enteric hyperoxaluria is often present in patients after the operations of RYGB and BPD-DS that utilize an element of intestinal malabsorption as a mechanism for weight loss", "Whether free fatty acid ( FFA ) rate of appearance ( R(a ) ) is increased in type 2 diabetes is controversial . To characterize nocturnal and postpr and ial abnormalities in FFA kinetics and to determine the effects of treatment with insulin sensitizers on lipolysis , we measured palmitate R(a ) in control subjects ( n = 6 ) and individuals with poorly controlled , sulfonylurea-treated type 2 diabetes ( HbA(1c ) = 8.7 + /- 0.2 % , n = 20 ) , the latter before and at the end of 12 weeks of treatment with troglitazone ( 600 mg/day , n = 4 ) , metformin ( approximately 2,000 mg/day , n = 8) , or placebo ( n = 8) . Subjects consumed a st and ard breakfast at 0800 h. Results in control subjects and type 2 diabetic subjects were compared at baseline . Integrated nocturnal FFA R(a ) ( AUC(1:00 - 8:00 A.M. ) ) was approximately 50 % higher in type 2 diabetic subjects than in control subjects ( 29.4 + /- 3.0 vs. 19.4 + /- 3.9 mmol . m(-2 ) . 7 h(-1 ) , respectively , P postpr and ial palmitate R(a ) ( AUC(0 - 240 min ) ) was almost threefold higher in type 2 diabetic subjects than in control subjects ( 14.2 + /- 1.7 vs. 5.3 + /- 1.0 mmol . m(-2 ) . 4 h(-1 ) , respectively , P troglitazone treatment , nocturnal palmitate R(a ) did not change , but postpr and ial palmitate R(a ) decreased by approximately 30 % ( P Palmitate kinetics did not change with metformin or placebo treatment . In summary , nocturnal and postpr and ial FFA R(a ) is increased in type 2 diabetes . Postpr and ial lipolysis appears to be preferentially improved by thiazolidinediones compared with nocturnal lipolysis", "BACKGROUND The biological variation of some commonly assessed metabolic variables in healthy subjects has not been studied extensively . The aim of the study was to assess , in 12 healthy subjects ( 6 male and 6 female ; mean ( SD ) age ; 22.7 ( 1.5 ) years ) following an overnight fast , the day-to-day variation of body fat ( impedance method ) , triglycerides , nonesterified fatty acid ( NEFAs ) , glycerol , 3-hydroxybutyrate ( 3-OHB ) , lactate , glucose , insulin ( RIA ) , C-peptide , and glucagon on 12 consecutive days . METHODS Between- and within-subject coefficients of variation ( CVG and CVW ) were estimated using a r and om effects analysis of variance , and assay variation was subtracted to give the coefficient of within-subject biological variation ( CVI ) . Individuality indices were calculated as CVW/CVG . RESULTS The overall means , CVI , and individuality indices were as follows : for body fat , 24.2 % , 10 % , and 0.3 ; for triglycerides , 0.61 mmol/L , 21 % , and 1.1 ; for NEFAs , 376 micromol/L , 45 % , and 1.4 ; for glycerol , 48 micromol/L , 36 % , and 0.8 ; for 3-OHB , 43 micromol/L , 61 % , and 1.5 ; for lactate , 0.88 mmol/L , 31 % , and 1.1 ; for glucose , 4.9 mmol/L , 4.8 % , and 0.7 ; for insulin , 52 pmol/L , 26 % , and 1.0 ; for C-peptide , 0.39 nmol/L , 24 % , and 0.9 ; and for glucagon , 53 ng/L , 19 % , and 0.8 . CONCLUSIONS The data presented here are necessary for the evaluation of several important metabolic variables in individual and group studies . The biological variation of some metabolites makes it difficult to characterize the status of healthy subjects with a single measurement", "Objective This report documents that the gastric bypass operation provides long-term control for obesity and diabetes . Summary Background Data Obesity and diabetes , both notoriously resistant to medical therapy , continue to be two of our most common and serious diseases . Methods Over the last 14 years , 608 morbidly obese patients underwent gastric bypass , an operation that restricts caloric intake by ( 1 ) reducing the functional stomach to approximately 30 mL , ( 2 ) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet , and ( 3 ) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy . Even though many of the patients were seriously ill , the operation was performed with a perioperative mortality and complication rate of 1.5 % and 8.5 % , respectively . Seventeen of the 608 patients ( Gastric bypass provides durable weight control . Weights fell from a preoperative mean of 304.4 lb ( range , 198 to 615 lb ) to 192.2 lb ( range , 104 to 466 ) by 1 year and were maintained at 205.4 lb ( range , 107 to 512 lb ) at 5 years , 206.5 lb ( 130 to 388 lb ) at 10 years , and 204.7 lb ( 158 to 270 lb ) at 14 years . The operation provides long-term control of non-insulin-dependent diabetes mellitus ( NIDDM ) . In those patients with adequate follow-up , 121 of 146 patients ( 82.9 % ) with NIDDM and 150 of 152 patients ( 98.7 % ) with glucose impairment maintained normal levels of plasma glucose , glycosylated hemoglobin , and insulin . These antidiabetic effects appear to be due primarily to a reduction in caloric intake , suggesting that insulin resistance is a secondary protective effect rather than the initial lesion . In addition to the control of weight and NIDDM , gastric bypass also corrected or alleviated a number of other comorbidities of obesity , including hypertension , sleep apnea , cardiopulmonary failure , arthritis , and infertility", "Abstract Objective . Exogenous bile acid ( BA ) administration is associated with beneficial metabolic effects very similar to those seen after Roux-en-Y gastric bypass ( RYGB ) surgery . Re-routing of bile into a biliopancreatic limb with simultaneous exclusion of food occurs after RYGB , with subsequent increased fasting plasma BAs . The study assessed fasting and post-pr and ial plasma BA response before and 15 months after RYGB . Material and methods . The prospect i ve study recruited 63 obese individuals ( 43 females ) , aged 43 ( 36–56 ) [ median ( IQR ) ] years . Blood sample s were collected before and every 30 min for 120 min after a st and ard 400 kcal meal . Fasting and post-pr and ial plasma BAs , glucagons like peptide-1 ( GLP-1 ) , –tyrosine ( PYY ) , fasting C-reactive protein ( CRP ) , glucose and insulin were measured and homeostasis model assessment -insulin resistance ( HOMA-IR ) was calculated . Results . Following RYGB , body mass index , CRP , fasting glucose and HOMA-IR decreased ; 43.7 ( 39.3–49.2 ) kg/m2 to 29.2 ( 25.1–35.0 ) kg/m2 , 7.9 ( 4.1–11.9 ) mg/L to 0.4 ( 0.2–1.0 ) mg/L , 5.5 ( 5.0–6.0 ) mmol/L to 4.6 ( 4.3–4.9 ) mmol/L and 5.9 ( 3.5–9.2 ) to 1.7 ( 1.1–2.2 ) , respectively , all P 0.001 . Fasting total BAs , GLP-1 and PYY increased after RYGB ; 1.69 ( 0.70–2.56 ) µmol/L to 2.43 ( 1.23–3.82 ) µmol/L ( P = 0.02 ) , 6.8 ( 1.5–15.3 ) pmol/L to 17.1 ( 12.6–23.9 ) pmol/L ( P post-pr and ial total BAs , total glycine-conjugated BAs , GLP-1 and PYY were greater after RYGB ; 486 ( 312–732 ) µmol/L/min versus 1012 ( 684–1921 ) µmol/L/min , 315 ( 221–466 ) µmol/L/min versus 686 ( 424–877 ) µmol/L/min , 3679 ( 3162–4537 ) pmol/L/min versus 5347 ( 4727–5781 ) pmol/L/min and 1887 ( 1423–2092 ) pmol/L/min versus 3296 ( 2534–3834 ) pmol/L/min , respectively , all P in post-pr and ial plasma BA response due to larger amounts of glycine-conjugated BAs . This suggests up regulation of BA production and conjugation after RYGB", "A r and omized prospect i ve evaluation of the gastric and jejunoileal bypass procedures for morbid obesity was performed . The gastric bypass was performed predominantly as a 90 % gastric exclusion with a Roux-en-Y reconstitution . The jejunoileal bypass was an end-to-end anastomosis between 30 cm of", "BACKGROUND AND METHODS The Program on the Surgical Control of the Hyperlipidemias ( POSCH ) , a r and omized clinical trial , was design ed to test whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality or mortality due to coronary heart disease . The study population consisted of 838 patients ( 417 in the control group and 421 in the surgery group ) , both men ( 90.7 percent ) and women , with an average age of 51 years , who had survived a first myocardial infa rct ion . The mean follow-up period was 9.7 years . RESULTS When compared with the control group at five years , the surgery group had a total plasma cholesterol level 23.3 percent lower ( 4.71 + /- 0.91 vs. 6.14 + /- 0.89 mmol per liter [ mean + /- SD ] ; P less than 0.0001 ) , a low-density lipoprotein cholesterol level 37.7 percent lower ( 2.68 + /- 0.78 vs. 4.30 + /- 0.89 mmol per liter ; P less than 0.0001 ) , and a high-density lipoprotein cholesterol level 4.3 percent higher ( 1.08 + /- 0.26 vs. 1.04 + /- 0.25 mmol per liter ; P = 0.02 ) . Overall mortality and mortality due to coronary heart disease were reduced , but not significantly so ( deaths overall [ control vs. surgery ] , 62 vs. 49 , P = 0.164 ; deaths due to coronary disease , 44 vs. 32 , P = 0.113 ) . The overall mortality in the surgery subgroup with an ejection fraction greater than or equal to 50 percent was 36 percent lower ( control vs. surgery , 39 vs. 24 ; P = 0.021 ) . The value for two end points combined -- death due to coronary heart disease and confirmed nonfatal myocardial infa rct ion -- was 35 percent lower in the surgery group ( 125 vs. 82 events ; P less than 0.001 ) . During follow-up , 137 control-group and 52 surgery-group patients underwent coronary-artery bypass grafting ( P less than 0.0001 ) . A comparison of base-line coronary arteriograms with those obtained at 3 , 5 , 7 , and 10 years consistently showed less disease progression in the surgery group ( P less than 0.001 ) . The most common side effect of partial ileal bypass was diarrhea ; others included occasional kidney stones , gallstones , and intestinal obstruction . CONCLUSIONS Partial ileal bypass produces sustained improvement in the blood lipid patterns of patients who have had a myocardial infa rct ion and reduces their subsequent morbidity due to coronary heart disease . The role of this procedure in the management of hypercholesterolemia remains to be determined . These results provide strong evidence supporting the beneficial effects of lipid modification in the reduction of atherosclerosis progression", "CONTEXT The association of triglycerides with incident cardiovascular disease remains controversial . Although triglyceride levels are typically obtained in the fasting state , postpr and ial hypertriglyceridemia may play an important role in atherosclerosis . OBJECTIVE To determine the association of triglyceride levels ( fasting vs nonfasting ) and risk of future cardiovascular events . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve study of 26,509 initially healthy US women ( 20,118 fasting and 6391 nonfasting ) participating in the Women 's Health Study , enrolled between November 1992 and July 1995 and undergoing follow-up for a median of 11.4 years . Triglyceride levels were measured in blood sample s obtained at time of enrollment . MAIN OUTCOME MEASURE Hazard ratios for incident cardiovascular events ( nonfatal myocardial infa rct ion , nonfatal ischemic stroke , coronary revascularization , or cardiovascular death ) . RESULTS At baseline , triglyceride levels in fasting as well as nonfasting women correlated with traditional cardiac risk factors and markers of insulin resistance . During a median follow-up of 11.4 years , 1001 participants experienced an incident cardiovascular event ( including 276 nonfatal myocardial infa rct ions , 265 ischemic strokes , 628 coronary revascularizations , and 163 cardiovascular deaths ) , for an overall rate of 3.46 cardiovascular events per 1000 person-years of follow-up . After adjusting for age , blood pressure , smoking , and use of hormone therapy , both fasting and nonfasting triglyceride levels predicted cardiovascular events . Among fasting participants , further adjustment for levels of total and high-density lipoprotein cholesterol and measures of insulin resistance weakened this association ( fully adjusted hazard ratio [ 95 % confidence interval ] for increasing tertiles of triglyceride levels : 1 [ reference ] , 1.21 [ 0.96 - 1.52 ] , and 1.09 [ 0.85 - 1.41 ] [ P = .90 for trend ] ) . In contrast , nonfasting triglyceride levels maintained a strong independent relationship with cardiovascular events in fully adjusted models ( hazard ratio [ 95 % confidence interval ] for increasing tertiles of levels : 1 [ reference ] , 1.44 [ 0.90 - 2.29 ] , and 1.98 [ 1.21 - 3.25 ] [ P = .006 for trend ] ) . In secondary analyses stratified by time since participants ' last meal , triglyceride levels measured 2 to 4 hours postpr and ially had the strongest association with cardiovascular events ( fully adjusted hazard ratio [ 95 % confidence interval ] for highest vs lowest tertiles of levels , 4.48 [ 1.98 - 10.15 ] [ P initially healthy women , nonfasting triglyceride levels were associated with incident cardiovascular events , independent of traditional cardiac risk factors , levels of other lipids , and markers of insulin resistance ; by contrast , fasting triglyceride levels showed little independent relationship", "Objective : To evaluate the physiologic importance of the satiety gut hormones . Background : Controversy surrounds the physiologic role of gut hormones in the control of appetite . Bariatric surgery remains the most effective treatment option for obesity , and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass . Methods : We correlated peptide YY ( PYY ) and glucagon-like peptide 1 ( GLP-1 ) changes within the first week after gastric bypass with changes in appetite . We also evaluated the gut hormone responses of patients with good or poor weight loss after gastric bypass . Finally , we inhibited the gut hormone responses in gastric bypass patients and then evaluated appetite and food intake . Results : Postpr and ial PYY and GLP-1 profiles start rising as early as 2 days after gastric bypass ( P Changes in appetite are evident within days after gastric bypass surgery ( P appetite continues . However , in patients with poor weight loss after gastric bypass associated with increased appetite , the postpr and ial PYY and GLP-1 responses are attenuated compared with patients with good weight loss ( P return of appetite and increased food intake ( P appetite after gastric bypass is associated with elevated PYY and GLP-1 concentrations , and appetite returns when the release of gut hormones is inhibited . The results suggest a role for gut hormones in the mechanism of weight loss after gastric bypass and may have implication s for the treatment of 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", "Objective : To assess body composition , eating pattern , and basal metabolic rate in patients undergoing obesity surgery in a r and omized trial . Introduction : There is limited knowledge regarding how different bariatric surgical techniques function in terms of altering body composition , dietary intake , and basic metabolic rate . Methods : Non-superobese patients were r and omized to laparoscopic Roux-en-Y gastric bypass ( LGBP , n = 37 ) or laparoscopic vertical b and ed gastroplasty ( LVBG , n = 46 ) . Anthropometry , dual-energy x-ray absorptiometry ( DEXA ) , computed tomography ( CT ) , indirect calorimetry , and reported dietary intake were registered prior to and 1 year after surgery . Results : Follow-up rate was 97.6 % . LGBP patients had significantly greater reduction of waist circumference and sagittal diameter compared with LVBG . DEXA demonstrated a larger reduction of body fat in all compartments after LGBP , especially at the trunk ( P visceral fat ( P=0.016 ) . Patients were able to eat all types of food after LGBP , although about 30 % cl aim ed they avoided fats . LGBP patients decreased their proportion of dietary fat significantly more than those operated on with LVBG ( P = 0.005 ) , who consumed more sweet foods and avoided whole meat and vegetables . Lean tissue mass ( LTM ) was proportionally less reduced , especially in men , after LGBP . The decreases in BMR postoperatively reflected the lower body mass in a pattern that did not differ among the groups . Conclusion : LGBP patients demonstrated better outcomes compared with LVBG patients in terms of body composition . Energy expenditure developed as expected postoperatively . A “ steering ” away from fatty foods after LGBP may be an important mechanism of action in gastric bypass", "Bariatric surgery is the most effective treatment for achieving long‐term weight loss in morbidly obese patients . This study investigated prospect i ve changes in gut hormones and metabolic indices after Roux‐en‐$\\font\\ss = cmss10 scaled 1000 \\hbox{\\ss Y}$ gastric bypass ( RYGB )", "BACKGROUND To improve decision making in the treatment of extreme obesity , the risks of bariatric surgical procedures require further characterization . METHODS We performed a prospect i ve , multicenter , observational study of 30-day outcomes in consecutive patients undergoing bariatric surgical procedures at 10 clinical sites in the United States from 2005 through 2007 . A composite end point of 30-day major adverse outcomes ( including death ; venous thromboembolism ; percutaneous , endoscopic , or operative reintervention ; and failure to be discharged from the hospital ) was evaluated among patients undergoing first-time bariatric surgery . RESULTS There were 4776 patients who had a first-time bariatric procedure ( mean age , 44.5 years ; 21.1 % men ; 10.9 % nonwhite ; median body-mass index [ the weight in kilograms divided by the square of the height in meters ] , 46.5 ) . More than half had at least two coexisting conditions . A Roux-en-Y gastric bypass was performed in 3412 patients ( with 87.2 % of the procedures performed laparoscopically ) , and laparoscopic adjustable gastric b and ing was performed in 1198 patients ; 166 patients underwent other procedures and were not included in the analysis . The 30-day rate of death among patients who underwent a Roux-en-Y gastric bypass or laparoscopic adjustable gastric b and ing was 0.3 % ; a total of 4.3 % of patients had at least one major adverse outcome . A history of deep-vein thrombosis or pulmonary embolus , a diagnosis of obstructive sleep apnea , and impaired functional status were each independently associated with an increased risk of the composite end point . Extreme values of body-mass index were significantly associated with an increased risk of the composite end point , whereas age , sex , race , ethnic group , and other coexisting conditions were not . CONCLUSIONS The overall risk of death and other adverse outcomes after bariatric surgery was low and varied considerably according to patient characteristics . In helping patients make appropriate choices , short-term safety should be considered in conjunction with both the long-term effects of bariatric surgery and the risks associated with being extremely obese . ( Clinical Trials.gov number , NCT00433810 .", "BACKGROUND Treatment added to statin monotherapy to further modify the lipid profile may include combination therapy to either raise the high-density lipoprotein ( HDL ) cholesterol level or further lower the low-density lipoprotein ( LDL ) cholesterol level . METHODS We enrolled patients who had coronary heart disease or a coronary heart disease risk equivalent , who were receiving long-term statin therapy , and in whom an LDL cholesterol level under 100 mg per deciliter ( 2.6 mmol per liter ) and an HDL cholesterol level under 50 mg per deciliter for men or 55 mg per deciliter for women ( 1.3 or 1.4 mmol per liter , respectively ) had been achieved . The patients were r and omly assigned to receive extended-release niacin ( target dose , 2000 mg per day ) or ezetimibe ( 10 mg per day ) . The primary end point was the between-group difference in the change from baseline in the mean common carotid intima-media thickness after 14 months . The trial was terminated early , on the basis of efficacy , according to a prespecified analysis conducted after 208 patients had completed the trial . RESULTS The mean HDL cholesterol level in the niacin group increased by 18.4 % over the 14-month study period , to 50 mg per deciliter ( P mean LDL cholesterol level in the ezetimibe group decreased by 19.2 % , to 66 mg per deciliter ( 1.7 mmol per liter ) ( P Niacin therapy significantly reduced LDL cholesterol and triglyceride levels ; ezetimibe reduced the HDL cholesterol and triglyceride levels . As compared with ezetimibe , niacin had greater efficacy regarding the change in mean carotid intima-media thickness over 14 months ( P = 0.003 ) , leading to significant reduction of both mean ( P = 0.001 ) and maximal carotid intima-media thickness ( P LDL cholesterol level in association with ezetimibe were significantly associated with an increase in the carotid intima-media thickness ( R = -0.31 , P incidence of major cardiovascular events was lower in the niacin group than in the ezetimibe group ( 1 % vs. 5 % , P = 0.04 by the chi-square test ) . CONCLUSIONS This comparative-effectiveness trial shows that the use of extended-release niacin causes a significant regression of carotid intima-media thickness when combined with a statin and that niacin is superior to ezetimibe . ( Clinical Trials.gov number , NCT00397657 .", "The differences in cholesterol metabolism after the 2 most common forms of obesity surgery , Roux-en-Y gastric bypass ( RYGB ) and gastric b and ing ( GB ) , have not been well characterized . In this study , effects of RYGB and GB on cholesterol absorption and synthesis were investigated . To this aim , 1-year follow-up of cholesterol metabolism in 2 nonr and omized cohorts undergoing either RYGB ( n = 29 ; age , 45.2 + /- 7.7 years ; body mass index [ BMI ] , 46.0 + /- 6.1 kg/m(2 ) ) or GB ( n = 26 ; age , 45.9 + /- 8.6 years ; BMI , 50.1 + /- 7.7 kg/m(2 ) ) was performed in a university hospital center specializing in the treatment of morbid obesity . Serum markers of cholesterol synthesis ( cholestenol , desmosterol , and lathosterol ) and cholesterol absorption ( campesterol , sitosterol , avenasterol , and cholestanol ) were measured preoperatively and at follow-up and expressed as ratios to cholesterol . As expected based on observed weight loss ( 25 % after RYGB and 17 % after GB , P serum levels of cholesterol synthesis markers by 12 % to 28 % ( all Ps cholesterol absorption markers was only observed after RYGB ( -26 % for sitosterol ) and not after GB ( + 16 % , P = 2 x 10(-6 ) for difference between the groups ) . The difference in sitosterol ratio between the groups remained significant after adjustment for age , BMI , fasting insulin levels , and nutritional status ( P = 2 x 10(-4 ) ) , indicating a specific effect related to RYGB . We conclude that decrease in cholesterol absorption is a novel beneficial effect of RYGB . Together with an improved control of blood glucose , this may contribute to a better cardiovascular risk profile after RYGB", "CONTEXT It has been hypothesized that increased plasma bile acids ( BAs ) contribute to metabolic improvements after Roux-en-Y gastric bypass ( RYGB ) surgery by the G protein-coupled receptor TGR5-mediated effects on glucagon-like peptide-1 secretion and thyroid hormones . OBJECTIVE The objective of this study was to evaluate the importance of bariatric surgery-induced alterations in BA physiology on factors that regulate glucose homeostasis ( insulin secretion and sensitivity ) and energy metabolism ( resting energy expenditure and thyroid hormone axis ) . DESIGN , PARTICIPANTS , INTERVENTION , AND MAIN OUTCOME MEASURE : Eighteen extremely obese subjects were studied before and after 20 % weight loss , induced by either laparoscopic adjustable gastric b and ing ( LAGB ) ( n = 10 ) or RYGB surgery ( n = 8) . RESULTS Plasma BAs more than doubled after RYGB [ fasting : 1.08 ( 0.26 - 1.42 ) to 2.28 ( 1.59 - 3.28 ) μmol/L , P = .03 ; postpr and ial : 2.46 ± 1.59 to 6.00 ± 2.75 μmol/L , P = .01 ] but were either lower or did not change after LAGB [ fasting : 1.80 ( 1.49 - 2.19 ) to 0.92 ( 0.73 - 1.15 ) μmol/L , P = .02 ; postpr and ial : 3.71 ± 2.61 to 2.82 ± 1.75 μmol/L , P = .14 ] . Skeletal muscle expression of TGR5 targets , Kir6.2 and cyclooxygenase IV , increased after RYGB but not LAGB . Surgery-induced changes in BAs were associated with increased peak postpr and ial plasma glucagon-like peptide-1 ( r(2 ) = 0.509 , P = .001 ) and decreased serum TSH ( r(2 ) = 0.562 , P the change in insulin response to a meal ( r(2 ) = 0.013 , P = .658 ) , insulin sensitivity ( assessed as insulin stimulated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure ) ( r(2 ) = 0.001 , P = .995 ) , or resting energy expenditure ( r(2 ) = 0.004 , P = .807 ) . CONCLUSIONS Compared with LAGB , RYGB increases circulating BAs and TGR5 signaling , but this increase in BAs is not a significant predictor of changes in glucose homeostasis or energy metabolism", "Background Patient adherence to recommended eating and physical activity behaviors is considered important to weight loss outcomes following gastric bypass surgery , but there has been little systematic research in this area to investigate behavioral predictors of weight loss . Method We developed a measure of postsurgical behaviors , the bariatric surgery self-management question naire ( BSSQ ) . A survey was conducted of 200 patients attending postsurgical support groups ( mean time since surgery 14 months , mean age 40 years , 85 % female , presurgical weight 150 kg ) . Patients completed the BSSQ and measures of treatment regimen distress , perceived benefits of weight loss , and weight-related physical symptoms . Results Mean BSSQ adherence was in the 70 % range , with subscale scores varying considerably . Distress levels associated with the new lifestyle were consistently low ( ≈20 % ) and perceived benefits of weight loss were high early on and maintained consistently ( 70–90 % ) . A final predictive model showed premorbid weight , time since surgery , and BSSQ physical activity subscale were significant predictors of weight loss , accounting for 73 % of variance . Conclusions Physical activity adherence was the sole significant behavioral predictor of weight loss , although maladaptive dietary habits and patient selection issues were identified for future research . It will be important to replicate the current study in prospect i ve , longitudinal studies with representative patient cohorts . A challenge for research ers will be to develop novel , intensive recruiting and retention strategies to allow closer examination of these issues" ]

[ "BACKGROUND AND OBJECTIVE Cycle ergometer training is an important component of pulmonary rehabilitation for patients with COPD . However , incremental cycle tests from which individualized cycle training intensity can be prescribed may not be readily available to clinicians . The aims of the study were to ( i ) investigate the physiological and psychophysical responses to the 6-min walk test ( 6MWT ) , incremental shuttle walk test ( ISWT ) and cycle ergometer test ( CET ) ; and ( ii ) determine whether the distance walked in either the 6MWT or the ISWT could be used to estimate peak work rate on a cycle ergometer . METHODS A repeated measures study was undertaken in COPD patients in a stable condition . The 6MWT , ISWT and CET were performed in r and om order , and physiological responses , rate of perceived exertion and dyspnoea were measured . RESULTS Twenty-two patients with COPD completed the study . There was no significant difference in peak oxygen uptake between the 6MWT , ISWT and CET . The significant correlation between the 6MWD and incremental shuttle walk distance with peak watts on the CET ( r = 0.63 , P = 0.002 and r = 0.75 , P peak work rate measured on the CET and that estimated from either the 6MWT or the ISWT . CONCLUSIONS The significant relationships found between the three exercise tests , and the regression equations predicting peak work rate on the CET from the 6MWT or the ISWT , may allow for the estimation of intensity of cycle exercise training from walk tests in COPD patients", "BACKGROUND The protocol used for the 6-min walk test ( 6MWT ) influences its results . The only study to examine the effect of modifying track layout performed a retrospective analysis and concluded that institutions using continuous tracks yield greater distances than those using straight tracks . Agreement between the distances measured on different tracks could not be examined . We evaluated the effect of modifying track layout on walk distance and examined the agreement and repeatability of distances measured on different tracks . METHODS In a prospect i ve , r and omized , cross-over study , 27 COPD subjects ( FEV(1 ) , 38 + /- 14 % [ mean + /- SD ] ; 15 men ) attended three separate test sessions , completing six 6MWTs . To familiarize all subjects with both tracks , the first two sessions comprised two 6MWTs on either a circular or straight track . During the final session , each subject was tested once on the straight and once on the circular track . RESULTS The distance walked on the circular track exceeded the straight track by 13 + /- 17 m ( p limit of agreement between tracks was 33 m. Coefficient of repeatability values when the test was completed on different days for the straight and circular tracks were 51 m and 65 m , respectively . CONCLUSIONS When evaluating changes in 6-min walk distance in groups of patients , track layout should be st and ardized . However , the effect of modifying track layout on an individual 's walking distance is small compared to their daily variability in walk distance . Therefore , st and ardizing track layout for any given individual may be inconsequential when evaluating the change in distances from tests performed on different days", "BACKGROUND Patients with Chronic Heart Failure ( CHF ) develop similar symptoms of exertional breathlessness and fatigue as patients with COPD . Although pulmonary ( exercise based ) rehabilitation ( PR ) is an integral part of the management of COPD , the potential for exercise rehabilitation ( ER ) to assist patients with CHF may not be as readily appreciated . We investigated whether combined ER for patients with CHF and COPD was feasible and effective using the model of PR . METHODS 57 patients with CHF were r and omized 2:1 to 7 weeks ER ( CHF-ER ) or 7 weeks of usual care ( CHF-UC ) . As a comparator 55 patients with COPD were simultaneously recruited to the same ER program ( COPD -ER ) . The primary outcome measure was the Incremental Shuttle Walk Test ( ISWT ) and the secondary outcome measures were the Endurance Shuttle Walk Test ( ESWT ) , isometric quadriceps strength and health status . RESULTS 27 CHF and 44 COPD patients completed ER and 17 patients with CHF completed UC . The CHF-ER group made significant improvements , compared to CHF-UC , in the mean ( 95%CI ) ISWT distance ; 62(35 - 89)m vs -6(-11 to 33)m p improvements in health status . The improvements in exercise performance and health status were similar between patients with CHF and COPD , treated with ER . CONCLUSION Patients with CHF who undergo ER improve similarly in their exercise performance and health status to COPD . Combined training programs for COPD and CHF are effective and feasible , such that service provision could be targeted around common disability rather than the primary organ disease", "Background : The responsiveness of the endurance shuttle walk to functional changes following bronchodilation has recently been reported . The current literature suggests that the 6 min walking test ( 6MWT ) is less responsive to bronchodilation than the endurance shuttle walk . Aim : To compare bronchodilator-induced changes in exercise performance with the 6MWT and the endurance shuttle walk . Methods : In a r and omised , double-blind , placebo-controlled , crossover trial , 14 patients with chronic obstructive pulmonary disease ( forced expiratory volume in 1 s ( FEV1 ) 50 (8)% predicted ) completed two 6MWTs and two endurance shuttle walks , each preceded by nebulised placebo or 500 μg ipratropium bromide . Cardiorespiratory parameters were monitored during each walking test with a portable telemetric gas analyser . Quadriceps twitch force was measured by magnetic stimulation of the femoral nerve before and after each walking test . Results : The 6 min walking distance did not change significantly after bronchodilation despite a significant increase in FEV1 of 0.18 ( 0.09 ) litres ( p in FEV1 ( 0.18 ( 0.12 ) litres , p the distance walked on the endurance shuttle walk ( Δdistance ipratropium bromide – placebo = 144 ( 219 ) m , p = 0.03 ) . Quadriceps muscle fatigue was infrequent ( changes in exercise performance following bronchodilation", "Background The COPD ( chronic obstructive pulmonary disease ) assessment test ( CAT ) is a recently introduced , simple to use patient-completed quality of life instrument that contains eight questions covering the impact of symptoms in COPD . It is not known how the CAT score performs in the context of clinical pulmonary rehabilitation ( PR ) programmes or what the minimum clinical ly important difference is . Methods The introduction of the CAT score as an outcome measure was prospect ively studied by PR programmes across London . It was used alongside other measures including the St George 's Respiratory Question naire , the Chronic Respiratory Disease Question naire , the Clinical COPD Question naire , the Hospital Anxiety and Depression score , the Medical Research Council ( MRC ) dyspnoea score and a range of different walking tests . Patients completed a 5-point anchor question used to assess overall response to PR from ‘ I feel much better ’ to ‘ I feel much worse ’ . Results Data were available for 261 patients with COPD participating in seven programmes : mean ( SD ) age 69.0 ( 9.0 ) years , forced expiratory volume in 1 s ( FEV1 ) 51.1 ( 18.7 ) % predicted , MRC score 3.2 ( 1.0 ) . Mean change in CAT score after PR was 2.9 ( 5.6 ) points , improving by 3.8 ( 6.1 ) points in those scoring ‘ much better ’ ( n=162 ) , and by 1.3(4.5 ) in those who felt ‘ a little better ’ ( n=88 ) ( p=0.002 ) . Only eight individuals reported no difference after PR and three reported feeling ‘ a little worse ’ , so comparison with these smaller groups was not possible . Conclusion The CAT score is simple to implement as an outcome measure , it improves in response to PR and can distinguish categories of response", "QUESTIONS Does an eight-week program of walk training improve endurance walking capacity in people with COPD compared to cycle training ? Does walk training improve peak walking capacity , cycle capacity , and quality of life compared to cycle training ? Is the endurance shuttle walk test ( ESWT ) responsive to change in walking capacity elicited by exercise training ? DESIGN R and omised trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS 36 people with stable COPD recruited with four dropouts . INTERVENTION Participants were r and omised into either a walk or cycle training group . Both groups trained indoors for 30 to 45 minutes per session , three times weekly over eight weeks at Concord Hospital . Training intensities were based on baseline peak exercise tests and progressed as able . OUTCOME MEASURES The primary outcome was endurance walking capacity measured by the ESWT . Secondary outcomes included peak walking capacity , peak and endurance cycle capacity , and health-related quality of life . Measures were taken at baseline ( Week 0 ) and following training ( Week 8) . RESULTS The walk training group increased their endurance walking time by 279 seconds ( 95 % CI 70 to 483 ) more than the cycle training group . No significant differences between the groups were found for any other outcome . CONCLUSION Ground walk training increased endurance walking capacity more than cycle training and was similar to cycle training in improving peak walking capacity , peak and endurance cycle capacity and quality of life . This study provides evidence for ground walking as a mode of exercise training in pulmonary rehabilitation programs", "BACKGROUND high walking frames may improve exercise capacity in young patients with chronic obstructive pulmonary disease ( COPD ) . We have assessed the effect of Zimmer , rollator and gutter frames on 6-min walking distance and on arterial oxygenation during exercise in elderly patients with COPD . METHODS 27 out- patients ( 15 men ) aged 70 - 82 ( mean 75 ) years were recruited . Exclusions comprised : COPD exacerbation or oral steroid use within 6 weeks , confusional state , participation in a pulmonary rehabilitation programme and exercise limitation by other diseases . Subjects completed 6-min walk tests unaided and with the three frames on four separate days in r and om order 30 min after nebulized salbutamol ( 5 mg ) and ipratropium ( 0.5 mg ) and were accompanied by an investigator blinded to results of all other walk tests undertaken . Oxygen saturation ( SaO2 ) was monitored by finger probe during exercise . Grouped t-tests were used to compare distances and reductions in SaO2 . RESULTS Unaided , the mean ( SEM ) 6-min walk distance was 210 ( 16 ) m and fall in oxygen saturation was 6.0 (1.1)% . Use of a rollator frame did not significantly affect either of these values . Using the Zimmer frame reduced the mean distance to 165 ( 13 ) m ( t=5.2 , P SaO2 fall similar to that recorded during the unaided walk . Using the gutter frame increased the mean distance to 234 ( 150 ) m ( t=3 . 1 , P=0.004 vs unaided walk ) and reduced the fall in SaO2 to 3.7 (0.8)% ( t=2.3 , P=0.03 vs unaided walk ) . CONCLUSIONS gutter frames improve exercise capacity and SaO2 during exercise in elderly COPD patients who remain symptomatic on optimal therapy , whereas unwheeled Zimmer frames have a deleterious effect in such patients", "Supplemental oxygen has acute beneficial effects on exercise performance in patients with chronic obstructive pulmonary disease ( COPD ) . The purpose of this study was to investigate whether oxygen-supplemented training enhances the effects of training while breathing room air in patients with severe COPD . A r and omized controlled trial was performed in 24 patients with severe COPD who developed hypoxaemia during incremental cycle exercise ( arterial oxygen saturation ( Sa , O2 ) All patients participated in an in-patient pulmonary rehabilitation programme of 10 weeks duration . They were assigned either to general exercise training while breathing room air ( GET/RA group : forced expiratory volume in one second ( FEV1 ) 38 % of predicted ; arterial oxygen tension ( Pa , O2 ) 10.5 kPa at rest ; Pa , O2 7.3 kPa at peak exercise ) , or to GET while breathing supplemental oxygen ( GET/O2 group : FEV1 29 % pred ; Pa , O2 10.2 kPa at rest ; Pa , O2 7.2 kPa at peak exercise ) . Sa , O2 was not allowed to fall below 90 % during the training . The effects on exercise performance while breathing air and oxygen , and on quality of life were compared . Maximum workload ( Wmax ) significantly increased in the GET/RA group ( mean ( SD ) 17 ( 15 ) W , p Six minute walking distance ( 6MWD ) , stair-climbing , weight-lifting exercise ( all while breathing room air ) and quality of life significantly increased in both groups . Acute administration of oxygen improved exercise performance before and after training . Training significantly increased Wmax , peak carbon dioxide production ( V'CO2 ) and 6MWD while breathing oxygen in both groups . Differences between groups were not significant . Pulmonary rehabilitation improved exercise performance and quality of life in both groups . Supplementation of oxygen during the training did not add to the effects of training on room air", "OBJECTIVE To determine the repeatability of the 6-minute walk test ( 6MWT ) in adolescents and adults with cystic fibrosis ( CF ) . METHODS This was a prospect i ve cross-sectional study . We included consecutive patients ages > or=15 years attending an adult CF program . The patients underwent the 6MWT , pulmonary function tests , and clinical evaluation . The second 6MWT was performed following a rest period of 60 min . RESULTS Thirty-one patients were included . The mean+/-SD age was 23.5+/-6.7 y , and the mean FEV1 was 61+/-28 % of predicted . The mean+/-SD walked distance in the first 6MWT was 583.6+/-68.6 m and in the second 6MWT was 590.0+/-72.2 m. The mean difference between the first and second 6MWT was -6.5 m , with limits of agreement between -74.9 m and 61.9 m , and the coefficient of variation was 4.3 % . The mean oxygen desaturation in the first 6MWT was 2.5+/-4.5 % , and in the second test it was 1.8+/-4.0 % . The mean difference between the first and second test was 0.6 % , and the coefficient of variation was 104 % . CONCLUSIONS Although the 6MWT distance was reproducible , the wide limits of agreement exceeded the minimum important difference for this test . These findings indicate that , in the routine evaluation of CF patients , at least two 6MWTs are required on any testing occasion to obtain a reliable estimate of the 6MWT distance", "The 6-minute walk test is used in clinical practice and clinical trials of lung diseases ; however , it is not clear whether replicate tests need to be performed to assess performance . Furthermore , little is known about the impact of walking course layout on test performance . We conducted 6-minute walks on 761 patients with severe emphysema ( mean + /- SD FEV1 % predicted = 26.3 + /- 7.2 ) who were participants in the National Emphysema Treatment Trial . Four hundred seventy participants had repeated walks on a separate day . The second test was improved by an average of 7.0 + /- 15.2 % ( 66.1 + /- 146 feet , p distance walked . Participants tested on continuous ( circular or oval ) courses had a 92.2-foot longer walking distance than those tested on straight ( out and back ) courses . Course length had no significant effect on walking distance . The training effect found in these patients with severe emphysema is less than in previous reports of patients with chronic obstructive pulmonary disease . Furthermore , the layout of the track may influence the 6-minute walk performance", "Idiopathic pulmonary fibrosis ( IPF ) is a relentlessly progressive disease with a median survival of ∼3 yrs . Measurements of airflow and lung volumes at rest are generally used to monitor the clinical course in this disorder . This study was design ed to determine if a modified version of the 6-min walk test , called the timed walk test , accurately characterises disease severity and survival in IPF . The study population consisted of 28 patients with well-characterised progressive IPF . The timed walk test and concurrent measures of disease severity were assessed at baseline . Participants were prospect ively followed for ≥4 yrs to determine the relationship between parameters of the timed walk test and survival . There were strong correlations between the end-exercise saturation and walk-velocity parameters of the timed walk test and diffusing capacity , and arterial oxygen tension at rest . In univariate Cox proportional-hazards models , end-exercise saturation , change in saturation with exercise , walk distance and walk velocity were associated with survival . In unadjusted logistic regression models , odds of death at 2 yrs were associated with the same parameters . In conclusion , the timed walk test relates to disease severity and long-term outcome in progressive idiopathic pulmonary fibrosis", "UNLABELLED The 6-min walk ( 6MW ) test is commonly used to assess exercise capacity in patients with COPD and to track functional change result ing from disease progression or therapeutic intervention . Not surprisingly , distance covered has been the preferred outcome for this test . However , distance walked does not account for differences in body weight that are known to influence exercise capacity . OBJECTIVE The aim of this study was to evaluate the 6-min distance x body weight product ( 6MWORK ) as an improved outcome measure with a solid physiologic foundation . PATIENTS AND METHODS One hundred twenty-four men and women with moderate-to-severe COPD volunteered and completed the testing sequence , which included pulmonary function , a peak effort ramp cardiopulmonary exercise study with gas exchange , and the 6MW . Means and SD were generated for the variables of interest . Differences were analyzed using analysis of variance techniques . Correlation coefficients and receiver operating characteristic ( ROC ) curves were calculated for the 6-min walk distance ( 6MWD ) and 6MWORK with indexes of pulmonary function , work performance , and Borg scores for dyspnea and effort . RESULTS Men and women presented with a significant smoking history that also differed by gender ( 48 vs 66 pack-years , respectively ; p mean ( + /- SD ) FEV(1 ) values were 45 + /- 12.6 % and 48 + /- 12.1 % , respectively ( not significant ) , while the diffusing capacity of the lung for carbon monoxide ( DLCO ) was 14.7 + /- 6.1 vs 10.3 + /- 3.9 mL/min/mm Hg , respectively ( p 6MWD averaged 416.8 + /- 79.0 m for men and 367.8 + /- 78.6 m for women , and these differences were significant ( p 0.05 ) , respectively . 6MWORK averaged 35,370 + /- 9,482 kg/m and 25,643 + /- 9,080 kg/m ( p higher correlation coefficients than did 6MWD when correlated with DLCO , lung diffusion for alveolar ventilation , FEV(1 ) , FEV(1)/FVC ratio , watts , peak oxygen uptake , peak minute ventilation , and peak tidal volume . The ROC curve demonstrated that 6MWORK had a significantly larger calculated area under the curve ( p 6MWD when differentiating an objective ly selected definition of low work capacity vs high work capacity ( bike ergometry work , 55 W , respectively ) . CONCLUSIONS We conclude that work calculated as the product of distance x body weight is an improved outcome measure for the 6MW . 6MWORK can be used whenever the 6MW is required to estimate a patient 's functional capacity . This measure is also a common measure , which can be converted to indexes of caloric expenditure for direct cross-modality comparisons", "PURPOSE This study assessed the effect of a wheeled walking aid on disability , oxygenation , and breathlessness in patients with severe disability secondary to chronic irreversible airflow limitation . METHODS Eleven subjects with chronic irreversible airflow limitation , mean forced expired volume in 1 second ( FEV1 ) 0.71 L + /- .33 L , were studied . Subjects performed four 6-minute walk tests , two on each of two study days , twice unaided and twice with the assistance of a wheeled walking aid . A r and omized cross-over design was used . All subjects were oriented to 6-minute walk tests , use of bronchodilators was controlled , and st and ard encouragement was given during each walk test . Outcome measures were the distance walked in 6 minutes , change in oxyhemoglobin saturation during the walk , and breathlessness using a modified Borg Scale . RESULTS The use of a wheeled walker result ed in a significant increase in 6-minute walking distance , a significant reduction in hypoxemia with walking and a significant reduction in breathlessness during the walk test . CONCLUSIONS The use of a wheeled walker result ed in significant decreases in disability , hypoxemia , and breathlessness during a 6-minute walk test . By reducing disability and breathlessness , a wheeled walker may improve quality of life in individuals with severe impairment in lung function", "Objective This study determined the intensity of walking exercise prescribed from 70 % of peak speed achieved during the incremental shuttle walk test ( ISWT ) in people with chronic obstructive pulmonary disease and whether a steady-state response was achieved when exercising at this intensity . Design Each participant performed lung function tests , an incremental cycle test , two ISWTs , and a 10-min continuous walking exercise at 70 % peak ISWT speed . Oxygen consumption ( V˙O2 ) was collected using a portable system ( Cosmed K4b2 , Rome , Italy ) . The V˙O2 from the 10-min walking exercise was compared with V˙O2peak from the better ISWT as a measure of walking exercise intensity . Results Thirty-four participants completed the study . The mean intensity achieved during the 10-min walking exercise was 76 % ( 11 % ) V˙O2peak . Steady-state V˙O2 was achieved by minute 5 in the 10-min walking exercise . Conclusions Prescription of walking exercise at 70 % of the peak ISWT speed provided an intensity appropriate for achieving physiologic training responses", "Walking tests , frequently used to document effects of treatment on exercise capacity , have never been st and ardised . We studied the effects of encouragement on walking test performance in a r and omised study that controlled for the nature of the underlying disease , time of day , and order effects . We r and omised 43 patients with chronic airflow limitation or chronic heart failure or both to receive or not receive encouragement as they performed serial two and six minute walks every fortnight for 10 weeks . Simple encouragement improved performance ( p less than 0.02 for the six minute walk ) , and the magnitude of the effect was similar to that reported for patients in studies purporting to show beneficial effects of therapeutic manoeuvres . Age and test repetition also affected performance . These results demonstrate the need for careful st and ardisation of the performance of walking tests , and suggest caution in interpreting studies in which st and ardisation is not a major feature of the study design", "Background Sarcoidosis is a chronic disease with different phenotypic manifestations . Health-related quality of life is an important aspect in sarcoidosis , yet difficult to measure . The objective of this study was to identify clinical markers predictive of poor quality of life in sarcoidosis patients that can be followed over time and targeted for intervention . Methods We assessed the quality of life of 162 patients with confirmed sarcoidosis in a prospect i ve , cross-sectional study using the Sarcoidosis Health Question naire ( SHQ ) and Short Form-36 Health Survey ( SF-36 ) . We evaluated the validity of these question naires and sought to identify variables that would best explain the performance scores of the patients . Results On multivariate regression analyses , the very best composite model to predict total scores from both surveys was a model containing the distance-saturation product and Borg Dyspnea Scale score at the end of a 6-min walk test . This model could better predict SF-36 scores ( R2 = 0.33 ) than SHQ scores ( R2 = 0.24 ) . Substitution of distanced walked in 6 min for the distance-saturation product in this model result ed in a lesser ability to predict both scores ( R2 = 0.26 for SF-36 ; R2 = 0.22 for SHQ ) . Conclusions Both the SHQ and SF-36 surveys are valuable tools in the assessment of health-related quality of life in sarcoidosis patients . The best model to predict quality of life among these patients , as determined by regression analyses , included the distance-saturation product and Borg score after the 6-min walk test . Both variables represent easily obtainable clinical parameters that can be followed over time and targeted for intervention", "The 6-min walking test ( 6MWT ) is frequently used to assess functional capacity in chronic cardiopulmonary disorders because of its simplicity . The study examines the physiological responses during encouraged 6MWT in patients with chronic obstructive pulmonary disease . Pulmonary oxygen ( O2 ) uptake ( V′O2 ) was measured in 20 male patients ( age 66±6 yrs , forced expiratory volume in one second 45±14 % predicted ) during 6MWT and incremental cycling , in r and om order . O2 tension in arterial blood , carbon dioxide tension in arterial blood and arterial lactate concentration ( [La]art ) were obtained in the last 10 patients . During the 6MWT , V′O2 showed a plateau after the 3rd min ( 1.39±0.28 , 1.42±0.31 , and 1.40±0.30 L·min−1 , 4th , 5th and 6th min , respectively ) , and minute ventilation ( V′E ) ( 42±8 L·min−1 ) was 91 % maximal voluntary ventilation . No differences were shown between 6MWT ( 6th min ) and peak cycling exercise in V′O2 ( 1.40±0.30 versus 1.41±0.28 L·min−1 , respectively ) , cardiac frequency ( 126±13 versus 130±12 beats·min−1 ) , or arterial respiratory blood gases . The two tests were significantly different in V′E ( 42±8 versus 47±8 L·min−1 , 6MWT versus cycling , respectively ) , carbon dioxide production ( 1.30±0.31 versus 1.45±0.18 L·min−1 ) and [La]art ( 2.9±1.99 versus 5.9±1.51 M ) . The study demonstrates that an encouraged 6-min walking test generates a high but sustainable oxygen uptake . Since the oxygen uptake plateau reflects the integrated response of the system , it may explain the high prognostic value of the 6-min walking test ", "Background Measurements of Energy Expenditure ( EE ) at rest ( REE ) and during physical activities are increasing in interest in chronic patients . In this study we aim ed at evaluating the validity/reliability of the SenseWear ® Armb and ( SWA ) device in terms of REE and EE during assisted walking in Chronic Respiratory Failure ( CRF ) patients receiving long-term oxygen therapy ( LTOT ) . Methodology /Principal Findings In a two-phase prospect i ve protocol we studied 40 severe patients and 35 age-matched healthy controls . In phase-1 we determined the validity and repeatability of REE measured by SWA ( REEa ) in comparison with st and ard calorimetry ( REEc ) . In phase-2 we then assessed EE and Metabolic Equivalents-METs by SWA during the 6-minute walking test while breathing oxygen in both assisted ( Aid ) or unassisted ( No-Aid ) modalities . When compared with REEc , REEa was slightly lower in patients ( 1351±169 vs 1413±194 kcal/day respectively , p COPD patients with CRF patients reported a significant gain with Aid as compared with No-Aid modality in terms of meters walked , perceived symptoms and EE . Conclusions / Significance SWA provides a feasible and valid method to assess the energy expenditure in CRF patients on LTOT , and it shows that aided walking results in a substantial energy saving in this population", "Because additive effects of inhaled corticosteroids and long-acting anticholinergics are unclear , we undertook this study to compare the efficacy of tiotropium alone and tiotropium plus budesonide in patients with chronic obstructive pulmonary disease . The study subjects were r and omized to receive either tiotropium 18 µg once daily with or without budesonide 200 µg twice daily for 6 weeks . The efficacy variables were changes in trough forced expiratory volume in one second ( FEV1 ) , St. George 's Respiratory Question naire ( SGRQ ) , 6-minute walk distance ( 6MWD ) , and use of rescue medication . One hundred patients were r and omized and 81 completed the study . The mean age was 64.0 yr , and the mean FEV1 was 39.7 % predicted . Compared with tiotropium alone ( N=40 ) , the tiotropium/budesonide combination ( N=41 ) was related to an improvement in the SGRQ total score ( tiotropium -2.8 units and tiotropium/budesonide -5.6 units , p=0.003 ) . 6MWD was improved by 13.5 m in the tiotropium group and by 22.5 m in the tiotropium/budesonide group ( p=0.031 ) . Changes in trough FEV1 and the use of rescue medication were similar between two groups . In conclusion , compared with tiotropium alone , the tiotropium/budesonide combination was related to an improved health-related quality of life . These data support that low-dose budesonide may enhance the efficacy of tiotropium ", "The purpose of this study was to investigate the relationship between performance on the shuttle walking test and maximal oxygen uptake ( VO2max ) during a conventional treadmill test in patients with chronic airflow limitation . Two different techniques were used to measure oxygen consumption , i.e. conventional Douglas bag techniques ( treadmill test ) and a portable oxygen consumption meter ( shuttle test ) . Initially , 19 patients performed a shuttle walking test ( after one practice walk ) and a maximal treadmill walking test , in a r and omized , balanced design . Subsequently , 10 patients , ( after one practice ) completed an unencumbered shuttle walking test and one supporting the portable oxygen consumption meter , in r and om order . The results of the first experiment revealed a strong relationship between performance during the shuttle walking test and VO2max during the treadmill walking test ( r = 0.88 ) . The results of the second experiment consistently demonstrated an incremental increase in oxygen consumption and ventilation in response to the increasing intensity of the shuttle walking test . Again , a strong relationship between VO2max and performance on the shuttle test was demonstrated ( r = 0.81 ) . We concluded that the shuttle walking test is a valid field exercise test of functional capacity . Performance on the test relates strongly to VO2max , the traditional indicator of cardiorespiratory capacity", "L and -based exercise is often difficult for people with chronic obstructive pulmonary disease ( COPD ) who have coexisting obesity or musculoskeletal or neurological conditions . This r and omised controlled trial aim ed to determine the effectiveness of water-based exercise training in improving exercise capacity and quality of life compared to l and -based exercise training and control ( no exercise ) in people with COPD and physical comorbidities . Participants referred to pulmonary rehabilitation were r and omly allocated to a water-based exercise , l and -based exercise or the control group . The two exercise groups trained for 8 weeks , completing three sessions per week . 45 out of 53 participants ( mean±sd age 72±9 years ; forced expiratory volume in 1 s 59±15 % predicted ) completed the study . Compared to controls , water-based exercise training significantly increased 6-min walking distance , incremental and endurance shuttle walk distances , and improved Chronic Respiratory Disease Question naire ( CRDQ ) dyspnoea and fatigue . Compared to l and -based exercise training , water-based exercise training significantly increased incremental shuttle walk distance ( mean difference 39 m , 95 % CI 5–72 m ) , endurance shuttle walk distance ( mean difference 228 m , 95 % CI 19–438 m ) and improved CRDQ fatigue . Water-based exercise training was significantly more effective than l and -based exercise training and control in increasing peak and endurance exercise capacity and improving aspects of quality of life in people with COPD and physical comorbidities", "Our aim was to determine the minimal important difference ( MID ) for 6-min walk distance ( 6MWD ) and maximal cycle exercise capacity ( MCEC ) in patients with severe chronic obstructive pulmonary disease ( COPD ) . 1,218 patients enrolled in the National Emphysema Treatment Trial completed exercise tests before and after 4–6 weeks of pre-trial rehabilitation , and 6 months after r and omisation to surgery or medical care . The St George 's Respiratory Question naire ( domain and total scores ) and University of California San Diego Shortness of Breath Question naire ( total score ) served as anchors for anchor-based MID estimates . In order to calculate distribution-based estimates , we used the st and ard error of measurement , Cohen 's effect size and the empirical rule effect size . Anchor-based estimates for the 6MWD were 18.9 m ( 95 % CI 18.1–20.1 m ) , 24.2 m ( 95 % CI 23.4–25.4 m ) , 24.6 m ( 95 % CI 23.4–25.7 m ) and 26.4 m ( 95 % CI 25.4–27.4 m ) , which were similar to distribution-based MID estimates of 25.7 , 26.8 and 30.6 m. For MCEC , anchor-based estimates for the MID were 2.2 W ( 95 % CI 2.0–2.4 W ) , 3.2 W ( 95 % CI 3.0–3.4 W ) , 3.2 W ( 95 % CI 3.0–3.4 W ) and 3.3 W ( 95 % CI 3.0–3.5 W ) , while distribution-based estimates were 5.3 and 5.5 W. We suggest a MID of 26±2 m for 6MWD and 4±1 W for MCEC for patients with severe COPD", "Few studies have shown that the endurance shuttle walking test ( ESWT ) is responsive to treatment in patients with chronic obstructive pulmonary disease ( COPD ) . This exercise test needs to be further investigated because of its relevance for activity of daily living . The aim of the present study was to evaluate , in patients with COPD , the responsiveness of the ESWT in detecting improvement in walking performance after a single dose of salmeterol . In a r and omised , double-blind , placebo-controlled crossover trial , 20 patients with COPD performed two ESWT at 80 % of peak capacity 2.5 h after inhaling either a placebo or 50 µg of salmeterol . Cardiorespiratory parameters were monitored during each walking test . Inspiratory capacities and Borg ratings for dyspnoea were obtained every other minute throughout the tests . Compared with placebo , salmeterol produced a significant change in lung function and a significant improvement in walking performance ( mean±sd difference in time : 117±20 s ; difference in distance : 160±277 m ) . At isotime ( the latest exercise time that was reached on both ESWT ) , a significant reduction in dyspnoea was observed after bronchodilation . Bronchodilation with salmeterol reduced dyspnoea during walking and improved walking capacity in patients with chronic obstructive pulmonary disease . These findings provide further support for the use of the endurance shuttle walking test as an evaluative tool in chronic obstructive pulmonary disease", "PURPOSE To investigate whether the acute benefits of rollator use are consistent over time in individuals with moderate to severe chronic obstructive pulmonary disease . METHODS Thirty-one stable subjects with chronic obstructive pulmonary disease ( 13 men , 18 women ) , aged 68 + /- 8 years , with a forced expiratory volume in 1 second of 0.7 + /- 0.2 L ( 33 % + /- 12 % predicted ) and a baseline 6-minute walk ( 6MW ) of 261 + /- 68 m , were recruited from a respiratory clinic after completion of a pulmonary rehabilitation program . Two 6MWs were performed at baseline , 4 weeks , and 8 weeks , one walking unaided and the other walking with the assistance of a rollator . The test order was r and omly chosen at baseline , and the same test order was used at each time point . The primary outcome measures were distance walked in 6 minutes ( meters ) , perceived dyspnea using a modified Borg scale , and number of rests taken . RESULTS Subjects achieved higher 6MW distances during assisted compared with unassisted walking at baseline ( 292 + /- 67 vs 263 + /- 67 m ) , 4 weeks ( 296 + /- 62 vs 275 + /- 63 m ) , and 8 weeks ( 283 + /- 65 vs 259 + /- 68 m ) ( P = .013 ) , with no time effect ( P = .5 ) . In addition , use of a rollator result ed in a significant improvement in dyspnea ( P = .004 ) at baseline , 4 weeks , and 8 weeks , with no time effect ( P = .7 ) . The use of a rollator also reduced the number of rests taken during the 6MW ( P Rollator use result ed in improvements in performance in the 6MW , which were consistent over time among individuals with moderate to severe chronic obstructive pulmonary disease who walk less than 375 m during an unaided 6MW", "The effect of oxygen on breathlessness and exercise tolerance was examined in \" pink and puffing \" patients with fixed airways obstruction . When breathing oxygen , patients were less breathless and walked further . This was true whether the cylinder was carried by the patient or by an assistant . It was not possible to identify those patients who would benefit most . The best method of assessing improvement was by comparing breathlessness on a st and ardised progressive exercise test on a treadmill . Four patients had a greater than 30 % reduction in breathlessness on submaximum exercise when breathing oxygen . Breathing oxygen for five or fifteen minutes before exercise but not during exercise ( predose ) result ed in a similar improvement in exercise tolerance . For short periods of exercise predosing with oxygen provides a convenient alternative to continuous oxygen . For longer periods of exercise the benefits of portable oxygen in selected patients have been previously underestimated", "RATIONALE There is no consensus regarding which exercise test to use to evaluate the functional impact of bronchodilators in patients with chronic obstructive pulmonary disease . OBJECTIVE AND METHODS Bronchodilator-induced changes in endurance time were evaluated during cycling and walking in 17 patients with chronic obstructive pulmonary disease who completed two cycle endurance tests and two endurance shuttle walks at 80 % of peak capacity . Each endurance test was preceded by the nebulization of a placebo or 500 microg of ipratropium bromide using a r and omized , double-blind , crossover design . Quadriceps twitch force was measured with magnetic stimulation of the femoral nerve before and after each endurance test . RESULTS Cycling endurance time did not improve significantly after bronchodilation despite a significant increase in FEV1 ( delta endurance time ipratropium bromide - placebo : 51 + /- 255 s , p = 0.42 ) . A similar change in FEV1 was associated with a significant improvement in walking endurance time ( delta endurance time ipratropium bromide - placebo : 164 + /- 177 s , p quadriceps twitch force was observed after cycling , whereas no significant change was seen after walking . CONCLUSION The endurance shuttle walk is a sensitive test to detect changes in exercise tolerance after bronchodilation . Differences in the occurrence of quadriceps muscle fatigue may explain , in part , the different responsiveness to change between cycling and walking", "BACKGROUND Exercise tolerance is an important clinical aspect of chronic obstructive pulmonary disease that can be easily and reliably measured with the 6-minute walking test ( 6MWT ) . To improve the utility of the 6MWT for patient and health care system management , the interpretation of the functional status measure in relation to death and hospitalization should be eluci date d. METHODS Three-year , prospect i ve , multicenter observational study to evaluate the predictive power of 6MWD for death or exacerbation-related hospitalization and to evaluate the factors that help determine 6MWD . RESULTS We measured 6MWD at baseline and annually in 2110 patients with clinical ly stable Global Initiative for Obstructive Lung Disease ( GOLD ) stage II-IV COPD and recorded exacerbation-related hospitalizations and all-cause mortality . During the study , 200 patients died and 650 were hospitalized . Using receiver operating characteristics , the best predictive thresholds of the 6MWD were 334 m for increased risk of death and 357 m for exacerbation-related hospitalization ( area under the curve 0.67 and 0.60 respectively ) ; however , the discriminatory thresholds , especially for mortality , were influenced by age . The mean ( SE ) 6MWD declined by 1.6 ( 1.2 ) m per year in GOLD II , 9.8 ( 1.3 ) m per year in GOLD III , and 8.5 ( 2.4 ) m per year in GOLD IV . CONCLUSION The 6MWD provides prognostic information that may be useful for identifying high-risk patients with COPD", "STUDY OBJECTIVE We analyzed the effects of the use of a rollator on walking distance and physiologic variables : pulmonary gas exchange , heart rate , minute ventilation ( Ve ) , oxygen saturation , and symptoms during the 6-min walk test ( 6MWT ) in patients with COPD . SETTING Outpatient clinic at university hospital . PATIENTS Fourteen patients with COPD in stable clinical condition . One patient had mild COPD , five patients had moderate COPD , six patients had severe COPD , and two patients had very severe COPD . INTERVENTIONS Two 6MWTs were performed with a portable metabolic system ( VmaxST 1.0 ; Viasys Healthcare ; MEDA ; Aartselaar , Belgium ) with a rollator and without a rollator , in r and om order . In addition , maximal voluntary ventilation ( MVV ) was measured with and without a rollator , r and omly . RESULTS The median 6MWT distance increased significantly with a rollator : 416 m without a rollator ( interquartile range [ IQR ] , 396 to 435 m ) , vs 462 m with a rollator ( IQR , 424 to 477 m ) [ p = 0.04 ] . Significant increases were also seen in oxygen uptake ( 0.04 L/min [ IQR , - 0.002 to 0.09 L/min ] ) ; tidal volume ( 0.06 L/min [ IQR , - 0.001 to 0.11 L/min ] ) ; and Ve ( 0.95 L/min [ IQR , - 0.67 to 7.1 L/min ] ) , recorded in the last minute of the 6MWT ; as well as in MVV ( 3 L/min [ IQR , 0 to 12 L/min ] ) [ p Borg dyspnea scores tended to be lower with a rollator : 6 ( IQR , 4 to 7 ) without a rollator , vs 5 ( IQR , 4 to 7 ) with a rollator ( p = 0.10 ) . The variation in the 6MWT was explained by individual changes in walking efficiency ( partial R(2 ) = 0.31 ) and changes in Ve ( partial R(2 ) = 0.36 ) [ p model rollator improves walking distance of patients with COPD through an increased ventilatory capacity and /or better walking efficiency", "Background : There is a concern that comorbidity or frailty in older people could limit the usefulness of currently available exercise tests for chronic lung disease . This study evaluated the feasibility and reproducibility of the incremental shuttle walking test ( SWT ) in people aged 70 years or over , compared exercise tolerance with other disability markers , and assessed whether the SWT is responsive to change after bronchodilators . Methods : Fifty elderly patients with chronic airflow limitation ( CAL ) and 32 controls without airflow limitation attempted the SWT before and after combined nebulised salbutamol/ipratropium bromide . Subjects also completed the Nottingham Extended Activities of Daily Living index ( NEADL ) and the London H and icap score ( LHS ) . Results : Forty four subjects with CAL ( 88 % ) and 29 controls ( 84 % ) completed the SWT , including many with co-morbidities . Two week repeatability was good and the SWT was strongly associated with EADL ( r=0.51 , p LHS ( r=0.43 , p forced expiratory volume in 1 second ( FEV1 ) ( r=0.31 , p=0.05 ) . Subjects with CAL walked a mean distance of 177.7 m compared with 243.3 m in controls ( p distance walked increased in the CAL group by 13.2 % ( p=0.009 ) . Conclusion : The SWT is a feasible and reproducible measure of exercise tolerance in elderly people with and without airflow obstruction and correlates with other markers of disability . It is sensitive to change following bronchodilation in subjects with CAL , although the change correlates less well with improvements in FEV1 . Overall , these results suggest that the SWT might be an appropriate measure to assess interventions in elderly people", "Spencer LM , Alison JA , McKeough ZJ : Six-minute walk test as an outcome measure : are two six-minute walk tests necessary immediately after pulmonary rehabilitation and at three-month follow-up ? Am J Phys Med Rehabil 2008;87:224–228.A 3-mo prospect i ve , longitudinal , repeated- measures study was undertaken in subjects with chronic obstructive pulmonary disease ( COPD ) . The study aim ed to determine whether there was a difference in 6-min walk distance ( 6MWD ) when two 6-min walk tests were performed after pulmonary rehabilitation ( n = 44 ) and at 3-mo follow-up ( n = 40 ) , and whether the results reflected the program outcomes . There was a significant increase in 6MWD between two 6-min walk tests before rehabilitation ( P 6MWD from before to after pulmonary rehabilitation ( P Six-minute walk tests performed twice before and after pulmonary rehabilitation programs and at 3-mo follow-up assessment s ensure accuracy of measurement of the 6MWD and program outcomes", "OBJECTIVES ( 1 ) To examine the concurrent criterion validity of the modified shuttle walk test ( MSWT ) by using the 6- ( 6MWT ) and 12-minute walk test ( 12MWT ) , ( 2 ) to examine the concurrent criterion validity of the estimated maximum oxygen uptake ( Vo2max ) of the MSWT with actual Vo2max , and ( 3 ) to determine test-retest reliability of the MSWT in patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN Validation study . SETTING Outpatient pulmonary rehabilitation program . PARTICIPANTS Thirty clinical ly stable adults with COPD . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Subjects were r and omly assigned to receive either the 6MWT and 12MWT or the MSWT first . The MSWT was repeated 1 week later ( N = 30 ) . Estimated Vo2max was calculated , and actual Vo2max was conducted by using the Jones test . Validity of the MSWT was assessed by comparing endurance scores and Vo2max with results from the 6MWT and 12MWT and Jones test , respectively . RESULTS There was a moderately high correlation between the MSWT and the 6MWT and 12MWT at initial testing ( .82 and .74 , respectively ) . Correlation between estimated and actual Vo2max was r equal to .68 . Test-retest reliability for the entire sample was high ( intraclass correlation coefficient , .88 ) . Results remained quite stable across severity , age , and sex subgroups . CONCLUSIONS The MSWT is a st and ardized externally paced submaximal endurance walking test . The results indicate that the MSWT has high concurrent validity and test-retest reliability for patients with COPD", "OBJECTIVES To investigate cardiorespiratory and dyspnea responses to incremental and self-paced exercise tests in patients with COPD . DESIGN A prospect i ve within-subject design was used . PATIENTS Twenty stable subjects ( 15 men ) , with a mean ( + /- SD ) age of 64.0 + /- 7.5 years and moderate-to-severe COPD ( ie , mean FEV(1 ) , 0.8 + /- 0.3 L and 28.9 + /- 7.9 % predicted ) were studied . METHODS Each subject completed a 6-min walk test ( 6MWT ) , an incremental shuttle walking test ( ISWT ) , and a cycle ergometer test ( CET ) , within a 2-week period . The tests were performed at least 24 h apart . St and ardized encouragement was utilized in each test with the aim of maximizing performance . Heart rate ( HR ) and dyspnea were measured each minute throughout the tests , and pulse oximetric saturation ( Spo(2 ) ) was measured before and immediately after each test . The distances walked in the 6MWT and ISWT were compared to peak oxygen uptake ( Vo(2 ) ) values from the CET . RESULTS HR increased linearly with increasing workload during the CET and ISWT , but increased alinearly with a disproportionate increase early in the 6MWT . In contrast , dyspnea scores increased linearly during the 6MWT , but increased alinearly with a disproportionate increase late during the CET and ISWT . Peak HR and dyspnea were not significantly different between tests . Spo(2 ) was significantly lower at the end of both walking tests compared to that at the end of the CET ( p distance walked in both the ISWT and 6MWT were related to peak Vo(2 ) values on the CET ( for both tests , r = 0.73 ; p response in HR and dyspnea seen during the 6MWT suggest that patients with COPD titrate exertion against dyspnea to achieve a peak tolerable intensity . This strategy is not possible in an externally paced ISWT or CET . However , it is a limited strategy , with performance converging at higher workloads . Similar peak exercise responses were achieved in the 6MWT , ISWT , and CET . Greater oxygen desaturation was observed during the field walking tests , suggesting that both the ISWT and 6MWT are more sensitive than the CET in detecting exercise-induced hypoxemia and in assessing ambulatory oxygen therapy needs ", "The purpose of the present study was to compare the characteristics of three different exercise tests in evaluating the effects of oxitropium bromide on exercise performance . Thirty-eight males with stable chronic obstructive pulmonary disease ( COPD ) ( FEV(1 ) = 40.8 + /- 16.5 % predicted ; mean + /- SD ) completed r and omized , double-blind , placebo-controlled , crossover studies for each exercise test . The exercise tests were performed 60 min after the inhalation of either oxitropium bromide 400 microg or placebo . The patients performed 6-min walking tests ( 6MWT ) on Days 1 and 2 , progressive cycle ergometry ( PCE ) on Days 3 and 4 , and cycle endurance tests at 80 % of the maximal workload of PCE on Days 5 and 6 . Spirometry was conducted before and at 45 and 90 min after the inhalation . Oxitropium bromide significantly increased FEV(1 ) as compared with placebo . Oxitropium bromide increased the endurance time significantly , by 19 % ( p 6-min walking distance by 1 % ( p maximal oxygen consumption ( V O(2)max ) in PCE . The responses in these three exercise tests were different , and we conclude that the endurance test was the most sensitive in detecting the effects of inhaled anticholinergic agents on exercise performance in patients with stable COPD . An endurance procedure may be performed to detect clinical changes in evaluating the effects of oxitropium bromide on exercise performance", "STUDY OBJECTIVES To assess oxygen desaturation during activities and to evaluate the short-term effects of supplemental O(2 ) use in patients with severe COPD who do not qualify for long-term O(2 ) therapy . DESIGN A double-blind , r and omized , placebo-controlled trial . SETTING Out patients from the pulmonary diseases division of a tertiary-care university hospital . PATIENTS Twenty patients with stable COPD with FEV(1)/FVC ratios of 60 mm Hg when resting . INTERVENTIONS Patients were initially evaluated with pulmonary function tests , blood gas analysis , and Doppler echocardiography , and they underwent the following three 6-min walking tests ( WTs ) in a r and om sequence : basal WT ( BWT ) ; WT while breathing compressed air ( CAWT ) ; and WT while breathing O(2 ) ( O(2)WT ) . MEASUREMENTS AND RESULTS The distance walked was recorded in meters . Dyspnea was measured by Borg scale measurement before and after the tests , and arterial oxygen saturation measured by pulse oximetry ( SpO(2 ) ) was continuously monitored . Results were analyzed by grouping patients in the following manner : desaturators ( DSs ) ( ie , patients with a drop in SpO(2 ) of at least 5 % and walked and /or a decrease of at least 3 points in Borg index score ) vs nonresponders . During the BWT , 11 of 20 patients ( 55 % ) were defined as desaturators . During the O(2)WT , the SpO(2 ) remained at > 90 % in every patient . The distance walked increased by 22 % ( p dyspnea decreased 36 % ( p ) administration reduced dyspnea by 47 % ( p distance walked did not improve . Responses were markedly different from one patient to another . No significant differences were noticed between the results of the BWT and CAWT in any of the groups . Thirteen O(2 ) responders did not differ from 7 nonresponders either in basal data or in desaturation measure during the BWT , except that all walking responders ( five patients ) were above the median of basal left ventricle performance . CONCLUSIONS Most of the studied COPD patients desaturated during the BWT . O(2 ) administration avoided desaturation and could increase the distance walked and reduce dyspnea , but these effects were not related to walking desaturation in individual cases . Improvements were not a placebo effect . The therapeutic role of O(2 ) during activities in some patients with severe COPD needs to be individually assessed", "The 6-min walk test ( SMWT ) performed in the hallway ( HW ) is used as a clinical indicator of functional capacity in patients with lung disease . A 6-min walk test utilizing a treadmill ( TM ) is easier to perform and allows easier patient monitoring . Therefore , we formulated a st and ardized TM SMWT protocol and compared the results with those of a HW SMWT . All patients were enrolled in a pulmonary rehabilitation program . Patients with current infection , recent change in inhaled medications or oral steroid use , and significant cardiovascular disease were excluded . Each subject performed three HW SMWTs and three TM SMWTs assigned r and omly on subsequent days . There was a 30-min rest between each walk and at least a 48-h rest between each test day . All patients completed both HW and TM SMWT within 7 d. Supplemental oxygen was utilized or increased if the saturation fell below 88 % . The best of the three tests was used for data analysis . Twenty-one subjects completed the protocol . The mean age was 65 + /- 10.9 yr ( range , 35 to 79 yr ) . Ten subjects were receiving supplemental oxygen . The mean FEV(1 ) was 1.07 + /- 0.53 L. The mean HW SMWT distance was 1,228 + /- 255 ft ( range , 612 to 1,679 ft ) and the mean TM SMWT distance was 1,060 + /- 389 ft ( range , 475 to 1,819 ft ) , which were statistically different ( p = 0.01 ) . The mean difference was 168 + /- 280 ft ( range , -326 to 743 ft ) . Oxygen saturation and supplemental oxygen requirements did not differ significantly . The intra-test variability of the three HW SMWTs was similar to the three TM SMWTs and no significant difference in the coefficient of variation was found . A st and ardized TM SMWT is feasible and allows easier patient monitoring , but there is a statistically significant difference between the HW and TM SMWT distance and therefore they are not interchangeable . However , the intratest reproducibility of the TM and HW SMWTs are similar when three walks are performed in a single test session . The role of the TM SMWT in pulmonary rehabilitation requires further exploration", "It is unclear whether short-term benefits from supplemental oxygen translate into improved quality of life in patients with severe COPD . In a 12 wk double-blind r and omized crossover study , we assessed the effects of supplemental air and oxygen on exercise performance ( step tests and 6 min walking distance [ 6MWD ] ) initially and after two 6 wk periods at home using exertional cylinder air or oxygen . We measured quality of life at baseline and after the two 6 wk domiciliary periods . The 26 patients ( 24 males ) had a mean age of 73 + /- 6 yr ; mean FEV1 , 0.9 + /- 0.4 L ; mean DLCO , 10.6 + /- 2.4 ml/min/mm Hg ; mean resting PO2 , 69 + /- 8.5 ( range 58 to 82 ) mm Hg ; mean PCO2 , 41 + /- 3.3 mm Hg ; and mean resting SaO2 , 94 + /- 2.1 ( mean + /- SD ) . Laboratory tests were performed breathing intranasal air or oxygen at 4 L/min , and measurements were made of SaO2 and Borg dysnea scores . Supplemental oxygen increased 6MWD and steps by small , statistically significant increments acutely at baseline and after 6 and 12 wk , without corresponding falls in Borg score . Degree of desaturation at baseline did not correlate with increase in 6MWD or steps achieved at baseline or at 6 or 12 wk , nor with the domiciliary gas used . There was no difference in 6MWD or steps achieved while breathing supplemental oxygen after 6 wk of domiciliary oxygen compared with domiciliary air . Small improvements in quality of life indices were found after domiciliary oxygen , and mastery also improved after domiciliary air . There were no differences in quality of life , however , when domiciliary oxygen was compared with domiciliary air . Although oxygen supplementation induced small acute increments in laboratory exercise performance , such improvements had little impact on the patients ' daily lives", "BACKGROUND The goal of the 6-min walk test ( 6MWT ) is to enable patients to walk \" as far as possible \" as a measure of their functional ability . The impact of the specific walk instructions on patient 6MWT performance is unknown . METHODS Patients with pulmonary arterial hypertension ( PAH ) , idiopathic pulmonary fibrosis ( IPF ) , and other forms of interstitial lung disease ( ILD ) were recruited to perform four identical 6MWTs with one differing instructional phrase . The st and ard instruction to walk \" as far as possible \" was substituted in r and om order with \" as fast as possible , \" \" at your normal pace , \" or \" at a leisurely pace . \" RESULTS Twenty-four patients ( 10 with PAH , eight with IPF , six with other ILD ) were enrolled and completed all four 6MWTs . Patients attained the greatest distance with the fast instruction , exceeding the st and ard instruction distance by a mean of 52.7 m ( P mean difference between the fast and st and ard walks was 41.5 m in the PAH group , 66.5 m in the IPF group , and 53 m in the other ILD group . CONCLUSIONS Patients do not walk as far as they are able with the st and ard American Thoracic Society instruction for 6MWT . Changing the wording from \" far \" to \" fast \" may facilitate a better effort and greater distance during the test . It is possible that this modified 6MWT instruction may result in improved accuracy and reproducibility , thereby enhancing its clinical and research trial usefulness", "BACKGROUND There has been no direct comparison between an incremental and endurance walking test to detect the relative oxygen desaturation in patients with chronic obstructive pulmonary disease ( COPD ) . This is of some importance as current guidelines have suggested that ambulatory oxygen should only be prescribed after a st and ard assessment and desaturation documented . No clear advice about the nature of the required exercise task is given . This study therefore compared the relative desaturation between the incremental shuttle walking test ( ISWT ) and the constant speed walking test ( ESWT ) and response to ambulatory oxygen . METHODS Forty-one patients ( 29 male ) , mean ( SD ) , age 71.18 ( 7.48 ) yrs , FEV(1 ) 0.85 ( 0.29 ) l with stable COPD were recruited after completion of a 7-week pulmonary rehabilitation programme . Patients completed a baseline ( without carrying a cylinder ) ISWT and ESWT and then , in r and om order in double blind fashion , completed the walk tests with a cylinder of air or a cylinder of oxygen . Measurements included distance walked , oxygen saturation , heart rate , perceived breathlessness and exertion ( Borg scale ) . RESULTS All patients desaturated ( desaturation between the ISWT and the ESWT . There was a significant improvement in performance with supplementary oxygen compared to cylinder air ( p distance walked for either test . There was a significant decrease in walking performance on both the ISWT and the ESWT when carrying an air cylinder compared with the control walk . When comparing the percentage difference between oxygen and air for responders ( i.e. those that achieve a 10 % or more increase ) , the ESWT showed a greater percentage change 42.1 % compared to 26.1 % for the ISWT . CONCLUSIONS This study identifies that incremental and endurance walking provokes significant desaturation and that there is a short-term benefit of oxygen versus air in enhancing exercise performance . There was no significant difference in the level of desaturation between tests . Therefore the ISWT is a suitable exercise test that can be used to evaluate desaturation and is practically more realistic", "OBJECTIVE To establish the minimal important difference ( MID ) for the six-minute walk distance ( 6MWD ) in persons with chronic obstructive pulmonary disease ( COPD ) . DESIGN Analysis of data from an observational study using distribution- and anchor-based methods to determine the MID in 6MWD . SETTING Outpatient pulmonary rehabilitation program at 2 teaching hospitals . PARTICIPANTS Seventy-five patients with COPD ( 44 men ) in a stable clinical state with mean age 70 years ( SD 9 y ) , forced expiratory volume in one second 52 % ( SD 21 % ) predicted and baseline walking distance 359 meters ( SD 104 m ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Participants completed the six-minute walk test before and after a 7-week pulmonary rehabilitation program . Participants and clinicians completed a global rating of change score while blinded to the change in 6MWD . RESULTS The mean change in 6MWD in participants who reported themselves to be unchanged was 17.7 meters , compared with 60.2 meters in those who reported small change and 78.4 meters in those who reported substantial change ( P=.004 ) . Anchor-based methods identified an MID of 25 meters ( 95 % confidence interval 20 - 61 m ) . There was excellent agreement with distribution-based methods ( 25.5 - 26.5 m , kappa=.95 ) . A change in 6MWD of 14 % compared with baseline also represented a clinical ly important effect ; this threshold was less sensitive than for absolute change ( sensitivity .70 vs .85 ) . CONCLUSIONS The MID for 6MWD in COPD is 25 meters . Absolute change in 6MWD is a more sensitive indicator than percentage change from baseline . These data support the use of 6MWD as a patient-important outcome in research and clinical practice", "Background : Despite widespread use of the incremental shuttle walk distance ( ISWD ) , there are no reference equations for predicting it . Objectives : We aim ed to evaluate ISWD in healthy subjects and to establish a reference equation for its prediction . Methods : 131 Brazilian individuals ( 61 males ; 59 ± 10 years ) performed 2 walk tests in a 10-m long corridor . We assessed height , weight , body mass index , forced expiratory volume in 1 s , forced vital capacity and self-reported physical activity . Results : Mean ISWD was greater in males than in females ( 606 ± 167 vs. 443 ± 117 m ; p ) . ISWD correlated significantly ( p ISWD variance . In an additional group of 20 subjects prospect ively studied , the difference between measured and predicted ISWD was not statistically significant ( 534 ± 84 vs. 552 ± 87 m , respectively ) , representing 97 ± 12 % of the predicted value calculated with our reference equation for ISWD . Conclusions : This reference equation including demographic and anthropomorphic attributes could be useful for interpreting the walking performance of patients with chronic diseases that affect exercise capacity", "We prospect ively analysed the potential usefulness of a symptom-limited walk test , the shuttle walk test ( SWT ) , in the prediction of major cardiac events in 46 consecutive patients with chronic heart failure ( NYHA class II-IV , ejection fraction and compared it with that of a time-limited walk test , the six-minute walk test ( 6-MT ) . After a mean follow-up of 17 months ( range , 8 - 28 months ) , 15 of 46 patients ( 33 % ) experienced a major cardiac event , defined as a cardiac death , urgent transplantation , or hospital admission for continuous inotropic or mechanical support . Distance walked in the SWT was shown to be a predictor of outcome at one year of follow-up ( P=0.03 ) , but distance ambulated in the 6-MT was not ( P=0.07 ) . In multivariate analysis , percentage of age-gender predicted peak oxygen uptake was the best predictor of major cardiac events . When patients were divided into tertiles according to performance in both walk tests , there was an overall difference in event-free survival at 12 months among SWT tertiles ( P=0.004 ) , but not among 6-MT tertiles ( P=0.09 ) . A low performance in the SWT ( distance ambulated major cardiac events at short-term . We conclude that , in patients with chronic heart failure , distance ambulated in the SWT predicts event-free survival at one year better than that in the 6-MT", "STUDY OBJECTIVES This study was conducted to examine the short-term effects of using a rollator on functional exercise capacity among individuals with COPD and to characterize which individuals benefit most from its use . DESIGN Repeated- measures r and omized crossover design using the 6-min walk test ( 6MWT ) as the primary outcome measure . SETTING Respiratory rehabilitation center . PATIENTS Forty stable subjects who had received a diagnosis of COPD . INTERVENTIONS Two 6MWTs were performed on each study day . One 6MWT was performed unaided , and the other was performed with a rollator . The order was r and omized on the first day and reversed on the second day . RESULTS Use of the rollator was associated with a significant reduction in dyspnea ( p and duration of rest ( reduction for the total group , 19 s ; and reduction for those who walked distance walked ( p = 0.02 ) . No changes were found for the measures of cardiorespiratory function or gait ( p > 0.05 ) . The requirement to rest during an unaided 6MWT was a significant predictor of improved functional exercise capacity with the use of the rollator ( p rollator to walking unaided . CONCLUSIONS Use of a rollator was effective in improving functional exercise capacity by reducing dyspnea and rest duration among stable individuals with severe COPD . Individuals who walked rollator in terms of reduced dyspnea , reduced rest time , and improved distance walked", "QUESTIONS Do patients with chronic obstructive pulmonary disease ( COPD ) achieve a different distance on the six minute walk test ( 6MWT ) conducted on a 10 m course versus on a 30 m course ? When assessing the distance on a 6MWT conducted on a 10 m course , is it valid to use existing reference equations that were generated on longer courses ? DESIGN A r and omised double-crossover experimental study . PARTICIPANTS Forty-five patients with COPD in primary physiotherapy care . INTERVENTION All patients performed a 6MWT twice over a 10 m course and twice over a 30 m course . The 6MWTs were performed in accordance with the American Thoracic Society guidelines . OUTCOME MEASURES 6MWD was assessed and predicted distance was calculated based on a range of reference equations . RESULTS The 6MWD on the 10 m course was 49.5 m shorter than on the 30 m course , which was statistically significant ( 95 % CI 39.4 to 59.6 ) . By using existing reference equations for a 6MWT conducted on the 10 m course , the predicted distance is highly overestimated ( with a range of 30 % to 33 % ) and the average distance as a percentage of the predicted value is 8%pred lower compared to a 6MWT conducted on the 30 m course , result ing in a worse representation of a COPD patient 's functional exercise capacity . CONCLUSION This study shows that the impact of course length on the 6MWD and on the use of reference equations in patients with COPD is substantial and clinical ly relevant ( based on the most conservative published minimum clinical ly important difference ) . Therefore , existing reference equations established for a 6MWT conducted over a 30 m ( or longer ) course can not be applied to predict the distance achieved on the 6MWT on a 10 m course , which is frequently used in primary care physiotherapy practice s for patients with COPD", "RATIONALE Breathing supplemental oxygen reduces breathlessness during exercise in patients with chronic obstructive pulmonary disease ( COPD ) . Replacing nitrogen with helium reduces expiratory flow resistance and may improve lung emptying . Combining these treatments should be independently effective . OBJECTIVES Study the effect of changing oxygen or helium concentration in inspired gas during exercise in patients with stable COPD . METHODS In 82 patients ( mean age , 69.7 yr ; mean FEV(1 ) , 42.6 % predicted ) , we measured endurance shuttle walking distance , resting and exercise oxygen saturation , and end-exercise dyspnea ( Borg scale ) while patients breathed Heliox28 ( 72 % He/28 % O(2 ) ) , Heliox21 ( 79 % He/21 % O(2 ) ) , Oxygen28 ( 72 % N(2)/28 % O(2 ) ) , or medical air ( 79 % N(2)/21 % O(2 ) ) . Gases were administered using a r and omized , blinded , crossover design via a face mask and an inspiratory dem and valve . RESULTS Breathing Heliox28 increased walking distance ( mean+/-SD , 147+/-150 m ) and reduced Borg score ( -1.28+/-1.30 ) more than any other gas mixture . Heliox21 significantly increased walking distance ( 99+/-101 m ) and reduced dyspnea ( Borg score , -0.76+/-0.77 ) compared with medical air . These changes were similar to those breathing Oxygen28 . The effects of helium and oxygen in Heliox28 were independent . The increase in walking distance while breathing Heliox28 was inversely related to baseline FEV(1 ) breathing air . CONCLUSION Reducing inspired gas density can improve exercise performance in COPD as much as increasing inspired oxygen . These effects can be combined as Heliox28 and are most evident in patients with more severe airflow obstruction", "OBJECTIVES To investigate the feasibility of an outdoor 6-minute walk test ( 6MWT ) as a measure of functional status among individuals with chronic obstructive pulmonary disease ( COPD ) , and to examine the relationship between performance on an indoor and an outdoor 6MWT . DESIGN An experimental , repeated- measures crossover design . Subjects were studied on 2 separate days in the same week . Two 6MWTs-one indoors and the other outdoors-were performed on each study day , with a rest in between . The test order was r and omly selected on the first day and reversed on the second day . Outdoor tests were performed on days of moderate weather conditions ( mean temperature + /- st and ard deviation , 21 degrees + /-3 degrees C ; mean wind speed , 15+/-7 km/h ; no precipitation ) and on a flat surface ( sidewalk ) . SETTING Outpatient rehabilitation program in Ontario . PARTICIPANTS Eighteen subjects with COPD ( 10 men , 8 women ; age , 70+/-8y ) , 5 using supplemental oxygen at rest ( forced expiratory volume in 1s , 1.0+/-0.3L ; 42%+/-8 % of predicted ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Distance walked in 6 minutes ( in meters ) , duration of rest ( in seconds ) , and change in rate of perceived dyspnea . RESULTS There was no significant effect of setting ( indoors vs outdoors ) on distance walked ( 394+/-86 m vs 398+/-84 m , P=0.4 ) , duration of rest ( 13+/-28s vs 9+/-20s , P=0.4 ) , or change in rate of perceived dyspnea ( 2.3+/-1.7 vs 2.3+/-2.0 , P=0.8 ) . Testing day had no significant effect on walk test performance ( all P>0.1 ) . CONCLUSIONS The results indicate that the 6MWT performed outdoors within reasonable climatic parameters may be reflective of 6MWT performance indoors", "PURPOSE : The Incremental Shuttle Walk Test ( ISWT ) is an important functional and prognostic marker in chronic disease . Aging has a detrimental effect on exercise performance . The objective of this study was to produce normal age-specific values for the ISWT in a healthy British population and to explore whether additional variables improve the accuracy of a predictive equation . METHODS : Healthy subjects ( N = 152 ) , aged 40 to 90 years , were recruited . Data collection occurred over 2 study visits . Anthropometric and demographic data were collected , and lung function and quadriceps maximal voluntary contraction were measured . An accelerometer was worn for 2 consecutive days at home . The Duke Activity Status Index was completed , and the greatest distance from 2 ISWTs was recorded . RESULTS : One hundred forty subjects ( 56 men ) with mean age ( SD ) of 59.4 ( 11.0 ) years completed 2 ISWTs . Forced expiratory volume in 1 second ( FEV1 ) was 109.1 % ( 14.56 % ) predicted and ISWT distance was 737 m ( 183 m ) . Age-specific normal values for the ISWT were observed : mean ( lower limit of normal)—40 to 49 years , 824 m ( 765 m ) ; 50 to 59 years , 788 m ( 730 m ) ; 60 to 69 years , 699 m ( 649 m ) ; and 70 years and older , 633 m ( 562 m ) . A predictive equation was developed from 114 subjects . Age , body mass index , FEV1 , quadriceps maximal voluntary contraction , and Duke Activity Status Index contributed to ISWT distance predicting 50.4 % of the variation in performance . CONCLUSION : We have developed age-specific normal values for performance on the ISWT in a healthy British population . However , even using practical , clinical ly relevant variables , it is not possible to accurately predict exercise capacity from a regression equation", "UK guidelines for domiciliary oxygen have suggested the six-minute walk test or shuttle walk tests as suitable functional measures for the clinical assessment of ambulatory oxygen ( AO ) . To date , there is limited evidence that would support the use of shuttle walk tests as assessment tools for AO . The endurance shuttle walk test ( ESWT ) is used increasingly as an assessment tool within pulmonary rehabilitation ( PR ) but its potential as an investigative test for AO has not been explored . Using the same test for both PR and AO assessment is appealing since it would improve efficiency and act to st and ardise outcome measures in this patient population . The aim of this study was to examine the responsiveness and repeatability of the ESWT to AO and to compare the response with that of the six-minute walk test ( 6MWT ) . Twenty-three patients with chronic obstructive pulmonary disease ( COPD ) performed , in r and om order , the ESWT and the 6MWT on air and whilst breathing AO . Oxygen saturation and Borg ratings of breathlessness and perceived exertion were recorded . On a third day , eleven patients repeated the ESWT with AO in order to measure repeatability . There was a significantly greater change in the ESWT with oxygen than the change recorded from the 6MWT ( 66 [ 91 ] vs 6 [ 28 ] m respectively ; P difference ( 95 % CI ) between distances walked on the ESWT with AO was 0.91 ( -47 , 49 ) m. The ESWT was more responsive than the 6MWT for detecting improvements in walking endurance whilst breathing AO", "BACKGROUND Generally , the use of a rollator improves mobility in patients with COPD . Nevertheless , not all patients benefit from its use , and many patients feel embarrassed about using it . Therefore , other walking aids are worthwhile to consider . We compared the direct effects of a \" new \" ambulation aid ( a modern draisine ) with the effects of a rollator on 6-min walk distance ( 6MWD ) in patients with COPD . METHODS Twenty-one patients with COPD performed two 6-min walk tests ( 6MWTs ) during prerehabilitation assessment ( best 6MWD : 369 ± 88 m ) . Additionally , two extra 6MWTs were performed on two consecutive days in r and om order : one time with a rollator and one time with a modern draisine . Walking pattern ( n = 21 ) was determined using an accelerometer , and metabolic requirements ( n = 10 ) were assessed using a mobile oxycon . RESULTS Walking with the modern draisine result ed in a higher 6MWD compared with walking with the rollator ( 466 ± 189 m vs 383 ± 85 m ) . Moreover , patients had fewer strides ( 245 ± 61 vs 300 ± 49 ) and a greater stride length ( 1.89 ± 0.73 m vs 1.27 ± 0.14 m ) using the modern draisine compared with the rollator ( all P ≤ .001 ) . Oxygen uptake , ventilation , heart rate , oxygen saturation , and Borg symptom scores were comparable between both walking aids . Ten percent of the patients felt embarrassed using the modern draisine compared with 19 % for the rollator , and a significantly smaller proportion of patients would use the modern draisine in daily life . CONCLUSIONS The mean difference in 6MWD between a modern draisine and a rollator seems clinical ly relevant , with the same metabolic requirements and symptom Borg scores . Therefore , this \" new \" ambulation aid could be a good alternative to the rollator to improve functional exercise performance in patients with COPD . TRIAL REGISTRY The Netherl and s National Trial Registry ; No. : NTR1542 ; URL : www.trialregister.nl" ]

[ "Goals of workProstate cancer patients receiving and rogen deprivation therapy ( ADT ) are vulnerable to a number of potentially debilitating side effects , which can significantly impact quality of life . The role of alternate therapies , such as physical activity ( PA ) , in attenuating these side effects is largely understudied for such a large population . Thus , the purpose of this study was to investigate the effects of PA intervention for men receiving ADT on PA behavior , quality of life , and fitness measures . Patients and methods One hundred participants were r and omized into an intervention ( n = 53 ) or a wait-list control group ( n = 47 ) , with 11 dropping out of the intervention group and 23 dropping out of the wait-list control group prior to post-testing . The intervention consisted of both an individually tailored home-based aerobic and light resistant training program and weekly group sessions . PA , quality of life , fitness , and physiological outcomes were assessed pre and post the 16-week intervention . Results Significant increases in PA , supported by changes in girth measures and blood pressure , support the beneficial impact of the intervention . Positive trends were also evident for depression and fatigue . However , due to the high dropout rate , these results must be interpreted with caution . Conclusions PA effectively attenuates many of the side effects of ADT and should be recommended to prostate survivors as an alternate therapy . Determining the maintenance of this behavior change will be important for underst and ing how the long-term benefits of increased activity levels may alleviate the late effects of ADT", "BACKGROUND AND PURPOSE The interpretation of patient scores on clinical tests of physical mobility is limited by a lack of data describing the range of performance among people without disabilities . The purpose of this study was to provide data for 4 common clinical tests in a sample of community-dwelling older adults . SUBJECTS Ninety-six community-dwelling elderly people ( 61 - 89 years of age ) with independent functioning performed 4 clinical tests . METHODS Data were collected on the Six-Minute Walk Test ( 6MW ) , Berg Balance Scale ( BBS ) , and Timed Up & Go Test ( TUG ) and during comfortable- and fast-speed walking ( CGS and FGS ) . Intraclass correlation coefficients ( ICCs ) were used to determine the test-retest reliability for the 6MW , TUG , CGS , and FGS measurements . Data were analyzed by gender and age ( 60 - 69 , 70 - 79 , and 80 - 89 years ) cohorts , similar to previous studies . Means , st and ard deviations , and 95 % confidence intervals for each measurement were calculated for each cohort . RESULTS The 6MW , TUG , CGS , and FGS measurements showed high test-retest reliability ( ICC [2,1]=.95-.97 ) . Mean test scores showed a trend of age-related declines for the 6MW , BBS , TUG , CGS , and FGS for both male and female subjects . DISCUSSION AND CONCLUSION Preliminary descriptive data suggest that physical therapists should use age-related data when interpreting patient data obtained for the 6MW , BBS , TUG , CGS and FGS . Further data on these clinical tests with larger sample sizes are needed to serve as a reference for patient comparisons", "Background : Increased attention has focused on exercise as a quality of life intervention for breast cancer survivors during and after adjuvant therapy . Purpose : Our objective was to examine the effects of an oncologist ’s recommendation to exercise on self-reported exercise behavior in newly diagnosed breast cancer survivors attending their first adjuvant therapy consultation . Methods : Using a single-blind , 3-armed , r and omized controlled trial , 450 breast cancer survivors were r and omly assigned to receive an oncologist exercise recommendation only , an oncologist exercise recommendation plus referral to an exercise specialist , or usual care . The primary outcome was self-reported total exercise ( in metabolic equivalent [ MET ] hours per week ) at 5 weeks postconsultation . Results : The follow-up assessment rate was 73 % ( 329 of 450 ) . Intention-to-treat analysis based on participants with follow-up data indicated a significant difference in total exercise in favor of the recommendation -only group over the usual care group ( mean difference , 3.4 MET hr per week ; 95 % confidence interval [ CI ] , 0.7–6.1 MET hr per week ; p = .011 ) . There was no significant difference between the recommendation -plus-referral group and the usual care group ( mean difference , 1.5 MET hr per week ; 95 % CI , −1.0 to 4.0 MET hr per week ; p = .244 ) . Ancillary on-treatment analyses showed that participants who recalled an exercise recommendation reported significantly more total exercise than participants who did not recall an exercise recommendation ( mean difference , 4.1 MET hr per week ; 95 % CI , 1.9–6.4 MET hr per week ; p oncologist recommendation may increase exercise behavior in newly diagnosed breast cancer survivors , particularly if it is recalled 1 week after the recommendation", "Background And rogen deprivation therapy ( ADT ) is accompanied by a number of adverse side effects including reduced bone mass and increased risk for fracture , reduced lean mass and muscle strength , mood disturbance and increased fat mass compromising physical functioning , independence , and quality of life . The purpose of this investigation is to examine the effects of long term exercise on reversing musculoskeletal-related side effects , and cardiovascular and diabetes risk factors in men receiving and rogen deprivation for their prostate cancer . Specifically , we aim to investigate the effects of a 12-month exercise program design ed to load the musculoskeletal system and reduce cardiovascular and diabetes disease progression on the following primary endpoints : 1 ) bone mineral density ; 2 ) cardiorespiratory function and maximal oxygen capacity ; 3 ) body composition ( lean mass and fat mass ) ; 4 ) blood pressure and cardiovascular function ; 5 ) lipids and glycemic control ; and 6 ) quality of life and psychological distress . Methods / Design Multi-site r and omized controlled trial of 195 men ( 65 subjects per arm ) undergoing treatment for prostate cancer involving ADT in the cities of Perth and Brisbane in Australia . Participants will be r and omized to ( 1 ) resistance/impact loading exercise , ( 2 ) resistance/cardiovascular exercise groups and ( 3 ) usual care/delayed exercise . Participants will then undergo progressive training for 12 months . Measurements for primary and secondary endpoints will take place at baseline , 6 and 12 months ( end of the intervention ) . Discussion The principal outcome of this project will be the determination of the strength of effect of exercise on the well established musculoskeletal , cardiovascular and insulin metabolism side effects of and rogen deprivation in prostate cancer patients . As this project is much longer term than previous investigations in the area of exercise and cancer , we will gain knowledge as to the continuing effects of exercise in this patient population specifically targeting bone density , cardiovascular function , lean and fat mass , physical function and falls risk as primary study endpoints . In terms of advancement of prostate cancer care , we expect dissemination of the knowledge gained from this project to reduce fracture risk , improve physical and functional ability , quality of life and ultimately survival rate in this population . Clinical Trial RegistryA Phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer ;", "PURPOSE Men with prostate cancer are often advised to make changes in diet and lifestyle , although the impact of these changes has not been well documented . Therefore , we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen ( PSA ) , treatment trends and serum stimulated LNCaP cell growth in men with early , biopsy proven prostate cancer after 1 year . MATERIAL S AND METHODS Patient recruitment was limited to men who had chosen not to undergo any conventional treatment , which provided an unusual opportunity to have a nonintervention r and omized control group to avoid the confounding effects of interventions such as radiation , surgery or and rogen deprivation therapy . A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were r and omly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group . RESULTS None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and /or progression of disease on magnetic resonance imaging . PSA decreased 4 % in the experimental group but increased 6 % in the control group ( p = 0.016 ) . The growth of LNCaP prostate cancer cells ( American Type Culture Collection , Manassas , Virginia ) was inhibited almost 8 times more by serum from the experimental than from the control group ( 70 % vs 9 % , p Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle . CONCLUSIONS Intensive lifestyle changes may affect the progression of early , low grade prostate cancer in men . Further studies and longer term followup are warranted", "Advice to rest and take things easy if patients become fatigued during radiotherapy may be detrimental . Aerobic walking improves physical functioning and has been an intervention for chemotherapy‐related fatigue . A prospect i ve , r and omized , controlled trial was performed to determine whether aerobic exercise would reduce the incidence of fatigue and prevent deterioration in physical functioning during radiotherapy for localized prostate carcinoma", "PURPOSE We assessed the correlation of skeletal fracture with survival in men with prostate cancer on chronic and rogen suppressive therapy . MATERIAL S AND METHODS A total of 195 consecutive patients on chronic and rogen suppression for prostate cancer were evaluated for the history and type of skeletal fracture . Correlation with overall survival was performed via multivariate analysis . RESULTS Of these 195 men 24 reported skeletal fracture since the diagnosis of prostate cancer . Median overall survival was 121 and 160 months in men without and with a history of skeletal fracture since the diagnosis of prostate cancer , respectively ( p = 0.04 ) . A history of skeletal fracture was retained as a negative predictor of survival on forward stepwise regression analysis ( RR = 7.4 , p = 0.007 ) . CONCLUSIONS Our results suggest that skeletal fracture in patients with prostate cancer is an independent and adverse predictor of survival . Consideration for screening men at greatest risk via bone mineral density measurements and initiating empirical skeletal therapies ( bisphosphonates , estrogens and so forth ) may be warranted . This recommendation awaits validation through prospect i ve r and omized trials", "PURPOSE To examine the effect of progressive resistance training on muscle function , functional performance , balance , body composition , and muscle thickness in men receiving and rogen deprivation for prostate cancer . METHODS Ten men aged 59 - 82 yr on and rogen deprivation for localized prostate cancer undertook progressive resistance training for 20 wk at 6- to 12-repetition maximum ( RM ) for 12 upper- and lower-body exercises in a university exercise rehabilitation clinic . Outcome measures included muscle strength and muscle endurance for the upper and lower body , functional performance ( repeated chair rise , usual and fast 6-m walk , 6-m backwards walk , stair climb , and 400-m walk time ) , and balance by sensory organization test . Body composition was measured by dual-energy x-ray absorptiometry and muscle thickness at four anatomical sites by B-mode ultrasound . Blood sample s were assessed for prostate specific antigen ( PSA ) , testosterone , growth hormone ( GH ) , cortisol , and hemoglobin . RESULTS Muscle strength ( chest press , 40.5 % ; seated row , 41.9 % ; leg press , 96.3 % ; P muscle endurance ( chest press , 114.9 % ; leg press , 167.1 % ; P 6-m usual walk ( 14.1 % ) , 6-m backwards walk ( 22.3 % ) , chair rise ( 26.8 % ) , stair climbing ( 10.4 % ) , 400-m walk ( 7.4 % ) , and balance ( 7.8 % ) . Muscle thickness increased ( P Whole-body lean mass was preserved with no change in fat mass . There were no significant changes in PSA , testosterone , GH , cortisol , or hemoglobin . CONCLUSIONS Progressive resistance exercise has beneficial effects on muscle strength , functional performance and balance in older men receiving and rogen deprivation for prostate cancer and should be considered to preserve body composition and reduce treatment side effects", "OBJECTIVE To show fatigue prevention and quality of life ( QOL ) improvement from cardiovascular exercise during radiotherapy . DESIGN Prospect i ve enrollment ( n=21 ) , r and omized to exercise ( n=11 ) and control groups ( n=10 ) , with pre- and post-radiotherapy between- and within-group comparisons . SETTING Academic medical center . PARTICIPANTS Localized prostate cancer patients undergoing radiotherapy . INTERVENTIONS The interventional group received radiotherapy plus aerobic exercise 3 times a week for 8 weeks whereas the control group received radiotherapy without exercise . MAIN OUTCOME MEASURES Pre- and post-radiotherapy differences in cardiac fitness , fatigue , depression , functional status , physical , social , and functional well-being , leg strength , and flexibility were examined within and between 2 groups . RESULTS No significant differences existed between 2 groups at pre-radiotherapy assessment . At post-radiotherapy assessment , the exercise group showed significant within group improvements in : cardiac fitness ( P fatigue ( P=.02 ) , Functional Assessment of Cancer Therapy-Prostate ( FACT-P ) ( P=.04 ) , physical well-being ( P=.002 ) , social well-being ( P=.02 ) , flexibility ( P=.006 ) , and leg strength ( P=.000 ) . Within the control group , there was a significant increase in fatigue score ( P=.004 ) and a decline in social well-being ( P cardiac fitness ( P=.006 ) , strength ( P=.000 ) , flexibility ( P fatigue ( P FACT-P ( P=.006 ) , physical well-being ( P social well-being ( P=.002 ) , and functional well-being ( P=.04 ) . CONCLUSIONS An 8-week cardiovascular exercise program in patients with localized prostate cancer undergoing radiotherapy improved cardiovascular fitness , flexibility , muscle strength , and overall QOL and prevented fatigue", "This study examined the effects of and rogen suppression therapy ( AST ) on upper and lower body muscle strength and a range of direct measures of physical performance using a cross-sectional design with 118 men ( 48 men undertaking AST for prostate cancer and 70 healthy aged-matched controls ) from a single tertiary center . Primary end points included muscle strength for the upper- and lower-body ; functional performance — repeated chair rise , usual and fast 6-m walk , 6-m backwards walk and 400-m walk time ; and dual-energy X-ray absorptiometry assessment —whole body , regional soft tissue composition and bone mineral density ( BMD ) . Men on AST had significantly reduced muscle strength for the upper- and lower-body and impaired functional performance compared to controls ( P AST patients had significantly lower whole-body and hip BMD and higher percent of body fat than controls ( P lower whole-body lean mass ( −2.3 kg , P=0.077 ) . Appendicular skeletal muscle was positively associated with upper-body ( r=0.400–0.606 , P ( r=0.549–0.588 , P was related to functional performance . Men undertaking AST were consistently impaired across a broad range of physical and functional musculoskeletal performance assessment s compared with their age-matched normal controls . These findings are relevant for those patients considering AST for sub clinical disease management , but whose physical reserve is marginal . Strategies to counter these adverse effects of AST need to be initiated so that independent living and quality of life can be maintained", " Prostate carcinoma and treatments affect health‐related quality of life ( HRQOL ) . The authors prospect ively compared prostate and general HRQOL between prostate carcinoma cases and an age‐matched and ethnicity‐matched control group", "Background and Purpose : And rogen deprivation therapy ( ADT ) has become an increasingly st and ard intervention for both early and advanced stages of prostate cancer ; however , decreased physical function and hypogonadism have been reported in men receiving ADT . The objectives of this study were : ( 1 ) to determine whether ADT ( and hypogonadism ) result ed in decreased strength and mobility and ( 2 ) to examine the effect of ADT on an associated test of cognitive and motor function by assessing visuomotor performance . Subjects and Methods : Physical function , walking speed , visuomotor performance , gonadal status , body composition , and Comorbidity Disease Index ( CMDI ) scores were assessed in a cohort of 100 participants that included : ( 1 ) men with prostate cancer who were not on ADT , ( 2 ) men with prostate cancer who were on short-term ADT ( long-term ADT ( ≥6 months ) , and ( 4 ) control subjects who did not have prostate cancer . Results : Walking speed varied significantly across the 4 groups , even after adjusting for age , CMDI , and percentage of body fat . Age and CMDI were significantly associated with measurements of physical performance . Adjusted for covariates , men on long-term ADT walked 0.18 m/s slower than the control subjects . Physical function also varied significantly across the 4 groups . And rogen deprivation therapy did not have a significant effect on visuomotor performance . Discussion and Conclusion : The results suggest that ADT has a significant effect on walking speed and physical performance in men with prostate cancer", "Recent research has applied the theory of planned behavior ( TPB ) to underst and ing exercise after a cancer diagnosis , but studies are few and have been limited by retrospective design s , self-report measures of exercise and varied results . In the present study , we extended this research by using a prospect i ve design and an objective measure of exercise adherence . Participants were a convenience sample of 24 breast cancer survivors attending a twice weekly , 12-week training program in preparation for a dragon boat race competition . Participants completed a baseline question naire that assessed demographic and medical variables , past exercise , and the TPB ( i.e. beliefs , subjective norm , attitude , perceived behavioral control and intention ) . Program attendance was monitored over a 12-week period by the class instructor . Overall , participants attended 66 % of the training sessions . Multiple regression analyses indicated that : ( a ) intention was the sole determinant of program attendance and explained 35 % of the variance ; ( b ) the TPB constructs explained 49 % of the variance in intention with subjective norm being the most important determinant ; and ( c ) the key underlying beliefs were support from physician , spouse , and friends , and confidence in being able to attend the training class when having limited time , no one to exercise with , fatigue , and other health problems . Based on this preliminary study , it was concluded that the TPB may provide a good framework on which to base interventions design ed to promote exercise in breast cancer survivors", "The objectives were to ( 1 ) prospect ively evaluate fatigue utilizing vali date d instruments in patients with localized prostate cancer , and ( 2 ) examine the relationships between fatigue , depression , quality of life , and sleep disturbance . The instruments used included : Piper Fatigue Scale , Beck Depression Inventory , Epworth Sleepiness Scale , and Functional Assessment of Cancer Therapy for Prostate Scale . Data on cancer stage , prostate specific antigen levels , hematocrit , patient 's body weight and radiation dosage were recorded . Patients were evaluated preradiotherapy , middle of radiotherapy , completion of radiotherapy , and at 4 - 5 weeks follow-up . Thirty-six veterans with localized prostate cancer were studied . Mean age was 66.9 years ( range 55 - 79 ) . Duration of treatment was 7 - 8 weeks . Univariate procedure and Wilcoxon Signed Rank-test were used to examine changes in pretreatment scores for each of the three subsequent study periods . To adjust for multiple comparisons Bonferroni test was used . Spearman Correlations were calculated among parameters . No significant changes were noted in mean scores of hematocrit and body weight during the study period . On the Piper Fatigue Scale , adjusted for multiple comparisons , the median scores were significantly higher at completion of radiotherapy as compared with preradiotherapy values . Three patients ( 8 % ) were experienced fatigue according to Piper Fatigue Scale before treatment as compared to nine patients ( 25 % ) at completion of radiotherapy . On Prostate Cancer Specific and Physical Well Being subscales of the Functional Assessment for Prostate Cancer Therapy , the scores were significantly lower at middle and completion of radiotherapy than at pretreatment . At preradiotherapy , middle of radiotherapy , completion of radiotherapy and follow-up evaluation , patients scoring higher on the Piper Fatigue Scale were more likely to report a poorer quality of Physical Well Being on Functional Assessment of Cancer Therapy for Prostates . No significant changes were noted in the Beck Depression Inventory and Epworth Sleepiness Scale scores during treatment . Eight patients scored 10 or more on the Beck Depression Inventory before starting radiotherapy , suggesting depressive symptomatology . Of these , only seven patients scored 10 or more at completion of treatment . The incidence of fatigue is lower in our study than in previously published data . A relationship exists between fatigue scores and physical well being subscale scores . Higher scores on the Piper Fatigue Scale at the completion of radiotherapy , as well as no changes on depression and sleepiness scales , suggest that fatigue may not be the result of depression or sleep disturbance . Based upon our previous work , we propose that the physical expression of fatigue may be secondary to a decline in neuromuscular efficiency and enhanced muscle fatigue", "PURPOSE The efficacy of a home-based physical activity ( PA ) intervention for early-stage breast cancer patients was evaluated in a r and omized controlled trial . PATIENTS AND METHODS Eighty-six sedentary women ( mean age , 53.14 years ; st and ard deviation , 9.70 years ) who had completed treatment for stage 0 to II breast cancer were r and omly assigned to a PA or contact control group . Participants in the PA group received 12 weeks of PA counseling ( based on the Transtheoretical Model ) delivered via telephone , as well as weekly exercise tip sheets . Assessment s were conducted at baseline , after treatment ( 12 weeks ) , and 6 and 9 month after baseline follow-ups . The post-treatment outcomes are reported here . RESULTS Analyses showed that , after treatment , the PA group reported significantly more total minutes of PA , more minutes of moderate-intensity PA , and higher energy expenditure per week than controls . The PA group also out-performed controls on a field test of fitness . Changes in PA were not reflected in objective activity monitoring . The PA group was more likely than controls to progress in motivational readiness for PA and to meet PA guidelines . No significant group differences were found in body mass index and percent body fat . Post-treatment group comparisons revealed significant improvements in vigor and a reduction in fatigue in the PA group . There was a positive trend in intervention effects on overall mood and body esteem . CONCLUSION The intervention successfully increased PA and improved fitness and specific aspects of psychological well-being among early-stage breast cancer patients . The success of a home-based PA intervention has important implication s for promoting recovery in this population", "OBJECTIVES To assess the impact of lifestyle on health-related quality of life ( HR-QOL ) , perceived stress , and self-reported sexual function in men with early-stage prostate cancer electing active surveillance . METHODS A total of 44 intervention and 49 usual-care control participants were enrolled in a r and omized clinical trial examining the effects of lifestyle changes on prostate cancer progression . The intervention consisted of a low-fat , vegan diet , exercise , and stress management . Participants completed the Medical Outcomes Study Short Form-36 Health Status Survey ( a measure of mental and physical HR-QOL ) , the Perceived Stress Scale , the Sexual Function subscale of the University of California , Los Angeles , Prostate Cancer Index , and measures of lifestyle behaviors ( to yield an overall lifestyle index ) at baseline and 12 months . The data were analyzed using analysis of variance for repeated measures . The relationship between lifestyle and QOL was also analyzed using multiple linear regression analyses . RESULTS Intervention participants had significantly improved their lifestyle compared with controls at 12 months . The quality -of-life scores were high across groups and time points . However , a healthier lifestyle was related to better QOL at baseline . Participants in both groups who reported a healthier lifestyle also reported better mental and physical HR-QOL and sexual function . Furthermore , participants whose lifestyle improved over time showed enhanced physical HR-QOL and decreased perceived stress . CONCLUSIONS Men who choose active surveillance for early-stage prostate cancer are able to make comprehensive lifestyle changes . Although the average QOL was already high in this sample , individuals who improved their lifestyle enhanced their QOL further", "Background : Exercise can modify fall risk factors such as balance and mobility impairments . However , can exercise improve balance confidence ? In one strength-training study , research ers reported that a change in balance confidence was not uniformly associated with changes in objective measures of fall risk or physical performance . In fact , some participants ’ balance confidence decreased while their physical abilities increased and vice versa . Objective : The aim of this study was to compare changes in balance confidence and balance ability result ing from three exercise interventions ( home-based resistance and balance training ( RBT ) , group-based RBT and group-based walking ) , and the concomitant relationships between change in balance confidence and change in ability . It was hypothesized that participants in the group-based RBT program would improve their balance confidence and performance more than those in the home-based or walking programs . Methods : In a cluster-r and omized design , nine retirement villages were assigned to one of the three exercise groups . One hundred and sixty-seven independent-living residents ( aged 65–96 years ) participated . Each group exercised twice weekly for 20 weeks . Objective balance ability was measured using timed t and em and one-leg st and s ( static balance ) , and the 8-foot ( 2.5 m ) up- and -go test ( dynamic balance/agility ) . Balance confidence was assessed using the self-report Activities-specific Balance Confidence ( ABC ) Scale . Results : Participants in the group-based RBT program improved their static balance scores more than those in the home-based program ; however , improvements in balance confidence were greater among participants in the home-based program ( all p between static balance and balance confidence change scores was evident for up to 20 % of participants . Change in ABC score was weakly correlated with a change in the up- and -go test score . Conclusions : Exercise training can improve balance confidence and balance ability in retirement village residents . However , as has been shown previously , this study found that exercise interventions may improve balance ability without associated increases in balance confidence and vice versa . Whether the ABC score and balance ability can be enhanced by providing a tailored intervention to improve balance confidence in combination with a RBT program requires further study", "Prostate cancer patients receiving and rogen ablation therapy experience significant physical and psychological sequelae associated with their disease and treatment . Because physical activity improves physical and psychological well-being , a lifestyle physical activity intervention may help slow or reverse the associated decline in quality of life ( QOL ) . No studies have evaluated an intervention to improve multiple QOL domains in patients receiving and rogen ablation therapy . Active for Life After Cancer is a three-group r and omized controlled trial design ed to evaluate the effectiveness of a lifestyle physical activity intervention ( Lifestyle Program ) in improving QOL . The Lifestyle Program , a 6-month behavioral skills training group , is compared to an Educational Support Program and St and ard Care . The purpose of this paper is to describe the design of the r and omized trial and present baseline data that will characterize the QOL of the sample . Challenges to recruitment for the trial also will be presented and discussed", "BACKGROUND Whether physical activity has benefits against prostate cancer incidence or progression is unclear . Therefore , we assessed physical activity in relation to prostate cancer incidence , mortality , and Gleason histologic grade . METHODS We used data from the Health Professionals Follow-up Study , a prospect i ve cohort study , to determine the number of cases of incident , advanced ( seminal vesicle invasion , metastasis , or fatal ) , fatal , and high- grade prostate cancer in a cohort of 47,620 US male health professionals , followed up from February 1 , 1986 , to January 31 , 2000 . RESULTS During 14 years of follow-up , we documented 2892 new cases of prostate cancer , including 482 advanced cases ( 280 of which were fatal ) . For total prostate cancer , no association was observed for total , vigorous , and nonvigorous physical activity . In men 65 years or older , we observed a lower risk in the highest category of vigorous activity for advanced ( multivariable relative risk , 0.33 ; 95 % confidence interval , 0.17 - 0.62 , for more than 29 vs 0 metabolic equivalent hours ) and for fatal ( relative risk , 0.26 ; 95 % confidence interval , 0.11 - 0.66 ) prostate cancer . No associations were observed in younger men . Differential screening by prostate-specific antigen or a reduction in physical activity due to undiagnosed prostate cancer did not appear to account for the results . Among cases , men with high levels of physical activity were less likely to be diagnosed with poorly differentiated cancers ( Gleason grade > or = 7 ) . CONCLUSION Although the mechanisms are not yet understood , these findings suggest that regular vigorous activity could slow the progression of prostate cancer and might be recommended to reduce mortality from prostate cancer , particularly given the many other documented benefits of exercise", "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", "PURPOSE To compare the effects of functional home exercise of repeated sit-to-st and s with low-intensity progressive resistance training , on performance measures in mobility-limited adults over 80 years of age . SETTING Participants ' homes . DESIGN Community-dwelling older adults > or = 80 years of age were invited to participate in a r and omised controlled clinical trial . Baseline and outcome measures were : comfortable gait velocity , 30-s chair-st and test , 15-s step test , Berg Balance Scale , Modified Falls Efficacy Scale and the Late-Life Function and Disability Instrument-function component . Participants r and omised to the intervention group performed repeated sit-to-st and s using a Gr and St and System ; a biofeedback device that recorded and displayed the number of repetitions performed . Participants r and omised to the control group performed knee extensions using ankle cuff weights . Both groups performed the exercises daily for 6 weeks . RESULTS Sixty-six older adults took part . The intervention group had a statistically significant improvement in Berg Balance Scale mean score , 1.67 + /- 2.64 points , P = 0.001 ( control group 0.73 + /- 3.63 points , P = 0.258 ) , indicating an improvement in balance over the 6-week exercise period . There was no statistically significant effect of either intervention on the other outcome measures . CONCLUSIONS In a highly variable population of older adults with mobility limitations , low-intensity functional home exercise of repeated sit-to-st and s using the Gr and St and System improved Berg Balance Scale score while low-intensity progressive resistance training did not . While statistically significant , the improvement in Berg Balance Scale score was modest raising the issue of what extent of change in score is clinical ly significant in this population", "OBJECTIVES To examine dog walking among dog owners and the relationship between walking behavior of dog owners and non-dog owners and maintained gait speed over 3 years . DESIGN Cross-sectional and longitudinal analyses of a prospect i ve cohort study . SETTING Memphis , Tennessee , and Pittsburgh , Pennsylvania . PARTICIPANTS Two thous and five hundred thirty-three community-dwelling adults aged 71 to 82 at 36 months of the Health , Aging and Body Composition Study . MEASUREMENTS Dog ownership , reported walking behavior , change in walking behavior , and usual and rapid gait speed over 3 years . RESULTS Of 394 dog owners , only 36 % walked their dogs at least three times per week . Cross-sectionally , dog walkers were more likely to achieve 150 minutes of walking per week and had faster usual and rapid walking speeds ( 1.20 vs 1.14 m/s and 1.62 vs 1.52 m/s , respectively ; P .50 ) . Three years later , subjects who had been dog walkers at baseline were approximately twice as likely as any other group to achieve recommended walking levels , independent of covariates . Dog walkers experienced similar declines in usual and rapid walking speed as non-dog owners who walked at least three times per week but maintained their initial mobility advantage . CONCLUSION Although dog ownership appears to facilitate walking behavior , only a minority of older dog owners walk their dogs . The mobility advantage of dog ownership was seen only in dog walkers and was similar to that associated with any walking . Given suboptimal walking activity in older adults , examining the degree to which dog ownership promotes walking activity in persons who do little walking on their own appears worth pursuing", "OBJECTIVES To determine the feasibility of an eccentric resistance exercise training protocol in men with prostate cancer and to assess whether men with prostate cancer who are receiving and rogen deprivation therapy ( ADT ) have a blunted effect from the training as compared with prostate cancer survivors not receiving ADT . DESIGN Prospect i ve pilot study . SETTING Academic medical center . PARTICIPANTS Sixteen men with prostate cancer ( Gleason scores 3 + 3 to 4 + 4 ) were initially enrolled . Ten men ( mean age 66 , range 48 - 86 ) completed the study , 5 were currently receiving ADT . Analysis was performed on these 10 men . INTERVENTIONS Subjects were evaluated at baseline . All men underwent a 12-week resistance exercise training protocol using a recumbent , high-force eccentric , leg cycle ergometer 3 times per week at a \" somewhat hard \" perceived exertion for 12 to 15 minutes . Preexercise and postexercise training changes were examined within and between groups . MAIN OUTCOME MEASURES Quadriceps muscle volume ( magnetic resonance imaging ) , isometric knee extension strength , functional mobility ( Timed Up and Go Test [ TUG ] and 6-minute walk [ 6MW ] ) , health-related quality of life ( FACT-P ) , and fatigue ( FACIT-fatigue scale ) . RESULTS The ADT group demonstrated significant within-group improvements in the 6MW ( P = .01 ) and isometric knee extension strength ( P = .03 ) . This group also demonstrated a clinical ly relevant change in the FACT-P ; however , this did not meet statistical significance . The non-ADT group demonstrated significant within-group improvements in the physical subscale of the FACT-P ( P = .03 ) and an increase in muscle volume ( P = .04 ) . Their improvements in the TUG approached significance ( P = .08 ) . No between-group differences existed . CONCLUSIONS Eccentric resistance exercise was well tolerated , and both groups derived some benefits in strength and functional mobility . Men receiving ADT did not appear to have a blunted response to the exercise as compared with prostate cancer survivors not receiving ADT", "BACKGROUND Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males . When Asian men adopt the US lifestyle , clinical prostate cancer increases greatly . Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer . METHODS Serum was obtained from three groups of similar-aged men , Control , Diet and Exercise , and Exercise alone were used to stimulate LNCaP cells in culture . Growth and apoptosis of tumor cells were measured . Serum sample s were also used to measure insulin , IGF-1 , IGFBP-1 . RESULTS The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls . LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells . CONCLUSIONS A low-fat diet and /or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro", "OBJECTIVE To determine the effect of a home exercise program on strength , postural control , and mobility following hip fracture . DESIGN R and omized controlled trial of 1 month 's duration . SETTING Daily exercise carried out within the subjects ' home environments . PARTICIPANTS Forty-two people 64 to 94 years of age , 35 of whom were living independently in the community and 7 of whom were residing in institutional care . Subjects were recruited on average 7 months after a fall-related hip fracture and r and omly allocated to either the intervention or the control group ( n = 21 each ) . The groups were well matched in terms of medical conditions , medication use , disability , and activity levels . INTERVENTION A \" home-based \" program of weight-bearing exercise established at a visit by a physiotherapist . MAIN OUTCOME MEASURES Quadriceps strength , postural sway , functional reach , weight-bearing ability , walking velocity , and self-rated fall risk . The subjects undertook these assessment s at the beginning and end of the trial . RESULTS At pretest , exercisers and controls performed similarly in all tests . At the end of the trial , the intervention group showed significantly greater quadriceps strength in the affected ( hip-fractured ) leg and increased walking velocity . The intervention subjects also improved their weight-bearing ability and reported reduced subjective falls risk . In contrast , there were no significant improvements in any of the test measures in the controls . Within the intervention group , improvements in quadriceps strength were significantly associated with improved performances in the weight-bearing test measures and with increased walking velocity . CONCLUSIONS This exercise program improved strength and mobility following hip fracture . Further research is needed to ascertain whether the extent of this improvement in these fall risk factors is sufficient to prevent falls", "OBJECTIVES Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen ( PSA ) levels , inhibition of LNCaP cell growth , and fewer prostate cancer-related clinical events at the end of 1 year compared with controls . The aim of this study was to examine the clinical events in this trial during a 2-year period . METHODS The Prostate Cancer Lifestyle Trial was a 1-year r and omized controlled clinical trial of 93 patients with early-stage prostate cancer ( Gleason score The patients in the experimental arm were encouraged to adopt a low-fat , plant-based diet , to exercise and practice stress management , and to attend group support sessions . The control patients received the usual care . RESULTS By 2 years of follow-up , 13 of 49 ( 27 % ) control patients and 2 of 43 ( 5 % ) experimental patients had undergone conventional prostate cancer treatment ( radical prostatectomy , radiotherapy , or and rogen deprivation , P clinical events ( eg , cardiac ) , and no deaths occurred . Three of the treated control patients but none of the treated experimental patients had a PSA level of > or=10 ng/mL , and 1 treated control patient but no treated experimental patients had a PSA velocity of > 2 ng/mL/y before treatment . No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years . CONCLUSIONS Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle", "OBJECTIVE To prospect ively evaluate the prevalence and severity of fatigue and its impact on quality of life ( QOL ) during and after radical external beam radiotherapy ( RT ) for prostate cancer . METHOD AND MATERIAL S Twenty-eight men with prostate cancer undergoing RT over 6 - 8 consecutive weeks were prospect ively accrued . The Brief Fatigue Inventory ( BFI ) , a vali date d fatigue assessment tool , was administered at five time points : baseline ( week 1 ) , middle of RT ( week 3 - 4 ) , end of RT ( last week of RT ) , and follow-up ( median 6.5 weeks after RT ) . The BFI contained nine questions , each using 0 - 10 ratings to quantify fatigue severity and interference with six QOL domains . The prevalence of moderate-severe fatigue was plotted as a function of time . Mean sum and subscale scores at each time point were compared to baseline scores using Wilcoxon tests . Linear regression analyses were performed to assess associations between fatigue scores and age , tumor and treatment characteristics . RESULTS The median age was 69 years ( range 57 - 84 ) , Gleason score 7 ( range 6 - 10 ) , and presenting PSA 9.0 ng/mL ( range 2.5 ng/mL-103.0 ng/mL ) . Patients were treated once daily to a median dose of 74 Gy ( range 60 Gy-78 Gy ) over a median of 37 fractions ( range 30 - 39 ) . Hormone therapy was used in all patients ( median duration 12.2 months ) . The prevalence of moderate-severe present fatigue increased from 7 % at baseline to 8 % at mid-RT and 32 % at RT completion . Compared to baseline ( mean score 11.5 ) , fatigue increased significantly mid-RT ( mean score 14.6 , p = 0.03 ) and peaked at the end of RT ( mean score 23.5 , p = 0.001 ) . Fatigue significantly interfered with walking ability , normal work , daily chores , and enjoyment of life only at the end of RT . After RT completion , fatigue improved but remained higher compared to baseline at 6.5 weeks of follow-up ( mean score 15.0 , p = 0.02 ) . On linear regression analysis , age , Gleason score , PSA , T-stage , hormone therapy duration , RT dose and fractions were not significantly associated with mean fatigue scores . CONCLUSION Patients undergoing 6 - 8 weeks of RT experienced significant fatigue adversely affecting QOL persisting after therapy completion . Since walking ability was not affected until the end of RT , a walking exercise intervention to combat fatigue is likely feasible and is being investigated", "PURPOSE Radiotherapy for prostate cancer ( PCa ) may cause unfavorable changes in fatigue , quality of life ( QOL ) , and physical fitness . We report results from the Prostate Cancer Radiotherapy and Exercise Versus Normal Treatment study examining the effects of 24 weeks of resistance or aerobic training versus usual care on fatigue , QOL , physical fitness , body composition , prostate-specific antigen , testosterone , hemoglobin , and lipid levels in men with PCa receiving radiotherapy . PATIENTS AND METHODS Between 2003 and 2006 , we conducted a r and omized controlled trial in Ottawa , Canada , where 121 PCa patients initiating radiotherapy with or without and rogen deprivation therapy were r and omly assigned to usual care ( n = 41 ) , resistance ( n = 40 ) , or aerobic exercise ( n = 40 ) for 24 weeks . Our primary end point was fatigue assessed by the Functional Assessment of Cancer Therapy-Fatigue scale . RESULTS The follow-up assessment rate for our primary end point of fatigue was 92.6 % . Median adherence to prescribed exercise was 85.5 % . Mixed-model repeated measures analyses indicated both resistance ( P = .010 ) and aerobic exercise ( P = .004 ) mitigated fatigue over the short term . Resistance exercise also produced longer-term improvements ( P = .002 ) . Compared with usual care , resistance training improved QOL ( P = .015 ) , aerobic fitness ( P = .041 ) , upper- ( P lower-body ( P ( P = .036 ) , while preventing an increase in body fat ( P = .049 ) . Aerobic training also improved fitness ( P = .052 ) . One serious adverse event occurred in the group that performed aerobic exercise . CONCLUSION In the short term , both resistance and aerobic exercise mitigated fatigue in men with PCa receiving radiotherapy . Resistance exercise generated longer-term improvements and additional benefits for QOL , strength , triglycerides , and body fat" ]

[ "CONTEXT Hypothetically , topiramate can improve drinking outcomes among alcohol-dependent individuals by reducing alcohol 's reinforcing effects through facilitation of gamma-aminobutyric acid function and inhibition of glutaminergic pathways in the corticomesolimbic system . OBJECTIVE To determine if topiramate is a safe and efficacious treatment for alcohol dependence . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled , 14-week trial of 371 men and women aged 18 to 65 years diagnosed with alcohol dependence , conducted between January 27 , 2004 , and August 4 , 2006 , at 17 US sites . INTERVENTIONS Up to 300 mg/d of topiramate ( n = 183 ) or placebo ( n = 188 ) , along with a weekly compliance enhancement intervention . MAIN OUTCOME MEASURES Primary efficacy variable was self-reported percentage of heavy drinking days . Secondary outcomes included other self-reported drinking measures ( percentage of days abstinent and drinks per drinking day ) along with the laboratory measure of alcohol consumption ( plasma gamma-glutamyltransferase ) . RESULTS Treating all dropouts as relapse to baseline , topiramate was more efficacious than placebo at reducing the percentage of heavy drinking days from baseline to week 14 ( mean difference , 8.44 % ; 95 % confidence interval , 3.07%-13.80 % ; P = .002 ) . Prespecified mixed-model analysis also showed that topiramate compared with placebo decreased the percentage of heavy drinking days ( mean difference , 16.19 % ; 95 % confidence interval , 10.79%-21.60 % ; P other drinking outcomes ( P topiramate vs placebo , respectively , included paresthesia ( 50.8 % vs 10.6 % ) , taste perversion ( 23.0 % vs 4.8 % ) , anorexia ( 19.7 % vs 6.9 % ) , and difficulty with concentration ( 14.8 % vs 3.2 % ) . CONCLUSION Topiramate is a promising treatment for alcohol dependence . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00210925", "Objective : Anticonvulsant drugs have been used in the treatment of alcohol dependence . The purpose of the present study was to evaluate tolerance and safety of zonisamide in a sample of patients presenting alcohol dependence . Methods : Open-label zonisamide was examined in 22 out patients with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition alcohol dependence . Zonisamide was started at a dose of 50 mg/d and titrated to a maximun dose of 300 mg/d . Subjects received a baseline evaluation including Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition and the Severity of Alcohol Dependence Scale . Alcohol craving and alcohol consumption were assessed at weeks 2 , 4 , 6 , 8 , 10 , and 12 . The concentration of & ggr;-glutamyltransferase was used as an indirect measure of alcohol consumption . Results : Significant improvement was observed in visual analog scale for craving severity scores , weekly drink consumption , and & ggr;-glutamyltransferase . Zonisamide was well tolerated , with only a dropout due to adverse events . Conclusions : Zonisamide is safe and well tolerated in this sample and associated with improvement in alcohol craving and alcohol consumption . A placebo-controlled study would be of interest", "Fifteen volunteers received cannabidiol ( CBD ) ( 320 μg/kg ) or placebo ( both orally , T0 ) , and 60 min later they consumed an ethanolic beverage ( 0.54 g/kg ) or placebo . The effects were measured at T1 ( 100 min after CBD ingestion ) , T2 ( 160 min ) and T3 ( 220 min ) using cognitive , perceptual and motor function tests . Factorial analysis indicated that test procedures could be adequately expressed by three rotated factors : A reaction speed factor ( I ) , a st and ing steadiness factor ( II ) and a psychomotor coordination/cognitive factor ( III ) . Ethanol produced a significant decrement in factor III . There was no demonstrable effect of CBD , either alone or in combination with ethanol . Neither CBD nor ethanol produced any significant effect on pulse rate . Prior administration of CBD did not significantly affect the blood ethanol levels . Whilst the subjects were able to identify correctly when they were given ethanol , they did not report any subjective effects of CBD", "AIM Cannabinoid receptor type 1 ( CB1 ) antagonists show central side effects , whereas beneficial effects are most likely peripherally mediated . In this study , the peripherally selective CB1 antagonist TM38837 was studied in humans . METHODS This was a double-blind , r and omized , placebo-controlled , crossover study . On occasions 1 - 4 , 24 healthy subjects received 5 × 4 mg THC with TM38837 100 mg , 500 mg or placebo , or placebos only . During occasion 5 , subjects received placebo TM38837 + THC with rimonabant 60 mg or placebo in parallel groups . Blood collection s and pharmacodynamic ( PD ) effects were assessed frequently . Pharmacokinetics ( PK ) and PD were quantified using population PK-PD modelling . RESULTS The TM38837 plasma concentration profile was relatively flat compared with rimonabant . TM38837 showed an estimated terminal half-life of 771 h. THC induced effects on VAS feeling high , body sway and heart rate were partly antagonized by rimonabant 60 mg [ -26.70 % [ 90 % confidence interval ( CI ) -40.9 , -12.6 % ] ; -7.10 % , ( 90%CI -18.1 , 5.3 % ) ; -7.30 % , ( 90 % CI -11.5 % , -3.0 % ) respectively ] and TM38837 500 mg [ -22.10 % ( 90 % CI -34.9 , -9.4 % ) ; -12.20 % ( 90 % CI -21.6 % , -1.7 % ) ; -8.90 % ( 90 % CI -12.8 % , -5.1 % ) respectively ] . TM38837 100 mg had no measurable feeling high or body sway effects and limited heart rate effects . CONCLUSIONS Rimonabant showed larger effects than TM38837 , but the heart rate effects were similar . TM38837 100 mg had no impact on CNS effects , suggesting that this dose does not penetrate the brain . This TM38837 dose is predicted to be at least equipotent to rimonabant with regard to metabolic disorders in rodent models . These results provide support for further development of TM38837 as a peripherally selective CB1 antagonist for indications such as metabolic disorders , with a reduced propensity for psychiatric side effects ", "BACKGROUND Topiramate , a sulphamate fructopyranose derivative , might antagonise alcohol 's rewarding effects associated with abuse liability by inhibiting mesocorticolimbic dopamine release via the contemporaneous facilitation of gamma-amino-butyric acid activity and inhibition of glutamate function . We aim ed to see whether topiramate was more effective than placebo as a treatment for alcohol dependence . METHODS We did a double-blind r and omised controlled 12-week clinical trial comparing oral topiramate and placebo for treatment of 150 individuals with alcohol dependence . Of these 150 individuals , 75 were assigned to receive topiramate ( escalating dose of 25 - 300 mg per day ) and 75 had placebo as an adjunct to weekly st and ardised medication compliance management . Primary efficacy variables were : self-reported drinking ( drinks per day , drinks per drinking day , percentage of heavy drinking days , percentage of days abstinent ) and plasma gamma-glutamyl transferase , an objective index of alcohol consumption . The secondary efficacy variable was self-reported craving . FINDINGS At study end , participants on topiramate , compared with those on placebo , had 2.88 ( 95 % CI -4.50 to -1.27 ) fewer drinks per day ( p=0.0006 ) , 3.10 ( -4.88 to -1.31 ) fewer drinks per drinking day ( p=0.0009 ) , 27.6 % fewer heavy drinking days ( p=0.0003 ) , 26.2 % more days abstinent ( p=0.0003 ) , and a log plasma gamma-glutamyl transferase ratio of 0.07 ( -0.11 to -0.02 ) less ( p=0.0046 ) . Topiramate-induced differences in craving were also significantly greater than those of placebo , of similar magnitude to the self-reported drinking changes , and highly correlated with them . INTERPRETATION Topiramate ( up to 300 mg per day ) is more efficacious than placebo as an adjunct to st and ardised medication compliance management in treatment of alcohol dependence", "Objective To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol ( CBD ) in children with Dravet syndrome . Methods Patients aged 4–10 years were r and omized 4:1 to CBD ( 5 , 10 , or 20 mg/kg/d ) or placebo taken twice daily . The double-blind trial comprised 4-week baseline , 3-week treatment ( including titration ) , 10-day taper , and 4-week follow-up periods . Completers could continue in an open-label extension . Multiple pharmacokinetic blood sample s were taken on the first day of dosing and at end of treatment for measurement of CBD , its metabolites 6-OH-CBD , 7-OH-CBD , and 7-COOH-CBD , and antiepileptic drugs ( AEDs ; clobazam and metabolite N-desmethylclobazam [ N-CLB ] , valproate , levetiracetam , topiramate , and stiripentol ) . Safety assessment s were clinical laboratory tests , physical examinations , vital signs , ECGs , adverse events ( AEs ) , seizure frequency , and suicidality . Results Thirty-four patients were r and omized ( 10 , 8 , and 9 to the 5 , 10 , and 20 mg/kg/d CBD groups , and 7 to placebo ) ; 32 ( 94 % ) completed treatment . Exposure to CBD and its metabolites was dose-proportional ( AUC0–t ) . CBD did not affect concomitant AED levels , apart from an increase in N-CLB ( except in patients taking stiripentol ) . The most common AEs on CBD were pyrexia , somnolence , decreased appetite , sedation , vomiting , ataxia , and abnormal behavior . Six patients taking CBD and valproate developed elevated transaminases ; none met criteria for drug-induced liver injury and all recovered . No other clinical ly relevant safety signals were observed . Conclusions Exposure to CBD and its metabolites increased proportionally with dose . An interaction with N-CLB was observed , likely related to CBD inhibition of cytochrome P450 subtype 2C19 . CBD result ed in more AEs than placebo but was generally well-tolerated . Classification of evidence This study provides Class I evidence that for children with Dravet syndrome , CBD result ed in more AEs than placebo but was generally well-tolerated ", "BACKGROUND Patients with Lennox-Gastaut syndrome , a rare , severe form of epileptic encephalopathy , are frequently treatment resistant to available medications . No controlled studies have investigated the use of cannabidiol for patients with seizures associated with Lennox-Gastaut syndrome . We therefore assessed the efficacy and safety of cannabidiol as an add-on anticonvulsant therapy in this population of patients . METHODS In this r and omised , double-blind , placebo-controlled trial done at 24 clinical sites in the USA , the Netherl and s , and Pol and , we investigated the efficacy of cannabidiol as add-on therapy for drop seizures in patients with treatment-resistant Lennox-Gastaut syndrome . Eligible patients ( aged 2 - 55 years ) had Lennox-Gastaut syndrome , including a history of slow ( were r and omly assigned ( 1:1 ) using an interactive voice response system , stratified by age group , to receive 20 mg/kg oral cannabidiol daily or matched placebo for 14 weeks . All patients , caregivers , investigators , and individuals assessing data were masked to group assignment . The primary endpoint was percentage change from baseline in monthly frequency of drop seizures during the treatment period , analysed in all patients who received at least one dose of study drug and had post-baseline efficacy data . All r and omly assigned patients were included in the safety analyses . This study is registered with Clinical Trials.gov , number NCT02224690 . FINDINGS Between April 28 , 2015 , and Oct 15 , 2015 , we r and omly assigned 171 patients to receive cannabidiol ( n=86 ) or placebo ( n=85 ) . 14 patients in the cannabidiol group and one in the placebo group discontinued study treatment ; all r and omly assigned patients received at least one dose of study treatment and had post-baseline efficacy data . The median percentage reduction in monthly drop seizure frequency from baseline was 43·9 % ( IQR -69·6 to -1·9 ) in the cannibidiol group and 21·8 % ( IQR -45·7 to 1·7 ) in the placebo group . The estimated median difference between the treatment groups was -17·21 ( 95 % CI -30·32 to -4·09 ; p=0·0135 ) during the 14-week treatment period . Adverse events occurred in 74 ( 86 % ) of 86 patients in the cannabidiol group and 59 ( 69 % ) of 85 patients in the placebo group ; most were mild or moderate . The most common adverse events were diarrhoea , somnolence , pyrexia , decreased appetite , and vomiting . 12 ( 14 % ) patients in the cannabidiol group and one ( 1 % ) patient in the placebo group withdrew from the study because of adverse events . One patient ( 1 % ) died in the cannabidiol group , but this was considered unrelated to treatment . INTERPRETATION Add-on cannabidiol is efficacious for the treatment of patients with drop seizures associated with Lennox-Gastaut syndrome and is generally well tolerated . The long-term efficacy and safety of cannabidiol is currently being assessed in the open-label extension of this trial . FUNDING GW Pharmaceuticals", "Objectives : The objectives of this study are to assess the tolerability and efficacy of the anticonvulsant zonisamide in an open label trial of the treatment of alcohol dependence . Methods : In this trial , zonisamide ( 400-mg daily ) was administered to alcohol-dependent subjects ( ADS ) ( n = 16 ) over 13 weeks . The mean daily consumption of st and ard alcoholic drinks and performance on a verbal fluency task , the COWAT , and on a measure of attention and visuomotor speed , the DSMT were assessed , and the occurrence of adverse events was monitored weekly . Results : The mean number of drinks consumed daily was significantly reduced from baseline levels during the treatment period . Performances on the COWAT and on the DSMT were not significantly reduced by zonisamide treatment . Overall , zonisamide was well tolerated by the study subjects . Conclusion : These results indicate that zonisamide administration may not impair verbal fluency in ADS , and are consistent with other studies that found zonisamide administration may reduce alcohol intake", "Six male and four female healthy volunteers were given oral placebo ( glucose capsule and orange juice ) , cannabidiol ( CBD 200 mg capsule and orange juice ) , alcohol ( 1 g/kg in orange juice and glucose capsule ) , and CBD ( 200 mg capsule ) plus alcohol ( 1 g/kg in orange juice ) in a double-blind , crossover , r and omized design . Treatments were spaced one week apart . Parameters measured were a finger tap test ( motor performance ) , cancellation and differential aptitude tests ( psychomotor performance ) , a 1-min time production task , subjective effects ( 66 item adjective-pair semantic differential ) , and breathalyzer estimations of blood alcohol levels . Compared to placebo , alcohol and alcohol plus CBD , but not CBD alone , produced significant impairments of motor and psychomotor performances , overestimations of time production and subjective responses indicating an accurate self-perception of their intoxication and deficits . The combination of alcohol plus CBD result ed in significantly lower blood alcohol levels compared to alcohol given alone , however , there were few differences observed between the pharmacological effects of the two alcohol conditions . Thus , the inactivity of CBD , a major marijuana constituent , on motor and mental performance and effects also extends to its interaction with alcohol", "Background Cannabidiol has been used for treatment‐resistant seizures in patients with severe early‐onset epilepsy . We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox – Gastaut syndrome , a severe developmental epileptic encephalopathy . Methods In this double‐blind , placebo‐controlled trial conducted at 30 clinical centers , we r and omly assigned patients with the Lennox – Gastaut syndrome ( age range , 2 to 55 years ) who had had two or more drop seizures per week during a 28‐day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight ( 20‐mg cannabidiol group ) or 10 mg per kilogram ( 10‐mg cannabidiol group ) or matching placebo , administered in two equally divided doses daily for 14 weeks . The primary outcome was the percentage change from baseline in the frequency of drop seizures ( average per 28 days ) during the treatment period . Results A total of 225 patients were enrolled ; 76 patients were assigned to the 20‐mg cannabidiol group , 73 to the 10‐mg cannabidiol group , and 76 to the placebo group . During the 28‐day baseline period , the median number of drop seizures was 85 in all trial groups combined . The median percent reduction from baseline in drop‐seizure frequency during the treatment period was 41.9 % in the 20‐mg cannabidiol group , 37.2 % in the 10‐mg cannabidiol group , and 17.2 % in the placebo group ( P=0.005 for the 20‐mg cannabidiol group vs. placebo group , and P=0.002 for the 10‐mg cannabidiol group vs. placebo group ) . The most common adverse events among the patients in the cannabidiol groups were somnolence , decreased appetite , and diarrhea ; these events occurred more frequently in the higher‐dose group . Six patients in the 20‐mg cannabidiol group and 1 patient in the 10‐mg cannabidiol group discontinued the trial medication because of adverse events and were withdrawn from the trial . Fourteen patients who received cannabidiol ( 9 % ) had elevated liver aminotransferase concentrations . Conclusions Among children and adults with the Lennox – Gastaut syndrome , the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen result ed in greater reductions in the frequency of drop seizures than placebo . Adverse events with cannabidiol included elevated liver aminotransferase concentrations . ( Funded by GW Pharmaceuticals ; GWPCARE3 Clinical Trials.gov number , NCT02224560 .", "BACKGROUND Despite advances in the development of medications to treat alcohol dependence , few medications have been approved by the U.S. Food and Drug Administration . The use of certain anticonvulsant medications has demonstrated potential efficacy in treating alcohol dependence . Previous research suggests that the anticonvulsant levetiracetam may be beneficial in an alcohol-dependent population of very heavy drinkers . METHODS In this double-blind , r and omized , placebo-controlled clinical trial , 130 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites . Patients received either levetiracetam extended-release ( XR ) or placebo and a Brief Behavioral Compliance Enhancement Treatment intervention . Levetiracetam XR was titrated during the first 4 weeks to 2,000 mg/d . This target dose was maintained during weeks 5 through 14 and was tapered during weeks 15 and 16 . RESULTS No significant differences were detected between the levetiracetam XR and placebo groups in either the primary outcomes ( percent heavy drinking days and percent subjects with no heavy drinking days ) or in other secondary drinking outcomes . Treatment groups did not differ on a number of nondrinking outcomes , including depression , anxiety , mood , and quality of life . The only difference observed was in alcohol-related consequences . The levetiracetam XR treatment group showed significantly fewer consequences than did the placebo group during the maintenance period ( p = 0.02 ) . Levetiracetam XR was well tolerated , with fatigue being the only significantly elevated adverse event , compared with placebo ( 53 % vs. 24 % , respectively ; p = 0.001 ) . CONCLUSIONS This multisite clinical trial showed no efficacy for levetiracetam XR compared with placebo in reducing alcohol consumption in heavy drinking alcohol-dependent patients", "Introduction : Zonisamide is an anticonvulsant medication with GABAergic , glutamatergic , and monoaminergic effects . Zonisamide has also been shown to reduce alcohol intake in rodents and in risky drinkers in the context of a laboratory study . This pilot clinical trial evaluated the safety , tolerability , and efficacy of zonisamide for the treatment of alcohol dependence . Methods : Forty alcohol-dependent subjects ( 23 men ) were r and omly assigned to receive treatment with either placebo or zonisamide in a 12-week double-blind trial . Zonisamide was initiated at a dosage of 100 mg/d , which was increased by 100 mg/d every 2 weeks for 8 weeks to a maximum dosage of 500 mg/d . The medication was continued for 4 weeks at the target dosage and then tapered and discontinued . The primary outcomes were drinks per week , heavy drinking days per week , and abstinent days per week , which were measured using the Timeline Follow-Back method . Results : There was a significant medication by treatment week interaction effect favoring the zonisamide group for heavy drinking days ( HDD ; P = 0.012 ) , drinks per week ( P = 0.004 ) , and alcohol urge scores ( P = 0.006 ) . There was not a significant effect on the number or rate of increase in abstinent days . There were no serious adverse events reported and zonisamide treatment was well tolerated . Conclusion : The findings provide preliminary support for the use of zonisamide to treat alcohol dependence . Efforts to replicate and extend these findings are warranted", "Delayed reward discounting ( DRD ) is a behavioral economic index of impulsivity that reflects the extent to which an individual devalues a reward based on its delay in time ( i.e. , preference for smaller immediate rewards relative to larger delayed rewards ) . Current smokers exhibit greater DRD compared to non-smokers , but also exhibit greater DRD compared to ex-smokers , suggesting that either DRD is inversely associated with successful smoking cessation or that smoking cessation itself reduces DRD . In a sample of treatment-seeking smokers ( n=57 , 61 % male , 85 % Caucasian ) participating in a r and omized controlled smoking cessation trial , the current study prospect ively examined DRD for money in general and at three magnitudes in relation to time to the participants ' first lapse to smoking . Survival analysis using Cox proportional-hazards regression revealed that DRD predicted days to first lapse ( ps nicotine dependence , sensation-seeking , and income in covariate analyses , with the exception of small magnitude discounting . In addition , dichotomous comparisons revealed significantly more impulsive baseline discounting for individuals who had lapsed by the two-week and eight-week follow-up visits . These findings indicate that high levels of DRD reflect a risk factor for poor smoking cessation treatment response . Interrelationships among the variables assessed and clinical strategies to improve outcomes for smokers who are high in DRD are discussed", "Background Antiepileptics have been shown to reduce alcohol intake or to prevent relapse in patients with alcoholism . Goal To investigate if the new antiepileptic levetiracetam ( LEV ) prevents relapse after detoxification compared with placebo in patients with alcohol dependence . Methods Two hundred one patients were included in the prospect i ve , r and omized , double-blind , multicenter , placebo-controlled trial . After detoxification treatment and a screening period of 7 days , patients were r and omized to treatment with LEV or placebo . Medication was administered in a fixed-dose schedule for 16 weeks . Primary outcome parameters were the overall rate and time to relapse with heavy drinking . Secondary outcome parameters were time to the first drink , craving , adherence , tolerability , and safety data ( mean corpuscular volume , serum alanine aminotransferase , serum aspartate aminotransferase , & ggr;-glutamyltransferase ) . Results The rate of relapse and the time to relapse did not differ significantly between both groups , but less patients treated with LEV terminated treatment early compared with patients receiving placebo . Tolerability and safety data were similar in the LEV group compared with placebo . Conclusions Our data do not support a significant effect of LEV on relapse prevention in patients with alcohol dependence during the first 16 weeks of abstinence", "Objective : The purpose of this study is to examine the effects of zonisamide on ethanol self-administration and subjective effects in risky drinkers using a human laboratory paradigm . Method : We conducted a double-blind , placebo-controlled study of the effects of zonisamide 100 mg on ethanol self-administration and urge to drink in risky drinkers ( N = 10 ) ( 1 ) . Result : During the second hour of a 2-hour self-administration session ethanol consumption was 50 % lower in the zonisamide group as compared to the placebo group . Urge to drink was also significantly lower under the zonisamide condition . Conclusion : These results indicate that a single dose of zonisamide reduces urge to drink and the quantity of ethanol self-administered by risky drinkers during their second hour of access to alcohol . Scientific Significance : Zonisamide may help individuals drinking at risky levels reduce their intake of alcohol", "Anticonvulsant agents show promise in the treatment of the acute symptoms of alcohol withdrawal and may also treat some symptoms associated with the protracted abstinence syndrome . Impulsivity , hostility and irritability are common characteristics of alcohol-dependent individuals , and there is some evidence that anticonvulsant agents decrease these traits in individuals with a number of different psychiatric disorders . This pilot study is a 12-week , double-blind , placebo-controlled trial of an anticonvulsant agent , divalproex ( DVPX ) , in alcohol-dependent individuals . Alcohol use ( Timeline Follow Back ) , impulsivity ( Barratt Impulsivity Scale ) , irritability and aggression ( Buss-Durkee Hostility Index ; and Anger , Irritability , Aggression Scale ) were measured at baseline and throughout the 12-week treatment period . Drinking decreased significantly in both the placebo and the DVPX-treated groups . In the DVPX group , a significantly smaller percentage of individuals relapsed to heavy drinking , but there were no significant differences in other alcohol-related outcomes . There were significantly greater decreases in irritability in the DVPX-treated group and a trend towards greater decreases on measures of lability and verbal assault . There were no significant between-group differences on measures of impulsivity . While DVPX did not have a robust effect on alcohol-related outcomes , it did have modest impact on a measure of irritability . This is consistent with the findings of other investigators exploring the use of DVPX in schizophrenia , personality disorder and a number of other psychiatric disorders", "In phase 1 of the study , 3 mg/kg daily of cannabidiol ( CBD ) was given for 30 days to 8 health human volunteers . Another 8 volunteers received the same number of identical capsules containing glucose as placebo in a double-blind setting . Neurological and physical examinations , blood and urine analysis , ECG and EEG were performed at weekly intervals . In phase 2 of the study , 15 patients suffering from secondary generalized epilepsy with temporal focus were r and omly divided into two groups . Each patient received , in a double-blind procedure , 200 - 300 mg daily of CBD or placebo . The drugs were administered for along as 4 1/2 months . Clinical and laboratory examinations , EEG and ECG were performed at 15- or 30-day intervals . Throughout the experiment the patients continued to take the antiepileptic drugs prescribed before the experiment , although these drugs no longer controlled the signs of the disease . All patients and volunteers tolerated CBD very well and no signs of toxicity or serious side effects were detected on examination . 4 of the 8 CBD subjects remained almost free of convulsive crises throughout the experiment and 3 other patients demonstrated partial improvement in their clinical condition . CBD was ineffective in 1 patient . The clinical condition of 7 placebo patients remained unchanged whereas the condition of 1 patient clearly improved . The potential use of CBD as an antiepileptic drug and its possible potentiating effect on other antiepileptic drugs are discussed", "OBJECTIVE Alcoholism is associated with gray matter volume deficits in frontal and other brain regions . Whether persistent brain volume deficits in abstinence are predictive of subsequent time to alcohol relapse has not been established . The authors measured gray matter volumes in healthy volunteers and in a sample of treatment-engaged , alcohol-dependent patients after 1 month of abstinence and assessed whether smaller frontal gray matter volume was predictive of subsequent alcohol relapse outcomes . METHOD Forty-five abstinent alcohol-dependent patients in treatment and 50 healthy comparison subjects were scanned once using high-resolution ( T(1)-weighted ) structural MRI , and voxel-based morphometry was used to assess regional brain volume differences between the groups . A prospect i ve study design was used to assess alcohol relapse in the alcohol-dependent group for 90 days after discharge from 6 weeks of inpatient treatment . RESULTS Significantly smaller gray matter volume in alcohol-dependent patients relative to comparison subjects was seen in three regions : the medial frontal cortex , the right lateral prefrontal cortex , and a posterior region surrounding the parietal-occipital sulcus . Smaller medial frontal and parietal-occipital gray matter volumes were each predictive of shorter time to any alcohol use and to heavy drinking relapse . CONCLUSIONS These findings are the first to demonstrate that gray matter volume deficits in specific medial frontal and posterior parietal-occipital brain regions are predictive of an earlier return to alcohol use and relapse risk , suggesting a significant role for gray matter atrophy in poor clinical outcomes in alcoholism . Extent of gray matter volume deficits in these regions could serve as useful neural markers of relapse risk and alcoholism treatment outcome" ]

[ "We have compared the effects of three different margarines , one based on palm oil ( PALM-margarine ) , one based on partially hydrogenated soybean oil ( TRANS-margarine ) and one with a high content of polyunsaturated fatty acids ( PUFA-margarine ) , on serum lipids in 27 young women . The main purpose of the study was to test if replacement of trans fatty acids in margarine by palmitic acid results in unfavorable effects on serum lipids . The sum of saturated fatty acids ( 12∶0 , 14∶0 , 16∶0 ) was 36.3 % of total fatty acids in the PALM-diet , the same as the sum of saturated ( 12∶0 , 14∶0 , 16∶0 ) ( 12.5 % ) and trans ( 23.1 % ) fatty acids in the TRANS-diet . This sum was 20.7 % in the PUFA-diet . The content of oleic acid was 37.9 , 35.2 , and 38.6 % , respectively , in the three diets , whereas linoleic acid amounted to 16 , 13.5 , and 27.3 % , respectively . Total fat provided 30–31 % and the test margarines 26 % of total energy in all three diets . The subjects consumed each of the diets for 17 d in a Latin-square crossover design . There were no significant differences in total cholesterol , low density lipoprotein (LDL)-cholesterol and apolipoprotein B ( apoB ) between the TRANS- and the PALM-diets . High density lipoprotein (HDL)-cholesterol and apoA-I were significantly higher on the PALM-diet compared to the TRANS-diet whereas the ratio of LDL-cholesterol to HDL-cholesterol was lower , although not significantly ( P=0.077 ) on the PALM-diet . Total cholesterol , LDL-cholesterol , and apoB were significantly lower on the PUFA-diet compared to the two other diets . HDL-cholesterol was not different on the PALM- and the PUFA-diets but it was significantly lower on the TRANS-diet compared to the PUFA diet . Compared to the PUFA-diet the ratio of LDL-to HDL-cholesterol was higher on both the PALM- and the TRANS-diets whereas apoA-I was not different . Triglycerides and lipoprotein ( a ) were not significantly different among the three diets . We concluded that nutritionally , palmitic acid from palm oil may be a reasonable alternative to trans fatty acids from partially hydrogenated soybean oil in margarine if the aim is to avoid trans fatty acids . A palm oil-based margarine is , however , less favorable than one based on a more polyunsaturated vegetable oil", "Objective —To determine mechanisms contributing to decreased high-density lipoprotein cholesterol ( HDL-C ) and increased low-density lipoprotein cholesterol ( LDL-C ) concentrations associated with hydrogenated fat intake , kinetic studies of apoA-I , apoB-100 , and apoB-48 were conducted using stable isotopes . Methods and Results —Eight postmenopausal hypercholesterolemic women were provided in r and om order with 3 diets for 5-week periods . Two-thirds of the fat was soybean oil ( unsaturated fat ) , stick margarine ( hydrogenated fat ) , or butter ( saturated fat ) . Total and LDL-C levels were highest after the saturated diet ( P HDL-C levels were lowest after the hydrogenated diet ( P Plasma apoA-I levels and pool size ( PS ) were lower , whereas apoA-I fractional catabolic rate ( FCR ) was higher after the hydrogenated relative to the saturated diet ( P LDL apoB-100 levels and PS were significantly higher , whereas LDL apoB-100 FCR was lower with the saturated and hydrogenated relative to the unsaturated diet . There was no significant difference among diets in apoA-I or B-100 production rates or apoB-48 kinetic parameters . HDL-C concentrations were negatively associated with apoA-I FCR ( r=−0.56 , P=0.03 ) and LDL-C concentrations were negatively correlated with LDL apoB-100 FCR ( r=−0.48 , P=0.05 ) . Conclusions —The mechanism for the adverse lipoprotein profile observed with hydrogenated fat intake is determined in part by increased apoA-I and decreased LDL apoB-100 catabolism", "Although dietary trans fatty acids can affect plasma lipoproteins negatively in humans , no direct comparison with specific saturated fatty acids has been reported , even though trans fatty acids were design ed to replace saturates in foods and food processing . In this study , dietary trans 18:1 [ elaidic acid at 5.5 % energy ( en ) ] was specifically exchanged for cis 18:1 , 16:0 or 12:0 + 14:0 in 27 male and female subjects consuming moderate fat ( 31 % en ) , low cholesterol ( whole food diets during 4-wk diet periods in a crossover design . The trans-rich fat significantly elevated total cholesterol and LDL cholesterol relative to the 16:0-rich and 18:1-rich fats and uniquely depressed HDL cholesterol relative to all of the fats tested . Trans fatty acids also elevated lipoprotein ( a ) [ Lp(a ) ] values relative to all dietary treatments . Furthermore , identical effects on lipoproteins were elicited by 16:0 and cis 18:1 in these subjects . The current results suggest that elaidic acid , one of the principal trans isomers produced during industrial hydrogenation of edible oils , adversely affects plasma lipoproteins . Thus , the negative effect of elaidic acid on the lipoprotein profile of humans appears to be unmatched by any other natural fatty acid(s )", "BACKGROUND Dietary behenic acid ( 22:0 ) is poorly absorbed . Because of its low bioavailability compared with other fatty acids and because of its very long chain length , the effect of dietary behenic acid ( behenate ) on serum lipid concentrations in humans is assumed to be neutral . OBJECTIVE The objective was to establish the cholesterol-raising potential of behenic acid by comparing the effects on lipid and lipoprotein concentrations of a specially formulated fat enriched with behenic acid with those of palm oil ( rich in palmitic acid ; 16:0 ) and high-oleic acid sunflower oil ( rich in cis oleic acid ; 18:1 ) . DESIGN In a r and omized , crossover , metabolic-ward study , 7 mildly hypercholesterolemic men were fed 3 natural-food diets supplemented with behenate oil , palm oil , or high-oleic acid sunflower oil . Mean serum lipid and lipoprotein concentrations and plasma triacylglycerol fatty acid composition were determined from fasting blood drawn during the final 4 d of each 3-wk diet period . RESULTS Behenate oil produced mean concentrations of total cholesterol ( 5.87+/-0.8 mmol/L ) and LDL cholesterol ( 4.40+/-0.8 mmol/L ) not significantly different from those produced by palm oil ( 5.84+/-0.7 and 4.42+/-0.7 mmol/L , respectively ) but significantly higher than those produced by high-oleic acid sunflower oil ( 5.12+/-0.5 and 3.70+/-0.6 mmol/L , respectively ) . There were no significant differences in triacylglycerol or HDL-cholesterol concentrations . CONCLUSIONS Despite its low bioavailability compared with oleic acid , behenic acid is a cholesterol-raising fatty acid in humans and is therefore not a suitable substitute for palmitic acid in manufactured triacylglycerols", "Twenty-one healthy normocholesterolemic young adults , men and women , completed a r and omized 30-d/30-d crossover comparison of the effect of palmolein and olive oil on plasma lipids . The subjects were free-living volunteers who changed to low-fat diets to which one of the test oils was added ( used as a spread , for baking , or for frying ) in turn . Complete food records were kept throughout : the test oils were compared at 17 % of total dietary energy . Under the conditions of this experiment plasma total and low-density-lipoprotein ( LDL ) cholesterol were almost identical with the two oils , so that when the palmitic acid ( 16:0 ) in palm oil replaced oleic acid ( 18:1 ) in olive oil the expected increase in LDL cholesterol was not seen . These results indicate that 16:0 , though saturated , is not always a plasma cholesterol-raising fatty acid . Palmolein is rich in vitamin E , alpha-tocopherol , and especially tocotrienols , but the latter were barely detectable in plasma", "We examined the effect of the positional distribution of fatty acids within dietary triglycerides on serum lipoproteins . Sixty subjects consumed two diets of equal fatty acid composition for 3 wk each . In the palm oil diet 82 % of palmitic acid was attached to the outer two carbon atoms of glycerol , and 18 % to the middle carbon . In the diet rich in enzymatically modified palm oil these figures were 35 % and 65 % , respectively . On the modified-fat diet , average lipoprotein concentrations showed nonsignificant ( P > 0.13 ) increases of 0.06 mmol/L for total , 0.03 mmol/L for HDL , and 0.04 mmol/L for LDL cholesterol compared with palm oil . The small increases in total and LDL cholesterol were statistically significant in the men ( n = 23 ) but not in the women ( n = 37 ) . The ratio of HDL to LDL cholesterol and serum triglyceride concentrations were unchanged . Thus , a large difference in dietary fatty acid configuration had little effect on lipoprotein concentrations in humans", "Palm oil and soybean oil are the 2 most widely used cooking oils in the world . Palm oil is consumed mainly in developing countries , where morbidity and mortality due to cardiovascular disease ( CVD ) are on the rise . Although cl aims about adverse or protective effects of these oils are commonly made , there are no epidemiologic studies assessing the association between these oils and cardiovascular disease endpoints . We examined whether consumption of palm oil relative to soybean oil and other unsaturated oils ( predominantly sunflower ) is associated with myocardial infa rct ion ( MI ) in Costa Rica . The cases ( n = 2111 ) were survivors of a first acute MI and were matched to r and omly selected population controls ( n = 2111 ) . Dietary intake was assessed with a vali date d semiquantitative FFQ . Adipose tissue profiles of essential fatty acids were assessed to vali date cooking oil intake and found to be consistent with self-reported major oils used for cooking . The data were analyzed using conditional logistic regression . Palm oil users were more likely to have an MI than users of soybean oil [ odds ratio ( OR ) = 1.33 ; 95 % CI : 1.08 - 1.63 ] or other cooking oils ( OR = 1.23 ; CI : 0.99 - 1.52 ) , but they did not differ from users of soybean oil with a high trans-fatty acid content ( OR = 1.14 ; CI : 0.84 - 1.56 ) . These data suggest that as currently used in Costa Rica , and most likely in many other developing countries , the replacement of palm oil with a polyunsaturated nonhydrogenated vegetable oil would reduce the risk of MI", "Increased HDL-cholesterol levels have been associated with lower coronary heart disease ( CHD ) risk . However , HDL are heterogeneous lipoproteins , and particles enriched in apolipoprotein ( Apo ) AII have been associated with increased CHD risk . We examined the effect of dietary intervention on HDL composition in 14 postmenopausal women subjected to two consecutive diet periods , i.e. , an oleic acid sunflower oil diet followed by a palmolein diet , each lasting 4 wk . The linoleic acid was kept at 4 % total energy and the cholesterol intake at 400 mg/d . The palmolein diet increased serum total cholesterol ( TC ) ( P phospholipids ( P Apo AII ( P HDL cholesterol ( P HDL lipids ( P HDL proteins ( P HDL total mass ( P HDL cholesterol/Apo AI ratio was increased 22.0 % ( P HDL cholesterol/Apo AII and the Apo AI/Apo AII ratios were decreased 19.4 % ( P cholesterolemia status ( 6.2 mmol/L ) , the most significant changes ( P Apo AII levels . Moreover , a significant dietary oil by cholesterol level interaction was found for Apo AII and the HDL cholesterol/Apo AII ratio . In summary , a palmolein diet increased TC and HDL cholesterol compared with oleic acid sunflower oil diet ; however , the increase in Apo AII but not in Apo AI suggests the impairment of reverse cholesterol transport and potentially an increase in CHD risk . This effect was more marked in women with serum TC > 6.2", "The effects on serum lipids of palm oil ( PA ) used in Chinese diets were compared with those of soybean oil ( SO ) , peanut oil ( PE ) and lard ( LA ) in normocholesterolemic subjects and with that of PE in hypercholesterolemic subjects . Normocholesterolemic subjects [ 120 men , 18 - 25 y , total cholesterol ( TC ) 2.8 - 5.0 mmol/L ] were assigned to four groups to consume test diets for six consecutive weeks after a run-in period of 3 wk . About 30 % of dietary energy was derived from fat , 75 - 80 % of which came from test oils . In comparison with the entry level , the average serum TC and LDL cholesterol ( LDL-C ) were 6.7 and 13.1 % lower , respectively , in the PA group and 22.8 and 30.7 % higher , respectively , ( P serum TC , LDL-C and the ratio of TC/HDL cholesterol ( HDL-C ) in the PA group were significantly lower than those of the LA group . Hypercholesterolemic subjects ( 31 men , 20 women , 32 - 68 y , TC 5.5 - 7.0 mmol/L ) were divided into two groups . For 6 wk , one group ( 15 men , 10 women ) consumed the PA diet ; another group ( 16 men , 9 women ) consumed the PE diet . After a 3-wk interval , the two groups interchanged diets for another 6 wk . The test diets again contained about 30 % energy from fat , 60 - 65 % of which came from test oils . Compared with entry values , the PA diet caused significant reductions in serum TC , LDL-C and TC/HDL-C during the first 6 wk and also a significant reduction in TC/HDL-C during the second 6 wk . The PE diet had no significant influence on serum lipids in either experimental period", "Although medium-chain triacylglycerols ( MCTs , composed of medium-chain fatty acids 8:0 and 10:0 ) have long been described as having neutral effects on serum cholesterol concentrations , experimental evidence supporting this cl aim is limited . In a r and omized , crossover , metabolic-ward study , we compared the lipid effects of a natural food diet supplemented with either MCTs , palm oil , or high oleic acid sunflower oil in nine middle-aged men with mild hypercholesterolemia . Rather than having a neutral effect , MCT oil produced total cholesterol concentrations that were not significantly different from those produced by palm oil ( MCT oil : 5.87 + /- 0.75 mmol/L ; palm oil : 5.79 + /- 0.72 mmol/L ) but significantly higher than that produced by high oleic acid sunflower oil ( 5.22 + /- 0.52 mmol/L ) . Low-density-lipoprotein (LDL)-cholesterol concentrations paralleled those of total cholesterol . MCT oil tended to result in higher triacylglycerol concentrations than either palm oil or high oleic acid sunflower oil , but this difference was not significant . There were no differences in high-density-lipoprotein cholesterol concentrations . The palmitic acid and total saturated fatty acid content of plasma triacylglycerols in the MCT-oil diet was not significantly different from that in the palm oil diet . On the basis of percentage of energy , this study suggests that medium-chain fatty acids have one-half the potency that palmitic acid has at raising total and LDL-cholesterol concentrations", "The effects of lauric acid ( C12:0 ) on plasma lipids and lipoproteins were compared with the effects of palmitic acid ( C16:0 ) and oleic acid ( C18:1 ) in a metabolic-diet study of 14 men by using liquid-formula diets fed for 3 wk each in r and om order . Lauric acid was supplied in a synthetic high-lauric oil , palmitic acid was provided by palm oil and oleic acid in oleic-rich sunflower seed oil . The high-lauric oil result ed in higher concentrations of plasma total cholesterol ( 4.94 + /- 0.75 mmol/L [ mean + /- SE ] ) and LDL cholesterol ( 3.70 + /- 0.57 mmol/L ) when compared with high-oleic sunflower oil ( 4.44 + /- 0.54 and 3.31 + /- 0.44 mmol/L , respectively ) , but did not raise total and LDL cholesterol concentrations as much as did palm oil ( 5.17 + /- 0.65 and 3.93 + /- 0.51 mmol/L , respectively ) . No differences were noted in plasma triglycerides or HDL cholesterol . Lauric acid raises total and LDL cholesterol concentrations compared with oleic acid , but is not as potent for increasing cholesterol concentrations as is palmitic acid", "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 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", "Little is known about the physiological effects of red palm olein ( RPO ) . The effects of red palm olein and palm olein ( POL ) compared to sunflower oil ( SFO ) , on lipids , haemostatic factors and fibrin network characteristics in hyperfibrinogenaemic volunteers were investigated . Fifty-nine free-living , hyperfibrinogenaemic volunteers participated in this r and omized , controlled , single blind parallel study . After a 4-week run-in , during which subjects received sunflower oil products , they were paired and r and omly assigned to one of three intervention groups receiving products containing 25 g/day ( approximately 12 % of total energy intake ) of either red palm olein , palm olein or sunflower oil for another 4 weeks . Anthropometric measurements , blood sample s and dietary intakes were measured before run-in , and before and after intervention . The differences in changes in total serum cholesterol response between palm olein and red palm olein ( + 0.59 vs. + 0.18 mmol/l ; p=0.053 ) , and between palm olein and sunflower oil ( + 0.59 vs. -0.003 mmol/l ; p low-density lipoprotein cholesterol ( LDLC ) response in the palm olein- and sunflower oil-groups also differed significantly ( + 0.42 vs. -0.11 mmol/l ; p Tissue plasminogen activator antigen ( tPA(ag ) ) decreased significantly in the red palm olein group compared to the palm olein- and sunflower oil-groups . No effects were found in other haemostatic variables . Palm olein and red palm olein had no independent effect on fibrin network characteristics . In conclusion , compared to palm olein , red palm olein had less detrimental effects on the lipid profile and decreased tissue plasminogen activator antigen . Studies in larger groups are advised for confirmation of results , elucidation of mechanisms and effects of nonglyceride constituents of red palm oil ( PO )", "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", "We previously found no difference in healthy young adults ' plasma cholesterols between palmolein and olive oil as the major dietary lipid , although the former is high in palmitic acid ( 16:0 ) but the latter in oleic acid ( 18:1 cis ) . In the experiment reported here we compared the effects of palmolein against another monounsaturated oil , highly oleic sunflower oil ( HOSO ) , on plasma cholesterol in both young and middle-aged healthy adults . The test oils were provided as frying oil of potato crisps ( 150 g/day in men ; 100 g/day in women ) against low-fat background diets in free-living motivated volunteers . The design was a r and omised double-blind 4-week/3-week crossover trial . Compliance was monitored with continuous dietary diaries and by measuring ( fasting ) plasma lipid fatty-acid pattern . Plasma lipids and vitamin-E compounds were measured at the start and twice at the end of each test period . In combined young plus older subjects ( n = 42 ) mean plasma total and low-density-lipoprotein cholesterol ( LDL-c ) values were both 7 % ( significantly ) lower on HOSO than on palmolein , but because high-density-lipoprotein cholesterol ( HDL-c ) was also 5 % lower , the LDL-c/HDL-c ratio was only 3 % lower on HOSO than on palmolein . The difference between the present results with HOSO and previous results with olive oil both compared against palmolein suggest that olive oil is associated with higher plasma cholesterols than other monounsaturated oils . In both the young and older subgroup , LDL-c was lower on HOSO but because HDL-c moved down too in the young subgroup , the LDL-c/HDL-c ratio was lower on HOSO only in the older subjects . Palmolein has an unusual pattern of E vitamins , with a high content of tocotrienols , notably the gamma-isomer . Unlike alpha-tocopherol however , there was no sign of these tocotrienols in subjects ' plasmas", "BACKGROUND Dietary fat type is known to modulate the plasma lipid profile , but its effects on plasma homocysteine and inflammatory markers are unclear . OBJECTIVE We investigated the effects of high-protein Malaysian diets prepared with palm olein , coconut oil ( CO ) , or virgin olive oil on plasma homocysteine and selected markers of inflammation and cardiovascular disease ( CVD ) in healthy adults . DESIGN A r and omized-crossover intervention with 3 dietary sequences of 5 wk each was conducted in 45 healthy subjects . The 3 test fats , namely palmitic acid (16:0)-rich palm olein ( PO ) , lauric and myristic acid ( 12:0 + 14:0)-rich CO , and oleic acid (18:1)-rich virgin olive oil ( OO ) , were incorporated at two-thirds of 30 % fat calories into high-protein Malaysian diets . RESULTS No significant differences were observed in the effects of the 3 diets on plasma total homocysteine ( tHcy ) and the inflammatory markers TNF-α , IL-1β , IL-6 , and IL-8 , high-sensitivity C-reactive protein , and interferon-γ . Diets prepared with PO and OO had comparable nonhypercholesterolemic effects ; the postpr and ial total cholesterol for both diets and all fasting lipid indexes for the OO diet were significantly lower ( P decrease postpr and ial lipoprotein(a ) . CONCLUSION Diets that were rich in saturated fatty acids prepared with either PO or CO , and an OO diet that was high in oleic acid , did not alter postpr and ial or fasting plasma concentrations of tHcy and selected inflammatory markers . This trial was registered at clinical trials.gov as NCT00941837", "We studied the metabolic effects of stearic acid ( 18:0 ) on plasma lipoprotein levels in 11 subjects during three dietary periods of three weeks each . The three liquid-formula diets , which were used in r and om order , were high in palmitic acid ( 16:0 ) , stearic acid , and oleic acid ( 18:1 ) , respectively . Caloric intakes were the same during the three periods . As compared with the values observed when the subjects were on the high-palmitic-acid diet , plasma total cholesterol decreased by an average of 14 percent during consumption of the high-stearic-acid diet ( P less than 0.005 ) and by 10 percent during consumption of the high-oleic-acid diet ( P less than 0.02 ) . Low-density lipoprotein cholesterol levels fell by 21 percent in subjects on the high-stearic-acid diet ( P less than 0.005 ) and by 15 percent in subjects on the high-oleic-acid diet ( P less than 0.005 ) . No significant differences were observed in the plasma levels of triglycerides or high-density lipoprotein cholesterol among the three diets . Measurements of the intestinal absorption of palmitic , stearic , and oleic acids revealed essentially complete absorption of each during the three dietary periods . The oleic acid content of plasma triglycerides and cholesteryl esters increased significantly during the high-stearic-acid period , suggesting that stearic acid is rapidly converted to oleic acid . We conclude that stearic acid appears to be as effective as oleic acid in lowering plasma cholesterol levels when either replaces palmitic acid in the diet", "The effects of a diet containing soybean oil ( SBO ) , rice bran oil ( RBO ) , palm oil ( PO ) or a RBO/PO ( 3:1 ) mixture on the composition and oxidation of small dense low-density lipoproteins ( sdLDL ) in 16 hypercholesterolaemic women were investigated . During the 8-week control period , participants consumed a free-choice weight-maintaining diet comprising carbohydrate ( 55 % energy ) , protein ( 15 % energy ) and fat ( 30 % energy ) with During each 10-week study period , participants consumed this same diet but with the addition of one of the three test oils or the RBO/PO mixture . Total cholesterol and low-density lipoprotein (LDL)-cholesterol levels were significantly reduced during SBO , RBO and RBO/PO consumption , while high-density lipoprotein cholesterol was significantly decreased by SBO consumption . There was a significant reduction in sdLDL-cholesterol levels only after using SBO and it tended to be reduced during RBO/PO consumption , whereas it was significantly increased following PO consumption . The sdLDL oxidation lag time was significantly increased during PO , RBO/PO and RBO consumption , but significantly reduced following SBO . The results for the RBO/PO mixture suggest that this oil mixture might further reduce the risk of atherosclerosis", "UNLABELLED Although saturated fat acids have long known to have harmful effects on cholesterol and triacylglycerides levels in blood , new concepts have emerged form recent research on this matter . The purpose of this study was to know the effect of the consumption of palm olein on triacylglycerides and cholesterol levels as well as lipoprotein fractions in the blood plasma of healthy individuals from both sexes . MATERIAL S AND METHODS Different types of fats were administered for 12 weeks to 60 subjects , 45 male , 15 female , between 19 and 45 years of age , who were divided into three groups : the mix group ( MG ) was administered oil , margarine , and mayonnaise prepared with 50 % olein ; the olein group ( OG ) consumed fats prepared with 100 % olein ; and the control group ( CG ) consumed regular fats of customary use by the population . The diets provided 25 to 30 % of calories . Blood sample s were obtained for lipid analysis at the beginning and the end of the study . Plasma triacylglycerides and cholesterol concentrations were determined by means of enzyme and lipoprotein methods ( VLDL , LDL ; and HDL ) by ultracentrifugation . RESULTS AND DISCUSSION By comparing the groups ' means no significant differences were found ( p > 0.05 ) in blood lipids . Individual differences show a slight increase in VLDL-C in OG compared to MG and CG . No differences were found in LDL concentration . CONCLUSIONS These results contribute evidence to differentiate between the effects of saturated vegetables oils , such as coconut oil , and of palm olein . The authors recommend not extrapolate the effects of type of oil to another in connection with TC increase in blood", "Summary . Partial hydrogenation of oil results in fats containing unusual isomeric fatty acids characterized by cis and trans configurations . Hydrogenated fats containing trans fatty acids increase plasma total cholesterol ( TC ) and LDL-cholesterol while depressing HDL-cholesterol levels . Identifying the content of trans fatty acids by food labeling is overshadowed by a reluctance of health authorities to label saturates and trans fatty acids separately . Thus , it is pertinent to compare the effects of trans to saturated fatty acids using stable isotope methodology to establish if the mechanism of increase in TC and LDL-cholesterol is due to the increase in the rate of endogenous synthesis of cholesterol . Ten healthy normocholesterolemic female subjects consumed each of two diets containing approximately 30 % of energy as fat for a fourweek period . One diet was high in palmitic acid ( 10.6 % of energy ) from palm olein and the other diet exchanged 5.6 % of energy as partially hydrogenated fat for palmitic acid . This fat blend result ed in monounsaturated fatty acids decreasing by 4.9 % and polyunsaturated fats increasing by 2.7 % . The hydrogenated fat diet treatment provided 3.1 % of energy as elaidic acid . For each dietary treatment , the fractional synthesis rates for cholesterol were measured using deuterium-labeling procedures and blood sample s were obtained for blood lipid and lipoprotein measurements . Subjects exhibited a higher total cholesterol and LDL-cholesterol level when consuming the diet containing trans fatty acids while also depressing the HDL-cholesterol level . Consuming the partially hydrogenated fat diet treatment increased the fractional synthesis rate of free cholesterol . Consumption of hydrogenated fats containing trans fatty acids in comparison to a mixtur e of palmitic and oleic acids increase plasma cholesterol levels apparently by increasing endogenous synthesis of cholesterol" ]

[ "OBJECTIVE To conduct a prospect i ve study of the occurrence of psychological disorders and comorbidities after spinal cord injury ( SCI ) , determine psychotropic medication usage , and establish predictors of psychological disorders after transition to the community . DESIGN Longitudinal design with multiple measures . SETTING Assessment occurred in SCI units and the community . PARTICIPANTS Adults with SCI ( N=88 ) admitted over a period of 32 months into 3 SCI units . INTERVENTIONS Participants completed inpatient rehabilitation for an acute SCI . Longitudinal assessment occurred up to 6 months postdischarge . MAIN OUTCOME MEASURES Measures were chosen that had a theoretical and clinical foundation for contributing to recovery after SCI . The Mini International Neuropsychiatric Interview , a structured diagnostic psychiatric interview , was conducted to determine the presence of psychological disorders . Medical measures included severity of secondary conditions or complications . Psychological measures included measures of anxiety and depressive mood , resilience , pain catastrophization , self-efficacy , and cognitive capacity . RESULTS Rates of psychological disorders of 17 % to 25 % were substantially higher than rates found in the Australian community . The occurrence of psychological disorder comorbidities was also very high . Anxiety was significantly elevated in those with a psychological disorder . Psychotropic medications were prescribed to more than 36 % of the sample , with most being antidepressants . Factors predictive of psychological disorders included years of education , premorbid psychiatric/psychological treatment , cognitive impairment , secondary complications , resilience , and anxiety . CONCLUSIONS SCI can have a substantial negative impact on mental health that does not change up to 6 months postdischarge . Findings suggest a substantial minority experience increased psychosocial distress after the injury and after transitioning into the community . Additional re sources should be invested in improving the mental health of adults with SCI", "BACKGROUND This study aim ed to index the prevalence of posttraumatic stress disorder ( PTSD ) after injury requiring intensive care unit ( ICU ) admission to investigate whether an ICU admission after injury increases risk for PTSD and to identify predictors of PTSD after ICU admission . METHODS A two-group ( those admitted to the ICU vs. those not admitted to ICU ) , prospect i ve , cohort study of 829 r and omly selected injury patients from five major trauma hospitals across Australia . We collected information on factors that may increase risk for PTSD including demographic variables ( gender , age , income , education , and marital status ) , preinjury mental health status ( prior trauma , psychiatric history , and prior social support ) , and injury characteristics ( mild traumatic brain injury , injury severity , length of hospital admission , discharge destination , pain , and perceived threat ) . PTSD was measured at 12 months by structured clinical interview . RESULTS ICU patients were significantly more likely to have PTSD at 12 months than trauma controls ( 17 % vs. 7 % ) . Stepwise logistic regressions showed that an ICU admission significantly contributed to the development of PTSD after controlling for demographic , preinjury mental health status , and injury characteristic variables . CONCLUSIONS Injury patients are three times more likely to develop later PTSD if they have an ICU admission . Given we controlled for many risk variables , it seems that an ICU admission itself may contribute to the development of PTSD . Mental health services such as screening and early intervention may be particularly useful for this population", "OBJECTIVE To extend the findings of a pilot study that evaluated a brief group-based psychological intervention aim ed at improving psychological adjustment , self-perception and enhancing adaptive coping following spinal cord injury . The theoretical underpinnings of the Coping Effectiveness Training ( CET ) Programme are Lazarus and Folkman 's ( 1984 ) cognitive theory of stress and coping , and cognitive behavioural therapy techniques . DESIGN A controlled trial comparing patients that received the CET intervention with matched controls on measures of psychological adjustment and coping . METHOD A total of 45 intervention group participants and 40 matched controls were selected from in patients at a hospital-based spinal cord injury centre . Outcome measures of anxiety and depression , self-perception and coping were collected before , immediately after and 6 weeks following the intervention . RESULTS Intervention group participants showed a significant reduction in depression and anxiety , compared to the matched controls following the intervention . There was no evidence of a significant change in the pattern of coping strategies used by the intervention group compared to controls . The intervention group alone completed measures of self-perception . There was a significant decrease in the discrepancy between participants ' ' ideal ' self and ' as I am ' , and between ' as I would be without the injury ' and ' as I am ' following the intervention and at follow-up . Significant correlations were also found between self-perception , and anxiety and depression over time . CONCLUSIONS These results confirm the findings of the pilot study , that the CET intervention facilitated a significant improvement in psychological adjustment to spinal cord injury . It is proposed that this improvement may be understood in terms of changing participants ' negative appraisal s of the implication s of spinal cord injury with the result of increasing the perceived manageability of its consequences . Such decatastrophizing alters appraisal s which are associated with current mood . Participants found shared discussion and problem-solving to be particularly helpful . Avenues for further research are discussed", "The authors assessed effects of paraplegic and quadriplegic spinal cord injuries ( SCIs ) on posttraumatic stress disorder ( PTSD ) by comparing severity and prevalence of PTSD in these groups to a sample of controls who experienced traumatic injuries other than SCI . The authors found that veterans with quadriplegia reported significantly less severe current PTSD symptoms than controls who were not significantly different from veterans with paraplegia . These results suggest that sustaining a quadriplegic SCI decreases risk of current PTSD , whereas sustaining a paraplegic SCI is associated with greater risk of PTSD , although the risk is no greater than that incurred from experiencing the trauma itself", "OBJECTIVE With the exception of a few reports of higher rates of childhood trauma in Vietnam veterans with posttraumatic stress disorder ( PTSD ) , little is known about the influence of previous exposure to trauma on the PTSD effects of subsequent trauma . The authors examine interrelated questions about the effects of previous exposure to trauma . METHOD A representative sample of 2,181 individuals in southeast Michigan were interviewed by telephone to record lifetime history of traumatic events specified in DSM-IV as potentially leading to PTSD . PTSD was assessed with respect to a r and omly selected index trauma from the list of events reported by each respondent . RESULTS History of any previous exposure to traumatic events was associated with a greater risk of PTSD from the index trauma . Multiple previous events had a stronger effect than a single previous event . The effect of previous assaultive violence persisted over time with little change . When they examined several features of the previous exposure to trauma , the authors found that subjects who experienced multiple events involving assaultive violence in childhood were more likely to experience PTSD from trauma in adulthood . Furthermore , previous events involving assaultive violence -- single or multiple , in childhood or later on -- were associated with a higher risk of PTSD in adulthood . CONCLUSIONS Previous exposure to trauma signals a greater risk of PTSD from subsequent trauma . Although these results are consistent with a sensitization hypothesis , like the results from previous research on PTSD , they do not address the mechanism of increased responsivity to trauma . Long-term observational studies can further eluci date these observations", "OBJECTIVE To determine the impact of co-occurring traumatic brain injury ( TBI ) on functional motor outcome and cognition during acute spinal cord injury ( SCI ) rehabilitation . DESIGN Prospect i ve , longitudinal cohort . SETTING Single-center National Institute of Disability and Rehabilitation Research SCI Model System . PARTICIPANTS Persons aged 16 to 59 years ( N=189 ) admitted for acute SCI rehabilitation during the 18-month recruitment window who met inclusion criteria . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES FIM Motor Scale ( Rasch transformed ) and acute rehabilitation length of stay ( LOS ) . RESULTS In the tetraplegia sample , co-occurring TBI was not related to FIM Motor Scale scores or acute rehabilitation LOS despite having negative impacts on memory and problem solving . Persons with paraplegia who sustained co-occurring severe TBI had lower admission and discharge FIM Motor Scale scores and longer acute rehabilitation LOS than did persons with paraplegia and either no TBI or mild TBI . Persons with paraplegia and severe TBI had lower functional comprehension , problem solving , and memory and impairments on tests of processing speed compared with persons with paraplegia and no TBI , mild TBI , and moderate TBI . Persons with paraplegia and co-occurring mild and moderate TBI had equivalent acute rehabilitation motor outcomes and cognitive functioning compared with persons with paraplegia and no TBI . CONCLUSIONS This study provides evidence that persons aged 16 to 59 years with paraplegia and co-occurring severe TBI had worse motor outcomes and longer acute rehabilitation LOS than did persons with paraplegia and no TBI . Impairments in processing speed , comprehension , memory , and problem solving may explain suboptimal motor skill acquisition . Research with larger sample s is required to determine whether mild and moderate TBI impact acute rehabilitation motor outcomes and LOS", "This study identified coping strategies associated with caregiver outcomes following pediatric injury and examined injury type as a moderator of coping efficacy . Families of 103 children with traumatic brain injury ( TBI ) and 71 children with orthopedic injuries were followed prospect ively during the initial year postinjury . The groups had comparable preinjury characteristics and hospitalization experiences but differed on neurological insult . In hierarchical regression analyses , acceptance was associated with lower burden and denial was associated with greater distress in both groups . Active coping result ed in higher distress following TBI but not orthopedic injuries . Conversely , the use of humor was related to diminishing distress following TBI but unrelated to distress following orthopedic injuries . Results are discussed in terms of the implication s for intervention following TBI" ]

[ "BACKGROUND AND OBJECTIVES Red cell transfusion is commonly used in orthopaedic surgery . Evidence suggests that a restrictive transfusion strategy may be safe for most patients . However , concern has been raised over the risks of anaemia in those with ischaemic cardiac disease . Perioperative silent myocardial ischaemia ( SMI ) has a relatively high incidence in the elderly population undergoing elective surgery . This study used Holter monitoring to compare the effect of a restrictive and a liberal red cell transfusion strategy on the incidence of SMI in patients without signs or symptoms of ischaemic heart disease who were undergoing lower limb arthroplasty . MATERIAL S AND METHODS We performed a multicentre , controlled trial in which 260 patients undergoing elective hip and knee replacement surgery were enrolled and r and omized to transfusion triggers that were either restrictive ( 8 g/dl ) or liberal ( 10 g/dl ) . Participants were monitored with continuous ambulatory electrocardiogram ( ECG ) ( Holter monitoring ) , preoperatively for 12 h and postoperatively for 72 h. The tapes were analysed for new ischaemia by technicians blinded to treatment . The total ischaemia time in minutes was divided by the recording time in hours and an ischaemic load in min/h was calculated . Haemoglobin levels were measured preoperatively , postoperatively in the recovery room , and on days one , three and five after surgery . RESULTS The mean postoperative haemoglobin concentration was 9.87 g/dl in the restrictive group and 11.09 g/dl in the liberal group . In the restrictive group , 34 % were transfused a total of 89 red cell units , and in the liberal group 43 % were given a total of 119 red cell units . A postoperative episode of silent ischaemia was experienced by 21/109 ( 19 % ) patients in the restrictive group and by 26/109 ( 24 % ) patients in the liberal group [ mean difference -4.6 % ; 95 % confidence interval ( CI ) : -15.5 % to 6 % , P = 0.41 ) . There was no significant difference ( P = 0.53 ) between the overall ischaemic load in the restrictive group ( median 0 min/h , range 0 - 4.18 ) and the liberal group ( median 0 min/h , range 0 - 19.48 ) . In those patients who did experience postoperative SMI , the mean ischaemic load was 0.48 min/h in the restrictive group and 1.51 min/h in the liberal group ( ratio 0.32 , 95 % CI : 0.14 - 0.76 , P = 0.011 ) . The median postoperative length of hospital stay in the restrictive group was 7.3 days [ range 5 - 11 ; interquartile range ( IQR ) 6 - 8 ] compared with 7.5 days ( range 5 - 13 ; IQR 7 - 8 ) in the liberal group . The numbers were not large enough to conclude equivalence . CONCLUSIONS In patients without preoperative evidence of myocardial ischaemia undergoing elective hip and knee replacement surgery , a restrictive transfusion strategy seems unlikely to be associated with an increased incidence of SMI . A proportion of these patients experience moderate SMI , regardless of the transfusion trigger . Use of a restrictive transfusion strategy did not increase length of hospital stay , and use of this strategy would lead to a significant reduction in red cell transfusion in orthopaedic surgery . Our data did not indicate any potential for harm in employing such a strategy in patients with no prior evidence of cardiac ischaemia who were undergoing elective orthopaedic surgery", "Two groups of patients having primary or revision total hip replacement were studied during a period of 11 months . The first group of 40 consecutive patients consented to have whole blood collected coincident with acute normovolemic hemodilution . An inventory of autologous red blood cells , plasma , and platelets was prepared in the operating room as a preliminary to surgery . Subsequently , the same supplies and equipment were used for autotransfusion intraoperatively . In a case-control study , another 40 patients having total hip replacements were matched for age , gender , and weight . The second group of patients refused hemodilution and received autotransfusion alone . The perioperative transfusion requirements of the two groups were compared . The total blood product donor exposure rate of the first group was ¼ of the controls ( 0.6 and 2.4 donor units per patient , respectively ) . The average length of stay in the hospital after surgery for the first group was shortened significantly ( 6.2 versus 8.4 days ) , possibly from less immunogenic insult associated with increased transfusions of autologous blood products . Hemodilution , followed by autotransfusion , was cost effective in primary and revision total hip replacements , autotransfusion alone was cost effective only in revision arthroplasty", "BACKGROUND / AIM Total knee replacement ( TKR ) surgery is one of the most frequent and the most extensive procedures in orthopedic surgery , accompanied with some serious complications . Perioperative blood loss is one of the most serious losses , so it is vital to recognize and treat such losses properly . Autologous blood transfusion is the only true alternative for the allogeneic blood . The aim of this study was to to examine if autologous blood transfusion reduces usage of allogenic blood in total knee replacement surgery , as well as to examine possible effect of autologous blood transfusion on postoperative complications , recovery and hospital stay of patients after total knee replacement surgery . METHODS During the controlled , prospect i ve , r and omised study we compared two groups of patients ( n = 112 ) with total prosthesis implanted in their knee . The group I consisted of the patients who received the transfusion of other people 's ( allogeneic ) blood ( n = 57 ) and the group II of the patients whose blood was collected postoperatively and then given them [ their own ( autologous ) blood ] ( n = 55 ) . The transfusion trigger for both groups was hemoglobin level of 85 g/L. RESULTS In the group of patients whose blood was collected perioperatively only 9 ( 0.9 % ) of the patients received transfusion of allogeneic blood , as opposed to the control group in which 98.24 % of the patients received the transfusion of allogeneic blood ( p stayed in hospital for 6.18 days , while the patients of the control group stayed 7.67 days ( p Autologous blood transfusion is a very effective method for reducing consumption of allogenic blood and thus , indirectly for reducing all complications related to allogenic blood transfusion . There is also a positive influence on postoperative recovery after total knee replacement surgery due to the reduction of hospital stay , and indirectly on the reduction of hospital costs", "Background Total hip replacement ( THR ) is associated with a significant perioperative blood loss , and 30–50 % of these patients receive allogeneic blood transfusion ( ABT ) . We evaluated the clinical utility of washed shed blood ( WSB ) return to reduce ABT in THR patients . Study design and methods Data from 108 consecutive THR patients were prospect ively collected . WSB salvage and reinfusion ( OrthoPAT ) was intended for 60 ( Reinfusion group ) , whereas the remaining 48 patients served as control group . Patients received ABT if haemoglobin the ABT rate ( 48 vs. 15 % , for control and reinfusion groups , respectively ; P = 0.001 ) and the ABT index ( 371 ± 154 ml RBC vs. 53 ± 117 ml RBC , respectively ; P = 0.001 ) , without differences between cemented and uncemented THR . In addition , patients from reinfusion group showed a trend to lower postoperative infection rate ( 10 vs. 2 % , respectively ; P = 0.086 ) . Conclusions Perioperative salvage and return of WSB in THR seems to effectively reduce the requirements for ABT . However , for patients with preoperative Hb , some additional blood saving method should be associated to WSB return", "BACKGROUND Unilateral total knee replacement ( TKR ) results in a substantial blood loss and 30 to 50 percent of patients receive allogeneic blood transfusion ( ABT ) . Therefore , the effectiveness of a restrictive transfusion trigger ( hemoglobin [ Hb ] level in TKR patients . STUDY DESIGN AND METHODS A series of 139 consecutive of primary TKR patients received perioperative iron sucrose ( 2 x 200 mg/48 hr , intravenously [ IV ] ) , plus preoperative erythropoietin ( EPO ; 1 x 40.000 UI , sc ) if preoperative Hb level was less than 130 g per L ( Group A ) . This protocol was applied to another series of 173 consecutive TKR patients who also received postoperative unwashed shed blood ( USB ) if preoperative Hb level was less than 130 g per L ( Group B ) . Perioperative clinical and laboratory data were gathered . RESULTS No adverse effects of iron sucrose , EPO , or USB administration were witnessed , and only 13 patients received ABT overall ( 4 % ) . No major differences in perioperative blood counts or iron metabolism variables were observed between groups , but stimulation of erythropoiesis seemed to be more pronounced in those patients receiving EPO ( p postoperative complications between groups , but length of hospital stay for patients with a preoperative Hb level of less than 130 g per L was shorter in Group B ( p ABT in TKR patients . Which patients are more likely to benefit from either perioperative iron administration or selective addition of postoperative blood salvage to pharmacologic treatment , however , needs to be further evaluated", "BACKGROUND The purpose of this study was to assess current practice s in blood management in elective orthopedic surgery in Europe . STUDY DESIGN AND METHODS For this 225-center prospect i ve survey , data were collected on 3996 patients . Actual perioperative blood loss was compared to preoperative estimates . Differences in Hb levels and other outcome variables for patients receiving allogeneic versus autologous transfusions were evaluated . The probability of allogeneic transfusion based on selected predictor variables was estimated . RESULTS A total of 2640 ( 67 % ) hip and 1305 ( 33 % ) knee arthroplasty patients were evaluated . Estimated blood loss ( median , 750 mL ) was significantly lower than computed blood loss ( median , 1944 mL ) . A total of 2762 ( 69 % ) patients received transfusions , including 1393 ( 35 % ) autologous-only and 1024 ( 25 % ) allogeneic-only . The probability of allogeneic transfusion decreased with increasing baseline Hb , but differentially so for men and women . Transfusion triggers were Hb levels of 8.93 + /- 1.83 g per dL for allogeneic transfusions , and 21 percent of these occurred when the Hb level was greater than 10 g per dL. Autologous blood transfusion was associated with a significantly lower rate ( 1 % ) of wound infections than allogeneic blood transfusion ( 4.2 % ) . CONCLUSION Accurate assessment of preoperative Hb levels , better estimation of perioperative blood loss , efficient use of autologous blood , adherence to transfusion guidelines , and pharmacologic alternatives contribute to effective and comprehensive blood and anemia management", "BACKGROUND Immunosuppression after major surgery increases the risk of infections . Natural killer cells play a pivotal part in defence against infection . We aim ed to investigate the immunomodulatory effects of different types of postoperative blood transfusion by use of a new assay for measuring the frequency of peripheral blood natural killer precursor cells ( NKpf assay ) . METHODS We measured the natural killer cell precursor ( NKp ) frequency before and 5 days after surgery in 120 patients undergoing joint replacement surgery . The patients were assigned to one of five groups according to the type of transfusion received : non-transfused ( n=32 ) , allogeneic non-leukodepleted blood ( eight ) , allogeneic leukodepleted blood ( 30 ) , autologous predeposited blood ( ten ) , and autologous salvaged blood collected within the first 24 h after surgery ( 40 ) . We also measured interferon gamma and interleukin 10 concentrations before and after surgery . FINDINGS The mean postoperative NKp frequency for all patients was lower than the preoperative values , except in patients receiving autologous salvaged blood , which was higher than all other groups ( p Postoperative NKp frequencies for patients receiving allogeneic or autologous predeposited blood responded similarly ( p=0.99 ) , but these patients had lower NKp frequencies than did the non-transfused group ( p Postoperative interferon gamma concentrations were higher in the autologous salvaged blood group ( p Interleukin 10 concentrations were similar across all groups ( p=0.49 ) . INTERPRETATION Immunosuppression associated with surgery and blood loss was reflected in a reduced frequency of NKp and decreased interferon gamma . This immunosuppression was reversed by transfusion of autologous salvaged blood , suggesting that this fluid contained immunostimulants", "To determine the safety , efficacy and user-friendliness of two different postoperative autologous blood re-infusion systems , an open , r and omized , controlled study was performed . Eligible consecutive primary and revision total hip and knee replacement patients were r and omized for one of the two systems or for a control group in which shed blood was not re-infused . The nursing staff scored user-friendliness . Patients were monitored after re-infusion . In all three patient groups , a restrictive transfusion trigger was used . Sixty-nine of 70 r and omized patients were evaluated . Ease of use , efficacy and safety of both re-infusion systems were comparable . There was no difference in allogeneic blood use between the groups . Thirty per cent of the patients re-infused with autologous blood developed a mainly mild , febrile transfusion reaction . No other adverse reactions were seen . Signs of coagulopathy after re-infusion were not found . In multivariate analysis , autologous re-infusion was an independent factor associated with a shorter hospital stay . Both postoperative autologous blood re-infusion systems were of equal efficacy and safety . The contribution of autologous wound blood re-infusion to reduce allogeneic transfusions must be investigated in a larger study", "The purpose of our study was to determine the effectiveness of a postoperative autologous blood reinfusion system as an alternative to homologous , banked blood transfusions in total knee arthroplasty . We carried out a prospect i ve r and omised controlled study on 60 patients having unilateral total knee replacements . In all these patients , the same surgical team applied the same surgical technique , and all patients followed the same rehabilitation program . In 30 of these patients ( group A ) , a reinfusion system of unwashed salvaged blood was applied , and they were supplemented postoperatively with banked blood transfusions when required . A control group of 30 patients ( group B ) , in whom st and ard suction drains were used , received one unit of homologous banked blood transfusion intraoperatively and additional blood transfusions postoperatively when required . The administration of banked blood transfusion was determined by the haemoglobin value ( blood pressure , pulse , etc . ) . The values of haemoglobin , haematocrit and platelets were recorded preoperatively and the first , fifth and 15th postoperative days , respectively . Five patients of group A required nine units of homologous blood ( 0.3 units/patient ) postoperatively . Ten patients of group B required an additional 15 banked blood units postoperatively ( in total 45 banked blood units for group B ; 1.5 units/patient ) . In the study group , the total homologous blood requirements were reduced by 80 % , while the postoperative blood requirements were reduced by 50 % . There was no significant difference in the postoperative haematocrit and haemoglobin values between the two groups . The cost of the blood management in the study group was reduced by 36 % . The use of an autologous blood reinfusion system reduces highly effectively the dem and s of homologous banked blood transfusion in total knee arthroplasty . RésuméLe but de cette étude était de déterminer l’efficacité d’un système de réinjection post-opératoire de sang autologue comme alternative à la transfusion homologue dans l’arthroplastie totale de genou . Nous avons fait une étude prospect i ve r and omisée sur 60 patients opérés d’une prothèse totale du genou unilatérale . Chez 30 patients ( groupe A ) un système de réinjection sans lavage du sang préservé était utilisé avec supplémentation post-opératoire par du sang de banque si nécessaire . Un groupe de contrôle de 30 patients ( groupe B ) , chez qui un drainage aspiratif classique était utilisé , recevait une unité de sang homologue pendant l’intervention et des transfusions post-opératoires si nécessaire . L’indication de transfusion homologue était posé sur un taux d’hémoglobine 5 patients du groupe A eurent besoin après l’opération de 9 unités de sang homologue ( 0,3 unité par patient ) . 10 patients du groupe B eurent besoin de 15 unités supplémentaires de sang homologue après l’opération ( au total 45 unités de sang homologue pour le groupe B ; 1,5 unités par patient ) . Dans le groupe étudié la nécessité globale de sang homologue était réduite de 80 % et la nécessité de transfusion post-opératoire de 50 % . Le coût de la gestion du sang était réduite de 36 % dans le groupe étudié . l’utilisation d’un système de réinjection du sang autologue réduit significativement la nécessité de transfusion homologue dans l’arthroplastie totale du genou", "Introduction In patients undergoing total knee replacement ( TKR ) , most of the measured blood loss occurs during the postoperative period , and 30–50 % of these patients receive allogeneic blood transfusion ( ABT ) . For this reason , the salvage and return of unwashed filtered shed blood ( USB ) from postoperative drainage may represent an alternative to ABT in these patients . We have , therefore , evaluated the clinical utility of USB return in TKR patients , with a special focus on patients with mild anaemia . Material s and methods Data from 200 TKR patients ( group 2 ) receiving USB within the first 6 postoperative hours ( ConstaVac CBC II , Sryker ) were prospect ively collected . A retrospective series of 100 TRK patients served as the control group ( group 1 ) . Results USB return was possible in 162 patients who received a mean of 0.98±0.4 U/pte , without any clinical ly relevant incident . Return of USB decreased both the percentage of patients with ABT ( 48 % vs 11 % , for groups 1 and 2 , respectively ; p the ABT units/patient index ( 1.31±1.27 vs 0.29±0.87 units/patient , respectively ; p transfusion protocol was not established , but there was no difference between groups with respect to either perioperative Hb levels or overall transfusion index , indicating that the transfusion criteria were uniform . However , for the subgroups of patients who needed ABT , the preoperative Hb level was 1 g/dL lower in those receiving USB ( 13.4±1.4 vs 12.4±1.2 g/dL ; p in the postoperative complication rate , and patients in group 2 recovered the ability to walk 1 day earlier , and their hospital stay was 3 days shorter than in group 1 ( p shorten the hospital stay and effectively reduce postoperative requirements for ABT , especially in patients with preoperative Hb > 13 g/dL. For patients with preoperative Hb the requirements for ABT , a further reduction will probably be obtained with the addition of another blood-saving method", "Introduction Joint replacement is associated with massive blood loss . Various techniques have been used to avoid the use of allogeneic blood . One of the techniques used is postoperative salvage and reinfusion of shed blood that was found to reduce the use of banked blood with its potential risk . Material s and methods We prospect ively studied 365 patients who underwent knee joint replacement ( TKR ) and were divided in two groups . Group A ’s shed blood ( SureTrans System ) was collected ( n=194 ) and reinfused and group B ’s was not ( n=171 , “ controls ” ) . Hemoglobin levels before and after the operation were recorded . Results Allogeneic blood requirement for TKR decreased by 65 % in group A compared to group B. The packed cell/patient index dropped from 0.91 to 0.29 in group 2A . Statistical analysis yielded the odds ratio for blood replacement , a “ predicting formula ” for blood replacement depending on hemoglobin levels , and a cutoff point for a patient ’s receiving blood replacement . Conclusion We recommend using this system in TKR for decreasing allogeneic blood replacement and potential associated risks . The predicting formula for blood replacement may be a helpful tool when making a decision of whether or not to use the collector system and for whom", "BACKGROUND A before and after study was undertaken to investigate the effect of universal leukoreduction ( ULR ) in the UK on postoperative length of hospital stay ( LOS ) and infections . STUDY DESIGN AND METHODS Consecutive patients undergoing elective coronary artery bypass grafting or total hip and /or knee replacement in 11 hospitals received non-WBC-reduced RBCs before implementation of ULR ( T1 , n=997 ) or WBC-reduced RBCs after implementation of ULR ( T2 , n=1098 ) . RESULTS Patients in T1 and T2 were comparable except patients in T2 received on average more units of RBCs but had lower discharge Hct levels . Postoperative LOS ( T1 , 10 + /- 8.9 days ; T2 , 9.6 + /- 6.9 days ) and the proportion of patients with suspected and proven postoperative infections ( T1 , 21.0 % ; T2 , 20.0 % ) were unchanged before and after ULR ( LOS , hazard ratio 1.01 , 95 % CI 0.92 - 1.10 ; infections , OR 0.83 , 95 % CI 0.77 - 1.02 ) . Subgroup analysis showed no significant interaction between storage age or dose of blood on responsiveness of primary outcomes to ULR . Secondary outcomes were unchanged overall . Analysis by surgical procedure gave conflicting results with both increased mortality ( p=0.031 ) and an increased proportion of cardiac patients with proven infections ( p=0.004 ) , whereas the proportion of orthopedic patients with proven infections was reduced ( p=0.002 ) after ULR . CONCLUSION Implementation of ULR had no major impact on postoperative infection or LOS in patients undergoing elective surgical procedures who received transfusion(s ) . Smaller effects , either detrimental or beneficial of ULR , can not be excluded", "We prospect ively r and omised 104 consecutive patients undergoing primary cemented total knee arthroplasty into two groups of 52 patients each , with one group to receive a st and ard suction drain ( Redivac ) and the other , an autologous transfusion drain ( Bellovac ) . R and omisation was achieved using the software programme MINIM , which was set to r and omly allocate patients to either of the two groups based on their age , sex and body mass index ( BMI ) . All procedures were performed under pneumatic tourniquet . Drains were released in the recovery room 20 min after surgery and removed 24 h following surgery . Blood collected in the st and ard suction drain ( control group ) was discarded , while blood collected in the autologous transfusion drains ( study group ) was transfused unwashed back to the patient within 6 h of collection . Thirteen patients ( 25 % ) in the study group had two or more units of homologous blood transfused in addition to the blood collected postoperatively and re-transfused ( average : 438 ml ) . Twelve patients ( 23 % ) in the control group had two or more units of homologous blood transfused . No sepsis , transfusion reactions or coagulopathies were associated with the autologous blood transfused in the study group . The use of the autologous transfusion system ( Bellovac ) proved to be safe but failed to reduce the need for postoperative homologous blood transfusion following uncomplicated total knee arthroplasty . RésuméNous avons étudié , de façon prospect i ve r and omisée , 104 patients consécutifs ayant bénéficié d’une prothèse totale du genou cimentée . Chaque patient a reçu soit un drain aspiratif st and ard ( Redivac ) soit un drain permettant une retransfusion ( Bellovac ) . 52 patients ont été r and omisés dans chaque groupe à l’aide d’un programme software avec une excellente concomitance entre l’âge , le sexe et le BMI . Toutes les interventions ont été réalisées avec garrot . Les drains ont été mis en aspiration en salle de réveil , 20 minutes après la fin de l’acte chirurgical . Ces drains ont été ôtés 24 heures après la chirurgie . Le sang collecté dans le drain st and ard a été rejeté alors que le drain Bellovac a permis de récupérer le sang , le retransfuser sans lavage six heures après l’intervention . 39 patients ( 25 % ) dans le groupe st and ard ont eu deux , ou plus de deux , unités sanguines de transfusion en plus du sang récupéré dans le drain ( 438 ml en moyenne ) . 12 patients ( 23 % ) dans le groupe contrôle ont eu deux , ou plus de deux , transfusions . Il n’y a pas eu d’infection , de réaction sanguine après ré-infusion du sang du redon . L’utilisation d’un système de réutilisation du sang de type Bellovac n’entraîne pas de problèmes particuliers mais il ne permet pas de diminuer la nécessité de transfusions post-opératoires après une prothèse totale du genou st and ard sans complication", "Background : Oral iron therapy is often used after orthopaedic surgery to improve haemoglobin levels . The aim of the present trial was to determine if administration of oral iron after orthopaedic surgery results in a better improvement of haemoglobin levels than a control treatment", "A controlled , r and omized , prospect i ve study was performed evaluating the need for perioperative blood salvage for primary total hip arthroplasty patients who had donated autologous blood before surgery . One hundred fifty-three patients able to donate at least 2 units of autologous blood were divided into four groups . In group 1 ( 35 patients ) , intraoperative and postoperative Cell-Saver ( Haemonetics , Braintree , MA ) was employed . In group 2 ( 40 patients ) , a postoperative Solcotrans ( Smith & Nephew Richards , Memphis , TN ) reinfusion protocol was followed . In group 3 ( 40 patients ) , a closed-suction Hemovac drain ( Zimmer , Warsaw , IN ) was placed . In group 4 , ( 38 patients ) , no drain was used . Decisions for transfusion were based on clinical and laboratory parameters and made in conjunction with medical consultation . All autologous blood was routinely reinfused . There was no statistically significant difference in transfusion requirements or wound complications among the four groups . Hemoglobin and hematocrit changes between groups also were not statistically significant , but a power test suggested insufficient patient numbers for absolute reliability of this observation . Only five patients ( 3.3 % ) in this study received homologous blood . Four of these patients were in the Solcotrans group and one was in the Cell-Saver group . Two reoperations were performed : one for hematoma ( Solcotrans group ) and one for a sewn-in drain . It is concluded that expensive perioperative blood salvage techniques are usually not needed in patients who have a primary total hip arthroplasty without cement and who have donated 2 units of blood before operation ", "We prospect ively r and omized 415 total joint replacements for either a closed wound-drainage system or no postoperative drainage . Drainage was not used in 200 total joint replacements , of which 138 were total knee replacements and sixty-two , total hip replacements . Drainage was used in 215 total joint replacements , of which 137 were total knee replacements and seventy-eight , total hip replacements . All patients were evaluated for the presence of excessive postoperative drainage that necessitated cessation of the range-of-motion exercises , the amount of transfused blood ( homologous and autologous ) , and the preoperative and postoperative hemoglobin levels . The range of motion was assessed daily in the patients who had a total knee replacement . No statistical difference was found in the number of patients who had excessive postoperative drainage from a drained or non-drained wound . There was also no statistical difference with respect to the amount of transfused blood and the preoperative and postoperative hemoglobin levels . Furthermore , in the patients who had a total knee replacement , there were no statistical differences between drained and non-drained wounds with respect to the daily range of motion during the first seven days postoperatively . The mean amount of blood transfused was 157 milliliters in the total knee replacements with drains , 160 milliliters in the total knee replacements without drains , 188 milliliters in the total hip replacements with drains , and ninety-three milliliters in the total hip replacements without drains . ( ABSTRACT TRUNCATED AT 250 WORDS", "We undertook a prospect i ve , r and omised study in order to evaluate the efficacy of clamping the drains after intra-articular injection of saline with 1:500 000 adrenaline compared with post-operative blood salvage in reducing blood loss in 212 total knee arthroplasties . The mean post-operative drained blood volume after drain clamping was 352.1 ml compared to 662.3 ml after blood salvage ( p Allogenic blood transfusion was needed in one patient in the drain group and for three in the blood salvage group . Drain clamping with intra-articular injection of saline with adrenaline is more effective than post-operative autologous blood transfusion in reducing blood loss during total knee arthroplasty", "We determined interleukin-6 ( IL-6 ) concentrations in collected shed drainage blood intended for retransfusion in a prospect i ve study in 81 patients after total knee replacement . We found large increases in IL-6 levels , averaging 6.5 ( SD 3.9 ) ng/mL , in shed blood collected in the first 6 postoperative hours . 3 patients had febrile reactions after collected blood was retransfused . The IL-6 levels in the drainage blood of these patients were very high ( 9.6 - 13.4 ng/mL ) . In the blood collected after 6 hours , IL-6 concentrations increased to 47 ( SD 33 ) ng/mL ( p interleukin-6 concentrations in shed drainage blood and the occurrence of febrile reactions after retransfusion of such blood", "Aim The aim of this study was to evaluate the efficacy of two different autotransfusion methods in total knee replacement ( TKR ) performed without tourniquet , in comparison to allogeneic blood transfusion ( ABT ) only . Method In a comparative study , 248 patients with knee osteoarthritis were r and omized in three groups : in control Group 85 the patients underwent only ABT post-operatively , in Group 1 ( n:92 ) an intraoperative and postoperative autotransfusion were utilized , and in Group 2 ( n:71 ) only a postoperative autotransfusion was applied . Post-operative ABT was utilized according to predetermined criteria . Results Comparing Group 0 to Group 1 and 2 the difference in need for ABT post-operatively was statistically highly significant ( p auto-transfusion reduces the need for ABT in TKR performed without tourniquet", "BACKGROUND This study was design ed to obtain data on the incidence of postoperative infection in patients undergoing elective orthopedic surgery and receiving white blood cell (WBC)-filtered blood components prepared according to current st and ards . STUDY DESIGN AND METHODS A total of 308 consecutive orthopedic patients who opted for preoperative autologous blood donation ( PAD ) for primary unilateral hip and knee replacement surgery were enrolled in a prospect i ve observational study of the incidence of postoperative infection . Patients with contraindications for PAD or with any infectious disease were not included in the study . To identify probably confounding factors , differences between patient groups were analyzed first . Identified factors , which differed between groups , and variables describing blood supply were further tested in uni- and multivariate logistic regression analysis for their independent influence on development of postoperative infection . Infection rates were compared on the basis of actual transfusion groups . RESULTS Of the 308 study patients , 101 were not transfused , 85 received their PAD , 100 received allogeneic WBC-filtered red blood cells ( RBCs ) , and 22 were given autologous RBCs and additionally allogeneic WBC-filtered RBCs . Overall the infection rate was 6.82 percent ( 21/308 ) . Infection rates varied significantly between transfusion groups ( no transfusion , 6.9 % ; autologous RBCs , 1.2 % ; allogeneic WBC-filtered RBCs , 12.0 % ; both transfusion types , 4.6 % ; p = 0.03 ) . Allogeneic recipients showed significantly more infections compared to autologous recipients ( p = 0.0053 ) . Multivariate regression analysis confirmed transfusion of allogeneic WBC-filtered RBCs as an independent variable predicting postoperative infection ( odds ratio , 23.65 ; confidence interval , 1.3 - 422.1 ; p = 0.01 ) . CONCLUSION Differences in postoperative infection rates between allogeneic and autologous recipients are still observable , although universal WBC filtration has been introduced into clinical practice", "We have carried out a r and omised , controlled trial on 70 patients having unilateral total knee replacement in which transfusion was either with homologous bank blood or by reinfusion of unwashed blood salvaged after operation . No complications or adverse effects were observed from reinfusion . The need for bank blood was reduced by 86 % in the reinfusion group but , more importantly , the number of infective episodes was significantly less when the use of bank blood was avoided . The mean length of stay in hospital was also reduced by more than two days", "We undertook a prospect i ve r and omised controlled trial to investigate the efficacy of autologous retransfusion drains in reducing the need for allogenic blood requirement after unilateral total knee replacement . We also monitored the incidence of post-operative complications . There were 86 patients in the control group , receiving st and ard care with a vacuum drain , and 92 who received an autologous drain and were retransfused postoperatively . Following serial haemoglobin measurements at 24 , 48 and 72 hours , we found no difference in the need for allogenic blood between the two groups ( control group 15.1 % , retransfusion group 13 % ( p = 0.439 ) ) . The incidence of post-operative complications , such as wound infection , deep-vein thrombosis and chest infection , was also comparable between the groups . There were no adverse reactions associated with the retransfusion of autologous blood . Based on this study , the cost-effectiveness and continued use of autologous drains in total knee replacement should be question ed", "Purpose : To determine whether salvaged autologous blood collected postoperatively contains complement split products ( SC5b-9 ) , and pro-inflammatory cytokines ( IL-6 and IL-8 ) and whether there are any differences between blood collected during hip or knee surgery . Methods : Fifty-eight consecutive patients undergoing hip or knee replacement surgery were studied . Thirty-eight had postoperative bleeding large enough to require infusion of salvaged blood . The salvaged blood was filtered during collection through a 200 µm filter and before infusion a 40 µm filter was used . Sample s for complement and cytokine determinations were drawn from the circulation and from the collected blood . Results : High concentrations of SC5b-9 , IL-6 , and IL-8 were found in salvaged blood . The concentrations were higher than in the circulation ( P The circulating concentrations of IL-6 and IL-8 were increased 60 min and 12–18 hr after transfusion . There were no differences regarding SC5B-9 , IL-6 , and IL-8 in the blood collected after hip or knee surgery . Conclusion : Blood collected from a surgical wound contains large concentrations of inflammatory mediators . There were no differences between blood collected during hip or knee surgery . RésuméObjectif : Déterminer si la récupération postopératoire de sang autologue contient des produits de dégradation du complément ( SC 5b-9 ) et des cytokines pro-inflammatoires ( IL-6 et IL-8 ) , et s’il y a des différences avec le sang prélevé pendant l’opération de la hanche ou du genou . Méthode : L’étude a porté sur 58 patients successivement admis pour la mise en place d’une prothèse de hanche ou du genou . Chez 38 d’entre eux , les pertes sanguines postopératoires ont été assez importantes pour nécessiter la transfusion de sang récupéré . Ce sang a été filtré pendant le prélèvement avec un filtre de 200 µm et avant la transfusion avec un filtre de 40 µm . Des échantillons retenus de la circulation et du sang récupéré ont servi à déterminer la cytokine et le complément . Résultats : De fortes concentrations de SC5B-9 , IL-6 et IL-8 ont été trouvées dans le sang récupéré . Elles étaient plus élevées que celles de la circulation ( P concentrations circulantes de IL-6 et de IL-8 ont augmenté 60 min et 12–18 h après la transfusion . Aucune différence n’a été enregistrée concernant les SC5b-9 , IL-6 et IL-8 dans le sang prélevé après l’opération de hanche ou du genou . Conclusion : Le sang prélevé au site d’incision chirurgicale contient de gr and es concentrations de médiateurs de l’inflammation . Ce sang ne présente pas de différence avec celui qui est prélevé pendant une opération de hanche ou du genou", "We prospect ively r and omised 100 patients undergoing cemented total knee replacement to receive either a single deep closed-suction drain or no drain . The total blood loss was significantly greater in those with a drain ( 568 ml versus 119 ml , p blood into the dressings ( 55 ml versus 119 ml , p postoperative swelling or pain score , or in the incidence of pyrexia , ecchymosis , time at which flexion was regained or the need for manipulation , or in the incidence of infection at a minimum of five years after surgery in the two groups . We have been unable to provide evidence to support the use of a closed-suction drain in cemented knee arthroplasty . It merely interferes with mobilisation and complicates nursing . Reinfusion drains may , however , prove to be beneficial", "BACKGROUND Allogeneic blood transfusions are associated with a number of well-recognized risks and complications . Postoperative retransfusion of filtered shed blood is an alternative to ( reduce ) allogeneic blood transfusion . The objectives of this study were to evaluate the clinical efficacy of retransfusion of filtered shed blood and to evaluate the complications , in particular febrile reactions . STUDY DESIGN AND METHODS In this clinical trial 160 patients undergoing primary total hip or knee replacement were r and omly assigned to receive either a retransfusion system ( Bellovac , AstraTech AB ) or a regular drain ( Abdovac , AstraTech AB ) . Patients with a preoperative hemoglobin ( Hb ) level of between 13.0 and 14.6 g per dL were included . The shed blood was returned 6 hours after operation . After surgery the anesthesiologist determined the transfusion trigger . When Hb level dropped below this trigger , an allogeneic blood transfusion was given . The following data were obtained : number of allogeneic blood transfusions , total volume of blood collected in the bag used for retransfusion , perioperative Hb levels , febrile reaction , and other complications . RESULTS In the control group 19 percent of the patients received at least one allogeneic blood transfusion . In the study group this percentage was 6 percent of the patients ( p = 0.015 ) . Comparing total knee and total hip arthroplasty ( control vs. study ) the percentages were , respectively , 16 percent versus 2 percent ( p = 0.040 ) and 21 percent versus 11 percent ( NS ) . On average 308 mL of filtered shed blood was retransfused in the study group . In the study group 18 percent of patients had febrile reactions compared to 20 percent in the control group . CONCLUSION Postoperative retransfusion of filtered shed blood is effective for decreasing allogeneic blood transfusions after total hip and knee arthroplasty . There was no relationship between retransfusions and postoperative febrile reactions", "BACKGROUND Total knee arthroplasty ( TKA ) or total hip arthroplasty ( THA ) regularly results in postoperative requirement of blood transfusion . Because of the disadvantages of allogeneic blood transfusion ( ABT ) such as the risk of transfusion-associated infections , incompatibility-related transfusion fatalities , or immunomodulatory effects , a continuing effort to reduce allogeneic blood transfusion is important . For this purpose , the effect of reinfusion of drain blood , via a postoperative wound drainage and reinfusion system , on the need for allogeneic blood transfusion was evaluated . STUDY DESIGN AND METHODS Using a prospect i ve observational quality assessment design , we compared 135 patients scheduled for TKA or THA with a historic group of 96 patients . In the study group the Bellovac ABT autotransfusion system was used . The shed blood was returned either when 500 mL were collected or at most 6 hours after surgery . Compared were the preoperative , postoperative , and discharge hemoglobin , as well as the number of allogeneic blood transfusions . RESULTS There were no statistical differences between preoperative , postoperative , and discharge hemoglobin levels . Autologous transfusion reduced the number of patients receiving ABT overall from 35 percent ( control ) to 22 percent ( study ) . The decrease of allogeneic transfusion requirement was most significant after TKA : from 18 percent to 6 percent ( p Bellovac ABT device reduces allogeneic blood transfusions in TKA and THA", "One hundred thirty-six primary total knee arthroplasty patients were r and omized for the use of closed-suction , nonreinfusable wound drains . Blood loss was identical in the drained and undrained groups . Forty percent of undrained wounds compared with 0 % of drained wounds required dressing reinforcement . Sixty-nine percent of undrained wounds compared with 39 % of drained wounds developed ecchymosis , measuring 92 cm2 in the undrained group and 28 cm2 in the drained group . This study concludes that a simple wound drain effectively minimizes the undesirable accumulation of blood in the surrounding soft tissues and the postoperative wound dressing after total knee arthroplasty", "OBJECTIVES Definitive evidence that red blood cell transfusion improves outcome after vascular surgery is lacking . The aims of the study were to determine , among stable consecutive patients who underwent elective major vascular surgery , ( 1 ) the association between postoperative transfusion and 30-day death , myocardial infa rct ion , and both , and ( 2 ) and if this association differs according to the presence of postoperative anaemia ( haemoglobin value less than 9.0 g/dL within 7 days after surgery ) . METHODS A retrospective observational study was conducted on 359 patients prospect ively screened according to the ACC/AHA guidelines for preoperative risk in non-cardiac surgery . Main outcome was 30-day death ; secondary outcomes 30-day myocardial infa rct ion , and composite of 30-day myocardial infa rct ion or death . RESULTS Of the patients included , 95 ( 26.5 % ) received at least one unit of red blood cells . Patients who received transfusion had a significantly increased hazard of 30-day death ( hazard ratio [ HR ] 11.72 , 95 % confidence interval [ CI ] 3.92 - 35.10 ; p myocardial infa rct ion ( HR 3.3 , 95 % CI 1.7 - 6.1 ; p=0.0003 ) , and both ( HR 4.0 95 % CI 2.2 - 7.3 ; p risk of 30-day death ( HR 19.20 , 95 % CI 3.99 - 92.45 ; p=0.007 ) , myocardial infa rct ion ( HR 5.05 , 95 % CI 2.23 - 11.44 ; p=0.0001 ) , and both . Conversely , in patients with anaemia this association was not significant . CONCLUSIONS In patients who underwent elective major vascular surgery , perioperative transfusion was associated with a significantly increased risk of 30-day events which was more attributable to patients with lesser degree of anaemia . Our data caution against the use of liberal transfusion in stable vascular surgery patients" ]

[ "To evaluate the effects of filtering short wavelength light on visual performance under intense light conditions among pseudophakic patients previously implanted with a clear intraocular lens ( IOL ) . This was a patient-masked , r and omized crossover study conducted at 6 clinical sites in the United States between September 2013 and January 2014 . One hundred fifty-four bilaterally pseudophakic patients were recruited . Photostress recovery time and glare disability thresholds were measured with clip-on blue-light-filtering and placebo ( clear ; no blue-light filtration ) glasses worn over patients ' habitual correction . Photostress recovery time was quantified as the time necessary to regain sight of a grating target after intense light exposure . Glare disability threshold was assessed as the intensity of a white-light annulus necessary to obscure a central target . The order of filter used and test eye were r and omized across patients . Photostress recovery time and glare disability thresholds were significantly improved ( both P used blue-light-filtering glasses compared with clear , nonfiltering glasses . Compared with a nonfiltering placebo , adding a clip-on blue-absorbing filter to the glasses of pseudophakic patients implanted with clear IOLs significantly increased their ability to cope with glare and to recover normal viewing after an intensive photostress . This result implies that IOL design s with blue-light-filtering characteristics may be beneficial under intense light conditions", "Purpose This study aims to evaluate the effect of blocking short-wavelength light on critical flicker frequency ( CFF ) . Design This study is a prospect i ve clinical study . Methods Thirty-three participants ( 17 men and 16 women ; age range , 28–39 years ) were divided into 3 groups . Each group wore 1 of 3 types of lenses while performing an intensive computer task for 2 hours . To evaluate the effect of blocking short-wavelength light before and after the task , we measured the CFF and evaluated subjective question naires . We used the analysis of variance test to examine whether the type of lenses tested affected any of the visual fatigue-related parameters . Results The type of lens worn significantly affected the CFF ; however , answers to the subjective question naires did not differ significantly between the groups . Two of the 13 question items showed a statistical difference between lens transparency and increase in the CFF ( lens 3 > lens 2 > lens 1 ) . Conclusions The higher the blocking effect of the lens , the lower the reduction in the CFF , suggesting that blocking short-wavelength light can reduce eye fatigue", "& NA ; Detection and resolution thresholds for blue and yellow targets against blue , green , and yellow background s were measured while wearing yellow and blue filters . Yellow filters improved thresholds for yellow targets against blue background s. Their effectiveness decreased ( i ) as the wavelength of the background increased , ( ii ) as the size of the target decreased , and ( iii ) with the age of the observer . The blue filters were generally ineffective . The results are for the most part explained on the basis of changes in target contrast brought about by the filters . The effectiveness of yellow facemasks for divers under certain conditions is discussed", "Purpose s To evaluate the optical performance of blue-light filtering spectacle lenses and investigate whether a reduction in blue light transmission affects visual performance and sleep quality . Methods Experiment 1 : The relative changes in phototoxicity , scotopic sensitivity , and melatonin suppression of five blue-light filtering plano spectacle lenses were calculated based on their spectral transmittances measured by a spectrophotometer . Experiment 2 : A pseudo-r and omized controlled study was conducted to evaluate the clinical performance of two blue-light filtering spectacle lenses ( BF : blue-filtering anti-reflection coating ; BT : brown-tinted ) with a regular clear lens ( AR ) serving as a control . A total of eighty computer users were recruited from two age cohorts ( young adults : 18–30 yrs , middle-aged adults : 40–55 yrs ) . Contrast sensitivity under st and ard and glare conditions , and colour discrimination were measured using st and ard clinical tests . After one month of lens wear , subjective ratings of lens performance were collected by question naire . Results All tested blue-light filtering spectacle lenses theoretically reduced the calculated phototoxicity by 10.6 % to 23.6 % . Although use of the blue-light filters also decreased scotopic sensitivity by 2.4 % to 9.6 % , and melatonin suppression by 5.8 % to 15.0 % , over 70 % of the participants could not detect these optical changes . Our clinical tests revealed no significant decrease in contrast sensitivity either with ( 95 % confidence intervals [ CI ] : AR – BT [ –0.05 , 0.05 ] ; AR – BF [ –0.05 , 0.06 ] ; BT – BF [ –0.06 , 0.06 ] ) or without glare ( 95 % CI : AR – BT [ –0.01 , 0.03 ] ; AR – BF [ –0.01 , 0.03 ] ; BT – BF [ –0.02 , 0.02 ] ) and colour discrimination ( 95 % CI : AR – BT [ –9.07 , 1.02 ] ; AR – BF [ –7.06 , 4.46 ] ; BT – BF [ –3.12 , 8.57 ] ) . Conclusion Blue-light filtering spectacle lenses can partially filter high-energy short-wavelength light without substantially degrading visual performance and sleep quality . These lenses may serve as a supplementary option for protecting the retina from potential blue-light hazard . Trial Registration Clinical Trials.gov", "ABSTRACT Short wavelength absorbing filters ( SWAF 's ) have become very popular in the prescription and commercial sunglass markets . Like other chromatic filters SWAF 's have the potential to alter color vision . Performance on the Farnsworth Panel D‐15 ( D‐15 ) test was measured to determine whether any of 4 popular SWAF 's , in the form of sunglasses , produced color vision changes in 22 color normal adults . Using st and ard illuminant C , observers were tested under the following conditions : wearing no filter , a 1.0 log unit neutral density filter ( NDF ) , or one of the following SWAF 's : Corning CPF 550 ; NoIR Amber 40 % ; Blu Blocker ; and Vuarnet 4006 . In addition , the Vuarnets were tested outdoors in shaded daylight to determine the effects of increased illumination . The NDF served as the control and had no effect on D‐15 performance . Compared to it , only the Blu Blockers and Vuarnets affected D‐15 cap arrangements for these SWAF 's significantly . Blu Blocker error patterns had no predominant axis , whereas the predominant axis of errors in both Vuarnet conditions was tritan . Results of quantitative analysis performed on three factors confirmed these findings and indicated the Blu Blockers and Vuarnet SWAF 's caused moderate and moderate‐to‐severe levels of color confusion , respectively . Increasing the illumination level improved performance with the Vuarnets , but it remained significantly outside the normal range", "Purpose The purpose of this study was to determine whether subjects who wear short wavelength-blocking eyeglasses during computer tasks exhibit less visual fatigue and report fewer symptoms of visual discomfort than subjects wearing eyeglasses with clear lenses . Methods A total of 36 healthy subjects ( 20 male ; 16 female ) was r and omized to wearing no-block , low-blocking , or high-blocking eyeglasses while performing a 2-hour computer task . A masked grade r measured critical flicker fusion frequency ( CFF ) as a metric of eye fatigue and evaluated symptoms of eye strain with a 15-item question naire before and after computer use . Results We found that the change in CFF after the computer task was significantly more positive ( i.e. , less eye fatigue ) in the high-block versus the no-block ( P = 0.027 ) and low-block ( P = 0.008 ) groups . Moreover , r and om assignment to the high-block group but not to the low-block group predicted a more positive change in CFF ( i.e. , less eye fatigue ) following the computer task ( adjusted β = 2.310 ; P = 0.002 ) . Additionally , subjects wearing high-blocking eyeglasses reported significantly less feeling pain around/inside the eye ( P = 0.0063 ) , less feeling that the eyes were heavy ( P = 0.0189 ) , and less feeling that the eyes were itchy ( P = 0.0043 ) following the computer task , when compared to subjects not wearing high-blocking lenses . Conclusions Our results support the hypothesis that short-wavelength light-blocking eyeglasses may reduce eye strain associated with computer use based on a physiologic correlate of eye fatigue and on subjects ' reporting of symptoms typically associated with eye strain", "All light is not equal : blue wavelengths are the most potent portion of the visible electromagnetic spectrum for circadian regulation . Therefore , blocking blue light could create a form of physiologic darkness . Because the timing and quantity of light and darkness both affect sleep , evening use of amber lenses to block blue light might affect sleep quality . Mood is also affected by light and sleep ; therefore , mood might be affected by blue light blockade . In this study , 20 adult volunteers were r and omized to wear either blue-blocking ( amber ) or yellow-tinted ( blocking ultraviolet only ) safety glasses for 3 h prior to sleep . Participants completed sleep diaries during a one-week baseline assessment and two weeks ' use of glasses . Outcome measures were subjective : change in overall sleep quality and positive/negative affect . Results demonstrated that sleep quality at study outset was poorer in the amber lens than the control group . Two- by three-way ANOVA revealed significant ( p quality of sleep over the three weeks and experimental condition . At the end of the study , the amber lens group experienced significant ( p sleep quality relative to the control group and positive affect ( p = .005 ) . Mood also improved significantly relative to controls . A replication with more detailed data on the subjects ' circadian baseline and objective outcome measures is warranted", "PURPOSE To evaluate quantitatively the effects of tinted spectacle lenses on visual performance in individuals without visual pathology . METHODS Twenty-five subjects were assessed by measuring contrast sensitivity with and without glare . Gray , brown , yellow , green , purple , and blue lens tints were evaluated . Measurements were repeated with each lens tint and with a clear lens , and the order was counterbalanced within and between subjects . Glare was induced with a modified brightness acuity tester . RESULTS All subjects demonstrated an increase in contrast thresholds under glare conditions for all lens tints . However , purple and blue lens tints result ed in the least amount of contrast threshold increase ; the yellow lens tint result ed in the largest contrast threshold increase . CONCLUSIONS Purple and blue lens tints may improve contrast sensitivity in control subjects under glare conditions" ]

[ "BACKGROUND Vitamin B6 , or pyridoxine , plays an intrinsic role in the synthesis of certain neurotransmitters that take part in development of psychotic states . Several reports indicate that vitamin B6 may be a factor in a number of psychiatric disorders and related conditions , such as autism , Alzheimer 's disease , hyperactivity , learning disability , anxiety disorder , and depression . Moreover , there are anecdotal reports of a reduction in psychotic symptoms after vitamin B6 supplementation of psychopharmacologic treatment of patients suffering from schizophrenia or organic mental disorder . The aim of this study was to examine whether vitamin B6 therapy influences psychotic symptoms in patients suffering from schizophrenia and schizoaffective disorder . METHOD The effects of the supplementation of vitamin B6 to antipsychotic treatment on positive and negative symptoms in 15 schizophrenic and schizoaffective patients ( DSM-IV criteria ) were examined in a double-blind , placebo-controlled , crossover study spanning 9 weeks . All patients had stable psychopathology for at least 1 month before entry into the study and were maintained on treatment with their pre study psychoactive and antiparkinsonian medications throughout the study . All patients were assessed using the Positive and Negative Syndrome Scale ( PANSS ) for schizophrenia on a weekly basis . Patients r and omly received placebo or vitamin B6 , starting at 100 mg/day in the first week and increasing to 400 mg/day in the fourth week by 100-mg increments each week . RESULTS PANSS scores revealed no differences between vitamin B6- and placebo-treated patients in amelioration of their mental state . CONCLUSION Further studies with larger population s and shorter duration of illness are needed to clarify the question of the possible efficacy of vitamin B6 in treatment of psychotic symptoms in schizophrenia", "IMPORTANCE More effective treatments are needed for negative symptoms of schizophrenia , which are typically chronic , disabling , and costly . Negative symptoms have previously been associated with reduced blood folate levels , especially among patients with low-functioning variants in genes that regulate folate metabolism , suggesting the potential utility of folate supplementation . OBJECTIVES To determine whether folic acid plus vitamin B12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response . DESIGN Parallel-group , r and omized , double-blind , placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 μg of vitamin B12 . SETTING Three community mental health centers affiliated with academic medical centers in the United States . PARTICIPANTS Out patients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment . Eligible patients were 18 to 68 years old , were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more , and scored 60 or more on the Positive and Negative Syndrome Scale . INTERVENTION One hundred forty subjects were r and omized to receive daily oral folic acid plus vitamin B12 or placebo . MAIN OUTCOME MEASURES Change in negative symptoms ( Scale for the Assessment of Negative Symptoms [ SANS ] ) , as well as positive and total symptoms ( Positive and Negative Syndrome Scale ) . RESULTS Folate plus vitamin B12 improved negative symptoms significantly compared with placebo ( group difference , -0.33 change in SANS score per week ; 95 % CI , -0.62 to -0.05 ) when genotype was taken into account but not when genotype was excluded . An interaction of the 484C > T variant of FOLH1 ( rs202676 ) with treatment was observed ( P = .02 ) , where only patients homozygous for the 484 T allele demonstrated significantly greater benefit with active treatment ( -0.59 change in SANS score per week ; 95 % CI , -0.99 to -0.18 ) . In parallel , we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load ( P = .03 ) , which persisted until 8 weeks of treatment . Change in positive and total symptoms did not differ between treatment groups . CONCLUSIONS Folate plus vitamin B12 supplementation can improve negative symptoms of schizophrenia , but treatment response is influenced by genetic variation in folate absorption . These findings support a personalized medicine approach for the treatment of negative symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00611806", "OBJECTIVE Taurine is an inhibitory neuromodulatory amino acid in the central nervous system that activates the GABA- and glycine-insensitive chloride channel and inhibits the N-methyl-D-aspartate receptor . It also functions as a neuroprotective agent and has a role in neural development and neurogenesis . The aim of this study was to determine the efficacy of adjunctive taurine in improving symptomatology and cognition among patients with a DSM-IV first-episode psychotic disorder . METHODS 121 patients with first-episode psychosis , aged 18 - 25 years , attending early intervention services consented to participate in this r and omized , double-blind , placebo-controlled trial conducted from January 2007 to May 2009 . Patients taking low-dose antipsychotic medication were r and omly assigned to receive once-daily taurine 4 g or placebo for 12 weeks . The co primary outcomes were change in symptomatology ( measured by the Brief Psychiatric Rating Scale [ BPRS ] total score ) and change in cognition ( measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia [ MATRICS ] Consensus Cognitive Battery composite score ) at 12 weeks . Secondary outcomes included tolerability and safety and additional clinical and functioning measures . RESULTS 86 participants ( n = 47 taurine ; n = 39 placebo ) were included in the final analysis . Taurine significantly improved symptomatology measured by the BPRS total score ( 95 % CI , 1.8 - 8.5 ; P = .004 ) and psychotic subscale ( 95 % CI , 0.1 - 1.5 ; P = .026 ) compared to placebo . Additionally , improvements were observed in the Calgary Depression Scale for Schizophrenia ( 95 % CI , 0.1 - 3.0 ; P = .047 ) and Global Assessment of Functioning ( 95 % CI , 0.3 - 8.8 ; P = .04 ) scores . There was no group difference in composite cognitive score ( 95 % CI , -1.7 to 1.0 ; P = .582 ) . A significant group difference was found on one safety and tolerability item ( psychic item 2 , asthenia/lassitude/increased fatigability ) of the Udvalg for Kliniske Undersogelser , with the taurine group showing a more favorable outcome ( P = .006 ) . CONCLUSIONS Adjunctive taurine did not improve cognition , but it appears to improve psychopathology in patients with first-episode psychosis . The use of taurine warrants further investigation in larger r and omized studies , particularly early in the course of psychosis . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00420823", "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 : Zinc can modulate fast-excitatory transmission , facilitate the release of amino butyric acid and potentiate nicotinic acetylcholine receptors . There are also emerging evidence s discussing the implication of these neurotransmitters in pathophysiology of schizophrenia . Objectives : The purpose of this study was to evaluate the efficacy of Zn sulfate as an add-on therapy in the treatment of schizophrenia in a 6-week , double-blind and placebo-controlled trial . Patients and Methods : Eligible participants were 30 in patients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision criteria . Patients were r and omly allocated into two equal groups ; one group of patients received risperidone 6 mg/day plus capsules of Zn sulfate ( each containing 50 mg elemental Zn ) three times a day and another group received risperidone 6 mg/day plus placebo . The Positive and Negative Syndrome Scale ( PANSS ) was applied to assess the psychotic symptoms and aggression risk at baseline , week 2 , 4 , and 6 of the study . Results : The results of this study showed that both protocol s significantly decreased the scores on all subscales of the PANSS and supplemental aggression risk subscale as well as PANSS total score over the study . However , this improvement was significantly higher in Zn sulfate receiving group compared to the placebo group . No major clinical side-effects were detected . Conclusions : It may be concluded that Zn is an effective adjuvant agent in the management of patients with schizophrenia", "Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia . We examined the clinical effect of adding an omega-3 fatty acid and /or vitamins E+C to antipsychotics . It was hypothesized that lower baseline levels of polyunsaturated fatty acids ( PUFAs ) would predict more benefit from the add-on treatment . The trial had a multicenter , r and omized , double-blind , placebo-controlled 2 × 2 factorial design . Patients aged 18–39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway . They received active or placebo ethyl-eicosapentaenoate ( EPA ) 2 g day−1 and active or placebo vitamin E 364 mg day−1+vitamin C 1000 mg day−1 ( vitamins ) for 16 weeks . The main outcome measures were Positive and Negative Syndrome Scale ( PANSS ) total and subscales scores , analyzed by linear mixed models . Ninety-nine patients were included . At baseline , erythrocyte PUFA were measured in 97 subjects . Given separately , EPA and vitamins increased drop-out rates , whereas when combined they did not differ from placebo . In low PUFA patients , EPA alone impaired the course of total PANSS ( Cohen ’s d=0.29 ; P=0.03 ) and psychotic symptoms ( d=0.40 ; P=0.003 ) , especially persecutory delusions ( d=0.48 ; P=0.0004 ) . Vitamins alone impaired the course of psychotic symptoms ( d= 0.37 ; P=0.005 ) , especially persecutory delusions ( d=0.47 ; P=0.0005 ) . Adding vitamins to EPA neutralized the detrimental effect on psychosis ( interaction d=0.31 ; P=0.02 ) . In high PUFA patients , there were no significant effects of trial drugs on PANSS scales . In conclusion , given separately during an acute episode , EPA and vitamins E+C induce psychotic symptoms in patients with low levels of PUFA . Combined , these agents seem safe", "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 Brain glutathione levels are decreased in schizophrenia , a disorder that often is chronic and refractory to treatment . N-acetyl cysteine ( NAC ) increases brain glutathione in rodents . This study was conducted to evaluate the safety and effectiveness of oral NAC ( 1 g orally twice daily [ b.i.d . ] ) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period . METHODS A r and omized , multicenter , double-blind , placebo-controlled study . The primary readout was change from baseline on the Positive and Negative Symptoms Scale ( PANSS ) and its components . Secondary readouts included the Clinical Global Impression ( CGI ) Severity and Improvement scales , as well as general functioning and extrapyramidal rating scales . Changes following a 4-week treatment discontinuation were evaluated . One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were r and omized ; 84 completed treatment . RESULTS Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [ -5.97 ( -10.44 , -1.51 ) , p = .009 ] , PANSS negative [ mean difference -1.83 ( 95 % confidence interval : -3.33 , -.32 ) , p = .018 ] , and PANSS general [ -2.79 ( -5.38 , -.20 ) , p = .035 ] , CGI-Severity ( CGI-S ) [ -.26 ( -.44 , -.08 ) , p = .004 ] , and CGI-Improvement ( CGI-I ) [ -.22 ( -.41 , -.03 ) , p = .025 ] scores . No significant change on the PANSS positive subscale was seen . N-acetyl cysteine treatment also was associated with an improvement in akathisia ( p = .022 ) . Effect sizes at end point were consistent with moderate benefits . CONCLUSIONS These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia", "BACKGROUND There is evidence that offenders consume diets lacking in essential nutrients and this could adversely affect their behaviour . AIMS To test empirically if physiologically adequate intakes of vitamins , minerals and essential fatty acids cause a reduction in antisocial behaviour . METHOD Experimental , double-blind , placebo-controlled , r and omised trial of nutritional supplements on 231 young adult prisoners , comparing disciplinary offences before and during supplementation . RESULTS Compared with placebos , those receiving the active capsules committed an average of 26.3 % ( 95 % CI 8.3 - 44.33 % ) fewer offences ( P=0.03 , two-tailed ) . Compared to baseline , the effect on those taking active supplements for a minimum of 2 weeks ( n=172 ) was an average 35.1 % ( 95 % CI 16.3 - 53.9 % ) reduction of offences ( P placebos remained within st and ard error . CONCLUSIONS Antisocial behaviour in prisons , including violence , are reduced by vitamins , minerals and essential fatty acids with similar implication s for those eating poor diets in the community", "OBJECTIVE To compare two micronutrient ( vitamins and minerals ) formulas ( Berocca ™ and CNE ™ ) and assess their impact on emotions and stress related to the 6.3 earthquake on February 22(nd ) 2011 in Christchurch , New Zeal and . METHODS 91 adults experiencing heightened anxiety or stress 2 - 3 months following the earthquake were r and omized to Berocca ™ , CNE ™ low dose ( CNE4 ) , or CNE ™ high dose ( CNE8 ) , for 28 days and monitored weekly via on-line question naires and followed 1 month post-trial . A nonr and omized control group ( n = 25 ) completed question naires at baseline and 4 weeks . RESULTS All treatment groups experienced significant declines in psychological symptoms ( p ) . CNE ™ groups experienced greater reduction in intrusive thoughts as compared with Berocca ™ ( p = .05 ) , with no group differences on other measures of psychological symptoms . However , CNE8 group reported greater improvement in mood , anxiety , and energy ( p taking CNE ™ post-trial than Berocca ™ group . Treated participants had better outcomes on most measures over 4 weeks as compared to controls . CONCLUSIONS This study supports micronutrients as an inexpensive and practical treatment for acute stress following a natural disaster with a slight advantage to higher doses ACTRN 12611000460909", "BACKGROUND The role of nutrition in the treatment of attention-deficit hyperactivity disorder ( ADHD ) is gaining international attention ; however , treatments have generally focused only on diet restriction or supplementing with one nutrient at a time . AIMS To investigate the efficacy and safety of a broad-based micronutrient formula consisting mainly of vitamins and minerals , without omega fatty acids , in the treatment of ADHD in adults . METHOD This double-blind r and omised controlled trial assigned 80 adults with ADHD in a 1:1 ratio to either micronutrients ( n = 42 ) or placebo ( n = 38 ) for 8 weeks ( trial registered with the Australian New Zeal and Clinical Trials Registry : ACTRN12609000308291 ) . RESULTS Intent-to-treat analyses showed significant between-group differences favouring active treatment on self- and observer- but not clinician-ADHD rating scales . However , clinicians rated those receiving micronutrients as more improved than those on placebo both globally and on ADHD symptoms . Post hoc analyses showed that for those with moderate/severe depression at baseline , there was a greater change in mood favouring active treatment over placebo . There were no group differences in adverse events . CONCLUSIONS This study provides preliminary evidence of efficacy for micronutrients in the treatment of ADHD symptoms in adults , with a reassuring safety profile", "Rationale Several investigators implicated role of free radical-mediated pathology in schizophrenia . No study has ever examined the effect of vitamin C with atypical antipsychotics in the treatment of schizophrenia . Objective The aim of this study was to examine the effect of oral vitamin C with atypical antipsychotics on serum malondialdehyde ( MDA ) , plasma ascorbic acid levels , and brief psychiatric rating scale ( BPRS ) score in schizophrenic patients . Method Forty schizophrenic patients participated in a prospect i ve , double-blind , placebo-controlled , noncrossover , 8-week study . The patients with schizophrenia were divided r and omly into placebo and vitamin C group of 20 each . Serum MDA and plasma ascorbic acid were estimated by methods of Nischal and Aye , respectively . Result Increased serum MDA and decreased plasma ascorbic acid levels were found in schizophrenic patients . These levels were reversed significantly after treatment with vitamin C along with atypical antipsychotics compared to placebo with atypical antipsychotics . BPRS change scores at 8 weeks improved statistically significant with vitamin C as compared to placebo . Conclusion Oral supplementation of vitamin C with atypical antipsychotic reverses ascorbic acid levels , reduces oxidative stress , and improves BPRS score , hence both the drugs in combination can be used in the treatment of schizophrenia", "BACKGROUND Folate deficiency and the methylenetetrahydrofolate reductase ( MTHFR ) 677C > T polymorphism have been linked to negative symptoms in schizophrenia both independently and synergistically . This study examined the effect of folate supplementation on negative symptoms overall and in relation to MTHFR 677C > T genotype . METHOD Forty-six stable adult schizophrenia out patients were enrolled and 32 were r and omised , double-blind , in a parallel-group , twelve week add-on trial of folate 2mg/d or matching placebo . The primary outcome measure was change from baseline to week 12 on the modified SANS total score using a mixed-model analysis . In addition , we measured the effect of MTHFR genotype on treatment effects and on changes in serum folate by grouping participants with T/T genotype together with C/T genotype and comparing their interactions to patients with C/C genotype . RESULTS Twenty-eight participants completed the trial . Folate supplementation did not significantly affect negative symptoms compared to placebo across the entire cohort . However , there was a significant genotype × treatment effect on negative symptoms ( F=7.13 , df=1,39 , p=0.01 ) . In addition , MTHFR status significantly moderated the relationship between change in serum folate and change in negative symptoms : among participants with at least one copy of the T allele negative symptoms were more likely to improve with increased serum folate ( p=0.03 ) . CONCLUSION We did not detect a therapeutic benefit of folate supplementation in a sample of patients with residual negative symptoms . However , a possible association between genotypes associated with reduced MTHFR activity and benefit from folate supplementation should be investigated further", "One of the major problems associated with long-term neuroleptic treatment is persistent tardive dyskinesia ( TD ) , for which there is no satisfactory treatment . We have recently proposed that some cases of TD are associated with neuronal dysfunction result ing from excess free radical production occurring during catecholamine metabolism . We therefore decided to assess the efficacy of a powerful free radical scavenging agent , alpha-tocopherol ( vitamin E ) , on the clinical signs of TD . We treated 15 patients with persistent TD with alpha-tocopherol and matched placebo in a r and omized crossover design . Patients demonstrated a significant overall reduction in scores on the Abnormal Involuntary Movements Scale ( AIMS ) after treatment with alpha-tocopherol , but not after placebo . The mean reduction in the AIMS score with alpha-tocopherol was 43 percent , with seven patients showing a greater than 50 percent reduction in their dyskinesia . There was also a trend for a decrease in scores on the Brief Psychiatric Rating Scale , but no change was observed in scores on the Simpson-Angus Scale for Extrapyramidal Side Effects . Our findings are consistent with the possibility that alpha-tocopherol is beneficial in the treatment of some patients with TD , but further research is necessary to establish the efficacy of this agent", "BACKGROUND Treatment strategies for acute neuroleptic-induced akathisia ( NIA ) contain anticholinergic ( antimuscarinic ) agents , dopamine agonists , gamma-aminobutyric acid (GABA)-ergic agents , beta-blockers , benzodiazepines , and serotonin antagonists . Nevertheless , many patients who suffer from acute akathisia fail to respond to treatment . In earlier studies , vitamin B6 was found to be effective in the treatment of neuroleptic-induced movement disorders . The purpose of this study was to evaluate the efficacy of vitamin B6 in the treatment of acute NIA . This is the first report of B6 as a treatment for NIA . METHOD This study was conducted in 2 mental health centers from February 2003 to November 2003 . Twenty schizophrenia and schizoaffective in patients with a DSM-IV diagnosis of NIA were r and omly divided to receive vitamin B6 600 mg/day b.i.d . ( N = 10 ) or placebo ( N = 10 ) twice a day for 5 days in a double-blind design . The Barnes Akathisia Scale ( BAS ) , the Brief Psychiatric Rating Scale ( BPRS ) , and the Clinical Global Impressions scale ( CGI ) were used to assess the severity of NIA and psychotic symptoms . The BAS assessment was made at baseline and every day during the study . The BPRS and CGI were completed at baseline and at the end of the study . RESULTS The vitamin B6-treated patients in comparison with the placebo group showed a significant improvement on the subjective-awareness of restlessness ( p = .0004 ) , subjective-distress ( p = .01 ) , and global ( p = .004 ) subscales of the BAS . The objective subscale did not demonstrate significant positive results ( p = .079 ) , but there was a trend of symptom amelioration in the vitamin B6 group . A reduction of at least 2 points on the BAS global subscale was noted in 8 patients in the vitamin B6 group ( 80 % ) , and in only 3 patients in the placebo group ( 30 % ) ( p = .037 ) . CONCLUSION Our preliminary results indicate that high doses of vitamin B6 may be useful additions to the available treatments for NIA , perhaps due to its combined effects on various neurotransmitter systems", "The aim of our study was to provide further information as to the efficacy of vitamin E for the management of tardive dyskinesia", "Abstract : Treatment strategies against acute neuroleptic-induced akathisia ( NIA ) include anticholinergic ( antimuscarinic ) agents , dopamine agonists , GABAergic agents , & bgr;-blockers , benzodiazepines , and serotonin antagonists . However , many patients who have acute akathisia fail to respond . In previous studies , mianserin and vitamin B6 were found to be effective in the treatment of acute akathisia . The purpose of this study was to compare the efficacy of B6 , mianserin and placebo in the treatment of acute NIA . Sixty schizophrenia and schizoaffective in patients who have NIA were r and omly divided to receive vitamin B6 1200 mg/d , mianserin 15 mg/d , or placebo for 5 days , in a double-blind design . The Barnes Akathisia Rating Scale , Brief Psychiatric Rating Scale , and Clinical Global Impression were used to assess the severity of NIA and psychotic symptoms . The assessment was made at baseline and daily for the duration of the study . Compared with the placebo group , the vitamin B6-treated and mianserin-treated patients showed a significant improvement in the subjective ( P subjective distress ( P global ( P subscales . The objective subscale did not show significant positive results ( P = 0.056 ) , but there was a trend toward symptom amelioration in both groups . A reduction of at least 2 points on the Barnes Akathisia Rating Scale global subscale was noted in the vitamin B6 group ( 13/23 , 56 % ) as well as in the mianserin groups ( 13/20 , 65 % ) , and in only one patient in the placebo group ( 1/17 , 6 % ; P B6 and a low dose of mianserin may be a useful addition to current treatments of NIA . The efficacy of vitamin B6 and mianserin suggests that the pathophysiology of acute NIA is heterogeneous with the various subtypes of acute NIA responding differently to the various pharmacological approaches", "The anti-oxidant vitamin E has been reported to be effective in the treatment of tardive dyskinesia . The present open label study examined the effect of supplemental therapy with vitamin E on acute extrapyramidal symptoms and cell enzymes in patients receiving neuroleptic drugs . Thirty-nine hospitalized schizophrenic patients were r and omly assigned to two groups : group 1 ( n = 20 ) was treated with neuroleptics , and group 2 ( n = 19 ) with neuroleptics combined with a fixed dose of vitamin E ( 600 IU/day ) , administered for two weeks . All patients were assessed with the Simpson-Angus Rating Scale ( Simpson and Angus , 1970 ) for neuroleptic induced Parkinsonism ( NIP ) , Barnes ' Akathisia Scale ( Barnes , 1989 ) , and Brief Psychiatric Rating Scale : laboratory parameters included serum creatine kinase ( CK ) activity , serum glutamate oxaloacetic transaminase ( SGOT ) and white blood cell count ( WBC ) . The addition of vitamin E to neuroleptic agents was associated with a trend ( p = 0.08 ) towards prevention of the emergence of NIP compared to neuroleptic treatment alone . Addition of vitamin E to neuroleptics may reduce the severity of acute NIP in schizophrenic patients", "The phosphatidylinositol ( PI ) cycle represents a key signal-transduction system for many neurotransmitters in the brain ( Berridge et al 1982 ) . Inositol is present in high concentration in brain tissue ( Sherman et al 1985 ) and reduction of inositol levels by lithium ( Li ) treatment may be related to Ll 's mechanism of action ( Berridge et al 1982 ) . Indeed , addition of inositol to Ll-treated rats reverses several of iithium 's behavioral effects in vivo ( Kofman and Belmaker 1990 ) as well as many of its biological effects in vitro ( Busa and Gimlich 1989 ) . As a second-messenger system for numerous neurotransmitters , the PI cycle may well be involved in psychiatric disorders other than manic-depressive illness ( Kaiya et al 1989 ) . Recently , we found that inositol-lphosphatase was elevated in red blood cells of chronic schizophrenic patients ( Zilberman-Kaufman et al 1992 ) . This suggested to us that inositol might be lacking in such patients and that the increased enzyme activity represented an attempted physiological compensation . We therefore decided on a clinical trial of inositol therapy in schizophrenia . lnositol passes the blood-brain barrier poorly ( Spector 1988 ) . The behavioral effects noted in rats were done with intracerebroventricular ( ICV ) inositol ( Kofman and Belmaker 1990 ) . However , Belmaker et al ( 1992 ) showed that large doses of inositol IP reversed Ll-pilocarpine seizures as effectively as small doses given ICV . As in the history of L-Dopa therapy ( Marks 1974 ) , it may be that simple compounds can have psychoactive effects only when given at high doses", "Classical antipsychotics like haloperidol are suggested to increase oxidative stress and oxidative cell injury in the brain . Pro-oxidant effect of haloperidol may influence the course and treatment outcomes of schizophrenia . Dietary supplementation of either antioxidants or omega-3 fatty acids was found to improve symptoms of schizophrenia . Thus we decided to assess the impact of combining omega-3 fatty acids , vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol . Ongoing haloperidol treatment of 17 schizophrenia patients was supplemented with 1000 mg capsule of omega-3 fatty acids ( 180 mg EPA+120 mg DHA ) bid , vitamin E 400 IU bid and vitamin C 1000 mg/day . Patients were assessed with Brief Psychiatric Rating Scale ( BPRS ) , Scale for the Assessment of Negative Symptoms ( SANS ) , Simpson Angus Scale ( SAS ) and Barnes Akathisia Rating Scale ( BARS ) over a 4 month period . Gluthatione peroxidase , superoxide dismutase , malondialdehyde , vitamin E and C levels were also evaluated at baseline and at the end of study . BPRS , SANS , SAS and BARS scores obtained at follow-up visits were significantly lower compared to baseline . Superoxide dismutase level was significantly lower at the end of study . No significant differences were detected in other laboratory parameters . Our results support the beneficial effect of the supplementation on positive and negative symptoms of schizophrenia as well as the severity of side effects induced by haloperidol . The effect of supplementation on akathisia is especially noteworthy and it has not been investigated in previous studies", "Inositol is a key metabolite in the phosphatidylinositol cycle , which is a second messenger system for serotonin-2 receptors that have been implicated in the pathophysiology of schizophrenia . Cerebrospinal fluid inositol levels were measured in 20 schizophrenic patients and 19 age- and sex-matched controls and no difference was found . However , the patients were all neuroleptic-treated . A controlled double-blind crossover trial of 12 g daily of inositol for a month in 12 anergic schizophrenic patients , twice the dose given before in schizophrenia , did not show any beneficial effects . However , the number of patients studied was small and the length of time of inositol administration may not have been sufficient", "Short-term clinical trials of omega-3 polyunsaturated fatty acids ( n-3 PUFA ) as add-on therapy in patients with schizophrenia revealed mixed results . The majority of these studies used an 8- to 12-week intervention based on ethyl-eicosapentaenoic acid . A r and omized placebo-controlled trial was design ed to compare the efficacy of 26-week intervention , composed of either 2.2 g/day of n-3 PUFA , or olive oil placebo , with regard to symptom severity in first-episode schizophrenia patients . Seventy-one patients ( aged 16 - 35 ) were enrolled in the study and r and omly assigned to the study arms . The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale ( PANSS ) . Mixed models repeated measures analysis revealed significant differences between the study arms regarding total PANSS score change favouring n-3 PUFA ( p = 0.016 ; effect size ( ES ) = 0.29 ) . A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group ( 69.4 vs 40.0 % ; p = 0.017 ) . N-3 PUFA intervention was also associated with an improvement in general psychopathology , measured by means of PANSS ( p = 0.009 ; ES = 0.32 ) , depressive symptoms ( p = 0.006 ; ES = 0.34 ) , the level of functioning ( p = 0.01 ; ES = 0.31 ) and clinical global impression ( p = 0.046 ; ES = 0.29 ) . The findings suggest that 6-month intervention with n-3 PUFA may be a valuable add-on therapy able to decrease the intensity of symptoms and improve the level of functioning in first-episode schizophrenia patients" ]

[ "Background Patient aggression is a common problem in acute psychiatric wards and calls for preventive measures . The timely use of preventive measures presupposes a preceded risk assessment . The Norwegian Brøset-Violence-Checklist ( BVC ) is one of the few instruments suited for short-time prediction of violence of psychiatric in patients in routine care . Aims of our study were to improve the accuracy of the short-term prediction of violence in acute inpatient setting s by combining the Brøset-Violence-Checklist ( BVC ) with an overall subjective clinical risk- assessment and to test the application of the combined measure in daily practice . Method We conducted a prospect i ve cohort study with two sample s of newly admitted psychiatric patients for instrument development ( 219 patients ) and clinical application ( 300 patients ) . Risk of physical attacks was assessed by combining the 6-item BVC and a 6-point score derived from a Visual Analog Scale . Incidents were registered with the Staff Observation of Aggression Scale-Revised SOAS-R. Test accuracy was described as the area under the receiver operating characteristic curve ( AUCROC ) . Results The AUCROC of the new VAS-complemented BVC-version ( BVC-VAS ) was 0.95 in and 0.89 in the derivation and validation study respectively . Conclusion The BVC-VAS is an easy to use and accurate instrument for systematic short-term prediction of violent attacks in acute psychiatric wards . The inclusion of the VAS-derived data did not change the accuracy of the original BVC", "OBJECTIVE To examine factors associated with physical restraint in psychiatric emergency rooms . METHOD We extracted variables likely to predict use of physical restraints from a large r and omised trial undertaken in three psychiatric emergency rooms in Rio de Janeiro . We fitted a Bayesian binary multivariate model using only variables clearly preceding the restraints . RESULTS Of 301 agitated , aggressive people admitted to emergency rooms , 73 ( 24 % ) were restrained during the first 2 h of admission . In Rio , younger people ( OR=1.03 for each year younger ) , exhibiting intense ( OR=2.53 ) or extreme agitation ( OR=7.71 ) , thought to result from substance misuse ( OR=1.75 ) or diagnoses other than psychosis ( OR=1.88 ) , arriving in the morning ( OR=1.64 ) were at greater risk of physical restraints than older , less severely aggressive or agitated people , arriving at the hospital during the afternoon or night . Hospital , gender , first admission to hospital and medication were not associated with risk of being restrained . CONCLUSION Restraint practice s in Rio are predictable and based on a limited clinical assessment . Predictive factors for physical restraint may vary worldwide , but should be monitored and studied to assist training , and to establish programs to evaluate and refine this controversial practice", "BACKGROUND Psychiatric emergency situations ( PES ) are of high importance to the German prehospital physician-based emergency medical system . So far , however , no prospect i ve studies regarding the incidence of PES have been performed , neither have effects of training programs on diagnostic and therapeutic accuracy been studied . METHOD The protocol s of two emergency medical services ( EMS ) were collected and analyzed prospect ively . Emergency physicians ( EPs ) in Kaiserslautern ( KL ) attended a st and ardized educational program and underwent daily supervision . EPs in Homburg ( HOM ) had not been informed about the study . In KL , sociodemographic variables were collected . An investigator who was not involved in the individual EMS mission assessed the correct classification of PES . RESULTS Among all calls for an EP , 11.8 % were classified as PES . There was no difference between the two centers . Correct classification of PES in KL was significantly higher than that in HOM ( 94.3 % vs. 80.6 % ) . Documentation of suicidal behavior was deficient in both centers . EPs in KL gave verbal crisis intervention significantly more often , administered less medication overall , and dispensed more specific drugs in psychotic disorders and significantly less drugs in substance abuse disorders . Patients were more often treated at the scene and were less often transported to a hospital . Some sociodemographic variables were associated with psychiatric morbidity of treatment . CONCLUSION Accounting for 12 % of all missions , psychiatric emergencies are a frequent reason for calls for EPs , equaling trauma-related and neurological emergencies . The most frequent reasons for calls were alcohol intoxication , states of agitation and suicidal behavior . The diagnostic and therapeutic accuracy of EPs may be improved with a concise st and ardized teaching program", "This study determined the inter-rater reliability of the Sedation-Agitation Scale ( SAS ) when used by staff in a tertiary level general intensive care unit ( ICU ) . The study was design ed to answer the question in the ' real world ' , with minimum patient exclusion criteria , do nurses and doctors rate ICU patient 's sedation levels using the SAS similarly ? A convenient sample of 35 nursing and seven medical staff and a r and omly selected sample of 69 patients were used . A nurse and a doctor rated each patient simultaneously using the SAS , with a systematic five-stage arousal process . The results showed that there was exact agreement between the nurses ' and doctors ' scores in 74 % of assessment s. The weighted kappa finding of 0.82 indicates very good agreement ( reliability ) . The mean SAS scores recorded for nurses ( 2.33+/-1.21 ) and doctors ( 2.36+/-1.35 ) were similar . Intraclass correlations for single measures ( r=.921 , p SAS away from each other . This research indicates nurses and doctors rate patients ' levels of sedation similarly using the SAS . It also provides support for the use of the instrument in general ICUs outside the USA . Research is now needed to determine the value of the SAS in guiding clinical decision-making related to sedation management", "PURPOSE To describe physical restraint ( PR ) rates and context s in U.S. hospitals . DESIGN This 2003 - 2005 descriptive study was done to measure PR prevalence and context s ( census , gender , age , ventilation status , PR type , and rationale ) at 40 r and omly selected acute care hospitals in six U.S. metropolitan areas . All units except psychiatric , emergency , operative , obstetric , and long-term care were included . METHODS On 18 r and omly selected days between 0500 and 0700 ( 5:00 am and 7:00 am ) , data collectors determined PR use and context s via observation and nurse report . FINDINGS PR prevalence was 50 per 1,000 patient days ( based on 155,412 patient days ) . Preventing disruption of therapy was the chief reason cited . PR rates varied by unit type , with adult ICU rates the highest obtained . Intra- and interinstitutional variation was as high as 10-fold . Ventilator use was strongly associated with PR use . Elderly patients were over-represented among the physically restrained on some units ( e.g. , medical ) but on many unit types ( including most ICUs ) their PR use was consistent with those of other adults . CONCLUSIONS Wide rate variation indicates the need to examine administratively mediated variables and the promotion of unit-based improvement efforts . Anesthetic and sedation practice s have contributed to high variation in ICU PR rates . Determining the types of units to target to achieve improvements in care of older adults requires study of PR sequelae rate by unit type", "OBJECTIVE The objective of the study was to evaluate the effectiveness of the sedation assessment tool ( SAT ) in assessing patient response to treatment for acute behavioural disturbance ( ABD ) . METHODS The SAT is a simplified version of the altered mental status score ( AMSS ) and is a 7-point scale assessing levels of agitation and sedation using only two descriptors . To assess the SAT we firstly compared plots of the SAT and the AMSS versus time in patients with ABD recruited to a clinical trial . AMSS were converted to the SAT for this comparison . Second , the sensitivity and specificity were calculated for an increase in the SAT to + 2 or + 3 as a predictor of whether additional sedation was required in a prospect i ve cohort of 138 patients . Third , interrater reliability was assessed using two individuals to score the same patient at two different time points and finally the time to record the score was measured . RESULTS Plots of AMSS and SAT for 91 patients in the clinical trial illustrated similar trends in agitation/sedation . Seventeen of 138 patients in the second cohort had an increase in the SAT . Fifteen of 17 ( 88 % ) received additional sedation . The sensitivity and specificity of the SAT for additional sedation was 100 % ( 95 % CI 75 - 100 % ) and 98 % ( 95 % CI 94 - 100 % ) , respectively . The median time for staff to assign the SAT was 10 s ( range 3 - 15 s ) . Interrater reliability was high with a kappa of 0.87 . CONCLUSION The SAT is a simple , rapid and useful measure of the level of agitation/sedation in patients with ABD . Increases in the score reliably indicated the need for further sedation", "Introduction : Studies of aggressive behaviors in a nonforensic mental health setting have focused primarily on the inpatient ward and , on event prediction , using behavior-based clinical rating scales . Few studies have specifically targeted aggressive behaviors in the psychiatric emergency service or determined whether assessing the demographic and clinical characteristics of such patients might prove useful for their more rapid identification . Methods : We used a prospect ively acquired data base of over 20,900 visits to four services in the province of Quebec , Canada , over a two-year period from September 2002 onwards . A maximum of 72 variables could be acquired per visit . Visits with aggression ( any verbally or physically intimidating behavior ) , both present and past , were tagged . Binary logistic regressions and cross-tabulations were used to determine whether the profile of a variable differed in visits with aggression from those without aggression . Results : About 7 % of visits were marked by current aggression ( verbal 49 % , physical 12 % , verbal and physical 39 % ) . Including visits with a “ past only ” history of aggression increased this number to 20 % . Variables associated with aggression were gender ( male ) , marital status ( single/separated ) , education ( high school or less ) , employment ( none ) , judicial history ( any type ) , substance abuse ( prior or active ) , medication compliance ( poor ) , type of arrival to psychiatric emergency services ( involuntary , police , judiciary , l and lord ) , reason for referral ( behavioral dyscontrol ) , diagnosis ( less frequent in anxiety disorders ) , and outcome ( more frequently placed under observation or admitted ) . Conclusion : Our results suggest that many state-independent variables are associated with aggressive behaviors in the psychiatric emergency service . Although their sum may not add up to a specific patient profile , they can nevertheless be useful in service planning , being easily integrated alongside state-dependent rating scales in a triage and /or observation instrument for daily use in the psychiatric emergency service", "OBJECTIVE To describe the Psychiatric Emergency Research Collaboration ( PERC ) , the methods used to create a structured chart review tool and the results of our multicenter study . METHOD Members of the PERC Steering Committee created a structured chart review tool design ed to provide a comprehensive picture of the assessment and management of psychiatric emergency patients . Ten primary indicators were chosen based on the Steering Committee 's professional experience , the published literature and existing consensus panel guidelines . Eight emergency departments completed data abstract ion of 50 r and omly selected emergency psychiatric patients , with seven providing data from two independent raters . Inter-rater reliability ( Kappas ) and descriptive statistics were computed . RESULTS Four hundred patient charts were abstract ed . Initial concordance between raters was variable , with some sites achieving high agreement and others not . Reconciliation of discordant ratings through re- review of the original source documentation was necessary for four of the sites . Two hundred eighty-five ( 71 % ) subjects had some form of laboratory test performed , including 212 ( 53 % ) who had urine toxicology screening and 163 ( 41 % ) who had blood alcohol levels drawn . Agitation was present in 220 ( 52 % ) , with 98 ( 25 % ) receiving a medication to reduce agitation and 22 ( 6 % ) being physically restrained . Self-harm ideation was present in 226 ( 55 % ) , while other-harm ideation was present in 82 ( 20 % ) . One hundred seventy-nine ( 45 % ) were admitted to an inpatient or observation unit . CONCLUSION Creating a common st and ard for documenting , abstract ing and reporting on the nature and management of psychiatric emergencies is feasible across a wide range of health care institutions", "OBJECTIVE Assessing risk for violence is a complex task often based on not objective or structured clinical evaluations . HCR-20 Assessing Risk for Violence has been used in several countries to increase the accuracy of this exam . The purpose of this study was to inform on central aspects of this instrument , as well as the results of the reliability assessment of the HCR-20 Assessing Risk for Violence in a Brazilian inpatient criminal population . METHOD Two examiners independently assessed a r and om sample of 30 patients that were under criminal commitment at the Mauricio Cardoso Forensic Psychiatric Institute RESULTS Mean consensus values means were as follows : Historical = 13.1 ; Clinical = 4.8 and Risk management = 5.8 . The value of the Intraclass Correlation Coefficient for the score of subscale Historical was 0.97 , for subscale Clinical it was 0.94 , and for subscale Risk management , 0.96 . As to the individual items of the HCR-20 Assessing Risk for Violence , the result of the Intraclass Correlation Coefficient was good to excellent ( mean = 0.97 ; interval , from 0.60 to 0.99 ) . CONCLUSION The interrater reliability of the Brazilian version of the HCR-20 Assessing Risk for Violence scale was similar to the results of studies in other countries", "OBJECTIVE To compare the effectiveness of intramuscular olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol alone as the first medication(s ) used to treat patients with agitation and aggressive behavior . METHOD One hundred fifty patients with agitation caused by psychotic or bipolar disorder were r and omly assigned under double-blind conditions to receive olanzapine , ziprasidone , haloperidol plus midazolam , haloperidol plus promethazine or haloperidol alone . The Overt Agitation Severity Scale , Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage . RESULTS All medications produced a calming effect within one hour of administration , but only olanzapine and haloperidol reduced agitation by less than 10 points , and only olanzapine reduced aggression by less than four points in the first hour . After twelve hours , only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects . Ziprasidone , olanzapine and haloperidol alone had more stable results for agitation control , while ziprasidone , haloperidol plus promethazine and olanzapine had stable results for aggression control . CONCLUSION Olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours . Although all the drugs had advantages and disadvantages , haloperidol plus midazolam was associated with the worst results in all the observed parameters", "OBJECTIVES The aim was to carry out a prospect i ve study about the characteristics of the public seen at a psychiatric emergency room and of its service . METHODS The data were acquired though a protocol developed for this study and applied to all the patients seen during two months . RESULTS 600 protocol s were filled out , corresponding to 96.5 % ( 487 patients ) of the attendance during the study period . Most of the patients seen were males , single , with a low educational level , professionally inactive and living with their families . The most frequent diagnoses were psychoactive substance use disorders ( 26.3 % ) , schizophrenia ( 15.5 % ) , manic episode ( 11.8 % ) , major depression ( 10.9 % ) and non-psychotic disorders ( 10.9 % ) . There were differences between gender in some diagnostic categories . After initial evaluation , 2/3 were medicated , ( 1/2 ) stayed under observation , and ( 1/4 ) stayed more than 10 hours in the service unit . About 20 % of the attendance result ed in hospitalization and 60 % in referrals to outpatient services . Discharges due to evasion represented only 2.0 % of the total . Returning service users did not differ from those seen only once to what concern marital status , professional situation and household conditions . However , returning users presented a higher frequency of previous hospitalization and psychotic disorders . CONCLUSIONS Individuals with severe psychiatric disorders were seen in an actual emergency situation . The psychiatric emergency service has been exp and ing its actions and has been an effective part of the mental health service network", "Two studies tested the reliability and validity of the Overt Agitation Severity Scale ( OASS ) , a new instrument developed to define and objective ly rate the severity of agitated behavior . The authors postulate that agitation should be conceptualized as vocal and motor behaviors on a continuum of expressions that extends from anxiety to aggression . Content validity through expert agreement was achieved in the development of test construction over a 2-year period . Results of two pilot studies ( n = 25 and n = 14 subjects ) established the reliability and validity of the OASS to measure agitation severity . The OASS differs from other agitation scales in that it confines its rating exclusively to observable behavioral manifestations of agitation ", "A 10-month prospect i ve study of 148 restraints on the acute psychiatric wards of a general hospital aim ed to describe the institutional context of restraints . Nursing and medical staff were inquired according to a st and ardised procedure about ward atmosphere , staffing , medication and other factors . 81 % of restraints lasted up to 2 hours , danger of harm to others was found the principal indication criterion ( 70 % ) . 41 % restraints occurred during the first 3 days after admission , mainly within the late shift of nursing staff and outside the regular office hours of the doctors . Ward atmosphere was rated rather relaxed , whereas nursing staff twice as often as doctors rated medication as insufficient . Implication s for indication on the use of restraints and for future research are discussed", "Agitation is a vexing problem frequently observed in emergency department acute psychiatric patients , yet no instruments to measure agitation in this setting and population were found upon review of the literature . Previously developed agitation rating scales are limited by the length of observation they require , their need for participation by the patient , complexity in scoring , and a lack of validity in this setting and population . The purpose of this study was to psychometrically evaluate and refine an observation-based agitation scale for use with emergency department acute psychiatric patients . Using a method ological design , the 21-item Agitation Severity Scale was utilized to assess 270 adult psychiatric patients in the emergency setting in a prospect i ve , observational fashion . Reliability analysis , item analysis , exploratory factor analysis , and validity assessment s were completed . The relationship between Agitation Severity Scale scores and scores on the previously established Overt Agitation Severity Scale was evaluated . The instrument was reduced to 17 items representing four factors ( Aggressive Behaviors , Interpersonal Behaviors , Involuntary Motor Behaviors , and Physical Stance ) that accounted for nearly 70 % of observed variance , Cronbach 's & agr ; = 0.91 . Evidence of internal consistency reliability , equivalence reliability , construct validity , and convergent validity was established . Through this study , the 17-item Agitation Severity Scale demonstrated acceptable levels of reliability and validity when used with acute psychiatric patients in the emergency setting . This instrument holds promise as a method of enhancing clinical communication about agitation , evaluating the efficacy of interventions aim ed at decreasing agitation , and as a research tool", "BACKGROUND The pharmacological management of violence in people with psychiatric disorders is under- research ed . AIMS To compare interventions commonly used for controlling agitation or violence in people with serious psychiatric disorders . METHOD We r and omised 200 people to receive intramuscular lorazepam ( 4 mg ) or intramuscular haloperidol ( 10 mg ) plus promethazine ( 25 - 50 mg mix ) . RESULTS At blinded assessment s 4 h later ( 99.5 % follow-up ) , equal numbers in both groups ( 96 % ) were tranquil or asleep . However , 76 % given the haloperidol-promethazine mix were asleep compared with 45 % of those allocated lorazepam ( RR=2.29,95 % CI 1.59 - 3.39 ; NNT=3.2,95 % CI 2.3 - 5.4 ) . The haloperidol-promethazine mix produced a faster onset of tranquillisation/sedation and more clinical improvement over the first 2 h. Neither intervention differed significantly in the need for additional intervention or physical restraints , numbers absconding , or adverse effects . CONCLUSIONS Both interventions are effective for controlling violent/agitated behaviour . If speed of sedation is required , the haloperidol-promethazine combination has advantages over lorazepam", "We report psychometric results of the Behavioural Activity Rating Scale ( BARS ) using data from three Phase III clinical trials of intramuscular ziprasidone in acutely agitated patients with psychosis ( Studies 1 and 2 ) or in stable psychotic patients ( Study 3 ) . Convergent validity and divergent validity were assessed with baseline data from Studies 1 and 2 in subjects with acute agitation . To investigate convergent validity , we sought Pearson and Spearman correlation of BARS scores with scores on the Clinical Global Impression of Severity ( CGI-S ) Scale and a predefined cluster of agitation-related items from the Positive and Negative Syndrome Scale ( PANSS ) . For divergent validity , we sought Pearson and Spearman correlation between BARS scores and a predefined cluster of PANSS items measuring negative symptoms . Discriminant validity was investigated with the help of subjects with moderate psychopathology ( Study 3 ) . Wilcoxon rank-sum and two- sample t tests determined whether mean ( or median ) BARS scores differed between subjects with acute agitation ( Studies 1 and 2 ) and moderate psychopathology ( Study 3 ) . Responsiveness to treatment effect and rater reliability were also evaluated . In Study 2 , Pearson correlation coefficients of BARS scores with PANSS agitation items and CGI-S were moderate ( convergent validity ) and statistically significant ( P correlation between BARS scores and PANSS negative component scores was low ( divergent validity ) . Treatment effect size was larger for BARS than for PANSS agitation items and CGI-S ( responsive to treatment differences ) . Virtually perfect inter- and intra-rater reliability was achieved . Study 1 produced similar results . BARS showed psychometrically valid properties for measurement of behavioral activity in acutely agitated patients with psychosis", "BACKGROUND After de-escalation techniques have failed , restraints , seclusion and /or rapid tranquillization may be used for people whose aggression is due to psychosis . Most coercive acts of health care have not been evaluated in trials . METHOD People admitted to the emergency room of Instituto Philippe Pinel , Rio de Janeiro , Brazil , whose aggression/agitation was thought due to psychosis and for whom staff were unsure if best to restrict using physical restraints or a seclusion room , were r and omly allocated to one or the other and followed up to 14 days . The primary outcomes were ' no need to change intervention early - within 1 h ' and ' not restricted by 4 h ' . RESULTS A total of 105 people were r and omized . Two-thirds of the people secluded were able to be fully managed in this way . Even taking into account the move out of seclusion into restraints , this study provides evidence that embarking on the less restrictive care pathway ( seclusion ) does not increase overall time in restriction of some sort [ not restricted by 4 h : relative risk 1.09 , 95 % confidence interval 0.75 - 1.58 ; mean time to release : restraints 337.6 ( s.d.=298.2 ) min , seclusion room 316.3 ( s.d.=264.5 ) min , p=0.48 ] . Participants tended to be more satisfied with their care in the seclusion group ( 17.0 % v. 11.1 % ) but this did not reach conventional levels of statistical significance ( p=0.42 ) . CONCLUSIONS This study should be replicated , but suggests that opting for the least restrictive option in circumstances where there is clinical doubt does not harm or prolong coercion", "Psychiatric acute units use different levels of segregation to satisfy needs for containment and decrease in sensory input for behaviourally disturbed patients . Controlled studies evaluating the effects of the procedure are lacking . The aim of the present study was to compare effects in acutely admitted patients with the use of a psychiatric intensive care unit ( PICU ) and not in a psychiatric acute department . In a naturalistic study , one group of consecutively referred patients had access only to the PICU , the other group to the whole acute unit . Data were obtained for 56 and 62 patients using several scales . There were significant differences in reduction of behaviour associated with imminent , threatening incidents ( Broset Violence Checklist ) , and actual number of such incidents ( Staff Observation Aggression Scale-Revised ) in favour of the group that was treated in a PICU . The principles of patient segregation in PICUs have favourable effects on behaviours associated with and the actual numbers of violent and threatening incidents" ]

[ "The effects of intravenous 1,25 dihydroxycholecalciferol [ (OH)2D3 ] on glucose tolerance and insulin secretion were studied in eleven uremic patients on regular hemodialysis and compared with eleven healthy controls . Intravenous glucose tolerance tests ( IVGTT ) were used to assess glucose tolerance , and the hyperglycemic clamp technique was used to quantitate endogenous insulin secretion . Three days after they had discontinued oral 1,25(OH)2D3 , the dialysis patients were then studied with ( + D ) and without ( -D ) a single intravenous dose of 1,25(OH)2D3 at 2 micrograms/m2 , given two hours before the IVGTT or clamp studies . During the -D studies , the uremic patients were glucose intolerant but not hyperinsulinemic . Intravenous 1,25(OH)2D3 in dialysis patients increased glucose uptake ( K values ) during IVGTT by 38 % ( P less than 0.02 ) and increased early component of insulin secretion during hyperglycemic clamps by 48 % ( P less than 0.01 ) and the late component by 32 % ( P less than 0.01 ) . After intravenous 1,25(OH)2D3 , the dialysis patients became hyperinsulinemic and regained glucose tolerance . Intravenous 1,25(OH)2D3 did not change the K values during IVGTT nor the insulin secretion during hyperglycemic clamps in the control subjects . During the -D studies , serum concentrations of 1,25(OH)2D3 were significantly lower in uremic patients compared with controls . Serum 1,25(OH)2D3 during the + D studies increased to supraphysiological levels in both uremic patients and controls . Serum concentrations of intact parathyroid hormone , total and ionized calcium , magnesium , potassium , urea nitrogen and creatinine were not different between the + D and -D studies in neither the uremic patients nor the controls . These results suggest that 1,25(OH)2D3 deficiency , independent of parathyroid hormone and calcium , may contribute to the abnormalities in glucose tolerance and insulin secretion in dialysis patients", "CONTEXT Vitamin D is associated with decreased cardiovascular-related morbidity and mortality , possibly by modifying cardiac structure and function , yet firm evidence for either remains lacking . OBJECTIVE To determine the effects of an active vitamin D compound , paricalcitol , on left ventricular mass over 48 weeks in patients with an estimated glomerular filtration rate of 15 to 60 mL/min/1.73 m(2 ) . DESIGN , SETTING , AND PARTICIPANTS Multinational , double-blind , r and omized placebo-controlled trial among 227 patients with chronic kidney disease , mild to moderate left ventricular hypertrophy , and preserved left ventricular ejection fraction , conducted in 11 countries from July 2008 through September 2010 . INTERVENTION Participants were r and omly assigned to receive oral paricalcitol , 2 μg/d ( n = 115 ) , or matching placebo ( n = 112 ) . MAIN OUTCOME MEASURES Change in left ventricular mass index over 48 weeks by cardiovascular magnetic resonance imaging . Secondary end points included echocardiographic changes in left ventricular diastolic function . RESULTS Treatment with paricalcitol reduced parathyroid hormone levels within 4 weeks and maintained levels within the normal range throughout the study duration . At 48 weeks , the change in left ventricular mass index did not differ between treatment groups ( paricalcitol group , 0.34 g/m(2.7 ) [ 95 % CI , -0.14 to 0.83 g/m(2.7 ) ] vs placebo group , -0.07 g/m(2.7 ) [ 95 % CI , -0.55 to 0.42 g/m(2.7 ) ] ) . Doppler measures of diastolic function including peak early diastolic lateral mitral annular tissue velocity ( paricalcitol group , -0.01 cm/s [ 95 % CI , -0.63 to 0.60 cm/s ] vs placebo group , -0.30 cm/s [ 95 % CI , -0.93 to 0.34 cm/s ] ) also did not differ . Episodes of hypercalcemia were more frequent in the paricalcitol group compared with the placebo group . CONCLUSION Forty-eight week therapy with paricalcitol did not alter left ventricular mass index or improve certain measures of diastolic dysfunction in patients with chronic kidney disease . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00497146", "The aim of this study was to evaluate the effect of calcitriol treatment on glucose intolerance in uraemia . Thirty one patients on haemodialysis who had never been treated with vitamin D or related drugs , and 12 healthy control subjects with normal renal functions were studied . Uraemic patients were r and omly divided into two groups ; 16 patients were treated with oral calcitriol ( 0.5 micrograms/day ) for 8 weeks , and 15 uraemic patients and 12 healthy subjects were given a placebo . In all these cases , before and 8 weeks after treatment , baseline serum glucose , insulin , calcium , parathormone ( PTH ) , and 1,25 (OH)2D3 were measured . After an oral load of 75 g glucose , blood glucose and insulin were determined at 30 , 60 , 90 , and 120 min . The same measurements were repeated after 8 weeks . HbA1c and fructosamine were also measured at 0 and 8 weeks . Baseline serum insulin was significantly elevated after calcitriol treatment ( 7.81 versus 11.63 microIU/ml ) there was also a significant increase in insulin following calcitriol treatment at 30 , 60 , 90 , and 120 min . On the other h and , glycosylated haemoglobin ( HbA1c ) and fructosamine decreased after calcitriol treatment ( HbA1c 7.09 % versus 5.22 % P Blood glucose significantly decreased after calcitriol treatment at 0 , 30 , 60 , 90 , and 120 min . In the other two groups there were no significant changes in any parameters . These results seem to confirm that vitamin D influences pancreatic beta ( beta ) cell secretion and suggest that calcitriol may improve glucose intolerance in uraemic haemodialysis patients . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVE To more clearly eluci date the conflicting results that have been obtained after oral calcitriol pulse therapy on lipid , glucose , and calcium levels in hemodialysis ( HD ) patients , and to determine safety of oral calcitriol pulse therapy in a combination with calcium carbonate . DESIGN A r and omized , crossover , placebo-controlled study . SETTING HD centers in 3 teaching university hospitals . PATIENTS Forty-eight chronic HD patients . METHODS HD patients were r and omized into 2 groups . Each group ( n = 24 ) , in addition to 4.5 g calcium carbonate daily , received either oral calcitriol pulse therapy or placebo twice weekly at the end of HD , sessions for 3 months , after which the 2 therapeutic groups were crossed-over , and for an additional 3 months , the calcitriol group received placebo , and the placebo group was put on calcitriol . Serum triglyceride , total cholesterol , low-density lipoprotein cholesterol ( LDL-c ) , high-density lipoprotein cholesterol ( HDL-c ) , total calcium , alkaline phosphatase , proteins , phosphorus , parathyroid hormone ( PTH ) , blood pH , and glucose were measured at r and om and at the end of 3 and 6 months of the trial . RESULTS After calcitriol therapy , triglyceride , serum PTH , total alkaline phosphatase , and fasting blood sugar significantly decreased , but total serum calcium significantly increased , whereas other examined parameters remained unchanged compared with the other groups . Calcium , phosphorus , calcium x phosphorus product , PTH levels , and all of these parameters were optimized in 18 ( 37.5 % ) , 22 ( 45.8 % ) , 34 ( 70.8 % ) , 30 ( 62.5 % ) , and 12 ( % 25 ) cases , respectively , in the calcitriol groups . No significant side effect was seen during the trial . CONCLUSION Our findings indicate that short-term oral calcitriol pulse therapy in combination with calcium carbonate is safe and beneficial for metabolic abnormalities of HD patients ; however , its safety for prolonged therapy is yet to be proved", "1 . Secondary hyperparathyroidism in chronic renal failure may contribute to abnormalities of lipid metabolism and glucose tolerance . Amelioration of secondary hyperparathyroidism has been reported to mitigate the hyperlipidaemia and improve glucose tolerance experimentally . 2 . The effect of the partial suppression of hyperparathyroidism by intravenous calcitriol on lipid levels and glucose tolerance was studied in 15 haemodialysis patients with secondary hyperparathyroidism . All received intravenous calcitriol 1 microgram at the end of haemodialysis thrice weekly for eight weeks . Oral glucose tolerance test and plasma lipid profiles including triglyceride , total cholesterol , high density lipoprotein cholesterol ( HDL-C ) , low density lipoprotein cholesterol ( LDL-C ) , apoprotein A-I and apoprotein B were determined simultaneously before and after eight weeks of therapy . 3 . Before calcitriol treatment , uraemic patients with secondary hyperparathyroidism displayed a significant higher triglyceride and a significant lower HDL-C and apoprotein A-I as well as marked glucose intolerance with an increment of the area below the glucose curve when compared with healthy control subjects . 4 . After eight weeks of calcitriol treatment , there was a significant decrement in serum intact parathyroid hormone ( 476.45 + /- 48.33 versus 191.37 + /- 30.17 ng/l , P plasma triglyceride ( 2.24 + /- 0.34 versus 1.80 + /- 0.29 mmol/l , P plasma apoprotein A-I ( 38.13 + /- 2.14 versus 44.19 + /- 2.18 mumol/l , P < 0.05 ) , whereas there was no significant change in serum total cholesterol , LDL-C , HDL-C , and apoprotein B. ( ABSTRACT TRUNCATED AT 250 WORDS", "Introduction : Many studies support the role of vitamin D in the pathogenesis of both types of diabetes . Pancreatic tissues express the vitamin D receptor ( VDR ) and vitamin D-binding protein ; some allelic variations in genes involved in vitamin D metabolism and VDR are associated with glucose intolerance , defective insulin secretion , and sensitivity . Epidemiological links have been established between type 2 diabetes mellitus ( DM ) and hepatitis C virus ( HCV ) infection . Aim : To explore the possible therapeutic potential of pharmacologic doses of 1-α-hydroxy vitamin D therapy in improving pancreatic β-cell function in HCV seropositive hemodialysis ( HD ) patients . Patients and methods : Twenty HCV seropositive HD patients and 20 HCV seronegative patients as control group were r and omly selected from HD units . 1-α-Hydroxy vitamin D therapy was administrated in the dose ranged from 0.25 to 0.5 μg/day for 3 months . Corrected total serum calcium , phosphorus , intact parathyroid hormone ( iPTH ) , 25-hydroxy vitamin D [ 25(OH ) vitamin D ] , 1,25-dihydroxy vitamin D , and glucoparameters [ fasting blood glucose , glycohemoglobin test ( HbA1c% ) , homeostatic model assessment (HOMA)-insulin resistance , and HOMA-β-cell function% ( B% ) ] were measured under basal conditions and after 3 months of therapy . Results : There was highly significant improvement in the concentrations of fetal bovine serum ( FBS ) , serum insulin , HbA1c% , 25(OH ) vitamin D , and HOMA-β-cell function in HCV seropositive and HCV seronegative groups after oral 1-alphacalcidiol therapy ( p increase in serum insulin and that in HOMA-β-cell function versus 25(OH ) vitamin D ( p Conclusion : 1-α-Hydroxy vitamin D oral therapy may improve glycemic control in HCV seropositive and HCV seronegative HD patients", "OBJECTIVE Insulin resistance ( IR ) is associated with increased cardiovascular risk in multiple patient population s , including those undergoing chronic hemodialysis ( CHD ) . Active vitamin D deficiency has been proposed to play a role in the extent of IR observed in patients with CHD . We postulated that administration of paracalcitol , an active vitamin D medication , influences IR in patients with CHD . DESIGN AND METHODS This was a pilot r and omized controlled trial . Ten prevalent CHD patients receiving a stable dose of paracalcitol were recruited . Paracalcitol was withheld for 8 weeks in all patients ( phase I ) . Parathyroid hormone levels were managed with the calcium-sensing receptor agonist cinacalcet . At week 8 , patients were r and omized to continue cinacalcet or to restart paracalcitol for 8 weeks ( phase II ) . The primary outcome was the change in IR measured by the glucose disposal rate ( GDR ) using hyperinsulinemic euglycemic clamp ( HEGC ) method . Secondary outcomes included changes in IR between groups in indirect indices of IR , biomarkers of inflammation , and adipokine levels . RESULTS The mean age was 49 years ( range , 46 - 57 years ) and 40 % of patients were women . There was no detectable change in the GDR at the end of phase I ( P = .7 ) when compared with baseline values . There was also no statistically significant difference in GDR between groups at the end of phase II ( P = .9 ) . No changes were observed in indirect indices of IR , adipokine levels , or biomarkers of inflammation in either phase . CONCLUSION The results of this pilot study suggest that withdrawal of paracalcitol over 8 to 16 weeks and replacement for 8 weeks after withdrawal does not influence IR measured by HEGC in patients receiving CHD", "This study was conducted to assess the effect of oral calcitriol on glucose metabolism in patients on hemodialysis ( HD ) . A total of 27 patients on HD at the Mashhad University of Medical Sciences , Iran , none of whom had received calcitriol or had history of diabetes , were selected . The patients were r and omly divided into two groups ; Group I : patients who received oral calcitriol for eight weeks and , Group II : patients who received placebo . In all cases , levels of fasting glucose , insulin , lipid profile , calcium , phosphorous , parathormone ( PTH ) , HbA1C and blood sugar after administration of 75 grams of glucose , insulin resistance and beta cell function were measured , before and after the treatment period . The two sets of results were then compared with one another . In Group l patients , the levels of the parameters studied before and after the study period were as follows : blood sugar after 75 grams of glucose ( 88.67 + /- 8.68 versus 99.83 + /- 34.42 mg/dL , p = 0.045 ) , HOMA-IR ( 2.05 + /- 1.42 versus 2.42 + /- 1.33 , p = 0.035 ) , HbA1C ( 5.99 + /- 1.00 versus 6.14 + /- 1.19 , p= total cholesterol ( 153.3 + / 43.80 mg/dl versus 157.0 + /52.62 , p = 0.037 ) and triglycerides ( 175.30 + /- 99.65 versus 214.9 + /- 117.7 mg/dL , p = 0.036 ) . Thus , there was a significant decrease after the study period . In Group II , fasting blood sugar ( 110.7 + /- 26.12 versus 81.14 + /- 13.31 mg/dL , p = 0.002 ) , HbA1C ( 6.99 + /- 1.44 versus 6.17 + /- 1.66 , p = 0.004 ) and HOMA-IR ( 5.85 + /- 5.11 versus 3.20 + /- 2.39 , p = 0.036 ) significantly increased and beta cell function significantly decreased ( 149.5 + /- 90.57 versus 355.7 + /- 299.3 , p = 0.032 ) after the study period . In conclusion , our results show that vitamin D has a significant influence on glucose metabolism . Similar studies on larger sample size are required to confirm this observation" ]

[ "Aims : To identify the work factors that predict intense low back pain ( LBP ) and LBP related sick leaves in nurses ’ aides . Methods : The sample comprised 4266 r and omly selected Norwegian nurses ’ aides , not bothered or only a little bothered by LBP during the previous three months , and not on sick leave when completing a mailed question naire in 1999 . Of these , 3808 ( 89.3 % ) completed a second question naire 3 months later and 3651 ( 85.6 % ) completed a third question naire 15 months later . Intensity of low back symptoms and certified sick leaves attributed to LBP during the observation period were assessed by self reports at the follow ups . Results : After adjustments for LBP during the three months prior to baseline , baseline health complaints , demographic and familial factors , and a series of physical , psychological , and social work factors , logistic regression analyses revealed the following associations : intense low back symptoms were predicted by frequent positioning of patients in bed , perceived lack of support from immediate superior , and perceived lack of pleasant and relaxing culture in the work unit . LBP related sick leaves were predicted by frequent h and ling of heavy objects , medium level of work dem and s , perceived lack of supportive and encouraging culture in the work unit , working night shifts , and working in a nursing home . Long term LBP related sick leaves were associated with changes of work or work tasks during the observation period that result ed in a perceived reduction of support and encouragement at work . Conclusions : Not only frequent mechanical exposures , but also organisational , psychological , and social work factors , such as night shift work , perceived lack of support from superior , and perceived lack of a pleasant and relaxing or supporting and encouraging culture in the work unit , are associated with an increased risk of intense low back symptoms and LBP related sick leaves in nurses ’ aides", "To investigate the associations between psychosocial factors and the development of chronic disabling low back pain ( LBP ) in Japanese workers . A 1 yr prospect i ve cohort of the Japan Epidemiological Research of Occupation-related Back Pain ( JOB ) study was used . The participants were office workers , nurses , sales/marketing personnel , and manufacturing engineers . Self-administered question naires were distributed twice : at baseline and 1 yr after baseline . The outcome of interest was the development of chronic disabling LBP during the 1 yr follow-up period . Incidence was calculated for the participants who experienced disabling LBP during the month prior to baseline . Logistic regression was used to assess risk factors for chronic disabling LBP . Of 5,310 participants responding at baseline ( response rate : 86.5 % ) , 3,811 completed the question naire at follow-up . Among 171 eligible participants who experienced disabling back pain during the month prior to baseline , 29 ( 17.0 % ) developed chronic disabling LBP during the follow-up period . Multivariate logistic regression analysis implied reward to work ( not feeling rewarded , OR : 3.62 , 95%CI : 1.17–11.19 ) , anxiety ( anxious , OR : 2.89 , 95%CI : 0.97–8.57 ) , and daily-life satisfaction ( not satisfied , ORs : 4.14 , 95%CI : 1.18–14.58 ) were significant . Psychosocial factors are key to the development of chronic disabling LBP in Japanese workers . Psychosocial interventions may reduce the impact of LBP in the workplace", "Objectives Studies from western countries show that dentists are vulnerable to work-related musculoskeletal disorders ( WMSDs ) of the neck and upper extremities , but little is known about their epidemiology among members of this rapidly growing profession in China . This study aims to investigate the prevalence of WMSDs and identify potential risk factors associated with their occurrence in the dental profession in China . Setting and participants A cross-sectional survey was carried out in 52 different hospitals in a large metropolitan city in China . A total of 304 question naires were distributed to respondents identified via stratified r and om sampling and 272 dentists ( 121 females and 151 males ) completed the survey . The response rate was 89.5 % . Outcomes Visual analogue score was used to record neck and upper limb musculoskeletal symptoms on a body chart . Work-related risk factors , including physical and psychosocial factors , were accounted for in the regression analysis . Results 88 % of the dentists reported at least one musculoskeletal disorder and 83.8 % suffered from neck pain . In the multivariate analyses , working hours per day were associated with neck pain ( OR=1.43 ; 95 % CI 1.03 to 1.98 ) . Inability to select the appropriate size of dental instrument was associated with shoulder ( OR=2.07 ; 95 % CI 1.00 to 4.32 ) and wrist/h and ( OR=2.47 ; 95 % CI 1.15 to 5.32 ) pain . As for psychosocial factors , high job dem and was associated with symptoms in the shoulder ( OR=1.09 ; 95 % CI 1.00 to 1.18 ) , elbow ( OR=1.11 ; 95 % CI 1.03 to 1.19 ) and wrist/h and ( OR=1.09 ; 95 % CI 1.02 to 1.17 ) . Regular physical exercise was associated with decreased neck pain ( OR=0.37 ; 95 % CI 0.14 to 1.00 ) . Conclusions The prevalence of WMSDs among Chinese dentists is high . Specifically , long working hours , inability to select the appropriate size of dental instrument and high job dem and are the most significant risk factors", "Study Design Two-year , prospect i ve cohort data from the Japan epidemiological research of occupation-related back pain study in urban setting s were used for this analysis . Objective To examine the association between aggravated low back pain and psychosocial factors among Japanese workers with mild low back pain . Summary of Background Data Although psychosocial factors are strongly indicated as yellow flags of low back pain ( LBP ) leading to disability , the association between aggravated LBP and psychosocial factors has not been well assessed in Japanese workers . Methods At baseline , 5,310 participants responded to a self-administered question naire including questions about individual characteristics , ergonomic work dem and s , and work-related psychosocial factors ( response rate : 86.5 % ) , with 3,811 respondents completing the 1-year follow-up question naire . The target outcome was aggravation of mild LBP into persistent LBP during the follow-up period . Incidence was calculated for the participants with mild LBP during the past year at baseline . Logistic regression was used to explore risk factors associated with persistent LBP . Results Of 1,675 participants who had mild LBP during the preceding year , 43 ( 2.6 % ) developed persistent LBP during the follow-up year . Multivariate analyses adjusted for individual factors and an ergonomic factor found statistically significant or almost significant associations of the following psychosocial factors with persistent LBP : interpersonal stress at work [ adjusted odds ratio ( OR ) : 1.96 and 95 % confidence interval ( 95%CI ) : 1.00–3.82 ] , job satisfaction ( OR : 2.34 , 95%CI : 1.21–4.54 ) , depression ( OR : 1.92 , 95%CI : 1.00–3.69 ) , somatic symptoms ( OR : 2.78 , 95%CI : 1.44–5.40 ) , support from supervisors ( OR : 2.01 , 95%CI : 1.05–3.85 ) , previous sick-leave due to LBP ( OR : 1.94 , 95%CI : 0.98–3.86 ) and family history of LBP with disability ( OR : 1.98 , 95%CI : 1.04–3.78 ) . Conclusions Psychosocial factors are important risk factors for persistent LBP in urban Japanese workers . It may be necessary to take psychosocial factors into account , along with physical work dem and s , to reduce LBP related disability", "Objectives To assess dental students ' posture on two different seats in order to determine if one seat predisposes to a difference in working posture . Design A between-subject experimental design was selected . Setting The study was undertaken at the University of Birmingham School of Dentistry in 2006 . Subjects ( material s ) and methods Sixty second year dental students at the University of Birmingham who were attending their fi rst classes in the phantom head laboratory were r and omly selected and allocated to two different seats ( 30 Bambach Saddle Seats and 30 conventional seats ) . Students were trained in the use of the seats . After ten weeks , the students were observed , photographs were taken by the research er and these were assessed using Rapid Upper Limb Assessment ( RULA ) . Main outcome measures The posture of the students was assessed using the RULA . Each student was given a risk score . A Mann Whitney test was used for statistical analysis . Results The results indicated that the students using the conventional seat recorded signifi cantly higher risk scores ( p Bambach Saddle Seat , suggesting an improvement in posture when using the Bambach Saddle Seat . Conclusion RULA has identifi ed that dental students using a Bambach Saddle Seat were able to maintain an acceptable working posture during simulated dental treatment and this seating may reduce the development of work-related musculoskeletal disorders", "This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . \" Quality \" as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence", "Activation of back musculature during work tasks leads to fatigue and potential injury . This is especially prevalent in dentists who perform much of their work from a seated position . We examined the use of an ergonomic dental stool with mid-sternum chest support for reducing lower back muscle activation . Electromyography of lower back extensors was assessed from 30 dental students for 20 s during three conditions in r and om order : ( a ) sitting upright at 90 ° of hip flexion on a st and ard stool , ( b ) leaning forward at 80 ° of hip flexion on a st and ard stool , and ( c ) leaning forward at 80 ° of hip flexion while sitting on an ergonomic stool . Muscular activity of the back extensors was reduced when using the ergonomic stool compared to the st and ard stool , by 33–50 % ( p < 0.01 ) . This suggests a potential musculoskeletal benefit with use of a dental stool with mid-sternum chest support", "BACKGROUND CONTEXT Sitting spinal alignment is increasingly recognized as a factor influencing strategy for deformity correction . Considering that most individuals sit for longer hours in a \" slumped \" rather than in an erect posture , greater underst and ing of the natural sitting posture is warranted . PURPOSE This study aim ed to investigate the differences in sagittal spinal alignment between two common sitting postures : a natural , patient-preferred posture ; and an erect , investigator-controlled posture that is commonly used in alignment studies . DESIGN / SETTING This is a r and omized , prospect i ve study of 28 young , healthy patients seen in a tertiary hospital over a 6-month period . PATIENT SAMPLE Twenty-eight patients ( 24 men , 4 women ) , with a mean age of 24 years ( range 19 - 38 ) , were recruited for this study . All patients with first episode of lower back pain of less than 3 months ' duration were included . The exclusion criteria consisted of previous spinal surgery , radicular symptoms , red flag symptoms , previous spinal trauma , obvious spinal deformity on forward bending test , significant personal or family history of malignancy , and current pregnancy . OUTCOME MEASURES Radiographic measurements included sagittal vertical axis ( SVA ) , lumbar lordosis ( LL ) , thoracolumbar angle ( TL ) , thoracic kyphosis ( TK ) , and cervical lordosis ( CL ) . St and ard spinopelvic parameters ( pelvic incidence , pelvic tilt [ PT ] , and sacral slope ) and sagittal apex and end vertebrae were also measured . METHODS Basic patient demographics ( age , gender , ethnicity ) were recorded . Lateral sitting whole spine radiographs were obtained using a slot scanner in the imposed erect and the natural sitting posture . Statistical analyses of the radiographical parameters were performed comparing the two sitting postures using chi-squared tests for categorical variables and paired t tests for continuous variables . RESULTS There was forward SVA shift between the two sitting postures by a mean of 2.9 cm ( p increase in CL by a mean of 11.62 ° ( p TL kyphosis by a mean of 11.48 ° ( p loss of LL by a mean of 21.26 ° ( p mean PT increased by 17.68 ° ( p increase in CL and PT , as well as a constant SVA . These findings lend insight into the body 's natural way of energy conservation using the posterior ligamentous tension b and while achieving sitting spinal sagittal balance . It also provides information on one of the possible causes of proximal junctional kyphosis or proximal junctional failure" ]

[ "PURPOSE The present follow-up study was carried out to evaluate the performance of Class II Cerec inlays after 10 years of clinical service . MATERIAL S AND METHODS Sixty-six Class II CAD/CAM ceramic inlays were placed in 27 patients . Each patient received at least one inlay luted with a dual-cured resin composite and one inlay luted with a chemically cured resin composite . At the 10-year recall , 25 ( 93 % ) patients with 61 ( 92 % ) inlays were available for evaluation using a slight modification of the USPHS criteria . RESULTS Fifty-four ( 89 % ) of the 61 inlays reevaluated still functioned well at the 10-year recall . During the follow-up period , seven ( 11 % ) of the inlays required replacement because of : four inlay fractures , one cusp fracture , endodontic problems in one case , and postoperative symptoms in one case . All the replaced inlays had been luted with the dual-cured resin composite . The fractured inlays were all placed in molars . The estimated survival rate after 10 years was 89 % , 77 % for the dual-cured resin composite-luted inlays and 100 % for the chemically cured resin composite-luted ones . The difference was statistically significant . CONCLUSION Patient satisfaction with and acceptance of the Cerec inlays were high , and the performance after 10 years of clinical service was acceptable , especially regarding the inlays luted with the chemically cured resin composite . The properties of the luting agents seem to affect the longevity of the type of ceramic inlays evaluated", "PURPOSE The objective of this follow-up study was to examine the performance of Cerec inlays and onlays in terms of clinical quality over a functional period of 10 years . MATERIAL S AND METHODS Of 200 Cerec inlays and onlays placed in a private practice between 1989 and early 1991 , 187 restorations were observed over a period of 10 years . The restorations were fabricated chairside using the Cerec-1 computer-aided design /manufacturing ( CAD/CAM ) method and Vita MK I feldspathic ceramic . An adhesive technique and luting composite resin were used for seating the restorations . After 10 years , the clinical performance of the restorations was evaluated using modified USPHS criteria . The results were used to classify success and failure . RESULTS According to Kaplan-Meier analysis , the success rate of Cerec inlays and onlays dropped to 90.4 % after 10 years . A total of 15 ( 8 % ) failures were found in 11 patients . Of these failures , 73 % were caused by either ceramic fractures ( 53 % ) or tooth fractures ( 20 % ) . The reasons for the remaining failures were caries ( 20 % ) and endodontic problems ( 7 % ) . The three-surface Cerec reconstructions were found to have the most failures . CONCLUSION The failure rate of 8 % and the drop of the survival probability rate to 90.4 % after 10 years of clinical service of Cerec-1 CAD/CAM restorations made of Vita MK I feldspathic ceramic appear to be acceptable in private practice . This is particularly true in light of the very high patient satisfaction", "This study evaluated the quality of fired ceramic inlay restorations consisting of a feldspathic porcelain system ( G-Cera Cosmotech II , GC Co , Tokyo , Japan ) after eight years in vivo . Forty-five fired ceramic inlays ( for 26 premolars and 19 molars ; Class I in 12 teeth , Class II in 31 teeth and onlay in two teeth ) were placed in 25 patients . All restorations were evaluated at the time of placement and at 6 months , 1 , 2 , 4 , 6 and 8 years after placement using modified USPHS criteria . Replicas of the restorations were observed with a scanning electron microscope ( SEM ) to evaluate the degradation of the marginal area and wear loss of the restoration . Longevity was observed in 80 % of the fired ceramic inlay restorations at eight years ( Kaplan-Meier method ) , although it was 92 % at the six-year observation . Marginal fracture was detected in 11 restorations ( 22 % ) , including bulk fracture in five ( 11 % ) , which had first occurred during the last two years . Recurrent caries was observed in three ( 7 % ) cases and marginal discoloration in 14 ( 31 % ) . SEM evaluation disclosed marginal microfractures in 77 % of the restorations , wear in 36 % and wear of the resin cement along the margin in 74 % at eight years . No significant difference was observed in each of these three characteristics between molars and premolars . This longitudinal eight-year clinical observation suggested that fired ceramic inlay restorations made by the G-Cera Cosmotech II system are clinical ly acceptable . However , critical failure as bulk fracture may become a future problem since marginal disintegration was detected in 77 % of the restorations from microscopic and macroscopic perspectives", "AIM This study compared the fracture resistance of endodontically-treated m and ibular molars with mesio-occluso-distal ( MOD ) cavities restored using different restoration techniques . METHODOLOGY Sixty sound extracted m and ibular molars were r and omly assigned to six groups ( n=10 ) . Group 1 did not receive any preparation . The teeth in Groups 2 - 6 received root canal treatment and a MOD cavity preparation . The teeth in Group 2 were kept unrestored . Group 3 was restored conventionally with amalgam . Group 4 was restored with a dentin bonding system ( DBS , Clearfil SE Bond ) and resin composite ( CR ) ( Clearfil Photoposterior ) . Group 5 was restored with indirect hybrid ceramic inlay material ( Estenia ) . In Group 6 , polyethylene ribbon fiber ( Ribbond ) was inserted into cavities in a buccal-to-lingual direction and the teeth were then restored with DBS and CR . After finishing and polishing , the specimens , except for Group 2 , were loaded to failure by a chewing simulation device ( 60,000 cycles x 50 N load , 1.3 Hz frequency ) in an artificial environment at 37 degrees C. Each tooth was subjected to compressive loading perpendicular to the occlusal surface at a crosshead speed of 1 mm/minute . The mean loads necessary to fracture were recorded in Newtons and the results were statistically analyzed . RESULTS The mean fracture values were as follows : Group 1 : 2485.3 + /- 193.98a , Group 2 : 533.9 + /- 59.4a , Group 3 : 1705.8 + /- 135.7a , Group 4 : 2033.3 + /- 137.6cd , Group 5 : 2121.3 + /- 156.5d , Group 6 : 1908.9 + /- 132.2cd . There were statistically significant differences between the groups annotated with different letters . Thus , Group 1 ( intact teeth ) had the greatest fracture resistance and Group 2 ( non-restored teeth ) the poorest . No statistically significant differences were found between Groups 3 ( amalgam ) , 4 ( resin composite ) and 6 ( polyethylene ribbon fiber reinforced composite ) ( p > 0.05 ) . Group 5 ( indirect hybrid ceramic inlay ) had greater fracture resistance than Group 3 ( p indirect hybrid inlay restorations in these teeth may be recommended , because this restoration technique indicated more favorable fracture failure modes than other restoration techniques used in this study and particularly greater fracture strength than amalgam restorations . The promising result of indirect hybrid inlay restorations may need to be confirmed by long-term clinical studies", "PURPOSE The aim of the present study was to clinical ly evaluate the effect of two different adhesive/resin composite combinations for luting IPS Empress inlays with a special focus on luting gap wear and marginal adaptation . MATERIAL S AND METHODS In the course of a controlled prospect i ve clinical split-mouth study , 94 IPS Empress restorations were placed in 31 patients . The inlays were luted with EBS Multi + Compolute ( EC ; 3 M ESPE ) or with Syntac + Variolink II low ( SV ; Ivoclar Vivadent ) . At baseline and after 0.5 , 1 , 2 , 4 , and 8 years , the ceramic restorations were examined according to modified USPHS codes and criteria . Thirty-five selected sample s were investigated under an SEM regarding morphological changes ; marginal quality analysis was carried out using a stereo light microscope , and luting composite wear was scanned with a profilometer . RESULTS Eight patients ( including 25 restorations ) missed the recalls ; the recall rate at the last investigation was 72 % . After 96 months of clinical service , seven restorations in five patients ( six EC , one SV ) had to be replaced due to hypersensitivities ( n = 5 ) or inlay fractures ( n = 2 ) result ing in a survival rate of 90 % . Over the 8-year period , the restorations revealed no statistically significant differences in terms of surface roughness , color matching , proximal contact , sensitivity , or complaints ( p > 0.05 , Friedman test ) . Significant deteriorations were found for marginal integrity ( p 0.05 ; Mann-Whitney U-test ) , however , the scans of the luting gap showed that Compolute was more prone to wear ( p overall failure rate after 8 years was 10 %", "In a dental practice , 2328 ceramic inlays were placed in 794 patients . The restorations were manufactured chairside using Cerec technology and adhesively inserted at the same appointment . The clinical performance of the restorations was evaluated with the Kaplan-Meier analysis . The probability of survival was 95.5 % after 9 years ; 35 Cerec restorations were judged as failures . The prognosis for success was not significantly influenced by restoration size , tooth vitality , treatment of caries profunda ( CP ) , type of tooth treated , or whether the restoration was located in the maxilla or m and ible . The most common type of failure was the extraction of a tooth . In a clinical follow-up light-microscopic examination of 44 r and omly selected restorations , an average composite joint width of 236.3 microns was found . 45.1 % of the restorations exhibited a perfect margin , and 47.4 % of the investigated joint sections showed underfilled margins", "PURPOSE The aim of the study was to clinical ly evaluate Empress II inlays cemented with a dual-curing bonding agent and a self-curing luting system . MATERIAL S AND METHODS Forty patients were selected to receive one Empress II inlay . Empress II is a heat-pressed glass ceramic containing lithium disilicate and lithium orthophosphate crystals , purported to provide higher stress resistance and improved strength . The restorations were placed between March and May 2000 . Recalls were performed after 6 , 12 , 24 , and 36 months . At the 3-year recall , 7 patients were lost to follow-up . Inlays were evaluated for postoperative sensitivity , marginal integrity , marginal leakage , color stability , surface staining , retention , and surface crazing ( microcracks ) . RESULTS At the 3-year recall , all the restorations were in place and only one showed postoperative sensitivity ( at the first recall , 1 week after placement ) . Only 3 inlays showed slight marginal staining , and 4 inlays showed gaps , with little surface staining or microcracks . CONCLUSIONS No inlay debonded or fractured during theobservation period . All the evaluated inlays were in place and acceptable", "OBJECTIVES To measure subcritical crack growth parameters in vitro and to correlate those with clinical observations from the 12 years recall of a prospect i ve clinical study . METHODS Bending bars were manufactured and the inert fracture strength was determined in four-point bending and silicon oil . Weibull statistics were applied and the parameters m and sigma(0 ) were calculated . Dynamic fatigue experiments were performed in water at four decreasing loading rates from 1.3 to 0.0013MPa/s . The parameters of subcritical crack growth n and A were calculated . Strength-fracture probability-life time ( SPT ) predictions were derived for 1 , 4 , 8 and 12 years , based on a static crack growth mechanism . The 12 years clinical recall of a prospect i ve clinical study on the same material was performed . Bulk , chipping and marginal fractures or detoriations were focused here . Failure rates were calculated according to Kaplan-Meier survival analysis and merged into the SPT diagram . RESULTS Inert fracture strength of the glassceramic was measured to sigma(0)=134MPa and the Weibull modulus to m=8.1 . The subcritical crack growth parameter n was calculated to n=19.2 and the extrapolated crack velocity to A=0.0014 m/s . Based on a clinical relevant failure probability of P(F)=5 % , material strength was predicted to decrease from initial sigma(0.05)=93MPa down to sigma(0.05)=33MPa after 12 years ( -64 % ) . The clinical survival rate dropped from 100 % ( 1 year ) to 93 % ( 4 years ) , 92 % ( 8 years ) and 86 % after 12 years . The incidence of inlay defects like chipping and marginal fractures increased from 1 % at baseline , 7 % after 4 years , 26 % after 8 years to 57 % after 12 years . SIGNIFICANCE Clinical data match the slow crack growth measurements in terms of dramatically increased clinical bulk fractures and detoriations from marginal and chipping fractures after 12 years . Clinical survival rate seems to converge towards the in vitro lifetime predictions with increasing time . A failure level of P(F)=5 % is clinical ly exceeded after 4 years of clinical service , which corresponds to an experimental prediction of fracture releasing static loading of 35.5MPa . Since average chewing pressure over time is less deleterious compared to static loading , this regression analysis provides a conservative threshold value", "PURPOSE This controlled clinical trial aim ed to evaluate IPS Empress inlays and onlays over 12 years . The None hypothesis was that different luting resins would have no influence on clinical outcome . MATERIAL S AND METHODS In the course of a prospect i ve clinical long-term trial , 96 ceramic inlays and onlays were placed in 34 patients using one adhesive ( Syntac ) and four different luting composites ( Tetric , Variolink Low , Variolink Ultra , Dual Cement ) . Recalls were carried out by two calibrated investigators using modified USPHS codes and criteria at baseline , 1 , 2 , 4 , 6 , 8 , and 12 years . RESULTS Fifteen of the 96 restorations had to be replaced ( failure rate 16 % ; Kaplan-Meier ) ; 12 of them suffered bulk fractures . After twelve years of clinical service , significantly more bulk fractures were found when light-curing composite was used for luting ( p Fractures were noticed between 3 and 4 years of clinical service and later after 11 to 12 years ; aside from those times , no single fracture occurred . Secondary caries was not observed . CONCLUSION IPS Empress inlays and onlays exhibited satisfactory clinical outcomes over a 12-year clinical period . Restorations luted with dual-cured resin composites revealed significantly fewer bulk fractures", "OBJECTIVES Midterm-evaluation of a 5-year prospect i ve clinical splitmouth-investigation on survival rate and long-term behavior of all-ceramic partial coverage restorations ( PCRs ) on molars . Pressed ceramic and CAD/CAM fabricated PCRs were compared . METHODS 80 vital molars of 25 patients were restored with all-ceramic PCRs ( 40 IPS e.max Press*[IP ] and 40 ProCAD*[PC ] ) . IP-PCRs were heat pressed following the lost-wax method . PC-PCRs were fabricated with Cerec 3 * * and Cerec InLab * * CAD/CAM system ( * * Sirona Dental Systems , Bensheim , Germany ) . All PCRs were adhesively luted with a light-polymerizing composite ( Syntac*/Tetric * ) ( * Ivoclar Vivadent , Schaan , Liechtenstein ) . Clinical reevaluations were performed at baseline and 13 , 25 , and 36 months after insertion of the PCRs according to the modified United States Public Health Services ( USPHS ) criteria . Absolute failures were demonstrated by Kaplan-Meier survival rate . RESULTS After an observation time up to 3 years , survival rate of IP-PCRs was 100 % and 97 % for PC-PCRs due to one severe fracture . The PC-PCR had to be replaced after 9 months . Secondary caries and endodontic complications did not occur . Increased clinical service time result ed in significant decrease of marginal adaptation ( p=0.031 ) and enhanced marginal discoloration ( p deteriorations in color match ( p surface roughness ( p IP-PCRs were significantly more affected ( p < or = 0.005 ) . Regarding anatomic form IP-PCRs performed significantly better ( p=0.0012 ) . CONCLUSION Pressed ceramic and CAD/CAM fabricated partial coverage restorations exhibited a reliable treatment option to restore larger defects in posterior teeth . Marginal degradation of the resin cement and deterioration of the all-ceramic material s during clinical function determine the clinical long-term performance of partial coverage restorations" ]

[ "& NA ; The feasibility of altering a Type A style of life was investigated in 1012 nonsmoking predominantly male postinfa rct ion volunteers in the San Francisco Bay area . A total of 862 were r and omly allocated into an experimental section receiving a combination of Type A and cardiac counseling , or a control section receiving cardiac counseling alone . The remaining 150 formed a nonr and om but statistically equivalent comparison section . Assessment s of change in Type A behavior were made by the participant , his or her spouse , a work colleague , and an independent rater of a videotaped structured interview . Psychometric analyses indicated that these instruments were valid and reliable measures of Type A behavior . After 24 months , participants receiving Type A/cardiac counseling exhibited a significantly greater reduction in Type A behavior than the other two sections , and had a lower cardiovascular recurrence rate than the comparison section only . No differences among the three sections were observed in total cholesterol or resting blood pressure . The results suggest that Type A behavior can be altered by group counseling in postinfa rct ion volunteers and that such alteration is superior to no group counseling at all in the secondary prevention of coronary heart disease", "OBJECTIVE Although the Enhancing Recovery in Coronary Heart Disease ( ENRICHD ) treatment was design ed to include individual therapy and cognitive behavioral group training for patients with depression and /or low perceived social support , only 31 % of treated participants received group training . Secondary analyses classified intervention participants into two subgroups , ( 1 ) individual therapy only or ( 2 ) group training ( i.e. , coping skills training ) plus individual therapy , to determine whether medical outcomes differed in participants who received the combination of group training and individual therapy compared to participants who received individual therapy only or usual care . METHODS Secondary analyses of 1243 usual care , 781 individual therapy only , and 356 group plus individual therapy myocardial infa rct ion ( MI ) patients were performed . Depression was diagnosed using modified Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) criteria ; low perceived social support was determined by the ENRICHD Social Support Instrument . Psychosocial treatment followed MI , and for participants with severe or unremitting depression , was supplemented with a selective serotonin reuptake inhibitor . Cox proportional hazards regression was used to estimate intervention effects on time to first occurrence of the composite end point of death plus nonfatal MI . To control for confounding of group participation with survival ( because individual sessions preceded group ) , we used risk set sampling to match minimal survival time of those receiving or not receiving group training . RESULTS Analyses correcting for differential survival among comparison groups showed that group plus individual therapy was associated with a 33 % reduction ( hazard ratio=0.67 ; 95 % confidence interval , 0.49 - 0.92 , P=.01 ) in medical outcome compared to usual care . No significant effect on event-free survival was associated with individual therapy alone . The group training benefit was reduced to 23 % ( hazard ratio=0.77 ; 95 % confidence interval : 0.56 - 1.07 , P=.11 ) in the multivariate-adjusted model . CONCLUSIONS Findings suggest that adding group training to individual therapy may be associated with reduction in the composite end point . A r and omized controlled trial is warranted to definitively resolve this issue", "& NA ; A trial of brief group therapy as part of a rehabilitation program for postmyocardial infa rct ion ( MI ) patients was carried out . Forty‐four patients surviving their first MI were r and omly allocated to either group therapy or control group status and were followed over 4 years . An additional group of 17 patients were referred for post‐MI group therapy sessions after the termination of the controlled experiment and were followed for 3 years . Patients who received group therapy had significantly less follow‐up coronary morbidity and mortality , and returned to work at significant higher percentages than control patients . Although neither group therapy nor control group patients meaningfully altered conventional coronary risk factors , group therapy patients ( in the controlled trial ) successfully altered selected coronary‐prone behaviors . Educational information regarding the physiological and psychological aspects of coronary heart disease , presented in the group therapy sessions , was forgotten over follow‐up . It is concluded that the supportive aspects of the group therapy experience played the most important role in determining the rehabilitation advantages seen for treatment patients", "CONTEXT There has been little research on the treatment of depression after coronary artery bypass surgery . OBJECTIVE To test the efficacy of 2 nonpharmacological interventions for depression after coronary artery bypass surgery compared with usual care . DESIGN A 12-week , r and omized , single-blind clinical trial with outcome evaluations at 3 , 6 , and 9 months . SETTING Outpatient research clinic at Washington University School of Medicine , St Louis , Missouri . PATIENTS One hundred twenty-three patients who met the DSM-IV criteria for major or minor depression within 1 year after surgery . INTERVENTION Twelve weeks of cognitive behavior therapy or supportive stress management . Approximately half of the participants were taking non study antidepressant medications . MAIN OUTCOME MEASURE Remission of depression , defined as a score of less than 7 on the 17-item Hamilton Rating Scale for Depression . RESULTS Remission of depression occurred by 3 months in a higher proportion of patients in the cognitive behavior therapy ( 71 % ) and supportive stress-management ( 57 % ) arms than in the usual care group ( 33 % ) ( chi(2)(2 ) = 12.22 , P = .002 ) . Covariate-adjusted Hamilton scores were lower in the cognitive behavior therapy ( mean [ st and ard error ] , 5.5 [ 1.0 ] ) and the supportive stress-management ( 7.8 [ 1.0 ] ) arms than in the usual care arm ( 10.7 [ 1.0 ] ) at 3 months . The differences narrowed at 6 months , but the remission rates differed again at 9 months ( 73 % , 57 % , and 35 % , respectively ; chi(2)(2 ) = 12.02 , P = .003 ) . Cognitive behavior therapy was superior to usual care at most points on secondary measures of depression , anxiety , hopelessness , stress , and quality of life . Supportive stress management was superior to usual care only on some of the measures . CONCLUSIONS Both cognitive behavior therapy and supportive stress management are efficacious for treating depression after coronary artery bypass surgery , relative to usual care . Cognitive behavior therapy had greater and more durable effects than supportive stress management on depression and several secondary psychological outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00042198", "Objective : The Enhancing Recovery in Coronary Heart Disease study was a multicenter clinical trial in which patients with depression and /or low perceived social support after an acute myocardial infa rct ion were r and omly assigned to an intervention consisting of cognitive behavior therapy and , in some cases , sertraline , or to usual care . There was no difference in survival between the groups . A possible reason why the intervention failed to affect survival is that too many patients with mild , transient depression were enrolled . Another is that some patients died too soon to complete the intervention . This analysis evaluates whether there was a difference in late ( ie , ≥6 months after the myocardial infa rct ion ) mortality among initially depressed patients who had a Beck Depression Inventory score ≥10 and a past history of major depression , and who completed the 6-month post-treatment assessment . It also examines the relationship between change in depression and late mortality . Methods : Out of the 1,165 ( 47 % ) of the Enhancing Recovery in Coronary Heart Disease study participants who met our criteria , 57 died in the first 6 months , and 858 ( 409 usual care , 449 intervention ) completed the 6-month assessment . Cox regression was used to analyze survival . Results : The intervention did not affect late mortality . However , intervention patients whose depression did not improve were at higher risk for late mortality than were patients who responded to treatment . Conclusions : Patients whose depression is refractory to cognitive behavior therapy and sertraline , two st and ard treatments for depression , are at high risk for late mortality after myocardial infa rct ion", " One hundred fifty-six myocardial infa rct ion patients were r and omly assigned to either exercise plus relaxation and breathing therapy ( treatment A , n = 76 ) or to exercise training only ( treatment B , n = 80 ) . Effects on exercise testing showed a more pronounced training bradycardia and a remarkable improvement in ST abnormalities in treatment A ( p less than 0.005 ) . A model was developed to integrate the various exercise parameters into a single measure for training benefit . Approximately half the patients showed a training success , with a more positive and less negative outcome in treatment A ( p = 0.09 ) . The odds for failure were 0.25 for treatment A and 0.51 for treatment B ( odds ratio : 2.04 ; 95 % confidence interval , 0.94 to 4.6 ) . Thus the risk of failure was reduced by half when relaxation was added to exercise training . These results indicate that exercise training is not successful in all MI patients and that relaxation therapy enhances training benefit", "Objective Depression is common following an acute cardiac event and can occur at a time when behaviour change is strongly recommended to reduce the risk of further cardiovascular events . The ‘ Beating Heart Problems ’ programme was design ed to support cardiac patients in behaviour change and mood management . Methods The programme was based on cognitive behaviour therapy and motivational interviewing . A r and omized controlled trial ( RCT ) comparing the 8-week group programme with usual care was undertaken between 2007 and 2010 . All patients attended a hospital-based clinic for assessment of physiological risk factors at baseline ( 6 weeks after their acute event ) , and at 4- and 12-month follow up . Psychological and behavioural indicators were assessed by self-report question naires . Of the 275 patients enrolled into the RCT , 42 ( 15 % ) had Beck Depression Inventory-II scores > 13 at baseline . Treatment and control group comparisons were undertaken for this subgroup , using growth curve modelling and testing for group differences over time in psychological , physiological , health behaviour , and self-efficacy measures . Results Significantly greater improvements ( p depression symptoms and self-rated health were reported for the intervention group , as well as significantly larger gains in confidence in managing depression ( p anger ( p anxiety symptoms and confidence in managing anxiety . Conclusion A group secondary -prevention programme that integrates behavioural and mood management strategies leads to decreased depression , increased confidence , and improved health perceptions in depressed cardiac patients", "Background —Blacks have disproportionately high rates of cardiovascular disease . Psychosocial stress may contribute to this disparity . Previous trials on stress reduction with the Transcendental Meditation ( TM ) program have reported improvements in cardiovascular disease risk factors , surrogate end points , and mortality in blacks and other population s. Methods and Results —This was a r and omized , controlled trial of 201 black men and women with coronary heart disease who were r and omized to the TM program or health education . The primary end point was the composite of all-cause mortality , myocardial infa rct ion , or stroke . Secondary end points included the composite of cardiovascular mortality , revascularizations , and cardiovascular hospitalizations ; blood pressure ; psychosocial stress factors ; and lifestyle behaviors . During an average follow-up of 5.4 years , there was a 48 % risk reduction in the primary end point in the TM group ( hazard ratio , 0.52 ; 95 % confidence interval , 0.29–0.92 ; P=0.025 ) . The TM group also showed a 24 % risk reduction in the secondary end point ( hazard ratio , 0.76 ; 95 % confidence interval , 0.51–0.1.13 ; P=0.17 ) . There were reductions of 4.9 mmHg in systolic blood pressure ( 95 % confidence interval −8.3 to –1.5 mmHg ; P=0.01 ) and anger expression ( P with survival . Conclusions —A selected mind – body intervention , the TM program , significantly reduced risk for mortality , myocardial infa rct ion , and stroke in coronary heart disease patients . These changes were associated with lower blood pressure and psychosocial stress factors . Therefore , this practice may be clinical ly useful in the secondary prevention of cardiovascular disease . Clinical Trial Registration —URL : www . clinical trials.gov Unique identifier : NCT01299935", "The report aims to review the literature and describe the methods used for retention of patients in a clinical study . The Enhanced Recovery in Coronary Heart Disease ( ENRICHD ) trial was a multicenter , r and omized clinical trial design ed to evaluate the effects of a psychosocial intervention on cardiovascular morbidity and mortality . A total of 2481 patients met the criteria for depression , low social support , or both after a myocardial infa rct ion and needed to be followed . Follow-up evaluation consisted of telephone interviews 3 , 9 , 12 , 24 , 36 , and 48 months after enrollment and clinic visits scheduled at 6 , 18 , 30 , 42 , and 54 months . Creative strategies used to achieve optimum retention of this complex patient population over a long follow-up period are presented . Strategies to enhance adherence throughout the course of the trial required adequate tracking of patients to ensure minimum dropout , follow-up evaluation optimized through multiple methods of contact to guarantee completeness of data collection ; and development of procedures to address the needs of patients at risk for dropout . Patients in the group that completed the study participated for a mean of 28.3 months , and those lost to follow-up evaluation participated for a mean of 19 months . Retention was not substantially different by gender or minority status . The results of this project can assist investigators in planning studies that require patient follow-up evaluation , and can provide clinicians with specific strategies for maximizing retention-to-treatment recommendations . As a result of the retention strategies described in this report , 93.02 % of the patients completed their study participation or died . This is a very high retention rate given the complexity of the study sample , protocol , and required duration of follow-up evaluation", "Objective Depression and low social support are risk factors for medical morbidity and mortality after acute MI . The ENRICHD study is a multicenter , r and omized , controlled clinical trial of a cognitive-behavioral treatment for depression and low social support in post-MI patients . A total of 2481 patients were recruited ( 26 % with low social support , 39 % with depression , and 34 % with low social support and depression ) . Our objective is to describe the rationale , design , and delivery of the ENRICHD intervention . Methods Key features of the intervention include the integration of cognitive-behavioral and social learning approaches to the treatment of depression and a diverse set of problems that can contribute to low social support ; rapid initiation of treatment after MI ; a combination of individual and group modalities ; adjunctive pharmacotherapy for severe or intractable depression ; training , certification , and supervision of therapists ; and quality assurance procedures . Results The trial ’s psychosocial and medical outcomes will be presented in future reports . Conclusions The ENRICHD protocol targets two complex psychosocial risk factors with a multifaceted intervention , which is delivered in an individualized manner to accommo date a demographically , medically , and psychiatrically diverse patient population . Additional research will be needed to identify optimal matches between patient characteristics and specific components of the intervention", "Psychosocial factors , particularly depression and lack of social support , are important predictors of morbidity and mortality in patients with coronary heart disease . This article describes the design and methods of the Enhancing Recovery in Coronary Heart Disease Patients ( ENRICHD ) study , a multicenter , r and omized clinical trial involving 3000 patients enrolled after acute myocardial infa rct ion . ENRICHD aims to investigate the effects of a psychosocial intervention that targets depression and /or low social support on survival and reinfa rct ion among adult men and women who are at high risk for recurrent cardiac events because of psychosocial factors ( depressive or social isolation ) . Design features include the use of an individually tailored yet st and ardized intervention , rigorous clinical trial methods , and enrollment of a large number of women and minorities", "Background Coronary heart disease ( CHD ) and depression are leading causes of disease burden globally and the two often co-exist . Depression is common after Myocardial Infa rct ion ( MI ) and it has been estimated that 15 - 35 % of patients experience depressive symptoms . Co-morbid depression can impair health related quality of life ( HRQOL ) , decrease medication adherence and appropriate utilisation of health services , lead to increased morbidity and suicide risk , and is associated with poorer CHD risk factor profiles and reduced survival . We aim to determine the feasibility of conducting a r and omised , multi-centre trial design ed to compare a tele-health program ( MoodCare ) for depression and CHD secondary prevention , with Usual Care ( UC ) . Methods Over 1600 patients admitted after index admission for Acute Coronary Syndrome ( ACS ) are being screened for depression at six metropolitan hospitals in the Australian states of Victoria and Queensl and . Consenting participants are then contacted at two weeks post-discharge for baseline assessment . One hundred eligible participants are to be r and omised to an intervention or a usual medical care control group ( 50 per group ) . The intervention consists of up to 10 × 30 - 40 minute structured telephone sessions , delivered by registered psychologists , commencing within two weeks of baseline screening . The intervention focuses on depression management , lifestyle factors ( physical activity , healthy eating , smoking cessation , alcohol intake ) , medication adherence and managing co-morbidities . Data collection occurs at baseline ( Time 1 ) , 6 months ( post-intervention ) ( Time 2 ) , 12 months ( Time 3 ) and 24 months follow-up for longer term effects ( Time 4 ) . We are comparing depression ( Cardiac Depression Scale [ CDS ] ) and HRQOL ( Short Form-12 [ SF-12 ] ) scores between treatment and UC groups , assessing the feasibility of the program through patient acceptability and exploring long term maintenance effects . A cost-effectiveness analysis of the costs and outcomes for patients in the intervention and control groups is being conducted from the perspective of health care costs to the government . Discussion This manuscript presents the protocol for a r and omised , multi-centre trial to evaluate the feasibility of a tele-based depression management and CHD secondary prevention program for ACS patients . The results of this trial will provide valuable new information about potential psychological and wellbeing benefits , cost-effectiveness and acceptability of an innovative tele-based depression management and secondary prevention program for CHD patients experiencing depression . Trial Registration NumberAustralia and New Zeal and Clinical Trials Register ( ANZCTR ) :", "OBJECTIVE The objective of this study was to evaluate the effects of a home-based intervention program ( HBIP ) on anxiety and depression 6 months after coronary artery bypass grafting ( CABG ) . METHODS In a prospect i ve r and omized controlled trial , 203 elective CABG patients were included . An HBIP structured for respondents in the intervention group was performed 2 and 4 weeks after surgery . Anxiety and depression symptoms were measured by the Hospital Anxiety and Depression Scale ( HADS ) in both patient groups before surgery , 6 weeks after surgery , and 6 months after surgery . RESULTS A total of 185 patients completed the study : 93 patients in the intervention group and 92 patients in the control group . On 6-week and 6-month follow-ups , significant improvements in anxiety and depression symptoms were found in both groups . These improvements did not differ significantly between the groups . However , in a predefined subgroup of patients with anxiety and /or depression symptoms at baseline ( n=65 ) , improvement was significantly larger in the intervention group ( n=29 ) than in the control group ( n=36 ) after 6 months ( P Patients experiencing high levels of psychological distress before CABG surgery benefited from a structured informational and psychological HBIP . Implementation of psychological screens of patients scheduled for CABG might serve to identify patients experiencing anxiety and /or depression . These patients could then be targeted to receive individualized HBIP", "Coronary heart disease ( CHD ) is the leading cause of death for both men and women in the Western world . Some studies show that the observed decline in cardiovascular mortality is not as pronounced among women as among men . There is a growing awareness that most earlier studies both on primary and secondary risk factors , diagnosis , prognosis , and rehabilitation have focused mainly on men . Thus , there is a need to develop knowledge about women with CHD and to address gender issues in treatment and rehabilitation strategies . Negative affect and emotions increase risk and may interfere with effective cardiac rehabilitation . Therefore , methods for coping with emotional stress need to be included in treatment regimens after a coronary event . The feasibility of a stress management program for women with CHD was assessed in a pilot study . The program consisted of twenty 2-hr group sessions during 1 year , with 5 to 9 participants per group . The pilot study showed that this treatment program had a low dropout rate and result ed in improvement in quality of life and reduction in stress and symptoms . Further work to optimize psychosocial interventions for women with CHD is needed", "Abstract Objective : To evaluate rehabilitation after myocardial infa rct ion . Design : R and omised controlled trial of rehabilitation in unselected myocardial infa rct ion patients in six centres , baseline data being collected on admission and by structured interview ( of patients and spouses ) shortly after discharge and outcome being assessed by structured interview at six months and clinical examination at 12 months . Setting : Six district general hospitals . Subjects : All 2328 eligible patients admitted over two years with confirmed myocardial infa rct ion and discharged home within 28 days . Interventions : Rehabilitation programmes comprising psychological therapy , counselling , relaxation training , and stress management training over seven weekly group outpatient sessions for patients and spouses . Main outcome measures : Anxiety , depression , quality of life , morbidity , use of medication , and mortality . Results : At six months there were no significant differences between rehabilitation patients and controls in reported anxiety ( prevalence 33 % ) or depression ( 19 % ) . Rehabilitation patients reported a lower frequency of angina ( median three versus four episodes a week ) , medication , and physical activity . At 12 months there were no differences in clinical complications , clinical sequelae , or mortality . Conclusions : Rehabilitation programmes based on psychological therapy , counselling , relaxation training , and stress management seem to offer little objective benefit to patients who have experienced myocardial infa rct ion compared with previous reports of smaller trials . Key messages In this series there were no important differences by age , sex , hospital , or baseline anxiety or depression At six months the prevalence rates of clinical anxiety and depression remained high ( 33 % and 19 % respectively ) Patients and spouses rated programmes highly , which suggests a “ quality of care ” role for", "Aims : Depression is not treated adequately after myocardial infa rct ion ( MI ) . This study evaluates the interpersonal counselling ( IPC ) implemented by a registered nurse on outcomes for depressive symptoms and distress in MI patients . Methods : We studied MI patients ( n = 103 ) r and omized into intervention group ( n = 51 ) and control group ( n = 52 ) in hospital and at 6 and 18 months after discharge using vali date d question naires , Beck 's Depression Inventory ( BDI ) and the Symptom Checklist-25 ( SCL-25 ) . Results : During the 18-month follow-up , depressive symptoms decreased statistically significantly ( P = 0.009 ) in the intervention group compared with the control group . In the IPC intervention group , depressive symptoms decreased from 37.3 % to 20.4 % at 6 months ( P = 0.014 ) , and to 16.7 % at 18 months ( P = 0.001 ) , while distress decreased from 37.3 % to 26.5 % ( P = 0.132 ) during the 6-month follow-up , and to 20.8 % ( P = 0.015 ) . In the control group with normal care , the number of patients with depressive symptoms and distress varied slightly at the three measurements , from 30.2 to 39.6 % . Conclusions : The number of patients with depressive symptoms and distress decreased in the intervention group and remained high in the control group . The progress of severity level of depressive symptoms was toward milder symptoms in the intervention group during the 18-month follow-up . This brief intervention that can rapidly be adopted may result in enduring benefits of clinical value", "OBJECTIVES To determine the effectiveness of individualised educational behavioural treatment delivered by cardiac nurses in hospital compared to usual care for patients following acute myocardial infa rct ion . METHODS One hundred and fourteen consecutive patients were r and omised to receive the intervention or usual care . Outcome assessment was by self-report question naire ( the Hospital Anxiety and Depression Scale and Dartmouth COOP Health Status ) , interview at 1 month , and self-report at 3 and 12 months . The primary outcome was improvement in the Dartmouth COOP total score from baseline to 3 months . RESULTS Four patients needed to be treated to give an additional patient with improvement in health status at 3 months ( number needed to treat [ NNT ] 4 , 95 % confidence intervals [ CIs ] 3 to 12 ) . The intervention group were more confident about returning to activities 1 month after discharge from hospital . Treated patients had fewer further treatment needs . CONCLUSIONS An individualised educational behavioural treatment delivered by cardiac nurses in hospital may have substantial benefits . A large-scale pragmatic RCT is needed", "OBJECTIVE To compare the impact of network support and different types of perceived functional support on all-cause mortality or nonfatal reinfa rct ion for patients with a recent acute myocardial infa rct ion ( AMI ) . DESIGN Participants were recruited from the Enhancing Recovery in Coronary Heart Disease ( ENRICHD ) trial ; 2,481 AMI patients with depression or low social support were r and omized to a cognitive-behavioral intervention or to a usual care control group . Data collection for certain measures of social support was limited : 2,466 participants completed the ENRICHD Social Support Inventory ; 2,457 completed the Perceived Social Support Scale ; 1,296 completed the Social Network Question naire ; and 707 completed the Interpersonal Support and Evaluation List , Tangible Support subscale . Patients also completed the Beck Depression Inventory and were followed for up to 4.5 years . MAIN OUTCOME MEASURE Time to death or nonfatal reinfa rct ion . RESULTS Over the follow-up period , 599 patients ( 24 % ) died or had a nonfatal AMI . Survival models controlling age , sex , race , socioeconomic status , smoking , antidepressant use , and a composite measure of increased risk revealed that higher levels of perceived social support were associated with improved outcome for patients without elevated depression but not for patients with high levels of depression . Neither perceived tangible support nor network support were associated with more frequent adverse events . CONCLUSION AMI patients should be assessed for multiple dimensions of perceived functional support and depression to identify those at increased psychosocial risk who may benefit from treatment", "Background : Extreme fatigue is a common complaint in percutaneous coronary intervention ( PCI ) patients , and is associated with an increased risk for new cardiac events . The objective of the Exhaustion Intervention Trial ( EXIT ) was to determine whether a behavioral intervention on exhaustion reduces the risk of a new coronary event after PCI . Methods and Results : Seven hundred ten consecutive patients , ages 35 to 68 years , who felt exhausted after PCI were r and omized into an intervention group and a usual-care group . The intervention was based on group therapy focusing on stressors leading to exhaustion , and on support for recovery by promoting rest and making rest more efficient . One month after PCI , 50 % of the patients felt exhausted . The intervention reduced the odds of remaining exhausted at 18 months by 56 % in those without a previous history of coronary artery disease ( CAD ) ( OR = 0.44 ; 95 % CI 0.29–0.66 ) , but had no effect on exhaustion in those with a history of CAD ( OR = 0.93 ; 95 % CI 0.56–1.55 ; p = .78 ) . The intervention did not reduce the risk of a new coronary event within 2 years ( RR = 1.14 ; 95%CI 0.82–1.57 ) . Post-hoc analyses suggest that the effect of the intervention was limited by a positive history of CAD , the presence of a chronic , painful condition ( especially rheumatism ) , and by opposite effects on early and late cardiac events . Conclusion : A behavioral intervention in PCI patients has a beneficial effect on feelings of exhaustion . It could not be demonstrated that the intervention reduces the risk of a new coronary event within 2 years . PCI = percutaneous coronary intervention ; CAD = coronary artery disease ; MQ = Maastricht Question naire ; MIVE = Maastricht Interview Vital Exhaustion ; EXIT = Exhaustion Intervention Trial ; CABG = coronary artery bypass graft ; MI = myocardial infa rct ion", "OBJECTIVES Psychosocial factors , including depression and vital exhaustion ( VE ) are associated with adverse outcome in coronary heart disease ( CHD ) . Women with CHD are poor responders to psychosocial treatment and knowledge regarding which treatment modality works in them is limited . This r and omized controlled clinical study evaluated the effect of a 1-year stress management program , aim ed at reducing symptoms of depression and VE in CHD women . DESIGN Patients were 247 women , and r and omly assigned to either stress management ( 20 2-h sessions ) and medical care by a cardiologist , or to obtaining usual health care as controls . Measurements at ; baseline ( 6 - 8 weeks after r and omization ) , 10 weeks ( after 10 intervention sessions ) , 1 year ( end of intervention ) and 1 - 2 years follow-up . RESULTS For VE , intention to treat analysis showed effects for time ( P VE was more pronounced in the intervention group . However , the level of VE was higher in the intervention group than amongst controls at baseline , 22.7 vs. 19.4 ( P = 0.036 ) but it did not differ later . The change in depressive symptoms did not differ between the groups . CONCLUSIONS CHD women attending our program experienced a more pronounced decrease in VE than controls . However , as they had higher baseline levels , due to regression towards the mean we can not attribute the decrease in VE to the intervention . Whether the program has long-term beneficial effects needs to be evaluated", "A r and omized trial using controls tested whether psycho-social rehabilitation of acute myocardial infa rct ion ( MI ) patients would improve significantly their return to work rate and assessed the importance of various psychological , social , occupational , socio-demographic , and medical factors in facilitating or impeding rapid return to work . Eighty-nine patients were assigned r and omly to participate in an experimental cardiac rehabilitation program ( rehab care ) , and 91 patients were controls who received conventional hospital rehabilitation ( usual care ) . By the first follow-up interview at three months , patients assigned to experimental treatment were significantly less distressed psychologically and less dependent on family support than controls ( P = 0.04 and P = 0.05 , respectively ) . By the final follow-up interview at 13 months , there was a marginally significant difference in favor of the experimental group in the frequency of reported deterrents to work resumption ( P = 0.07 ) . However , the intervention did not result in a statistically significant difference in the return to work rate ( P greater than 0.10 ) . In each group , 88 % were back at work by approximately the first year after infa rct ion . In addition , the two groups were similar in the amount of time patients remained out of the workforce ( median days rehab care = 75 , usual care = 81 ; P greater than 0.10 ) . A multi-stage data analysis procedure utilizing the Cox regression technique indicated that while several independent variables had significant univariate associations with the length of time patients convalesced , outcome was most influenced by the patient 's initial cardiological status and clinical course , by the patterns of family support , and by the several variables measuring the presence of obstacles to resuming work . Our findings suggest that rehabilitation programs intervening on multiple levels ( psychological , social , occupational , and physical ) may best meet the needs of chronically ill cardiac patients . Results indicate that implementing measures addressing the patient 's general psycho-social adjustment to MI may improve existing programs", "PURPOSE The Enhancing Recovery in Coronary Heart Disease Patients ( ENRICHD ) clinical trial was design ed to test whether intervening on depression or low perceived social support reduces mortality and reinfa rct ion in patients with acute myocardial infa rct ion ( MI ) . This report analyzes the effect of the intervention on quality of life ( QOL ) , which was an important secondary outcome . METHODS ENRICHD was a r and omized controlled clinical trial comparing a psychosocial intervention based on cognitive behavioral therapy to usual medical care in 2,481 patients from 8 clinical centers . Patients with acute MI were included if they met criteria for depression , low perceived social support , or both . QOL was assessed at the 6-month clinic visit in the first 1,296 patients . QOL measures included the Medical Outcomes Study Short Form summary measures of physical functioning ( SF12-PCS ) and mental functioning ( SF12-MCS ) , a Life Satisfaction Scale ( LSS ) , and a measure of overall QOL based on the ladder of life ( LOL ) technique . RESULTS There were significant treatment differences on the SF12-MCS ( difference 2.2 , 95 % confidence interval [ CI ] 1.2 - 3.2 ) , the LSS ( difference 1.0 , 95 % CI 0.5 - 1.5 ) , and the LOL ( difference 0.3 , 95 % CI 0.1 - 0.6 ) , but not on the SF12-PCS ( difference 0.8 ; 95 % CI = -0.5 - 2.0 ) . Effect sizes for the intervention on QOL outcomes were modest . CONCLUSIONS Psychosocial interventions of limited duration confer modest QOL benefits in post-MI patients who are depressed or have low perceived social support . Interventions of longer duration or greater intensity may be required to produce more substantial improvements in QOL in these patients", "OBJECTIVES Psychosocial factors , such as stress and vital exhaustion , are associated with an increased risk of cardiovascular events , and women report more psychosocial ill-being after an acute myocardial infa rct ion than men . We have earlier shown that a cognitive-behavioural intervention in women with ischaemic heart disease ( IHD ) improved psychosocial well-being . In the present study , we tested the hypothesis that the improvement in psychosocial well-being is associated with an improvement in biochemical indicators of cardiovascular risk . DESIGN R and omized-controlled trial in northern Sweden . SETTING Outpatient care . SUBJECTS Women with IHD were r and omized to either a 1-year cognitive-behavioural stress management programme or usual care . Of the 159 women who completed the study , 77 were in the intervention group , and 82 in the control group . INTERVENTIONS A 1-year cognitive-behavioural stress management programme versus conventional care . RESULTS Group assignment was not found to be a determinant of waist circumference , high sensitive C-reactive protein ( hs-CRP ) , fibrinogen , von Willebr and factor ( vWF ) , plasminogen activator inhibitor type 1 ( PAI-1 ) activity , tissue plasminogen activator ( tPA ) activity , tPA antigen , tPA-PAI-1 complex , leptin , or HOMA2 insulin resistance index ( HOMA2-IR ) at follow up . Changes in psychosocial variables were not associated with changes in any of the biological risk indicators . CONCLUSIONS Even if our cognitive-behavioural stress management programme had effects on proximal targets , such as stress behaviour and vital exhaustion , we found no improvement in intermediate biochemical targets related to the metabolic syndrome and IHD . Our results challenge the proposition that the relationship between psychological well-being and biological cardiovascular risk indicators is a direct cause-effect phenomenon", "PURPOSE The large and well-characterized population of acute myocardial infa rct ion ( AMI ) patients studied in the recently completed Enhancing Recovery in Coronary Heart Disease ( ENRICHD ) multicenter clinical trial provides a unique opportunity to examine the importance of self-reported regular physical exercise in a large cohort of patients with a recent AMI who are depressed or report low levels of social support . METHODS We prospect ively examined the association between self-reported physical exercise and all-cause mortality and cardiovascular morbidity among 2078 men ( N = 1175 ; 56.5 % ) and women ( N = 903 ; 43.5 % ) with an AMI participating in the ENRICHD Trial . Six months after suffering an AMI , patients were surveyed about their exercise habits and were then followed for up to 4 yr . RESULTS During an average 2 yr of follow-up , 187 fatal events occurred . Patients reporting regular exercise had less than half the events ( 5.7 % ) of those patients reporting they did not regularly exercise ( 12.0 % ) . After adjustment for medical and demographic variables , the hazard ratio for fatal events was 0.62 ( 95 % CI = 0.44 - 0.86 , P = 0.004 ) . The rate of nonfatal AMI among the exercisers was 6.5 % compared with 10.5 % who reported no regular exercise . After adjustment for covariates , the hazard ratio for nonfatal AMI was 0.72 ( 95 % CI = 0.52 - 0.99 , P = 0.044 ) . CONCLUSIONS The present findings demonstrate the potential value of exercise in reducing mortality and nonfatal reinfa rct ion in AMI patients at increased risk for adverse events by virtue of their either being depressed or having low social support", "Background Depression is common after a cardiac event ; however it often remains untreated . Previously , we reported the efficacy and feasibility of a 6-month tele-health programme ( MoodCare ) , which integrates depression management into a cardiovascular disease ( CVD ) risk reduction programme for Acute Coronary Syndrome ( ACS ) patients with low mood . Here , we evaluate the long-term efficacy of the programme at 12-month follow-up . Design A two-arm , parallel , r and omized design to compare the long-term effects of ‘ MoodCare ’ ( n = 61 ) to usual care ( UC ) ( n = 60 ) at 12 months . Method 121 ACS patients recruited from six hospitals in Victoria and Brisbane , Australia were r and omized to a telephone-delivered cognitive behavioural therapy and risk-reduction programme or usual medical care . Mixed-model repeated measurements ( MMRM ) analysis was applied with results expressed as estimated marginal mean changes in depression and health-related quality of life ( HRQOL ) outcomes by group . Results After 12 months , treatment effects were observed for those with major depressive disorder ( MDD ) for PHQ-9 depression ( MoodCare : mean score : 6.5 ; 95 % CI : 4.9–8.0 versus UC : 9.3 ; 95 % CI : 7.7–10.9 , p = 0.012 ) ) and SF-12 mental health scores ( MoodCare : 42.5 ; 95 % CI : 39.8–45.2 versus UC : 36.8 ; 95 % CI : 34.1–39.6 , p = 0.005 ) . No beneficial treatment effects were observed in those with no MDD at baseline . Conclusion After 12 months , MoodCare was superior to UC for improving mental health outcomes for those with a clinical diagnosis of major depression . Our findings support the implementation of depression-based interventions for cardiac patients with a clinical diagnosis of depression and provide evidence of longer term efficacy to one year", "OBJECTIVE The effects of a short intervention on behavioral risk factor modification in patients with coronary artery disease ( CAD ) on Type A behavior , vital exhaustion , and depression were studied in a r and omized controlled trial . METHODS Acute myocardial infa rct ion patients or patients who underwent coronary artery bypass grafting ( CABG ) were r and omly assigned to an 8-week multiple risk modification group program ( n = 94 ) or to a control group ( n = 90 ) that received usual care with st and ard physical exercise training . Patients were assessed before intervention , directly after intervention , and at 9-month follow-up . RESULTS The intervention was effective in reducing hostility and total Type A behavior at postintervention ( P = .01 ) and at 9-month follow-up ( P = .03 ) . The intervention had no overall impact on vital exhaustion and depression , measured by the Beck Depression Inventory ( BDI ) , whereas we unexpectedly found that the percentage of patients with major depression was reduced in the control group but not in the intervention group . CONCLUSION The results indicate that a short behavioral intervention for coronary patients can result in relatively large and persistent reductions in cognitive aspects of Type A behavior and hostility , in particular . In view of the unwanted findings on the diagnosis of depression , however , we do not unequivocally advise the intervention to the general population of AMI and CABG patients", "The hypothesis under investigation was that the beneficial effect of type A behavioral counseling on survival after acute myocardial infa rct ion ( AMI ) was conditional on the functioning of the cardiovascular system , as determined by the severity of the prior AMI . Subjects were 862 nonsmoking coronary patients in the San Francisco Bay Area , r and omized in 1978 to receive , over 4.5 years , cardiac counseling or cardiac counseling plus type A behavioral counseling . Sixteen baseline factors plus an interaction term ( severity of AMI X behavioral counseling ) were evaluated for their prognostic significance . Behavioral counseling was not a significant predictor of coronary death in the total cohort , but the interaction between counseling and severity of the prior AMI was ( p less than 0.05 ) . Thus , the total cohort was divided into 2 subgroups of mild or serious prior AMI , and independent predictors of survival were isolated within each subgroup . In the subgroup with mild prior AMI , independent predictors were anterior AMI ( p = 0.02 ) , plasma cholesterol ( p = 0.02 ) and behavioral counseling ( p = 0.05 ) . In the subgroup with serious prior AMI , none of the factors evaluated made a significant independent contribution . These findings suggest that a reduction in type A behavior may exert the greatest protection against coronary death in that subgroup of patients for whom the biologic aspects of coronary artery disease are not advanced . They also demonstrate the importance of considering the level of cardiac functioning before determining predictors of survival or optimum postcoronary care", "Comprehensive cardiac rehabilitation aims primarily at improving quality of life , but an effect on morbidity and mortality may also be expected , especially when changes in behaviour and life-style are induced . The value of relaxation therapy and exercise training in post myocardial infa rct ion ( MI ) patients was investigated . A group of 90 post MI patients were r and omly assigned to either exercise training plus individual relaxation and breathing therapy ( treatment A ) , or exercise training only ( treatment B ) . The occurrence of cardiac events , consisting of cardiac death and of readmission to hospital for unstable angina pectoris , coronary artery bypass grafting ( CABG ) or recurrent infa rct ion , differed significantly for the two treatment groups in the 2 - 3 years after infa rct ion . Seven out of 42 patients in treatment group A ( 17 % ) experienced a cardiac event , in contrast to 17 out of 46 ( 37 % ) patients in treatment group B , ( P = 0.05 , two-tailed ) . The results suggest that a combination of a behavioural treatment such as relaxation therapy with exercise training is more favourable for the long-term outcome after myocardial infa rct ion than is exercise training alone", " One thous and thirteen post myocardial infa rct ion patients were observed for 4.5 years to determine whether their type A ( coronary-prone ) behavior could be altered and the effect such alteration might have on the subsequent cardiac morbidity and mortality rates of these individuals . Eight hundred sixty-two of these individuals were r and omly assigned either to a control section of 270 participants who received group cardiac counseling or an experimental section of 592 participants who received both group cardiac counseling and type A behavioral counseling . The remaining 151 patients , serving as a \" comparison group , \" did not receive group counseling of any kind . Using the \" Intention-to-Treat \" principle , we observed markedly reduced type A behavior at the end of 4.5 years in 35.1 % of participants given cardiac and type A behavior counseling compared with 9.8 % of participants given only cardiac counseling . The cumulative 4.5-year cardiac recurrence rate was 12.9 % in the 592 participants in the experimental group that received type A counseling . This recurrence rate was significantly less ( p less than 0.005 ) than either the recurrence rate ( 21.2 % ) observed in the 270 participants in the control group or the recurrence rate ( 28.2 % ) in those of the comparison group not receiving any special treatment . After the first year , a significant difference in number of cardiac deaths between the experimental and control participants was observed during the remaining 3.5 years of the study . Overall , the results of this study demonstrate for the first time , within a controlled experimental design , that altering type A behavior reduces cardiac morbidity and mortality in post infa rct ion patients", "Objective : To determine whether a six-session group cognitive behaviour therapy ( CBT ) programme results in a greater reduction in depression symptoms than a brief intervention alone in cardiac patients with clinical ly significant symptoms of depression . Method : Fifty-seven community dwelling cardiac patients scoring > 13 on the Beck Depression Inventory-II ( BDI-II ) received a single-session brief intervention . They were then block r and omised to either six sessions of group CBT ( n = 25 ) or no further intervention ( BI ; n = 32 ) . All were re-assessed at 2 , 6 and 12 months . Differences between treatment groups in the primary ( BDI-II ) and secondary [ rates of depression ; anxiety symptoms , as measured by the Hospital Anxiety and Depression Scale-Anxiety ( HADS-A ) ] outcomes were examined using generalised linear mixed models with a r and om intercept term for the individual . Results : Significant improvements were seen for the total group from baseline to 12 months on BDI-II and HADS-A scores . However , no differences were found between the CBT and BI conditions on change in BDI-II score , rates of major depressive episode or HADS-A score . Post hoc analysis on the total group found 12-month symptom non-remission was associated with higher baseline BDI-II score ( p = 0.03 ) , more visits to health professionals 12 months prior to baseline ( p = 0.05 ) and a greater likelihood of either drinking alcohol over recommended levels or smoking at baseline ( p = 0.01 ) . Conclusions : Group CBT of up to six sessions did not result in greater reductions in depression or anxiety symptoms compared with a single-session brief intervention . Further work should focus on the efficacy and role of brief interventions , and addressing smoking and alcohol misuse in cardiac patients with depression", " One hundred six postmyocardial infa rct ion subjects who either achieved a mean work load of less than seven mets on treadmill testing , who were rated as anxious and /or depressed , or who met both criteria , participated in a controlled study comparing the rehabilitation effectiveness of exercise therapy and group counseling . Each intervention lasted 12 weeks . Follow-up evaluations were scheduled at three months , six months and one year . Exercise substantially increased mean work capacity , decreased fatigue , lessened anxiety and depression , and promoted independence and sociability . Counseling substantially reduced depression and promoted a sense of friendliness , and decreased interpersonal friction as well as greater independence and sociability . The control group reported no substantial change on any measured factor . Neither counseling nor exercise had an effect on mortality though subjects in the exercise group reported fewer major cardiovascular sequelae", "Background : Stress reduction and comprehensive lifestyle modification programs have improved atherosclerosis and cardiac risk factors in earlier trials . Little is known about the impact of such programs on quality -of-life ( QoL ) and psychological outcomes . Given recent significant improvements in cardiac care , we evaluated the current benefit of stress reduction/lifestyle modification on QoL and emotional distress in patients with coronary artery disease ( CAD ) . Methods : 101 patients ( 59.4 ± 8.6 years , 23 female ) with CAD were r and omized to a 1-year lifestyle/stress management program ( n = 48 ) or written advice ( n = 53 ) . QoL and psychological outcomes were assessed with the SF-36 , Beck Depression , Spielberger State/Trait Anxiety , Spielberger State/Trait Anger and Perceived Stress Inventories . Group repeated- measures analyses of variance were performed for all measures . Results : Adherence to the program was excellent ( daily relaxation practice 39 ± 5vs . 5 ± 8 min , respectively ; p most dimensions of QoL , and significantly greater improvements for the lifestyle group were found for physical function and physical sum score ( p = 0.046 and p = 0.045 ) . Depression , anxiety , anger and perceived stress were reduced similarly in both groups . However , intervention × gender interaction effects revealed greater benefits among women in the lifestyle intervention vs. advice group for depression and anger ( p = 0.025 and p = 0.040 ) , but no effects for men . Conclusions : A comprehensive lifestyle modification and stress management program did not improve psychological outcomes in medically stable CAD patients . The program did appear to confer psychological benefits for women but not men . Further trials should investigate gender-related differences in coronary patient responses to behavioral interventions", "Background : Little is known about the impact of interventions targeting chronic stress levels on clinical outcomes among myocardial infa rct ion ( MI ) patients with increased levels of stress . Objectives : To examine the impact of the addition of brief strategic therapy ( BST ) to usual care ( UC ) on clinical outcomes in first MI patients with increased levels of stress . Design : Eighty-one patients were r and omly assigned to BST in conjunction with UC ( medical treatment , risk factor information , and guidance on unhealthy behavior change ) or to UC . Methods : The outcome measures were scores on the Perceived Stress Scale , reinfa rct ion and cardiac mortality rates , and scores on the Health Survey . Measures were taken before , post-treatment , and at two follow-ups . Results : Patients subjected to BST showed reduced perceived stress at post-treatment and maintained decreased levels at follow-ups . At 1-year follow-up , they had a lower rate of non-fatal reinfa rct ion , and at 2.5-year follow-up , they had a lower rate of fatal reinfa rct ion . Their mental and physical health was improved at post-treatment and this was sustained at follow-ups . Conclusion : The addition of BST to UC favorably influences the disease course after MI in patients with increased levels of stress", "BACKGROUND Depressive symptoms are an established predictor of mortality and major adverse cardiac events ( defined as nonfatal myocardial infa rct ion or hospitalization for unstable angina or urgent/emergency revascularizations ) in patients with acute coronary syndrome ( ACS ) . This study was conducted to determine the acceptability and efficacy of enhanced depression treatment in patients with ACS . METHODS A 3-month observation period to identify patients with ACS and persistent depressive symptoms was followed by a 6-month r and omized controlled trial . From January 1 , 2005 , through February 29 , 2008 , 237 patients with ACS from 5 hospitals were enrolled , including 157 persistently depressed patients r and omized to intervention ( initial patient preference for problem-solving therapy and /or pharmacotherapy , then a stepped-care approach ; 80 patients ) or usual care ( 77 patients ) and 80 nondepressed patients who underwent observational evaluation . The primary outcome was patient satisfaction with depression care . Secondary outcomes were depressive symptom changes ( assessed with the Beck Depression Inventory ) , major adverse cardiac events , and death . RESULTS At the end of the trial , the proportion of patients who were satisfied with their depression care was higher in the intervention group ( 54 % of 80 ) than in the usual care group ( 19 % of 77 ) ( odds ratio , 5.4 ; 95 % confidence interval [ CI ] , 2.2 - 12.9 [ P Beck Depression Inventory score decreased significantly more ( t(155 ) = 2.85 [ P = .005 ] ) for intervention patients ( change , -5.7 ; 95 % CI , -7.6 to -3.8 ; df = 155 ) than for usual care patients ( change , -1.9 ; 95 % CI , -3.8 to -0.1 ; df = 155 ) ; the depression effect size was 0.59 of the st and ard deviation . At the end of the trial , 3 intervention patients and 10 usual care patients had experienced major adverse cardiac events ( 4 % and 13 % , respectively ; log-rank test , chi(2)(1 ) = 3.93 [ P = .047 ] ) , as well as 5 nondepressed patients ( 6 % ) ( for the intervention vs nondepressed cohort , chi(2)(1 ) = 0.48 [ P = .49 ] ) . CONCLUSION Enhanced depression care for patients with ACS was associated with greater satisfaction , a greater reduction in depressive symptoms , and a promising improvement in prognosis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00158054", "A health education and counselling programme was offered to myocardial infa rct ion patients during and after hospitalization . A r and omized pre-test-post-test control group design was used to evaluate the effects of the experimental intervention . During hospitalization the intervention consisted of two individual counselling sessions and two group health education sessions focusing on medication , healthy habits , anxiety and depression . On completion of these sessions , weekly telephone calls were made to patients for a period of six weeks after discharge from hospital . The intervention was offered to 30 myocardial infa rct ion patients and their partners ( the experimental group ) in addition to st and ard medical care . Thirty control patients received st and ard medical care only . Two months after myocardial infa rct ion , patients in the experimental condition reported a significantly greater increase in physical activity , and a significantly greater decrease in unhealthy eating habits . No effects were found regarding smoking cessation , anxiety and depression . Twelve months after discharge from hospital patients in the experimental condition reported a significantly greater decrease in unhealthy eating habits . No effects were found regarding smoking cessation , physical activity , anxiety and depression . In addition , two months after myocardial infa rct ion , it was found that patients whose partners participated in the health education sessions showed a significantly greater decrease in smoking and unhealthy eating habits and a significantly greater increase in physical activity than patients with no partner participating . Twelve months after discharge the only significant result favouring the patients whose partner participated in the health education sessions concerned smoking cessation", "Background Psychosocial stress may play a causative role in development and progression of coronary artery disease ( CAD ) . Purpose We investigated the effects of a 1-year stress management program on daily stress behavior and social support among female CAD patients . Method Women , 247 ( ≤75 years ) , hospitalized for a cardiac event were r and omized to either a control or an intervention group . Controls obtained usual health care ; intervention patients participated in 20 2-h group sessions of stress management therapy and obtained health care by a cardiologist . Measurements were at baseline , 10 weeks ( after ten sessions ) , 1-year ( end of intervention ) , and at a 1- to 2-year follow-up . Results Daily stress scores for the intervention and control groups were at baseline 39.5 ± 8.1 vs. 37.2 ± 9.1 ( p = 0.06 ) , 10 weeks 37.2 ± 8.0 vs. 35.5 ± 9.4 ( p = 0.20 ) , 1-year 36.1 ± 7.2 vs. 35.9 ± 8.5 ( p = 0.85 ) , and at 1–2 year follow-up 34.0 ± 7.8 vs. 35.3 ± 8.7 ( p = 0.32 ) , respectively . Intention to treat analyses showed interaction between treatment and time [ F(3,213 ) = 2.72 ; p = 0.01 ] reflecting that the decrease was more pronounced in the intervention group . There was no evidence for a difference in change concerning social support . Conclusion CAD women in the intervention group had a more pronounced reduction of self-rated daily stress behavior over time compared to controls . However , as the intervention group had higher baseline values , due to regression toward the mean , we have no evidence that the difference in decrease of daily stress was due to the intervention", "BACKGROUND Psychosocial factors are independently associated with increased risk of cardiovascular disease ( CVD ) morbidity and mortality , but the effects of psychosocial factor intervention on CVD are uncertain . We performed a r and omized controlled clinical trial of cognitive behavioral therapy ( CBT ) to measure its effects on CVD recurrence . METHODS The study included 362 women and men 75 years or younger who were discharged from the hospital after a coronary heart disease event within the past 12 months . Patients were r and omized to receive traditional care ( reference group , 170 patients ) or traditional care plus a CBT program ( intervention group , 192 patients ) , focused on stress management , with 20 two-hour sessions during 1 year . Median attendance at each CBT session was 85 % . Outcome variables were all-cause mortality , hospital admission for recurrent CVD , and recurrent acute myocardial infa rct ion . RESULTS During a mean 94 months of follow-up , the intervention group had a 41 % lower rate of fatal and nonfatal first recurrent CVD events ( hazard ratio [ 95 % confidence interval ] , 0.59 [ 0.42 - 0.83 ] ; P = .002 ) , 45 % fewer recurrent acute myocardial infa rct ions ( 0.55 [ 0.36 - 0.85 ] ; P = .007 ) , and a nonsignificant 28 % lower all-cause mortality ( 0.72 [ 0.40 - 1.30 ] ; P = .28 ) than the reference group after adjustment for other outcome -affecting variables . In the CBT group there was a strong dose-response effect between intervention group attendance and outcome . During the first 2 years of follow-up , there were no significant group differences in traditional risk factors . CONCLUSIONS A CBT intervention program decreases the risk of recurrent CVD and recurrent acute myocardial infa rct ion . This may have implication s for secondary preventive programs in patients with coronary heart disease . Trial Registration clinical trials.gov Identifier : NCT00888485", "& NA ; The Recurrent Coronary Preventive Project ( RCPP ) demonstrated that the addition of Type A counseling to st and ard cardiac counseling result ed in significant reductions in Type A behavior and in a 44 % reduction in reinfa rct ion in post‐myocardial infa rct ion patients . The purpose of the present study was to describe the specific behavioural and psychosocial changes that occurred during this Type A treatment . Patients undergoing Type A counseling showed significant reductions not only in Type A behavior , but also in the Type A components of hostility , time urgency , and impatience , when compared with patients in the cardiac control group . They also showed significant decreases in depression and anger , and gains in self‐efficacy , and marginally significant gains in social support and well‐being . Type A counseling result ed in a dose‐response relationship with most psychosocial outcomes , such that an increasing amount of treatment contacts was associated with increasing change . These data are important in that they specify a range of psychosocial factors that were influenced by treatment . These factors can be considered to be among the possible explanations for the efficacy of the RCPP treatment on the reduction of cardiac recurrences", "PURPOSE This r and omized controlled study aim ed to evaluate the effects on psychosocial variables of a 1-year group-based cognitive-behavioral stress management program developed specifically for women with ischemic heart disease . METHODS The present explanatory ( per protocol ) analyses include 80 women who were r and omized to a 1-year cognitive-behavioral stress management program and 86 who were r and omized to usual care ( age = 35 - 77 years ) . Data were obtained before r and omization and after 1 year , when the intervention group had completed the program . RESULTS There were no statistically significant differences between the intervention and usual care groups in the psychosocial endpoints at r and omization . Both groups improved in all psychosocial variables during the 1-year study period , but the rate of improvement was significantly greater in the intervention group for self-rated stress behavior ( P = .006 ) and vital exhaustion ( P = .03 ) . Although changes were in favor of the treatment group also for depressive mood and quality of life , the rates of improvement between the 2 groups did not reach statistical significance ( P = .23 and P = .10 , respectively ) . CONCLUSION A 1-year cognitive-behavioral stress management program design ed specifically for women improved psychological well-being in some aspects in comparison with usual care", "BACKGROUND Previous studies on cognitive and interpersonal interventions have yielded inconsistent results in ischemic heart disease patients . METHODS 101 patients aged ≤ 70 years , and enrolled one week after complete revascularization with urgent/emergent angioplasty for an AMI , were r and omized to st and ard cardiological therapy plus short-term humanistic-existential psychotherapy ( STP ) versus st and ard cardiological therapy only . Primary composite end point was : one-year incidence of new cardiological events ( re-infa rct ion , death , stroke , revascularization , life-threatening ventricular arrhythmias , and the recurrence of typical and clinical ly significant angina ) and of clinical ly significant new comorbidities . Secondary end points were : rates for individual components of the primary outcome , incidence of re-hospitalizations for cardiological problems , New York Heart Association class , and psychometric test scores at follow-up . RESULTS 94 patients were analyzed at one year . The two treatment groups were similar across all baseline characteristics . At follow-up , STP patients had had a lower incidence of the primary endpoint , relative to controls ( 21/49 vs. 35/45 patients ; p=0.0006 , respectively ; NNT=3 ) ; this benefit was attributable to the lower incidence of recurrent angina and of new comorbidities in the STP group ( 14/49 vs. 22/45 patients , p=0.04 , NNT=5 ; and 5/49 vs. 25/45 , p fewer re-hospitalizations , a better NYHA class , higher quality of life , and lower depression scores . CONCLUSION Adding STP to cardiological therapy improves cardiological symptoms , quality of life , and psychological and medical outcomes one year post AMI , while reducing the need for re-hospitalizations . Larger studies remain necessary to confirm the generalizability of these results . CLINICAL TRIAL REGISTRATION Clinical Trial.gov : NCT00769366", "The psychological impact of exercise training and relaxation therapy was investigated in 156 myocardial infa rct ion patients . They were r and omly assigned to either exercise plus relaxation and breathing therapy ( Treatment A : n = 76 ) or exercise training only ( Treatment B : n = 80 ) . Patients in Treatment A improved on three out of eight psychological measurements ( anxiety , well-being , feelings of invalidity ) . No change was demonstrable in Treatment B. The difference between the treatments was significant for wellbeing ( p less than 0.005 ) . Physical outcome , measured by exercise testing was positive in about half of the patients ( Treatment A : 55 % , Treatment B : 46 % ) . A negative outcome occurred less in Treatment A ( p less than 0.05 ) . Training success was not associated with psychic benefit . The association differed for the two treatments . It was concluded that exercise training was effective for some but not for all cardiac patients , and that a psychic effect of exercise could not be demonstrated . Relaxation therapy enhanced physical and psychic outcome of rehabilitation", "Objective : The objective of this study was to evaluate the effectiveness of a telephone-based intervention on psychological distress among patients with cardiac illness . Methods : We recruited hospitalized patients surviving an acute coronary syndrome with scores on the Hospital and Anxiety Depression Scale ( HADS ) indicating mild to severe depression and /or anxiety at 1 month postdischarge . Recruited patients were r and omized into either an intervention or control group . Intervention patients received up to six 30-minute telephone-counseling sessions focused on identifying cardiac-related fears . Control patients received usual care . For both groups , we collected patients ’ responses to the HADS and to the Global Improvement ( CGI-I ) subscale of the Clinical Global Impressions ( CGI ) Scale at baseline and at 2 , 3 , and 6 months postbaseline using Interactive Voice Recognition ( IVR ) technologies . We used mixed-effects analysis to estimate patients ’ changes in CGI-I measures over the three time points of data collection postbaseline . Results : We enrolled 100 patients , and complete CGI-I measures were collected for 79 study patients . The mean age was 60 years ( st and ard deviation = 10 ) , and 67 % of the patients were male . A mixed-effects analysis confirmed that patients in the intervention group had significantly greater improvements in self-rated health ( SRH ) between baseline and month 3 than the control group ( p = .01 ) . Between month 3 and month 6 , no significant differences in SRH improvements were observed between the control and intervention groups . Conclusions : Study patients reported greater SRH improvement result ing from the telephone-based intervention compared with control subjects . Future research should include additional outcome measures to determine the effect of changes in SRH on patients with comorbid physical and emotional disorders . ACS = acute coronary syndrome ; ADL = activities of daily living ; CAD = coronary artery disease ; CGI = Clinical Global Impressions Scale ; CGI-I = Global Improvement subscale of the Clinical Global Impressions ( CGI ) Scale ; ENRICHD = Enhancing Recovery in Heart Disease Patients trial ; HADS = Hospital and Anxiety Depression Scale ; HTS = Healthcare Technology Systems ; ICD-9 = International Classification of Diseases , Ninth Edition ; IRB = Institutional Review Boards ; IVR = interactive voice recognition ; MI = myocardial infa rct ion ; SADHART = the Sertraline Antidepressant Heart Attack R and omized Trial ; SRH = self-rated health ", "Introduction : Patients with cardiovascular disease who stop smoking lower their risk of subsequent morbidity and mortality . However , patients who have suffered a myocardial infa rct ion ( MI ) are more likely to be depressed than the general population , which may make smoking cessation more difficult . Poor social support may also make smoking cessation more difficult for some patients . This study examines the effect of cognitive behavior therapy ( CBT ) for depression , low perceived social support or both on smoking behavior in post-MI patients . Methods : Participants were 1233 patients with a history of smoking enrolled in the Enhancing Recovery in Coronary Heart Disease Patients ( ENRICHD ) trial who provided 7-day point-prevalence smoking behavior information at baseline and at two or more follow-up assessment s. The ENRICHD trial enrolled post-MI patients with depression , low perceived social support or both . Participants were r and omly assigned to either CBT intervention or usual care . We used mixed effects models to accommo date data from multiple smoking point-prevalence measures for each individual participant . Results : CBT did not significantly reduce post-MI smoking across all intervention patients with a history of smoking . However , CBT did reduce post-MI smoking among the subgroup of depressed patients with adequate perceived social support ( OR , 0.68 ; 95 % CI , 0.47–0.98 ) . Conclusion : CBT for depression without more specific attention to smoking cessation may have little overall value as a strategy for helping post-MI patients refrain from smoking . However , use of CBT to treat depression may have the gratuitous benefit of reducing smoking among some post-MI patients . ENRICHD = Enhancing Recovery in Coronary Heart Disease Patients ; MI = myocardial infa rct ion ; CBT = cognitive behavioral therapy ; LPSS = low perceived social support ; MDD = major depressive disorder ; BDI = Beck Depression Inventory ; OR = odds ratio", "Psychosocial factors affect the development of coronary heart disease and morbidity and mortality of patients with known coronary heart disease . A prior study has shown that psychological distress in patients with known coronary heart disease increased medical and economic costs . This study examined the effects of commonly available psychological interventions offered to patients entering cardiac rehabilitation after hospitalization for angina , myocardial infa rct ion , angioplasty , or coronary artery bypass grafting . A total of 380 patients were screened with the Symptom Checklist-90-Revised ( SCL-90-R ) . Those with T-scores > or = 63 ( > or = 91 percentile ) on the General Severity Index ( GSI ) subscale were r and omly assigned to usual care or special intervention . Special intervention included a psychiatric evaluation , plus one to seven sessions of behavioral therapy . The percentage of patients rehospitalized for cardiac symptoms within 12 months of psychological evaluation was 43 % for special intervention and 40 % for usual care ( NS ) . A correction for crossover between the treatment groups result ed in a favorable trend toward intervention , with 35 % of the psychologically treated patients rehospitalized vs. 48 % of the untreated patients ( NS ) . Although there was a nonsignificant reduction of the SCL-90-R 's GSI T-score , the depression score was significantly reduced in the special intervention group", "BACKGROUND Evidence suggests that breathing and relaxation therapy may influence cardiac events in persons after acute myocardial infa rct ion ( MI ) . The authors studied the effects of breathing and relaxation therapy on rates of cardiac events and cost effectiveness in past MI patients . METHODS Patients ( n = 156 ) were chosen r and omly to receive either exercise training plus relaxation therapy ( relaxation group ; n = 76 ) or exercise training only ( control group ; n = 80 ) . The occurrence of major cardiac events and cardiac rehospitalizations in the two treatment groups was compared . RESULTS At 5-year follow-up , 12 cardiac deaths had occurred , 5 in the relaxation group and 7 in the control group , reinfa rct ion occurred in 10 and 12 patients , and cardiac surgery was performed in 2 and 11 , respectively . In total , 15 ( 20 % ) and 26 ( 33 % ) patients , respectively , experienced at least one cardiac event ( odds ratio [ OR ] for the relaxation group : 0.55 , 95 % confidence interval [ CI ] 0.29 - 1.05 ; adjusted for risk factors OR 0.52 , 95 % CI 0.28 - 0.99 ) . Regarding all cardiac rehospitalizations , in the relaxation group , 30 patients ( 39 % ) had experienced 52 cardiac events , for which the patients were hospitalized for a total of 476 days . In the control group , 38 patients ( 48 % ) had experienced 78 cardiac events ( OR 0.72 ; 95 % CI 0.38 - 1.36 ) , comprising 719 days of hospitalization . The total number of hospitalizations was reduced by 31 % as a result of relaxation instruction . CONCLUSIONS In the long-term , the disease course after myocardial infa rct ion is influenced favorably by giving relaxation therapy in addition to cardiac rehabilitation . The extra costs of the therapy are compensated by a decrease in hospitalization for cardiac problems", "Objective A number of previous studies addressed the effect of psychological interventions in patients after acute myocardial infa rct ion ( AMI ) , but it is not known whether psychotherapy might be beneficial after medical and interventional therapy of AMI . We design ed a r and omized , controlled study to assess the effects of a short-term psychotherapy ( STP ) on the clinical outcomes of patients who underwent an emergency percutaneous coronary intervention after AMI . Methods One hundred consecutive patients undergoing an emergency percutaneous coronary intervention will be r and omized 1 week after AMI to medical therapy ( control group , C group ) or to medical therapy and STP ( STP group ) . Clinical follow-up visits are scheduled at 6 months , 1 and 5 years , whereas psychometric tests ( Self-Evaluation test , Modified Maastricht Question naire , Social Support Question naire , Recent Life Change Question naire , Beck Depression Inventory , the MacNew Heart Disease Health-Related Quality of Life Question naire , Type D Personality test ) are scheduled 1 week after AMI and at 1 year . The primary outcome measures of the study are the cumulative incidence of new cardiological events ( myocardial reinfa rct ion , death , stroke , life-threatening ventricular arrhythmias , and recurrence of angina ) and the occurrence of new medical disorders . Secondary outcome measures are the incidence of rehospitalizations due to cardiological problems , the prevalence of patients with New York Heart Association class ≥ II , left ventricular function , as assessed by echocardiography , and mean score of psychometric tests in the two groups at follow-up . Conclusion Our study has been planned to obtain an insight into how a STP influences clinical outcomes after interventional and medical treatment of AMI", "Depression and sub-syndromal depressive symptoms are important predictors of morbidity and mortality after acute coronary syndrome ( ACS ) . Prior trials of depression treatment in post-ACS patients have demonstrated no improvement for event-free survival , and only modest improvement in depression symptoms . These trials have raised a number of important issues regarding timing of depression intervention , acceptability of depression treatment to ACS patients , and safety for subsets of the treated population . This article describes Project COPES ( Coronary Psychosocial Evaluation Studies ) , a multi-center Phase-I r and omized clinical trial . Project COPES uses a patient preference depression treatment that has previously been found acceptable to medical patients , and a 3-month pre-r and omization observation period to insure depression status . The study sample will include 200 post-ACS patients . The primary outcome is patient satisfaction with depression care . Secondary , exploratory aims include the acceptability of depression treatment , reduction in depressive symptoms , and the effects of treatment on two key pathways -- medication adherence and inflammation -- hypothesized to link depression to post-ACS prognosis . These analyses will provide important data to inform subsequent clinical trials with this population", "BACKGROUND The presence of depression after an acute coronary syndrome ( ACS ) is associated with worse prognosis and lower adherence to risk-reducing behaviors . We reported earlier that an enhanced depression care intervention reduces depression symptoms and major adverse cardiac events . This study evaluates the impact of the depression intervention on health behavior and blood pressure control . METHODS Between 2005 and 2008 , 157 patients who remained persistently depressed 3 months after ACS were r and omized to a 6-month depression intervention ( initial patient preference for problem-solving therapy and /or pharmacotherapy , followed by stepped care ; 80 patients ) or to usual care ( 77 patients ) . At r and omization , and then 2 , 4 , and 6 months later , patients were asked if they ( 1 ) missed taking their aspirin ; ( 2 ) followed a heart healthy diet ; ( 3 ) exercised regularly ; and ( 4 ) used tobacco products . Blood pressure was measured before r and omization and 6 months later . RESULTS At the end of the intervention , there was no significant improvement in the percentage of intervention compared to control group patients who adhered to aspirin ( + 3 % versus -1 % , P = .23 ) , followed a healthy diet ( + 10 % versus + 8 % , P = .39 ) , exercised regularly ( + 5 % versus + 4 % , P = .65 ) , abstained from tobacco ( -3 % versus -1 % , P = .77 ) , or had controlled blood pressure ( + 6 % versus + 16 % , P = .26 ) . CONCLUSION Despite improving depression , enhanced depression care after an ACS did not improve health behavior or blood pressure control compared to usual care . Research is needed to test whether adding an adherence intervention to enhanced depression care can improve adherence and cardiovascular prognosis in depressed patients post-ACS", "Objective : Intervening in depression and /or low perceived social support within 28 days after myocardial infa rct ion ( MI ) in the Enhancing Recovery in Coronary Heart Disease ( ENRICHD ) clinical trial did not increase event-free survival . The purpose of the present investigation was to conduct post hoc analyses on sex and ethnic minority subgroups to assess whether any treatment subgroup is at reduced or increased risk of greater morbidity/mortality . Methods : The 2481 patients with MI ( 973 white men , 424 minority men , 674 white women , 410 minority women ) who had major or minor depression and /or low perceived social support were r and omly allocated to usual medical care or cognitive behavior therapy . Total mortality or recurrent nonfatal MI ( ENRICHD primary endpoint ) and cardiac mortality or recurrent nonfatal MI ( secondary endpoint ) were analyzed as composite endpoints by group for time to first event using Cox proportional hazards regression . Results : There was a trend in the direction of treatment efficacy for white men for the primary endpoint ( hazard ratio [ HR ] , 0.80 ; 95 % confidence interval , 0.61–1.05 ; p = .10 ) and a significant ( p ENRICHD intervention , suggesting that future studies need to attend to issues of treatment design and delivery that may have prevented benefit among sex and ethnic subgroups other than white men", "PURPOSE The purpose of this research was to assess whether short-term psychotherapy enhances long-term clinical outcomes in patients with a recent acute myocardial infa rct ion ( AMI ) . METHODS Patients ≤70 years old were r and omized within 1 week of their AMI to short-term ontopsychological psychotherapy plus routine medical therapy vs routine medical therapy only . The primary composite outcome was defined as the combined incidence of new cardiovascular events ( re-infa rct ion , death , stroke , revascularization , life-threatening ventricular arrhythmias , and the recurrence of clinical ly significant angina ) and clinical ly significant new comorbidities . Secondary outcome measures were : rates for individual components of the primary composite outcome ; the rate of re-hospitalization for cardiovascular problems ; and New York Heart Association functional class . RESULTS Ninety-four patients were analyzed , translating into 425 patient-years . The 2 treatment groups were similar across baseline characteristics . At 5-year follow-up , psychotherapy patients had a lower incidence of primary outcome , relative to controls ( 77/223 vs 98/202 patient-years , respectively ; P = .035 ; absolute risk reduction = 19 % , number needed to treat = 8) ; this benefit was attributable to the lower incidence of new comorbidities and clinical ly significant angina in the psychotherapy group . Gains in the primary outcome , relative to controls , among psychotherapy patients occurred in the first year and subsequently remained stable over the following 4 years . CONCLUSIONS Adding short-term ontopsychological psychotherapy to routine secondary prevention of myocardial infa rct ion improves clinical outcomes overall up to 5 years post AMI . Study ing time trends may aid in better targeting of psychological interventions during follow-up . Larger studies remain necessary to confirm these results . TRIAL REGISTRATION www . Clinical Trial.gov NCT00769366", "Background : Anxiety is frequent in patients with coronary heart disease ( CHD ) and influences the course of the disease , but no r and omized controlled trial has investigated the effects of a psychotherapy intervention in CHD patients with elevated anxiety scores . The main aim of this study was to evaluate the effects of a 6-month psychotherapy intervention on anxiety in this group of patients . Methods : Fifty-two patients ( 61 ± 8.0 years , 14 female ) with CHD and elevated levels of anxiety completed the study after r and omization into a 6-month psychotherapy intervention or a control condition . Medically eligible patients were screened for anxiety with the Hospital Anxiety and Depression Scale ( HADS ) and were included if they had a score of 8 or higher . Anxiety scores were reevaluated at 6-month follow-up ( after the treatment ) . Results : At 6-month follow-up significant reductions ( intervention group : –2.0 ± 2.3 ; control group : –1.8 ± 2.8 ; p the HADS anxiety scale but no significant differences between the groups were observed . Adjustment for baseline differences and disease severity did not change these results . Conclusions : Our study showed that elevated anxiety scores were reduced over time but there was no statistically significant effect of the psychotherapy intervention in anxious patients with CHD . Changes in the design of the intervention and study might be useful to further investigate this topic in the future", "Background — Cardiac rehabilitation ( CR ) is the st and ard of care for patients with coronary heart disease . Despite considerable epidemiological evidence that high stress is associated with worse health outcomes , stress management training ( SMT ) is not included routinely as a component of CR . Methods and Results — One hundred fifty-one out patients with coronary heart disease who were 36 to 84 years of age were r and omized to 12 weeks of comprehensive CR or comprehensive CR combined with SMT ( CR+SMT ) , with assessment s of stress and coronary heart disease biomarkers obtained before and after treatment . A matched sample of CR-eligible patients who did not receive CR made up the no-CR comparison group . All participants were followed up for up to 5.3 years ( median , 3.2 years ) for clinical events . Patients r and omized to CR+SMT exhibited greater reductions in composite stress levels compared with those r and omized to CR alone ( P=0.022 ) , an effect that was driven primarily by improvements in anxiety , distress , and perceived stress . Both CR groups achieved significant , and comparable , improvements in coronary heart disease biomarkers . Participants in the CR+SMT group exhibited lower rates of clinical events compared with those in the CR-alone group ( 18 % versus 33 % ; hazard ratio=0.49 ; 95 % confidence interval , 0.25–0.95 ; P=0.035 ) , and both CR groups had lower event rates compared with the no-CR group ( 47 % ; hazard ratio=0.44 ; 95 % confidence interval , 0.27–0.71 ; P CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with st and ard CR . Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00981253" ]

[ "The effects of a stabilized 0.454 % stannous fluoride dentifrice , currently marketed as Crest Gum Care , on supragingival plaque , gingivitis , gingival bleeding and oral soft tissue condition were studied in 328 adult male and female subjects who completed a six-month , double blind clinical study . Following initial examinations , subjects presenting with a minimum of five gingival bleeding sites received a thorough dental prophylaxis and were instructed to brush at least twice a day for three months with a commercially available fluoride dentifrice , packaged in such a way as to blind its identity to the study subjects . This constituted the three-month pre-test period . At the end of this period , subjects were again examined , given a second oral prophylaxis , and r and omly assigned to brush with one of the following dentifrices : 1 ) stabilized 0.454 % stannous fluoride , 2 ) 0.243 % sodium fluoride control , or 3 ) one of three experimental dentifrices . Subjects were instructed to brush their teeth as they normally would , at least twice a day for one minute per brushing . Follow-up examinations after three and six months of dentifrice use evaluated supragingival plaque , gingivitis , gingival bleeding , extrinsic tooth stain and oral soft tissue status . After six months , the stabilized stannous fluoride dentifrice significantly reduced gingivitis and gingival bleeding by 20.5 % and 33.4 % compared to the sodium fluoride control group . However , the stabilized stannous fluoride dentifrice group was not significantly different from the control dentifrice group with respect to supragingival plaque scores . As expected , accumulation of extrinsic tooth stain was greater in the stabilized stannous fluoride group than the control group . No unexpected nor clinical ly significant oral soft tissue health effects were associated with the use of the test dentifrices . The results from this clinical study demonstrate that over a six-month period , twice-daily use of a dentifrice containing 0.454 % stabilized stannous fluoride significantly reduced gingivitis and gingival bleeding , relative to a 0.243 % sodium fluoride control dentifrice", "A 6-month double-blind , controlled clinical study was conducted on 107 healthy adult subjects to determine the efficacy of a mouthrinse used as a supplement to regular oral hygiene measures on supragingival dental plaque and gingivitis . 115 healthy adult patients were recruited for the study . Following screening examinations for minimal entry levels of existing gingivitis and plaque in patients with a minimum of 20 sound natural teeth , extrinsic tooth stain , gingivitis and plaque index scores were recorded . Soft tissues were evaluated . All subjects then received a complete dental prophylaxis , removing plaque , calculus and extrinsic stain . Utilizing their normal oral hygiene , subjects began a regimen of rinsing with 20 ml of the r and omly assigned rinse , twice daily for 30 s for 6 months . 7 days after prophylaxis , gingivitis was again scored ( baseline 2 ) . Soft tissue , gingivitis , plaque area and extrinsic stain were evaluated again at 3 and 6 months . Results demonstrated that after 6 months , listerine produced a 34 % inhibition of both plaque and of gingivitis compared to a hydroalcohol control ( p less than 0.001 )", "This double-blind parallel- design clinical study compared the efficacy of a stabilized stannous fluoride dentifrice ( Crest Plus Gum Care ) , baking soda and peroxide ( NaF ) dentifrice ( Mentadent ) , and essential oil mouthrinse ( Listerine ) to a conventional NaF dentifrice ( Crest ) for the control of plaque , gingivitis and gingival bleeding over six months . Following an initial baseline examination and stratification , subjects received a complete oral prophylaxis and were distributed assigned test products . Following three and six months , subjects re-visited the clinic for examinations . Evaluations at baseline and at 3 and 6 months included soft tissue status . Löe-Silness gingivitis/gingival bleeding , Silness-Löe plaque and dental stain . Results subsequent to six months of product use were as follows : At six months , the stabilized stannous fluoride dentifrice was observed to produce statistically significant 17.5 % reductions in gingivitis and 27.5 % reductions in gingival bleeding relative to the NaF dentifrice . The combination of sodium fluoride dentifrice and essential oil mouthrinse produced statistically significant reductions of 7.4 % in gingivitis and 10.8 % in plaque as compared with the NaF dentifrice . The stabilized stannous fluoride dentifrice produced statistically significant reductions in both gingivitis ( 10.8 % ) and gingival bleeding ( 23.0 % ) relative to the combination of sodium fluoride dentifrice and essential oil mouthrinse . The baking soda and peroxide ( NaF ) dentifrice did not provide reductions in gingivitis , plaque or gingival bleeding as compared with the conventional NaF dentifrice . The stabilized stannous fluoride dentifrice provided statistically significant reductions in gingivitis as compared with the baking soda and peroxide dentifrice following six months of use , and both the essential oil mouthrinse and stabilized stannous fluoride dentifrice provided statistically significant reductions in gingivitis as compared with the baking soda and peroxide dentifrice following three months of use . These results support : 1 ) the efficacy of stabilized stannous fluoride dentifrice and the combination of sodium fluoride dentifrice and essential oil mouthrinse for the prevention of gingivitis ; 2 ) the superior activity of stabilized stannous fluoride dentifrice as compared with a combination of sodium fluoride dentifrice and essential oil mouthrinse for the control of gingivitis and gingival bleeding ; and 3 ) the lack of efficacy for baking soda and peroxide dentifrice for the control of plaque , gingivitis and gingival bleeding as compared with conventional fluori date d dentifrice", "A total of one hundred twenty-one ( 121 ) adult male and female subjects completed a 6-month , double-blind clinical study comparing the effect on supragingival plaque formation and gingivitis of a dentifrice containing 0.3 % Triclosan and 2.0 % of a copolymer of methoxyethylene and maleic acid to a placebo dentifrice . Both the Triclosan/copolymer and placebo dentifrices contained 0.243 % sodium fluoride in a silica base . Subjects were stratified into two balanced groups according to baseline plaque and gingivitis scores . They then received an oral prophylaxis and were assigned to use either the Triclosan/copolymer dentrifrice or the placebo dentifrice for the next 6 months . Subjects were evaluated for supragingival plaque formation and gingivitis after 3 and 6 months ' use of the dentifrices . After 6 months , the Triclosan/copolymer dentifrice was shown to provide a 32.32 % statistically significant reduction ( 99 % level of confidence ) in supragingival plaque formation , as compared to the placebo dentifrice . Also , after 6 months , the Triclosan/copolymer dentifrice was shown to provide a 25.64 % statistically significant reduction ( 99 % level of confidence ) in gingivitis , as compared to the placebo dentifrice . It thus can be concluded from this clinical study that the twice daily use of the dentifrice containing 0.3 % Triclosan and 2.0 % of a copolymer in a 0.243 % sodium fluoride/silica base provides statistically significant reductions in both supragingival plaque formation and gingivitis", "A total of 294 adult male and female subjects completed a 6-month , double-blind clinical trial design ed to evaluate the effects of a dentifrice which contained 0.3 % triclosan in conjunction with 2 % of a methoxyethylene/maleic acid copolymer in a 0.243 % sodium fluoride/silica base , relative to a control dentifrice , on supragingival plaque accumulation and gingivitis . Plaque and gingivitis were scored after 3 and 6-month use of the assigned dentifrice . At the end of the study , the triclosan group showed an average reduction , relative to the control group , of 12 % in plaque accumulation and 20 % in gingivitis . Both were statistically significant at p triclosan dentifrice was most pronounced on the more severe manifestations of plaque and gingivitis . The improvement in the gingival parameters at 6-months relative to the control dentifrice was statistically significant at p triclosan-containing dentifrice result ed in significant reduction in supragingival plaque formation and a significant improvement in gingival health without the presence of any extrinsic staining or objectionable taste", "PURPOSE To evaluate the effects of a novel mouthrinse containing 0.07 % high bioavailable cetylpyridinium chloride ( Crest Pro-Health Rinse ) on the development of gingivitis and plaque versus a placebo control over a period of 6 months . METHODS This was a r and omized , 6-month , placebo-controlled , parallel groups , double blind , single center clinical trial . One hundred thirty-nine generally healthy adults with mild-to-moderate gingivitis were enrolled in the study . Subjects were given Modified Gingival Index ( MGI ) , Gingival Bleeding Index ( GBI ) and Modified Quigley-Hein Plaque Index ( MQH ) examinations followed by a dental prophylaxis . Subjects were then r and omly assigned to either the cetylpyridinium chloride ( CPC ) rinse or placebo rinse and instructed to begin rinsing twice a day with 20 ml of their assigned mouthrinse for 30 seconds after brushing their teeth . Subjects were assessed for MGI , GBI and MQH scores after 3 and 6 months of product use . Oral hard and soft tissue examinations were also performed at all visits . RESULTS 124 subjects were evaluable at Month 3 and 119 at Month 6 . After 6 months , subjects rinsing with the CPC rinse showed 15.4 % less gingival inflammation , 33.3 % less gingival bleeding , and 15.8 % less plaque relative to the placebo group . All reductions were highly statistically significantly different ( P well-tolerated . CLINICAL SIGNIFICANCE This study demonstrates that the Crest Pro-Health 0.07 % CPC mouthrinse provided significant antiplaque and antigingivitis benefits when used twice daily for 6 months as an adjunct to toothbrushing", "PURPOSE To evaluate the effects of two experimental cetylpyridinium chloride ( CPC ) mouthrinses containing 0.075 % and 0.10 % CPC on the development of gingivitis and plaque versus a placebo control over a period of 6 months . METHODS This was a r and omized , single center , parallel group , double blind , positive and placebo controlled clinical trial . A 0.12 % chlorhexidine rinse served as the positive control for validation of the methodology . At the beginning of the trial , 366 subjects were balanced and r and omly assigned to treatment groups . Subjects received a dental prophylaxis and began rinsing twice a day with 15 ml of their assigned mouthwash for 30 seconds after brushing their teeth . Subjects were assessed for gingivitis and gingival bleeding by the Löe-Silness Gingival Index method and plaque by the Turesky modification of Quigley Hein Plaque Index at baseline and after 3 and 6 months of product use . Oral soft tissue health was also assessed . RESULTS After 3 and 6 months , subjects rinsing with either 0.075 % or 0.10 % CPC had significantly ( P gingivitis , gingival bleeding , and plaque , on average , than those on placebo . The 6-month mean reductions in gingivitis , gingival bleeding , and plaque for the 0.075 % and 0.10 % CPC rinses versus placebo were 23 % , 30 % and 17 % , and 20 % , 27 % and 19 % , respectively . There was no statistically significant difference in efficacy between the two CPC mouthrinses . Reductions at 3 months were similar to those seen at 6 months . Significant benefits were observed with chlorhexidine , thereby validating the study . CLINICAL SIGNIFICANCE This study clearly demonstrates that CPC mouthrinses formulated to deliver therapeutic benefits when used twice daily can significantly prevent the development of gingivitis , gingival bleeding , and plaque over a 6-month period", "A total of 159 adult male and female subjects between 18 and 63 years of age , were entered into a 6-month , double-blind clinical study to assess the effects of a dentifrice containing 0.3 % triclosan and 2 % of a copolymer of methoxyethylene and maleic acid on supragingival plaque formation and gingivitis , as compared to a placebo dentifrice . Both the triclosan and placebo dentifrices contained 0.243 % sodium fluoride in a silica base . The subjects had to demonstrate at least mild gingivitis ( modified Loe-Silness score > or = 1.0 ) , be free of advanced periodontal disease , have a modified Quigley-Hein Plaque Index score of at least 1.5 and have a minimum of 20 natural , uncrowned teeth . The subjects were stratified into two balanced groups according to baseline plaque and gingivitis scores . At zero time or baseline , all subjects received a complete and thorough oral prophylaxis and were assigned to the use of either the placebo dentifrice or the triclosan/copolymer dentifrice for the next 6 months . Subjects were evaluated for gingivitis and supragingival plaque formation after 3 and 6 months product use . After 3 months , when compared to the placebo dentifrice , the triclosan/copolymer dentifrice provided the following statistically significant reductions ( at 99 % confidence levels ) : ( 1 ) a 10.0 % reduction in supragingival plaque formation ; ( 2 ) a 20.8 % reduction in plaque formation on tooth surfaces with highest baseline plaque scores ; ( 3 ) a 21.9 % reduction in gingivitis , and ( 4 ) 30.5 % less sites with severe gingivitis , i.e. gingival bleeding . ( ABSTRACT TRUNCATED AT 250 WORDS", "A double-blind , parallel , r and omized and controlled clinical trial was conducted on 186 subjects over six months to assess the effects of a 0.28 % triclosan/5 % pyrophosphate ( with NaF/silica ) dentifrice on dental plaque and gingivitis as compared to a NaF/silica negative control dentifrice . An initial examination was performed to assess the health of the oral soft and hard tissues and to measure plaque ( by Turesky modified Quigley-Hein Plaque Index ) , gingivitis ( by Löe-Silness Gingival and Ainamo and Bay Gingival Bleeding [ GBI ] indices ) . Only those subjects with a GBI score > or = 5 were accepted into the study . Each enrolled subject received an oral prophylaxis and was requested to brush and floss twice per day with the negative control NaF/silica dentifrice . After one month , the subjects were recalled and a baseline examination was performed for each of the previously described parameters . Following the baseline examination , the subjects received another oral prophylaxis . The subjects were then separated by gender and by baseline GBI scores of 7 and arrayed by the changes in GBI bleeding sites from initial to baseline . Within strata , subjects were r and omly assigned to brush twice per day with either the triclosan/pyrophosphate dentifrice or the negative control dentifrice . The subjects were subsequently examined for all of the above-described parameters following use of the test dentifrices for five weeks , three and six months . The data generated in this trial were analyzed using an analysis of covariance on all indices for all subjects completing the examinations . The results from this study demonstrated that the use of the triclosan/pyrophosphate dentifrice result ed in statistically significant reductions of dental plaque compared to the control by 10 % ( p gingivitis or gingival bleeding evaluations throughout the study . Based on 1 ) the fact that subjects possessed plaque-induced gingivitis in this clinical study , 2 ) the similarity in the magnitude of the plaque reductions observed from the triclosan/pyrophosphate dentifrice relative to those reported for other triclosan-containing dentifrices , 3 ) the similarity in the dose of triclosan relative to other triclosan dentifrices , and 4 ) the reported magnitude of gingivitis reductions from other triclosan-containing dentifrices , these findings were unexpected . Possible explanations of these results are that the triclosan/pyrophosphate dentifrice may be uniquely different from other triclosan dentifrices relative to its effects on gingivitis , or alternatively , the clinical design utilized here may not be optimized for triclosan/pyrophosphate dentifrice ", "The effects of stabilized 0.454 % stannous fluoride dentifrices on supragingival plaque , gingival inflammation and gingival bleeding were studied in 549 adult male and female subjects who completed a six-month , double blind clinical study . Following an oral prophylaxis , subjects were r and omly assigned to brush with one of the following dentifrices : 1 ) 0.454 % SnF2 stabilized with 2.08 % sodium gluconate , 2 ) 0.454 % SnF2 stabilized with 4.16 % sodium gluconate , 3 ) an experimental dentifrice , or 4 ) 0.243 % NaF control dentifrice . Follow-up examinations were conducted at 3 and 6 months . Compared to the control dentifrice at 6 months , stannous fluoride dentifrices stabilized with 2.08 % or 4.16 % sodium gluconate significantly reduced gingivitis by 18.8 % and 18.0 % , respectively . There were no statistically significant differences between the two stabilized SnF2 groups with respect to their beneficial effects on gingival health . Gingival bleeding was also reduced , relative to the control dentifrice , for both stabilized SnF2 dentifrices . However , these differences were not statistically significant at p=0.05 . The stabilized SnF2 dentifrices were not significantly different from the control dentifrice in their effects on supragingival plaque . No significant differences in adverse oral soft tissue effects were observed between the test and control groups . As expected , accumulation of extrinsic tooth stain increased in the stabilized SnF2 groups . However , the difficulty in removing accumulated dental stain was similar between the control and stabilized SnF2 dentifrices . Since use of SnF2 dentifrices has been reported to produce tooth stain , gingivitis examinations were done with and without custom-made tooth covers to evaluate the potential for examiner bias . Comparable gingivitis and gingival bleeding benefits were observed when the evaluations were conducted with or without the tooth covers . Results from this study support that 0.454 % stabilized stannous fluoride dentifrices can provide an important adjunct to the prevention and control of gingivitis when used in combination with regular personal oral hygiene procedures and professional care", "Abstract Evidence suggests that brushing with a toothpaste may slow plaque reformation over 24 h. This study measured the effect of toothpaste alone on plaque regrowth over a 96 h period and compared the effect with water and the known antiplaque agent chlorhexidine . At 9 a.m. at the beginning of 7,4-day no oral hygiene periods , 10 volunteers were scaled and polished . Al 5 p.m. subjects brushed their own teeth with water until plaque free . Each subject rinsed for I min with 10 ml of a r and omly allocated rinse . Rinsing was repeated at 10 a.m. and 10 p.m. on subsequent days . The rinses were water , chlorhexidine 0.2 % or 3 g/10 ml slurries of toothpastes containing ( 1 ) monofluorophosphate(MFP ) , ( 2 ) monofluorophosphate + sodium fluoride ( MFP+NaF ) ( 3 ) monofluorophosphate + zinc citrate ( MFP+ZCT ) ( 4 ) stannous fluoride ( SnF2 ) ( 5 ) sodium fluoride ( NaF ) . At 16 , 24 , 48 and 72 h plaque on the buccal surface of the upper and lower premolars , canines and incisors was scored by the Gingival Margin Plaque Index ( GMPI ) and gram films of plaque sample s made . At 96 h plaque was recorded diagraromatically and areas of coverage measured visually ( Debris Index ) and by planimetry . Progressive plaque formation to a Gingival Margin Plaque Index of 100 % at 72 h was observed for toothpaste and water rinses . For chlorhexidine the Gingival Margin Plaque Index at 72 h was 6 % , At 96 h plaque areas were significantly less with toothpaste rinses compared with water . Chlorhexidine very significantly reduced plaque areas compared with toothpaste and water . The bacteriological assessment of smears revealed essentially similar plaque development during toothpaste and water rinses and was consistent with previous reports . However , with chlorhexidine the densities of organisms in the smears were greatly reduced . It was concluded that the small effect of toothpaste rinses on plaque accumulation compared with chlorhexidine would not alone represent a true antiplaque effect result ing in therapeutic benefit", "The objective of this six-month , placebo-controlled , double-blind clinical study , conducted in harmony with American Dental Association guidelines , was to provide an assessment of the effectiveness of a new dentifrice formulation of Colgate Total Toothpaste containing a special grade of silica ( Colgate Total Plus Whitening Toothpaste ) , vs. Colgate Total Fresh Stripe Toothpaste as a control , and a placebo dentifrice without triclosan and the copolymer , for the control of supragingival dental plaque and gingivitis . Adult male and female subjects from the state of New Jersey were entered into the study , and stratified into three treatment groups which were balanced for baseline Quigley-Hein Plaque Index scores and baseline Löe-Silness Gingival Index scores . Subjects received an oral prophylaxis , and were instructed to brush their teeth twice daily ( morning and evening ) for one minute with their assigned dentifrice , using a soft-bristled toothbrush . Examinations for supragingival plaque and gingivitis were conducted after three-months ' and again after six-months ' participation in the study . One-hundred ten ( 110 ) subjects complied with the protocol and completed the entire six-month clinical study . At both the three- and six-month study examinations , the Colgate Total Plus Whitening Toothpaste group and the Colgate Total Fresh Stripe Toothpaste group exhibited statistically significantly less supragingival plaque and gingivitis than did the placebo toothpaste group . At the six-month examination , the magnitude of these differences exceeded 23.0 % for all four parameters measured in the Colgate Total Plus Whitening Toothpaste group ( 29.9 % for Plaque Index , 59.2 % for Plaque Severity Index , 23.2 % for Gingival Index , and 75.1 % for Gingivitis Severity Index ) . Also , at the six-month examination , the magnitude of these differences exceeded 21.0 % for each of the four parameters measured in the Colgate Total Fresh Stripe Toothpaste group ( 27.9 % for Plaque Index , 54.9 % for Plaque Severity Index , 21.4 % for Gingival Index and 69.2 % for Gingivitis Severity Index ) . The results of this six-month clinical study support the conclusion that Colgate Total Plus Whitening Toothpaste and Colgate Total Fresh Stripe Toothpaste provided a statistically significant , clinical ly relevant level of efficacy for the control of supragingival plaque and gingivitis , in accordance with the criteria provided by current American Dental Association guidelines", "BACKGROUND Mechanical methods of oral hygiene can be complemented by the use of chemotherapeutic mouthrinses . The authors sought to quantify the additional benefit provided by an essential oil- , or EO- , containing mouthrinse in reducing plaque and gingivitis in patients who brush and floss regularly . METHODS The authors r and omly assigned patients with gingivitis to one of three treatment groups : brushing and rinsing with a control mouthrinse , or BC ; brushing , flossing and rinsing with a control mouthrinse , or BFC ; or brushing , flossing and rinsing with an EO-containing mouthrinse , or BFEO . Patients received a dental prophylaxis at baseline , and the authors followed them for six months . RESULTS Of 246 enrolled subjects enrolled in the study , 237 subjects were evaluable at the study 's conclusion . After six months , the subjects using the BFEO regimen had statistically and clinical ly significant lower mean Modified Gingival Index , or MGI , scores and Plaque Index , or PI , scores than did subjects in the BC group ( 29.9 percent and 56.3 percent , respectively ; P mean MGI and PI scores than did subjects in the BC group ( 11.2 percent and 9.3 percent , respectively ; P mean scores for MGI and PI than did subjects in the BFC group ( 21 percent and 51.9 percent , respectively ; P patients with gingivitis who brush and floss routinely , the adjunctive use of an EO-containing mouthrinse provides a clinical ly significant and meaningful additional benefit in reducing plaque and gingivitis . CLINICAL IMPLICATION S An EO-containing mouthrinse is an effective adjunct to regular brushing and flossing . Therefore , the BFEO regimen can be beneficial for patients with gingival inflammation", "BACKGROUND The efficacy of an essential oil-containing antiseptic mouthrinse ( Listerine Antiseptic , Pfizer ) and an antiplaque/antigingivitis dentifrice ( Colgate Total , Colgate-Palmolive ) has been demonstrated in numerous double-blind clinical studies . This study was conducted to determine their comparative efficacy . METHODS Three hundred sixteen subjects with mild-to-moderate gingival inflammation and plaque received a dental prophylaxis and began their r and omly assigned brushing and rinsing regimen in an unsupervised setting . Subjects brushed for one minute and rinsed with 20 milliliters for 30 seconds twice daily for six months . The three groups were L ( control toothpaste/Listerine rinse ) , T ( Colgate Total toothpaste/control rinse ) and P ( control toothpaste/control rinse ) . RESULTS Subjects in the L and T groups demonstrated statistically significantly lower ( P Modified Gingival Index , or MGI ; Bleeding Index , or BI ; and Plaque Index , or PI , at both three and six months than subjects in the P group . The magnitude of reduction for the L group was 22.9 percent , 70 percent and 56.1 percent , respectively , and for the T group , 20.8 percent , 58 percent and 22.1 percent , respectively . Subjects in the L group were not different from subjects in the T group in regard to visual signs of gingivitis ( MGI ) , but were more effective ( P BI and PI . No product-related adverse events were reported . CONCLUSION Although the Listerine Antiseptic and Colgate Total antiplaque/antigingivitis products produced similar , clinical ly significant reductions in gingivitis ( as measured by MGI and BI ) , Listerine , when used in conjunction with a fluoride dentifrice and usual oral hygiene , provided a greater benefit in reducing plaque . CLINICAL IMPLICATION S When considering an antiplaque/antigingivitis product to recommend to patients , clinicians should consider Listerine Antiseptic , in conjunction with usual oral hygiene , if more rigorous plaque control is desired", "The purpose of this study was to assess the efficacy of supragingival irrigation with 0.06 % chlorhexidine gluconate ( CHX ) on naturally occurring gingivitis . The relative benefit of CHX irrigation in comparison with CHX rinsing , water irrigation , and normal oral hygiene was evaluated . In a blind , placebo-controlled 6-month study 222 patients were assigned to one of four groups : Group 1 : Once daily irrigation with 300 ml water followed by irrigation with 200 ml 0.06 % chlorhexidine gluconate ( experimental ) ; Group 2 : Twice daily rinsing with 15 ml 0.12 % chlorhexidine ( positive control ) ; Group 3 : Once daily irrigation with 500 ml water ( irrigation control ) and Group 4 : Sodium fluoride dentifrice for normal oral hygiene only ( negative control ) . All groups used the same sodium fluoride dentifrice for tooth brushing . At baseline , 3 months , and 6 months patients were examined for Gingival Index ( GI ) , Bleeding on Probing ( BOP ) , Plaque Index ( PLI ) , Pocket probing depth ( PD ) , Calculus Index ( CI ) , and stain . After the baseline visit all patients received a supra- and subgingival oral prophylaxis . At 6 months GI and BOP were significantly ( P less than or equal to 0.05 ) reduced by adjunctive CHX irrigation ( 42.5 % and 35.4 % , respectively ) , CHX rinse ( 24.1 % and 15.0 % ) , and water irrigation ( 23.1 % and 24.0 % ) compared to tooth brushing alone . Plaque was significantly ( P less than or equal to 0.05 ) reduced only by CHX irrigation ( 53.2 % ) and CHX rinse ( 43.3 % ) while calculus and staining were significantly ( P less than or equal to 0.05 ) increased in the two chlorhexidine groups ( 276.4 % ( irrigation ) and 273.2 % ( rinse ) ) . Although significant ( P less than or equal to 0.05 ) , pocket probing depth reduction was minimal after CHX irrigation ( 4.6 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "The basic design for human clinical trials which examine prevention of gingivitis recurrence is well known . However , the anti-gingivitis efficacy of triclosan-containing dentifrices has not been routinely demonstrated using this design , regardless of formulation . In an effort to better underst and the subtleties of design which show triclosan efficacy , a study was undertaken to prospect ively test how subjects with a range of baseline disease levels ( which encompassed the range of gingivitis severity documented in the triclosan literature ) benefit from a triclosan dentifrice . This trial was a r and omized , double-blind , parallel group , six-month study where subjects brushed twice daily with either triclosan/pyrophosphate , triclosan/copolymer , triclosan placebo or sodium fluoride control ( NaF ) dentifrice following a prophylaxis . Both gingivitis and bleeding were measured using the Löe-Silness Gingival Index ( GI ) and plaque was measured using the Turesky Plaque Index . Comparisons between treatments were performed using an analysis of covariance . At month 3 , the triclosan/pyrophosphate group had a relative mean plaque benefit of 14.4 % versus the triclosan placebo group ( with an associated p-value of 0.004 ) , and subjects using triclosan/copolymer had a mean reduction in GI bleeding sites of 16.2 % relative to those brushing with the NaF control ( with an associated p-value of 0.031 ) . The overall results did not demonstrate a treatment effect for gingivitis or plaque for either triclosan-containing dentifrice at month 6 . There was evidence of modest anti-gingivitis efficacy in the triclosan placebo . In an effort to better underst and how baseline disease severity may have impacted the trial outcome , additional analyses were performed to investigate whether the magnitude of a triclosan effect was related to baseline gingivitis levels . An analysis of covariance model incorporating a baseline group interaction effect indicated that the magnitude of the treatment differences depended on the baseline scores The effect was most pronounced for GI bleeding sites . Further analysis showed that differences between triclosan dentifrices and the NaF control dentifrice were only present for subjects with more than 33 to 63 bleeding sites , depending on the specific comparison . These findings were illustrated through a series of subset analyses on subjects with > or = 20 ( entire study population ) , > or = 31 , > or = 40 and > or = 45 baseline GI bleeding sites . The magnitude of the treatment effect for both GI and GI bleeding sites increased with each succeeding subset . Unlike that required for other antimicrobial agents used in oral care products , these findings suggest that a study design which includes subjects with more severe gingivitis at baseline has the required sensitivity to demonstrate treatment benefits for triclosan dentifrices", "In order to compare the antiplaque and antigingivitis activity of three commercially-available triclosan containing dentifrices with that of a placebo dentifrice without triclosan , a double-blind clinical study was conducted on 194 subjects over six months . Following baseline supragingival plaque and gingivitis examinations and a complete oral prophylaxis , subjects were stratified by their whole mouth baseline plaque ( modified Quigley-Hein ) and gingivitis ( modified Löe-Silness ) scores and then r and omly assigned to one of four dentifrice using groups . Plaque and gingivitis examinations were then performed after six weeks , three months and six months use of the dentifrices . Subjects brushed twice daily in their customary manner . The triclosan/soluble pyrophosphate and the triclosan/zinc citrate commercially available dentifrices did not provide statistically significant reductions in either supragingival plaque accumulation or gingivitis at any of the examination intervals , as compared to the placebo dentifrice . The subjects using the commercially available triclosan/copolymer dentifrice had , after six months , statistically significant reductions in supragingival plaque ( 11.3 per cent ) , plaque severity ( 18.8 per cent ) , gingivitis ( 19.9 per cent ) and gingivitis severity ( 27.8 per cent ) , as compared to the placebo dentifrice", "This study compared the clinical efficacy of three mouthrinses containing either 0.12 % chlorhexidine , phenolic compounds , or sanguinarine , which were used unsupervised , in a placebo-controlled , double-blind study of 6 months ' duration . The study was conducted according to ADA clinical guidelines for evaluation of antigingivitis agents and was completed by 481 adults . Following baseline exams and a prophylaxis , subjects were r and omly divided into treatment groups matched for age , gender , and gingivitis severity , and were instructed to use the rinses in accordance with manufacturer 's directions . Followup examinations evaluated supragingival plaque , gingivitis , and gingival bleeding . Compared to placebo at 6 months , the group rinsing with 0.12 % chlorhexidine had significantly less gingivitis ( 31 % reduction ) , gingival bleeding ( 39 % reduction ) , and plaque ( 49 % reduction ) and was significantly better than any of the other treatment groups ( P less than 0.05 ) . Both the phenolic and sanguinarine groups showed moderate , yet significant , reductions in plaque compared to placebo ( 24 % and 12 % respectively ) yet were significantly less effective than the 0.12 % chlorhexidine rinse ( P less than 0.05 ) . However , neither the phenolic nor sanguinarine rinses were significantly different than placebo in their effects on gingivitis or gingival bleeding . These results support previous published results on the superiority of 0.12 % chlorhexidine when used in conjunction with professional care and as an adjunct to routine oral hygiene practice", "BACKGROUND The use of dental floss has long been considered to be effective in controlling interproximal plaque and gingivitis . The authors compared this method with that of use of a mouthrinse . METHODS Subjects with mild-to-moderate gingivitis enrolled in a long-term , six-month study . They received a dental prophylaxis and were r and omized into one of the three following treatment groups : brushing and rinsing with an essential oil-containing mouthrinse ( the BEO group ) , brushing and flossing ( the BF group ) and brushing and rinsing with a control rinse ( the B group ) . RESULTS A total of 326 subjects were evaluated . The BEO and BF had significantly lower ( P mean interproximal Modified Gingival Index , or MGI , scores than did the B group at six months . The BEO group had lower mean interproximal Plaque Index , or PI , scores than the other two groups at both three and six months . The BF group 's mean PI score was significantly lower than the B group 's mean score at six months only . The magnitude of reductions for the BEO and the BF groups ( vs. the B group ) in MGI were 11.1 percent and 4.3 percent and for PI were 20.0 percent and 3.4 percent , respectively . CONCLUSIONS In conjunction with professional care ( prophylaxis ) and toothbrushing over six months , rinsing twice daily with an essential oil-containing mouthrinse was at least as good as flossing daily in reducing interproximal plaque and gingivitis . Clinical Implication s. When weighing recommendations for oral hygiene home care , clinicians should consider that an essential oil-containing mouthrinse may be a useful adjunct in patients with gingival inflammation", "The objective of this six-month , double-blind clinical study , conducted in harmony with American Dental Association guidelines , was to provide a comparison between Colgate Total Toothpaste and Crest Gum Care Toothpaste with respect to their levels of efficacy for the control of supragingival dental plaque and gingivitis , and with respect to the levels of tooth staining associated with their use . Adult male and female subjects from the Edinburgh , Scotl and area were entered into the study and stratified into two treatment groups which were balanced for age , sex , baseline Quigley-Hein Plaque Index scores and baseline Löe-Silness Gingival Index scores . Subjects received an oral prophylaxis , and were instructed to brush their teeth twice daily ( morning and evening ) for one minute with their assigned dentifrice , using a soft-bristled toothbrush . Examinations for plaque , gingivitis and extrinsic tooth staining were conducted after three months ' and again after six months ' use of the study dentifrices . One-hundred and nine ( 109 ) subjects complied with the protocol and completed the entire six-month clinical study . At both the three- and six-month study examinations , the Colgate Total Toothpaste group exhibited statistically significantly less plaque , gingivitis and extrinsic tooth staining compared to the Crest Gum Care Toothpaste group . At the six-month examination , the magnitude of these differences exceeded 18 % for all six parameters measured ( 18.7 % for Plaque Index , 60.5 % for Plaque Severity Index , 22.2 % for Gingival Index , 85.1 % for Gingivitis Severity Index , 45.3 % for stain intensity , and 46.3 % for stain area ) . Thus , the results of this six-month clinical study support the conclusion that Colgate Total Toothpaste provides a statistically significant , substantive advantage in efficacy for the control of plaque and gingivitis over Crest Gum Care Toothpaste , while , at the same time , providing better control against the development of extrinsic tooth staining", "BACKGROUND Dentifrices traditionally have been formulated as pastes or gels . However , liquid varieties recently have become available The authors conducted a study to determine whether a fluori date d liquid product with added triclosan and a polyvinyl methyl ether/maleic acid , or PVM/MA , copolymer delivery system is efficacious for the control of supragingival plaque and gingivitis . METHODS The authors conducted a six-month , double-blind , parallel , stratified clinical study in accordance with American Dental Association guidelines for the clinical evaluation of antiplaque/antigingivitis products . Subjects who qualified with a suitable amount of existing plaque and gingivitis were given one of two dentifrices : an \" experimental \" liquid dentifrice containing 0.3 percent triclosan , 2.0 percent PVM/MA copolymer and 0.243 percent sodium fluoride , or NaF , in a silica base ; or a \" placebo \" dentifrice containing 0.243 percent NaF in a silica base . The authors collected subjects ' plaque and gingival index scores at baseline , three months and six months . RESULTS The results of the study indicate that the use of the experimental liquid dentifrice provided a significant reduction in existing levels of plaque and gingivitis as compared with the placebo st and ard dentifrice . At six months , the experimental group demonstrated a 34.9 percent reduction in plaque formation and a 25.7 percent reduction in gingivitis as compared with the placebo group ( P placebo , the experimental dentifrice had a significantly better ability to reduce plaque and gingivitis . When compared with results reported in the literature , this new form of dentifrice achieved results comparable in efficacy to those of traditional dentifrice pastes with matching active ingredients . CLINICAL IMPLICATION S This study confirms that a liquid dentifrice containing a triclosan/copolymer/NaF delivery system is efficacious in its ability to reduce existing plaque and gingivitis", "A total of one hundred fifty three healthy male and female adults were entered into a six month , double-blind clinical study design ed to evaluate the effect of a dentifrice containing 0.3 % triclosan and 2.0 % PVM/MA copolymer in a 0.243 % sodium fluoride/silica base , relative to a 0.243 % sodium fluoride silica base control dentifrice on supragingival plaque accumulation and gingivitis . Plaque and gingivitis were scored after 3 and 6 months ' use of the assigned dentifrice . At the end of the study , the dentifrice containing triclosan/copolymer demonstrated an average reduction , relative to the control dentifrice of 16.1 % in plaque accumulation and 24.3 % in gingivitis . Both were statistically significant(P triclosan/copolymer containing dentifrice result ed in a significant reduction in plaque formation and a significant improvement in gingival health . No side-effects were observed", "OBJECTIVES The objective of this study was to compare the antiplaque and antigingivitis effectiveness and the side-effect profiles of an essential oil-containing mouthrinse and a chlorhexidine-containing mouthrinse . MATERIAL AND METHODS One hundred and eight qualifying subjects , aged 20 - 57 years , were r and omized into three groups : essential oil mouthrinse ( ListerineAntiseptic ) ; 0.12 % chlorhexidine mouthrinse ( Peridex ) ; or 5 % hydroalcohol negative control . At baseline , subjects received a complete oral soft tissue examination and scoring of the Loe-Silness gingival index ( GI ) , Quigley-Hein plaque index ( PI ) , Volpe-Manhold calculus index ( CI ) , and Lobene extrinsic tooth stain index ( SI ) . Following a complete dental prophylaxis , subjects started rinsing twice daily with their respective mouthrinse as an adjunct to their usual mechanical oral hygiene procedures . One of the rinses on each weekday was supervised . Subjects were reexamined at 3 and 6 months . The treatment groups were compared with respect to baseline demographic and clinical variables . The primary efficacy variables were GI and PI . Intergroup differences for all clinical variables were tested at 3 and 6 months using appropriate statistical procedures . RESULTS All of the 108 r and omized subjects were evaluable at 3 months , and 107 subjects were evaluable at 6 months . There were no statistically significant differences among the three groups at baseline , with the exception that the control group PI was significantly lower than that of the essential oil group ( p chlorhexidine group ( p essential oil mouthrinse group had a significantly greater number of subjects than the control group with body region SI scores > or = 1.0 ( p=0.021 ) . At 6 months , the essential oil and chlorhexidine mouthrinses produced statistically significant ( p GI reductions of 14.0 % and 18.2 % , respectively , and statistically significant ( p PI reductions of 18.8 % and 21.6 % , respectively , compared with the control and were not statistically significantly different from each other with respect to plaque and gingivitis reduction . The chlorhexidine mouthrinse group had significantly more calculus and extrinsic tooth stain than either the essential oil mouthrinse group or the control group . CONCLUSION This 6-month controlled clinical study demonstrated that the essential oil mouthrinse and the chlorhexidine mouthrinse had comparable antiplaque and antigingivitis activity . Insofar as side effects associated with the chlorhexidine mouthrinse may limit patient compliance , it is suggested that each product can have a distinct role in the management of patients with periodontal diseases", "A 6-month double-blind , controlled clinical study was completed with 124 healthy adult subjects to determine the efficacy of 2 mouthrinses , Listerine ( LA ) and Peridex ( PX ) , used as supplements to regular oral hygiene measures in reducing supragingival dental plaque and gingivitis . Following screening examinations for entry levels of existing gingivitis and plaque , baseline gingival and plaque area indices , extrinsic tooth stain , supragingival calculus , bleeding and soft tissue condition were recorded . All subjects then received a complete dental prophylaxis to remove plaque , calculus and extrinsic stain . Subjects were r and omly assigned to 1 of 3 groups and performed supervised rinses twice daily for 30 s in addition to their normal oral hygiene , for 6 months . All indices were again evaluated at 3 and 6 months . After 6 months , LA and PX significantly ( p less than 0.001 ) inhibited development of plaque by 36.1 % and 50.3 % , respectively , and the development of gingivitis by 35.9 % and 30.5 % , respectively , compared to a hydroalcohol control . PX was more effective in inhibiting plaque and both mouthrinses appeared to be equally effective in inhibiting gingivitis . LA patients did not develop significant levels of stain or supragingival calculus at 6 months , compared to baseline or control . PX patients developed significant levels of extrinsic stain and supragingival calculus compared to baseline and control . Though PX was more effective than LA in the control of plaque , this study indicates that both LA and PX were effective agents in a regimen for the control of plaque and gingivitis", "3 triclosan-containing dentifrices were compared in a 6-month , unsupervised tooth brushing study . The effects on plaque , gingival bleeding and certain salivary micro-organisms ( mutans streptococci , lactobacilli , total counts of streptococci and total counts of micro-organisms ) were evaluated . 123 subjects were divided into 4 groups according to severity of gingival bleeding index . 112 subjects completed the study . Following a 4-week pre-experimental period , using a sodium monofluorophosphate dentifrice ( placebo ) , the subjects were assigned to use one of 3 triclosan-containing dentifrices , available on the Swedish market : Colgate Paradent ( a triclosan/copolymer dentifrice ) ( n = 26 ) ; Pepsodent Gum Health ( a triclosan/zinc citrate dentifrice ) ( n = 31 ) ; Dentosal Friskt T and kött ( a triclosan/pyrophosphate dentifrice ) ( n = 28 ) ; or to continue with the placebo ( n = 27 ) . The results revealed that Colgate Paradent reduced baseline plaque values by 39 % ( Quigley and Hein ) over the 6-month experimental period . The corresponding values for the other modalities were : a reduction of 6 % for Pepsodent Gum Health , an increase of 5 % for Dentosal Friskt T and kött , and an increase of 2 % for placebo . A significant difference in the plaque levels ( p gingival bleeding index was improved in all 4 groups . A significant difference ( p bleeding between Colgate Paradent and placebo ( p < 0.05 ) at the 3-month registration . A statistically significant increase over time in total number of streptococci and total colony forming units were found for the Dentosal , Pepsodent and placebo groups , but not for Colgate . ( ABSTRACT TRUNCATED AT 250 WORDS", "A 6-month , single-blind and parallel clinical study was conducted to compare the effects of dentifrice containing 0.3 % triclosan and 2.0 % of copolymer ( methoxyethylene and maleic acid ) with a customary oral hygiene procedure on supragingival plaque formation and gingivitis . The 124 subjects were stratified into two balanced groups on the basis of their baseline plaque and gingivitis scores . After complete oral prophylaxis , subjects were assigned to use either a triclosan/copolymer dentifrice or to practice their customary oral hygiene care for 6 months . Plaque formation and gingivitis were scored at 3 and 6 months . After 3 and 6 months , triclosan/copolymer produced 7.17 % and 12.07 % significantly greater reduction of plaque formation than the customary oral hygiene group , respectively . Triclosan/copolymer significantly reduced gingivitis by 5.20 % at 3 months , while no significant differences between the two groups were observed at 6 months . Likewise , triclosan/copolymer provided 8.70 % and 16.33 % significantly greater reduction of plaque severity index at 3- and 6-month evaluation , respectively . Gingivitis severity index was significantly reduced by 25 % at 3 months , but there were no differences between the two groups at 6 months . These results indicate that the triclosan/copolymer dentifrice was better than the customary oral hygiene care in preventing supragingival plaque formation up to 6 months and in reducing gingivitis up to 3 months", "A number of compounds have been added to toothpastes to inhibit plaque regrowth . The inclusion of cationic antiseptics , such as chlorhexidine , poses formulation difficulties because of interactions with other ingredients particularly anionic detergents . More recently , Triclosan/zinc citrate formulations have been shown effective plaque inhibitors . The aim of this study was to compare a commercially available 0.2 % Triclosan/0.5 % zinc citrate toothpaste with a number of experimental 0.5 % chlorhexidine/detergent toothpastes for effects on plaque regrowth over 4 days . Subjects rendered plaque free at each baseline rinsed twice a day with toothpaste slurries and disclosed plaque was scored at the end of each period . All toothpastes significantly reduced plaque by comparison with a control toothpaste , but were significantly less effective than a 0.2 % chlorhexidine rinse . Some significant differences in favour of one chlorhexidine toothpaste were noted but these were small in magnitude . Whether the plaque inhibition obtained with Triclosan/zinc citrate toothpaste was greater than would be expected from other commercially available preparations can not be determined from this study and is the subject of a further investigation", "PURPOSE To compare the effectiveness of rinsing with an essential oil-containing antimicrobial mouthrinse with that of dental floss in reducing interproximal gingivitis and plaque in an unsupervised 6-month clinical trial design ed in accordance with ADA Acceptance Program Guidelines . MATERIAL S AND METHODS 319 qualifying subjects , aged 18 - 63 , were r and omized into one of three groups : essential oil mouthrinse ( Listerine Antiseptic ) ; dental floss ( Reach Dental Floss ) ; or a negative control rinse . At baseline , subjects received a complete oral soft tissue examination and scoring of the Modified Gingival Index ( MGI ) , modified Quigley-Hein Plaque Index ( PI ) , and bleeding index ( BI ) . Following a complete dental prophylaxis and receiving flossing or rinsing instructions , subjects started on their respective regimen . They continued on their assigned regimen unsupervised at home , in addition to toothbrushing , and were reexamined at 3 and 6 months . The treatment groups were compared with respect to baseline demographic and clinical variables . The primary efficacy variables were mean interproximal MGI and PI at 6 months . Intergroup differences at 3 and 6 months were tested using a one-way analysis of covariance model with treatment as a factor and the respective baseline value as the covariate . In addition , the essential oil mouthrinse was compared to floss for interproximal gingivitis reduction using \" at least as good as \" statistical criteria . RESULTS 301 subjects were considered evaluable . There were no statistically significant differences among the 3 groups at baseline , with the exception of the essential oil mouthrinse group having significantly fewer AfroAmerican subjects than the other two groups . For the interproximal MGI , the essential oil mouthrinse and flossing were both significantly more effective than the negative control ( P essential oil mouthrinse was shown to be \" at least as good as \" dental floss for the control of interproximal gingivitis . For the interproximal PI , the essential oil mouthrinse was significantly more effective than the negative control at 3 and 6 months ( P essential oil mouthrinse was significantly more effective than floss ( P < 0.001 ) at both these time periods", "The intraoral antimicrobial activity of four commercial oral products-conventional NaF dentifrice ( Crest ) , baking soda/peroxide/NaF dentifrice ( Mentadent ) , essential oil mouthrinse ( Listerine ) and SnF2 dentifrice ( Crest Plus Gum Care)-have been compared in three test regimens . Formulations were compared for their ability to suppress the regrowth and apical extension of dental plaque following toothbrushing during thirty hours of non-brushing where products were used as oral rinses ( 30-hour plaque regrowth model ) . Formulations were also compared for their ability to suppress the colony-forming units ( cfu ) of facultative anaerobic bacteria sample d from buccal gingival surfaces following use ( Gingival Surface Microbial Index-GSMI model ) . Lastly , formulations were compared for effects in suppressing the glycolytic metabolic activity and regrowth activity of in vivo-treated dental plaques sample d at various periods following topical use and incubated under controlled ex vivo conditions ( Plaque Glycolysis and Regrowth-PGRM model ) . In thirty-hour plaque regrowth testing , the rank ordered antimicrobial efficacy of formulations followed SnF2 > essential oils > NaF = water = baking soda/peroxide . In GSMI testing , all formulations were shown to suppress the cfu of facultative anaerobic bacteria relative to baseline , although SnF2 treatment was observed to reduce bacterial levels to a significantly greater degree than NaF dentifrice or baking soda/peroxide dentifrice up to two hours following brushing . In PGRM testing , the SnF2 dentifrice provided significant inhibition of bacterial metabolism and regrowth following topical application when compared with the NaF dentifrice as control . The baking soda/peroxide dentifrice provided no reduction in either bacterial metabolism or regrowth in PGRM . Previous studies had demonstrated modest effects for essential oil rinse in reducing PGRM plaque regrowth , with no effects for this treatment on plaque metabolism . Overall , these results demonstrate that SnF2 dentifrice provides substantial intraoral antimicrobial effects . The essential oil mouthrinse also exhibits significant intraoral antimicrobial effects , albeit apparently less than SnF2 dentifrice . The baking soda/peroxide dentifrice did not produce any antimicrobial effects following in vivo use compared with conventional dentifrice . These results provide mechanistic rationale for the chemotherapeutic efficacy of SnF2 and essential oil formulations in reducing gingivitis , while providing no support for the expectation of clinical efficacy for formulations containing baking soda and peroxide", "A number of substances have been incorporated into toothpastes or gels to inhibit plaque regrowth . The aim of this study was to evaluate triclosan and stannous fluoride products for plaque inhibitory properties by comparison with a chlorhexidine or saline rinse and a control product which was a conventional commercially available toothpaste . In a blind 8 cell cross-over study , 15 volunteers rinsed 2 x a day for 4 days with slurries of the products or the saline and chlorhexidine solutions . No other form of oral hygiene was performed and plaque regrowth from a zero baseline was recorded by plaque score and plaque area . Plaque regrowth was significantly less with the chlorhexidine rinse and significantly greater with the saline rinse compared to the toothpaste and gel products . No significant differences were found between the test and control products . The results again demonstrate that commercially available toothpastes have plaque inhibitory effects which so far appear difficult to improve upon by the addition of specific ingredients , in this case stannous fluoride or triclosan . Commercially available products of known activity would appear useful benchmarks for comparison of experimental formulations", "The objective of this 6-month , double-blind , clinical study , conducted following the American Dental Association ( ADA ) guidelines , was to provide an assessment of the effectiveness of a newly developed mouthrinse containing 0.05 % cetylpyridinium chloride ( CPC ) for the control of supragingival dental plaque and gingivitis . Adult men and women from the Manchester , Engl and , area were entered in the study , and stratified into two treatment groups ( CPC mouthrinse and control mouthrinse ) , which were balanced for baseline Quigley-Hein Plaque Index scores and baseline Löe-Silness Gingival Index scores . Participants were given an oral prophylaxis and instructed to brush their teeth twice daily ( morning and evening ) for 1 minute with a soft-bristled toothbrush and fluoride dentifrice provided , immediately followed by rinsing for 30 seconds with 15 cc of their assigned mouthrinse . Examinations for supragingival plaque and gingivitis were conducted after 3 months ' and again after 6 months ' participation in the study . One hundred eleven participants complied with the protocol and completed the entire 6-month clinical study . At both the 3- and 6-month study examinations , the CPC mouthrinse group exhibited statistically significantly less supragingival plaque and gingivitis than did the control mouthrinse group . At the 6-month examination , the magnitude of these differences met or exceeded 24 % for all 4 parameters measured ( 28.2 % for Quigley-Hein Plaque Index , 63.4 % for Plaque Severity Index , 24.0 % for Löe-Silness Gingival Index , and 66.9 % for Gingivitis Severity Index ) . The magnitude of the reductions in supragingival plaque and gingivitis were adequately large to support a cl aim of efficacy , in accordance with the criteria provided by the published guidelines of the ADA for the demonstration of the efficacy of a chemotherapeutic agent for the control of supragingival plaque and gingivitis . Thus , the results of this 6-month clinical study support the conclusion that a newly developed mouthrinse containing 0.05 % cetylpyridinium chloride provides a statistically significant , clinical ly relevant level of efficacy for the control of supragingival plaque , and for the control of gingivitis , in accordance with the criteria provided by current ADA guidelines", "A 9-month double-blind controlled clinical study was conducted on adult subjects using either Listerine antiseptic , its vehicle control , or a water control in order to determine the efficacy of the antiseptic mouthrinse in inhibiting the development of plaque and gingivitis . Following screening examinations for minimal entry levels of plaque and gingivitis , all subjects received a complete prophylaxis . Subjects then continued their usual oral hygiene habits for a 3-week normalization period and were examined for soft tissue abnormalities and baseline measurements of plaque , gingivitis , and tooth stain . 2 additional prophylaxes were then performed , followed by a second baseline gingival examination . Zero plaque was re-established by rubber cup polishing and twice daily rinsing was begun . Soft tissue , plaque , gingivitis , and extrinsic tooth stain were evaluated after 1 , 3 , 6 and 9 months of rinsing with the r and omly assigned mouthrinses . Results demonstrated that Listerine antiseptic significantly reduced the development of plaque at 1 , 3 , 6 and 9 months and the development of gingivitis at 9 months , as compared to its vehicle control or water control", "This parallel-group , double-blind , placebo-controlled clinical trial directly compared the efficacy of two antimicrobial dentifrice formulations for the control of plaque , gingivitis and gingival bleeding during six months of use following a pre-test r and omization period . Test antimicrobial dentifrices for the study included : a stabilized stannous fluoride formulation ( Crest Plus Gum Care-currently marketed in U.S. ) comprised of 0.454 % SnF2 in a stabilized silica abrasive base ; and a formulation containing triclosan ( Colgate Total , currently marketed outside the U.S. in numerous countries ) comprised of 0.30 % triclosan . 2.0 % Gantrez co-polymer and 0.243 % NaF in a silica abrasive base . The control dentifrice was a conventional fluoride dentifrice comprised of 0.243 % NaF in a silica abrasive base . Clinical evaluations included Turesky et al. plaque , Löe-Silness gingivitis and gingival bleeding , and Meckel stain . The stabilized stannous fluoride dentifrice exhibited significant efficacy in the reduction of both gingivitis ( 20.5 % ) and gingival bleeding ( 33.4 % ) after six months relative to the placebo control ( p stannous fluoride dentifrice reduced gingivitis and gingival bleeding significantly relative to the triclosan/copolymer dentifrice ( p clinical efficacy of a stabilized stannous fluoride dentifrice relative to a triclosan/copolymer dentifrice in the chemotherapeutic control of gingivitis and gingival bleeding ; 2 ) the important contribution of clinical test design /sensitivity in assessing the therapeutic efficacy of antimicrobial agents ; and 3 ) the value of head-to-head comparative studies in establishing the therapeutic relevance of clinical effects of formulations for the reduction of gingivitis", "The aim of the present clinical trial was to study the effect on existing plaque and gingivitis of an oral hygiene regimen which utilized a dentifrice which contained triclosan . 120 subjects were recruited for the trial . They were examined for plaque and gingivitis using the criteria of ( i ) the Turesky modification of the Quigley & Hein plaque index and ( ii ) the Löe & Silness gingival index . Plaque and gingivitis were assessed in all parts of the dentition and at 6 location points around each tooth . Following a baseline examination , the subjects were stratified in 2 balanced groups based on age , plaque and gingivitis scores . The subjects were r and omly assigned to the following treatment : 1 test group used a dentifrice containing triclosan/copolymer/fluoride and 1 control group used a traditional fluoride containing dentifrice . The participants were given the assigned dentifrice and a soft-bristled toothbrush for home use . They were instructed to brush their teeth in the morning and in the evening for one minute each time . They were reexamined 6 weeks , 3 and 6 months after the baseline examination . The findings from the re-examinations revealed that an oral hygiene regimen which utilized a dentifrice which contained triclosan/copolymer significantly reduced pre-existing plaque and gingivitis above what was accomplished by a traditional fluoride containing dentifrice . The improvement of the gingival conditions occurred in all parts of the dentition and at all tooth surfaces and units . In addition , the present data support the hypothesis that triclosan may induce alterations in the quality of existing plaque", "A CPC-detergent formulation in a foam vehicle , was compared with a fluoride toothpaste for its ability to prevent plaque and gingivitis over a period of 12 days . Whilst refraining from all other oral hygiene procedures , the foam or toothpaste was applied to the teeth in fluoride application trays , in a group of 14 volunteers . At days 8 and 12 of this crossover study , the following assessment s were made : gingival crevicular fluid ; gingival index ; bleeding on probing ; plaque index ; plaque area . Except for plaque area at day 8 of the study , there were no significant differences between the 2 products at either day 8 or day 12 . It is therefore concluded that the CPC-detergent formulation , in its present form , does not inhibit plaque and gingivitis more effectively than a conventional fluoride toothpaste", "The present study was performed in 10 adults in order to evaluate the effect of an antiseptic mouthrinse ( Listerine ) on the rate of dental plaque formation and gingivitis development during a 2-week period when all efforts towards active mechanical oral hygiene were withdrawn . The study was performed as a crossover study and was carried out during four consecutive 2-week periods . During the first and third periods ( preparatory periods ) the participants were subjected to repeated professional tooth cleanings in order to establish plaque- and gingivitis-free dentitions . During the second and fourth periods ( test and control periods ) the participants were not allowed to brush their teeth but rinsed their mouths three times a day with Listerine or a placebo mouthwash . Plaque Index , Gingival Index , gingival fluid flow , and crevicular leukocytes were assessed on d 0 , 2 , 4 , 7 , and 14 . On d 7 and 14 , dental plaque was removed from the right and left jaws respectively and the wet weights determined . The chemotactic activity elaborated by the plaques was studied in Boyden chambers . During the Listerine test period , significantly lower Plaque and Gingival Index values were scored and lower amounts of plaque could be sample d in comparison to the control period", "A six-month , double-blind clinical study was entered into by three hundred twenty-five ( 325 ) male and female adult subjects to assess the efficacy of a dentifrice containing 0.3 % triclosan ( Irgacare MP , Ciba-Geigy Corp. ) and 2.0 % of a copolymer of methoxyethylene and maleic acid ( Gantrez , ISP Corp. ) on supragingival plaque formation and gingivitis , compared to a placebo dentifrice over a six-month period . Each dentifrice , the triclosan and the placebo , contained 0.243 % sodium fluoride in a silica base . Only those subjects who were free of periodontal disease ( no pockets > 4 mm ) , demonstrated a level of at least mild gingivitis ( modified Loe-Silness score > or = 1.0 ) and had a modified Quigley-Hein Plaque Index score of > or = 1.5 were admitted into the study . Baseline plaque and gingivitis scores were used to stratify the subjects into two balanced groups . A thorough oral prophylaxis was administered to all subjects . They were then assigned either the triclosan/copolymer dentifrice or the placebo dentifrice to use for the next six months . Evaluation for gingivitis and supragingival plaque formation was made after three and six months . Evaluations made after six ( 6 ) months demonstrated a 17.0 % statistically significant ( at the 99 % level of confidence ) reduction in supragingival plaque formation was provided by the triclosan/copolymer dentifrice , compared to the placebo dentifrice . An 18.6 % statistically significant ( at the 99 % level of confidence ) reduction in plaque formation on the tooth surfaces with the highest plaque formation was provided by the triclosan/copolymer dentifrice , compared to the placebo dentifrice . ( ABSTRACT TRUNCATED AT 250 WORDS", "A total of 108 adult male and female subjects completed a six-month , double-blind clinical study design ed to compare the effect of a dentifrice containing 0.3 % triclosan and 2.0 % of a copolymer of methoxyethylene and maleic acid ( Gantrez copolymer ) in a 0.243 % sodium fluoride/silica base to a 0.243 % sodium fluoride/silica placebo dentifrice on supragingival plaque formation and gingivitis . Subjects were stratified into two balanced groups by their baseline plaque and gingivitis scores . They received an oral prophylaxis and were assigned to use either the triclosan/copolymer dentifrice or the placebo dentifrice for the next six months . After six months , the dentifrice containing triclosan/copolymer provided a 24.93 % statistically significant ( 99 % level of confidence ) reduction in supragingival plaque , and a 19.72 % statistically significant ( 99 % level of confidence ) reduction in gingivitis compared to the placebo dentifrice . Twice daily use of a dentifrice containing 0.3 % triclosan , 2.0 % of a copolymer , and 0.243 % sodium fluoride in a silica base , over a six-month period , reduces supragingival plaque formation and gingivitis to a significant degree compared to a sodium fluoride/silica base placebo dentifrice" ]

[ "OBJECTIVE To use two different exercise programs over a 2-year period to reduce falls and their sequelae among residents of two long-term care facilities . DESIGN R and omized , controlled trial . SETTING The study took place at two long-term care facilities with services ranging from independent living to skilled nursing . PARTICIPANTS One hundred and ten participants whose average age was 84 and who were capable of ambulating with or without assistive devices and could follow simple directions . INTERVENTION Participants were r and omized to one of two exercise groups ( resistance/endurance plus basic enhanced programming or tai chi plus basic enhanced programming ) or to a control group ( basic enhanced programming only ) . Exercise classes were held three times per week throughout the study . MEASUREMENTS Participants were evaluated for cognitive and physical functioning at baseline and 6 , 12 , and 24 months . Falls were determined from incident reports filed by the nursing staffs at the facilities . RESULTS Time to first fall , time to death , number of days hospitalized , and incidence of falls did not differ among the treatment and control groups ( P>.05 ) . Among all participants , those who fell had significantly lower baseline Folstein Mini-Mental State Examination and instrumental activities of daily living scores and experienced significantly greater declines in these measures over the 2-year program . CONCLUSION There were no significant differences in falls among the two exercise groups and the control group . Lack of treatment differences and low adherence rates suggest that residents of long-term care facilities may require individualized exercise interventions that can be adapted to their changing needs", "OBJECTIVES To establish the effectiveness of a fall-prevention program in reducing falls and injurious falls in older residential care residents . DESIGN Cluster , r and omized , controlled trial . SETTING Fourteen r and omly selected residential care homes in Auckl and , New Zeal and . PARTICIPANTS All older residents ( n=628 , 95 % participation rate ) . INTERVENTION Residential care staff , using existing re sources , implemented systematic individualized fall-risk management for all residents using a fall-risk assessment tool , high-risk logo , and strategies to address identified risks . MEASUREMENTS Number of residents sustaining a fall , falls , and injurious-falls incidence rates . RESULTS During 12 months of follow-up , 103 ( 43 % ) residents in the control group and 173 ( 56 % ) residents in the intervention group fell ( P higher incidence rate of falls in intervention homes than in control homes ( incident rate ratio=1.34 , 95 % confidence interval=1.06 - 1.72 ) during the intervention period after adjusting for dependency level ( type of home ) , baseline fall rate , and clustering . There was no difference in the injurious fall incidence rate or incidence of serious injuries . CONCLUSION This fall-prevention intervention did not reduce falls or injury from falls . Low-intensity intervention may be worse than usual care", "OBJECTIVE to determine the effect of risk factor modification and balance exercise on falls rates in residential care homes . DESIGN cluster r and omised controlled trial . PARTICIPANTS 196 residents ( aged 60 years or over ) in 20 residential care homes were enrolled ( 38 % response rate ) . Homes were r and omly allocated to intervention and control arms . A total of 102 residents were consigned to the intervention arm and 94 to the control arm . INTERVENTION a multifactorial falls prevention programme including 3 months gait and balance training , medication review , podiatry and optometry . MAIN OUTCOME MEASURES number of falls/recurrent falls per person , number of medications per person , and change in Tinetti gait and balance measure . RESULTS in the intervention group there was a mean of 2.2 falls per resident per year compared with 4.0 in the control group ; this failed to reach statistical significance ( P = 0.2 ) once the intra-cluster correlation ( ICC , 0.10 ) had been accounted for . Several risk factors were reduced in the intervention arm . CONCLUSIONS falls risk factor reduction is possible in residents of care homes . A modest reduction in falls rates was demonstrated but this failed to reach statistical significance", "Background Regular physical activity may improve different aspects of wellbeing in older people , such as quality of life , vitality and depression . However , there is little experimental evidence to support this assumption . Therefore , we examined the effect of different training protocol s on quality of life , vitality and depression of older adults living in long-term care facilities . Methods Subjects ( n = 173 , aged 64 to 94 years , living in long-term care facilities ) , were r and omized to six months of three different moderate-intensity group exercise training protocol s , or to an ' educational ' control condition . Exercise consisted of two 45–60-minute training sessions per week of 1 ) resistance training ; 2 ) all-round , functional training ; or 3 ) a combination of both . Perceived health , the Geriatric Depression Scale ( GDS ) , the Vitality Plus Scale ( VPS ) and the Dementia Quality of Life question naire ( DQoL ) were administered at baseline and after six months . Results In the combined training group a small but significant decline was seen in perceived health , DQoL and VPS score compared to the control group . Conclusions We conclude that neither strength training nor all-round , functional training of moderate intensity is effective in improving quality of life , vitality or depression of older people living in long-term care facilities", "BACKGROUND Physical activity programs in nursing homes typically consist of seated , range of motion ( ROM ) exercises , regardless of resident abilities . The Functional Fitness for Long-Term Care ( FFLTC ) Program was design ed not only to maintain ROM , but also to improve strength , balance , flexibility , mobility , and function . In addition , it was tailored to meet the needs of both high and low mobility residents . METHODS The feasibility and efficacy of the FFLTC Program were evaluated with 68 residents ( mean age 80 ) from five institutions . Persons were classified as low or high mobility and r and omized into either the FFLTC program or a seated ROM program . Classes were conducted in groups of 4 to 10 residents by trained facility staff for 45 minutes , three times per week . Assessment s at baseline and 4 months consisted of mobility , balance , gait , flexibility , functional capacity , and several upper and lower extremity strength measures . RESULTS Attendance averaged 86 % for the FFLTC and 79 % for the ROM classes . Four months of exercise led to significant improvements in mobility ( 16 % ) , balance ( 9 % ) , flexibility ( 36 % ) , knee ( 55 % ) , and hip ( 12 % ) strength for the FFLTC group . Shoulder strength was the only improvement found for the ROM group . The ROM group significantly deteriorated in some areas , particularly hip strength , mobility , and functional ability . CONCLUSIONS Institutionalized seniors , even those who are physically frail , incontinent and /or have mild dementia , can respond positively to a challenging exercise program . The FFLTC program demonstrated clear benefits over typical , seated ROM exercises . Moreover , with minimal training , the program can be safely delivered at low cost by institutional staff and volunteers", "BACKGROUND AND PURPOSE Knowledge concerning the applicability and the effect of high-intensity exercise programs is very limited for older people with severe cognitive and physical impairments . The primary aim of this study was to evaluate the applicability of a high-intensity functional weight-bearing exercise program among older people who are dependent in activities of daily living and living in residential care facilities . A second aim was to analyze whether cognitive function was associated with the applicability of the program . SUBJECTS The subjects were 91 older people ( mean age=85.3 years , SD=6.1 , range=68 - 100 ) who were dependent in personal activities of daily living and r and omly assigned to participate in an exercise intervention . Their mean score for the Mini-Mental State Examination ( MMSE ) was 17.5 ( SD=5.0 , range=10 - 29 ) . METHODS A high-intensity functional weight-bearing exercise program was performed in groups of 3 to 7 participants who were supervised by physical therapists . There were 29 exercise sessions over 13 weeks . Attendance , intensity of lower-limb strength and balance exercises , and occurrence and seriousness of adverse events were the outcome variables in evaluating the applicability of the program . RESULTS The median attendance rate was 76 % . Lower-limb strength exercises with high intensity were performed in a median of 53 % of the attended exercise sessions , and balance exercises with high intensity were performed in a median of 73 % of the attended exercise sessions . The median rate of sessions with adverse events was 5 % . All except 2 adverse events were assessed as minor and temporary , and none led to manifest injury or disease . No significant differences were observed in applicability when comparing participants with dementia and participants without dementia . In addition , there was no significant correlation between applicability and the MMSE score . DISCUSSION AND CONCLUSION The results suggest that a high-intensity functional weight-bearing exercise program is applicable for use , regardless of cognitive function , among older people who are dependent in activities of daily living , living in residential care facilities , and have an MMSE score of 10 or higher", "OBJECTIVES To evaluate the effectiveness of a multifaceted , nonpharmaceutical intervention on incidence of falls and fallers . DESIGN Prospect i ve , cluster-r and omized , controlled 12-month trial . SETTING Six community nursing homes in Germany . PARTICIPANTS Long-stay residents ( n = 981 ) aged 60 and older ; mean age 85 ; 79 % female . INTERVENTIONS Staff and resident education on fall prevention , advice on environmental adaptations , progressive balance and resistance training , and hip protectors . MEASUREMENTS Falls , fallers , and fractures . RESULTS The incidence density rate of falls per 1,000 resident years ( RY ) was 2,558 for the control group ( CG ) and 1,399 for the intervention group ( IG ) ( relative risk ( RR ) = 0.55 , 95 % confidence interval ( CI ) = 0.41 - 0.73 ) . Two hundred forty-seven ( 52.3 % ) fallers were detected in the CG and 188 ( 36.9 % ) in the IG ( RR = 0.75 , 95 % CI = 0.57 - 0.98 ) . The incidence density rate of frequent fallers ( > 2/year ) was 115 ( 24.4 % ) for the CG and 66 ( 13.0 % ) for the IG ( RR = 0.56 , 95 % CI = 0.35 - 0.89 ) . The incidence density rate of hip fractures per 1,000 RY was 39 for the CG and 43 for the IG ( RR = 1.11 , 95 % CI = 0.49 - 2.51 ) . Other fractures were diagnosed with an incidence density rate of 52 per 1,000 RY for CG and 41 per 1,000 RY for IG ( RR = 0.78 , 95 % CI = 0.57 - 1.07 ) . CONCLUSION The incidence density rate of falls and fallers differed considerably between the control and intervention groups . The study was underpowered to demonstrate a significant difference of hip or nonhip fractures . Because of a low fracture rate in both groups , the investigation of fracture rates would have required a larger sample size to detect an effect of the intervention", "OBJECTIVES To determine the effects of moderate intensity group-exercise programs on falls , functional performance , and disability in older adults ; and to investigate the influence of frailty on these effects . DESIGN A 20-week , multicenter r and omized controlled trial , with 52-week follow-up . SETTING Fifteen homes for the elderly . PARTICIPANTS Two hundred seventy-eight men and women ( mean age + /- st and ard deviation , 85+/-6y ) . INTERVENTIONS Two exercise programs were r and omly distributed across 15 homes . The first program , functional walking ( FW ) , consisted of exercises related to daily mobility activities . In the second program , in balance ( IB ) , exercises were inspired by the principles of Tai Chi . Within each home participants were r and omly assigned to an intervention or a control group . Participants in the control groups were asked not to change their usual pattern of activities . The intervention groups followed a 20-week exercise program with 1 meeting a week during the first 4 weeks and 2 meetings a week during the remaining weeks . MAIN OUTCOME MEASURES Falls , Performance Oriented Mobility Assessment ( POMA ) , physical performance score , and the Groningen Activity Restriction Scale ( GARS ) ( measuring self-reported disability ) . RESULTS Fall incidence rate was higher in the FW group ( 3.3 falls/y ) compared with the IB ( 2.4 falls/y ) and control ( 2.5 falls/y ) groups , but this difference was not statistically significant . The risk of becoming a faller in the exercise groups increased significantly in the subgroup of participants who were classified as being frail ( hazard ratio [ HR ] = 2.95 ; 95 % confidence interval [ CI ] , 1.64 - 5.32 ) . For participants who were classified as being pre-frail , the risk of becoming a faller decreased ; this effect became significant after 11 weeks of training ( HR = .39 ; 95 % CI , .18-.88 ) . Participants in both exercise groups showed a small , but significant improvement in their POMA and physical performance scores . In the FW group , this held true for the GARS score as well . Post hoc analyses revealed that only the pre-frail participants improved their POMA and physical performance scores . CONCLUSIONS Fall-preventive moderate intensity group-exercise programs have positive effects on falling and physical performance in pre-frail , but not in frail elderly", "Background Large-scale RCTs comparing different types of exercise training in institutionalised older people are scarce , especially regarding effects on habitual physical activity and constipation . This study investigated the effects of different training protocol s on habitual physical activity and constipation of older adults living in long-term care facilities . Methods A r and omized controlled trial with 157 participants , aged 64 to 94 years , who were r and omly assigned to 1 ) resistance training ; 2 ) all-round functional-skills training ; 3 ) both ; or 4 ) an ' educational ' control condition . Habitual physical activity was assessed with a physical activity question naire and accelerometers . Constipation was assessed by a question naire . Measurements were performed at baseline and after six months of training . Results At baseline the median time spent sitting was 8.2 hr/d , the median time spent on activity of at least moderate intensity was 32 min/d . At baseline , about 22 % of the subjects were diagnosed with constipation and 23 % were taking laxatives . There were no between-group differences for changes in habitual physical activity or constipation over 6-months . ConclusionS ix months of moderate intensity exercise training neither enhances habitual physical activity nor affects complaints of constipation among older people living in long-term care facilities", "Objective : To evaluate the specific effects of balance and gait exercises among frail elderly individuals . Design : A r and omized three-group parallel controlled study . Setting : Geriatric health services facility in Japan . Subjects : Thirty-four frail elderly subjects attending the care facility were r and omized into a control group , an exercise group with emphasis on balance or an exercise group with emphasis on gait re-education . Interventions : The two exercise groups received balance or gait exercise for 40 minutes , 2–3 times weekly , for 12 weeks . Main outcome measures : One Leg St and ing Test , Functional Reach Test , Manual Perturbation Test , Functional Balance Scale , Performance-Oriented Mobility Assessment , Timed ‘ Up and Go ’ Test and Stair Climbing/Descending Test . These assessment s were performed before and after 12-week intervention . Results : Comparison of the performance before and after intervention demonstrated significant improvement in One Leg St and ing Test , Functional Reach Test and Functional Balance Scale in the balance exercise group , and Functional Balance Scale , Timed ‘ Up and Go ’ Test and Stair Descending Test showed improvement in the gait exercise group . All test items showed no significant differences in the control groups . Among the three groups , the balance exercise group showed more significant improvement in Functional Balance Scale , and the gait exercise group showed more significant improvement in Performance-Oriented Mobility Assessment than the control group . The balance exercise group showed greater improvement in performance in Functional Reach Test than the gait exercise group . Conclusions : Balance exercises led to improvements in static balance function , and gait exercises result ed in improvements to dynamic balance and gait functions in the very frail elderly", "BACKGROUND Past studies suggest multidisciplinary interventions that include physical therapy ( PT ) can improve function of nursing home residents . This trial specifically evaluates effects of PT for frail long-stay nursing home residents . DESIGN R and omized , controlled trial . SETTING One academic nursing home and eight community nursing homes . PATIENTS A total of 194 elderly nursing home residents dependent in at least two activities of daily living residing in the nursing home for at least 3 months . INTERVENTIONS Patients were r and omized to individually tailored one-on-one PT sessions or friendly visits ( FVs ) three times a week for 4 months . Physical therapy included range-of-motion , strength , balance , transfer , and mobility exercises . MAIN OUTCOME MEASURES Performance-based physical function assessed by the Physical Disability Index ; self-perceived health status assessed with the Sickness Impact Profile ; observer-reported activities of daily living ; and falls . RESULTS Eighty-nine percent and 92 % of PT and FV sessions , respectively , were attended ; 5 % and 9 % of subjects dropped out in the PT group and FV group , respectively . Compared with the FV group , the PT group experienced no significant improvements in overall Physical Disability Index , Sickness Impact Profile , or activities of daily living scores . A 15.5 % improvement in the mobility subscale of the Physical Disability Index was seen ( 95 % confidence interval [ CI ] , 6.4 % to 24.7 % ) ; no benefits in range-of-motion , strength , or balance subscales were found . Compared with the FV group , the PT group used assistive devices for bed mobility tasks less often ( P = .06 ) and were less likely to use assistive devices and wheelchairs for locomotion ( P group vs 60 falls in the FV group ( P = .11 ) . Charge for the 4-month PT program was $ 1220 per subject ( 95 % CI , $ 412 to $ 1832 ) . CONCLUSION This st and ardized physical therapy program provided modest mobility benefits for very frail long-stay nursing home residents with physical disability due to multiple comorbid conditions", "BACKGROUND The purpose of this efficacy study was to measure the dose-response effect of a free weight-based resistance training program by comparing the effects of two training intensities ( low-moderate and high ) of the knee extensor ( KE ) muscles on muscle function , functional limitations , and self-reported disability . METHODS The authors conducted a single-blinded , r and omized , placebo-controlled trial . Twenty-two institutionalized elders ( mean age , 81.5 years ) were assigned to either high-intensity strength training ( HI ; n = 8) , low-moderate intensity strength training ( LI ; n = 6 ) , or weight-free placebo-control training ( PC ; n = 8) . The HI group trained at 80 % of their 1-repetition maximum and the LI group trained at 40 % . All groups performed 3 sets of 8 repetitions , 3 times per week for 10 weeks . Outcome measures included KE maximal strength , KE endurance , and functional performance as assessed by 6-minute walking , chair-rising , and stair-climbing tests , and by self-reported disability . RESULTS KE strength and endurance , stair-climbing power , and chair-rising time improved significantly in the HI and LI groups compared with the PC group . Six-minute walking distance improved significantly in the HI group but not in the LI group compared with the PC group . Changes observed in HI were significantly different from those observed in the LI group for KE strength and endurance and the 6-minute walking test , with a trend in the same direction for chair-rising and stair-climbing . Changes in strength were significantly related to changes in functional outcomes , explaining 37 % to 61 % of the variance . CONCLUSIONS These results show strong dose-response relationships between resistance training intensity and strength gains , and between strength gains and functional improvements after resistance training . Low-moderate intensity resistance training of the KE muscles may not be sufficiently robust from a physiologic perspective to achieve optimal improvement of functional performance . Supervised HI , free weight-based training for frail elders appears to be as safe as lower intensity training but is more effective physiologically and functionally", "The objective of this paper is to present the design and participants of an ongoing r and omized controlled trial on a network-based geriatric rehabilitation programme , targeted at frail elderly persons with progressively declining health and a high risk of institutionalization . Forty-one municipalities , seven rehabilitation centres and a total of 741 frail elderly ( 65+years ) community-living persons participated in the study . Assessment s included measurements of physical capacity ( balance , h and grip strength , walking speed ) , Functional Independence Measure , Geriatric Depression Scale , 15 Dimension quality of life question naire and Mini Mental State Examination . Question naires covered physical , social and psychological factors . The participants were old ( mean age 78 years , range 65–96 ) and mainly female ( 86 % ) . They were physically frail and most of them ( 66 % ) had experienced deterioration of health within 1 year . The majority lived alone ( 72 % ) and received regular help from other people ( 99 % ) . The mean Mini Mental State Examination and Geriatric Depression Scale scores were 25.2 and 4.1 points , respectively . Depressive mood ( Geriatric Depression Scale>6 points ) was found in 17 % and declined cognitive function ( Mini Mental State Examination ältere Menschen mit progressivem körperlichen Verfall und einem hohen Risiko der Institutionalisierung abzielt . An dieser Studie nahmen 41 Stadtverwaltungen , sieben Reha-Zentren und insgesamt 741 gebrechliche ältere Menschen ( 65 + Jahre ) aus der Gemeinde teil . Durchgeführt wurden u. a. Messungen der körperlichen Leistungsfähigkeit ( Gleichgewicht , Stärke des Händedrucks , Gehgeschwindigkeit ) , der funktionalen Selbständigkeit sowie Untersuchungen anh and der Geriatric Depression Scale ( GDS ) und des 15-teiligen Fragebogens zur Lebensqualität und der Mini Mental State Examination . Die Fragebögen befassten sich mit körperlichen , sozialen und psychologischen Faktoren . Die Teilnehmer waren alt ( Durchschnittsalter von 78 Jahren , Altersspanne von 65–96 Jahren ) und vorwiegend Frauen ( 86 % ) . Sie waren körperlich gebrechlich , und bei den meisten von ihnen ( 66 % ) war innerhalb von einem Jahr eine gesundheitliche Verschlechterung beobachtet worden . Die meisten lebten allein ( 72 % ) und erfuhren regelmäßig Unterstützung ( 99 % ) . Die durchschnittlichen Werte anh and der Mini Mental State Examination und der Geriatric Depression Scale lagen bei 25.2 bzw . 4.1 Punkten . Depressionen ( Geriatric Depression Scale>6 Punkte ) lagen bei 17 % und eine verminderte kognitive Funktion ( Mini Mental State Examination Unterschiede zwischen der r and omisierten Interventions - und der Kontrollgruppe waren unwesentlich . Da die Anzahl der Teilnehmer statistisch betrachtet gering ist , sind die Aussichten für die Bewertung der Wirksamkeit des Programms und für die Ermittlung potenzieller Nutznießer gut . El objetivo de este estudio es presentar el diseño , y a los participantes , de un estudio clínico comparativo aleatorizado sobre un programa en red de rehabilitación geriátrica , diseñado para pacientes ancianos frágiles cuya salud se deteriora de manera progresiva y que presentan un alto riesgo de necesitar hospitalización . En el estudio participaron 41 municipalidades , siete centros de rehabilitación y un total de 741 ancianos ( de más de 65 años de edad ) frágiles que viven en la comunidad . Se utilizaron la evaluación de la capacidad física ( equilibrio , presión de agarre en las manos , velocidad al caminar ) , la Medida de Independencia Funcional , la Escala de Depresión Geriátrica , el cuestionario Dimensión 15 sobre la calidad de vida y la Mini Evaluación del Estado Mental . Los cuestionarios exploraron factores físicos , sociales y sicológicos . Los participantes fueron ancianos ( de más de 78 años de edad , de un intervalo de 65 a 96 ) y principalmente mujeres ( 86 % ) . Todos presentaban fragilidad física y la salud de la mayoría de ellos ( 66 % ) se había deteriorado en el último año . La mayoría vivía solo ( 72 % ) y recibía ayuda de otras personas ( 99 % ) . Las puntuaciones medias obtenidas mediante la Mini Evaluación del Estado Mental y la Escala de Depresión Geriátrica fueron de 25.2 y 4.1 puntos , respectivamente . Se constataron sentimientos depresivos ( Escala de Depresión Geriátrica>6 puntos ) en el 17 % de los participantes y disminución en las funciones cognitivas ( Mini Evaluación del Estado Mental personnes âgées et fragilisées do nt la santé décline progressivement et présentant un risque de totale dépendance . Quarante et une municipalités , sept centres de rééducation et un total de 741 personnes âgées fragiles ( 65 + ans ) vivant dans la collectivité ont participé à l'étude . Parmi les données évaluées , citons la capacité physique ( équilibre , force de préhension , vitesse de marche ) , l'indépendance fonctionnelle , l'échelle de dépression gériatrique , un question naire de qualité de la vie en 15 dimensions et l'examen Mini Mental State . Les question naires portaient sur des facteurs physiques , sociaux et psychologiques . Les participants étaient âgés ( âge moyen 78 ans , fourchette 65–96 ans ) et principalement féminins ( 86 % ) . Ils étaient physiquement fragiles et la plupart d'entre eux ( 66 % ) avait subi une détérioration de leur santé au cours de l'année passée . La majorité vivait seule ( 72 % ) et recevait régulièrement de l'aide ( 99 % ) . Les scores moyens pour l'examen Mini Mental State et la chaîne de dépression gériatrique s'élevaient respectivement à 25.2 et 4.1 points . L'humeur dépressive ( échelle de dépression gériatrique > 6 points ) a été identifiée dans 17 % des cas et un déclin des fonctions cognitives ( examen Mini Mental State interventions r and omisées et les groupes contrôlés étaient insignifiantes . Dans la mesure où le nombre de participants est statistiquement suffisant , les perspectives d'évaluation de l'efficacité du programme et d ' identification des bénéficiaires potentiels sont bonnes", "OBJECTIVE To study the long-term outcome of a physical training regimen of ambulant postward rehabilitation in community-dwelling geriatric patients with a history of injurious falls . DESIGN Prospect i ve 2-year follow-up of a r and omized placebo-controlled intervention trial . SETTING Postward rehabilitation in a geriatric hospital in Germany . PARTICIPANTS Fifty-seven geriatric patients ( mean age , 84.3+/-4.4 y ) with a history of severe falls . INTERVENTION Ambulatory training of strength , functional performance , and balance 3 times a week for 3 months for 31 patients versus placebo activities for 26 patients . MAIN OUTCOME MEASURES Strength , functional performance , fall-related psychologic parameters , and physical activity assessed by st and ardized protocol s 2 years after the training intervention , compared with baseline results . RESULTS Motor performance decreased substantially in both groups . As patients in the intervention group declined from significantly improved motor performance levels achieved in the initial training intervention , differences between the groups were still significant in most functional performances 2 years later . Functional decline was greater in persons who were institutionalized or being cared for by family members . Physical activity , which increased during the exercise intervention , returned to low baseline levels . CONCLUSIONS Improved functional performance in the training group did not lead to an increased level of physical activity after training , which might have preserved the functional improvements . In mobility-restricted , frail , geriatric patients such as our study population , training programs should continue to keep patients active and to prevent the decline in strength and functional performance that precedes loss of autonomy", "Background and aims : Impaired mobility is one of the strongest predictors for falls in older people . We hypothesized that exercise as part of a fall prevention program would have positive effects , both short- and long-term , on gait , balance and strength in older people at high risk of falling and with varying levels of cognition , residing in residential care facilities . A secondary hypothesis was that these effects would be associated with a reduced risk of falling . Methods : 187 out of all residents living in 9 facilities , ≥65 years of age were at high risk of falling . The facilities were clusterr and omized to fall intervention or usual care . The intervention program comprised : education , environment , individually design ed exercise , drug review , post-fall assessment s , aids , and hip protectors . Data were adjusted for baseline performance and clustering . Results : At 11 weeks , positive intervention effects were found on independent ambulation ( FAC , p=0.026 ) , maximum gait speed ( p=0.002 ) , and step height ( ≥10 cm , p the Berg Balance Scale . At 9 months ( long-term outcome ) , 3 intervention and 15 control residents had lost the ability to walk ( p=0.001 ) . Independent ambulation and maximum gait speed were maintained in the intervention group but deteriorated in the control group ( p=0.001 ) . Residents with both higher and lower cognition benefited in most outcome measures . No association was found between improved mobility and reduced risk of falling . Conclusions : Exercise , as part of a fall prevention program , appears to preserve the ability to walk , maintain gait speed , ambulate independently , and improve step height . Benefits were found in residents with both lower and higher cognitive impairment , but were not found to be associated with a reduced risk of falling ", "OBJECTIVES To evaluate the effectiveness of a multifactorial fall and injury prevention program in older people with higher and lower levels of cognition . DESIGN A preplanned subgroup comparison of the effectiveness of a cluster-r and omized , nonblinded , usual-care , controlled trial . SETTING Nine residential facilities in Umeå , Sweden . PARTICIPANTS All consenting residents living in the facilities , aged 65 and older , who could be assessed using the Mini-Mental State Examination ( MMSE ; n = 378 ) . An MMSE score of 19 was used to divide the sample into one group with lower and one with higher level of cognition . The lower MMSE group was older ( mean + /- st and ard deviation = 83.9 + /- 5.8 vs 82.2 + /- 7.5 ) and more functionally impaired ( Barthel Index , median ( interquartile range ) 11 ( 6 - 15 ) vs 17 ( 13 - 18 ) ) and had a higher risk of falling ( 64 % vs 36 % ) than the higher MMSE group . INTERVENTION A multifactorial fall prevention program comprising staff education , environmental adjustment , exercise , drug review , aids , hip protectors , and postfall problem-solving conferences . MEASUREMENTS The number of falls , time to first fall , and number of injuries were evaluated and compared by study group ( intervention vs control ) and by MMSE group . RESULTS A significant intervention effect on falls appeared in the higher MMSE group but not in the lower MMSE group ( adjusted incidence rates ratio of falls P = .016 and P = .121 and adjusted hazard ratio P MMSE group , 10 femoral fractures were found , all of which occurred in the control group ( P = .006 ) . CONCLUSION The higher MMSE group experienced fewer falls after this multifactorial intervention program , whereas the lower MMSE group did not respond as well to the intervention , but femoral fractures were reduced in the lower MMSE group", "OBJECTIVES To test the effects of a rehabilitative intervention directed at continence , mobility , endurance , and strength ( Functional Incidental Training ( FIT ) ) in older patients in Department of Veterans Affairs ( VA ) nursing homes . DESIGN R and omized , controlled , crossover trial . SETTING Four VA nursing homes . PARTICIPANTS All 528 patients in the nursing homes were screened ; 178 were eligible , and 107 were r and omized to an immediate intervention group ( Group 1 ; n=52 ) and a delayed intervention group ( Group 2 ; n=55 ) . INTERVENTION Trained research staff provided the FIT intervention , which included prompted voiding combined with individualized , functionally oriented endurance and strength-training exercises offered four times per day , 5 days per week , for 8 weeks . Group 1 received the intervention while Group 2 served as a control group ; then Group 2 received the intervention while Group 1 crossed over to no intervention . A total of 64 subjects completed the intervention phase of the trial . MEASUREMENTS Timed measures of walking or wheeling a wheelchair ( mobility ) , sit-to-st and exercises , independence in locomotion and toileting as assessed using the Functional Independence Measure ( FIM ) , one-repetition maximum weight for several measures of upper and lower body strength , frequency of urine and stool incontinence , and appropriate toileting ratios . RESULTS There was a significant effect of the FIT intervention on virtually all measures of endurance , strength , and urinary incontinence but not on the FIM for locomotion or toileting . The effects of FIT were observed when Group 1 received the intervention and was compared with the control group and when Group 2 crossed over to the intervention . Group 1 deteriorated in all measures during the 8-week crossover period . Within-person comparisons also demonstrated significant effects on all measures in the 64 participants who completed the intervention ; 43 ( 67 % ) of these participants were \" responders \" based on maintenance or improvement in at least one measure of endurance , strength , and urinary incontinence . No adverse events related to FIT occurred during the study period . CONCLUSION FIT improves endurance , strength , and urinary incontinence in older patients residing in VA nursing homes . Translating these positive benefits achieved under research conditions into practice will be challenging because of the implication s of the intervention for staff workload and thereby the costs of care", "Health in older adults can best be measured in terms of functional status . Skeletal muscle strength has been reported to be a determinant of functional status in older individuals . Two major contributors to the decline in muscle function as a person ages are disuse and physical inactivity . Declining muscle function through a loss of muscular strength may decrease functional independence and mobility and increase the risk for falls and injuries , physical frailty , and disability . Older individuals lacking an appropriate amount of muscular strength may not be able to perform various activities of daily living , which are important indicators of independence", "OBJECTIVES To determine whether a 12-month program of group exercise can improve physical functioning and reduce the rate of falling in frail older people . DESIGN Cluster r and omized , controlled trial of 12 months duration . SETTING Retirement villages in Sydney and Wollongong , Australia . PARTICIPANTS Five hundred fifty-one people aged 62 to 95 ( mean+/-st and ard deviation=79.5+/-6.4 ) who were living in self- and intermediate-care retirement villages . MEASUREMENTS Accidental falls , choice stepping reaction time , 6-minute walk distance postural sway , leaning balance , simple reaction time , and lower-limb muscle strength . RESULTS Two hundred eighty subjects were r and omized to the weight-bearing group exercise ( GE ) intervention that was design ed to improve the ability of subjects to undertake activities for daily living . Subjects r and omized to the control arm ( n=271 ) attended flexibility and relaxation ( FR ) classes ( n=90 ) or did not participate in a group activity ( n=181 ) . In spite of the reduced precision of cluster r and omization , there were few differences in the baseline characteristics of the GE and combined control ( CC ) subjects , although the mean age of the GE group was higher than that of the CC group , and there were fewer men in the GE group . The mean number of classes attended was 39.4+/-28.7 for the GE subjects and 31.5+/-25.2 for the FR subjects . After adjusting for age and sex , there were 22 % fewer falls during the trial in the GE group than in the CC group ( incident rate ratio=0.78 , 95 % confidence interval (CI)=0.62 - 0.99 ) , and 31 % fewer falls in the 173 subjects who had fallen in the past year ( incident rate ratio=0.69 , 95 % CI=0.48 - 0.99 ) . At 6-month retest , the GE group performed significantly better than the CC group in tests of choice stepping reaction time , 6-minute walking distance , and simple reaction time requiring a h and press . The groups did not differ at retest in tests of strength , sway , or leaning balance . CONCLUSION These findings show that group exercise can prevent falls and maintain physical functioning in frail older people", "Background : Balance training programs have not shown consistent results among older adults , and it remains unclear how different training methods can be adapted to frail elderly people . Objective : The purpose of this study was to investigate the effects of a 4-week visual feedback-based balance training on the postural control of frail elderly women living in residential care homes . Methods : Elderly women of two residential care facilities were r and omized to an exercise group ( EG , n = 20 ) and to a control group ( CG , n = 7 ) . The EG participated in training sessions three times/week for 4 weeks . The exercises were carried out with a computerized force platform with visual feedback screen . The dimensions of balance function studied were st and ing body sway , dynamic weight shifting , and Berg Balance Scale performance . Results : The EG showed significant improvement in balance functions . The performance time in dynamic balance tests improved on average by 35.9 % compared with a 0.6 % increase in the CG ( p = 0.025–0.193 ) . The performance distance in these tests decreased on average by 28.2 % in the EG as compared with a 9.8 % decrease seen in the CG . The Berg Balance Scale performance improved by 6.9 % compared with a 0.7 % increase in the CG ( p = 0.003 ) . The st and ing balance tests in the more dem and ing st and ing positions showed improvements in the EG , whereas similar changes in the CG were not found . Conclusions : Our findings suggest that balance training based on visual feedback improves the balance control in frail elderly women living in residential care , also enhancing the performance of functional balancing tasks relevant to daily living . The subjects were motivated to participate in the training , as indicated by the high compliance ( 97.5 % ) with the program", "The quadriceps strength of a group of residents homes for the elderly ( mean age 83 years ) was assessed in a r and omized controlled trial of seated group exercise versus group reminiscence therapy . Fifty-five of 65 volunteers completed the 6-month study , with 4 dropouts from the exercise group , and 6 dropouts from the reminiscence group . There were no adverse effects . Average of attendance at the exercise sessions was 72 % ( range , 18 % to 98 % ) and 62 % ( range , 29 % to 100 % ) at the reminiscence sessions . The reminiscence sessions comprised group interaction and discussion prompted by the use of reminiscence aids . By the end of the study , the change observed in the exercise group was significantly different from the reminiscence group in terms of quadriceps strength ( p ability to climb up steps , but neither cognitive function ( Mini-Mental State Examination ) nor reaction time altered significantly ", "OBJECTIVE The purpose of this pilot was to determine whether a strength and flexibility program in frail long-term care facility ( LTC ) residents would result in improved function . DESIGN A prospect i ve , r and omized , controlled , semicrossover trial was design ed with participants assigned either to group exercise ( EX ) or recreational therapy ( C ) . In the EX group , the intervention continued for 1 year . In the C group , recreation continued for 6 months ; these controls were then crossed over to the same exercise intervention as the EX group and followed for an additional 6 months . Functional outcomes were measured at baseline and 3 , 6 , 9 , and 12 months for both groups . SETTING A LTC facility , which included both assisted living ( AL ) and nursing home ( NH ) residents . PARTICIPANTS Twenty frail residents ( 5 from NH , 15 from AL ) aged 75 to 99 years at one LTC facility . INTERVENTION After r and om group assignment , the EX group met 1 hour three times per week . An exercise physiologist and LTC staff conducted sessions which included seated range of motion ( ROM ) exercises and strength training using simple equipment such as elastic resistance b and s ( therab and s ) and soft weights . The C group met three times per week and participated in activities such as painting during the first 6 months , before crossing over to exercise . MEASUREMENTS AND METHODS Objective measures of physical and cognitive function were obtained at baseline and 3 , 6 , 9 , and 12 months using the timed get-up- and -go test ( TUG ) , Berg balance scale , physical performance test ( PPT ) , and mini-mental status exam ( MMSE ) . Because we were interested in the impact of exercise on multiple endpoints and to protect the type I error rate , a global hypothesis test was used . RESULTS There was a significant overall impact across the four measures of the exercise intervention ( P = 0.013 ) . Exercise benefit as indicated by the difference between exercise and control conditions showed exercise decreased TUG by 18 seconds , which represents an effect size ( in st and ard deviation units ) of 0.50 , increased PPT scores by 1.3 , with effect size = 0.40 , increased Berg scores by 4.8 , with effect size of 0.32 , and increased MMSE by 3.1 , with effect size = 0.54 . Except for the Berg , 90 % confidence intervals on these exercise effects excluded 0 . CONCLUSION Frail elderly in a LTC facility were able to participate and benefit from a strength training program . The program was delivered with low-cost equipment by an exercise physiologist and LTC staff . The advantage of such a program is that it provides recreational and therapeutic benefits ", "OBJECTIVE Resistance and endurance training result in gains in fitness in the aged . It is unclear whether the debilitated elderly can perform moderate-intensity training and whether such training results in short-term improvements in strength , endurance , and function in this population . DESIGN R and omized , controlled trial . SETTING S AND PATIENTS Subjects were from a Veterans Affairs nursing home and rehabilitation unit and a community nursing home . They were older than 60 yrs with impairment in at least one physical activity of daily living . Seventy-eight subjects volunteered and 58 ( mean age , 75 yrs ; 9 women , 49 men ) completed the intervention and initial posttest . Only one subject withdrew because of injury or disinterest . INTERVENTION Thrice-weekly resistance training ( using an isokinetic dynamometer ) and twice-weekly endurance training for 4 to 8 weeks . MAIN OUTCOMES Isometric strength in dominant arm and leg , heart rate response to timed endurance test , and activities of daily living score . RESULTS The mean change in isometric strength across the muscle movements tested was 32.8 % in the training group and 10.2 % in the control group ( difference , 22.6 % ; 95 % confidence interval , 6.2 % to 39.0 % ) . No change in heart rate during exercise was seen in the training group . Trained subjects tended to have a greater improvement in functional activity than control subjects , which was statistically significant ( p = .04 ) for those subjects who at enrollment were most dysfunctional ( i.e. , activities of daily living score less than 13 [ maximum score 26 ] ) . CONCLUSION This group of debilitated elderly patients effectively performed resistance training and increased their strength , with the most impaired gaining the most function . Few in the group could effectively perform endurance training", "Context In frail older people living in residential care facilities , hip protectors reduce fall-related femoral and pelvic injuries . In older people living in the community , prevention programs that target exercise and fall-related risk factors reduce falls and injuries . In older people living in residential care facilities , fall prevention programs , other than the use of hip protectors , have had mixed results . Contribution This r and omized trial shows that a multidisciplinary fall prevention program reduces falls and femoral fractures in older people living in residential care facilities . The program included general as well as resident-specific , tailored strategies . Editors ' Note The Cochrane Library ( Issue 3 , 2001 ) has two systematic review s that summarize r and omized trial evidence about interventions to prevent falls . The Editors Falls are a major problem in older people ( 1 , 2 ) . Hip fractures result ing from falls are particularly common in elderly persons living in residential care facilities ( 3 , 4 ) ; they account for a substantial proportion of dependency and mortality ( 5 ) . During the past decade , r and omized , controlled trials study ing fall prevention have shown both positive and negative results ( 6 - 8 ) . Differences in target groups , interventions , and outcome measures may explain the inconsistent results . In residential care facilities and nursing homes , only one trial demonstrated that intervention programs may help prevent falls ; however , this trial studied only people who fell repeatedly ( 9 ) . Other trials have not shown reductions in falls or injuries ( 10 - 13 ) but have shown fewer hospital admissions ( 11 ) and improvements in mobility ( 12 ) , visual acuity , and hypotension ( 13 ) . The use of hip protectors has consistently proved effective in preventing hip fractures in selected high-risk population s ( 14 ) . Some trials that have included cognitively healthier older people in the community have shown reduced falls and injuries when specific risk factors are targeted ( 15 - 18 ) . However , evidence is lacking for older people living in institutions ( 19 ) . We hypothesized that an intervention program that targeted multiple risk factors for falls in older people living in residential care facilities , in particular those with a high risk for falling , would reduce falls and fall-related injuries . We therefore conducted a cluster r and omized trial for preventing falls in nine residential care facilities . Methods Design Study participants were older people living in residential care facilities located in Ume , a city in northern Sweden . The selected facilities had to have more than 25 residents . The nine that met this criterion were divided into group A and group B. The distribution was based on the age and number of residents , type of setting ( care and service offered as well as corridor or private home design ) , and record of previous falls as routinely reported to the local authority . To keep the groups distinct from one another , the physicians , registered nurses , physical therapists , and occupational therapists who were responsible for working with the residents in group A could not also work with group B residents . Group A consisted of four facilities that accommo date d 224 residents ; the facilities had 29 to 74 residents each , and the median age by facility ranged from 82 to 85 years . Group B consisted of five facilities with a total of 215 residents ; there were 31 to 66 residents per facility , and the median age by facility ranged from 79 to 85 years . The number of falls reported to the local authorities in the 2.5 years preceding the trial was similar for both groups : 1.26 per resident per year for group A and 1.29 for group B. After baseline assessment of all residents , groups A and B were r and omly assigned by lots to an intervention or a control group ( Figure 1 ) . The r and om allocation was conducted by a person with no knowledge of the study . Two sealed , dark envelopes were used . In each envelope , a letter specified one of the groups . Before the lot was drawn , the first envelope drawn was design ated as the intervention group . The local authorities , residents , staff of the nine facilities , and the research group were then informed of the results of the r and omization . Figure 1 . Study design . All residents in the study received written and oral information . All participants ( or the relatives and guardians of participants with severe cognitive dysfunction ) gave informed consent . The administrators and staff of the nine facilities involved also received information about the study and agreed to participate . The Ethics Committee of the Medical Faculty of Ume University approved the study . Definition of a Fall and an Injury A fall was defined as an event in which the resident unintentionally came to rest on the ground or floor , regardless of whether an injury was sustained . Thus , this definition also includes falls that result ed from acute illness or epileptic seizure and incidents that result ed in a resident 's falling and being found on the floor by staff or another resident . An injury was defined according to the Abbreviated Injury Scale ( 20 ) . Classifications were minor for injuries limited to superficial wounds and bruises ; moderate for intermediate-level injuries , such as vertebral and wrist fractures ; and serious for major fractures , such as hip fractures and other femoral fractures . Participants and Setting s All residents in the nine facilities who were 65 years of age or older were selected in a cross-sectional manner . Thirty-seven of these residents declined to participate , were admitted to hospitals , or died before r and omization . Sex and age of the 37 non participants were similar to those of the remaining 402 residents . In Sweden , older people living in residential care facilities are disabled by cognitive or physical impairment and thus require supervision , functional support , or nursing care . In this study , some residents lived in private apartments and others had private rooms but shared dining and living rooms . In all facilities , residents had 24-hour daily access to assistance with activities of daily living , household issues , and medical care . The median age was 83 years ( range , 65 to 100 years ) , and most residents were female ( 72 % ) . Few residents could walk outdoors without a walking aid ( 14 % ) or shower without assistance ( 18 % ) ; few were nonambulatory ( 19 % ) or entirely dependent when eating ( 8 % ) . Additional baseline characteristics are presented in the Table . Table . Baseline Characteristics of the 402 Residents Participating in the Study All members of the permanent staff , regardless of profession , participated in the study . In addition , eight physiotherapists were employed part-time ( a total of 200 h/wk ) until the end of the intervention period , and three physiotherapists were employed part-time ( a total of 10 h/wk ) during the follow-up period . A total of 273 nurses ' aides or licensed practical nurses and 20 registered nurses worked at the nine facilities . Baseline Assessment Each resident 's physician completed a question naire regarding clinical characteristics and drugs prescribed . A registered nurse reported delirium episodes ( Table ) . Physiotherapists interviewed and assessed all residents . Hearing was rated as impaired if the resident could not hear normal speech from a distance of 1 meter or used a hearing aid . Vision was rated as impaired when the resident , with or without glasses , could not read a word written in 5-mm capital letters at reading distance . Global cognitive function was screened by using the Mini-Mental State Examination ( MMSE ) ( 21 ) . Licensed practical nurses or nurses ' aides were interviewed to determine the number of falls that had occurred during the 6 months preceding the study and the extent of use of physical restraints . Activities of daily living were assessed according to the Barthel index ( 22 , 23 ) . All residents were screened for the risk for falling . First , by using the Mobility Interaction Fall Chart ( 24 ) , a resident was classified to be at higher risk for falling if he or she stopped walking when talking to an accompanying person ( 25 ) , walked more slowly when carrying a glass of water ( 26 ) , or had impaired vision or difficulty concentrating . Second , a physiotherapist globally rated the fall risk as higher if the resident showed risk-taking behavior considered to jeopardize balance . If the residents were not classified to be at higher risk for falling by any of these described measures , they were considered to be at lower risk for falling . Residents at higher risk were likely to be older than those at lower risk ( median age , 84 years [ range , 65 to 98 years ] vs. 83 years [ range , 65 to 100 years ] ) , to have lower MMSE scores ( median score , 17 [ range , 0 to 30 ] vs. 21 [ range , 0 to 30 ] ) , and to have more medical diagnoses ( median , 4 vs. 3 ) . The main areas of each facility were also screened according to a checklist for environmental hazards , such as lighting , flooring , obstacles inside the facility , and dangerous areas outside the facility ( for example , icy areas ) . Twelve residents in the control group and six in the intervention group died or moved during the 11-week intervention period ( Figure 1 ) . Intervention Program The intervention program comprised strategies that targeted both general and resident-specific risk factors for falling . The strategies were design ed to be meaningful to the residents without compromising mobility . The 89 residents screened as being at higher risk as well as the 19 residents at lower risk who fell during the 11-week intervention period were the focus of the individualized intervention program . Increasing the staff 's knowledge about fall prevention was believed to be the starting point of a process that would produce long-term results . Staff Education All staff were invited to a 4-hour educational session , and more than half attended . The sessions were led by a physician and a physiotherapist and covered risk factors for falls and intervention", "Although exercise is usually promoted for weight loss and better heart health , there is growing evidence that regular physical activity helps people preserve their mental ability . We describe the results of a pilot longitudinal study addressing the impact of a moderate intensity exercise program on behavioral problems of frail , elderly , demented patients living in nursing home . Overall , patients in the treatment group ( combination of aerobic/endurance activities , strength training , balance , and flexibility training ) showed a statistically significant reduction in the behavioral problems , such as w and ering , physical and verbal abuse , and in the sleep disorders . As a consequence , a significant reduction in the use of antipsychotic and hypnotic medications was observed in subjects of the treated group . In conclusion , our preliminary results suggest that engaging in regular physical activity , among other health benefits , may delay or prevent the onset of behavior problems in demented frail elderly people living in nursing home", "Objective : To establish the effect of a short , individualized exercise programme on balance dysfunction in the elderly . Design : A single-blind , r and omized , controlled , multicentre trial . Setting : Physical and recreational therapy departments from two rehabilitation centres . Participants : Ninety-four subjects of ≥75 years with functional balance problems living independently or in a residential care facility . Seventy-seven subjects completed the intervention period and four-week follow-up . At a one-year follow-up 49 subjects were evaluated on balance functioning . Interventions : Twelve sessions of an individualized balance training programme ( experimental group ) or 12 sessions of an individualized extra attention programme ( control group ) given in 4–6 weeks . Main outcome measures : Berg Balance Scale and the Dynamic Gait Index to establish balance functioning , a visual analogue scale to establish fear of falling in daily life and the Hospital Anxiety Depression Scale to verify feelings of anxiety and depression . Results : Subjects in the experimental group improved significantly more on the Berg Balance Scale and the Dynamic Gait Index than those in the control group ( p ≤ 0.001 , p ≤ 0.001 , respectively ) . However the effect disappeared at a one-year follow-up on the Berg Balance Scale . No prognostic factors could be identified to determine who would benefit most from the individualized exercise programme . Results on the other response variables revealed no effect of the intervention . Conclusion : A short individualized exercise programme can improve functional balance in people aged 75 years and older . This improvement was maintained at least for one month but had worn off by one year", "The purpose of this study was to determine the influence of simple , progressive lower body exercise training , focusing on strength and power , on functional abilities in frail older adults . Twenty-five residents of a long-term care facility ( 75 - 94 yrs ) participated in this r and omized controlled trial of 10-wks duration . The exercise group ( Ex , n = 18 ) underwent simple , progressive lower body resistance exercises , specifically aim ed at improving muscle power , 3 times/wk ; the control subjects ( Con , n = 7 ) maintained their usual daily activities . Knee extensor strength and power were measured on an isokinetic dynamometer ( 180 degrees/s ) , and functional performance was assessed from a 6-m walk timed test , a 30-s chair st and , and an 8-ft up- and -go timed test , before and after the 10-wk intervention period . Significant increases were found in the Ex group for eccentric ( 44 % ) and concentric ( 60 % ) average power ( p functional test : the 8-foot up- and -go , chair st and , and walk time improved by 31 % , 66 % , and 33 % , respectively ( p No significant change occurred in the Con group . In conclusion , simple progressive exercise training , even in the 10th decade , increases muscle power and is associated with an improved performance of functional activities using the trained muscles", "This study tested a 3-month ankle-strengthening and walking program design ed to improve or maintain the fall-related outcomes of balance , ankle strength , walking speed , risk of falling , fear of falling , and confidence to perform daily activities without falling ( falls efficacy ) in elderly nursing home residents . Nursing home residents ( N = 81 ) between the ages of 64 and 100 years participated in the study . Two of the fall-related outcomes , balance and fear of falling , were maintained or improved for the exercise group in comparison to the control group", "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", "OBJECTIVE To evaluate the effectiveness of three different training protocol s on physical function of older adults living in long-term care facilities . Emphasis was placed on feasibility in real-life situations . METHODS Subjects ( N=224 ) were r and omised to 6 months of twice weekly ( 1 ) resistance training ; ( 2 ) all-round functional-skills training ; ( 3 ) a combination of both ; or ( 4 ) a control program . Fitness and performance measures and self-reported disability were measured at baseline and after 24 weeks intervention . RESULTS Attendance to the strength training was 76 % , to the functional-skills training 70 % and to the combined training 73 % . In those who attended at least 75 % of all classes ( n=97 ) the functional-skills and combined training program improved several fitness and performance measures compared to the control group . CONCLUSION Twice weekly functional-skills training , or a combination of resistance and functional-skills training can improve several fitness and performance measures of institutionalised older people . PRACTICE IMPLICATION S An important finding from our study was that less than twice a week exercise training is not enough for functional improvement , while it proved difficult for the elderly subjects to exercise twice weekly . Education on the health benefits of regular exercise , and a larger availability of classes in long-term care facilities may improve attendance" ]

[ "BACKGROUND & AIMS The Rome III criteria for functional dyspepsia have been changed to include 2 distinct syndromes : postpr and ial distress syndrome and epigastric pain syndrome . We investigated risk factors for functional dyspepsia among the functional dyspepsia subgroups defined by the Rome III criteria . METHODS We performed a cross-sectional population -based study in a primary care setting ( the Kalix and a study ) . A r and om sample ( n = 2860 ) of the adult population from 2 northern Swedish municipalities ( n = 21,610 ) was surveyed using a vali date d postal question naire to assess gastrointestinal symptoms ( response rate , 74.2 % ; n = 2122 ) . A r and omly selected subgroup ( n = 1001 ) of responders was invited to undergo an esophagogastroduodenoscopy ( participation rate , 73.3 % ) including biopsy specimen collection , Helicobacter pylori culture and serology , and symptom assessment s. RESULTS Of the 1001 subjects examined by endoscopy , 202 ( 20.2 % ; 95 % confidence interval [ CI ] , 17.7 - 22.7 ) were classified as having uninvestigated dyspepsia and 157 ( 15.7 % ; 95 % CI , 13.4 - 18.0 ) as having functional dyspepsia . Major anxiety ( Hospital Anxiety and Depression Scale score > or = 11 ) was associated with uninvestigated dyspepsia ( odds ratio [ OR ] , 3.01 ; 95 % CI , 1.39 - 6.54 ) , as was obesity ( body mass index > or = 30 kg/m(2 ) ) ( OR , 1.86 ; 95 % CI , 1.15 - 3.01 ) . Major anxiety was associated with functional dyspepsia and postpr and ial distress syndrome ( OR of 2.56 [ 95 % CI , 1.06 - 6.19 ] and 4.35 [ 95 % CI , 1.81 - 10.46 ] , respectively ) , as was use of nonsteroidal anti-inflammatory drugs ( OR , 2.49 [ 95 % CI , 1.29 - 4.78 ] and 2.75 [ 95 % CI , 1.38 - 5.50 ] , respectively ) . Depression was not associated with any dyspepsia group . CONCLUSIONS Anxiety but not depression is linked to uninvestigated dyspepsia , functional dyspepsia , and postpr and ial distress syndrome but not to epigastric pain syndrome", "BACKGROUND Visceral hypersensitivity is one of the proposed underlying mechanisms in functional dyspepsia ( FD ) . It is not clear whether visceral hypersensitivity in FD is a manifestation of a central sensitization also encompassing somatic sensitization . Transient receptor potential vanilloid-1 ( TRPV(1 ) ) pathways are involved in gastric mechanosensory physiology and the TRPV(1 ) receptor agonist , capsaicin , has been used as a chemical stimulant . METHODS In this double-blind , r and omized study we evaluated both visceral and somatic sensory function in 34 FD patients and 42 healthy controls using quantitative sensory testing . Visceral pain sensitivity was assessed using a vali date d gastric pain model with oral capsaicin capsule titration and somatic pain sensitivity was determined by foot heat and h and electric stimulation . KEY RESULTS The median capsaicin dose required to attain moderate pain was 0.5 mg in FD and 1 mg in controls ( P = 0.03 ) . At these doses , mean pain intensities on a 0 - 100 visual analog scale were greater for FD than controls [ 56.9 ( 95 % confidence intervals , 52.2 - 61.5 ) vs 45.1 ( 41.6 - 48.6 ) , resp . ] ( P = 0.005 ) . Overall , mean somatic sensory and pain thresholds were similar in FD and control groups , but in a subgroup of FD pain hypersensitivity was seen on the h and and on the foot at different stimulation thresholds . CONCLUSIONS & INFERENCES A majority of patients with FD have visceral chemo-hypersensitivity involving TRPV(1 ) pathways . A substantial subgroup also has somatic hypersensitivity as evidence of central sensitization", "BACKGROUND & AIMS Functional abnormalities of the duodenum have been observed in non-ulcer dyspepsia . We aim ed to identify whether eosinophils in the upper gastrointestinal tract are a biomarker for non-ulcer dyspepsia . METHODS A r and om sample of an adult Swedish population ( n = 1001 ; mean age , 54 y ; 51 % female ) underwent upper endoscopy . Non-ulcer dyspepsia cases ( n = 51 , Rome II ) and r and omly selected controls ( n = 48 ) were identified . Two blinded independent observers assessed the gastroduodenal eosinophil counts . Eosinophils were quantified by counting the number per 5 high-power fields at each of 5 sites ( cardia , body , antrum , D1 duodenal bulb , and D2 second portion of duodenum ) , and total counts were summed over the 5 fields at each site . RESULTS The odds ratio for non-ulcer dyspepsia ( vs asymptomatic controls ) in subjects with high duodenal bulb eosinophil counts ( median , > /=22 , relative to number of eosinophil clusters was detected in the duodenum , with higher values in non-ulcer dyspepsia ( P eosinophil degranulation was observed in non-ulcer dyspepsia ( 7 of 15 vs 0 of 5 controls ; P = .11 ) . Gastric eosinophil counts were overall not significantly increased in non-ulcer dyspepsia vs controls . Early satiety was associated with eosinophilia in D1 ( P = .01 ) and D2 ( P = .02 ) , adjusting for age , sex , and H pylori . CONCLUSIONS Duodenal eosinophilia may characterize a subset of adults with non-ulcer dyspepsia", "AIM To evaluate sertraline , a selective serotonin reuptake inhibitor in the treatment of patients with functional dyspepsia . METHODS Consecutive tertiary hospital patients with a clinical diagnosis of functional dyspepsia ( FD ) according to the Rome II criteria with a Hong Kong dyspepsia index ( HKDI ) of greater than 16 were recruited . Patients commenced enrolment prior to the inception of the Rome III criteria for functional dyspepsia . All patients were ethnic Chinese , had a normal upper endoscopy and were Helicobacter pylori negative prior to enrolment . Study patients were r and omized to receive sertraline 50 mg or placebo daily for 8 wk . HKDI symptom scores , quality of life , hospital anxiety and depression ( HAD ) scale and global symptom relief were evaluated before , during and after treatment . Adverse effects were monitored during and after treatment . RESULTS A total of 193 patients were r and omized in the intention to treat ( ITT ) , and 150 patients were included in the per protocol ( PP ) analysis . In both the ITT and PP , there was no difference in the primary outcome of global dyspepsia symptoms between the sertraline and placebo groups at week 8 . In the ITT analysis , 98 and 95 patients were r and omized to the sertraline and placebo groups respectively . A total of 43 patients withdrew from the study ( 22.3 % ) by week 8 , with 23 of the 24 drop-outs in the sertraline group occurring prior to week 4 ( 95.8 % ) . In contrast , in the placebo arm , 11 of 19 patients dropped out by week 4 ( 57.9 % ) . Utilizing the last response carried forward to account for the drop-outs , there were no differences between the sertraline and placebo groups at baseline in terms of the HKDI , HKDI 26.08 ± 6.19 vs 26.70 ± 5.89 , P = 0.433 ; and at week 8 , HKDI 22.41 ± 6.36 vs 23.25 ± 7.30 , P = 0.352 respectively . In the PP analysis , 74 and 76 patients were r and omized to the sertraline and placebo groups respectively . At baseline , there were no statistically significant differences between the sertraline and placebo groups , HKDI 25.83 ± 6.313 vs 27.19 ± 5.929 respectively , P = 0.233 ; however by week 8 , patients in the sertraline group demonstrated a statistically significant difference in their Hong Kong Dyspepsia Index compared to placebo , HKDI 20.53 ± 6.917 vs 23.34 ± 7.199 , P = 0.02 , respectively ) . There was also no statistically significant difference in overall quality of life measures or the HAD scale related to treatment in either the ITT or PP analysis at week 8 . CONCLUSION This pilot study , the first to examine sertraline , a selective serotonin reuptake inhibitor , for the management of FD , did not find that it was superior to placebo", "BACKGROUND : Low-dose tricyclic antidepressants have been used to treat chronic somatic and gastrointestinal pain disorders , including refractory functional dyspepsia . However , there are only limited data on the effects of these drugs on upper gastrointestinal function . AIM : To compare the effects of two doses of amitriptyline ( AMT ) and placebo on gastric accommodation , emptying , satiation , and postpr and ial symptoms in healthy volunteers . METHODS : Using a parallel-group , double-blind , placebo-controlled design , 41 healthy volunteers were r and omized to AMT 25 mg , AMT 50 mg , or placebo for 2 wk . During the final 3 days of therapy , the following end points were assessed : fasting and postpr and ial gastric volumes , 2- and 4-h gastric emptying , time and volume to maximum satiation using a nutrient drink test , and postpr and ial symptoms 30 min later using 10-cm visual analog scales . AMT and metabolite levels were measured . RESULTS : AMT slowed gastric emptying at 2 h ( median 75 % for placebo , 57 % for AMT 25 mg , 67 % for AMT 50 mg ; P= 0.037 ) and 4 h ( median 98 % for placebo , 96 % for AMT 25 mg , 92 % for AMT 50 mg ; P= 0.003 ) . AMT did not affect gastric volumes or satiation volume , but it did reduce nausea scores at 30 min in a dose-dependent manner ( median 2.1 for placebo , 0.9 for AMT 25 mg , and 0.0 for AMT 50 mg ; P= 0.009 ) . CONCLUSION : In healthy volunteers , AMT slows gastric emptying of solids , but it does not significantly affect gastric volumes or satiation . AMT reduces nausea after challenge with a high calorie liquid load", "Acute studies suggested a therapeutic benefit for fundus-relaxing drugs in functional dyspepsia ( FD ) with visceral hypersensitivity ( VH ) to gastric distention or impaired accommodation ( IA ) , but long-term studies are lacking . R-137696 is a serotonin-1A ( 5-HT(1A ) ) receptor agonist which relaxes the proximal stomach in man . Our aim was to investigate the influence of R-137696 on symptoms in FD with VH or IA . R and omized , double-blind , placebo-controlled , parallel group study of 4 weeks R-137696 2 mg t.i.d . in FD with VH or IA . Symptoms were assessed using the patient assessment of upper gastrointestinal symptom severity index ( PAGI-SYM ) total score and individual symptom subscales . Barostat studies were performed before and after 4 weeks of treatment . Fifty-three patients ( 33 VH and 20 IA ) , 18 men , mean age 40 + /- 13 years were recruited . Twenty-four received placebo and 29 received R-137696 . In VH patients , both placebo and R-137696 improved total symptom scores , with a tendency for superiority of placebo ( -1.12 vs-0.51 , P = 0.07 ) . Placebo was superior for the subscales of early satiety , bloating , fullness and discomfort ( all P placebo and R-137696 had no significant influence on total or individual symptom scores ( -0.08 and -0.27 ) . In VH , both placebo and R-137696 increased the discomfort volume , without a statistical difference between both arms ( + 120 and + 164 mL ) . In IA , both placebo and R-137696 enhanced accommodation , without a statistical difference between both ( + 77 and + 159 mL ) . Adverse events were similar for drug and placebo . A 4-week administration of the fundus-relaxing 5-HT(1A ) agonist R-137696 failed to significantly improve symptoms , VH or gastric accommodation compared to placebo", "This guideline presents recommendations for the evaluation and management of patients with gastroparesis . Gastroparesis is identified in clinical practice through the recognition of the clinical symptoms and documentation of delayed gastric emptying . Symptoms from gastroparesis include nausea , vomiting , early satiety , postpr and ial fullness , bloating , and upper abdominal pain . Management of gastroparesis should include assessment and correction of nutritional state , relief of symptoms , improvement of gastric emptying and , in diabetics , glycemic control . Patient nutritional state should be managed by oral dietary modifications . If oral intake is not adequate , then enteral nutrition via jejunostomy tube needs to be considered . Parenteral nutrition is rarely required when hydration and nutritional state can not be maintained . Medical treatment entails use of prokinetic and antiemetic therapies . Current approved treatment options , including metoclopramide and gastric electrical stimulation ( GES , approved on a humanitarian device exemption ) , do not adequately address clinical need . Antiemetics have not been specifically tested in gastroparesis , but they may relieve nausea and vomiting . Other medications aim ed at symptom relief include unapproved medications or off-label indications , and include domperidone , erythromycin ( primarily over a short term ) , and central ly acting antidepressants used as symptom modulators . GES may relieve symptoms , including weekly vomiting frequency , and the need for nutritional supplementation , based on open-label studies . Second-line approaches include venting gastrostomy or feeding jejunostomy ; intrapyloric botulinum toxin injection was not effective in r and omized controlled trials . Most of these treatments are based on open-label treatment trials and small numbers . Partial gastrectomy and pyloroplasty should be used rarely , only in carefully selected patients . Attention should be given to the development of new effective therapies for symptomatic control", "Background and aims : Patients with functional dyspepsia who have hypersensitivity to gastric distension have more prevalent pain , suggesting the presence of hyperalgesia . It is unclear whether this reflects activation of pain specific afferent pathways or multimodal afferent pathways that also mediate non-painful sensations . In the former case , hyperalgesia should occur when intensity of non-painful sensations is still low . The aim of the study was to analyse whether the symptom profile during gastric dissentions in functional dyspepsia patients with hyperalgesia reflects sensitisation of pain specific or multimodal pathways . Methods : Forty eight consecutive dyspeptic patients ( 35 female ) underwent gastric sensitivity testing with a barostat balloon using a double r and om staircase protocol . At the end of every distending step , patients scored perception of upper abdominal sensations on a graphic 0–6 rating scale and completed visual analogue scales ( VAS 0–100 mm ) for pain , nausea , satiety , and fullness . The end point was a rating scale of 5 or more . Results : Hypersensitivity was present in 20 patients ( 40 % ) ; gastric compliance did not differ between normo- and hypersensitive patients . At maximal distension ( score 5 or more ) , hypersensitive patients had significantly lower distending pressures and intra-balloon volumes , but similar VAS scores for pain , nausea , satiety , and fullness compared with normosensitive patients . In both normosensitive and hypersensitive patients , elevation of pain VAS scores with increasing distending pressures paralleled the elevation in VAS scores for nausea , satiety , and fullness . Conclusions : Hypersensitive dyspeptic patients reach the same intensity of painful and non-painful sensations as normosensitive patients but at lower distending pressures . Hyperalgesia occurs in hypersensitive dyspeptic patients at distending pressures that also induce intense non-painful sensations . These findings argue against isolated upregulation of pain specific afferents in functional dyspepsia patients with visceral hypersensitivity", "Objectives Levosulpiride is the levo-enantiomer of sulpiride , a well-known antiemetic , antidyspeptic and antipsychotic drug . This study was undertaken to investigate the effects of levosulpiride on dyspeptic symptoms and gastric motor function in a group of patients with functional dyspepsia showing delayed gastric emptying . Method Forty two eligible patients were entered into a 3 week , double-blind r and omized comparison of 25 mg of levosulpiride or placebo t.i.d .. Symptom assessment and gastric scintigraphy following the intake of scrambled egg s and wich , were performed in each patient before and after treatment . Results The improvement of symptom score in levosulpiride group was higher than the placebo group ( p global efficacy , which was excellent in 1 ( 6 % ) , good 11 ( 65 % ) , fair 4 ( 24 % ) , nil 1 ( 6 % ) of those receiving levosulpiride , and fair 9(60 % ) , nil 5 ( 33 % ) , poor 1 ( 6 % ) of those receiving placebo . Levosulpiride tended to be more effective than placebo in relieving the dyspeptic symptoms especially in the subgroups of dysmotility-like ( p reduction of gastric emptying time after levosulpiride treatment was more marked than Placebo group ( p symptom score and gastric emptying time ( r=0.47 , p=0.01 . No serious adverse effects were reported after administration of either levosulpiride or placebo . Only two patients reported mild somnolence during levosulpiride administration . Conclusions Levosulpiride is effective and well tolerated in patients with functional dyspepsia accompanied by delayed gastric emptying . Its efficacy may be related to its action on the gastric motor function by improving the delayed gastric emptying", "OBJECTIVES : Functional dyspepsia ( FD ) is a common condition in the general population ; however , its treatment remains a challenge . The aim of this study was to examine the efficacy of t and ospirone citrate , a new partial agonist of the 5-hydroxytryptamine 1A ( 5-HT1A ) receptor , in improving the symptoms of patients with FD . METHODS : In this double-blind , placebo-controlled , multicenter study , FD patients were r and omized to treatment with 10 mg t.i.d . t and ospirone citrate or to placebo for 4 weeks . The primary end point was change in abdominal symptom scores . The difference in the proportion of responders ( a total abdominal symptom score of 0 or 1 ) was also assessed . The quality -of-life question naire , the SF-8 , and a psychological test question naire , the State-Trait Anxiety Inventory ( STAI ) , were completed at baseline and at weekly intervals . RESULTS : Data were available for 144 patients : 73 for t and ospirone and 71 for placebo . Improvements in total abdominal scores were significantly larger with t and ospirone than placebo at weeks 1 , 2 , and 4 . Significantly greater improvements in the t and ospirone group were observed in upper abdominal pain ( P=0.02 ) and discomfort ( P=0.002 ) at week 4 . The proportion of responders was significantly greater in the active treatment arm at weeks 3 ( P=0.017 ) and 4 ( P=0.0016 ) . Significant improvements in STAI ( P serious adverse events were reported , with similar rates in both study arms . CONCLUSIONS : Despite a considerable placebo effect , the benefits of t and ospirone were shown in terms of improvement in abdominal symptom scores", "BACKGROUND & AIMS Functional gastrointestinal disorders ( FGID ) are common in the community . The natural history of FGID is unknown because of a lack of prospect i ve population -based studies and the indistinct nature of the phenotype . We sought to report the natural history of FGID in a US population . METHODS This prospect i ve cohort study used data from multiple vali date d surveys of r and om sample s of Olmsted County , MN , residents over a mean of a 12-year period between 1988 and 2003 ( n = 1365 ) . The surveys measured gastrointestinal symptoms experienced during the past year . Each subject received a minimum of 2 surveys . Point prevalence , onset , and disappearance rates and transition probabilities were calculated for individual FGIDs . RESULTS Between the initial and final surveys , the point prevalences ( per 100 residents ) were stable for irritable bowel syndrome ( 8.3 % and 11.4 % , respectively ) and functional dyspepsia ( 1.9 % and 3.3 % , respectively ) . The onset of each of the disorders studied was greater than the disappearance rate , but the transition probabilities varied across the different subgroups . Among people with symptoms at baseline , approximately 20 % had the same symptoms , 40 % had no symptoms , and 40 % had different symptoms at follow-up . CONCLUSIONS Although the prevalence of the FGID was stable over time , the turnover in symptom status was high . Many episodes of symptom disappearance were due to subjects changing symptoms rather than total symptom resolution . This transition between different FGIDs suggests a common etiopathogenesis", "Background : 50 % of patients with functional dyspepsia have delayed gastric emptying . Levosulpiride is an orthopramide drug that stimulates gastrointestinal motility . Aim of our study was to evaluate the effect of levosulpiride on symptoms and gastric and gall‐bladder emptying , in dyspeptic patients", "BACKGROUND & AIMS Antidepressants could be effective in the treatment of functional gastrointestinal disorders through their anticholinergic and pain-modulating effects . Previous studies with these drugs lacked sufficient power and were predominantly conducted in patients with irritable bowel syndrome . This study aim ed to assess the effectiveness of the serotonin and norepinephrine reuptake inhibitor venlafaxine in patients with functional dyspepsia . METHODS This was a multi-center , r and omized , double-blind , placebo-controlled trial . Participants had persistent dyspeptic symptoms and underwent upper gastrointestinal endoscopy in a secondary care hospital to exclude organic abnormalities . They were r and omly assigned to receive 8 weeks of treatment with either venlafaxine XR ( 2 weeks 75 mg once daily , 4 weeks 150 mg once daily , and 2 weeks 75 mg once daily ) or placebo . Symptoms , health-related quality of life , anxiety , and depression were assessed before and at 4 , 8 , 12 , and 20 weeks after inclusion . RESULTS One hundred sixty patients were r and omized ; 56 % and 73 % of participants completed treatment with venlafaxine or placebo , respectively , according to protocol . There was no difference in proportions of symptom-free patients after 8 weeks of treatment or at 20 weeks after inclusion , with venlafaxine in comparison to placebo ( 37 % and 39 % , respectively ; odds ratio [ OR ] , 0.8 ; 95 % confidence interval [ CI ] , 0.3 - 2.1 ; and 42 % and 41 % , respectively ; OR , 3.1 ; 95 % CI , 0.9 - 12.6 ) . Per- protocol analysis did not reveal any differences between venlafaxine and placebo either ( 38 % and 39 % symptom-free , respectively ; OR , 1.0 ; 95 % CI , 0.4 - 2.4 at 8 weeks ) . CONCLUSIONS Treatment with the selective serotonin and norepinephrine reuptake inhibitor venlafaxine is not more effective than placebo in patients with functional dyspepsia", "Background : The role of 5‐hydroxytryptamine in the control of gastric fundus tone in humans is still unknown . Selective 5‐hydroxytryptamine re‐uptake inhibitors act both central ly and peripherally to enhance the availability of physiologically released 5‐hydroxytryptamine", "Background : Functional dyspepsia ( FD ) is a common disorder but there is currently little efficacious drug therapy . Itopride , a prokinetic approved in several countries , showed promising efficacy in FD in a phase IIb trial . The aim of this study was to test the efficacy and safety of this drug in FD . Methods : Two similar placebo-controlled clinical trials were conducted ( International and North America ) . Males and females , 18–65 years old , with a diagnosis of FD ( Rome II ) and the absence ( by upper endoscopy ) of any relevant structural disease were recruited . All were negative for Helicobacter pylori and , if present , heartburn could not exceed one episode per week . Following screening , patients were r and omised to itopride 100 mg three times daily or identical placebo . The co- primary end points were : ( 1 ) global patient assessment ( GPA ) of efficacy ; and ( 2 ) Leeds Dyspepsia Question naire ( LDQ ) . Symptoms were evaluated at weeks 2 , 4 and 8 . Secondary measures of efficacy included Nepean Dyspepsia Index ( NDI ) quality of life . Results : The GPA responder rates at week 8 on itopride versus placebo were similar in both trials ( 45.2 % vs 45.6 % and 37.8 vs 35.4 % , respectively ; p = NS ) . A significant benefit of itopride over placebo was observed for the LDQ responders in the International ( 62 % vs 52.7 % , p = 0.04 ) but not the North American trial ( 46.9 % vs 44.8 % ) . The safety and tolerability profile were comparable with placebo , with the exception of prolactin elevations , which occurred more frequently on itopride ( 18/579 ) than placebo ( 1/591 ) . Conclusion : In this population with FD , itopride did not show a difference in symptom response from placebo", "BACKGROUND The efficacy of unselected monoamine reuptake inhibitors ( tricyclic antidepressants ) in the treatment of patients with functional gastrointestinal disorders ( FGD ) has not been convincingly demonstrated . We investigated the efficacy of an antidepressant ( mianserin ) with a different receptor profile ( combined 5-hydroxytryptamine-2 + 3 and alpha-2 antagonist ) in FGD . METHODS After excluding patients with psychopathology and initial placebo responders from the study , eligible patients ( n = 49 ) were r and omized to 7 weeks of double-blind treatment with either mianserin , 120 mg/day , or placebo . Efficacy was assessed by using observer-completed ratings , the Global Improvement Scale , and patient self-ratings , Visual Analog Scale , and Disability Scales . RESULTS Patients taking mianserin reported less abdominal pain , symptoms of abdominal distress , and functional disability than those given placebo ( p efficacy was significant across different lengths of illness periods and types of functional disorder . There was no major change 4 weeks after tapering . CONCLUSION Mianserin may be an effective and well-tolerated pharmacologic short-term treatment for functional gastrointestinal disorders in patients with no clinical evidence of psychopathology", "BACKGROUND & AIMS Impaired accommodation and hypersensitivity to gastric distention are believed to be involved in the development of functional dyspepsia ( FD ) . Buspirone , a 5-hydroxytryptamine 1A receptor agonist , relaxes the proximal stomach in healthy individuals . We studied the effects of buspirone on symptoms and mechanisms of FD . METHODS We performed a r and omized , double-blind , placebo-controlled , crossover study of 17 patients ( 13 women ; mean age , 38.5 ± 2.4 years ) . The study included 2 treatment periods of 4 weeks each , separated by a 2-week washout period . In the first period , 7 participants were given buspirone ( 10 mg , 3 times daily for 4 weeks ) and 10 were given placebo 15 minutes before meals ; patients switched groups for the second period . We assessed meal-related symptoms and severity , along with gastric sensitivity , accommodation , and emptying ( by using barostat and breath tests ) before and after 4 weeks of treatment . RESULTS Buspirone significantly reduced the overall severity of symptoms of dyspepsia ( 7.5 ± 1.3 vs 11.5 ± 1.2 for placebo ; P and individual symptoms of postpr and ial fullness , early satiation , and upper abdominal bloating , whereas placebo had no significant effect ( all P ) . Buspirone did not alter the rate of gastric emptying of solids or sensitivity to gastric distention , but it significantly increased gastric accommodation , compared with placebo ( 229 ± 28 vs 141 ± 32 mL , respectively ; P .05 ) , and delayed gastric emptying of liquids ( half-life = 64 ± 5 vs 119 ± 24 minutes , respectively ) . Adverse events were similar when patients were given buspirone or placebo . CONCLUSIONS In patients with FD , 4 weeks of administration of buspirone significantly improved symptoms and gastric accommodation , compared with placebo , whereas gastric emptying of liquids was delayed", "The efficacy of several prokinetic drugs on dyspeptic symptoms and on gastric emptying rates are well‐established in patients with functional dyspepsia , but formal studies comparing different prokinetic drugs are lacking", "IMPORTANCE Many medications have anticholinergic effects . In general , anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy . However , a few studies suggest that anticholinergics may be associated with an increased risk for dementia . OBJECTIVE To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve population -based cohort study using data from the Adult Changes in Thought study in Group Health , an integrated health care delivery system in Seattle , Washington . We included 3434 participants 65 years or older with no dementia at study entry . Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003 . Beginning in 2004 , continuous replacement for deaths occurred . All participants were followed up every 2 years . Data through September 30 , 2012 , were included in these analyses . EXPOSURES Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure , which was defined as the total st and ardized daily doses ( TSDDs ) dispensed in the past 10 years . The most recent 12 months of use was excluded to avoid use related to prodromal symptoms . Cumulative exposure was up date d as participants were followed up over time . MAIN OUTCOMES AND MEASURES Incident dementia and Alzheimer disease using st and ard diagnostic criteria . Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics , health behaviors , and health status , including comorbidities . RESULTS The most common anticholinergic classes used were tricyclic antidepressants , first-generation antihistamines , and bladder antimuscarinics . During a mean follow-up of 7.3 years , 797 participants ( 23.2 % ) developed dementia ( 637 of these [ 79.9 % ] developed Alzheimer disease ) . A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease ( test for trend , P dementia , adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 ( 95 % CI , 0.74 - 1.16 ) for TSDDs of 1 to 90 ; 1.19 ( 95 % CI , 0.94 - 1.51 ) for TSDDs of 91 to 365 ; 1.23 ( 95 % CI , 0.94 - 1.62 ) for TSDDs of 366 to 1095 ; and 1.54 ( 95 % CI , 1.21 - 1.96 ) for TSDDs greater than 1095 . A similar pattern of results was noted for Alzheimer disease . Results were robust in secondary , sensitivity , and post hoc analyses . CONCLUSIONS AND RELEVANCE Higher cumulative anticholinergic use is associated with an increased risk for dementia . Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time", "Aliment Pharmacol Ther 2011 ; 33 : 395–402", "BACKGROUND & AIMS Antidepressants are frequently prescribed to treat functional dyspepsia ( FD ) , a common disorder characterized by upper abdominal symptoms , including discomfort or postpr and ial fullness . However , there is little evidence of the efficacy of these drugs in patients with FD . We performed a r and omized , double-blind , placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms , gastric emptying ( GE ) , and meal-induced satiety in patients with FD . METHODS We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants . Patients ( n = 292 ; 44 ± 15 years old , 75 % were female , 70 % with dysmotility-like FD , and 30 % with ulcer-like FD ) were r and omly assigned to groups given placebo , 50 mg amitriptyline , or 10 mg escitalopram for 10 weeks . The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks ( of 12 ) . Secondary end points included GE time , maximum tolerated volume in Nutrient Drink Test , and FD-related quality of life . RESULTS An adequate relief response was reported by 39 subjects given placebo ( 40 % ) , 51 given amitriptyline ( 53 % ) , and 37 given escitalopram ( 38 % ) ( P = .05 , after treatment , adjusted for baseline balancing factors including all subjects ) . Subjects with ulcer-like FD given amitriptyline were > 3-fold more likely to report adequate relief than those given placebo ( odds ratio = 3.1 ; 95 % confidence interval : 1.1 - 9.0 ) . Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group . Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE ( odds ratio = 0.4 ; 95 % confidence interval : 0.2 - 0.8 ) . Both antidepressants improved overall quality of life . CONCLUSIONS Amitriptyline , but not escitalopram , appears to benefit some patients with FD , particularly those with ulcer-like ( painful ) FD . Patients with delayed GE do not respond to these drugs . Clinical Trials.gov ID : NCT00248651" ]

[ "Purpose We design ed American College of Surgeons Oncology Group ( ACOSOG ) Z6041 , a prospect i ve , multicenter , single-arm , phase II trial to assess the efficacy and safety of neoadjuvant chemoradiation ( CRT ) and local excision ( LE ) for T2N0 rectal cancer . Here , we report tumor response , CRT-related toxicity , and perioperative complications ( PCs ) . Methods Clinical ly staged T2N0 rectal cancer patients were treated with capecitabine and oxaliplatin during radiation followed by LE . Because of toxicity , capecitabine and radiation doses were reduced . LE was performed 6 weeks after CRT . Patients were evaluated for clinical and pathologic response . CRT-related complications and PCs were recorded . Results Ninety patients were accrued ; 6 received non protocol treatment . The remaining 84 were 65 % male ; median age 63 years ; 83 % Eastern Cooperative Oncology Group performance score 0 ; 92 % white ; mean tumor size 2.9 cm ; and average distance from anal verge 5.1 cm . Five patients were considered ineligible . Therapy was completed per protocol in 79 patients , but two patients did not undergo LE . Among 77 eligible patients who underwent LE , 34 patients achieved a pathologic complete response ( 44 % ) and 49 ( 64 % ) tumors were downstaged ( ypT0–1 ) , but 4 patients ( 5 % ) had ypT3 tumors . Five LE specimens contained lymph nodes ; one T3 tumor had a positive node . All but one patient had negative margins . Thirty-three ( 39 % ) of 84 patients developed CRT-related grade ≥3 complications . Rectal pain was the most common PC . Conclusions CRT before LE for T2N0 tumors results in a high pathologic complete response rate and negative resection margins . However , complications during CRT and after LE are high . The true efficacy of this approach will ultimately be assessed by the long-term oncologic outcomes ", "Accurate identification of lymph nodes facilitates nodal assessment by size , morphological or MR lymphographic criteria . We compared the MR detection of lymph nodes in patients with pelvic cancers using T2-weighted imaging , and fusion of diffusion-weighted imaging ( DWI ) and T2-weighted imaging . Twenty patients with pelvic tumours underwent 5-mm axial T2-weighted and DWI ( b-values 0 - 750 s/mm(2 ) ) on a 1.5 T system . Fusion images of b = 750 s/mm(2 ) diffusion-weighted MR and T2-weighted images were created . Two radiologists evaluated in consensus the T2-weighted images and fusion images independently . For each image set , the location and diameter of pelvic nodes were recorded , and nodal visibility was scored using a 4-point scale ( 0 - 3 ) . Nodal visualisation was compared using Relative to an Identified Distribution ( RIDIT ) analysis . The mean RIDIT score describes the probability that a r and omly selected node will be better visualised relative to the other image set . One hundred fourteen pelvic nodes ( mean 5.9 mm ; 2 - 10 mm ) were identified on T2-weighted images and 161 nodes ( mean 4.3 mm ; 2 - 10 mm ) on fusion images . Using fusion images , 47 additional nodes were detected compared with T2-weighted images alone ( eight external iliac , 24 inguinal , 12 obturator , two peri-rectal , one presacral ) . Nodes detected only on fusion images were 2 - 9 mm ( mean 3.7 mm ) . Nodal visualisation was better using fusion images compared with T2-weighted images ( mean RIDIT score 0.689 vs 0.302 ) . Fusion of diffusion-weighted MR with T2-weighted images improves identification of pelvic lymph nodes compared with T2-weighted images alone . The improved nodal identification may aid treatment planning and further nodal characterisation", "Background Transanal endoscopic microsurgery ( TEM ) represents a surgical option in the treatment of selected early rectal cancers . However , when definitive histopathology shows negative prognostic factors , rectal resection with total mesorectal excision ( TME ) is recommended to reduce the risk of recurrence . No studies have yet analyzed the impact of previous TEM on the perioperative outcomes of immediate laparoscopic TME ( LTME ) for rectal cancer . The aim of this study was to evaluate the perioperative outcomes of LTME after TEM for rectal cancer . Methods This study was a retrospective analysis of a prospect i ve data base . All patients undergoing LTME within 8 weeks after full-thickness TEM for rectal cancer between January 2001 and December 2011 were included . Each patient was matched on the basis of demographic and clinical characteristics with two patients undergoing primary LTME for rectal cancer during the same period . Age , gender , body mass index , tumor distance from the anal verge , tumor size , neoadjuvant chemoradiation , previous TEM , rectal wall defect size created during TEM , and intraoperative complications were included in a multivariate analysis to identify risk factors for abdominoperineal resection ( APR ) . Results A total of 17 patients undergoing TEM followed by LTME were compared to 34 patients undergoing primary LTME . Mean operative time of LTME after TEM was significantly higher ( 206 vs. 188 min , P = 0.025 ) . APR was more frequently performed after TEM [ odds ratio ( OR ) 5.25 , P = 0.028 ] and in male patients ( OR 9.04 , P = 0.034 ) . On multivariate analysis , a previous TEM was the only independent predictor of APR ( OR 4.13 , P = 0.046 ) . The incidence and severity of postoperative complications were similar in both groups . Mesorectum integrity was complete in all cases . Conclusions LTME after TEM is a challenging procedure , with a significantly higher risk of APR compared to primary LTME . Future improvements in preoperative patient selection for TEM are needed to reduce this risk", "Summary Background Preoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer . However , improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed . We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy . Methods We undertook a r and omised trial in 80 centres in four countries . 1350 patients with operable adenocarcinoma of the rectum were r and omly assigned , by a minimisation procedure , to short-course preoperative radiotherapy ( 25 Gy in five fractions ; n=674 ) or to initial surgery with selective postoperative chemoradiotherapy ( 45 Gy in 25 fractions with concurrent 5-fluorouracil ) restricted to patients with involvement of the circumferential resection margin ( n=676 ) . The primary outcome measure was local recurrence . Analysis was by intention to treat . This study is registered , number IS RCT N 28785842 . Findings At the time of analysis , which included all participants , 330 patients had died ( 157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy ) , and median follow-up of surviving patients was 4 years . 99 patients had developed local recurrence ( 27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy ) . We noted a reduction of 61 % in the relative risk of local recurrence for patients receiving preoperative radiotherapy ( hazard ratio [ HR ] 0·39 , 95 % CI 0·27–0·58 , p in disease-free survival of 24 % for patients receiving preoperative radiotherapy ( HR 0·76 , 95 % CI 0·62–0·94 , p=0·013 ) , and an absolute difference at 3 years of 6·0 % ( 95 % CI 5·3–6·8 ) ( 77·5 % vs 71·5 % ) . Overall survival did not differ between the groups ( HR 0·91 , 95 % CI 0·73–1·13 , p=0·40 ) . Interpretation Taken with results from other r and omised trials , our findings provide convincing and consistent evidence that short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer . Funding Medical Research Council ( UK ) and the National Cancer Institute of Canada", "BACKGROUND AND STUDY AIMS This multicenter , prospect i ve , country-wide quality -assurance study at more than 300 hospitals in Germany was design ed to characterize and analyze the diagnostic accuracy of rectal endoscopic ultrasound ( EUS ) in the routine clinical staging of rectal carcinoma ( depth of tumor infiltration ) . PATIENTS AND METHODS Patients were surveyed between 1 January 2000 and 31 December 2008 . Those who received neoadjuvant therapy after EUS were excluded . The correspondence between the EUS assessment of tumor depth ( uT ) and that determined by histology ( pT ) was calculated , and the influence of hospital volume upon the sensitivity , specificity , and positive and negative predictive values was investigated . RESULTS At 384 hospitals providing care at all levels , 29 206 patients were included ; of the 27 458 treated by surgical resection , EUS was performed for 12 235 ( 44.6 % ) . Of these , 7096 did not receive neoadjuvant radiochemotherapy , allowing a uT-pT comparison . The uT-pT correspondence was 64.7 % ( 95 % confidence interval [ CI ] 63.6 % - 65.8 % ) ; the frequency of understaging was 18 % ( 95 % CI 17.1 % - 18.9 % ) and that of overstaging was 17.3 % ( 95 % CI 16.4 % - 18.2 % ) . The kappa coefficient was greatest in the category T1 ( κ = 0.591 ) . For T3 tumors κ was 0.468 . The poorest correspondence was found for T2 and T4 tumors ( κ = 0.367 and 0.321 , respectively ) . A breakdown by hospital volume showed that the uT-pT correspondence was 63.2 % ( 95 % CI 61.5 % - 64.9 % ) for hospitals undertaking ≤ 10 EUS/year , 64.6 % ( 95 % CI 62.9 % - 66.2 % ) for doing 11 - 30 EUS/year , and 73.1 % ( 95 % CI 69.4 % - 76.5 % ) for those hospitals performing > 30 EUS/year . CONCLUSIONS In clinical routine , the diagnostic accuracy of transrectal ultrasound in staging rectal carcinoma does not attain the very good results reported in the literature . Only in the h and s of diagnosticians with a large case volume of rectal carcinoma patients can EUS lead to therapy-relevant decisions", "BACKGROUND Postoperative chemoradiotherapy is the recommended st and ard therapy for patients with locally advanced rectal cancer . In recent years , encouraging results with preoperative radiotherapy have been reported . We compared preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally advanced rectal cancer . METHODS We r and omly assigned patients with clinical stage T3 or T4 or node-positive disease to receive either preoperative or postoperative chemoradiotherapy . The preoperative treatment consisted of 5040 cGy delivered in fractions of 180 cGy per day , five days per week , and fluorouracil , given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per square meter of body-surface area per day during the first and fifth weeks of radiotherapy . Surgery was performed six weeks after the completion of chemoradiotherapy . One month after surgery , four five-day cycles of fluorouracil ( 500 mg per square meter per day ) were given . Chemoradiotherapy was identical in the postoperative-treatment group , except for the delivery of a boost of 540 cGy . The primary end point was overall survival . RESULTS Four hundred twenty-one patients were r and omly assigned to receive preoperative chemoradiotherapy and 402 patients to receive postoperative chemoradiotherapy . The overall five-year survival rates were 76 percent and 74 percent , respectively ( P=0.80 ) . The five-year cumulative incidence of local relapse was 6 percent for patients assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-treatment group ( P=0.006 ) . Grade 3 or 4 acute toxic effects occurred in 27 percent of the patients in the preoperative-treatment group , as compared with 40 percent of the patients in the postoperative-treatment group ( P=0.001 ) ; the corresponding rates of long-term toxic effects were 14 percent and 24 percent , respectively ( P=0.01 ) . CONCLUSIONS Preoperative chemoradiotherapy , as compared with postoperative chemoradiotherapy , improved local control and was associated with reduced toxicity but did not improve overall survival", "Background This study was design ed to investigate short-term and long-term consequences from perforation to the peritoneal cavity during transanal endoscopic microsurgery ( TEM ) for rectal cancer , with special emphasis on local recurrence and complications . Methods Data from TEM procedures with peritoneal perforations were collected from six prospect i ve data bases . Patient , procedure , and follow-up data were extracted . Participating centers were the United Kingdom TEM data base , the German TEM data base from Mainz , the National Danish TEM data base , and data bases from the three major Norwegian TEM centers . A total of 888 TEM procedures were registered , and 22 perforations were identified . Results Median age was 82 years . Tumor stages were 14 pT1 , 4 pT2 , 3 pT3 , and 1 pTx . The mean tumor size was 4.1 cm . Radical resection was achieved in 17 patients . All perforations were h and led endoscopically . There were no severe complications and no deaths related to the procedure . The mean time of observation was 37 ( median 36 ; range 3–164 ) months . Local recurrence occurred in two patients , three patients died from the cancer ( distant metastasis ) , and six died from other causes . Conclusions Breaching the peritoneum during TEM is not associated with major short-term complications or long-term oncological consequences provided that primary endoscopic repair is undertaken", "Abstract Background The last 30 years have witnessed a significant increase in the diagnosis of early-stage rectal cancer and the development of new strategies to reduce the treatment-related morbidity . Currently , there is no consensus on the definition of early rectal cancer ( ERC ) , and the best management of ERC has not been yet defined . The European Association for Endoscopic Surgery in collaboration with the European Society of Coloproctology developed this consensus conference to provide recommendations on ERC diagnosis , staging and treatment based on the available evidence . Methods A multidisciplinary group of experts selected on their clinical and scientific expertise was invited to critically review the literature and to formulate evidence -based recommendations by the Delphi method . Recommendations were discussed at the plenary session of the 14th World Congress of Endoscopic Surgery , Paris , 26 June 2014 , and then posted on the EAES website for open discussion . Results Tumour biopsy has a low accuracy . Digital rectal examination plays a key role in the pre-operative work-up . Magnification chromoendoscopy , endoscopic ultrasound and magnetic resonance imaging are complementary staging modalities . Endoscopic submucosal dissection and transanal endoscopic microsurgery are the two established approaches for local excision ( LE ) of selected ERC . The role of all organ-sparing approaches including neoadjuvant therapies followed by LE should be formally assessed by r and omized controlled trials . Rectal resection and total mesorectal excision is indicated in the presence of unfavourable features at the pathological evaluation of the LE specimen . The laparoscopic approach has better short-term outcomes and similar oncologic results when compared with open surgery . Conclusions The management of ERC should always be based on a multidisciplinary approach , aim ing to increase the rate of organ-preserving procedures without jeopardizing survival", "BACKGROUND : Transanal local excision has been suggested as an attractive approach for patients with rectal cancer who show a major clinical response after preoperative chemoradiotherapy . OBJECTIVE : To evaluate the impact of transanal local excision on the local recurrence of rectal cancer in patients who had a major clinical response after preoperative chemoradiotherapy . DESIGN : Sequential 2-stage phase II study for early efficacy . SETTING : Multicenter study . PATIENTS : Patients with clinical T3 or low-lying T2 rectal adenocarcinoma that showed a major clinical response after a preoperative chemoradiotherapy . Eligible patients underwent a full-thickness transanal local excision . According to their histopathology , the patients staged as ypT0 - 1 were observed , while the remaining patients were recommended to undergo a subsequent total mesorectal excision . MAIN OUTCOME MEASURES : A local recurrence rate of ⩽5 % was set as a successful rate for stopping the trial early after the first stage . RESULTS : The study group included 63 patients . Before chemoradiotherapy , patients were staged as clinical T3 ( n = 42 ) and T2 ( n = 21 ) . After the local excision , 43 patients fulfilled the criteria to be observed with no further treatment . Nine of the remaining 20 patients for whom a subsequent total mesorectal excision was recommended refused surgery . Two of these patients who refused surgery had intraluminal local recurrence ; both had a ypT2 tumor and underwent salvage surgery . The estimated cumulative 3-year overall survival , disease-free survival and local disease-free survival were 91.5 % ( 95 % CI : 75.9–97.2 ) , 91.0 % ( 95 % CI : 77.0–96.6 ) and 96.9 % ( 95 % CI : 80.3–99.5 ) , respectively . LIMITATIONS : The time of follow-up is still short and the sample size is limited . CONCLUSIONS : Our data suggest that local excision is a good option for patients with a major clinical response after chemoradiotherapy . A longer period of follow-up is required to confirm these findings", "Objective To determine the ability of dynamic contrast enhanced ( DCE-MRI ) to predict pathological complete response ( pCR ) after preoperative chemotherapy for rectal cancer . Methods In a prospect i ve clinical trial , 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5 T . Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s . Using a two-compartmental model of vascular space and extravascular extracellular space , Ktrans , kep , ve , AUC90 , and AUC180 were calculated . Surgical specimens were the gold st and ard . Baseline , post-treatment and changes in these quantities were compared with clinico-pathological outcomes . For quantitative variable comparison , Spearman ’s Rank correlation was used . For categorical variable comparison , the Kruskal – Wallis test was used . P ≤ 0.05 was considered significant . Results Percentage of histological tumour response ranged from 10 to 100 % . Six patients showed pCR . Post chemotherapy Ktrans ( mean 0.5 min−1 vs. 0.2 min−1 , P = 0.04 ) differed significantly between non-pCR and pCR outcomes , respectively and also correlated with percent tumour response and pathological size . Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone . Conclusion After neoadjuvant chemotherapy in rectal cancer , MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR.Key PointsDynamic contrast enhanced ( DCE ) MRI provides perfusion characteristics of tumours . These objective quantitative measures may be more helpful than subjective imaging aloneSome parameters differed markedly between completely responding and incompletely responding rectal cancers . Thus DCE-MRI can potentially offer treatment-altering imaging biomarkers", "Background Indications and results of local excision of rectal lesions are currently under debate . Transanal endoscopic microsurgery ( TEM ) , allowing a precise , full-thickness excision , could improve oncological results in early rectal tumors . Methods A prospect i ve data base was analyzed with the intent to identify risk factors for recurrence after TEM . Results Among 355 patients subjected to TEM , 107 had an adenocarcinoma : 48 pT1 , 43 pT2 , and 16 pT3 . Comparing pre- and postoperative data , histological discrepancy was 20 % and staging discrepancy was 34 % . Mortality was nil , morbidity was 9 % . Mean follow-up was 54.2 months ( range = 12–164 ) , follow-up rate was 100 % . The 5-year disease-free survival rate was 85.9 , 78.4 , and 49.4 % for pT1 , pT2 , and pT3 , respectively ( p = 0.006 ) . Recurrence rate was 0 % ( 0/26 ) in pT1sm1 cancers and 22.7 % ( 5/22 ) in sm2 - 3 ( p submucosal infiltration represented a significant risk factor for recurrences : 0 % sm1 , 16.7 % sm2 , and 30 % sm3 . Recurrence in pT2 was 0 % in patients who had neoadjuvant therapy and 26 % in the others . At univariate analysis , diameter , sm stage , pT stage , tumor grading , margin infiltration , and lymphovascular invasion demonstrated statistical significance . Multivariate analysis indicated sm stage , pT stage , and tumor grading as independent predictors of recurrence . Conclusions TEM represents an effective curative treatment for pT1 sm1 rectal malignancies . pT1 sm2 - 3 patients should be considered high-risk cases if treated only by TEM . A consistent improvement in the preoperative assessment of the risk factors identified by the present study will be a crucial development for optimal treatment of early rectal cancers", "Purpose The efficacy of local excision in the treatment of some early-stage distal rectal cancers is still being debated , because few high- quality , long-term prospect i ve data on outcomes are available . Methods Fifty-nine patients with T1 lesions were treated with local excision alone , whereas 51 patients with T2 lesions received external beam irradiation ( 5,400 cGY ) and 5-fluorouracil ( 500 mg/m2 intravenously Days 1–3 , Days 29–31 ) after local excision . Kaplan-Meier curves were used to estimate the primary outcomes . The log-rank test and Cox ’s proportional hazards model were used to compare subgroups relative to these outcomes . Results With a median follow-up of 7.1 ( range , 2.1–11.4 ) years , ten-year rates of overall survival were 84 percent for patients with T1 and 66 percent for T2 rectal cancer . Disease-free survival was 75 percent for T1 and 64 percent for T2 disease . Local recurrence rates for patients with T1 and T2 lesions were 8 and 18 percent , respectively , and rates of distant metastases were 5 percent for T1 and 12 percent for T2 lesions . T stage was a statistically significant predictor of overall survival ( P = 0.04 ) and approached statistical significance as a predictor of disease-free survival ( P = 0.07 ) . Conclusions Local excision alone for T1 rectal adenocarcinomas is associated with low recurrence and good survival rates that remain durable with long-term follow-up . T2 lesions treated via local excision and adjuvant therapy are associated with higher recurrence rates ", "BACKGROUND AND PURPOSE During the first decade of the 21st century a number of important European r and omized studies were published . In order to help shape clinical practice based on best scientific evidence from the literature , the International Conference on ' Multidisciplinary Rectal Cancer Treatment : Looking for an European Consensus ' ( EURECA-CC2 ) was organized in Italy under the endorsement of European Society of Medical Oncology ( ESMO ) , European Society of Surgical Oncology ( ESSO ) , and European Society of Therapeutic Radiation Oncology ( ESTRO ) . METHODS Consensus was achieved using the Delphi method . The document was available to all Committee members as a web-based document customized for the consensus process . Eight chapters were identified : epidemiology , diagnostics , pathology , surgery , radiotherapy and chemotherapy , treatment toxicity and quality of life , follow-up , and research questions . Each chapter was subdivided by a topic , and a series of statements were developed . Each member commented and voted , sentence by sentence thrice . Sentences upon which an agreement was not reached after voting round # 2 were openly debated during a Consensus Conference in Perugia ( Italy ) from 11 December to 13 December 2008 . A h and -held televoting system collected the opinions of both the Committee members and the audience after each debate . The Executive Committee scored percentage consensus based on three categories : \" large consensus \" , \" moderate consensus \" , and \" minimum consensus \" . RESULTS The total number of the voted sentences was 207 . Of the 207 , 86 % achieved large consensus , 13 % achieved moderate consensus , and only 3 ( 1 % ) result ed in minimum consensus . No statement was disagreed by more than 50 % of the members . All chapters were voted on by at least 75 % of the members , and the majority was voted on by > 85 % . CONCLUSIONS This Consensus Conference represents an expertise opinion process that may help shape future programs , investigational protocol s , and guidelines for staging and treatment of rectal cancer throughout Europe", "Objective Tumours of the upper rectum , and many in the middle third , are not accessible to endorectal ultrasound staging because of the difficulty in reaching all sites of the rectum with a rigid probe . The aim of this prospect i ve study was to assess whether using a dedicated rectosigmoidoscope , endorectal ultrasonography ( ERUS ) can accurately stage any rectal lesion irrespective of its distance from the anal verge", "BACKGROUND : Transanal endoscopic microsurgery has gained increasing popularity as a treatment alternative for early stage rectal neoplasms . With continued advances in technique and experience , more proximal rectal tumors are being surgically managed by using transanal endoscopic microsurgery with an intraperitoneal anastomosis . OBJECTIVE : The purpose of this study was to review the outcomes of patients who have undergone intraperitoneal anastomosis with the use of the transanal endoscopic microsurgery technique . DESIGN : A prospect i ve , single-surgeon data base documented 445 consecutive patients undergoing transanal endoscopic microsurgery from October 1 , 1996 through January 1 , 2012 . We retrospectively review ed information from all patients who underwent transanal endoscopic microsurgery with an intraperitoneal anastomosis in this prospect i ve data base . SETTING S : All procedures took place in an inpatient hospital setting . PATIENTS : All patients satisfied workup criteria to undergo surgery for rectal neoplasm . INTERVENTIONS : All patients underwent transanal endoscopic microsurgery for rectal neoplasm . MAIN OUTCOME MEASURES : Size and pathology of lesion , length of procedure , hospital stay , estimated blood loss , margin status , and complications were the outcomes measured . RESULTS : Twenty-eight patients who underwent transanal endoscopic microsurgery had definitively documented intraperitoneal entry and anastomosis . Median follow-up was 12 months ( range , 0.5–111 months ) . There were no operative mortalities . Procedure-related complications included urinary retention ( 11 % ) , fever ( 11 % ) , and fecal seepage ( 4 % ) . Four patients ( 14 % ) had positive margins on final pathology . One patient ( 3 % ) required abdominal exploration for an anastomotic leak but did not require diversion . LIMITATIONS : Although this study analyzes prospect ively collected data , it is nonetheless a retrospective analysis that can introduce bias . Because this is a single-center study with a relatively homogenous population , the results may not be generalizable . Our sample size may also be underpowered to detect clinical ly significant outcomes . CONCLUSIONS : Transanal endoscopic microsurgery with intraperitoneal anastomosis can be safely performed without fecal diversion by experienced surgeons", "PURPOSE : The aims of this prospect i ve study were 1 ) to evaluate the accuracy of high-resolution three-dimensional endorectal ultrasonography in distinguishing slight from massive submucosal invasion of early rectal tumors , and 2 ) to determine the technology 's role in treatment selection . METHODS : A total of 142 consecutive patients with clinical ly possible pT1 rectal cancers underwent three-dimensional endorectal ultrasonography . Slight or massive irregularity of the hyperechoic submucosal layer was considered to characterize uT1-slight or uT1-massive tumors . Treatment was selected on the basis of ultrasonographic findings : endoscopic resection or full-thickness transanal local excision was selected for uT1-slight lesions , and radical resection was selected for uT1-massive tumors . Ultrasonographic staging was compared with histopathologic staging . RESULTS : One hundred twenty-six patients were included in the final analyses . Three-dimensional endorectal ultrasonography staged 77 lesions as uT0 , 25 as uT1-slight , 20 as uT1-massive , and 4 as uT2 . Histologically , adenomas were found in 75 patients and tumor invasion was found in 44 lesions ( 24 pT1-slight , 16 pT1-massive , 4 pT2 ) . The overall kappa for the concordance between ultrasonographic and histopathologic stagings was 0.81 ( 95 % confidence interval , 0.72–0.89 ) . No invasive carcinomas remained undetected . The depth of invasion was correctly determined in 87.2 % of both pT1-slight and pT1-massive lesions . Considering the complete series of 126 patients , the accuracy of this modality in selecting appropriate management was 95.2 % ( kappa , 0.84 ; 95 % confidence interval , 0.71–0.96 ) . Adequate surgery was performed in 87.5 % of pT1 tumors . CONCLUSION : Three-dimensional endorectal ultrasonography is useful for assessing the depth of submucosal invasion in early rectal cancer and for selecting therapeutic options", "Background Three-dimensional ( 3D ) imaging offers improved knowledge of various anatomic structures and tumors by providing 3D images . This prospect i ve study was performed to verify whether 3D endorectal ultrasonography ( EUS ) enhances the accuracy of rectal cancer staging , as compared with conventional EUS . Methods Using both 3D and conventional EUS , 33 consecutive patients with operable rectal cancer were preoperatively staged . A rigid 3D probe with a scanner was used for 3D EUS , and a rigid endorectal probe with a scanner was used for conventional EUS . Results The accuracy of 3D EUS was 90.9 % for pT2 and 84.8 % for pT3 , whereas that of conventional EUS was 84.8 % and 75.8 % , respectively , thereby showing no difference between these two methods . The lymph node metastasis was accurately predicted by 3D EUS in 28 patients ( 84.8 % ) , whereas conventional EUS predicted the disorder in 22 patients ( 66.7 % ) . The difference was not statistically significant . The average infiltration grade of the circumference on transverse 3D EUS scans was associated closely with advancement of the TNM stage ( p a cone-shaped surface on the deep tumor border correlated with the infiltration grade shown on all of the sectional displays ( p 3D EUS to have a significant advantage over conventional EUS for the accurate evaluation of rectal cancer , a numeric advantage may possibly be statistically significant in a further study with larger cases . Furthermore , stereoscopic visualization provided easier and complete underst and ing of both focal lesions and lymph nodes", "Objective : To prospect ively assess the accuracy of gadofosveset-enhanced magnetic resonance imaging ( MRI ) for nodal staging and restaging in rectal cancer . Background : Accurate preoperative assessment of nodal disease in rectal cancer impacts treatment management . Staging with modern imaging techniques ( computed tomography , MRI and endorectal ultrasound ) is insufficiently accurate for clinical decision making . This study aims to assess the accuracy of MRI using a novel lymph node magnetic resonance contrast , gadofosveset , for nodal staging and restaging in rectal cancer using a per node comparison with histology as the reference st and ard . Methods : Sixty-eight patients underwent gadofosveset-enhanced MRI at 1.5 T . Twenty-six patients ( primary staging group I ) were treated with total mesorectal excision ( with or without preoperative 5 × 5 Gy ) and 42 ( restaging group II ) underwent a long course of chemoradiation followed by a restaging MRI and resection . Nodes were scored as benign or malignant by 2 radiologists ( experienced and junior reader ) first on st and ard MRI , then on gadofosveset-enhanced MRI . For group I the primary staging MRI was compared with histology . In group II the second , restaging MRI was compared with histology . Results : For the experienced reader , sensitivity , specificity , and area under the ROC-curve ( AUC ) improved from 76 % , 82 % and 0.84 on st and ard MRI to 80 % , 97 % and 0.96 on gadofosveset-MRI ( P . Interobserver agreement was good on both st and ard MRI ( & kgr ; 0.73 ) and gadofosveset-MRI ( & kgr ; 0.71 ) . Conclusions : This study shows high reproducibility and significantly improved accuracy compared to st and ard MRI for gadofosveset-enhanced MRI for nodal staging and restaging in rectal cancer", "To address issues regarding the fractionation of radiotherapy ( RT ) and timing of surgery for rectal cancer , a multicentre trial has r and omized patients to preoperative short‐course RT with two different intervals to surgery , or long‐course RT with delayed surgery . The present interim analysis assessed feasibility , compliance and complications after RT and surgery" ]

[ "BACKGROUND As a continuation of two large-scale , multicentre studies on the development of 5-year-old ICSI children , we present results of the follow-up study undertaken on the cognitive and motor development of 8-year-old ICSI children . METHODS Developmental outcomes of 151 8-year-old singletons born through ICSI after 32 weeks of gestation were compared with those of 153 singletons of the same age born after spontaneous conception ( SC ) . Part of this population was seen in a cohort at the age 5 years . Outcome measures include Wechsler Intelligence Scale for Children-Revised ( WISC-R ) and Movement Assessment Battery for Children ( ABC ) . RESULTS Regarding intellectual functioning , ICSI children tend to obtain significantly higher total ( P than SC children , nevertheless remaining in similar ranges . These effects are small ( Cohen 's d maternal educational level stayed in the regression as a factor accounting for some of the variance in total IQ between the groups . In terms of motor development , no significant differences were found between ICSI and SC children regarding overall motor skills , manual , balance and ball skills . CONCLUSION In this follow-up study , ICSI and SC children show a comparable cognitive and motor development until the age of 8 years", "STUDY QUESTION Do children born after assisted reproductive techniques ( ART ; IVF/ICSI ) display more mental health issues or social and cognitive developmental problems at 7 - 8 years than naturally conceived ( NC ) controls , and does child gender play a role ? SUMMARY ANSWER ART children do not differ with regard to mental health or social and cognitive developmental problems when compared with controls , but some gender-specific differences do exist . WHAT IS KNOWN ALREADY Systematic review s have not found any evidence of delays in neurocognitive or sensorimotor development in ART children . However findings on the effect of the type of ART treatment ( IVF versus ICSI ) on the offspring 's physical and mental development have not been uniform . Knowledge of the role of child gender in ART research is scarce . STUDY DESIGN , SIZE , DURATION This prospect i ve follow-up study compares mental health and social and cognitive developmental problems between 7 - 8-year-old ART and NC children , controlling for the father 's age , length of the parents ' partnership , mother 's parity , child 's gestational age , and the need of neonatal intensive care unit ( NICU ) . Further , within the ART group , we analysed whether the treatment type ( IVF versus ICSI ) and the child 's gender are associated with the mental health and developmental outcomes . PARTICIPANTS / MATERIAL S , SETTING , METHODS In this study , 255 singleton ART children ( IVF and ICSI ) were compared with 278 NC children on parent-reported internalizing and externalizing symptoms , and social ( social skills and peer relations ) and cognitive development ( executive functioning , perception , memory , and language ) . Within the ART group , 164 IVF and 76 ICSI children were compared on the same outcomes . Statistics included analyses of covariates ( ANCOVA ) with group main effects , group and gender interaction effects , and Bonferroni post hoc tests . MAIN RESULTS AND THE ROLE OF CHANCE ART and NC children did not differ generally in terms of their internalizing and externalizing symptoms or in the number of social and cognitive developmental problems ( Group main effects , P > 0.05 ) , but gender-specific group differences existed . The ART boys showed lower levels of cognitive problems than the NC boys , whereas ART girls showed higher levels of cognitive problems than the NC girls ( Group × Gender-interaction effects with Bonferroni post hoc tests on mother-reports , P externalizing symptoms and social and cognitive developmental problems than girls ( Group × Gender-interaction effects with Bonferroni post hoc tests for both parents ' reports , P ) , gender differences were not found in the ART group . Within the ART group , IVF and ICSI children did not differ in terms of mental health or developmental outcomes , and no significant gender differences emerged . LIMITATIONS , REASONS FOR CAUTION The information on children 's mental health and development was based on parental reports only . The dropout rate between the child 's first year and the school age assessment s was very high for fathers ( 57.4 % ) and substantial for mothers ( 30.1 % ) , and the participating group was biased for older age of both parents and for better education of the fathers . WIDER IMPLICATION S OF THE FINDINGS The findings indicate the importance of considering child gender in learning about multiple developmental outcomes among children born after ART . STUDY FUNDING /COMPETING INTERESTS This study was supported by the Academy of Finl and ( # 11232276 ) , the Emil Aaltonen Foundation , The Family Federation of Finl and , Helsinki University Central Hospital Research Funds , and the National Graduate School of Psychology . None of authors has any competing interests to declare", "OBJECTIVES : The objective of this study was to document the psychological adjustment of adolescents who were conceived through donor insemination by lesbian mothers who enrolled before these offspring were born in the largest , longest running , prospect i ve , longitudinal study of same-sex – parented families . METHODS : Between 1986 and 1992 , 154 prospect i ve lesbian mothers volunteered for a study that was design ed to follow planned lesbian families from the index children 's conception until they reached adulthood . Data for the current report were gathered through interviews and question naires that were completed by 78 index offspring when they were 10 and 17 years old and through interviews and Child Behavior Checklists that were completed by their mothers at corresponding times . The study is ongoing , with a 93 % retention rate to date . RESULTS : According to their mothers ' reports , the 17-year-old daughters and sons of lesbian mothers were rated significantly higher in social , school/academic , and total competence and significantly lower in social problems , rule-breaking , aggressive , and externalizing problem behavior than their age-matched counterparts in Achenbach 's normative sample of American youth . Within the lesbian family sample , no Child Behavior Checklist differences were found among adolescent offspring who were conceived by known , as-yet-unknown , and permanently unknown donors or between offspring whose mothers were still together and offspring whose mothers had separated . CONCLUSIONS : Adolescents who have been reared in lesbian-mother families since birth demonstrate healthy psychological adjustment . These findings have implication s for the clinical care of adolescents and for pediatricians who are consulted on matters that pertain to same-sex parenting", "BACKGROUND Contemporary data on visual memory and learning in survivors born extremely preterm ( EP ; are lacking . METHODS Geographically determined cohort study of 298 consecutive EP/ELBW survivors born in 1991 and 1992 , and 262 r and omly selected normal-birth-weight controls . RESULTS Visual learning and memory data were available for 221 ( 74.2 % ) EP/ELBW subjects and 159 ( 60.7 % ) controls . EP/ELBW adolescents exhibited significantly poorer performance across visual memory and learning variables compared with controls . Visual learning and delayed visual memory were particularly problematic and remained so after controlling for visual-motor integration and visual perception and excluding adolescents with neurosensory disability , and /or IQ EP/ELBW adolescents or those treated with corticosteroids had poorer outcomes . CONCLUSION EP/ELBW adolescents have poorer visual memory and learning outcomes compared with controls , which can not be entirely explained by poor visual perceptual or visual constructional skills or intellectual impairment", "Objective To investigate how pregnancy planning , time to conception , and infertility treatment influence cognitive development at ages 3 and 5 . Design Prospect i ve population based cohort study . Setting Millennium Cohort Study in the United Kingdom . Participants 18 818 children recruited at 9 months and followed up at 3 and 5 years . 11 790 singletons with available data on pregnancy , cognitive outcomes , and confounders were included in analyses at age 3 and 12 136 at age 5 . Exposure measures Mothers reported whether the pregnancy was planned , and their feelings when first pregnant ; those in whom the pregnancy was planned provided time to conception , and details of any assisted reproductive technologies . The population was divided into “ unplanned ” ( unplanned and unhappy ) , “ mistimed ” ( unplanned but happy ) , “ planned ” ( planned , time to conception “ subfertile ” ( planned , time to conception ≥12 months ) , “ induced ovulation ” ( received clomiphene citrate ) , and “ assisted reproduction ” ( in vitro fertilisation or intracytoplasmic sperm injection ) . The “ planned ” group was the comparison group in all analyses . Outcome measures Three components of the British Ability Scales ( BAS II ) . Naming vocabulary assessed verbal ability at age 3 ; this test was repeated at age 5 with the picture similarities and pattern construction subscales , which measure non-verbal and spatial abilities . Results In unadjusted analyses , the scores on all scales in children from unplanned pregnancies were significantly lower than in those from planned pregnancies — for example , the difference in mean verbal ability score at age 3 was −4.8 ( 95 % confidence interval −6.0 to −3.7 ; P in verbal ability tests ( 3.8 ( −0.2 to 7.9 ) at age 3 and 3.5 ( 0.2 to 6.8 ) at age 5 ) , which suggests that on average these children are three to four months ahead ; this difference did not completely disappear with adjustment for confounders . Children born after infertility treatment had lower mean scores in non-verbal tests ( −1.2 ( −4.1 to 1.6 ) after assisted reproduction and −1.5 ( −3.5 to 0.4 ) after induced ovulation ) and in spatial ability tests ( −2.7 ( −6.9 to 1.6 ) after assisted reproduction ) , though the differences were not significant . Conclusions Pregnancy planning , subfertility , or assisted reproduction do not adversely affect children ’s cognitive development at age 3 or 5 . The differences observed in the unadjusted analyses are almost entirely explained by marked inequalities in socioeconomic circumstances between the groups", "Growing public awareness of the use of donor insemination ( DI ) to enable infertile couples to become parents has been accompanied by increasing concern regarding the potentially negative consequences for family relationships and child development . Findings are presented from a prospect i ve study of the quality of parenting and psychological adjustment of DI children at age 12 . Thirty-seven DI families , 49 adoptive families , and 91 families with a naturally conceived child were compared on st and ardized interview and question naire measures administered to mothers , fathers , children , and teachers . The differences between DI families and the other family types reflected greater expressive warmth of DI mothers toward their children and less involvement in the discipline of their children by DI fathers . The DI children were well adjusted in terms of their social and emotional development . The findings are discussed with respect to the secrecy surrounding DI and the imbalance in genetic relatedness between the parents and the child", "BACKGROUND The aim of the present study was to determine language levels in twins and singletons born after at least 34 weeks gestation and without identifiable neurological abnormality and to evaluate whether in vitro fertilization ( IVF ) affects language development in twin pregnancies . METHODS A prospect i ve study of a large cohort of all children born between 1 January 2001 and 31 December 2003 was carried out at Gazi University Hospital . All live-born twin pairs in which both twins survived were identified , and a comparable sample of families with pairs of singletons were chosen . The Stanford-Binet Intelligence Scale Form and the translated Turkish form of the Peabody Picture Vocabulary Test were completed at 60 months . RESULTS Even after excluding the most premature twins and those with diagnosable neurological damage , twins performed worse than singletons on language development tests . Twin girls had better scores than twin boys . A statistically significant difference was found between the scores of term and preterm twins . No significant difference was noted when compared according to birth order . Appropriate for gestational age ( AGA ) twins did better than small for gestational age ( SGA ) twins in the test scores . All twin girls did not differ from singleton girls , but all twin boys performed worse than singleton boys . Term twins had similar results with term singletons , but preterm twins had lower scores than preterm singletons . SGA singletons had better scores than SGA twins , while AGA twins and singletons did not differ . When the children were compared with regard to method of conception , IVF children had significantly lower scores on the tests than those in the spontaneous conception group . CONCLUSION It is hoped that the present findings could lead to a more precise assessment of children for speech impairment and , above all , to more efficient preventive intervention . Whatever mechanisms are involved , the present results indicate that twins born as a result of IVF , are at a disadvantage in terms of language development in comparison with spontaneously conceived twins", "STUDY QUESTION Do preschool preimplantation genetic diagnosis ( PGD ) children differ in their cognitive and psychomotor development from children born after ICSI and spontaneous conception ( SC ) ? SUMMARY ANSWER The cognitive development of PGD pre-schoolers was comparable to children born after ICSI and SC but motor development differed between ICSI and SC groups . STUDY DESIGN , SIZE DURATION The cognitive abilities and motor skills of 5- to 6-year-old singletons born after PGD ( n = 47 ) were assessed in comparison with 49 ICSI and 48 SC children in a prospect i ve , case-controlled , matched follow-up study between April 2011 and May 2013 . PARTICIPANTS / MATERIAL S , SETTING , METHODS PGD singletons , ICSI and SC children of preschool age were examined with the Wechsler Preschool and Primary Scale of Intelligence ( WPSSI-III-NL ) and the Movement ABC ( M ABC ) . The WPSSI-III-NL revealed scores for Full IQ , Verbal IQ and Performance IQ . The M ABC yields a total score and comprising scores for measurements of balance , dexterity and ball skills . Since embryo biopsy is the only technical difference between the PGD and ICSI procedures , ICSI children were included as controls . These children were part of a Dutch-speaking cohort of children conceived after assisted reproduction technology ( ART ) at the Universitair Ziekenhuis Brussel ( UZ Brussel ) who received longitudinal follow-up . The SC children acted as a second control group similar to the fertile PGD sample and in contrast to the ICSI group . The SC group was recruited through announcements in a variety of media . The children were matched for age , gender , birth order and educational level of the mother . The assessment s carried out for the ART groups were blinded whenever possible . The data were analysed using analysis of covariance ( ANCOVA ) and partial eta squared ( η(2 ) ) , which was used as a measurement of effect size . MAIN RESULTS AND THE ROLE OF CHANCE The overall cognitive development of PGD singletons did not differ from controls [ P = 0.647 , η(2 ) = 0.006 ; 95 % confidence interval ( CI ) ( 0 , 0.043 ) ] . The partial IQ scores for Verbal and Performance intelligence revealed similar results . Analysis of motor development based on the total score as well as subscales did indicate a significant difference between the three conception groups [ P = 0.033 , η(2 ) = 0.050 , 95 % CI ( 0 , 0.124 ) ] . Post hoc analysis indicated that the significant difference was situated between performances of ICSI and SC children . Balance capacities [ P = 0.004 , η(2 ) = 0.079 , 95 % CI ( 0.025 , 0.163 ) ] and its post hoc analysis yielded equivalent results . Motor capacities of PGD singletons , however , did not differ from any of the two other conception groups . LIMITATIONS , REASONS FOR CAUTION Given that we only assessed Caucasian singletons born after PGD , caution is required when drawing more general inferences from our results . The small sample size may be a limitation . A priori power analysis , however , revealed that at least 52 children per group were needed to detect a medium effect and 80 % power using ANCOVA . Originally our sample met this threshold but we had to exclude six cases in order to remove outliers and due to missing data . WIDER IMPLICATION S OF THE FINDINGS Long-term follow-up of children born after embryo biopsy , in this case for PGD , is needed to confirm that the development of these children remains comparable to ICSI and SC children . Our findings do support the safety of the PGD technique and will reassure patients with hereditary genetic diseases regarding the health of their future offspring conceived with PGD . STUDY FUNDING /COMPETING INTERESTS Funding for this study was obtained from the OZR ( Research group of the Vrije Universiteit Brussel ) , the FWO ( Fonds Wetenschappelijk Onderzoek ) and the Wetenschappelijk Fonds Willy Gepts . The UZ Brussel and the Centre of Medical Genetics received funding from pharmaceutical firms for data collection . UZ Brussel and the Centre for Medical Genetics have received many educational grants for organizing the data collection , from IBSA , Ferring , Organon , Shering-Plough , Merck and Merck Belgium . M.B. has received consultancy and speaker 's fees from Organon , Serono Symposia and Merck", "OBJECTIVE To assess the neurodevelopmental health of children born after intracytoplasmatic sperm injection ( ICSI ) . DESIGN Prospect i ve controlled blinded study . SETTING Tertiary care center . PATIENT(S ) A total of 276 term-born singletons conceived by ICSI and 273 matched spontaneously conceived ( SC ) singletons at the age of 5.5 years . MAIN OUTCOME MEASURE(S ) Neuromotor development assessed by a detailed neurologic examination , including the st and ardized motor test MOT 4 - 6 , and emotional/behavioral development and intelligence assessed with the Kaufman- Assessment Battery for Children . RESULT ( S ) There were no significant differences between ICSI children and control children regarding the neurologic examination , motor skills , emotional/behavioral development , and intelligence . CONCLUSION ( S ) The ICSI children born at term develop normally , similar to SC children", "OBJECTIVE To assess the somatic , psychomotor , and intellectual development of children conceived through intracytoplasmic single sperm injection ( ICSI ) over the whole preschool period . DESIGN Prospect i ve , controlled , cohort study . SETTING Fertility clinic in Brussels , Belgium . PATIENT(S ) Sixty-six ICSI-conceived children prospect ively compared with 52 IVF-conceived and 59 spontaneously conceived children . All children were full-term singletons . INTERVENTION(S ) Home visits by a trained psychologist . St and ardized interviews . Assessment s using the revised Brunet-Lézine scale and the revised Wechsler preschool and primary scale of intelligence . MAIN OUTCOME MEASURE(S ) Physical growth and general health . Formal developmental and intellectual assessment s. RESULT ( S ) Children conceived by ICSI were healthy : no significant differences appeared in the incidence of combined congenital malformations ( 11.3 % ) , health problems ( 44.1 % ) , surgical interventions ( 18.6 % ) , and hospitalizations ( 6.8 % ) , nor for the developmental assessment s ( mean developmental quotient at 9 months : 93.9 ; at 18 months : 102.0 ) . For the intellectual assessment s , the between-group differences disappeared when adjusted for levels of parental education ( mean intelligence quotient at 3 years : 97.0 ; at 5 years : 103.3 ) . CONCLUSION ( S ) This pilot study shows that throughout the preschool period , ICSI-conceived children have psychomotor and intellectual development similar to that of IVF-conceived and spontaneously conceived children . These conclusions need to be confirmed by multicenter studies", "Objective To assess the mental health of children born after fertility treatment by comparing their risk of mental disorders with that of spontaneously conceived children . Design Prospect i ve register based cohort study . Setting Nationwide register based information from Danish National Health Registers cross linked by a unique personal identification number assigned to all citizens in Denmark . Participants All children born in Denmark in 1995 - 2003 with follow-up in 2012 when the children were aged 8 - 17 ; 33 139 children were conceived after fertility treatment and 555 828 children were born after spontaneous conception . Main outcome measures Absolute risks and hazard ratios for overall and specific mental disorders estimated with adjustment for potential confounding variables . Estimated association between the risk of mental disorders and subtypes of procedures , hormone treatments , gamete types , and cause of infertility . Results The risk of mental disorders in children born after in vitro fertilisation or intracytoplasmic sperm injection was low , and was no higher than in spontaneously conceived children , except for a borderline significant increased risk of tic disorders ( hazard ratio 1.40 , 95 % confidence interval 1.01 to 1.95 ; absolute risk 0.3 % ) . In contrast , children born after ovulation induction with or without insemination had low but significantly increased risks of any mental disorder ( 1.20 , 1.11 to 1.31 ; absolute risk 4.1 % ) , autism spectrum disorders ( 1.20 , 1.05 to 1.37 ; 1.5 % ) , hyperkinetic disorders ( 1.23 , 1.08 to 1.40 ; 1.7 % ) , conduct , emotional , or social disorder ( 1.21 , 1.02 to 1.45 ; 0.8 % ) , and tic disorders ( 1.51 , 1.16 to 1.96 ; 0.4 % ) . There was no risk systematic ally related to any specific type of hormone drug treatment . Conclusions There was a small increase in the incidence of mental disorders in children born after ovulation induction/intrauterine insemination . Children born after in vitro fertilisation/intracytoplasmic sperm injection were found to have overall risk comparable with children conceived spontaneously" ]

[ "BACKGROUND Outcome measurement following surgery is increasingly the focus of attention in current health-care debates because of the rising costs of medical care and the large variety of operative options . The purpose of the present study was to correlate quality of life after volar locked plate fixation of unstable intra-articular distal radial fractures with functional and radiographic results as well as with quality -of-life data from population norms . METHODS Fifty-four consecutive patients with intra-articular distal radial fractures and a mean age of sixty-three years were managed with a volar locked plate system . Range of motion , grip strength , and radiographs were assessed at a mean of six years postoperatively . The wrist-scoring systems of Gartl and and Werley and Castaing were adopted for the assessment of objective outcomes . The Disabilities of the Arm , Shoulder and H and and Short Form-36 question naires were completed as subjective outcome measures , and the results were compared with United States and Austrian population norms . RESULTS Functional improvement continued for two years postoperatively . At the time of the latest follow-up , > 90 % of all patients had achieved good or excellent results according to the scoring systems of Gartl and and Werley and Castaing . The results of the Short Form-36 question naire were similar to the United States and Austrian population norms . The mean Disabilities of the Arm , Shoulder and H and score was 5 points at two years , and it increased to 13 points at six years . The twenty patients with radiocarpal arthritis had significantly poorer results in the physical component summary measure of the Short Form-36 question naire ( p = 0.012 ) . CONCLUSIONS The results of the present single-center study show that , following distal radial fracture fixation , wrist arthritis may affect the patient 's subjective well-being , as documented with the Short Form-36 , without influencing the functional outcome . Well- design ed longitudinal clinical trials are needed to confirm the findings of the present investigation in terms of quality of life after surgical treatment of intra-articular distal radial fractures", "Background At present , there is no conclusive evidence regarding the best treatment method for reducible unstable fractures of the distal radius . This study compared the effectiveness of two methods used in surgical treatment of such fractures : percutaneous pinning and external fixation . Methods We r and omly allocated 100 patients into two groups treated surgically with modified De Palma percutaneous pinning and bridging external fixation . Independent but not blinded evaluators administered the DASH quality -of-life question naire at postoperative months 6 and 24 , performed functional assessment of pain , range of motion , and palm grip strength , and radiographic examinations ( volar and radial angle , and height of the radius ) before the operation , immediately afterwards , and at 6 and 24 months postoperative . Modified De Palma percutaneous pinning patients used an above-elbow cast whereas external fixation group had unrestricted elbow motion after surgery . Patients who for any reason demonstrated treatment failure or required additional interventions were followed up and their results were included in the group into which these patients had initially been r and omised according to the intention-to-treat principle . A significance level of 5 % ( alpha = 0.05 ) . was used for all statistical tests , such that tests presenting a p-value less than 0.05 were considered statistically significant . Results Ninety one ( 58.8 mean age and 66 participants were female ) were included in the final assessment at 24 months . The DASH question naire evaluation showed a statistically significant result favouring the De Palma group ( mean difference = -7.1 p = 0.044 ) after six months , but this was not maintained at 24 months . There were no statistically differences between the groups with respect to palm grip strength . Analysis of the range-of-motion limitation index ( uninjured side minus affected side motion of ) showed a statistical difference ( mean difference = 2.4 p = 0.043 ) favoring the external fixator group with regard to the supination movement 6 months after the operation ; however , this was not maintained at 24 months . The final results of the radiographic evaluation were similar for the two groups . Overall , five patients developed complications : two with De Palma pinning and three with external fixation . Conclusion There was a small statistically significant difference favouring the De Palma method in early functional at 6 months according to the DASH question naire , and for supination movement favouring the fixator group . However , both were not clinical relevant . By 24 months the groups were similar for all outcomes Trial registration Current Controlled Trials IS RCT", "The Patient Evaluation Measure ( PEM ) , The Michigan H and Outcome Question naire ( MHQ ) and the Disabilities of the Arm , Shoulder and H and ( DASH ) score were assessed independent of their originators for reliability , construct and criterion validity and acceptability , using an ease of use question naire . These were administered in r and om order to 100 patients with different h and and wrist disorders and with different impairments of movement , pain , sensation and strength . The internal consistency of all three question naires was very high suggesting redundancy in the questions . All question naires were reproducible and valid for finger and wrist disorders , but less for nerve disorders . All had poor construct validity . The PEM was the easiest to underst and and complete , taking the least time . Correlation between the scales is high and conversion equations were calculated . All three are reliable and reproducible patient completed question naires , but the PEM is the easiest to use . The validity of all is suspected for nerve disorders", "We performed a prospect i ve , r and omised trial to evaluate the outcome after surgery of displaced , unstable fractures of the distal radius . A total of 280 consecutive patients were enrolled in a prospect i ve data base and 88 identified who met the inclusion criteria for surgery . They were r and omised to receive either bridging external fixation with supplementary Kirschner-wire fixation or volar-locked plating with screws . Both groups were similar in terms of age , gender , h and dominance , fracture pattern , socio-economic status and medical co-morbidities . Although the patients treated by volar plating had a statistically significant early improvement in the range of movement of the wrist , this advantage diminished with time and in absolute terms the difference in range of movement was clinical ly unimportant . Radiologically , there were no clinical ly significant differences in the reductions , although more patients with AO/OTA ( Orthopaedic Trauma Association ) type C fractures were allocated to the external fixation group . The function at one year was similar in the two groups . No clear advantage could be demonstrated with either treatment but fewer re-operations were required in the external fixation group", "Background . This paper aim ed to identify condition-specific patient-reported outcome measures used in clinical trials among people with wrist osteoarthritis and summarise empirical peer- review ed evidence supporting their reliability , validity , and responsiveness to change . Methods . A systematic review of r and omised controlled trials among people with wrist osteoarthritis was undertaken . Studies reporting reliability , validity , or responsiveness were identified using a systematic reverse citation trail audit procedure . Psychometric properties of the instruments were examined against predefined criteria and summarised . Results . Thirteen clinical trials met inclusion criteria . The most common patient-reported outcome was the disabilities of the arm , shoulder , and h and question naire ( DASH ) . The DASH , the Michigan H and Outcomes Question naire ( MHQ ) , the Patient Evaluation Measure ( PEM ) , and the Patient-Reported Wrist Evaluation ( PRWE ) had evidence supporting their reliability , validity , and responsiveness . A post-hoc review of excluded studies revealed the AUSCAN Osteoarthritis H and Index as another suitable instrument that had favourable reliability , validity , and responsiveness . Conclusions . The DASH , MHQ , and AUSCAN Osteoarthritis H and Index instruments were supported by the most favourable empirical evidence for validity , reliability , and responsiveness . The PEM and PRWE also had favourable empirical evidence reported for these elements . Further psychometric testing of these instruments among people with wrist osteoarthritis is warranted", "Background and purpose Promising results have been reported after volar locked plating of unstable dorsally displaced distal radius fractures . We investigated whether volar locked plating results in better patient-perceived , objective functional and radiographic outcomes compared to the less invasive external fixation . Patients and methods 63 patients under 70 years of age , with an unstable extra-articular or non-comminuted intra-articular dorsally displaced distal radius fracture , were r and omized to volar locked plating ( n = 33 ) or bridging external fixation . Patient-perceived outcome was assessed with the Disability of the Arm , Shoulder , and H and ( DASH ) question naire and the Patient-Rated Wrist Evaluation ( PRWE ) question naire . Results At 3 and 6 months , the volar plate group had better DASH and PRWE scores but at 12 months the scores were similar . Objective function , measured as grip strength and range of movement , was superior in the volar plate group but the differences diminished and were small at 12 months . Axial length and volar tilt were retained slightly better in the volar plate group . Interpretation Volar plate fixation is more advantageous than external fixation , in the early rehabilitation period", "Background and purpose In unstable distal radial fractures that are impossible to reduce or to maintain in reduced position , the treatment of choice is operation . The type of operation and the choice of implant , however , is a matter of discussion . Our aim was to investigate whether open reduction and internal fixation would produce a better result than traditional external fixation . Methods 50 patients with an unstable or comminute distal radius fracture were r and omized to either closed reduction and bridging external fixation , or open reduction and internal fixation using the TriMed system . The primary outcome parameter was grip strength , but the patients were followed for 1 year with objective clinical assessment , subjective outcome using DASH , and radiographic examination . Results At 1 year postoperatively , grip strength was 90 % ( SD 16 ) of the uninjured side in the internal fixation group and 78 % ( 17 ) in the external fixation group . Pronation/supination was 150 ° ( 15 ) in the internal fixation group and 136 ° ( 20 ) in the external fixation group at 1 year . There were no differences in DASH scores or in radiographic parameters . 5 patients in the external fixation group were reoperated due to malunion , as compared to 1 in the internal fixation group . 7 other cases were classified as radiographic malunion : 5 in the external fixation group and 2 in the internal fixation group . Interpretation Internal fixation gave better grip strength and a better range of motion at 1 year , and tended to have less malunions than external fixation . No difference could be found regarding subjective outcome ", "In a r and omised prospect i ve study , 20 patients with intra-articular fractures of the distal radius underwent arthroscopically- and fluoroscopically-assisted reduction and external fixation plus percutaneous pinning . Another group of 20 patients with the same fracture characteristics underwent fluoroscopically-assisted reduction alone and external fixation plus percutaneous pinning . The patients were evaluated clinical ly and radiologically at follow-up of 24 months . The Disabilities of the Arm , Shoulder , and H and ( DASH ) question naire and modified Mayo wrist score were used at 3 , 9 , 12 and 24 months postoperatively . In the arthroscopically- and fluoroscopically-assisted group , triangular fibrocartilage complex tears were found in 12 patients ( 60 % ) , complete or incomplete scapholunate ligament tears in nine ( 45 % ) , and lunotriquetral ligament tears in four ( 20 % ) . They were treated either arthroscopically or by open operation . Patients who underwent arthroscopically- and fluoroscopically-assisted treatment had significantly better supination , extension and flexion at all time points than those who had fluoroscopically-assisted surgery . The mean DASH scores were similar for both groups at 24 months , whereas the difference in the mean modified Mayo wrist scores remained statistically significant . Although the groups are small , it is clear that the addition of arthroscopy to the fluoroscopically-assisted treatment of intra-articular distal radius fractures improves the outcome . Better treatment of associated intra-articular injuries might also have been a reason for the improved outcome", "Background The ulnar styloid is a supportive structure for the capsular ligament complex of the distal radioulnar joint . The relation between fractures of the ulna and distal radius is not clear , especially in regard to whether ulnar fractures predict worse outcomes for distal radius fractures . The objective of this study was to analyze the influence of ulnar styloid fractures in patients with reducible and unstable distal radius fractures . Methods A total of 100 patients with unstable and reducible distal radius fractures , with or without an ulnar styloid fracture , were r and omly assigned to treatment with transarticular bridging external fixation or transulnar percutaneous pinning . Follow-up was obtained for 91 patients . For the secondary data analysis , three patient cohorts were created : a no ulnar styloid fracture group with the radius fracture treated by pinning or external fixation ( n = 30 ) ; an ulnar styloid fracture with radius fracture group treated by external fixation ( n = 31 ) ; and an ulnar styloid fracture with radius fracture treated by pinning ( n = 30 ) . Functional and radiological outcomes were measured at 6 and 24 months . Functional outcome measures included wrist pain ( visual analogue scale ) and the Disabilities of the Arm , Shoulder , and H and ( DASH ) question naire . Results At 24 months , patients with both fractures had worse wrist pain and worse scores on the DASH question naire than the patients with an isolated distal radius fracture ; and those treated by pinning had less wrist pain and showed better scores on the DASH question naire than the patients treated by fixation . Conclusions Ulnar styloid fracture may be a predictive factor of worse functional outcome for distal radius fracture . Pinning and above-the-elbow casting , used to treat ulnar styloid fractures , led to better function than fixation", "Objective The purpose of this study was to evaluate the early results of patients with displaced and unstable distal radius fractures treated with fragment-specific fixation . Design Prospect i ve and consecutive . Setting Private orthopaedic practice . Patients / Participants Twenty-five patients with 27 fractures with an average follow-up of 29 months ( range 24–36 months ) treated with fragment-specific fixation for unstable radius fractures . Main Outcome Measurements Clinical and radiographic examination . Disabilities of the arm , h and , and shoulder and patient-rated wrist evaluation outcome measures . Results Patients had an average 61 ° of dorsiflexion and 54 ° of palmarflexion at the wrist . Twenty-five fractures healed in acceptable alignment , with one loss of reduction and one patient death . Mean ± st and ard deviation DASH score was 17 ± 18 , and PRWE score was 19 ± 22 . Conclusion Unstable distal radius fractures can be reliably and anatomically reduced and stabilized using fragment-specific fixation . Fixation of markedly comminuted fractures is secure enough to allow immediate motion and does not require casting or external fixation . Preliminary clinical and radiographic results are excellent , and patient satisfaction is high . Anatomic reduction with early motion can be achieved in a routine fashion on unstable distal radius fractures using the described technique", "Abstract Purpose : To investigate the effects of mirror therapy ( MT ) in restoring h and function in patients with active range of motion ( AROM ) impairments following orthopaedic injuries . Method : In a r and omized controlled trial ( RCT ) , 30 patients with active ROM impairment ( 8 men and 22 women ; mean age : 38 years ) were measured . Intervention group received MT , 30 min a day , five days a week for three weeks , as well , half an hour conventional rehabilitation after each MT session . Patients in the control group received the same treatment programme , but instead of mirror , they observed directly the affected h and . In addition , both groups performed a 15 min home programme , including MT for intervention group and AROM with direct observation of the affected h and for control group , twice daily . Outcome measures , including total active motion ( TAM ) and Disabilities of Arm , Shoulder and H and ( DASH ) question naire , were administered pre- and post-treatment and three weeks later . This study was registered as an RCT , no. NCT01503762 in http:// clinical trials.gov/. Results : Final analysis was performed on 23 patients . The mean ( SD ) changes at post-test from baseline TAM was 154 ( 32 ) in the MT ( N = 12 ) and 61 ( 24 ) in the control group ( N = 11 ) ; mean difference ( 95 % CI ) 93 ( 68–118 ) , p = 0.001 . The mean ( SD ) change at post-test from baseline DASH was −34 ( 7 ) in the MT ( N = 12 ) and −15 ( 11 ) in the control group ( N = 11 ) ; mean difference ( 95 % CI ) 19 ( −27 to −11 ) , p = 0.001 . Conclusions : Despite significant improvement at post-test in both groups and maintenance of improvement during the follow-up period , MT combined with conventional rehabilitation produced more improvement in h and function than control group . Implication s for Rehabilitation H and orthopaedic injuries can result in disabilities in activities of daily living . Mirror therapy ( MT ) provides perception of two healthy limbs through reflection of the healthy limb as the injured limb . In a r and omized controlled trial , our study shows positive effects of MT combined with a classical rehabilitation programme to improve h and function in patients with orthopaedic injuries", "BACKGROUND Currently screw fixation of the scaphoid is a well-established method to treat unstable scaphoid fractures . PATIENTS AND METHODS Between June 1995 and December 2000 , 68 patients with an unstable acute scaphoid fracture were treated with screw fixation ; 46 patients were reexamined on an average 35 months postoperatively . Range of motion and grip strength ( Jamar dynamometer ) were measured . The total data rating result ed from the Krimmer wrist score . RESULTS The subjective results were evaluated with the DASH question naire . The average postoperative pain score was documented with a visual analogous pain scale from zero to 100 ( VAS 0 - 100 ) . X-rays as well as computed tomography were performed postoperatively . The average range of motion was 124 degrees for extension/flexion ( 92 % of the opposite site ) , 57 degrees for radial/ulnarduction ( = 90 % ) , and 177 degrees for pronation/supination ( = 98 % ) . Postoperative strength was 47 kg ( = 90 % of the opposite site ) . The postoperative pain score was 13 ( 0 - 100 ) after stress and 2 during resting conditions . Bony consolidation was reached in 44 cases . The Krimmer wrist score demonstrated a very good result in 39 cases , a good result in 5 cases , and a satisfactory result in 3 cases . The average DASH score was 8.3 points . CONCLUSIONS The results demonstrate the reliability of internal screw fixation as treatment for acute scaphoid fractures . Functional results as well as subjective satisfaction of the patients are very good . Postoperative CT scans help to evaluate exact bony consolidation , position of the screw , and postoperative morphology of the scaphoid", "OBJECTIVE To evaluate the effects of cross-education ( contralateral effect of unilateral strength training ) during recovery from unilateral distal radius fractures on muscle strength , range of motion ( ROM ) , and function . DESIGN R and omized controlled trial ( 26-wk follow-up ) . SETTING Hospital , orthopedic fracture clinic . PARTICIPANTS Women older than 50 years with a unilateral distal radius fracture . Fifty-one participants were r and omized and 39 participants were included in the final data analysis . INTERVENTIONS Participants were r and omized to st and ard rehabilitation ( Control ) or st and ard rehabilitation plus strength training ( Train ) . St and ard rehabilitation included forearm casting for 40.4±6.2 days and h and exercises for the fractured extremity . Nonfractured h and strength training for the training group began immediately postfracture and was conducted at home 3 times/week for 26 weeks . MAIN OUTCOME MEASURES The primary outcome measure was peak force ( h and grip dynamometer ) . Secondary outcomes were ROM ( flexion/extension ; supination/pronation ) via goniometer and the Patient Rated Wrist Evaluation question naire score for the fractured arm . RESULTS For the fractured h and , the training group ( 17.3±7.4 kg ) was significantly stronger than the control group ( 11.8±5.8 kg ) at 12 weeks postfracture ( P no significant strength differences between the training and control groups at 9 ( 12.5±8.2 kg ; 11.3±6.9 kg ) or 26 weeks ( 23.0±7.6 kg ; 19.6±5.5 kg ) postfracture , respectively . Fractured h and ROM showed that the training group had significantly improved wrist flexion/extension ( 100.5 ° ±19.2 ° ) than the control group ( 80.2 ° ±18.7 ° ) at 12 weeks postfracture ( P for flexion/extension ROM at 9 ( 78.0 ° ±20.7 ° ; 81.7 ° ±25.7 ° ) or 26 weeks ( 104.4 ° ±15.5 ° ; 106.0 ° ±26.5 ° ) or supination/pronation ROM at 9 ( 153.9 ° ±23.9 ° ; 151.8 ° ±33.0 ° ) , 12 ( 170.9 ° ±9.3 ° ; 156.7 ° ±20.8 ° ) or 26 weeks ( 169.4 ° ±11.9 ° ; 162.8 ° ±18.1 ° ) , respectively . There were no significant differences in Patient Rated Wrist Evaluation question naire scores between the training and control groups at 9 ( 54.2±39.0 ; 65.2±28.9 ) , 12 ( 36.4±37.2 ; 46.2±35.3 ) , or 26 weeks ( 23.6±25.6 ; 19.4±16.5 ) , respectively . CONCLUSIONS Strength training for the nonfractured limb after a distal radius fracture was associated with improved strength and ROM in the fractured limb at 12 weeks postfracture . These results have important implication s for rehabilitation strategies after unilateral injuries ", "Background Non-bridging external fixation has been introduced to achieve better fracture fixation and functional outcomes in distal radius fractures , but has not been specifically evaluated in a r and omized study in the elderly . The purpose of this trial was to compare wrist-bridging and non-bridging external fixation for displaced distal radius fractures . Method The inclusion criteria were women ≥ 50 or men ≥ 60 years , acute extraarticular or intraarticular fracture , and dorsal angulation of ≥20 ° or ulnar variance ≥ 5 mm . The patients completed the disabilities of the arm , shoulder and h and ( DASH ) question naire before and at 10 , 26 and 52 weeks after surgery . Pain ( visual analog scale ) , range of motion and grip strength were measured by a blinded assessor . Results 38 patients ( mean age 71 years , 31 women ) were r and omized at surgery ( 19 to each group ) . Mean operating time was shorter for wrist-bridging fixation by 10 ( 95 % CI 3–17 ) min . There was no significant difference in DASH scores between the groups . No statistically significant differences in pain score , range of motion , grip strength , or patient satisfaction were found . The non-bridging group had a significantly better radial length at 52 weeks ; mean difference in change in ulnar variance from baseline was 1.4 ( 95 % CI 0.1–2.7 ) mm ( p = 0.04 ) . Volar tilt and radial inclination were similar in both groups . Interpretation For moderately or severely displaced distal radius fractures in the elderly , non-bridging external fixation had no clinical ly relevant advantage over wrist-bridging fixation but was more effective in maintaining radial length", "PURPOSE OF THE STUDY Fractures of the distal radius are common . No one implant has demonstrated superior efficacy in terms of maintaining the reduction over time . We report our experience with plate fixation using a locking screw . MATERIAL AND METHODS Between September 2003 and June 2004 , 67 displaced fractures of the distal radius were treated by plate fixation using the LCP-DRP 2.4 ( Synthès ) . Three different plates ( anterior , posterior , and external ) were used . The patients wore a removable anatomic brace for three weeks . Self-controlled rehabilitation exercises began directly after surgery with mobilization of the digital chains . The Fern and ez , Castaing and AO classifications were noted . Ulnar variance , anteversion of the radial glenoid , radial slope and the alpha angle were measured intraoperatively and at last follow-up to assess maintenance of reduction over time . The DASH test and Green and O'Brien and PRWE scores were used to assess clinical outcome . RESULTS Mean follow-up was eight months . Mean age was 55.8 years . Eight patients were lost to follow-up . The analysis included 59 patients who could respond to the question naires . Bone healing was achieved at six weeks . There were no cases of secondary displacement nor loss of reduction . The Green and O'Brien score was good or very good for 85 % . The mean DASH was 20.6 and the mean PRWE 32.8 . DISCUSSION The appropriate fixation method for distal fractures of the radius remains a controversial issue , leading to a variety of material s and fixation methods . Primary stability achieved with the locking screw in a plate enables early mobilization associated with more rapid recovery of function . The absence of secondary displacement , irrespective of the quality of the underlying bone enabled us to achieve equivalent results in young patients and older patients with osteoporotic bone . This study also confirmed the preference for the anterior approach , irrespective of the direction of the displacement . To date , no other material has enabled equivalent results . This is a major achievement in terms of fixation stability", "BACKGROUND The purpose of the present study was to investigate the influence of the radiological parameters on the functional outcome of patients with a fracture of the distal radius and to find out to which extent a deformity can be tolerated . PATIENTS AND METHODS A total of 344 patients with an isolated fracture of the distal radius were treated during a 3-year period ; 211 of them were evaluated at an average of 16 months after the accident according to the score of Gartl and and Werley as modified by Sarmiento . Furthermore , we developed our own score for evaluating the influence of radiological parameters on the functional outcome . RESULTS According to the AO classification , there were 20 patients with an A2 , 71 an A3 , 11 a B , 35 a C1 , 44 a C2 , and 30 a C3 fracture . Of 211 patients , 28 ( 13 % ) had a step-off in the articular surface of over 1 mm , result ing in a 24 % reduction of the range of motion compared to the non-injured wrist ( p reduction of pro- and supination compared to the non-injured side ( p radial tilt and the palmar inclination did not have a direct influence on the functional outcome . Patients treated with K-wire pinning and with an initial palmar inclination of less then -15 degrees had a significantly higher secondary loss of palmar inclination of 9 degrees compared to all others ( p<0.05 ) at the final follow-up . CONCLUSION The main radiological factors influencing the functional outcome of fractures of the distal radius are radial shortening and a step-off in the articular surface", "Background : There are many plating systems available for treating distal radius fractures , and deciding which to use can be difficult . This prospect i ve cohort study compared outcomes of two commonly used fixation systems : fragment-specific fixation and a fixed-angle volar locking plate system . Methods : Consecutive distal radius fractures were prospect ively evaluated in a fragment-specific fixation cohort and a volar locking plate system cohort . Radiographic , functional , and patient-rated outcomes were collected immediately postoperatively and at 6 and 12 months postoperatively . Complications were recorded and grade d by severity . Results : Fourteen distal radius fractures treated with fragment-specific fixation and 85 treated with the volar locking plate system were enrolled . Radial inclination was similar in both cohorts ( 23 degrees versus 25 degrees ) ; however , volar tilt was worse in the fragment-specific fixation cohort ( −10 degrees versus 10 degrees , p loss of relative radial length . Grip strength , pinch strength , Michigan H and Outcomes Question naire scores , and most range of motion measurements were superior in the volar locking plate system cohort at 6 months , although not all differences were statistically significant . By 12 months the differences in functional and patient-rated outcomes were smaller , suggesting that the fragment-specific fixation cohort tended to reach the outcomes of the volar locking plate system cohort over time . Complications requiring reoperation were higher in the fragment-specific fixation cohort ( p volar locking plate system results in more stable fixation and better objective and subjective outcomes early in the postoperative period . It has fewer complications requiring reoperation than fragment-specific fixation", "Abstract This is a r and omised study to compare two types of osteo synthesis to mobilise wrists after distal fractures of the radius . Inclusion criteria were Older type 2 and 3 fractures . External fixation was managed with Hoffmann II compact non-bridging . Internal fixation was managed with Micronail . Patients were followed up for 12 weeks . The primary outcome was the results of the disabilities of arm , shoulder and h and ( DASH ) question naire . The secondary outcomes were answers to the patient-rated wrist evaluation ( PRWE ) , grip strength , satisfaction , radial length , and volar tilt . Thirty patients were r and omised to have external fixation and 31 to have internal fixation . There were no significant differences in DASH score . Internal fixation gave significantly better grip strength at five ( p = 0.00 ) and 12 weeks ( p = 0.03 ) . The operating time was significantly shorter ( p = 0.00 ) when non-bridging external fixation was used , and there were minor radiological differences . An activity-based costing analysis showed that external fixation cost three times more overall", "Background : Minimally angulated fractures of the distal radius are common in children and have excellent outcomes . We conducted a r and omized controlled trial to determine whether the use of a prefabricated splint is as effective as a cast in the recovery of physical function . Methods : We included 96 children 5 to 12 years of age who were treated for a minimally angulated ( ≤ 15 ° ) greenstick or transverse fracture of the wrist between April 2007 and September 2009 at a tertiary care pediatric hospital . Participants were r and omly assigned to receive either a prefabricated wrist splint or a short arm cast for four weeks . The primary outcome was physical function at six weeks , measured using the performance version of the Activities Scale for Kids . Additional outcomes included the degree of angulation , range of motion , grip strength and complications . Results : Of the 96 children , 46 received a splint and 50 a cast . The mean Activities Scale for Kids score at six weeks was 92.8 in the splint group and 91.4 in the cast group ( difference 1.44 , 95 % confidence interval [ CI ] −1.75 to 4.62 ) . Thus , the None hypothesis that the splint is less effective by at least seven points was rejected . The between-group difference in angulation at four weeks was not statistically significant ( 9.85 ° in the splint group and 8.20 ° in the cast group ; mean difference 1.65 ° , 95 % CI −1.82 ° to 5.11 ° ) , nor was the between-group differences in range of motion , grip strength and complications . Interpretation : In children with minimally angulated fractures of the distal radius , use of a splint was as effective as a cast with respect to the recovery of physical function . In addition , the devices were comparable in terms of the maintenance of fracture stability and the occurrence of complications . ( Clinical Trials.gov trial register no. NCT00610220 .", "BACKGROUND A prospect i ve , r and omized multicenter study was conducted to evaluate closed reduction and immobilization with and without Norian SRS ( Skeletal Repair System ) cement in the management of distal radial fractures . Norian SRS is a calcium-phosphate bone cement that is injectable , hardens in situ , and cures by a crystallization reaction to form dahllite , a carbonated apatite equivalent to bone mineral . METHODS A total of 323 patients with a distal radial fracture were r and omized to treatment with or without Norian SRS cement . Stratification factors included fracture type ( intra-articular or extra-articular ) , h and dominance , bone density , and the surgeon 's preferred conventional treatment ( cast or external fixator ) . The subjects receiving Norian SRS underwent a closed reduction followed by injection of the cement percutaneously or through a limited open approach . Wrist motion , beginning two weeks postoperatively , was encouraged . Control subjects , who had not received a Norian SRS injection , underwent closed reduction and application of a cast or external fixator for six to eight weeks . Supplemental Kirschner wires were used in specific instances in both groups . Patients were followed clinical ly and radiographically at one , two , four , and between six and eight weeks and at three , six , and twelve months . Patients rated pain and the function of the h and with use of a visual analog scale . Quality of life was assessed with use of the Short Form-36 ( SF-36 ) health status question naire . Complications were recorded . RESULTS Significant clinical differences were seen at six to eight weeks postoperatively , with better grip strength , wrist range of motion , digital motion , use of the h and , and social and emotional function , and less swelling in the patients treated with Norian SRS than in the control group ( p Norian SRS ( p = 0.015 ) . At one year , no clinical differences were detected . Radiographically , the average change in ulnar variance was greater in the patients treated with Norian SRS ( + 2.0 mm ) than in the control group ( + 1.4 mm ) ( p total number of complications , including loss of reduction . The infection rate , however , was significantly higher ( p Norian SRS ( 2.5 % ) and the infections were always related to external fixator pins or Kirschner wires . Four patients with intra-articular extravasation of cement were identified ; no sequelae were observed at twenty-four months . Cement was seen in extraosseous locations in 112 ( 70 % ) of the SRS-treated patients ; loss of reduction was highest in this subgroup ( 37 % ) . The extraosseous material had disappeared in eighty-three of the 112 patients by twelve months . CONCLUSIONS Our results indicate that fixation of a distal radial fracture with Norian SRS cement may allow for accelerated rehabilitation . A limited open approach and supplemental fixation with Kirschner wires are recommended . Additional or alternate fixation is necessary for complex articular fractures", "Objectives : To compare final functional and radiographic outcomes of closed reduction and casting ( CAST ) with open reduction and internal fixation ( ORIF ) with palmar locking plate for unstable Colles type distal radius fractures ( DRFs ) in low-dem and patients older than 70 years . Design : Retrospective , clinical study . Setting : Level 1 university trauma center . Patients : Over a mean period of 4 years and 7 months , 130 consecutive patients older than 70 years were treated for an unstable dorsally displaced DRF of which 114 or 87 % were followed for 1 year or longer . Intervention : ORIF ( n = 53 ) using volar locking plate or closed reduction and casting ( n = 61 ) . Main Outcome Measurements : Objective and subjective functional results ( active range of motion ; grip strength ; disabilities of the arm , shoulder and h and ( DASH ) score ; patient-rated wrist evaluation ( PRWE ) score ; visual analog scale ; and Green and O'Brien score ) and radiographic assessment ( dorsal tilt , radial inclination , radial shortening , fracture union , and posttraumatic arthritis ) were assessed . Results : At final follow-up , there was no significant difference between the 2 groups for mean ranges of motion , grip strength , DASH score , PRWE score , and Green and O'Brien score . Pain level was significantly less for the patients in the CAST group . An obvious clinical deformity was present in 77 % of cast group and none in the ORIF group . At final follow-up , in the ORIF group , there was a mean loss of dorsal tilt of 1.3 degrees , radial inclination of 0.3 degrees , and radial length of 0.5 mm compared with the postoperative measurements . No primary acceptable reduction was achieved in 44 % of the CAST group . At final follow-up , in the CAST group , dorsal tilt , radial inclination , and radial shortening averaged −24.4 ± 12 degrees , 19.2 ± 6.5 degrees , and + 3.9 ± 2.7 mm , respectively . Malunion occurred in 89 % primarily reduced fractures . Dorsal tilt , radial inclination , and radial shortening were significantly better in the ORIF group . Conclusions : Radiographic results ( dorsal tilt , radial inclination , and radial shortening ) after unstable dorsally displaced DRFs are significantly better in patients treated by ORIF using a volar fixed-angle plate rather than those treated by cast immobilization ( P of active range of motion , the PRWE , DASH , and Green and O'Brien scores do not differ between the 2 methods of treatment . The pain level was significantly less in the CAST group ( P subjective and functional outcomes for the surgical and the nonsurgical treatments in a cohort of patients older than 70 years . Unsatisfactory radiographic outcome in older patients does not necessarily translate into unsatisfactory functional outcome . Nonoperative treatment may be the preferred method of treatment in this age group", " Sixty-six adult patients with minimally displaced distal radial fractures were r and omly assigned to treatment with either a plaster cast or a lightweight removable wrist splint . Outcome assessment was by clinical and radiological evaluation and an independent physiotherapy assessment . There were significant differences between the treatments for cast satisfaction , cast problems and the functional assessment score at 6 weeks , with the removable splint scoring better in all cases", "Introduction : Physiotherapy is considered by some authorities to be an important aspect of management in patients following distal radius fractures . There is evidence of improvement in impairment with physiotherapy ; however , there is no evidence to support early return of functional activity . Traditional physiotherapy management has focussed on improving impairment ; however , there are no trials with emphasis on skill acquisition via motor re-learning principles . Material s and methods : Forty-one participants with conservatively managed distal radius fractures were studied in a r and omised , single-blinded , prospect i ve trial . Two treatment options were compared : exercise and advice versus activity-focussed physiotherapy with measurement periods of 6 weeks after removal of cast and follow-up at 24 weeks . Results : Participants allocated to the exercise and advice group consulted a physiotherapist an average of 0.9 ( SD 0.4 ) times , while the participants allocated to the more intensive activity-focussed group consulted with physiotherapy a mean of 4.4 ( SD 2.3 ) times . At both 6 and 24 weeks there were no significant differences between the groups for change in impairment ( as measured by grip strength , range of motion of wrist flexion and extension and pain intensity ) , activity limitation and participation restriction , as measured by the Patient-Rated Wrist Evaluation ( PRWE ) . Exercise and advice given by a physiotherapist were equally as effective as activity-focussed physiotherapy in recovery both at 6 and 24 weeks . Conclusion : The results suggest that after removal of cast from fracture of distal radius , patients may routinely require no more than a single session of advice and exercise provided by a physiotherapist", "We evaluated the responsiveness of patient question naires and physical testing in the assessment of recovery after distal radius fracture . Patients ( n = 59 ) were assessed at their baseline clinic visit and again 3 and 6 months after injury . At each visit patients completed a short form-36 , Disability of the Arm , Shoulder , and H and question naire , and patient-rated wrist evaluation ( PRWE ) . At 3 and 6 months grip strength , range of motion , and dexterity were analyzed . St and ardized response means ( SRM ) and effects sizes were calculated to indicate responsiveness . The PRWE was the most responsive . Both the PRWE ( SRM = 2.27 ) and the Disability of the Arm , Shoulder , and H and ( SRM = 2.01 ) question naire were more responsive than the short form-36 ( SRM = 0.92 ) . The physical component summary score of the short form-36 was similar to that of the physical component subscales . Question naires were highly responsive during the 0- to 3-month time period when physical testing could not be performed . Of the physical tests , grip strength was most responsive , followed by range of motion . Responsive patient-rating scales and physical performance evaluations can assist with outcome evaluation of patients with distal radius fracture" ]

[ "BACKGROUND While physical therapy is an effective element in the rehabilitation of rotator cuff ( RC ) disease , the most effective sequence of exercise training interventions has not been defined . HYPOTHESIS/ PURPOSE The purpose of this study is to determine if there is a difference in pain or function in patients who are given RC strengthening prior to or after initiating scapular stabilization exercises . STUDY DESIGN Level I r and omized crossover trial . METHODS This was a prospect i ve study of 26 men and 14 women with a mean age 51 who were diagnosed with subacromial impingement syndrome ( SAIS ) . They were r and omly assigned to one of two groups for a comprehensive and st and ardized rehabilitation program over six visits at an orthopedic outpatient clinic . One group was prescribed a 4-week program of scapular stabilization exercises while the other group began with RC strengthening exercises . The crossover design had each group add the previously excluded four exercises to their second month of rehabilitation . RESULTS The results showed significant improvements in pain ( p function ( p patient satisfaction ( p pain or function at any follow-up period for initiating one group of exercise before the other ( p > 0.05 ) . There was a statistically significant interaction between the patient 's global rating of change at the 4 week follow-up as compared to 8 weeks ( p = 0.04 ) or 16 ( p CONCLUSION Patients with SAIS demonstrate improvement in pain and function with a st and ardized program of physical therapy regardless of group exercise sequencing . LEVEL OF EVIDENCE 1b", "Background and purpose A programme based on eccentric exercises for treating subacromial pain was in a previous study found effective at 3-month follow-up . The purpose s of the present study were to investigate whether the results were maintained after 1 year and whether the baseline Constant-Murley score , rotator cuff status and radiological findings influenced the outcome . Patients and methods 97 patients on the waiting list for arthroscopic subacromial decompression had been r and omised to a specific exercise programme or unspecific exercises ( controls ) . After 3 months of exercises , the patients were asked whether they still wanted surgery and this option was available until a 1-year follow-up . 1 year after inclusion or 1 year after surgery , the number of patients who decided to have surgery in each group was compared . The choice of surgery was related to the baseline Constant-Murley score , ultrasound and radiographs taken at inclusion . Results All patients had improved significantly ( p Constant-Murley score at the 1-year follow-up . Significantly more patients in the control group decided to have surgery ( 63 % ) than those in the specific exercise group ( 24 % ; p lower baseline Constant-Murley score and more often a full-thickness tear . Patients with partial tears did not differ from those with intact tendons . Interpretation The positive short-term results of specific exercises were maintained after 1 year , and this exercise strategy reduces the need for surgery . Full-thickness tear and a low baseline Constant-Murley score appear to be a predictive marker for a less good outcome . Trial registration number Clinical trials NCT01037673", "STUDY DESIGN A prospect i ve r and omized clinical trial . OBJECTIVE To compare the effectiveness of 2 physical therapy treatment approaches for impingement syndrome of the shoulder . BACKGROUND Manual physical therapy combined with exercise is a commonly applied but currently unproven clinical treatment for impingement syndrome of the shoulder . METHODS AND MEASURES Thirty men and 22 women ( age 43 years + /- 9.1 ) diagnosed with shoulder impingement syndrome were r and omly assigned to 1 of 2 treatment groups . The exercise group performed supervised flexibility and strengthening exercises . The manual therapy group performed the same program and received manual physical therapy treatment . Both groups received the selected intervention 6 times over a 3-week period . The testers , who were blinded to group assignment , measured strength , pain , and function before treatment and after 6 physical therapy visits . Strength was a composite score of isometric strength tests for internal rotation , external rotation , and abduction . Pain was a composite score of visual analog scale measures during resisted break tests , active abduction , and functional activities . Function was measured with a functional assessment question naire . The visual analog scale used to measure pain with functional activities and the functional assessment question naire were also measured 2 months after the initiation of treatment . RESULTS Subjects in both groups experienced significant decreases in pain and increases in function , but there was significantly more improvement in the manual therapy group compared to the exercise group . For example , pain in the manual therapy group was reduced from a pretreatment mean ( + /- SD ) of 575.8 ( + /- 220.0 ) to a posttreatment mean of 174.4 ( + /- 183.1 ) . In contrast , pain in the exercise group was reduced from a pretreatment mean of 557.1 ( + /- 237.2 ) to a posttreatment mean of 360.6 ( + /- 272.3 ) . Strength in the manual therapy group improved significantly while strength in the exercise group did not . CONCLUSION Manual physical therapy applied by experienced physical therapists combined with supervised exercise in a brief clinical trial is better than exercise alone for increasing strength , decreasing pain , and improving function in patients with shoulder impingement syndrome", "Objectives : To compare the long term effectiveness of local steroid injections administered by general practitioners with practice based physiotherapy for treating patients presenting in primary care with new episodes of unilateral shoulder pain . Methods : Adults consulting with shoulder pain were recruited by their general practitioner . Patients were r and omly allocated to receive either corticosteroid injections or community based physiotherapy . Primary outcome was self reported disability from shoulder problems at six months . Secondary outcomes included participant ’s global assessment of change ; pain ; function ; “ main complaint ” ; range of shoulder movement ; co- interventions . A study nurse unaware of the treatment allocation performed baseline and follow up assessment s. Analysis was by intention to treat . Results : Over 22 months 207 participants were r and omised , 103 to physiotherapy and 104 to injection . Prognostic variables were similar between the two groups at baseline . Mean ( SD ) improvements in disability scores at six weeks were 2.56 ( 5.4 ) for physiotherapy and 3.03 ( 6.3 ) for injection ( mean difference=−0.5 , 95 % confidence interval ( 95 % CI ) : −2.1 to 1.2 ) and at six months were 5.97 ( 5.4 ) for physiotherapy and 4.55 ( 5.9 ) for injection ( mean difference=1.4 , 95 % CI −0.2 to 3.0 ) . A “ successful outcome ” ( a minimum 50 % drop in the disability score from baseline ) at six months was achieved by 59/99 ( 60 % ) in the physiotherapy group and 51/97 ( 53 % ) in the injection group ( percentage difference=7 % , 95 % CI −6.8 % to 20.4 % ) . Co- interventions were more common in the injection group during follow up . Conclusion : Community physiotherapy and local steroid injections were of similar effectiveness for treating new episodes of unilateral shoulder pain in primary care , but those receiving physiotherapy had fewer co- interventions", "Objective The objective of this study was to evaluate the effectiveness of proprioceptive exercises on shoulder proprioception , range of motion , pain , muscle strength , and function in patients with subacromial impingement syndrome . Design Sixty-one patients with subacromial impingement syndrome participated in this prospect i ve , single-blind r and omized controlled trial . All patients were r and omly divided into two groups : control group ( conventional physiotherapy , n = 30 ) and intervention group ( proprioceptive exercise and conventional physiotherapy , n = 31 ) . The primary outcome measures were sense of kinesthesia and active and passive repositioning for proprioception at 0 degrees and 10 degrees external rotation at 12 wks . The secondary outcome measures were pain at rest , at night , and during activities of daily living with the visual analog scale ( 0–10 cm ) , the Western Ontario Rotator Cuff index , the American Shoulder and Elbow Surgeons index , range of motion , and isometric muscle strength at both 6 and 12 wks . Results After treatment , significant improvement was found in range of motion , pain , isometric muscle strength , kinesthesia at 0 degrees external rotation , and functional tests in both groups . The intervention group showed a significant improvement in kinesthesia at 10 degrees external rotation and active and passive repositioning at 10 degrees external rotation . When groups were compared , there were no statistically significant differences in any of the parameters at 12 wks . Conclusions Although proprioceptive exercises may provide better proprioceptive acuity , no additional positive effect on other clinical parameters was observed", "Generalized shoulder pain is a common problem that is difficult to treat and frequently recurrent . The asymptomatic cervical spine must be ruled out as a cause of any shoulder pain , as it can have a similar presentation to an isolated shoulder disorder . Previous studies have shown that lateral cervical glide mobilizations to the asymptomatic cervical spine at C5/6 can affect peripheral pain , but none have examined shoulder pain . A r and omized , blinded , placebo-controlled , cross-over trial was used to examine the immediate effects of cervical lateral glide mobilizations on pain intensity and shoulder abduction painful arc in subjects with shoulder pain . Twenty-one subjects received interventions of both cervical mobilization and placebo over two sessions . Pain intensity using a visual analog scale ( VAS ) and painful arc were assessed prior to and following application of cervical mobilization or placebo intervention . Evaluation of cervical mobilization revealed the shoulder abduction painful arc ( 12.5 degrees + /-15.6 degrees , p=0.002 ) and shoulder pain intensity ( 1.3+/-1.1 cm , p shoulder pain or active shoulder range of motion following cervical mobilizations indicate that treatment directed toward the asymptomatic cervical spine may expedite recovery", "Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials", "Objectives : To conduct a feasibility study to compare concentric and eccentric rotator cuff strengthening exercises for rotator cuff tendinopathy . Methods : A total of 11 patients with rotator cuff tendinopathy who were on the waiting list for arthroscopic subacromial decompression surgery were r and omised to perform eccentric rotator cuff strengthening exercises , concentric strengthening exercises or no exercises . Patients were evaluated in terms of levels of pain and function using the Oxford Shoulder Score and a Visual Analogue Scale initially , at 4 weeks and at 8 weeks . Results : The study design was found to be acceptable to patients and achieved a high level of 86 % compliance . The drop-out rate was 0 % . Two patients performing eccentric strengthening exercises improved sufficiently to cancel their planned surgery . Conclusion : Further research in this area is recommended . The study design was feasible and power calculations have been conducted to aid future research planning", "OBJECTIVES : Conflicting results were reported about the effectiveness of Low level laser therapy on musculoskeletal disorders . The aim of this study was to investigate the effectiveness of 850‐nm gallium arsenide aluminum ( Ga‐As‐Al ) laser therapy on pain , range of motion and disability in subacromial impingement syndrome . METHODS : A total of 52 patients ( 33 females and 19 males with a mean age of 53.59±11.34 years ) with subacromial impingement syndrome were included . The patients were r and omly assigned into two groups . Group I ( n = 30 , laser group ) received laser therapy ( 5 joule/cm2 at each point over maximum 5‐6 painful points for 1 minute ) . Group II ( n = 22 , placebo laser group ) received placebo laser therapy . Initially cold pack ( 10 minutes ) was applied to all of the patients . Also patients were given an exercise program including range of motion , stretching and progressive resistive exercises . The therapy program was applied 5 times a week for 14 sessions . Pain severity was assessed by using visual analogue scale . Range of motion was measured by goniometer . Disability was evaluated by using Shoulder Pain and Disability Index . RESULTS : In group I , statistically significant improvements in pain severity , range of motion except internal and external rotation and SPADI scores were observed compared to baseline scores after the therapy ( p except range of motion of external rotation were improved ( p0.05 ) . CONCLUSIONS : The Low level laser therapy seems to have no superiority over placebo laser therapy in reducing pain severity , range of motion and functional disability", "Background : Repetitive or sustained elevated shoulder postures have been identified as a significant risk factor for occupationally related shoulder musculoskeletal disorders . Construction workers exposed to routine overhead work have high rates of shoulder pain that frequently progresses to functional loss and disability . Exercise interventions have potential for slowing this progression . Aims : To evaluate a therapeutic exercise programme intended to reduce pain and improve shoulder function . Methods : Construction worker volunteers were screened by history and clinical examination to test for inclusion /exclusion criteria consistent with shoulder pain and impingement syndrome . Sixty seven male symptomatic workers ( mean age 49 ) were r and omised into a treatment intervention group ( n = 34 ) and a control group ( n = 33 ) ; asymptomatic subjects ( n = 25 ) participated as an additional control group . Subjects in the intervention group were instructed in a st and ardised eight week home exercise programme of five shoulder stretching and strengthening exercises . Subjects in the control groups received no intervention . Subjects returned after 8–12 weeks for follow up testing . Results : The intervention group showed significantly greater improvements in the Shoulder Rating Question naire ( SRQ ) score and shoulder satisfaction score than the control groups . Average post-test SRQ scores for the exercise group remained below levels for asymptomatic workers . Intervention subjects also reported significantly greater reductions in pain and disability than controls . Conclusions : Results suggest a home exercise programme can be effective in reducing symptoms and improving function in construction workers with shoulder pain", "Objective To investigate the efficacy of a programme of manual therapy and exercise treatment compared with placebo treatment delivered by physiotherapists for people with chronic rotator cuff disease . Design R and omised , participant and single assessor blinded , placebo controlled trial . Setting Metropolitan region of Melbourne , Victoria , Australia . Participants 120 participants with chronic ( > 3 months ) rotator cuff disease recruited through medical practitioners and from the community . Interventions The active treatment comprised a manual therapy and home exercise programme ; the placebo treatment comprised inactive ultrasound therapy and application of an inert gel . Participants in both groups received 10 sessions of individual st and ardised treatment over 10 weeks . For the following 12 weeks , the active group continued the home exercise programme and the placebo group received no treatment . Main outcome measures The primary outcomes were pain and function measured by the shoulder pain and disability index , average pain on movement measured on an 11 point numerical rating scale , and participants ’ perceived global rating of overall change . Results 112 ( 93 % ) participants completed the 22 week trial . At 11 weeks no difference was found between groups for change in shoulder pain and disability index ( 3.6 , 95 % confidence interval −2.1 to 9.4 ) or change in pain ( 0.7 , −0.1 to 1.5 ) ; both groups showed significant improvements . More participants in the active group reported a successful outcome ( defined as “ much better ” ) , although the difference was not statistically significant : 42 % ( 24/57 ) of active participants and 30 % ( 18/61 ) of placebo participants ( relative risk 1.43 , 0.87 to 2.34 ) . The active group showed a significantly greater improvement in shoulder pain and disability index than did the placebo group at 22 weeks ( between group difference 7.1 , 0.3 to 13.9 ) , although no significant difference existed between groups for change in pain ( 0.9 , −0.03 to 1.7 ) or for the percentage of participants reporting a successful treatment outcome ( relative risk 1.39 , 0.94 to 2.03 ) . Several secondary outcomes favoured the active group , including shoulder pain and disability index function score , muscle strength , interference with activity , and quality of life . Conclusion A st and ardised programme of manual therapy and home exercise did not confer additional immediate benefits for pain and function compared with a realistic placebo treatment that controlled for therapists ’ contact in middle aged to older adults with chronic rotator cuff disease . However , greater improvements were apparent at follow-up , particularly in shoulder function and strength , suggesting that benefits with active treatment take longer to manifest . Trial registration Clinical trials NCT00415441", "Abstract Fifty patients with impingement syndrome refractory to long-term conservative treatment were r and omized to three treatment groups . All patients received an injection of 10 ml 0.5 % bupivacaine , in group 1 without corticosteroid , in group 2 with crystalline corticosteroid and in group 3 with lipoid corticosteroid . Treatment in group 1 had to be stopped because of inefficacy . In groups 2 and 3 favorable results were achieved in 19 out of 40 patients .Résumé 50 patients avec conflit sous-aeromial , qui ne montraient pas d’amélioration après un long trâitement conservatif récevaient une injection dans la bourse subacromiale . Le premier groupe récevait une injection contenant un anaesthétique local pur , groupe 2 une mixture d’anaesthétique avec des corticostéroides cristalins et groupe 3 avec des corticostéroides lipoides . Le trâitement du groupe 1 devait être arrété cause d’inificacité . 19 de 40 patients du groupe 2 et 3 montraient une amélioration après 6 mois", "OBJECTIVE The aim of this study was to determine the effectiveness of Kinesio taping ( KT ) application added to the exercise treatment of subacromial impingement syndrome ( SIS ) . METHODS Thirty-eight ( 25 female , 13 male ) patients with SIS were r and omly divided into therapeutic KT ( n=19 ) and sham KT ( n=19 ) groups . All patients received the same exercise therapy in addition to therapeutic or sham KT at 3-day intervals for 12 days . The groups were compared according to pain , range of motion ( ROM ) , muscle strength and DASH and Constant scores before treatment and at the 5th and 12th treatment days . RESULTS Within group comparisons showed significant improvements in both groups at the 5th and 12th day evaluations ( p pain with movement and DASH scores in the therapeutic group were significantly lower at the 5th day ( p night pain , pain with movement , DASH score , shoulder external rotation muscle strength , and pain free shoulder abduction ROM in the therapeutic group at the 12th day ( p Passive shoulder flexion ROM increased more in the sham group at the 12th day ( p addition of KT application to the exercise program appears to be more effective than the exercise program alone for the treatment of SIS", "Summary Background Arthroscopic sub-acromial decompression ( decompressing the sub-acromial space by removing bone spurs and soft tissue arthroscopically ) is a common surgery for subacromial shoulder pain , but its effectiveness is uncertain . We did a study to assess its effectiveness and to investigate the mechanism for surgical decompression . Methods We did a multicentre , r and omised , pragmatic , parallel group , placebo-controlled , three-group trial at 32 hospitals in the UK with 51 surgeons . Participants were patients who had subacromial pain for at least 3 months with intact rotator cuff tendons , were eligible for arthroscopic surgery , and had previously completed a non-operative management programme that included exercise therapy and at least one steroid injection . Exclusion criteria included a full-thickness torn rotator cuff . We r and omly assigned participants ( 1:1:1 ) to arthroscopic subacromial decompression , investigational arthroscopy only , or no treatment ( attendance of one re assessment appointment with a specialist shoulder clinician 3 months after study entry , but no intervention ) . Arthroscopy only was a placebo as the essential surgical element ( bone and soft tissue removal ) was omitted . We did the r and omisation with a computer-generated minimisation system . In the surgical intervention groups , patients were not told which type of surgery they were receiving ( to ensure masking ) . Patients were followed up at 6 months and 1 year after r and omisation ; surgeons coordinated their waiting lists to schedule surgeries as close as possible to r and omisation . The primary outcome was the Oxford Shoulder Score ( 0 [ worst ] to 48 [ best ] ) at 6 months , analysed by intention to treat . The sample size calculation was based upon a target difference of 4·5 points ( SD 9·0 ) . This trial has been registered at Clinical Trials.gov , number NCT01623011 . Findings Between Sept 14 , 2012 , and June 16 , 2015 , we r and omly assigned 313 patients to treatment groups ( 106 to decompression surgery , 103 to arthroscopy only , and 104 to no treatment ) . 24 [ 23 % ] , 43 [ 42 % ] , and 12 [ 12 % ] of the decompression , arthroscopy only , and no treatment groups , respectively , did not receive their assigned treatment by 6 months . At 6 months , data for the Oxford Shoulder Score were available for 90 patients assigned to decompression , 94 to arthroscopy , and 90 to no treatment . Mean Oxford Shoulder Score did not differ between the two surgical groups at 6 months ( decompression mean 32·7 points [ SD 11·6 ] vs arthroscopy mean 34·2 points [ 9·2 ] ; mean difference −1·3 points ( 95 % CI −3·9 to 1·3 , p=0·3141 ) . Both surgical groups showed a small benefit over no treatment ( mean 29·4 points [ SD 11·9 ] , mean difference vs decompression 2·8 points [ 95 % CI 0·5–5·2 ] , p=0·0186 ; mean difference vs arthroscopy 4·2 [ 1·8–6·6 ] , p=0·0014 ) but these differences were not clinical ly important . There were six study -related complications that were all frozen shoulders ( in two patients in each group ) . Interpretation Surgical groups had better outcomes for shoulder pain and function compared with no treatment but this difference was not clinical ly important . Additionally , surgical decompression appeared to offer no extra benefit over arthroscopy only . The difference between the surgical groups and no treatment might be the result of , for instance , a placebo effect or postoperative physiotherapy . The findings question the value of this operation for these indications , and this should be communicated to patients during the shared treatment decision-making process . Funding Arthritis Research UK , the National Institute for Health Research Biomedical Research Centre , and the Royal College of Surgeons ( Engl and )", "Background Subacromial pain syndrome ( SAPS ) accounts for around 50 % of all cases of shoulder pain . The most commonly used treatments are glucocorticosteroid ( steroid ) injections and exercise therapy ; however , despite treatment SAPS patients often experience relapse of their symptoms . Therefore the clinical effect of combining steroid and exercise therapy is highly relevant to clarify . The aim of this r and omized controlled trial was to investigate if exercise therapy added to steroid injection in patients with SAPS will improve the effect of the injection therapy on shoulder pain . Methods In this two-arm r and omized trial running over 26 weeks , patients with unilateral shoulder pain ( > 4 weeks ) and thickened subacromial bursa ( > 2 mm on US ) were included . At baseline all participants received two steroid injections into the painful shoulder with an interval of one week . Subsequently they were r and omized ( 1:1 ) to either 10 weeks exercise of the involved shoulder ( intervention group ) or exercise of the uninvolved shoulder ( control group ) . The patients were re-examined after the exercise program ( at week 13 ) and again at week 26 . The primary outcome assessed after 26 weeks was change in shoulder pain analyzed using the intention-to-treat principle ( non-responder imputation ) . Results Ninety-nine SAPS patients ( 58 female ) participated ( 49 intervention/50 control ) . At both follow up visits ( week 13 and 26 ) no statistically significant between-group differences in pain changes on a visual analog scale ( mm ) were seen ( 13 weeks : pain at rest 1.7 ( 95 % CI –3.6 to 7.0 ; P = 0.53 ) ; pain in activity 2.2 ( 95 % CI –6.5 to 10.9 ; P = 0.61 ) , 26 weeks : rest 5.6 ( 95 % CI –0.9 to 12.1 ; P = 0.09 ) ; activity 2.2 ( 95 % CI –6.8 to 11.2 ; P = 0.62 ) . The reduction in pain was most evident in the control group at all four pain measurements . The only difference between groups was seen by US examination at week 13 , where fewer participants with impingement were observed in the intervention group compared with the controls ( 9 vs. 19 participants ; P = 0.03 ) . Conclusion Exercise therapy in the painful shoulder in SAPS patients did not improve the effectiveness of steroid injections for shoulder pain in patients with unilateral SAPS and enlarged subacromial bursa on US examination . Trial registration Clinical Trials.gov ( NCT01506804 ) . Registration date 5 May 2011", "OBJECTIVES To investigate the effect of manual physiotherapy and exercises compared with exercises alone in patients with shoulder impingement syndrome one year after inclusion . DESIGN R and omized controlled trial . SUBJECTS Patients with shoulder impingement of more than 4 weeks . METHODS The intervention group received individualized manual physiotherapy plus individualized exercises ; the control group received individualized exercises only . Both groups had 10 treatments over 5 weeks ; afterwards all patients continued their exercises for another 7 weeks at home . Primary outcomes were the Shoulder Pain and Disability Index and Patients ' Global Impression of Change . The Generic Patient-Specific Scale was used as secondary outcome . Costs were recorded in a log-book . RESULTS Ninety patients were included in the study and 87 could be analyzed at 1-year follow-up . Both groups showed significant improvements in all outcome measures , but no difference was detected between the groups . Only costs differed significantly in favour of the control group ( p = 0.03 ) after 5 weeks . CONCLUSION Individualized exercises result ed in lower costs than manual physiotherapy and showed a significant effect on pain and functioning within the whole group after one year . Exercises should therefore be considered as a basic treatment . Due to the progressive improvement that occurred during the follow-up period with individualized exercises further treatments should be delayed for 3 to 4 months", "Objective To evaluate if a specific exercise strategy , targeting the rotator cuff and scapula stabilisers , improves shoulder function and pain more than unspecific exercises in patients with subacromial impingement syndrome , thereby decreasing the need for arthroscopic subacromial decompression . Design R and omised , participant and single assessor blinded , controlled study . Setting Department of orthopaedics in a Swedish university hospital . Participants 102 patients with long st and ing ( over six months ) persistent subacromial impingement syndrome in whom earlier conservative treatment had failed , recruited through orthopaedic specialists . Interventions The specific exercise strategy consisted of strengthening eccentric exercises for the rotator cuff and concentric/eccentric exercises for the scapula stabilisers in combination with manual mobilisation . The control exercise programme consisted of unspecific movement exercises for the neck and shoulder . Patients in both groups received five to six individual guided treatment sessions during 12 weeks . In between these supervised sessions the participants performed home exercises once or twice a day for 12 weeks . Main outcome measures The primary outcome was the Constant-Murley shoulder assessment score evaluating shoulder function and pain . Secondary outcomes were patients ’ global impression of change because of treatment and decision regarding surgery . Results Most ( 97 , 95 % ) participants completed the 12 week study . There was a significantly greater improvement in the Constant-Murley score in the specific exercise group than in the control exercise group ( 24 points ( 95 % confidence interval 19 to 28.0 ) v 9 points ( 5 to 13 ) ; mean difference between group : 15 points ( 8.5 to 20.6 ) ) . Significantly more patients in the specific exercise group reported successful outcome ( defined as large improvement or recovered ) in the patients ’ global assessment of change because of treatment : 69 % ( 35/51 ) v 24 % ( 11/46 ) ; odds ratio 7.6 , 3.1 to 18.9 ; P specific exercise group subsequently chose to undergo surgery : 20 % ( 10/51 ) v 63 % ( 29/46 ) ; odds ratio 7.7 , 3.1 to 19.4 ; P specific exercise strategy , focusing on strengthening eccentric exercises for the rotator cuff and concentric/eccentric exercises for the scapula stabilisers , is effective in reducing pain and improving shoulder function in patients with persistent subacromial impingement syndrome . By extension , this exercise strategy reduces the need for arthroscopic subacromial decompression within the three month timeframe used in the study . Trial registration Clinical trials", "Subacromial impingement syndrome ( SAIS ) is a major contributing factor of shoulder pain ; and treatment approaches ( Kinesio ® taping [ KT ] , Exercise [ EX ] , manual therapy [ MT ] , and high-intensity laser therapy [ HILT ] ) have been developed to treat the pain . The key objective of this study was to compare the effects of KT , MT , and HILT on the pain , the range of motion ( ROM ) , and the functioning in patients with SAIS . Seventy patients with SAIS were r and omly divided into four groups based on the treatment(s ) each group received [ EX ( n = 15 ) , KT + EX ( n = 20 ) , MT + KT + EX ( n = 16 ) , and MT + KT + HILT + EX ( n = 19 ) ] . All the patients were assessed before and at the end of the treatment ( 15th day ) . The main outcome assessment s included the evaluation of severity of pain by visual analogue scale ( VAS ) and shoulder flexion , abduction , and external rotation ROM measurements by a universal goniometry . Shoulder pain and disability index ( SPADI ) was used to measure pain and disability associated with shoulder pathology . Statistically significant differences were found in the treatment results of all parameters in MT + KT + EX and HILT + MT + KT + EX groups ( p means of ROM and SPADI results of three groups were compared , statistically significant differences were found between all the groups ( p groups MT + KT + EX and KT + EX ( p and HILT + MT + KT + EX and KT + EX ( p 0.05 ) . HILT and MT were found to be more effective in minimizing pain and disability and increasing ROM in patients with SAIS . Further studies with follow-up periods are required to determine the advantages of these treatments conclusively", "OBJECTIVE To evaluate the effects of pulsed electromagnetic field ( PEMF ) and exercises in reducing pain and improving function and muscle strength in patients with shoulder impingement syndrome ( SIS ) . DESIGN Double-blind , r and omized controlled trial with a 3-month posttreatment follow-up . SETTING Outpatient rehabilitation of a public hospital . PARTICIPANTS Patients ( N=56 ) between 40 and 60 years of age , with a diagnosis of SIS , were r and omly assigned to receive active PEMF ( n=26 ; mean age , 50.1y ) or placebo PEMF ( n=30 ; mean age , 50.8y ) . INTERVENTIONS After 3 weeks of active or placebo PEMF , both groups performed the same program of exercises that focused on shoulder strengthening . MAIN OUTCOME MEASURES A visual analog scale , the University of California/Los Angeles shoulder rating scale , the Constant-Murley shoulder score , and h and held dynamometry for muscle strength were used as outcome measures at baseline ( pretreatment ) , at 3 weeks ( after active or placebo PEMF ) , at 9 weeks ( postexercise ) , and at 3 months posttreatment . RESULTS Patients in the active PEMF group had a higher level of function and less pain at all follow-up time frames compared with baseline ( P PEMF group had increased function and reduced pain only at the 9-week and 3-month follow-ups (P shoulder dynamometry , the active PEMF group had increased strength for lateral rotation at 9 weeks ( P increased strength for medial rotation at 9 weeks and 3 months ( both P shoulder strength in the placebo PEMF group ( P>.05 ) , as well as no significant differences ( P>.05 ) for all outcome measures . CONCLUSIONS The combination of PEMF and shoulder exercises is effective in improving function and muscle strength and decreasing pain in patients with SIS . However , these results should be carefully interpreted because of the lack of differences between groups", "BACKGROUND AND PURPOSE Exercise therapy is a commonly used conservative therapy for long-term subacromial pain . However , there is no consensus regarding what type of exercises and dosage is most effective . The aim of this study was to compare the effect of two exercise programmes : 1 ) high-dosage ( HD ) medical exercise therapy versus 2 ) low-dosage ( LD ) exercise therapy programme for subjects with long-term subacromial pain . METHODS This study used a r and omized , controlled clinical trial with an intention-to-treat analysis . Sixty-one subjects were r and omly assigned by concealment either to an HD medical exercise therapy group ( n = 31 ) or to an LD exercise therapy group ( n = 30 ) . Pain ( visual analogue scale [ VAS ] ) and function ( Shoulder Rating Question naire [ SRQ ] ) were measured at inclusion , at end of treatment and at 6 and 12 months follow-up . RESULTS There were no differences between groups at inclusion ( baseline ) regarding any variables . During the three months treatment period , five subjects ( 8 % ) dropped out , and another seven ( 11 % ) dropped out at one-year follow-up . At the end of treatment , both pain and function had improved significantly in favour of the HD therapy , between-group differences in VAS were -2.7 ( -3.9 to 0.9 ) , and for activity limitations , the between-group differences in the SRQ increased by 24.5 points ( 14.5 - 35.7 ) . The differences between groups were both statistically and clinical ly significant at 6 and 12 months follow-up . CONCLUSION In subjects with long-term subacromial pain syndrome , HD medical exercise therapy is superior to a conventional LD exercise programme . For clinicians to obtain similar positive results with HD medical exercise therapy , factors such as good communication skills , constant close personal supervision during exercise treatment and having from three to five subjects in a group setting are important", "Context The shoulder impingement syndrome includes conditions , such as rotator cuff tendinosis and shoulder bursitis . Conservative management may include corticosteroid injections ( CSIs ) or manual physical therapy ( MPT ) . Contribution In this r and omized , controlled trial , groups of patients with the shoulder impingement syndrome receiving CSI or MPT showed similar symptom improvements that did not differ significantly . Compared with the MPT group , the CSI group used more health care re sources during the 1-year follow-up . Caution The trial recruited only patients referred to MPT . Implication Manual physical therapy and CSI produced similar clinical outcomes in patients with the shoulder impingement syndrome . The Editors The shoulder impingement syndrome ( SIS ) is a generic term used for patients with shoulder pain that encompasses the rotator cuff syndrome , tendinosis of the rotator cuff muscles , and bursitis in the shoulder area ( 1 ) . It has a cumulative incidence between 5 and 30 per 1000 person-years ( 2 , 3 ) . Conservative treatment options include corticosteroid injections ( CSIs ) and physical therapy . Subacromial CSI is one of the most common procedures used by orthopedists , rheumatologists , and general practitioners ( 4 , 5 ) . However , evidence to support long-term efficacy is conflicting ( 610 ) . Clinical practice guidelines can not recommend for or against CSI for rotator cuff pathology without evidence of tears ( 11 ) . Four recent systematic review s have differing conclusions on the efficacy of CSI for SIS ( 6 , 8 , 9 , 12 ) , but the consensus suggests that any benefit may only be short-term . Although manual physical therapy ( MPT ) may be effective for SIS management ( 1321 ) , 2 recent systematic review s found no clear evidence to suggest additional benefits of MPT to other interventions ( 22 , 23 ) , indicating the need for further research . Data are also lacking about the patterns and timing of CSI and MPT use for patients with SIS . Studies suggest that a CSI is often considered initially ( 4 , 5 ) , whereas a referral to physical therapy may occur only 24 % of the time ( 24 ) . Other studies introduced CSI only after 6 weeks of physical therapy was unsuccessful ( 5 ) . Some investigations evaluated the effect of providing CSI before , or in conjunction with , MPT or shoulder exercises ( 14 , 25 , 26 ) , but CSI and MPT have not been directly compared . The objective of this study was to compare the 1-year effectiveness of CSI and MPT for SIS management . Methods Design Overview This pragmatic , r and omized , controlled trial compared 2 treatments for patients with SIS : subacromial CSI and MPT . The primary end point was 1-year improvement on the Shoulder Pain and Disability Index ( SPADI ) . Secondary outcomes included changes in Global Rating of Change ( GRC ) scale and Numeric Pain Rating Scale ( NPRS ) scores and shoulder-related health care use . We followed the SPIRIT ( St and ard Protocol Items : Recommendations for Interventional Trials ) statement at the time of protocol development ( 27 ) , and our reporting followed the CONSORT ( Consoli date d St and ards of Reporting Trials ) extension for pragmatic clinical trials ( 28 ) . The study was approved by the Madigan Army Medical Center Institutional Review Board , the trial was registered ( Clinical Trials.gov : NCT01190891 ) , and the protocol was published with open access ( 29 ) . Setting and Participants Consecutive patients aged 18 to 65 years with a primary symptom of unilateral shoulder pain referred from family practice and orthopedic clinics to the physical therapy department at Madigan Army Medical Center were screened for eligibility during their initial visit in the physical therapy clinic . Exclusion criteria included a history of shoulder dislocation , fracture , or adhesive capsulitis ; history of CSI or physical therapy for the shoulder pain in the past 3 months ; baseline SPADI score less than 20 % ; reproduction of shoulder symptoms with cervical spine examination ; history of systemic or neurologic disease affecting the shoulder ; positive rotator cuff lag sign or history of full-thickness rotator cuff tear ; pending litigation ; or inability to attend physical therapy for 3 consecutive weeks . Patients at this medical center included a mix of active-duty and retired military service members and their families . Copayments were not required for care . R and omization and Interventions The r and omization schedule was computer-generated , with assignments placed in opaque , sequentially numbered envelopes by an off-site investigator not involved with patient care or follow-up . Treatment allocation was revealed after collection of baseline outcomes . Patients and treating clinicians were not blind to the intervention . The research assistant who collected outcome assessment s at each time point was blind to group assignment . Two physical therapists provided the MPT , and 1 physician administered all of the injections . Patients were allowed to continue any current medications prescribed by their primary care providers ( PCPs ) . MPT Group At the first session , the physical therapists performed a st and ardized clinical examination to identify relevant impairments ( weakness , mobility , or pain ) . The MPT intervention consisted of a combination of joint and soft-tissue mobilizations ; manual stretches ; contractrelax techniques ; and reinforcing exercises directed to the shoulder girdle or thoracic or cervical spine . Specific details of the treatment are published ( 29 ) . Patients did not receive identical treatments , but the MPT techniques were matched to individual impairments identified on examination . Patients were treated twice weekly over a 3-week period , a typical episode of care for SIS , by the same physical therapy in most cases . Home exercises were prescribed to reinforce clinic interventions ( 29 ) . The physical therapists were fellowship-trained in MPT from an American Physical Therapy Associationcredentialed program . CSI Group A credentialed family practice physician with sports medicine fellowship training injected 40 mg of triamcinolone acetonide to the subacromial space of the symptomatic shoulder ( 29 ) . Each participant received a h and out explaining the effects of the steroid injection and how to manage potential side effects . As many as 3 total injections could be administered by the study physician ( > 1 month apart ) during the 1-year period . Patients received printed instructions to perform a gentle gravity-assisted distraction and oscillatory pendulum exercise . Patients were discouraged , but not prohibited , from seeking additional care for at least the first month ( study -related treatment period ) . At the 1- , 3- , and 6-month follow-up periods , patients were also given written instructions and a number to call if they believed that they were not improving and needed additional care . A study coordinator , who was not involved with data collection or treatment , fielded these calls . She advised patients in the MPT group to return to their PCP for additional care and facilitated contact with the physician providing the injection for patients in the CSI group . Each case was managed individually , and another CSI was administered if the patient and physician mutually agreed that it was appropriate . Patients in either group could return to their PCP if they felt the need , and the PCP would manage the patient as they thought best , potentially including a CSI or referral to physical therapy . These patients would not see the same physical therapist or physician who administered the initial study intervention . Outcomes and Follow-up Outcome measurements were administered at baseline , 1 month , 3 months , 6 months , and 1 year . The SPADI is a 100-point , 13-item , self-administered question naire that is divided into 2 subscales : a 5-item pain subscale and an 8-item disability subscale . It is valid , is responsive to change , and accurately discriminates between improving and worsening status ( 30 , 31 ) . The minimal clinical ly important difference for the SPADI is a change between 8 and 13 points ( 6 % to 10 % ) ( 32 ) . The GRC is an instrument that measures overall perceived changes in the participant 's quality of life ( 33 ) . It provides a valid measurement of change in patients ' perceived status ( 34 ) . A GRC score of 3 rating points or greater is clinical ly meaningful ( 35 ) . An 11-point NPRS ranging from 0 ( no pain ) to 10 ( worst imaginable pain ) was used to assess pain intensity ( 36 ) . This scale has been demonstrated to be a reliable , generalizable , and internally consistent measure of clinical and experimental pain intensity ( 37 , 38 ) . The suggested minimal clinical ly important difference for the NPRS is a change of 2 points ( 39 ) . A research assistant blinded to treatment allocation collected health care use information from electronic health records at the 1-year follow-up using an established process ( 40 , 41 ) . This included additional use after completion of the study interventions . We identified shoulder-related visits to physical therapists , PCPs , rheumatologists , and orthopedists , as well as frequency and types of procedures , including additional steroid injections , magnetic resonance imaging , and radiography , similar to other studies ( 42 ) . A second clinician manually verified the electronic health record information to ensure that the care was related to the same shoulder condition . Statistical Analysis The sample size estimated to achieve 80 % power to detect a 12-point difference ( or a 9.2 % change ) in the SPADI , based on a reported minimal clinical ly important difference range of 8 to 13 points ( 32 ) , with an SD of 10 points , a 2-tailed test , and an level of 0.05 was 43 participants per group . To allow for a conservative withdrawal rate of approximately 20 % , we recruited 104 participants . The primary analyses of effectiveness included all available data from patients who received their assigned treatment ( that is , the CSI or at least 1 session of MPT ) . We used a linear mixed-effects model , which is flexible in accommodating data assumed to be missing at", "STUDY DESIGN Single-blind r and omized trial . OBJECTIVES To compare the effects of cervical and shoulder thrust manipulation ( TM ) and exercise on pain sensitivity , and to explore associations with clinical outcomes in patients with shoulder pain . BACKGROUND Experimental studies indicate that spinal TM has an influence on central pain processes , supporting its application for treatment of extremity conditions . Direct comparison of spinal and peripheral TM on pain sensitivity has not been widely examined . METHODS Seventy-eight participants with shoulder pain ( 36 female ; mean ± SD age , 39.0 ± 14.5 years ) were r and omized to receive 3 treatments of cervical TM ( n = 26 ) , shoulder TM ( n = 27 ) , or shoulder exercise ( n = 25 ) over 2 weeks . Twenty-five healthy participants ( 13 female ; mean ± SD age , 35.2 ± 11.1 years ) were assessed to compare pain sensitivity with that in clinical participants at baseline . Primary outcomes were changes in local ( eg , shoulder ) and remote ( eg , tibialis anterior ) pressure pain threshold and heat pain threshold occurring over 2 weeks . Secondary outcomes were shoulder pain intensity and patient-rated function at 4 , 8 , and 12 weeks . Analysis -of-variance models and partial-correlation analyses were conducted to examine comparative effects and the relationship between measures . RESULTS At baseline , clinical participants demonstrated lower local ( mean difference , - 1.63 kg ; 95 % confidence interval [ CI ] : -2.40 , -0.86 ) and remote pressure pain threshold ( mean difference , -1.96 kg ; 95 % CI : -3.09 , -0.82 ) and heat pain threshold ( mean difference , -1.15 ° C ; 95 % CI : -2.06 , -0.24 ) compared to controls , suggesting enhanced pain sensitivity . Following intervention , there were no between-group differences in pain sensitivity or clinical outcome ( P>.05 ) . However , improvements were noted , regardless of intervention , for pressure pain threshold ( range of mean differences , 0.22 - 0.32 kg ; 95 % CI : 0.03 , 0.43 ) , heat pain threshold ( range of mean differences , 0.30 - 0.58 ; 95 % CI : 0.06 , 0.96 ) , pain intensity ( range of mean differences , -1.79 to -1.45 ; 95 % CI : -2.34 , -0.94 ) , and function ( range of mean differences , 3.15 - 3.82 ; 95 % CI : 0.69 , 6.20 ) at all time points . We did not find an association between pain sensitivity changes and clinical outcome ( P>.05 ) . Conclusion Clinical participants showed enhanced pain sensitivity , but did not respond differently to cervical or peripheral TM . In fact , in this sample , cervical TM , shoulder TM , and shoulder exercise had similar pain sensitivity and clinical effects . The lack of association between pain sensitivity and clinical pain and function outcomes suggests different ( eg , nonspecific ) pain pathways for clinical benefit following TM or exercise . LEVEL OF EVIDENCE Therapy , level 1b", "Aim : To test the hypothesis that work related mechanical and psychosocial factors predict new onset shoulder pain in newly employed workers . Methods : Two year prospect i ve study of newly employed workers from 12 diverse occupational setting s. At baseline , 1081 subjects provided information on work related mechanical and psychosocial risk factors , and current pain status . Results : In all , 803 ( 74 % ) subjects were free from shoulder pain at baseline . Of those , 638 ( 79 % ) responded at 12 months and 476 ( 88 % ) at 24 months . New onset shoulder pain was reported by 93 ( 15 % ) and 73 ( 15 % ) subjects respectively . An increased risk of symptom onset was found in subjects reporting mechanical exposures involving heavy weights including lifting with one or two h and s , carrying on one shoulder , lifting at or above shoulder level , and pushing or pulling . Working with h and s above shoulder level was also predictive of new onset shoulder pain . Of the psychosocial factors examined , the strongest predictor was monotonous work . Those individuals with any other previous pain also had an increased risk of new onset shoulder pain at follow up . In multivariate analysis , lifting heavy weights with one or two h and s , pushing or pulling heavy weights , working with h and s above shoulder level , and monotonous work were independently associated with new onset shoulder pain . Conclusions : This study supports the hypothesised relation between mechanical risk factors and shoulder pain . In general , work related psychosocial factors were modestly associated with new onset shoulder pain . However , monotonous work was a strong risk factor for new onset shoulder pain", "STUDY DESIGN Prospect i ve , r and omized , double-blinded , clinical trial using a repeated- measures design . OBJECTIVES To determine the short-term clinical efficacy of Kinesio Tape ( KT ) when applied to college students with shoulder pain , as compared to a sham tape application . BACKGROUND Tape is commonly used as an adjunct for treatment and prevention of musculoskeletal injuries . A majority of tape applications that are reported in the literature involve nonstretch tape . The KT method has gained significant popularity in recent years , but there is a paucity of evidence on its use . METHODS AND MEASURES Forty-two subjects clinical ly diagnosed with rotator cuff tendonitis/impingement were r and omly assigned to 1 of 2 groups : therapeutic KT group or sham KT group . Subjects wore the tape for 2 consecutive 3-day intervals . Self-reported pain and disability and pain-free active ranges of motion ( ROM ) were measured at multiple intervals to assess for differences between groups . RESULTS The therapeutic KT group showed immediate improvement in pain-free shoulder abduction ( mean + /- SD increase , 16.9 degrees + /- 23.2 degrees ; P = .005 ) after tape application . No other differences between groups regarding ROM , pain , or disability scores at any time interval were found . CONCLUSION KT may be of some assistance to clinicians in improving pain-free active ROM immediately after tape application for patients with shoulder pain . Utilization of KT for decreasing pain intensity or disability for young patients with suspected shoulder tendonitis/impingement is not supported . LEVEL OF EVIDENCE Therapy , level 1b-", "Objectives : The primary aim of this study was to investigate the effect of medical exercise therapy in shoulder impingement patients , along with possible correlations between impairment variables . Study Design : A prospect i ve unblended r and omized clinical trial . Methods : Over four months , 61 participants were r and omly assigned into a high- grade d exercise therapy group ( HD ) ( n=31 ) and into a low- grade d exercise therapy group ( LD ) ( n=30 ) . Prognostic variables were similar between the groups at baseline . Five ( 8 % ) patients dropped out during the treatment period , and another four ( 6 % ) dropped out before followup . Pain was a composite score of a visual analogue scale ( VAS ) . Isometric strength was measured during four resisted break tests on the shoulder . Function was measured by means of a functional assessment question naire ( Shoulder Rating Question naire , SRQ ) . Both groups trained three times per week for twelve weeks , with tests pre- and posttraining and six months follow-up . Results : The HD group achieved significantly ( p pain , range of motion , isometric functional strength and function , but both groups increased function from pretest to posttest . Conclusions : In patients with uncomplicated subacromial pain syndrome , medical exercise therapy is an efficient treatment alternative , where high- grade doses should be emphasized . A major limitation is that the measurements were not undertaken by another person than the treating physiotherapists", "Our aim was to describe the differences in the presence of trigger points ( TrPs ) in the shoulder muscles and to investigate the presence of mechanical hypersensitivity in patients with unilateral shoulder impingement and healthy controls . Twelve patients with strictly unilateral shoulder impingement and 10 matched controls were recruited . TrPs in the levator scapula , supraspinatus , infraspinatus , subscapularis , pectoralis major , and biceps brachii muscles were explored . TrPs were considered active if the local and referred pain reproduced the pain symptoms and the patient recognized the pain as a familiar pain . Pressure pain thresholds ( PPT ) were assessed over the levator scapulae , supraspinatus , infraspinatus , pectoralis major , biceps brachii , and tibialis anterior muscles . Both explorations were r and omly done by an assessor blinded to the subjects ’ condition . Patients with shoulder impingement have a greater number of active ( mean ± SD : 2.5 ± 1 ; P Active TrPs in the supraspinatus ( 67 % ) , infraspinatus ( 42 % ) , and subscapularis ( 42 % ) muscles were the most prevalent in the patient group . Patients showed a significant lower PPT in all muscles when compared to controls ( P the number of TrPs and pain intensity ( rs = 0.578 ; P = 0.045 ) was found . Active TrPs in some muscles were associated to greater pain intensity and lower PPTs when compared to those with latent TrPs in the same muscles ( P between pain intensity and PPT levels were found . Patients with shoulder impingement showed widespread pressure hypersensitivity and active TrPs in the shoulder muscles , which reproduce their clinical pain symptoms . Our results suggest both peripheral and central sensitisation mechanisms in patients with shoulder impingement syndrome", "Background : Dysfunction in the kinetic chain caused by poor scapula stabilization can contribute to shoulder injuries and Shoulder Impingement Syndrome ( SIS ) . The purpose of this study was to compare the effectiveness of two treatment approaches scapular stabilization based exercise therapy and physical therapy in patients with SIS . Methods : The study is a r and omized clinical trial in which 68 patients with SIS were r and omly assigned in two groups of exercise therapy ( ET ) and physical therapy ( PT ) and received 18 sessions of treatment . Pain , shoulders ' range of abduction and external rotation , shoulder protraction , scapular rotation and symmetry as well as postural assessment and Pectoralis minor length were evaluated pre and post intervention . The paired- sample t test and the independent sample t test were applied respectively to determine the differences in each group and between two groups . Results : Our findings indicated significant differences in abduction and external rotation range , improvement of forward shoulder translation and increase in the flexibility of the involved shoulder between the two groups ( respectively ; p=0.024 , p=0.001 , p pain reduction between the groups ( p=0.576 ) . Protraction of the shoulder ( p forward head posture ( p mid thoracic curvature ( p scapular rotation and symmetry in both groups but no significant differences were observed between the two groups ( respectively ; p=0.183 , p=0.578 ) . Conclusion : The scapular stabilization based exercise intervention was successful in increasing shoulder range , decreasing forward head and shoulder postures and Pectoralis minor flexibility", "Objective The aim of this study was to compare the accuracy of blind vs. ultrasonography-guided corticosteroid injections in subacromial impingement syndrome and determine the correlation between accuracy of the injection location and clinical outcome . Design Forty-six patients with subacromial impingement syndrome were r and omized for ultrasonography-guided ( group 1 , n = 23 ) and blind corticosteroid injections ( group 2 , n = 23 ) . Magnetic resonance imaging analysis was performed immediately after the injection . Changes in shoulder range of motion , pain , and shoulder function were recorded . All patients were assessed before the injection and 6 wks after the injection . Results Accurate injections were performed in 15 ( 65 % ) group 1 patients and in 16 ( 70 % ) group 2 patients . There was no statistically significant difference in the injection location accuracy between the two groups ( P > 0.05 ) . At the end of the sixth week , regardless of whether the injected mixture was found in the subacromial region or not , all of the patients showed improvements in all of the parameters evaluated ( P Blind injections performed in the subacromial region by experienced individuals were reliably accurate and could therefore be given in daily routines . Corticosteroid injections in the subacromial region were very effective in improving the pain and functional status of patients with subacromial impingement syndrome during the short-term follow-up", "Abstract Scapula taping is a commonly used adjunctive treatment for shoulder im- pingement pathology . However , this intervention has not previously been subject to formal investigation . A pilot single-blind r and omized controlled trial was conducted to evaluate facilitatory taping as an adjunct to routine physiotherapy management . Twenty-two sub- jects with unilateral shoulder impingement symptoms were r and omized into a taping with routine physiotherapy or a routine physiotherapy only group . The intervention group had scapula taping applied three times per week for the first two weeks of their treatment . All subjects were assessed at baseline , then at 2 and 6 weeks after the commencement of treat- ment . Pain and functional ability were assessed using the Shoulder Pain and Disability In- dex , range of shoulder elevation , and self-reported pain on elevation . At 2 weeks , the taping group demonstrated a strong trend toward reduced pain both on self-reported activity ( SPADI pain subscale mean for taping 27.0 versus 41.5 for control ) and pain during mea- sured abduction ( mean VAS 22.8 for taped , 46.8 for control ) , statistical power being limited by small sample size . No similar trend was evident in the SPADI disability subscale . The magnitude of the differences was reduced at 6-week follow-up . This study provides prelimi- nary evidence for a short-term role for scapula taping as an adjunct to routine physiother- apy in the management of shoulder impingement symptoms but also highlights the need for consideration on a case basis relating to risk factors for skin reaction", "BACKGROUND Subacromial impingement syndrome ( SIS ) is the most common reason for shoulder pain . Ultrasound and laser are the physical therapy modalities , in conservative treatment of SIS . AIM The aim of this study was to define and compare the efficacy of ultrasound , laser and exercise in the treatment of SIS . DESIGN This was a r and omized controlled trial with-pre and post-treatment evaluations SETTING Out- patients referred to physical medicine and rehabilitation unit . POPULATION This study was performed on 52 patients with SIS . The patients were r and omly allocated into three groups METHODS The patients were treated five days a week for three weeks with hotpack+ultrasound+exercise ( the first group ) ; hotpack+laser+exercise ( the second group ) , or hotpack+exercise ( the third group ) . The pre and post treatment ranges of motion were measured in the patients . The visual analogue scale ( VAS ) was used to evaluate the severity of pain . Constant scoring was used to evaluate the shoulder functions and the results were compared after the treatment . RESULTS When the post-treatment results of the groups were compared with the pretreatment results , there was a statistically significant improvement in each of the three groups , in the pain , the range of motion and the functional improvement at the shoulder ( P0.05 ) . CONCLUSION The results of this study demonstrated that ultrasound and laser treatments were not superior to each other in the treatment of SIS . CLINICAL REHABILITATION IMPACT . Exercise treatment forms the base for the conservative treatment", "Abstract Study design : R and omized clinical trial . Objectives : To evaluate the effects of high-velocity , low-amplitude thrust manipulations ( HVLATMs ) and various messages on patients with musculoskeletal shoulder symptoms . Background : Previous studies indicated that HVLATM directed at the thoracic spine and ribs result ed in improvements of shoulder range of motion , pain , and disability in patients with musculoskeletal shoulder symptoms . These studies did not explore if the outcome was dependent on thrust location , clinician communication with the patient , or if there were any lasting effects . Methods : A consecutive sample of 100 patients with shoulder pain was r and omized into four groups . Patients received one intervention session including : six thoracic HVLATM ( spine versus scapula ) , a message about HVLATM ( neutral versus positive ) , and st and ardized home exercises . Outcome measures included shoulder Numeric Pain Rating Scale ( NPRS ) , NPRS with impingement testing , and Shoulder Pain and Disability Index ( SPADI ) . Measurements were recorded prior to intervention , immediately following intervention , and at short-term follow-up . Kruskal – Wallis statistics were used for between-group comparisons and Wilcoxon signed ranks for within-group comparisons . Results : Eighty-eight patients ( 22 per group ) completed the study . Statistically significant differences were found for within-group comparisons for most time points assessed . No statistical differences were found for between-group comparisons . Conclusion : Patients improved following the interventions . Neither the type of HVLATM nor the message conveyed to the patients had a significant effect on the patients ’ improvements . Level of evidence :", "BACKGROUND Shoulder pain in nursing professionals may lead to limitations in occupational and daily activities and consequently interfere with quality of life . OBJECTIVE To compare the effects of two physical therapy programs which differed in the proprioceptive exercises used on the nursing professionals with rotator cuff disorder , according to quality of life , work satisfaction indicators , and pain intensity . METHOD This study was an experimental , r and omized , prospect i ve , comparative trial with quantitative data analysis . The data sampling was carried out between the months of June 2010 and July 2011 by means of a question naire containing socio-demographic and professional information , the Western Ontario Rotator Cuff Index ( WORC ) , the Occupational Stress Indicator ( OSI ) , and the Visual Numeric Scale ( VNS ) . Based on r and omization , subjects were divided into two groups . Group 1 ( control ) was su bmi tted to stretching and strengthening exercises and cryotherapy . Group 2 ( experimental ) was treated with the same protocol as the control group , with the addition of proprioception exercises . The data was analyzed by means of the Statistical Package for the Social Science version 16.0 for Windows . RESULTS After physical therapy intervention , significant reduction in pain levels occurred in both groups , with a significant improvement in quality of life for Group 2 . No changes were observed in the work satisfaction indicators after the two types of physical therapy interventions . CONCLUSIONS The proprioceptive exercises were important in the treatment of musculoskeletal disorders , however the results did not allow us to determine which treatment was the most effective as there was no significant difference between groups", "OBJECTIVE To determine whether dexketoprofen administered by phonophoresis or iontophoresis is more effective for the treatment of subacromial impingement syndrome ( SIS ) than conventional ultrasound therapy . DESIGN R and omised clinical trial . SETTING University hospital . PARTICIPANTS Ninety-nine participants with SIS without a complete tear of the rotator cuff were assigned at r and om to three intervention groups . INTERVENTION GROUPS Participants received ultrasound ( n=32 ) , phonophoresis with dexketoprofen ( 50mg/session ) ( n=33 ) or iontophoresis with dexketoprofen ( 50mg/session ) ( n=34 ) . All participants completed 20 treatment sessions plus exercise therapy and cryotherapy . OUTCOME MEASURES A visual analogue scale ( VAS ) , the Constant-Murley Scale ( CMS ) and the Disabilities of the Arm , Shoulder and H and ( DASH ) question naire were administered pre-treatment ( baseline ) , post-treatment and 1 month post-treatment . RESULTS At baseline , there were no differences between the groups . Post-treatment , VAS score improved by -1.2 points and CMS score improved by 8.9 points in the ultrasound group compared with the iontophoresis group [ 95 % confidence interval ( CI ) -0.2 to -2.2 and 95 % CI 17.0 to 0.7 , respectively ] . CMS score improved by 7.1 points in the phonophoresis group compared with the iontophoresis group ( 95 % CI 14.8 to -0.7 ) . At 1 month post-treatment , no significant differences were detected between the groups . VAS , CMS and DASH scores of all groups improved post-treatment and at 1 month post-treatment . CONCLUSION Ultrasound , iontophoresis with dexketoprofen and phonophoresis with dexketoprofen can improve pain , shoulder function , and physical functioning and symptoms in the upper limb in patients with SIS without a complete tear of the rotator cuff . CLINICAL TRIALS . GOV REGISTRATION NUMBER NCT01748188", "OBJECTIVE To investigate the effect of individualized manual physiotherapy and exercises compared with individualized exercises alone in patients with shoulder impingement syndrome . DESIGN R and omized controlled trial . SUBJECTS Patients with shoulder impingement of more than 4 weeks ' duration . METHODS Patients in the intervention group were treated with individually adapted exercises and examination-based physiotherapy . Controls were treated with individually adapted exercises only . Both groups had 10 treatment sessions over a period of 5 weeks and subsequently continued their exercises at home for another 7 weeks . Results were analysed at 5 and 12 weeks after the start of the study . Primary outcome measures were : Shoulder Pain and Disability Index , and Patient 's Global Impression of Change . Secondary outcome measures were : mean weekly pain score ; Generic Patient-Specific Scale ; and Patients ' Satisfaction with Treatment . RESULTS A total of 46 patients were r and omized to the intervention group and 44 to the control group . Although both groups showed significant improvements , there was no difference between groups for the primary and secondary outcomes at any time . Only the results for mean pain differed at 5 weeks in favour of the intervention group . CONCLUSION Individually adapted exercises were effective in the treatment of patients with shoulder impingement syndrome . Individualized manual physiotherapy contributed only a minor amount to the improvement in pain intensity . However , further research is necessary to confirm these results before definite recommendations can be made", "Objective . To compare effects of ultrasound- ( US- ) guided percutaneous electrolysis combined with an eccentric exercise program of the rotator cuff muscles in subacromial pain syndrome . Methods . Thirty-six patients were r and omized and assigned into US-guided percutaneous electrolysis ( n = 17 ) group or exercise ( n = 19 ) group . Patients were asked to perform an eccentric exercise program of the rotator cuff muscles twice every day for 4 weeks . Participants assigned to US-guided percutaneous electrolysis group also received the application of galvanic current through acupuncture needle on each session once a week ( total 4 sessions ) . Shoulder pain ( NPRS ) and disability ( DASH ) were assessed at baseline , after 2 sessions , and 1 week after the last session . Results . The ANOVA revealed significant Group∗Time interactions for shoulder pain and disability ( all , P receiving US-guided percutaneous electrolysis combined with the eccentric exercises experienced greater improvement than those receiving eccentric exercise alone . Conclusions . US-guided percutaneous electrolysis combined with eccentric exercises result ed in small better outcomes at short term compared to when only eccentric exercises were applied in subacromial pain syndrome . The effect was statistically and clinical ly significant for shoulder pain but below minimal clinical difference for function . Future studies should investigate the long-term effects and potential placebo effect of this intervention", "Background Shoulder pain is a very common presentation in primary care . Evidence of benefit for subacromial corticosteroid injection is inconclusive and confined largely to studies with short follow-up . We plan a large , definitive , primary -care-based trial to determine efficacy and safety in patients with rotator cuff tendinopathy , and conducted a pilot trial to explore feasibility . Methods Six general practitioners ( GPs ) from Oxfordshire , UK underwent up date training in assessing painful shoulders and injecting the subacromial space . Each then recruited patients aged 35 to 74 years from primary care complaining of shoulder pain lasting no more than 6 months . Eligible participants were r and omized to receive either methylprednisolone acetate 40 mg with lidocaine 1 % ( total volume 1 ml ) , or lidocaine 1 % alone ( total volume 1 ml ) , injected into the subacromial space . The participants were blinded to treatment allocation . Feasibility outcomes were rates of recruitment , withdrawal , adherence to the protocol , completeness of follow-up , and success of patient masking . Clinical outcomes were the Oxford Shoulder Score ( OSS ) at baseline and at 4 and 12 weeks , and responses to three satisfaction questions at 2 , 4 and 12 weeks . Outcome data were collected by postal question naires . Results A total of 40 participants were r and omized ( 80 % of the target 50 participants ) over 26 weeks giving an overall recruitment rate of 1.5 participants per week . Rates of follow-up were maintained to a high level for the full 12 weeks . Four participants requested a ‘ rescue ’ corticosteroid injection but no patients withdrew . The trial GPs gave high scores for their confidence that the patient had remained blinded to treatment allocation during the procedure . The OSS at 4 and 12 weeks and the responses to the satisfaction questions are reported . Conclusions It is feasible to recruit participants with shoulder pain in the primary care setting for a blinded , r and omized trial of corticosteroid injection . Online r and omization of participants from the practice is also feasible , and postal question naires provide an effective means of gathering outcome data in this area of study . The lessons learned from this pilot will usefully inform the design of a large , definitive efficacy trial in primary care . Trial registration Current Clinical Trials IS RCT", "We have performed a double-blind placebo-controlled trial of moderate doses of extracorporeal shock-wave therapy ( ESWT ) for non-calcific tendonitis of the rotator cuff . Adults ( 74 ) with chronic tendonitis of the rotator cuff were r and omised to receive either active ( 1500 pulses ESWT at 0.12 mJ/mm2 ) or sham treatment , monthly for three months . All were assessed before each treatment , and at one and three months after the completion of treatment . The outcome was measured with regard to pain in the shoulder , including a visual analogue score for night pain , and a disability index . There were no significant differences between the two groups before treatment . The mean duration of symptoms in both groups was 23.3 months . Both showed significant and sustained improvements from two months onwards . There was no significant difference between them with respect to change in the Shoulder Pain and Disability Index ( SPADI ) scores or night pain over the six-month period . A mean ( + /-SD ; range ) change in SPADI of 16.1 + /- 27.2 ( 0 to 82 ) in the treatment group and 24.3 + /- 24.8 ( -11 to 83 ) in the sham group was noted at three months . At six months the mean changes were 28.4 + /- 25.9 ( -24 to 69 ) and 30.4 + /- 31.2 ( -12 to 88 ) , respectively . Similar results were noted for night pain . We conclude that there is a significant and sustained placebo effect after moderate doses of ESWT in patients with non-calcific tendonitis of the rotator cuff , but there is no evidence of added benefit when compared with sham treatment", "OBJECTIVES Rotator cuff tendinopathy is a common source of shoulder pain characterised by persistent and /or recurrent problems for a proportion of sufferers . The aim of this study was to pilot the methods proposed to conduct a substantive study to evaluate the effectiveness of a self-managed loaded exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy . DESIGN A single-centre pragmatic unblinded parallel group pilot r and omised controlled trial . SETTING One private physiotherapy clinic , northern Engl and . PARTICIPANTS Twenty-four participants with rotator cuff tendinopathy . INTERVENTIONS The intervention was a programme of self-managed loaded exercise . The control group received usual physiotherapy treatment . MAIN OUTCOMES Baseline assessment comprised the Shoulder Pain and Disability Index ( SPADI ) and the Short-Form 36 , repeated three months post r and omisation . RESULTS The recruitment target was met and the majority of participants ( 98 % ) were willing to be r and omised . 100 % retention was attained with all participants completing the SPADI at three months . Exercise adherence rates were excellent ( 90 % ) . The mean change in SPADI score was -23.7 ( 95 % CI -14.4 to -33.3 ) points for the self-managed exercise group and -19.0 ( 95 % CI -6.0 to -31.9 ) points for the usual physiotherapy treatment group . The difference in three month SPADI scores was 0.1 ( 95 % CI -16.6 to 16.9 ) points in favour of the usual physiotherapy treatment group . CONCLUSIONS In keeping with previous research which indicates the need for further evaluation of self-managed loaded exercise for rotator cuff tendinopathy , these methods and the preliminary evaluation of outcome offer a foundation and stimulus to conduct a substantive study", "Subacromial impingement syndrome ( SIS ) is a frequent cause of shoulder pain . Our purpose in this double-blinded , r and omized , and controlled study was to demonstrate whether the pulsed electromagnetic field ( PEMF ) provides additional benefit when used with other conservative treatment modalities in acute phase rehabilitation program of SIS . Forty-six patients with unilateral shoulder pain who had been diagnosed as having SIS were included in this trial . The cases were r and omly separated into two groups . All cases received a treatment program for 3 weeks consisting of Codman ’s pendulum exercises and subsequent cold pack gel application on shoulders with pain 5 times a day , restriction of daily activities that require the h and s to be used over the head , and meloxicam tablet 15 mg daily . One group was given PEMF ; the other group was given sham PEMF daily , 25 min per session , 5 days per week for 3 weeks . Shoulder pain during rest and activity and which causes disturbance of sleep was evaluated using a visual analogue scale , and total Constant score investigated shoulder function . Daily living activities were evaluated by shoulder disability question naire . Results were assessed before and after treatment . When compared with the baseline values , significant improvements in all these variables were observed at the end of the treatment in both groups ( p No significant difference between treatments was observed for any of these variables ( p > 0.05 ) . There is no convincing evidence that electromagnetic therapy is of additional benefit in acute phase rehabilitation program of SIS", "HYPOTHESIS The objective of this study was to compare the efficacy of subacromial injection of triamcinolone compared to injection of ketorolac in the treatment of external shoulder impingement syndrome . METHODS Thirty-two patients diagnosed with external shoulder impingement syndrome were included in this double-blinded r and omized controlled clinical trial . Each patient was r and omized into the steroid group or nonsteroidal anti-inflammatory drugs ( NSAID ) group . The steroid syringe contained 40 mg triamcinolone ; and the NSAID syringe contained 60 mg ketorolac . Each patient was evaluated in terms of arc of motion , visual analog scale ( VAS ) for evaluating pain , and the UCLA ( The University of California at Los Angeles ) shoulder rating scale . RESULTS At 1 month follow-up , both treatment arms result ed in increased range of motion and decreased pain . The steroid group decreased in active abduction while the NSAID group increased ( steroid : 134 ° , NSAID : 151 ° , P = .03 ) . The mean improvement in the UCLA shoulder rating scale at 4 weeks was 7.15 for the NSAID group and 2.13 for the steroid group ( P = .03 ) . Subgroup analysis of the UCLA scale demonstrated an increase in both forward flexion strength ( P = .04 ) and patient satisfaction ( P = .03 ) in the NSAID group . No significant difference could be seen in all other outcome measures . CONCLUSION In this study , an injection of ketorolac result ed in greater improvements in the UCLA shoulder rating scale than an injection of triamcinolone at 4 weeks follow-up . While both triamcinolone and ketorolac are effective in the treatment of isolated subacromial impingement , ketorolac appears to have equivalent if not superior efficacy ; all the while decreasing patient exposure to the potential side-effects of corticosteroids ", "STUDY DESIGN R and omized controlled trial with immediate follow-up . OBJECTIVES To evaluate the immediate effects of a low-amplitude , high-velocity thrust thoracic spine manipulation ( TSM ) on pain and scapular kinematics during elevation and lowering of the arm in individuals with shoulder impingement syndrome ( SIS ) . The secondary objective was to evaluate the immediate effects of TSM on scapular kinematics during elevation and lowering of the arm in individuals without symptoms . BACKGROUND Considering the regional interdependence among the shoulder and the thoracic and cervical spines , TSM may improve pain and function in individuals with SIS . Comparing individuals with SIS to those without shoulder pathology may provide information on the effects of TSM specifically in those with SIS . METHODS Fifty subjects ( mean ± SD age , 31.8 ± 10.9 years ) with SIS and 47 subjects ( age , 25.8 ± 5.0 years ) asymptomatic for shoulder dysfunction were r and omly assigned to 1 of 2 interventions : TSM or a sham intervention . Scapular kinematics were analyzed during elevation and lowering of the arm in the sagittal plane , and a numeric pain rating scale was used to assess shoulder pain during arm movement at preintervention and postintervention . RESULTS For those in the SIS group , shoulder pain was reduced immediately after TSM and the sham intervention ( mean ± SD preintervention , 2.9 ± 2.5 ; postintervention , 2.3 ± 2.5 ; P 0.2 ] ) . Scapular internal rotation increased 0.5 ° ± 0.02 ° ( P = .04 ; small effect size [ Cohen d received TSM and asymptomatic subjects who received the sham intervention had a significant increase ( 1.6 ° ± 2.7 ° ) in scapular upward rotation postintervention ( P significant . Scapular anterior tilt increased 1.0 ° ± 4.8 ° during elevation and lowering of the arm postmanipulation ( P TSM . CONCLUSION Shoulder pain in individuals with SIS immediately decreased after a TSM . The observed changes in scapular kinematics following TSM were not considered clinical ly important . LEVEL OF EVIDENCE Therapy , level 4 . J Orthop Sports Phys Ther 2014;44(7):475 - 487 . Epub 22 May 2014 . doi:10.2519/jospt.2014.4760", "OBJECTIVE To perform a cost-effectiveness analysis of subacromial corticosteroid injection combined with exercise compared with exercise alone in patients with moderate to severe shoulder pain from subacromial impingement syndrome . METHODS A within-trial cost-effectiveness analysis with 232 patients r and omized to physiotherapy-led injection combined with exercise ( n = 115 ) or exercise alone ( n = 117 ) . The analysis was from a health care perspective with 24-week follow-up . Re source use information was collected from all patients on interventions , medication , primary and secondary care contacts , private health care use and over-the-counter purchases . The measure of outcome was quality -adjusted life years ( QALYs ) , calculated from EQ-5D responses at baseline and three further time points . An incremental cost-effectiveness analysis was conducted . RESULTS Mean per patient NHS costs ( £ 255 vs £ 297 ) and overall health care costs ( £ 261 vs £ 318 ) were lower in the injection plus exercise arm , but this difference was not statistically significant . Total QALYs gained were very similar in the two trial arms ( 0.3514 vs 0.3494 QALYs ) , although slightly higher in the injection plus exercise arm , indicating that injection plus exercise may be the dominant treatment option . At a willingness to pay of £ 20,000 per additional QALY gained , there was a 61 % probability that injection plus exercise was the most cost-effective option . CONCLUSION Injection plus exercise delivered by therapists may be a cost-effective use of re sources compared with exercise alone and lead to lower health care costs and less time off work . TRIAL REGISTRATION International St and ard R and omised Controlled Trial Number Register , http://www.controlled-trials.com/is rct n/ , IS RCT 25817033", "Local steroid injections are common for treatment of impingement syndrome . Corticosteroid injections methods are basically in two formats , blind or with image guidance . The aim of this study is to compare the effect of ultrasound-guided in comparison with blind corticosteroid injections in patients with impingement syndrome . This study is a r and omized clinical trial study undertaken in patients with diagnosis of impingement syndrome done in Isfahan University of Medical Science clinics from February 2014 to February 2015 . The number of all patients registered in the study is 48 ; and then 40 patients were allocated to either control group r and omly which received blind steroid injection or case group that underwent ultrasound-guided steroid injection . The clinical symptoms were assessed using Shoulder Pain and Disability Index ( SPADI ) question naire , Visual Analogue Scale ( VAS ) and shoulder range of motion ( ROM ) using goniometer at baseline and six weeks after the injection . Data analysis revealed a significant difference in the mean of the VAS , SPADI and shoulder ROM in both groups 6 weeks after intervention ( P ultrasound guided corticosteroid injection had statistically significant improvements in function and shoulder ROM ( abduction , flexion ) compared to blind injection group after 6 weeks ( P differences in pain ( VAS ) and internal and external rotation between these two groups ( p>0.05 ) . Our findings suggest that US image guided can improve the shoulder function of patients with impingement syndrome , and thus can be considered in comprehensive care programs of these patients for fast speed of rehabilitation", "Introduction Return to work following an occupational injury is a multifactoral process although many traditional clinic-based rehabilitation programs do not appreciate the importance of workplace factors . A r and omized controlled trial was conducted to investigate the effect of workplace-based rehabilitation program on the return to work outcome of work-related rotator cuff disorder , which is based on the therapeutic use of actual work facilities and work environment . Methods A total of 103 workers were recruited and r and omly assigned into Clinic-based Work Hardening ( CWH ) or Workplace-based Work Hardening ( WWH ) groups . The CWH group were given traditional generic work hardening training while WWH group received workplace-based work hardening training with rehabilitative principles of athletic rotator cuff pathology , biomechanics and specific job activities . Results After four weeks , a higher return to work rate was obtained in WWH group compared to CWH group ( 71.4 % vs. 37 % , p lowering of self-reported shoulder problems and functional work capabilities in the WWH group versus the CWH group . Conclusion Workplace-based rehabilitation program appeared to be more effective in facilitating the return to work process of the injured worker as assessed immediately following intervention . In particular this approached was associated with many of the psychosocial workplace factors related to separation from the work routine . The influence of peer group and /or employer could be minimized . This initial attempt with rotator cuff injuries appears promising however long-term outcome needs to be determined", "The purpose of this clinical trial is to compare the effectiveness of a scapular-focused treatment with a control therapy in patients with shoulder impingement syndrome . Therefore , a r and omized clinical trial with a blinded assessor was used in 22 patients with shoulder impingement syndrome . The primary outcome measures included self-reported shoulder disability and pain . Next , patients were evaluated regarding scapular positioning and shoulder muscle strength . The scapular-focused treatment included stretching and scapular motor control training . The control therapy included stretching , muscle friction , and eccentric rotator cuff training . Main outcome measures were the shoulder disability question naire , diagnostic tests for shoulder impingement syndrome , clinical tests for scapular positioning , shoulder pain ( visual analog scale ; VAS ) , and muscle strength . A large clinical ly important treatment effect in favor of scapular motor control training was found in self-reported disability ( Cohen ’s d = 0.93 , p = 0.025 ) , and a moderate to large clinical ly important improvement in pain during the Neer test , Hawkins test , and empty can test ( Cohen ’s d 0.76 , 1.04 , and 0.92 , respectively ) . In addition , the experimental group demonstrated a moderate ( Cohen ’s d = 0.67 ) improvement in self-experienced pain at rest ( VAS ) , whereas the control group did not change . The effects were maintained at three months follow-up", "Shoulder pain is the third most common musculoskeletal problem and accounts for 5 % of general practitioner consultations . Although many treatments are described , there is no consensus on optimal treatment and up to 40 % of patients still have pain 12 months after initially seeking help for pain . Previously , the effect of transcutaneous pulsed radiofrequency treatment ( TCPRFT ) was evaluated in a retrospective audit that showed good pain relief for a mean 395 days and justified this r and omized sham controlled trial . In this study , 51 patients entered into a r and omized double-blinded , placebo controlled study of TCPRFT . Patients were assessed at 4 and 12 weeks by a blinded observer and compared with baseline . We observed sustained reductions in pain at night , pain with activity , and functional improvement at 4 and 12 weeks with active but not sham TCPRFT . The 25 subjects who received active treatment showed statistically significant reductions of 24/100 in pain at night and 20/100 of pain with activity at 4 weeks and 18/100 and 19/100 , respectively , at 12 weeks from baseline . Statistically significant lower Brief Pain Inventory pain and function scores ( 4 and 12 weeks ) , improved pain self-efficacy ( 4 weeks ) , Oxford Shoulder scores ( 12 weeks ) , and internal rotation ( 12 weeks ) were seen . Pain at both rest and shoulder elevation were not improved by active treatment . No complications were seen . This study of a simple , low risk , outpatient treatment confirms the findings of our earlier study of TCPRFT for knee pain and shoulder pain audit that transcutaneous pulsed radiofrequency treatment may help some people with painful shoulders", "OBJECTIVES To determine ( 1 ) the prevalence of selected common musculoskeletal disorders in patients referred for electrodiagnosis when cervical radiculopathy is suspected and ( 2 ) whether these findings predict electrodiagnostic study outcome . DESIGN Prospect i ve study . SETTING Electrodiagnostic laboratories in departments of physical medicine and rehabilitation at 5 participating institutions . PARTICIPANTS A total of 191 subjects undergoing electrodiagnostic evaluations for upper-limb symptoms when cervical radiculopathy was suspected . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Prevalence of certain musculoskeletal disorders ( myofascial pain , shoulder impingement , lateral epicondylitis , de Quervain 's tenosynovitis ) and outcomes of electrodiagnostic testing ( normal study , cervical radiculopathy , or another electrodiagnostically confirmed diagnosis ) . RESULTS The total prevalence of musculoskeletal disorders was 42 % . The prevalence in those with a normal study was 69 % , compared with 29 % in those with cervical radiculopathy ( P patients with suspected cervical radiculopathy . Although the presence of certain musculoskeletal disorders makes having a normal electrodiagnostic evaluation significantly more likely , the high prevalence among both patients with normal studies and those with radiculopathy and other disorders limits the usefulness of this information in precisely predicting study outcome . The presence of musculoskeletal disorders should not preclude electrodiagnostic testing when otherwise indicated", "Shoulder impingement syndrome ( SIS ) is a complex , multi-factorial problem that is treated with a variety of different conservative options . One conservative option that has shown effectiveness is manual therapy to the thoracic spine . Another option , manual therapy to the cervical spine , has been studied only once with good results , evaluating short-term outcomes , in a small sample size . The purpose of this study was to investigate the benefit of neck manual therapy for patients with SIS . The study was a r and omised , single blinded , clinical trial where both groups received pragmatic , evidence -based treatment to the shoulder and one group received neck manual therapy . Subjects with neck pain were excluded from the study . Comparative pain , disability , rate of recovery and patient acceptable symptom state ( PASS ) measures were analyzed on the 68 subjects seen over an average of 56.1 days ( st and ard deviation (SD)=55.4 ) . Eighty-six percent of the sample reported an acceptable change on the PASS at discharge . There were no between-groups differences in those who did or did not receive neck manual therapy ; however , both groups demonstrated significant within-groups improvements . On average both groups improved 59.7 % ( SD=25.1 ) for pain and 53.5 % ( SD=40.2 ) for the Quick Disabilities of the Shoulder and H and Question naire ( QuickDASH ) from baseline . This study found no value when neck manual therapy was added to the treatment of SIS . Reasons may include the lack of therapeutic dosage provided for the manual therapy approach or the lack of benefit to treating the neck in subjects with SIS who do not have concomitant neck problems", "Objective To compare the effectiveness of subacromial corticosteroid injection combined with timely exercise and manual therapy ( injection plus exercise ) or exercise and manual therapy alone ( exercise only ) in patients with subacromial impingement syndrome . Design Pragmatic r and omised clinical trial . Setting Primary care based musculoskeletal service . Patients Adults aged 40 or over with subacromial impingement syndrome with moderate or severe shoulder pain . Interventions Injection plus exercise or exercise only . Main outcome measures Primary outcome was the difference in improvement in the total shoulder pain and disability index at 12 weeks . Results 232 participants were r and omised ( 115 to injection plus exercise , 117 to exercise only ) . The mean age was 56 ( range 40 - 78 ) , 127 were women , and all had had a median of 16 weeks of shoulder pain ( interquartile range 12 - 28 ) . At week 12 there was no significant difference between the groups in change in total pain and disability index ( mean difference between change in groups 3.26 ( 95 % confidence interval −0.81 to 7.34 ) , P=0.116 ) . Improvement was significantly greater in the injection plus exercise group at week 1 ( 6.56 , 4.30 to 8.82 ) and week 6 ( 7.37 , 4.34 to 10.39 ) for the total pain and disability index ( P patients with subacromial impingement syndrome , injection plus exercise and exercise only are similarly effective at 12 weeks . Trial registration IS RCT 25817033 ; EudraCT No 2005 - 003628 - 20", "BACKGROUND Thoracic SMT can improve symptoms in patients with subacromial impingement syndrome . However , at this time the mechanisms of SMT are not well established . It is possible that changes in pain sensitivity may occur following SMT . OBJECTIVES To assess the immediate pain response in patients with shoulder pain following thoracic spinal manipulative therapy ( SMT ) using pressure pain threshold ( PPT ) , and to assess the relationship of change in pain sensitivity to patient-rated outcomes of pain and function following treatment . DESIGN R and omized Controlled Study . METHODS Subjects with unilateral subacromial impingement syndrome ( n = 45 ) were r and omly assigned to receive treatment with thoracic SMT or sham thoracic SMT . PPT was measured at the painful shoulder ( deltoid ) and unaffected regions ( contralateral deltoid and bilateral lower trapezius areas ) immediately pre- and post-treatment . Patient-rated outcomes were pain ( numeric pain rating scale - NPRS ) , function ( Pennsylvania Shoulder Score - Penn ) , and global rating of change ( GROC ) . RESULTS There were no significant differences between groups in pre-to post-treatment changes in PPT ( p ≥ 0.583 ) nor were there significant changes in PPT within either group ( p ≥ 0.372 ) following treatment . NPRS , Penn and GROC improved across both groups ( p pressure pain sensitivity between participants receiving thoracic SMT versus sham thoracic SMT . Both groups had improved patient-rated pain and function within 24 - 48 h of treatment , but there was no difference in outcomes between the groups", "STUDY DESIGN R and om allocation of subjects into a placebo-controlled , crossover study . OBJECTIVES To investigate the effect of changing thoracic and scapular posture on shoulder flexion and scapular plane abduction range of motion in asymptomatic subjects , and in subjects with subacromial impingement syndrome . BACKGROUND Changes in upper body posture and concomitant imbalance of the muscle system have been proposed as one of the etiological mechanisms leading to subacromial impingement syndrome . Although clinicians commonly assess posture and devise rehabilitation programs to correct posture , there is little evidence to support this practice . METHODS AND MATERIAL S Selected postural , range of movement , and pain measurements were investigated in 60 asymptomatic subjects and 60 subjects with subacromial impingement syndrome , prior to and following thoracic and scapular taping intended to change their posture . RESULTS Changing posture had an effect on all components of posture measured ( P range of motion in shoulder flexion and abduction in the plane of the scapula . Changing posture was not found to have a significant effect on the intensity of pain experienced by the symptomatic subjects , although the point in the range of shoulder elevation at which they experienced their pain was significantly higher ( P shoulder range of movement and the point at which pain is experienced", "Subacromial corticosteroid injection is one of the most frequently used management tools in subacromial impingement syndrome ( SIS ) despite controversial reports on the efficacy . Our purpose , in this single blinded , r and omised and controlled study was to clarify whether the corticosteroid injection provides additional benefit when used with other conservative treatment modalities in 48 patients with stage 2 SIS . The patients were r and omly divided into three groups according to the two therapeutic injections applied with a 10-day interval : group 1 : 10 cc of 1 % lignocaine + 40 mg of methylprednisolone for the first and second injections , group 2 : 10 cc of 1 % lignocaine + 40 mg of methylprednisolone for the first injection and only 10 cc of 1 % lignocaine for the second injection , group 3 : only 10 cc of 1 % lignocaine for the first and second injections . All the patients were prescribed 500 mg of naproxen sodium to use two times daily , instructed to rest and perform Codman ’s pendulum exercises during the first 15 days . Shoulder pain during rest , activity , and causing disturbance of sleep was evaluated using a visual analogue scale and shoulder function was investigated by total Constant score and its subsectional parameters which are pain , daily living activities , active range of motion and strength before the therapy and 1 and 3 months after the therapy onset . Significant improvements from the baseline values in all pain and function parameters were observed at the first and second evaluation in all groups . Group 1 patients had more favourably improved values in pain causing sleep disturbance and daily living activity parameters than group 2 and 3 patients only in the 1st month after therapy onset . We found that subacromial corticosteroid injections in the acute or subacute phase of SIS provided additional short-term benefit without any complication when used together with nonsteroidal anti-inflammatory drugs ( NSAIDs ) and exercise", "Background There is evidence supporting the use of extracorporeal shock wave therapy ( ESWT ) in calcific tendinopathy of the rotator cuff , but the best current evidence does not support its use in non-calcifying tendinopathy . We conducted a r and omized placebo-controlled trial to investigate the efficacy and safety of low energy ESWT for non-calcifying tendinopathy of the rotator cuff . Methods 20 patients with non-calcifying supraspinatus tendinopathy ( NCST ) were r and omized to an active or a sham treatment group . Physical , blood , roentgenographic , and MRI examinations of the shoulder were conducted to verify that patients met the inclusion and exclusion criteria . These examinations were repeated six and twelve weeks after treatments . Effectiveness was determined by comparison of the mean improvement in the Constant and Murley score ( CMS ) between the treatment and the placebo groups at three months . Safety was assessed by analyzing the number and severity of adverse events . Results All the patients completed the investigation protocol . At the final follow-up , significant improvement in the total CMS score and most of the CMS subscales was observed in the ESWT group when compared to the baseline values . Significantly higher total CMS , and significantly higher scores for CMS pain and ROM were observed in the ESWT group when compared to the placebo . No serious adverse events were noted after ESWT . Conclusions Patients suffering from NCST may benefit from low energy ESWT , at least in short-term . The application protocol of ESWT is likely to play a key-role in a successful treatment . Future investigations should be undertaken on the long-term effects of this technique for the treatment of NCST.Trial registration Current Controlled Trials IS RCT", "[ Purpose ] This study examined the effects of scapular stabilization exercises immediately after surgery on pain and function in patients diagnosed with shoulder impingement syndrome . [ Subjects ] The subjects were assigned by r and om sampling to an experimental group ( n=15 ) to which stabilization exercise was applied and a control group ( n=15 ) to which ordinary physical treatment was applied . [ Methods ] To evaluate the degree of pain , a 100 mm visual analogue scale ( VAS ) was used . The Constant-Murley Scale ( CMS ) was used to evaluate the functions of the shoulder joints . To determine the range of motion , a goniometer was used to measure range of shoulder motion . The simple shoulder test ( SST ) was used to determine the condition of the shoulder joints of the subjects . [ Results ] There were significant differences in all the items of the experimental group . The results of comparison of the therapeutic effect in the experimental and control groups revealed significant differences in active abduction , passive abduction , VAS , SST , and the CMS , except for pain . [ Conclusion ] The results suggest that shoulder stabilization exercise positively affects pain alleviation and functional recovery in shoulder impingement patients", "[ Purpose ] A prospect i ve , r and omized , single-blind study was performed in order to compare the efficacy of ultrasound treatments of various duration s for patients with subacromial impingement syndrome . [ Subjects and Methods ] One hundred patients who had been diagnosed with subacromial impingement syndrome by clinical examination and magnetic resonance imaging were included in this study . Patients were r and omly divided into two groups of fifty patients per group . The first group received 15 sessions of therapeutic ultrasound ( 4 minutes ) , superficial heat and transcutaneous electrical stimulation therapy combined with exercise . The second group received the same treatment except that each of the 15 ultrasound sessions were eight minutes in length . The patients were evaluated before and after the treatment . A visual analog scale ( VAS ) was used to assess pain , the University of California at Los Angeles ( UCLA ) and Constant Scale were used to assess shoulder function and the Beck Depression Inventory ( BDI ) was used to quantify depressive symptoms . [ Results ] There were no statistically significant differences between the groups in age , time since the onset of pain , sex , education and depression levels prior to the treatment . The post-treatment evaluation of patients VAS , UCLA , Constant , and BDI scores showed statistically significant within group improvements . When the two groups were compared , we found no statistically significant differences in the Constant activities of daily living , Constant external rotation , Constant force and BDI scores . However , the second group scored better than the first group in all the remaining parameters . [ Conclusion ] Ultrasound therapy was found to have beneficial effects on pain and functional status in the treatment of subacromial impingement syndrome . Eight minutes of ultrasound treatment was shown to be more effective than 4 minutes of ultrasound treatment", "BACKGROUND Various manual therapy procedures are increasingly more often being used in the treatment of shoulder complex dysfunctions . The objective of the present study was to investigate whether manual therapy can improve the range of motion in the glenohumeral joint and alleviate pain in patients with chronic rotator cuff injuries MATERIAL AND METHODS The participants were r and omly assigned to an experimental group and a control group of 15 patients each . Both groups received a st and ard combination therapy involving TENS , ultrasound therapy and kinesiotherapy . Additionally , the experimental group took part in a treatment programme design ed by the authors composed of selected elements of various manual therapy techniques . Outcome evaluation focused on changes in the range of motion in the glenohumeral joint and changes in pain intensity ( VAS scale ) during the performance of functional tests . The results were subjected to statistical analysis . RESULTS More rapid and more significant pain reduction and more significant improvement in the range of motion of the glenohumeral joint across all movements tested were obtained in the experimental group . CONCLUSION The inclusion of manual therapy in st and ard comprehensive physiotherapy applied in the rehabilitation of patients with chronic rotator cuff injuries of the glenohumeral joint significantly improves treatment effectiveness ", "Background Shoulder impingement syndrome is a common musculoskeletal complaint leading to significant reduction of health and disability . Physiotherapy is often the first choice of treatment although its effectiveness is still under debate . Systematic review s in this field highlight the need for more high quality trials to investigate the effectiveness of physiotherapy interventions in patients with subacromial impingement syndrome . Methods / Design This r and omized controlled trial will investigate the effectiveness of individualized physiotherapy in patients presenting with clinical signs and symptoms of subacromial impingement , involving 90 participants aged 18 - 75 . Participants are recruited from outpatient physiotherapy clinics , general practitioners , and orthopaedic surgeons in Germany . Eligible participants will be r and omly allocated to either individualized physiotherapy or to a st and ard exercise protocol using central r and omization . The control group will perform the st and ard exercise protocol aim ing to restore muscular deficits in strength , mobility , and coordination of the rotator cuff and the shoulder girdle muscles to unload the subacromial space during active movements . Participants of the intervention group will perform the st and ard exercise protocol as a home program , and will additionally be treated with individualized physiotherapy based on clinical examination results , and guided by a decision tree . After the intervention phase both groups will continue their home program for another 7 weeks . Outcome will be measured at 5 weeks and at 3 and 12 months after inclusion using the shoulder pain and disability index and patients ' global impression of change , the generic patient-specific scale , the average weekly pain score , and patient satisfaction with treatment . Additionally , the fear avoidance beliefs question naire , the pain catastrophizing scale , and patients ' expectancies of treatment effect are assessed . Participants ' adherence to the protocol , use of additional treatments for the shoulder , direct and indirect costs , and sick leave due to shoulder complaints will be recorded in a shoulder log-book . Discussion To our knowledge this is the first trial comparing individualized physiotherapy based on a defined decision making process to a st and ardized exercise protocol . Using high- quality method ologies , this trial will add evidence to the limited body of knowledge about the effect of physiotherapy in patients with SIS.Trial registration Current Controlled Trials IS RCT", "There is little known about the specific manual therapy techniques used to treat painfully limited shoulders and their effects on range of movement ( ROM ) and pressure pain threshold ( PPT ) . The objective of this study was to investigate the initial effects of a Mulligan 's mobilization with movement ( MWM ) technique on shoulder ROM in the plane of the scapula and PPT in participants with anterior shoulder pain . A repeated measures , double-blind r and omized-controlled trial with a crossover design was conducted with 24 subjects ( 11 males and 13 females ) . ROM and PPT were measured before and after the application of MWM , sham and control conditions . Significant and clinical ly meaningful improvements in both ROM ( 15.3 % , F (2,46)=16.31 P=0.00 ) and PPT ( 20.2 % , F(2,46)=3.44 , P=0.04 ) occurred immediately after post treatment . The results indicate that this specific manual therapy treatment has an immediate positive effect on both ROM and pain in subjects with painful limitation of shoulder movement . Further study is needed to evaluate the duration of such effects and the mechanism by which this occurs", "Objective To compare the effectiveness of ultrasound guided corticosteroid injection in the subacromial bursa with systemic corticosteroid injection in patients with rotator cuff disease . Design Double blind r and omised clinical trial . Setting Outpatient clinic of a physical medicine and rehabilitation department in Oslo , Norway . Patients 106 patients with rotator cuff disease lasting at least three months . Interventions Ultrasound guided corticosteroid and lidocaine injection in the subacromial bursa and lidocaine injection in the gluteal region ( local group ) ; corticosteroid and lidocaine injection in the gluteal region and ultrasound guided lidocaine injection in the subacromial bursa ( systemic group ) . Main outcome measures Difference in improvement in the overall shoulder pain and disability index score after six weeks . Results Six weeks after the intervention , the mean difference in improvement in overall shoulder pain and disability index score between the local group and the systemic group was −5.2 ( 95 % confidence interval −13.9 to 3.5 ) ; it was −4.1 ( −12.3 to 4.1 , P=0.32 ) after adjustment for baseline score . A small but statistically significant difference in improvement between groups occurred in favour of the local group for two secondary outcome measures : the Western Ontario rotator cuff index ( 8.1 , 0.7 to 15.6 ) and change in main complaint ( 2.0 , 0 to 4 ) . Conclusions No important differences in short term outcomes were found between local ultrasound guided corticosteroid injection and systemic corticosteroid injection in rotator cuff disease . Trial registration Clinical trials NCT00640575", "[ Purpose ] The aim of this prospect i ve , double-blind , r and omized , placebo-controlled study was to evaluate the effects of therapeutic continuous ultrasound ( US ) on patients with rotator cuff disease . [ Subjects and Methods ] Twenty-two patients were treated with a st and ard physiotherapy program consisting of a hot-pack , transcutaneous electrical nerve stimulation ( TENS ) , exercises , and US that was supervised by the same physiotherapist . The patients were r and omly assigned to either a group that received true US ( n=11 ) or one that received sham US ( n=11 ) . [ Results ] There were significant differences between the pre- and post-intervention UCLA Shoulder Rating Scale and Constant-Murley Shoulder Outcome scores , VAS , and external rotation ( ER ) peak torque 60 ° /second values for both the true and sham US groups . However , the between-group differences were not statistically significant . [ Conclusion ] In patients with rotator cuff disease , physiotherapy interventions effectively treat the pain , improve the clinical status , and increase the muscle strength of the shoulder ER at a low constant angular velocity , with functional improvement being seen immediately after treatment . However , at the end of the intervention , the US had yielded no additional efficacy to the physiotherapy treatment regimen of the patients with rotator cuff disease", "There is evidence for the efficacy of acupuncture treatment for chronic shoulder pain , but it remains unclear which acupuncture modes are most effective . We compared the effect of trigger point acupuncture ( TrP ) , with that of sham ( SH ) acupuncture treatments , on pain and shoulder function in patients with chronic shoulder pain . The participants were 18 patients ( 15 women , 3 men ; aged 42 - 65 years ) with nonradiating shoulder pain for at least 6 months and normal neurological findings . The participants were r and omized into two groups , each receiving five treatment sessions . The TrP group received treatment at trigger points for the muscle , while the other group received SH acupuncture treatment on the same muscle . Outcome measures were pain intensity ( visual analogue scale , VAS ) and shoulder function ( Constant-Murley Score : CMS ) . After treatment , pain intensity between pretreatment and 5 weeks after TrP decreased significantly ( p Shoulder function also increased significantly between pretreatment and 5 weeks after TrP ( p SH acupuncture therapy , TrP therapy appears more effective for chronic shoulder pain", "Objectives : To describe the effects of 2 pain treatments for shoulder impingement syndrome ( SIS ) , and illustrate how investigators can use pain quality information to underst and treatment response differences . Material s and Methods : This study presents pain quality data from a r and omized open-label study comparing the effects of an injection of triamcinolone and up to twice daily application of a heated lidocaine/tetracaine ( Trilexis ) patch in individuals with SIS . Study participants completed a measure of pain quality at baseline and again on study days 14 , 28 , and 42 following initiation of 2 treatments for SIS . Baseline and posttreatment pain quality scores were graphed to provide a visual representation of treatment-associated changes . Analyses of variance were used to examine the differences between treatment conditions in changes in pain quality with treatment . Results : Both treatments result ed in substantial ( and similar ) pretreatment to posttreatment improvements in many pain qualities . However , differences in the time course of treatment effects were observed for itchy and heavy qualities . Discussion : Although 2 different pain treatments appear to have the same effects when only pretreatment to posttreatment changes are examined , treatment differences emerged when the time course of treatment is examined . The findings support the importance of assessing both pain qualities and time course of treatment as outcome domains . The results illustrate how investigators can use data from clinical trials to provide a more fine-tuned description of treatment effects , providing knowledge that could be helpful in selecting treatment options at the individual patient level . Summary : Examination of the effects of pain treatments on pain qualities over time will help research ers and clinicians underst and if certain pain quality domains respond faster to one treatment versus another , and may identify differences between treatments that would not be observed by measures of global pain intensity alone", "Objectives Treatment for degenerative rotator cuff disease of the shoulder includes physiotherapy . Dynamic humeral centering ( DHC ) aims at preventing subacromial impingement , which contributes to the disease . The goal of this study was to assess the effectiveness of DHC . Method 69 patients with shoulder pain and impingement syndrome were prospect ively included in a single-centre r and omised trial with a 12-month follow-up . Patients and assessor were blinded to the study hypothesis and treatment , respectively . DHC and non-specific mobilisation as control were performed for 6 weeks , in 15 supervised individual outpatient sessions , and patients performed daily home exercises . The planned primary outcome was the Constant score including subscores for pain , activity , mobility and strength at 3 months . Secondary outcomes were the Constant score and subscores at 12 months , and medication use for pain at 3 and 12 months . Results The DHC group did not differ from the control group in the total Constant score at 3 months . However , the DHC group showed a higher Constant subscore for pain ( 12.2 ( SD 2.8 ) vs 9.9 ( 2.9 ) , least square means difference 2.1 , 95 % CI 0.7 to 3.5 , p=0.004 ) . At 3 months , the DHC group also showed a higher rate of no medication use ( 96.7 % vs 71 % , proportional difference 25.7 , 95 % CI 3.7 to 51.9 , p=0.012 ) . There was no other intergroup difference . Conclusions There was no difference in the total Constant score between DHC and controls . However , pain was improved at 3 months after DHC . The differences found in subscores for pain should be explored in future studies . Trial registration clinical trials.gov Identifier : NCT 01022775", "The effects of balneotherapy on chronic shoulder pain were studied . In this single-blind , r and omized , follow-up study involving 46 patients with chronic shoulder pain , one group of patients received physiotherapy — exercise and transcutaneous electrical nerve stimulation— and the other group received balneotherapy in addition to physiotherapy for 4 weeks on 15 occasions . The following parameters were recorded before treatment ( at week 0 ) and after treatment ( at weeks 4 , 7 , and 13 ) : Shoulder Pain and Disability Index ( SPADI ) , the Short Form ( 36 ) Health Survey ( SF-36 ) and EuroQuol-5D ( EQ-5D ) quality of life question naires , pain at rest and on movement on the visual analog scale ( VAS ) , and active and passive range of motion . The SPADI pain , function , and total scores and the VAS scores at rest and on movement significantly improved in both groups after treatments . A greater improvement was observed in the balneotherapy group compared to the control group ; regarding some parameters ( VAS score on movement and SPADI function score at visit 2 ; VAS score at rest at visits 3 and 4 ) , the difference between the groups was significant . The improvement of SF-36 and EQ-5D quality of life scores and the active range of motion was more pronounced in the balneotherapy group , the difference between the groups was not significant , except for EQ-5D at visit 2 . Improvement of passive range of motion was not significant . Balneotherapy may have a beneficial effect on the clinical parameters and quality of life of patients with chronic shoulder pain . The number of patients should be increased", "Objective Local injections are widely used in patients with a painful shoulder . The aim of this study was to evaluate the possible impact of patients ’ visual information on the effectiveness of ultrasound (US)-guided local injections on anxiety levels and shoulder pain . Design A total of 151 patients , scheduled for local injection owing to shoulder pain , were r and omly assigned into two groups in a consecutive order . Patients in group I ( n = 72 ) were provided information related to US findings and allowed to watch the procedures from the monitor , whereas patients in group II ( n = 79 ) received the injection only without any collaboration . Data were collected from both groups immediately before and after injections through visual analog scale and question naire ( the State-Trait Anxiety Inventory [ STAI ] forms 1 and 2 ) . Results US-guided local injections provided significant improvement of anxiety and pain in both groups , irrespective of providing visual information . Group I and group II comparisons with respect to the visual analog scale , STAI 1 , and STAI 2 yielded significant difference only for postinjection STAI 2 in group I ( P = 0.006 ) . Intragroup comparisons revealed significant differences between preinjection and postinjection values ( group I : visual analog scale , P = 0.001 ; STAI form 1 , P = 0.001 ; STAI form 2 , P = 0.002 ; group II : visual analog scale , P = 0.001 ; STAI form 1 , P = 0.002 ; STAI form 2 , P = 0.042 ) . There was no significant difference between the groups in terms of postinjection satisfaction levels from the procedures ( P = 0.824 ) . Conclusions Performing US-guided shoulder injections with patient visual information provides positive contributions to coping with pain and anxiety . In particular , the patient collaboration – based US-guided injections have positive consequences on patients ’ long-st and ing “ trait-anxiety ” levels", "Previous research suggests that Mulligan 's Mobilisation-with-Movement ( MWM ) technique for the shoulder produces an immediate improvement in movement and pain . The aims of this study were to investigate the time course of the effects of a single MWM technique and to ascertain the effects of adding tape following MWM in people with shoulder pain . Twenty-five participants ( 15 males , 10 females ) , who responded positively to an initial application of MWM , were r and omly assigned to MWM or MWM-with-Tape . Range of movement ( ROM ) , pressure pain threshold ( PPT ) and current pain severity ( PVAS ) were measured pre- and post-intervention , 30-min , 24-h and one week follow-up . Following a one-week washout period , participants were crossed over to receive a single session of the opposite intervention with follow-up measures repeated . ROM significantly improved with MWM-with-Tape and was sustained over one week follow-up ( p ) . MWM demonstrated an improvement in ROM ( 11.8 ° , 95 % CI 1.9 - 21.7 ) and PVAS ( 40.4 mm , 95 % CI 27.8 - 53.0 mm ) , but only up to 30-min follow-up . There was no significant improvement in PPT for either intervention at any time point . MWM-with-Tape significantly improved ROM over the one-week follow-up compared to MWM alone ( 15.9 ° , 95 % CI 7.4 - 24.4 ) . Both MWM and MWM-with-Tape provide a short-lasting improvement in pain and ROM , and MWM-with-Tape also provides a sustained improvement in ROM to one-week follow-up , which is superior to MWM alone", "STUDY DESIGN Planned secondary analysis of a r and omized clinical trial . OBJECTIVES To examine : 1 ) patients ' baseline expectations for treatment outcome of thoracic high velocity low amplitude thrust manipulations ( HVLATM ) to the thoracic spine for shoulder pain ; 2 ) if the message conveyed by the clinician changed the patients ' expectation ; 3 ) any differences in outcome based on expectation independent of messaging . ; and 4 ) any differences in outcome for those patients whose expectations significantly changed as a result of the messaging . BACKGROUND Thoracic HVLATM may be an effective intervention for patients suffering from musculoskeletal shoulder pain . The role of expectation in the treatment effectiveness of this intervention has not been established . METHODS Subjects ' expectations regarding the effectiveness of HVLATM on shoulder pain were recorded at baseline . This was reassessed immediately following the provision of positive or neutral instructional set . The subjects then received a thoracic or scapular HVLATM . The Shoulder Pain and Disability Index ( SPADI ) and the numeric pain rating scale ( NPRS ) were used as outcomes measures . RESULTS There was a 10 subject change ( 23 % ) in positive expectation that was statistically significant ( p = 0.019 ) following a positive message . There was no statistically significant difference in pain and function when these subjects were compared to all other subjects . CONCLUSION Although patients ' expectations of positive outcome significantly changed when providing a positive instructional set , these changes did not translate into clinical ly significant short term changes in shoulder pain and function . LEVEL OF EVIDENCE 1b", "BACKGROUND AND PURPOSE There is still a lack of evidence about the beneficial effects of ultrasound ( US ) intervention for the management of soft tissue problems . Thus , this study was design ed to assess the effectiveness of US over a placebo intervention when added to other physical therapy interventions and exercise in the management of shoulder disorders . SUBJECTS AND METHODS Forty patients who were diagnosed by ultrasonography or magnetic resonance imaging to have a periarticular soft tissue disorder of the shoulder were r and omly assigned to either a group that received true US ( n=20 ; mean time since onset of pain=8.7 months , SD=8.8 , range=1 - 36 ) or a group that received sham US ( n=20 ; mean time since onset of pain=8.1 months , SD=10.8 , range=1 - 42 ) . Besides true or sham US ( 10 minutes ) , superficial heat ( 10 minutes ) , electrical stimulation ( 15 minutes ) , and an exercise program ( 15 - 30 minutes ) were administered to both groups 5 days each week for 3 weeks . RESULTS Subjects showed within-group improvements in pain , range of motion , Shoulder Disability Question naire scores , and Health Assessment Question naire scores with the intervention , but the differences did not reach significance when compared between the groups . DISCUSSION AND CONCLUSION The results suggest that true US , compared with sham US , brings no further benefit when applied in addition to other physical therapy interventions in the management of soft tissue disorders of the shoulder", "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 r and omized , double-blind , clinical trial study was conducted with the aim of determining the efficacy of adding laser ( 830 nm ) to ultrasound ( US ) and exercise for the management of shoulder tendonitis . METHODS 42 subjects ( n=21 , in adding laser group and n=21 , in US and exercise group ) received a course of 10 sessions treatment over one month in the shoulder region . Outcome measures such as Visual Analogue Scale ( VAS ) , Tenderness Severity Scale ( TSS ) , Constant Murley Score ( CMS ) and Manual Muscle Testing ( MMT ) were performed before treatment and at the end of 4 weeks treatment . In addition , follow up were performed 2 months after the end of treatment based on the degree of pain improvement . RESULTS VAS , TSS and CMS improved significantly ( P=0.001 ) in both groups , however the muscle strengths only improved significantly in adding laser group ( P adding low level laser therapy ( LLLT ) to the US and exercise was more efficient in improving the muscle strength in patients with shoulder tendonitis over a period of three months . However , it should be emphasized that , the current results might be due to the effects of laser and exercise instead of laser , us and exercise ( as we had no independent group for US )", "Rotator cuff tendinitis is one of the main causes of shoulder pain . The objective of this study was to evaluate the possible additive effects of low-power laser treatment in combination with conventional physiotherapy endeavors in these patients . A total of 50 patients who were referred to the Physical Medicine and Rehabilitation Clinic with shoulder pain and rotator cuff disorders were selected . Pain severity measured with visual analogue scale ( VAS ) , abduction , and external rotation range of motion in shoulder joint was measured by goniometry , and evaluation of daily functional abilities of patients was measured by shoulder disability question naire . Twenty-five of the above patients were r and omly assigned into the control group and received only routine physiotherapy . The other 25 patients were assigned into the experimental group and received conventional therapy plus low-level laser therapy ( 4 J/cm2 at each point over a maximum of ten painful points of shoulder region for total 5 min duration ) . The above measurements were assessed at the end of the third week of therapy in each group and the results were analyzed statistically . In both groups , statistically significant improvement was detected in all outcome measures compared to baseline ( p control of pain ( reduction in VAS average ) and shoulder disability problems in the experimental group versus the control ( 3.1 ± 2.2 vs. 5 ± 2.6 , p = 0.029 and 4.4 ± 3.1 vs. 8.5 ± 5.1 , p = 0.031 , respectively ) after intervention . Positive objective signs also had better results in the experimental group , but the mean range of active abduction ( 144.92 ± 31.6 vs. 132.80 ± 31.3 ) and external rotation ( 78.0 ± 19.5 vs. 76.3 ± 19.1 ) had no significant difference between the two groups ( p = 0.20 and 0.77 , respectively ) . As one of physical modalities , gallium-arsenide low-power laser combined with conventional physiotherapy has superiority over routine physiotherapy from the view of decreasing pain and improving the patient ’s function , but no additional advantages were detected in increasing shoulder joint range of motion in comparison to other physical agents", "The aim of this clinical trial was to evaluate the effectiveness of therapeutic MD on pain , functional capacity , muscle strength , quality of life , and depression in patients with subacromial impingement syndrome ( SIS ) . A total of 40 inpatient subjects with definite SIS were included in this study . These patients were sequentially r and omized into 2 groups . Group 1 ( n = 20 ) received therapeutic MD . Group 2 ( n = 20 ) was served as control group and received sham MD . Superficial heat and exercise program were given to both groups . Both of the programs were performed 5 times weekly for 3 weeks . Patients were assessed before treatment ( BT ) , after treatment ( AT ) , and at a 1-month follow-up ( F ) . Outcome measures included visual analogue scale , goniometry , Shoulder Pain and Disability Index , Shoulder Disability Question naire , shoulder isokinetic muscle testing , h and grip strength , Short Form 36 , and Beck Depression Index . The patients with SIS in each group had significant improvements in pain , shoulder ROM , disability , shoulder muscles and grip strength , quality of life , and depression AT and F when compared with their initial status ( P 0.05 ) . A 2,450-MHz MD regimen showed no beneficial effects in patients with SIS , so the superficial heat and exercise program , as it is efficient , may be preferable for the treatment of SIS , alone", "BACKGROUND Research ers have demonstrated moderate evidence for the use of exercise in the treatment of subacromial impingement syndrome ( SAIS ) . Recent evidence also supports eccentric exercise for patients with lower extremity and wrist tendinopathies . However , only a few investigators have examined the effects of eccentric exercise on patients with rotator cuff tendinopathy . PURPOSE To compare the effectiveness of an eccentric progressive resistance exercise ( PRE ) intervention to a concentric PRE intervention in adults with SAIS . STUDY DESIGN R and omized Clinical Trial . METHODS Thirty-four participants with SAIS were r and omized into concentric ( n = 16 , mean age : 48.6 ± 14.6 years ) and eccentric ( n = 18 , mean age : 50.1 ± 16.9 years ) exercise groups . Supervised rotator cuff and scapular PRE 's were performed twice a week for eight weeks . A daily home program of shoulder stretching and active range of motion ( AROM ) exercises was performed by both groups . The outcome measures of the Disabilities of the Arm , Shoulder , and H and ( DASH ) score , pain-free arm scapular plane elevation AROM , pain-free shoulder abduction and external rotation ( ER ) strength were assessed at baseline , week five , and week eight of the study . RESULTS Four separate 2x3 ANOVAs with repeated measures showed no significant difference in any outcome measure between the two groups over time . However , all participants made significant improvements in all outcome measures from baseline to week five ( p outcome measures except scapular plane elevation AROM . CONCLUSION Both eccentric and concentric PRE programs result ed in improved function , AROM , and strength in patients with SAIS . However , no difference was found between the two exercise modes , suggesting that therapists may use exercises that utilize either exercise mode in their treatment of SAIS . LEVEL OF EVIDENCE Therapy , level 1b", "Objectives : To evaluate the clinical effectiveness of a self-managed single exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy . Design : Multi-centre pragmatic unblinded parallel group r and omised controlled trial . Setting : UK National Health Service . Participants : Patients with a clinical diagnosis of rotator cuff tendinopathy . Interventions : The intervention was a programme of self-managed exercise prescribed by a physiotherapist in relation to the most symptomatic shoulder movement . The control group received usual physiotherapy treatment . Main outcome measures : The primary outcome measure was the Shoulder Pain & Disability Index ( SPADI ) at three months . Secondary outcomes included the SPADI at six and twelve months . Results : A total of 86 patients ( self-managed loaded exercise n=42 ; usual physiotherapy n=44 ) were r and omised . Twenty-six patients were excluded from the analysis because of lack of primary outcome data at the 3 months follow-up , leaving 60 ( n=27 ; n=33 ) patients for intention to treat analysis . For the primary outcome , the mean SPADI score at three months was 32.4 ( SD 20.2 ) for the self-managed group , and 30.7 ( SD 19.7 ) for the usual physiotherapy treatment group ; mean difference adjusted for baseline score : 3.2 ( 95 % Confidence interval -6.0 to + 12.4 P = 0.49 ) . By six and twelve months there remained no significant difference between the groups . Conclusions : This study does not provide sufficient evidence of superiority of one intervention over the other in the short- , mid- or long-term and hence a self-management programme based around a single exercise appears comparable to usual physiotherapy treatment", "OBJECTIVE The aim of this study was to compare the effectiveness of low-level laser therapy and ultrasound therapy in the treatment of subacromial impingement syndrome . MATERIAL S AND METHODS Thirty one patients with subacromial impingement syndrome were r and omly assigned to low-level laser therapy group ( n=16 ) and ultrasound therapy group ( n=15 ) . Study participants received 10 treatment sessions of low-level laser therapy or ultrasound therapy over a period of two-consecutive weeks ( five days per week ) . Outcome measures ( visual analogue pain scale , Shoulder Pain and Disability Index -SPADI- , patient 's satisfactory level and sleep interference score ) were assessed before treatment and at the 1st and 3rd months after treatment . All patients were analyzed by the intent-to-treat principle . RESULTS Mean reduction in VAS pain , SPADI disability and sleep interference scores from baseline to after 1 month , and 3 months of treatment was statistically significant in both groups ( P change in VAS pain , SPADI disability and sleep interference scores between the two groups ( P > 0.05 ) . The mean level of patient satisfaction in group 1 at the first and third months after treatment was 72.45 ± 23.45 mm and 71.50 ± 16.54 mm , respectively . The mean level of patient satisfaction in group 2 at the first and third months after treatment was 70.38 ± 21.52 mm and 72.09 ± 13.42 mm , respectively . There was no significant difference in the mean level of patient satisfaction between the two groups ( p > 0.05 ) . CONCLUSIONS The results suggest that efficacy of both treatments were comparable to each other in regarding reducing pain severity and functional disability in patients with subacromial impingement syndrome . Based on our findings , we conclude that low-level laser therapy may be considered as an effective alternative to ultrasound based therapy in patients with subacromial impingement syndrome especially ultrasound based therapy is contraindicated", "BACKGROUND Muscle imbalance between serratus anterior ( SA ) , upper trapezius ( UA ) , middle trapezius ( MT ) , and lower trapezius ( LT ) muscles has been observed in subjects with subacromial impingement syndrome ( SAIS ) . OBJECTIVE ( 1 ) To investigate the effect of electromyography ( EMG ) biofeedback training on muscle balance ratios and scapular kinematics in healthy adults and subjects with SAIS . ( 2 ) To investigate whether the effects of EMG biofeedback on muscle balance ratios are different between groups . DESIGN Twelve healthy adults and 13 subjects with SAIS were recruited in this study . EMG was used to record the activity of scapular muscles . The ratios ( UT/SA , UT/MT , and UT/LT ) during exercises with/without EMG biofeedback were calculated . Scapular kinematics were recorded before and after exercises with/without EMG biofeedback . RESULTS For the subjects with SAIS , muscle balance ratios were lower during forward flexion with EMG biofeedback than during exercise only ( UT/SA : 70.3 - 45.2 ; UT/LT : 124.8 - 94.6 ) . Additionally , similar results were found during side-lying external rotation ( UT/MT : 58.5 - 36.4 ) . For the scapular upward rotation and tipping in both groups , there were no significant differences with and without EMG biofeedback . CONCLUSION EMG biofeedback improved the scapular muscular balance during training exercises in both groups . Further clinical trials should investigate the long-term effects of EMG biofeedback", "STUDY DESIGN Controlled laboratory study . OBJECTIVES To assess scapular kinematics and electromyographic signal amplitude of the shoulder musculature , before and after thoracic spine manipulation ( TSM ) in subjects with rotator cuff tendinopathy ( RCT ) . Changes in range of motion , pain , and function were also assessed . BACKGROUND There are various treatment techniques for RCT . Recent studies suggest that TSM may be a useful component in the management of pain and dysfunction associated with RCT . METHODS Thirty subjects between 18 and 45 years of age , who showed signs of RCT , participated in this study . Changes in scapular kinematics and muscle activity , as well as changes in shoulder pain and function , were assessed pre-TSM and post-TSM using paired t tests and repeated- measures analyses of variance . RESULTS TSM did not lead to changes in range of motion or scapular kinematics , with the exception of a small decrease in scapular upward rotation ( P = .05 ) . The only change in muscle activity was a small but significant increase in middle trapezius activity ( P = .03 ) . After TSM , subjects demonstrated decreased pain during performance of the Jobe empty-can ( mean ± SD change , 2.6 ± 1.1 ) , Neer ( 2.6 ± 1.3 ) , and Hawkins-Kennedy ( 2.8 ± 1.3 ) tests ( all , P decreased pain with shoulder flexion ( mean ± SD change , 2.0 ± 1.5 ; P improved shoulder function ( force production , 2.5 ± 1.4 kg ; Penn Shoulder Score , 7.7 ± 9.4 ; sports/performing arts module of the Disabilities of the Arm , Shoulder and H and question naire , 16.4 ± 13.2 ) ( all , P shoulder pain and function post-TSM are not likely explained by alterations in scapular kinematics or shoulder muscle activity . For people with pain associated with RCT , TSM may be an effective component of their treatment plan to improve pain and function . However , further r and omized controlled studies are necessary to better vali date this treatment approach . LEVEL OF EVIDENCE Therapy , level 4", "OBJECTIVE The purpose of this study was to compare the immediate effects of mobilization with movement ( MWM ) to a sham technique in patients with shoulder impingement syndrome . METHODS A r and omized controlled trial was performed . Forty-two patients ( mean ± SD age , 55 ± 9 years ; 81 % female ) satisfied eligibility criteria , agreed to participate , and were r and omized into an MWM group ( n = 21 ) or sham manual contact ( n = 21 ) . The primary outcome measures including pain intensity , pain during active range of motion , and maximal active range of motion were assessed by a clinician blinded to group allocation . Outcomes were captured at baseline and after 2 weeks of MWM treatment or sham intervention . The primary analysis was the group × time interaction . RESULTS The 2 × 2 analysis of variance revealed a significant group × time interaction for pain intensity during shoulder flexion ( F = 7.054 ; P = .011 ) , pain-free shoulder flexion ( F = 32.853 ; P maximum shoulder flexion ( F = 18.791 ; P and shoulder external rotation ( F = 7.950 ; P the MWM group . No other significant differences were found . CONCLUSIONS Patients with shoulder impingement syndrome who received 4 sessions of MWM exhibited significantly better outcomes for pain during shoulder flexion , pain-free range of shoulder flexion , maximal shoulder flexion , and maximal external rotation than those patients who were in the sham group", "QUESTION Are there different effects of home exercises and supervised exercises on pain and disability for people with subacromial impingement ? DESIGN R and omised trial with two treatment arms , concealed allocation , blinded assessment of some outcomes , and intention-to-treat analysis . PARTICIPANTS Forty-six patients with subacromial impingement were recruited from an interdisciplinary outpatient clinic of physical medicine and rehabilitation at a university hospital in Norway . INTERVENTION The home exercise group had one supervised exercise treatment followed by exercises at home for 6 weeks . The supervised exercise group had up to 10 supervised exercise treatments in addition to home exercises for 6 weeks . OUTCOME MEASURES The primary outcome was the Shoulder Pain and Disability Index ( SPADI ) . Secondary outcome variables were : average pain during the past week , the Fear Avoidance Beliefs Question naire , participant satisfaction with treatment , active range of motion , work status and clinical shoulder tests . Pain was assessed weekly and all outcomes were assessed at 6 weeks . Participants were free to seek ongoing treatment of their choice until 26 weeks , when the SPADI was assessed again . RESULTS While both groups improved considerably , the groups did not differ significantly on the SPADI after the intervention at 6 weeks ( 0 points , 95 % CI -14 to 14 ) or when followed up at 26 weeks ( -2 points , 95 % CI -21 to 17 ) . There were no between-group differences for pain at any time . The remaining outcomes also did not differ significantly , except for the clinical tests of shoulder impingement . In the supervised exercise group , 11 out of 23 participants had two or more positive tests , compared to 18 out of 21 in the home exercise group . CONCLUSION Supervision of more than the first session of a 6-week exercise regimen did not cause significant differences in pain and disability in people with subacromial impingement . TRIAL REGISTRATION NCT01257113", "OBJECTIVE Local steroid injections and community-based physiotherapy have been shown to be of similar benefit for treating shoulder pain presenting to primary care . This paper presents a cost consequences analysis of a prospect i ve economic evaluation , conducted alongside a r and omized clinical trial ( RCT ) of corticosteroid injections versus physiotherapy for new episodes of unilateral shoulder pain , to determine the economic implication s of injection versus physiotherapy . METHODS A pragmatic RCT with 207 patients r and omized to either physiotherapy ( n = 103 ) or local steroid injection ( n = 104 ) was conducted . The re source inputs required were identified for each treatment arm in terms of capital , staff and consumables . These were measured for the period up to 6 months post-r and omization . Outcome measures included shoulder disability , shoulder pain , global assessment of health change and the EQ5D , all at 6 months . A sensitivity analysis was performed around the general practitioner minor surgical fee . RESULTS Analysis is presented on the 199 patients for which the general practice record review ( 101 physiotherapy , 98 injection ) was available . The total mean costs , per patient , were 71.28 pound sterling for the injection group and 114.60 pound sterling for the physiotherapy group . The difference in average total cost per patient was 43.32 pound sterling ( 95 % bootstrap confidence interval : 16.21 pound sterling , 68.03 pound sterling ) . This is a statistically significant difference in cost . Outcome was similar in both groups across all measures following intervention . Smaller mean differences in cost were observed between the treatment groups in the sensitivity analysis , but the difference remained in favour of injection over physiotherapy . CONCLUSIONS This study has shown , given similar clinical outcomes across the treatment groups , that corticosteroid injections were the cost-effective option for patients presenting with new episodes of unilateral shoulder pain in primary care", "This prospect i ve , r and omized trial was performed to compare the results of treating subacromial impingement syndrome of the shoulder by a guided self-training program with the treatment by conventional physiotherapy or a functional brace . Sixty patients with the diagnosis of an outlet impingement syndrome of the shoulder ( Neer I and II ) were treated either by strengthening the depressors of the humeral head with a guided self-training program , by conventional physiotherapy , or by wearing a functional brace . The Constant-Murley score was assessed after 6 and 12 weeks . Shoulder pain was monitored with a visual analog scale . All three groups showed a significant improvement in shoulder function as well as a significant reduction in pain . There were no statistically significant differences among the groups . Guided self-training can lead to results similar to those of conventional physiotherapy . The comparable effect of the functional brace remains unclear and might be explained by an influence on proprioception", "OBJECTIVE Evaluate the efficacy of acupuncture associated with physiotherapy for patients with painful shoulder . METHODS In a multicentre controlled r and omized study , participants were recruited with a clinical diagnosis of unilateral subacromial syndrome from six rehabilitation medicine departments belonging to the Public Health System in two Spanish regions . All participants received 15 sessions of physiotherapy during the 3 weeks that the treatment lasted and were r and omized to additionally receive , once a week , acupuncture or mock TENS ( transcutaneous electrical nerve stimulation ) . The primary outcome measure was the change in the Constant-Murley Score ( CMS ) for functional assessment of the shoulder , at 4 weeks after r and omization . This study is registered as an International St and ard R and omized Controlled Trial , number IS RCT N28687220 . RESULTS A total of 425 patients were recruited . The mean score ( s.d . ) on the CMS had increased by 16.6 ( 15.6 ) points among the acupuncture group , compared with 10.6 ( 13.5 ) points in the control group , and the mean difference between the two groups was statistically significant ( 6.0 points ; 95 % CI 3.2 , 8.8 points ; P consumption of analgesics , compared with a corresponding 30 % among the control group ( P Single-point acupuncture in association with physiotherapy improves shoulder function and alleviates pain , compared with physiotherapy as the sole treatment . This improvement is accompanied by a reduction in the consumption of analgesic medicaments", "The subacromial syndrome is the most common source of shoulder pain . The mainstays of conservative treatment are non-steroidal anti-inflammatory drugs and exercise therapy . Recently , low-level laser therapy ( LLLT ) has been popularized in the treatment of various musculoskeletal disorders . The aim of this study is to evaluate the additive effects of LLLT with exercise in comparison with exercise therapy alone in treatment of the subacromial syndrome . We conducted a r and omised clinical study of 80 patients who presented to clinic with subacromial syndrome ( rotator cuff and biceps tendinitis ) . Patients were r and omly allocated into two groups . In group I ( n = 40 ) , patients were given laser treatment ( pulsed infrared laser ) and exercise therapy for ten sessions during a period of 2 weeks . In group II ( n = 40 ) , placebo laser and the same exercise therapy were given for the same period . Patients were evaluated for the pain with visual analogue scale ( VAS ) and shoulder range of motion ( ROM ) in an active and passive movement of flexion , abduction and external rotation before and after treatment . In both groups , significant post-treatment improvements were achieved in all parameters ( P = 0.00 ) . In comparison between the two groups , a significant improvement was noted in all movements in group I ( P = 0.00 ) . Also , there was a substantial difference between the groups in VAS scores ( P = 0.00 ) which showed significant pain reduction in group I. This study indicates that LLLT combined exercise is more effective than exercise therapy alone in relieving pain and in improving the shoulder ROM in patients with subacromial syndrome", "OBJECTIVE The study investigated the effectiveness of stretching , strengthening exercises , and the scapular stabilization exercises on the pain , shoulder range of motion ( ROM ) , muscle strength , joint position sense ( JPS ) , scapular dyskinesis and quality of life ( OL ) in the patients with subacromial impingement syndrome ( SIS ) . METHODS 27 women and 13 men , mean age 51 ( 24 - 71 ) years old , were included in this study . All the patients were separated into 2 groups according to simple r and om table . Stretching and strengthening exercises were given to the group I ( n=20 ) and scapular stabilization exercises were added to the group II ( n=20 ) . The pain severity , shoulder ROM , muscle strength , JPS , lateral scapular slide test ( LSST ) , Western Ontario Rotator Cuff ( WORC ) Index were evaluated before and after treatment . Patients completed a 6-week rehabilitation program , three times a week . RESULTS The results showed that all measurements improved statistically in both groups after treatment ( p muscle strength , JPS and scapular dyskinesia were significantly different in group II ( p scapular stabilization exercises , given with stretching and strengthening exercises , can be more effective in increasing the muscle strength , developing the JPS and decreasing the scapular dyskinesis", "Objective : To compare the short-term effectiveness of precut kinesiology tape ( PCT ) to a nonsteroidal anti-inflammatory drug ( NSAID ) as adjuvant treatment to exercise physiotherapy in improving pain and function in patients with shoulder impingement . Design : R and omized , controlled assessor-blind parallel- design trial with 3 groups . Setting : Academic-community hospital . Patients : One hundred patients ( mean age : 48 ± 12.3 , 61 men , 39 women ) with a diagnosis of subacromial impingement ( SAI ) syndrome were r and omized to a treatment group from October 2009 to June 2012 . Eighty-one patients completed the study . Interventions : Patients were r and omized to one of the 3 treatment groups : PCT and Exercise ( n = 33 ) , NSAID and Exercise ( n = 29 ) , or Exercise only ( n = 38 ) for a 4 session 2-week intervention with a registered physiotherapist . Main Outcome Measures : Numeric pain rating scales for pain at rest and pain with arm elevation , the Simple Shoulder Test ( SST ) , and the Constant Score were assessed pretreatment and post-treatment . Results : A statistically significant reduction in pain at rest and pain with arm elevation , as well as improvement in SST and Constant Score were observed in all 3 treatment groups , with minimal clinical ly important differences shown on pain with elevation and SST scores . Between-group differences on all outcome measures were not statistically significant or clinical ly meaningful . Conclusions : The improvements in pain and function observed with an NSAID or PCT as adjuvant treatments were no greater than with rehabilitation exercise alone . If adjuvant treatment is desired , PCT seems to be better tolerated than an NSAID , although the difference did not reach significance . Clinical Relevance : The routine addition of adjuvant treatment is not supported by the results of this study . As adjuvant therapy , PCT seems to be better tolerated than an NSAID . If desired , clinicians may consider incorporating PCT along with an exercise component in the conservative treatment of SAI syndrome", "BACKGROUND Kinesiological taping ( KT ) is commonly used to improve symptoms associated with musculoskeletal disorders . However , review of the literature revealed minimal evidence to support the use of KT in treatment of shoulder disorders and controversy exists regarding the effect of KT in patients with shoulder impingement syndrome ( SIS ) . OBJECTIVE The purpose of this study was to investigate the effect of KT on pain intensity during movement , pain experienced during the night ( nocturnal pain ) , and pain-free shoulder range of motion ( ROM ) immediately after taping , after three days and after one week , in patients with SIS . DESIGN R and omized , Double blinded , Placebo-controlled design . PARTICIPANTS A total of 30 patients with SIS participated in this study . Patients were assigned r and omly to a control ( N = 15 ) and an experimental group ( N = 15 ) . METHODS The patients in the experimental group received a st and ardized therapeutic KT . The st and ardized , placebo neutral KT was applied for control group . KT was applied two times with a three day interval , remaining on during the 3 day interval . Both groups followed the same procedures . Pain-free active ROM during shoulder abduction , flexion , and elevation in the scapular plane was measured . Visual analogue scale ( VAS ) for pain intensity during movement or nocturnal pain and was assessed at baseline , immediately after KT , after three days , and one week after KT . RESULTS The result of repeated measures ANOVA showed a significant change in pain level during movement , nocturnal pain , and pain-free ROM ( p = 0.000 ) after KT in the experimental group . In the ANCOVA , controlling for pre-test scores , change in pain level at movement ( p = 0.009 ) and nocturnal pain ( p = 0.04 ) immediately after KT was significantly greater in the experimental group than in control group . There was no significant difference in ROM measures ( p > 0.05 ) between groups immediately after KT . No significant differences were found between the two groups in the after one week measurements of pain intensity and shoulder ROM . CONCLUSION The KT produces an immediate improvement in the pain intensity at movement and nocturnal pain in patients with SIS . LEVEL OF EVIDENCE 1", "OBJECTIVE The aim of this study was to investigate the effects of h and -behind-back ( HBB ) Mulligan mobilization with movement ( MWM ) techniques on acute shoulder pain , impairment , and disability . METHODS This double-blind , r and omized , controlled trial recruited 44 patients with acute shoulder pain and movement impairment presenting to an Indian general hospital . Participants were allocated to receive either MWM and exercise/hot pack ( n = 22 ) or exercise/hot pack alone ( n = 22 ) . The average duration of symptoms was 4.1 and 4.7 weeks in the exercise and MWM groups , respectively . The primary outcome was HBB range of motion ( ROM ) . Secondary variables were shoulder internal rotation ROM , pain intensity score , and shoulder disability identified by the shoulder pain and disability index . All variables were evaluated by a blinded assessor before and immediately after 9 treatment sessions over 3 weeks . RESULTS Paired t tests revealed that both groups demonstrated statistically significant improvements ( P the MWM-with-exercise group showed significantly greater improvements ( P -behind-back ROM showed a mean difference of 9.31 ° ( 95 % confidence interval , 7.38 - 11.27 ) , favoring greater improvement in the MWM-with-exercise group . CONCLUSIONS In this study , the outcomes of patients with acute shoulder pain and disability receiving shoulder HBB MWM with exercise improved greater than those receiving exercise/hot packs alone ", "BACKGROUND Traditional rehabilitation improves pain and function in patients with shoulder impingement syndrome . Neurocognitive rehabilitation has shown to be highly effective after surgical reconstruction of the anterior cruciate ligament . However , its effects in patients with shoulder impingement syndrome have not yet been established . AIM The aim of the study was to compare the effects of neurocognitive therapeutic exercise , based on proprioception and neuromuscular control , on pain and function in comparison to traditional therapeutic exercise in patients with shoulder impingement syndrome . DESIGN Single-blind r and omized , non-inferiority clinical trial . SETTING Outpatient clinic of Geriatrics and Physiatrics , University Hospital . POPULATION Forty-eight patients with shoulder impingement syndrome ( Neer stage I ) and pain lasting for at least three months . METHODS Participants were r and omly allocated ( 1:1 ) to either neurocognitive therapeutic exercise or traditional therapeutic exercise . Both treatments were provided one-hour session , three times a week for five weeks . The primary outcome measure was the short form of the Disability of the Arm , Shoulder and H and Question naire ( Quick-DASH question naire ) for the assessment of physical ability and symptoms of the upper extremity . SECONDARY OUTCOME MEASURES Constant-Murley shoulder outcome score for the determination of range of motion , pain and strength ; American Shoulder and Elbow Surgeons Society st and ardized shoulder assessment form for the evaluation of physical ability in daily-living tasks ; a visual analogue scale for pain assessment at rest and during movements ; Likert score for the estimation of participant satisfaction . ENDPOINTS before treatment , end of treatment , 12 and 24 weeks after the completion of each intervention for all outcome measures , except for the Likert score that was evaluated only at the end of treatment . FOLLOW-UP 24 weeks . RESULTS At the end of treatment and at follow-up , both treatment groups experienced improvements in all outcomes measures relative to baseline values , except for the visual analogue scale at rest that was unaffected by traditional therapeutic exercise . For all outcome measures , changes over time were greater in the neurocognitive therapeutic exercise group relative to the traditional therapeutic exercise group . The level of satisfaction with treatment was higher for participants in the neurocognitive therapeutic exercise group . CONCLUSION Neurocognitive rehabilitation is effective in reducing pain and improving function in patients with shoulder impingement syndrome , with benefits maintained for at least 24 weeks . CLINICAL REHABILITATION IMPACT skills and function of the shoulder can greatly benefit from neurocognitive rehabilitation", "BACKGROUND Interference is an important feature of the waves . When two or more in phase light waves meet , a new and reinforced wave is generated . Shoulder pain is a common clinical problem and laser is one of the treatments frequently used to relieve it . OBJECTIVE To test the safety of interferential laser therapy generated by two independent low level lasers and compare its effectiveness with conventional single laser therapy in the reduction of shoulder musculoskeletal pain and associated disability . DESIGN R and omised and single-blind controlled clinical trial . SETTING Physiotherapy Unit and Rehabilitation Department of Ramon y Cajal University Hospital ( Madrid ) . PARTICIPANTS 200 patients with shoulder musculoskeletal pain were r and omly assigned in two groups , 100 people each . INTERVENTIONS Group I , experimental ( n=100 ) received interferential laser , placing two probes opposite each other over the shoulder joint . Group II , control ( n=100 ) received conventional laser therapy , using a single probe along with a second inactive dummy probe . Lasers used were GaAlAs diode ( 810 nm , 100 mW ) , in continuous emission . Laser was applied in contact mode through ten sessions , on 5 shoulder points ( 7 Joules/point ) per session . MAIN OUTCOME MEASURES visual analogue scale ( VAS ) score and shoulder pain disability index ( SPADI ) , recorded before and after laser treatment . RESULTS There were no differences between both groups in the reduction of pain , either assessed by VAS scale ( median difference=0 , 95 % CI of the difference = -.6 to .5 , p = 0.81 ) or SPADI index ( median difference = .4 , 95 % CI of the difference = -2.9 to 3.8 , p = 0.80 ) , using the Mann-Whitney U-test . Comparison between the scores recorded before and after the treatment , within each group , showed significant differences for VAS during movement ( median difference=3 , 95 % CI of the difference = 2.07 to 4 , p SPADI index ( median difference=3.5 , 95 % CI of the difference = 2.67 to 3.85 , Wilcoxon test , p low level lasers in order to generate interference inside the irradiated tissue showed to be a safe therapy . Both interferential and conventional laser therapy reduced shoulder pain and disability . Nevertheless , differences between them were not detected . Future research in this field could include applying this technique with other laser parameters or application forms", "Study Design Multicenter r and omized controlled trial . Background Cervicothoracic manual therapy has been shown to improve pain and disability in individuals with shoulder pain , but the incremental effects of manual therapy in addition to exercise therapy have not been investigated in a r and omized controlled trial . Objectives To compare the effects of cervicothoracic manual therapy and exercise therapy to those of exercise therapy alone in individuals with shoulder pain . Methods Individuals ( n = 140 ) with shoulder pain were r and omly assigned to receive 2 sessions of cervicothoracic range-of-motion exercises plus 6 sessions of exercise therapy , or 2 sessions of high-dose cervicothoracic manual therapy and range-of-motion exercises plus 6 sessions of exercise therapy ( manual therapy plus exercise ) . Pain and disability were assessed at baseline , 1 week , 4 weeks , and 6 months . The primary aim ( treatment group by time ) was examined using linear mixed-model analyses and the repeated measure of time for the Shoulder Pain and Disability Index ( SPADI ) , the numeric pain-rating scale , and the shortened version of the Disabilities of the Arm , Shoulder and H and question naire ( QuickDASH ) . Patient-perceived success was assessed and analyzed using the global rating of change ( GROC ) and the Patient Acceptable Symptom State ( PASS ) , using chi-square tests of independence . Results There were no significant 2-way interactions of group by time or main effects by group for pain or disability . Both groups improved significantly on the SPADI , numeric pain-rating scale , and QuickDASH . Secondary outcomes of success on the GROC and PASS significantly favored the manual therapy-plus-exercise group at 4 weeks ( P = .03 and P cervicothoracic manual therapy to an exercise program did not improve pain or disability in patients with shoulder pain , but did improve patient-perceived success at 4 weeks and 6 months and acceptability of symptoms at 4 weeks . More research is needed on the use of cervicothoracic manual therapy for treating shoulder pain . Level of Evidence Therapy , level 1b . Prospect ively registered March 30 , 2012 at www . Clinical Trials.gov ( NCT01571674 ) . J Orthop Sports Phys Ther 2016;46(8):617 - 628 . doi:10.2519/jospt.2016.6319", "OBJECTIVES The aim of this r and omized controlled study was to assess the efficacy of manual therapy in the treatment of patients with symptomatic supraspinatus tendinopathy . METHODS Seventy-seven patients ( age range , 30 to 55 years ) with supraspinatus tendinopathy , were r and omly assigned to one of the three treatment groups : a supervised exercise program ( Group 1 ) , a supervised exercise program combined with joint and soft tissue mobilization ( Group 2 ) , or a home-based rehabilitation program ( Group 3 ) . All patients had rehabilitation for 12 weeks . Pain level was evaluated with a visual analogue scale ( VAS ) and the range of motion ( ROM ) was measured with a goniometer . The Modified American Shoulder and Elbow Surgery ( MASES ) score was used in functional assessment . Flexion , abduction , internal and external rotation strengths were measured with a manual muscle test . All patients were evaluated before , and at the 4th and 12th week of the rehabilitation . RESULTS All groups experienced significant decrease in pain and an increase in shoulder muscle strength and function by both the 4th and 12th weeks of treatment ( p no significant difference between the groups in terms of function ( p>0.05 ) . However , the greatest improvement in functionality was found in Group 2 . CONCLUSION Supervised exercise , supervised and manual therapy , and home-based exercise are all effective and promising methods in the rehabilitation of the patients with subacromial impingement syndrome . The addition of an initial manual therapy may improve the results of the rehabilitation with exercise", "The evidence to guide use of spinal manipulative therapy ( SMT ) for patients with shoulder pain is limited . A vali date d sham comparator is needed to ascertain the unique effects of SMT . We investigated the plausibility of a thoracic sham-SMT comparator for SMT in patients with shoulder pain . Participants ( n = 56 ) with subacromial impingement syndrome were r and omized to thoracic SMT or a sham-SMT . An examiner blinded to group assignment took measures pre- and post-treatment of shoulder active range of motion ( AROM ) and perceived effects of the assigned intervention . Treatment consisted of six upper , middle and lower thoracic SMT or sham-SMT . The sham-SMT was identical to the SMT , except no thrust was applied . Believability as an active treatment was measured post-treatment . Believability as an active treatment was not different between groups ( χ(2 ) = 2.19 ; p = 0.15 ) . Perceptions of effects were not different between groups at pre-treatment ( t = 0.12 ; p = 0.90 ) or post-treatment ( t = 0.40 ; p = 0.69 ) , and demonstrated equivalency with 95 % confidence between groups at pre- and post-treatment . There was no significant change in shoulder flexion in either group over time , or in the sham-SMT for internal rotation ( p > 0.05 ) . The SMT group had an increase of 6.49 ° in internal rotation over time ( p = 0.04 ) . The thoracic sham-SMT of this study is a plausible comparator for SMT in patients with shoulder pain . The sham-SMT was believable as an active treatment , perceived as having equal beneficial effects both when verbally described and after familiarization with the treatment , and has an inert effect on shoulder AROM . This comparator can be considered for used in clinical trials investigating thoracic SMT . IRB number : HM 13182", "Abstract The purpose of this double-blind , r and omized controlled pilot study was to compare the effectiveness of four physical therapy interventions in the treatment of primary shoulder impingement syndrome : 1 ) supervised exercise only , 2 ) supervised exercise with glenohumeral mobilizations , 3 ) supervised exercise with a mobilization-with-movement ( MWM ) technique , or 4 ) a control group receiving only physician advice . Thirty-three subjects diagnosed with primary shoulder impingement were r and omly assigned to one of these four groups . Main outcome measures included 24-hour pain ( VAS ) , pain with the Neer and Hawkins-Kennedy tests , shoulder active range of motion ( AROM ) , and shoulder function ( SPADI ) . Repeated- measures analyses indicated significant decreases in pain , improved function , and increases in AROM . Univariate analyses on the percentage of change from pre- to post-treatment for each dependent variable found no statistically significant differences ( P MWM and mobilization groups had a higher percentage of change from pre- to post-treatment on all three pain measures ( VAS , Neer , Hawkins-Kennedy ) . The three intervention groups had a higher percentage of change on the SPADI . The MWM group had the highest percentage of change in AROM , and the mobilization group had the lowest . This pilot study suggests that performing glenohumeral mobilizations and MWM in combination with a supervised exercise program may result in a greater decrease in pain and improved function although studies with larger sample s and discriminant sampling methods are needed", "OBJECTIVE To assess pain , function , quality of life , and muscle strength in patients with shoulder impingement syndrome who participated in muscle strengthening exercises . METHODS A total of 60 patients diagnosed with shoulder impingement syndrome were selected from the clinics of the Federal University of São Paulo and r and omly distributed into experimental and control groups . Patients were evaluated regarding pain , function , quality of life , muscle strength , and the number of antiinflammatory drugs and analgesics taken . Patients then participated in the progressive resistance training program for the musculature of the shoulder , which was held twice a week for 2 months , while the control group remained on a waiting list . RESULTS Sixty patients were r and omly allocated to the experimental group ( 21 women and 9 men , mean age 56.3 years ) and control group ( 25 women and 5 men , mean age 54.8 years ) . Patients from the experimental group showed an improvement from 4.2 cm to 2.4 cm on a 10-cm visual analog scale ( P pain at rest and from 7.4 cm to 5.2 cm ( P pain during movement . Function went from 44.0 to 33.2 ( P Disabilities of the Arm , Shoulder , and H and assessment and domains from the Short Form 36 . There was a statistically significant difference in improvement in pain and function between patients in the experimental group and those in the control group ( P progressive resistance training program for the musculature of the shoulder in patients with shoulder impingement syndrome was effective in reducing pain and improving function and quality of life", "BACKGROUND AND PURPOSE There is no definitive evidence for the efficacy of the physical therapy interventions used for patients with impingement syndrome . The purpose of this study was to compare manual acupuncture and continuous ultrasound , both applied in addition to home exercises , for patients diagnosed with impingement syndrome . SUBJECTS AND METHODS Eighty-five patients with clinical signs of impingement syndrome were r and omly assigned to either a group that received acupuncture ( n=44 ) or a group that received ultrasound ( n=41 ) . Both interventions were given by physical therapists twice a week for 5 weeks in addition to a home exercise program . Scores from 3 shoulder disability measures , combined in the analysis , measured change during a period of 12 months . RESULTS Both groups improved , but the acupuncture group had a larger improvement in the combined score . DISCUSSION AND CONCLUSION The results suggest that acupuncture is more efficacious than ultrasound when applied in addition to home exercises", "Aim To compare the effectiveness of l and mark-guided local injections and ultrasonography ( USG ) guided injections for shoulder pain . Methods A total 60 consecutive patients with shoulder pain due to soft tissue disorders was enrolled , and r and omly assigned to receive triamcinolone ( 40 mg ) either by l and mark-guided ( LMG , n=30 ) or USG guided ( n=30 ) injection . The patients were evaluated on admission and 6 weeks after the injection . Clinical assessment included demographic and clinical data , a visual analoge scale ( VAS ) for pain ( 0 to 10 cm ) , the Constant scale ( 0 to 100 ) for function , passive and active shoulder range of motion ( ROM ) with goniometric evaluation , and postinjection adverse effects . Results Initial demographic , clinical and USG findings in the groups exhibited no significant differences . Six weeks after injection , the VAS and the Constant score showed a significantly better improvement in USG group compared with LMG group ( mean VAS score decrease : 4.0±1.7 for USG vs. 2.2±0.9 for LMG , P in active and passive ROM values in both groups , USG group values being better . Initially 18 patients in LMG and 24 patients in USG had limited shoulder ROM , of which 6 was returned to normal values in LMG group and 12 in USG group at 6 week after injection ( P corticosteroids to patients with shoulder pain due to soft tissue disorders under the USG-guidance may improve therapeutic effectiveness and reduce adverse effects ", "STUDY DESIGN R and omized controlled trial . OBJECTIVES To determine if thoracic spinal manipulative therapy ( SMT ) alters thoracic kinematics , thoracic excursion , and scapular kinematics compared to a sham SMT in individuals with subacromial impingement syndrome , and also to compare changes in patient-reported outcomes between treatment groups . BACKGROUND Prior studies indicate that thoracic SMT can improve pain and disability in individuals with subacromial impingment syndrome . However , the mechanisms underlying these benefits are not well understood . METHODS Participants with shoulder impingement symptoms ( n = 52 ) were r and omly assigned to receive a single session of thoracic SMT or sham SMT . Thoracic and scapular kinematics during active arm elevation and overall thoracic excursion were measured before and after the intervention . Patient-reported outcomes measured were pain ( numeric pain-rating scale ) , function ( Penn Shoulder Score ) , and global rating of change . RESULTS Following the intervention , there were no significant differences in changes between groups for thoracic kinematics or excursion , scapular kinematics , and patient-reported outcomes ( P>.05 ) . Both groups showed an increase in scapular internal rotation during arm raising ( mean , 0.9 ° ; 95 % confidence interval [ CI ] : 0.3 ° , 1.6 ° ; P = .003 ) and lowering ( 0.8 ° ; 95 % CI : 0.0 ° , 1.5 ° ; P = .041 ) , as well as improved pain reported on the numeric pain-rating scale ( 1.2 points ; 95 % CI : 0.3 , 1.8 ; P function on the Penn Shoulder Score ( 9.1 points ; 95 % CI : 6.5 , 11.7 ; P following thoracic SMT . There were small but likely not clinical ly meaningful changes in scapular internal rotation in both groups . Patient-reported pain and function improved in both groups ; however , there were no significant differences in the changes between the SMT and the sham SMT groups . Overall , patient-reported outcomes improved in both groups without meaningful changes to thoracic or scapular motion . LEVEL OF EVIDENCE Therapy , level 1b-", "AIM Rotator cuff problems are common causes of pain and restriction of movement in shoulder . The aim of this study to compare the effect of intra-articular injection of corticosteroid and conventional transcutaneous electrical nerve stimulator ( TENS ) treatment in treatment of rotator cuff tendinitis . METHODS Subjects were r and omly allocated into Group 1 ( intra-articular injection of corticosteroid ) and Group 2 ( conventional transcutaneous electrical nerve stimulation-TENS ) . Outcome measurements were performed using the Visual Analogue Scale ( VAS ) for pain , range of motion ( ROM ) , the Shoulder Disability Question naire ( SDQ ) , the Short Form-36 ( SF-36 ) , and Beck Depression Scale ( BDS ) question naires and paracetamol consumption . RESULTS In both groups , significant improvement was observed in all weeks in VAS , ROM and SDQ scores ( P SF36 scores at the end of the treatment in both groups ( P BDI score ( P>0.05 ) . In both treatment groups , paracetamol consumption decreased in time ( P VAS-at night and VAS-at rest in weeks 1 , 4 and 12 , and VAS-during movement in week 1 and 12 ( P passive abduction and the active and passive IR ROM measurements ( P SDQ scores ( P of corticosteroid and conventional TENS are efficient in the treatment of rotator cuff tendinitis . When two treatments are compared , it may be concluded that intra-articular steroid injection was more effective especially in the first weeks regarding pain , ROM and disability . Otherwise , use of TENS allow to patients to increase activity level , improve function and quality of life like that in our study . TENS , as it is cheaper , non-invasive , more easily performed and efficient , may be preferable for the treatment of shoulder pain . Further studies are needed to include these results in the prospect i ve treatment guidelines", "There is a lack of evidence about the efficacy of routinely used interventions in shoulder pain , such as corticosteroid injection and physiotherapy . This pilot study was set up to assess the feasibility of a larger , r and omized controlled trial . Patients with the clinical presentation of a painful arc of less than 6 months ' duration were recruited through their general practitioners . A total of 112 patients were r and omized to 4 groups : control , physiotherapy , a course of subacromial steroid injections , or both physiotherapy and steroid injections . The primary outcome measure was the Oxford Shoulder Score ( OSS ) . Follow-up was 18 weeks and by postal question naire at 1 year . No significant differences were found within groups between the OSS scores or the Physical Health total of the Medical Outcomes Study Short Form 36 ( SF-36 ) Health Survey at the beginning and end of the trial or at 1 year . By analysis of covariance , no significant differences were found between treatment groups . Larger studies are needed . A power calculation from our data suggests recruitment of more than 800 patients would be required to achieve a 90 % chance of a clinical ly significant difference being detected between these groups", "Purpose . To investigate the effectiveness of low-level laser therapy ( LLLT ) in addition to exercise programme on shoulder function in subacromial impingement syndrome ( SAIS ) . Method . Sixty-seven patients with SAIS were r and omly assigned to either a group that received laser ( n = 34 ) or a group that received placebo Laser ( n = 26 ) . Pain , functional assessment , disability and muscle strength of shoulder were assessed before and after a 3-week rehabilitation programme . Besides Laser or placebo Laser , superficial cold and progressive exercise programme were administered to both groups , 5 days a week , for 3 weeks . A progressive exercise programme that was done daily twice under supervision in clinic and at home was given to the patients . Results . After the treatment , all outcome measurements had shown significant improvement except muscle strength in both the groups . When the parameters of the improvement were compared , there were no significant differences between the two groups after treatment . Conclusion . We concluded that there is no fundamental difference between LLLT and placebo LLLT when they are supplementing an exercise programme for rehabilitation of patients with shoulder impingement syndrome", "OBJECTIVE The purpose of this study was to compare the effects of manual therapy with exercise to kinesiotaping with exercise for patients with subacromial impingement syndrome . METHODS R and omized clinical before and after trial was used . Fifty-four patients diagnosed as having subacromial impingement syndrome who were referred for outpatient treatment were included . Eligible patients ( between 30 and 60 years old , with unilateral shoulder pain ) were r and omly allocated to 2 study groups : kinesiotaping with exercise ( n = 28 ) or manual therapy with exercise ( n = 26 ) . In addition , patients were advised to use cold packs 5 times per day to control for pain . Visual analog scale for pain , Disability of Arm and Shoulder Question naire for function , and diagnostic ultrasound assessment for supraspinatus tendon thickness were used as main outcome measures . Assessment s were applied at the baseline and after completing 6 weeks of related interventions . RESULTS At the baseline , there was no difference between the 2 group characteristics ( P > .05 ) . There were significant differences in both groups before and after treatment in terms of pain decrease and improvement of Disability of Arm and Shoulder Question naire scores ( P ultrasound for tendon thickness after treatment in both groups ( P > .05 ) . The only difference between the groups was at night pain , result ing in favor of the kinesiotaping with exercise group ( P kinesiotaping with exercise and manual therapy with exercise . Both treatments may have similar results in reducing pain and disability in subacromial impingement in 6 weeks", "The purpose of this single blinded r and omised controlled trial was to investigate the effects of soft tissue massage on range of motion , reported pain and reported function in patients with shoulder pain . Twenty-nine patients referred to physiotherapy for shoulder pain were r and omly assigned to a treatment group that received six treatments of soft tissue massage around the shoulder ( n = 15 ) or to a control group that received no treatment while on the waiting list for two weeks ( n = 14 ) . Measurements were taken both before and after the experimental period by a blinded assessor . Active range of motion was measured for flexion , abduction and h and -behind-back movements . Pain was assessed with the Short Form McGill Pain Question naire ( SFMPQ ) and functional ability was assessed with the Patient Specific Functional Disability Measure ( PSFDM ) . The treatment group showed significant improvements in range of motion compared with the control group for abduction ( mean 42.2 degrees , 95 % CI 24.1 to 60.4 degrees ) , flexion ( mean 22.6 degrees , 95 % CI 12.4 to 32.8 degrees ) and h and -behind-back ( mean 11.0 cm improvement , 95 % CI 6.3 to 15.6 cm ) . Massage reduced pain as reported on the descriptive section of the SFMPQ by a mean of 4.9 points ( 95 % CI 2.5 to 7.2 points ) and on the visual analogue scale by an average of 26.5 mm ( 95 % CI 5.3 to 47.6 mm ) , and it improved reported function on the PSFDM by a mean of 8.6 points ( 95 % CI 4.9 to 12.3 points ) . We conclude that soft tissue massage around the shoulder is effective in improving range of motion , pain and function in patients with shoulder pain . The mechanisms behind these effects remain unclear", "Background : Subacromial corticosteroid injections are frequently performed for impingement syndrome of the shoulder . To improve the accuracy of injections , ultrasound can be used . Purpose : To assess the clinical outcome of ultrasound-guided subacromial injections compared with blind subacromial injections for subacromial impingement syndrome . Study Design : R and omized controlled clinical trial ; Level of evidence , 1 . Methods : A total of 56 shoulders with subacromial impingement syndrome were r and omized into 2 groups : 28 shoulders received a subacromial corticosteroid injection with ultrasound guidance ( ultrasound group ) , and 28 shoulders received a subacromial corticosteroid injection without ultrasound guidance ( blind group ) . The visual analog scale ( VAS ) for pain with overhead activities and the American Shoulder and Elbow Surgeons ( ASES ) score were obtained before the injection and at 6 weeks after the injection . Results : The VAS score for pain with overhead activities decreased from 59 ± 5 mm ( mean ± SEM ) before the injection to 33 ± 6 mm at 6 weeks after the injection in the ultrasound group ( P the VAS score was not significantly different between the groups ( P > .999 ) . The ASES score increased from 57 ± 2 before the injection to 68 ± 3 at 6 weeks after the injection in the ultrasound group ( P eventually needed surgery ( P = .7 ) . Conclusion : No significant differences were found in the clinical outcome when comparing ultrasound-guided subacromial injections to blind subacromial injections for subacromial impingement syndrome . Clinical Trial Registration : Australian New Zeal and Clinical Trials Registry :", "STUDY DESIGN Single-blind r and omized clinical trial , with a follow-up of 24 weeks . OBJECTIVE To determine the effects of hyperthermia via localized microwave diathermy on pain and disability in comparison to subacromial corticosteroid injections in patients with rotator cuff tendinopathy . BACKGROUND Hyperthermia improves symptoms and function in several painful musculoskeletal disorders . However , the effects of microwave diathermy in rotator cuff tendinopathy have not yet been established . METHODS Ninety-two patients with rotator cuff tendinopathy and pain lasting for at least 3 months were recruited from the outpatient clinic of the Department of Orthopaedics and Traumatology , University Hospital , Rome , Italy . Participants were r and omly allocated to either local microwave diathermy or subacromial corticosteroids . The primary outcome measure was the short form of the Disabilities of the Arm , Shoulder and H and Question naire ( QuickDASH ) . Secondary outcome measures were the Constant-Murley shoulder outcome score and a visual analog scale for pain assessment . RESULTS At the end of treatment and at follow-up , both treatment groups experienced improvements in all outcome measures relative to baseline values . Changes over time in QuickDASH , Constant-Murley , and visual analog scale scores were not different between treatment arms . CONCLUSION In patients with rotator cuff tendinopathy , the effects of localized microwave diathermy on disability , shoulder function , and pain are equivalent to those elicited by subacromial corticosteroid injections", "Background Soft tissue massage and exercise are commonly used to treat episodes of shoulder pain . Objective The study objective was to compare the effects of soft tissue massage and exercise with those of exercise alone on pain , disability , and range of motion in people with nonspecific shoulder pain . Design This was a r and omized controlled trial . Setting The study was conducted in public hospital physical therapy clinics in Sydney , New South Wales , Australia . Participants The study participants were 80 people with an average age of 62.6 years ( SD=12.2 ) who were referred to physical therapists for treatment of nonspecific shoulder pain . Intervention Participants were r and omly assigned to either a group that received soft tissue massage around the shoulder and exercises ( n=40 ) or a group that received exercise only ( n=40 ) for 4 weeks . Measurements The primary outcome was improvement in pain , as measured on a 100-mm visual analog scale , 1 week after the cessation of treatment . Secondary outcomes were disability and active flexion , abduction , and h and -behind-back range of motion . Measurements were obtained at baseline , 1 week after the cessation of treatment , and 12 weeks after the cessation of treatment . Results The between-group difference in pain scores from the baseline to 12 weeks after the cessation of treatment demonstrated a small significant difference in favor of the group receiving exercise only ( mean difference=14.7 mm ) . There were no significant differences between groups in any other variable . Limitations It was not possible to mask therapists or participants to group allocation . Diagnostic tests were not used on participants to determine specific shoulder pathology . Conclusions The addition of soft tissue massage to an exercise program for the shoulder conferred no additional benefit for improving pain , disability , or range of motion in people with nonspecific shoulder pain", "OBJECTIVE The aim of this study was to evaluate the initial effects of scapular mobilization ( SM ) on shoulder range of motion ( ROM ) , scapular upward rotation , pain , and function . DESIGN Pretest-posttest for 3 groups ( SM , sham , and control ) . SETTING A double-blinded , r and omized , placebo-controlled trial was conducted to evaluate the initial effect of the SM at a sports physiotherapy clinic . PARTICIPANTS 39 subjects ( 22 women , 17 men ; mean age 54.30 + /- 14.16 y , age range 20 - 77 y ) . INTERVENTIONS A visual analog scale , ROM , scapular upward rotation , and function were assessed before and just after SM . SM ( n = 13 ) consisted of the application of superoinferior gliding , rotations , and distraction to the scapula . The sham ( n = 13 ) condition replicated the treatment condition except for the h and positioning . The control group ( n = 13 ) did not undergo any physiotherapy and rehabilitation program . MAIN OUTCOME MEASURES Pain severity was assessed with a visual analog scale . Scapular upward rotation was measured with a baseline digital inclinometer . Constant Shoulder Score ( CSS ) was used to measure shoulder function . RESULTS After SM , we found significant improvements for shoulder ROM , scapular upward rotation , and CSS between pretreatment and posttreatment compared with the sham and control groups . In the sham group , shoulder-ROM values increased or decreased for the shoulder and scapular upward rotation was not changed . Pain , ROM , and physical function of the shoulder were not significantly different in the sham group than in controls ( P > .05 ) . CONCLUSIONS SM may be a useful manual therapy technique to apply to participants with a painful limitation of the shoulder . SM increases ROM and decreases pain intensity", "We have performed a controlled , r and omised study to analyse the effects of low-energy shock-wave therapy ( ESWT ) on function and pain in tendinitis of the supraspinatus without calcification . There were 20 patients in the treatment group and 20 in the control group . The former group received 6,000 impulses ( energy flux density , 0.11 mJ/mm2 ) in three sessions after local anaesthesia . The control group had 6000 impulses of sham ESWT after local anaesthesia . The patients were examined at six and 12 weeks after treatment by an independent observer who evaluated the Constant score and level of pain . We found an increase in function and a reduction of pain in both groups ( p Constant score and for pain . We therefore do not recommend ESWT for the treatment of tendinitis of supraspinatus", "The aim of this study was to determine the effect of radial extracorporeal shock-wave therapy ( rESWT ) on patients with chronic tendinitis of the rotator cuff . This was a r and omised controlled trial in which 82 patients ( mean age 47 years ( 24 to 67 ) ) with chronic tendinitis diagnosed clinical ly were r and omly allocated to a treatment group who received low-dose rESWT ( three sessions at an interval 10 to 14 days , 2000 pulses , 0.11 mJ/mm(2 ) , 8 Hz ) or to a placebo group , with a follow-up of six months . The patients and the treating orthopaedic surgeon , who were both blinded to the treatment , evaluated the results . A total of 44 patients were allocated to the rESWT group and 38 patients to the placebo group . A visual analogue scale ( VAS ) score for pain , a Constant-Murley ( CMS ) score and a simple shoulder test ( SST ) score significantly improved in both groups at three and six months compared with baseline ( all p ≤ 0.012 ) . The mean VAS was similar in both groups at three ( p = 0.43 ) and six months ( p = 0.262 ) . Also , the mean CMS and SST scores were similar in both groups at six months ( p = 0.815 and p = 0.834 , respectively ) . It would thus seem that low-dose rESWT does not reduce pain or improve function in patients chronic rotator cuff tendinitis compared with placebo treatment", "The aim of this prospect i ve , r and omized clinical study was to compare the effectiveness of two physical therapy treatment approaches for impingement syndrome , either by joint and soft tissue mobilization techniques or by a self-training program . Thirty patients ( Group 1 , n = 15 ; Group 2 , n = 15 ) with the diagnosis of an outlet impingement syndrome of the shoulder were treated either by strengthening the depressors of the humeral head with a guided self-training program ( Group 1 , age 49.5 ± 7.9 years ) , or by joint and soft tissue mobilization techniques ( Group 2 , age 48.1 ± 7.5 years ) . Group 1 was instructed with the active range of motion ( ROM ) , stretching and strengthening exercise program including rotator cuff muscles , rhomboids , levator scapulae and serratus anterior with an elastic b and at home at least seven times a week for 10–15 min and Group 2 received a prescription for 12 sessions of joint and soft tissue mobilization techniques , ice application , stretching and strengthening exercise programs and patient education in clinic for three times per week . All patients were tested with visual analog scale ( VAS ) for pain level , goniometric measurement for ROM and algometry for the pain threshold . Function was measured with a functional assessment question naire . The VAS ( 10 cm ) used to measure pain with functional activities and the functional assessment question naire ( Neer ) were also measured 3 months after the initiation of treatment . Subjects in both groups experienced significant decreases in pain and increases in shoulder function , but there was significantly more improvement in the manual therapy group compared to the exercise group . For example , pain in the manual therapy group was reduced from a pre-treatment mean ( ±SD ) of 6.7 ( ±0.3 ) to a post-treatment mean of 2.0 ( ±2.0 ) . In contrast , pain in the exercise group was reduced from a pre-treatment mean of 6.6 ( ±1.4 ) to a post-treatment mean of 3.0 ( ±1.8 ) . ROM at flexion , abduction and external rotation in the manual therapy group improved significantly while ROM in the exercise group did not . There were statistically differences among the groups in function ( P > 0.05 ) . Group 2 showed significantly greater improvements in the Neer Question naire score and shoulder satisfaction score than Group 1 . The patients treated with manual physical therapy applied by experienced physical therapists combined with supervised exercise in a brief clinical trial showed improvement of symptoms including increasing strength , decreasing pain and improving function earlier than with exercise program", "OBJECTIVE Local corticosteroid injections , commonly accepted by rheumatologists to be effective treating painful shoulder , have shown controversial results . High frequency ultrasonography is an accurate and safe imaging modality for guiding musculoskeletal injections . We prospect ively compared the short term response to r and omized blind injection versus sonographic-guided injection of local corticosteroid in patients with painful shoulder . METHODS We studied 41 consecutive patients with painful shoulder . Patients with previous trauma or chronic inflammatory arthritis were excluded . No patient had received previous physiotherapy or local steroid injection in the shoulder . Patients were r and omized to receive either a blind subacromial injection of 20 mg triamcinolone ( Group 1 , n = 20 ) or a sonographic guided injection of 20 mg triamcinolone ( Group 2 , n = 21 ) by the same rheumatologist blinded to the clinical evaluation . In both groups we recorded shoulder abnormalities and the location of the steroid postinjection by ultrasound . Each patient was clinical ly assessed within 5 days before injection and 6 weeks after injection by another rheumatologist without knowledge of the injection technique performed . Clinical assessment included demographic and clinical data , a visual analog scale ( VAS ) for pain ( 0 - 100 ) , the Shoulder Function Assessment ( SFA ) scale ( 0 - 70 ) , and postinjection adverse effects . No patient received physical therapy during the followup period . Initially , demographic , clinical , and ultrasonographic findings in both groups showed no significant differences . RESULTS Six weeks after injection , the VAS and the SFA score showed a significantly greater improvement in Group 2 compared with Group 1 ( mean VAS score change 34.9 for Group 2 vs 7.1 for Group 1 , p postinjection adverse effects . CONCLUSION We suggest that sonographic-guided corticosteroid injections should be indicated , at least , in patients with poor response to previous blind injection to ensure accurate medication placement in order to improve therapeutic effectiveness", "BACKGROUND Shoulder pain is common in primary health care . Nevertheless , information on the outcome of shoulder disorders is scarce , especially for patients encountered in general practice . AIM To study the course of shoulder disorders in general practice and to determine prognostic indicators of outcome . METHOD For this prospect i ve follow-up study , 11 Dutch general practitioners recruited 349 patients with new episodes of shoulder pain . The participants filled out a question naire at presentation and further ones after 1 , 3 , 6 and 12 months ; these contained questions on the nature , severity and course of the shoulder complaints . The association between potential prognostic indicators and the status of shoulder complaints ( absence or presence of symptoms ) was evaluated after one and 12 months of follow-up . RESULTS After one month , 23 % of all patients showed complete recovery ; this figure increased to 59 % after one year . A speedy recovery seemed to be related to preceding overuse or slight trauma and early presentation . A high risk of persistent or recurrent complaints was found for patients with concomitant neck pain and severe pain during the day at presentation . CONCLUSION A considerable number of patients ( 41 % ) showed persistent symptoms after 12 months . It may be possible to distinguish patients who will show a speedy recovery from those with a high risk of long-st and ing complaints by determining whether there is a history of slight trauma or overuse , an early presentation or an absence of concomitant neck pain", "OBJECTIVES This study aims to assess and compare the efficacy of subacromial tenoxicam and steroid injections in treating patients with shoulder impingement syndrome . PATIENTS AND METHODS Forty patients having shoulder impingement syndrome with findings of rotator cuff tendinitis or subacromial bursitis on magnetic resonance imaging were included in the study . Patients were r and omized into two subacromial injection groups : patients in the first group ( 10 males , 10 females ; mean age 45.3 years ; range 32 to 67 years ) were administered 20 mg tenoxicam three times by weekly intervals , and patients in the second group ( 8 males , 12 females ; mean age 46.5 years ; range 29 to 73 years ) were administered 40 mg methylprednisolone acetate just for once . Visual analog scale ( VAS ) , active range of motion ( ROM ) of the shoulder joint , and Disabilities of Arm , Shoulder and H and ( DASH ) question naire scores were evaluated at baseline , six weeks after treatment , and first year . RESULTS Visual analog scale , DASH , and active ROM scores in both groups were statistically significantly improved . No statistically significant difference was detected between subacromial tenoxicam and steroid injections in terms of post-treatment VAS , DASH , and active ROM scores . Mean pre- and post-treatment VAS scores in tenoxicam group were 7.8 ( range , 3 - 9 ) and 2.6 ( range , 2 - 4 ) , respectively . Mean pre- and post-treatment VAS scores in steroid group were 6.2 ( range , 3 - 10 ) and 3.6 ( range , 0 - 7 ) , respectively . Mean pre- and post-treatment DASH scores in tenoxicam group were 59.4 ( range , 45 - 80 ) and 14.7 ( range , 8.3 - 25.8 ) , respectively . Mean pre- and post-treatment DASH scores in steroid group were 56.7 ( range , 33.3 - 85.8 ) and 18.1 ( range , 0 - 69.2 ) , respectively . Although the improvement in active ROM was higher in the steroid group , difference between two groups was not statistically significant . CONCLUSION Both subacromial tenoxicam and steroid injections may be successfully used in the treatment of patients with impingement syndrome . Subacromial tenoxicam injection may be preferred as a first-line intervention in these patients thanks to its safe profile", "BACKGROUND Shoulder pain or omalgia is one of the main types of osteoarticular pain that can be observed in every-day clinical practice , frequently causing significant functional impairment . The most common cause of shoulder pain is impingement syndrome . OBJECTIVE To decrease the intensity of short- and mid-term pain in the injured shoulder by means of acupuncture . METHOD R and omized controlled trial with two groups of participants : one group received true acupuncture ( TA ) and the other received acupuncture at sham points ( SA ) . The treatment was carried out over 4 weeks , with the participants receiving a session every week . The results were measured immediately after the treatment ( T1 ) and 3 months later ( T2 ) . To evaluate the results , we used the 100 mm Visual Analogue Scale ( VAS ) , and to assess the functionality of the shoulder we employed the UCLA question naire ( 0 - 35 points ) . RESULTS A total of 68 participants were included in the analysis ( TA , n=35 ; SA , n=33 ) , with a mean age of 33.4 years ( SD 12.53 ) . We found significant differences in the analyzed results between the two groups , as we observed a decrease on the intensity of pain for the TA group of 44.13 mm at T1 ( CI 95 % 36.7 ; 51.5 ) and 87.58 mm at T2 ( CI 95 % 28.32 ; 46.81 ) , while the decrease in the FA group was of 19.84 mm at T1 ( CI 95 % 12.2 ; 27.4 ) and 20 mm at T2 ( CI 95 % 10.9 ; 29.09 ) . When the UCLA scores were analyzed , the results were clinical ly meaningful in support of TA in terms of functional assessment of the shoulder . No adverse effects were reported . CONCLUSIONS The use of acupuncture to treat impingement syndrome seems to be a safe and reliable technique to achieve clinical ly significant results and could be implemented in the therapy options offered by the health services", "The aim of the study was to compare the efficacy of kinesiological taping and subacromial injection therapy in patients with subacromial impingement syndrome ( SIS ) . Seventy patients diagnosed with SIS were r and omly assigned to group 1 ( n = 35 , injection group ) or group 2 ( n = 35 , kinesiological taping group ) . Betamethasone plus prilocaine was injected to subacromial space in the patients in group 1 . In group 2 , tape was applied three times for a period of five consecutive days with a 2-day recovery interval . A 3-month exercise program was prescribed for both groups including stretching and strengthening exercises . All patients were assessed at baseline and at 1 and 3 months post-intervention . Assessment s were made by visual analog scale ( VAS ) for pain , range of motion ( ROM ) measurements , specific tests , and Shoulder Pain and Disability Index ( SPADI ) . Significant differences were detected in VAS and SPADI scores as well as ROM measurements in both groups when compared to baseline ( p > 0.05 ) . No significant differences were detected between the groups except for active flexion degree in favor of group 1 ( p = 0.004 ) . Both kinesiological taping and steroid injection in conjunction with an exercise program were found to be effective in the treatment of SIS . Kinesio taping may be an alternative treatment option in the rehabilitation of SIS especially when a non-invasive technique is needed", "UNLABELLED Study Design Single-blind r and omized trial . Background Extracorporeal shockwave therapy ( ESWT ) has been shown to produce good results in the treatment of subacromial impingement syndrome ( SAIS ) . The efficacy of a combined administration of ESWT and isokinetic exercise ( IE ) has not yet been studied . Objectives To evaluate the efficacy of focused ESWT combined with IE for the rotator cuff versus focused ESWT alone in the treatment of SAIS . The secondary objective was to assess the isokinetic torque recovery ( external rotation at 210 ° /s , 180 ° /s , and 120 ° /s ) . Methods Thirty participants with SAIS were r and omly assigned to a focused-ESWT group or focused ESWT-plus-IE group . Subjects of both groups received 3 treatment sessions of focused ESWT over a period of 10 days . Participants in the second group also received IE for 10 therapy sessions . Outcome measures were the Constant-Murley score ( CMS ) , the visual analog scale ( VAS ) , and isokinetic parameters ( peak torque and total work calculated from 5 repetitions ) measured with the isokinetic test . Subjects were assessed at baseline , 10 days after the last treatment session with focused ESWT , and after 2 months of follow-up . Results At 2 months posttreatment , participants in the focused ESWT-plus-IE group showed significantly less pain ( focused-ESWT VAS , 3.4 ± 0.8 versus focused ESWT-plus-IE VAS , 1.5 ± 0.5 ; P and greater improvement in functionality ( focused-ESWT CMS , 75.9 ± 6.7 versus focused ESWT-plus-IE CMS , 92.1 ± 6.3 ; P ) and muscle endurance than the subjects in the focused-ESWT group . Conclusion In subjects with SAIS , combined administration of focused ESWT and IE for the rotator cuff result ed in greater reduction of pain , as well as superior functional recovery and muscle endurance in the short to medium term , compared with ESWT alone . Level of evidence Therapy , 2b . TRIAL REGISTRATION unregistered 2011 trial . J Orthop Sports Phys Ther 2016;46(9):714 - 725 . Epub 5 Aug 2016 . doi:10.2519/jospt.2016.4629", "We have carried out a prospect i ve double-blind r and omised controlled trial to compare the efficacy of a single subacromial injection of the non-steroidal anti-inflammatory drug , tenoxicam , with a single injection of methylprednisolone in patients with subacromial impingement . A total of 58 patients were r and omly allocated into two groups . Group A received 40 mg of methylprednisolone and group B 20 mg of tenoxicam as a subacromial injection along with lignocaine . The Constant-Murley shoulder score was used as the primary outcome measure and the Disability of Arm , Shoulder and H and ( DASH ) and the Oxford Shoulder Score ( OSS ) as secondary measures . Six weeks after injection the improvement in the Constant-Murley score was significantly greater in the methylprednisolone group ( p = 0.003 ) than in the tenoxicam group . The improvement in the DASH score was greater in the steroid group and the difference was statistically significant and consistent two ( p the OSS was consistently greater in the steroid group than in the tenoxicam group . Although the difference was statistically significant at two ( p tenoxicam does not offer an equivalent outcome to subacromial injection of corticosteroid at six weeks . Corticosteroid is significantly better than tenoxicam for improving shoulder function in tendonitis of the rotator cuff after six weeks", "BACKGROUND DATA AND OBJECTIVE Although previous studies have evaluated the effect of different kinds of physical therapy in subacromial impingement syndrome ( SIS ) , there have been few investigations assessing the effectiveness of low-level laser therapy ( LLLT ) in shoulder disorders . The goal of this prospect i ve r and omized study was to assess whether gallium-arsenide ( Ga-As ) laser therapy improves the outcome of a comprehensive home exercise program in patients with SIS . MATERIAL S AND METHODS Forty-four newly-diagnosed SIS patients were enrolled in this study . Group 1 patients ( n = 22 ) received Ga-As laser therapy combined with a 12-wk comprehensive home exercise program , and group 2 patients ( n = 22 ) received the same 12-wk comprehensive home exercise program alone . Night pain , shoulder pain and disability index ( SPADI ) , and University of California-Los Angeles end- result ( UCLA ) scores were used as outcome measures . RESULTS Both groups showed a significant reduction in night pain and SPADI scores at the second and 12th weeks with respect to baseline values , with the exception of the SPADI total score at the second week in group 1 . UCLA results improved significantly in both groups at the 12th in comparison to the second week . There were no significant differences between groups in mean actual changes in night pain and SPADI scores at the second week from baseline . When values at the 12th week were compared to baseline , mean actual changes in night pain differed significantly between the groups , with a larger change in group 1 , but there was no difference between groups in mean actual change in SPADI scores . Second- and 12th-week UCLA scores did not differ between the two groups . CONCLUSION Our study was unable to demonstrate any distinct advantage of low-level laser therapy over exercise alone . Comprehensive home exercise programs should be the primary therapeutic option in the rehabilitation process in SIS", "Objective : To compare the effect of acupuncture with placebo transcutaneous electrical nerve stimulation ( TENS ) when added to the exercise treatment of rotator cuff tendinitis with respect to pain , shoulder movements and function . Design : Prospect i ve alternate allocation controlled trial . Setting : Outpatient department . Patients : Thirty-three patients ( 12 women and 21 men ) were included in the study . All had clinical ly diagnosed rotator cuff tendinitis . Intervention : Both groups underwent a st and ardized training programme . Each patient received in addition either 10 treatments with acupuncture or placebo TENS , 1 - 2 times per week . Main outcome measures : The parameters investigated were intensity of pain ( measured with visual analogue scale ) , active , passive as well as functional movements in the shoulder ( h and in neck ( HIN ) and pour out of a pot ( POP ) ) . Patients were tested before treatment , after treatment and at a six-month follow-up . Medicine intake , ability to lie on the affected side and sleep disturbances were evaluated . A subjective assessment was made after the treatment and at follow-up . Results : Sixteen patients had acupuncture , 17 placebo TENS . Eight patients endured pain at rest in the placebo TENS group , and 10 in the acupuncture group . After treatment both groups improved , the improvement persisted at the six-month follow-up . Both groups increased range of movement . Except for the functional test HIN in the acupuncture group , there were no differences between the groups regarding other parameters investigated directly after treatment or at six-month follow-up . Conclusion : There is no difference between the effect of additional acupuncture treatment and placebo TENS in the treatment of rotator cuff tendinitis", "Objective : To compare the efficacy of pulse radiofrequency applied to the suprascapular nerve with the efficacy of conventional transcutaneous electrical nerve stimulation treatment in patients with shoulder pain . Design : A r and omized , controlled trial . Setting : An outpatient physical therapy and rehabilitation clinic . Subjects : Forty patients with shoulder pain lasting at least three months were included in the study . Subjects were r and omly allocated into either a pulsed radiofrequency treatment or a conventional transcutaneous electrical nerve stimulation treatment . All patients received exercise therapy . Main measurements : Outcome measurements were performed using the visual analogue scale for pain and range of motion ; the Shoulder Pain and Disability Index was used for disability ; and the Short Form-36 was used to establish quality of life . All of the measurements were assessed at four points in time ( before the intervention , and for 1 , 4 and 12 weeks afterwards ) . Results : When the groups were compared , no significant difference was found between the groups in terms of visual analogue scale , range of motion , the Shoulder Pain and Disability Index ( except for the Shoulder Pain and Disability Index total score ) , Short Form-36 subscores , and paracetamol consumption for all weeks ( P > 0.05 ) . Conclusion : Our results showed that there is no difference in effect between transcutaneous electrical nerve stimulation and pulsed radiofrequency treatment for shoulder pain", "Objective ( s ) : ( 1 ) To compare the effectiveness of customized exercises with that of st and ard exercises for the treatment of patients with shoulder disorders . ( 2 ) To determine whether four weeks or eight weeks would be needed to see improvement in outcome measures . Design : A single-blinded r and omized clinical trial . Setting : An outpatient physical therapy clinic affiliated with an academic institution . Subjects : Thirty patients with shoulder disorders were tested and treated between February 2003 and December 2004 . Interventions : Patients were r and omized to a customized or st and ard exercise group . Each patient first underwent a st and ardized physical therapy assessment . Based on the results of the assessment , a classification was determined and a classification-specific exercise programme was instructed to the patients in the customized exercise group . The st and ard exercise group , regardless of classification , received preselected st and ard exercises . Both groups were followed for eight weeks . Main measures : Shoulder range of motion , strength , pain intensity and function were assessed three times ( weeks 0 , 4 and 8) . Results : There were no significant differences between the customized and st and ard exercise groups in measures of shoulder range of motion , strength , pain intensity and function after four or eight weeks of exercise . Patients in both groups had significant improvements in shoulder strength , pain intensity and function . Significant improvements occurred at week 8 , but not at week 4 . Conclusion : The customized shoulder exercises did not provide additional benefit to our shoulder patients than the st and ard exercises", "OBJECTIVE To determine the effects of scapular mobilization on function , pain , range of motion , and satisfaction in patients with subacromial impingement syndrome ( SAIS ) . DESIGN R and omized , double-blind , placebo-controlled clinical trial . SETTING University hospital clinics in Turkey . PARTICIPANTS 66 participants ( mean ± SD age 52.06 ± 3.71 y ) with SAIS . INTERVENTIONS Participants were r and omized into 3 groups : scapular mobilization , sham scapular mobilization , and supervised exercise . Before the interventions transcutaneous electrical stimulation and hot pack were applied to all groups . Total intervention duration for all groups was 3 wk with a total of 9 treatment sessions . MAIN OUTCOME MEASURES Shoulder function and pain intensity were primary outcome measures ; range of motion and participant satisfaction were secondary outcome measures . Shoulder function was assessed with the short form of the Disabilities of the Arm , Shoulder and H and Question naire ( DASH ) . A visual analog scale was used to evaluate pain severity . Active range of motion was measured with a universal goniometer . A 7-point Likert scale was used to evaluate satisfaction . Outcome measurements were performed at baseline , before visits 5 and 10 , 4 wk after visit 9 , and 8 wk after visit 9 . RESULTS There was no group difference for DASH score ( P = .75 ) , pain at rest ( P = .41 ) , pain with activity ( P = .45 ) , pain at night ( P = .74 ) , and shoulder flexion ( P = .65 ) , external rotation ( P = .63 ) , and internal rotation ( P = .19 ) . There was a significant increase in shoulder motion and function and a significant decrease in pain across time when all groups were combined ( P . The level of satisfaction was not significantly different for any of the questions about participant satisfaction between all groups ( P > .05 ) . CONCLUSION There was not a significant advantage of scapular mobilization for shoulder function , pain , range of motion , and satisfaction compared with sham or supervised-exercise groups in patients with SAIS", "STUDY DESIGN R and omized controlled trial . OBJECTIVE To evaluate the effects of an exercise protocol , with and without manual therapy , on scapular kinematics , function , pain , and mechanical sensitivity in individuals with shoulder impingement syndrome . BACKGROUND Stretching and strengthening exercises have been shown to effectively decrease pain and disability in individuals with shoulder impingement syndrome . There is still conflicting evidence regarding the efficacy of adding manual therapy to an exercise therapy regimen . METHODS Forty-six patients were assigned to 1 of 2 groups , one of which received a 4-week intervention of stretching and strengthening exercises ( exercise alone ) and the other the same intervention , supplemented by manual therapy targeting the shoulder and cervical spine ( exercise plus manual therapy ) . All outcomes were measured preintervention and postintervention at 4 weeks . Outcome measures were scapular kinematics in the scapular and sagittal planes during arm elevation , function as determined through the Disabilities of the Arm , Shoulder and H and ( DASH ) question naire , pain as assessed with a visual analog scale , and mechanical sensitivity as assessed with pressure pain threshold . RESULTS Independent of the intervention group , small , clinical ly irrelevant changes in scapular kinematics were observed postintervention . A significant group-by-time interaction effect ( P = .001 ) was found for scapular anterior tilt during elevation in the sagittal plane , with a 3.0 ° increase ( 95 % confidence interval [ CI ] : -1.5 ° , 7.5 ° ) relative to baseline in the exercise-plus-manual therapy group compared to a decrease of 0.3 ° ( 95 % CI : -4.2 ° , 4.8 ° ) in the exercise-alone group . Pain , mechanical sensitivity , and the DASH score improved similarly for both groups by the end of the intervention period . CONCLUSION Adding manual therapy to an exercise protocol did not enhance improvements in scapular kinematics , function , and pain in individuals with shoulder impingement syndrome . The noted improvements in pain and function are not likely explained by changes in scapular kinematics", "Extracorporeal shock wave therapy ( ESWT ) is seen as a therapeutic option in the treatment of chronic supraspinatus tendinitis by some authors . To test whether ESWT comprising 3 x 2000 pulses with the positive energy flux density ED+ of 0.33 mJ/mm2 is clinical ly superior to a sham ESWT treatment , a prospect i ve , r and omized , single-blinded , placebo-controlled study with an independent observer was performed . Forty patients were treated either by verum ESWT or sham ESWT under local anesthesia . Target criteria were the age-corrected Constant score , pain at rest and during activity on a visual analogue scale , and subjective improvement . Patients who reported no subjective improvement after 12 weeks were deblinded and received verum ESWT if they had belonged to the placebo group ( partial crossover ) . The results of the verum group lie within the range of results for ESWT published by other authors . Patients in the placebo group with local anesthetic showed equally good results . At 12 weeks , and 1 year after intervention , no difference could be found between the verum and placebo groups regarding Constant score , pain , shoulder function , or subjective improvement . The nonresponders to the placebo ESWT continued to show no improvement after receiving verum ESWT . This contradicts a specific ESWT effect . Based on the results of this placebo-controlled study , ESWT appears to have no clinical ly relevant effect on supraspinatus tendinitis . The study underlines the importance of a control group in evaluating new treatment methods for diseases with unknown natural history", "BACKGROUND Rotator cuff syndrome is often treated with subacromial injection of corticosteroid and local anesthetic . It has not been established if the common injection routes of the bursa are equally accurate . METHODS We conducted a prospect i ve clinical trial involving seventy-five shoulders in seventy-five patients who were r and omly assigned to receive a subacromial injection through an anterior , lateral , or posterior route with respect to the acromion . An experienced physician performed the injections , which contained radiopaque contrast medium , corticosteroid , and local anesthetic . After the injection , a musculoskeletal radiologist , blinded to the injection route , interpreted all of the radiographs . RESULTS The rate of accuracy varied with the route of injection , with a rate of 56 % for the posterior route , 84 % for the anterior route , and 92 % for the lateral route ( p = 0.006 ; chi-square test ) . The accuracy of injection through the posterior route was significantly lower than that through either the anterior or the lateral route ( p accuracy of injection was significantly lower in females than in males ( p males , no differences between the routes were noted ( with accuracy rates of 89 % for the posterior route , 92 % for the anterior route , and 93 % for the lateral route ) . Among females , however , the accuracy of injection was lower for the posterior route than for either the anterior or the lateral route ( with accuracy rates of 38 % for the posterior route , 77 % for the anterior route , and 91 % for the lateral route ) ( p accuracy of subacromial bursal injection was significantly different between males and females , mainly because of a lower accuracy of bursal injection with use of the posterior route in females . The present study suggests that the posterior route is the least accurate method for injection of the subacromial bursa in females", "OBJECTIVE To explore the effectiveness of naturopathic care ( NC ) on rotator cuff tendinitis using a prospect i ve r and omized clinical trial design . METHODS Canadian postal workers with rotator cuff tendinitis for a duration of > 6 weeks were r and omized to receive NC ( n = 43 ) or st and ardized physical exercises ( PEs ; n = 42 ) over 12 weeks . Participants in the NC group received dietary counseling , acupuncture , and Phlogenzym ( 2 tablets 3 times/day ) . The PE intervention group received passive , active-assisted , and active range of motion exercises and matched placebo . The primary outcome measure was the Shoulder Pain and Disability Index ( SPADI ) , and secondary outcomes were the pain visual analog scale ( VAS ) , Short Form 36 ( SF-36 ) , Measure Yourself Medical Outcomes Profile ( MYMOP ) , and shoulder maximal range of motion . Participants and assessors were blinded to group and placebo allocation . RESULTS Seventy-seven participants ( 87 % ) completed > or=8 weeks of the trial . Final total SPADI scores decreased by 54.5 % ( P SPADI scores showed statistically significant decreases in shoulder pain and disability in the NC group compared with the PE group ( P pain VAS , MYMOP , SF-36 , and shoulder extension , flexion , and abduction , with the NC group showing superiority in each outcome . No serious adverse reactions were observed . CONCLUSION NC and PE provided significant improvements , with greater improvement in shoulder function in the NC group compared with the PE group . Statistically significant improvements in quality of life measures were observed in the NC group as compared with the PE group", "OBJECTIVES We studied the value of ultrasound ( US ) to define shoulder pathology and guide local steroid injection in comparison with a st and ard injection in the management of the acute painful shoulder . METHODS Seventy consecutive patients with acute shoulder pain were assessed clinical ly and by US . Patients were r and omized to receive either a st and ard subacromial infiltration of 7 mg of betamethasone or a US-guided injection according to the US diagnosis . Follow-up evaluations were performed by an independent assessor who was blinded to the results of the initial US and clinical assessment s. RESULTS Sixty-seven patients completed the study . Both groups showed a significant reduction in both daytime and night pain compared to baseline . The US injection group had significantly less pain at rest at 2 and 6 weeks ( NRS : 1.6 vs 3.3 , P percentage of good responders was significantly higher in US group at 2 weeks , ( 81 % vs 54 % , P responder rate and activity pain scores as well as Constant score were in favour of US , though did not reach statistical significance . CONCLUSION Local steroid injection for shoulder pain leads to significant improvements in pain and function for up to 12 weeks . An US examination to define the origin of shoulder pain as well as to guide injection provides significant additional benefits for up to 6 weeks . We recommend routine US examination as part of the management of acute shoulder pain", "Objectives : To test the safety of the diode light therapy and evaluate the advantages of the interferential effect of two light probes versus a conventional light probe in the relief of shoulder pain and disability caused by shoulder tendinopathies . Design : R and omized single-blind pilot study . Setting : Clinical electrotherapy unit . Participants : A total of 30 patients with shoulder pain from tendinopathies . Interventions : The patients were r and omly assigned into two groups . Group 1 ( n = 15 ) received interferential light therapy generated by two independent and identical cluster probes composed of light emitting and superluminescent diodes . Similarly , two applicators were applied in group 2 ( n = 15 ) , but only one was active , as in conventional clinical therapy . Each multi-diode cluster probe was composed of seven light-emitting diodes at 600 nm and 12 superluminescent diodes at 950 nm . Main outcome measures : Pain was evaluated by visual analogue scale ( VAS ) at day , at night and during several shoulder movements . Shoulder functional status was measured by means of the University California Los Angeles scale ( UCLA ) . Results : Comparison between both treatments using the Mann – Whitney U-test showed better results for the interferential treatment . There were significant differences in pain reduction during abduction ( P pain reductions in abduction and external rotation of 1.5 ( ± 1.3 ) and 0.5 ( ± 1.0 ) respectively . Conclusion : Interferential light therapy was safe and effective regarding the shoulder pain reduction during abduction and external rotation movements . The estimated size sample needed for future two-treatment parallel- design studies will require about 60 patients", "Objective : To estimate the effectiveness of ultrasonophoresis and iontophoresis with sodium diclofenac used in addition to an exercise program for patients with impingement syndrome . Design : Multicentre , double-blind , placebo r and omized controlled trial . Setting : “ Mancha Centro ” Outpatient primary care clinic ( Spain ) . Participants : A total of 175 patients were considered , of whom 88 met criteria and agreed . Intervention : The patients were r and omly assigned to one of three groups : a ) st and ard treatment ( supervised exercises and cryotherapy ) along with placebo iontophoresis and placebo ultrasonophoresis ; b ) st and ard treatment , iontophoresis , and placebo ultrasonophoresis ; and c ) st and ard treatment , ultrasonophoresis , and placebo iontophoresis . All patients received 15 treatment sessions . Outcome measures : Baseline , 6- , and 12-week evaluations were carried out . Functionality , pain , range of motion , strength and quality of life were assessed with the Disabilities of the Arm , Shoulder and H and Question naire ( DASH ) , Constant-Murley score , and SF-36 scale . Results : Ultrasonophoresis group experienced significant decreases in pain compared to the st and ard treatment group ( 12.7 and 13.5 points in “ bodily pain ” dimension of SF-36 ; and 1,5 and 2,2 points in “ pain ” dimension of Constant Murley after 6 and 12 weeks of therapy , respectively ) . They also reported improved range of motion compared to the exercises group ( 2,1 points in Constant-Murley after 6 weeks and 12 weeks ) , better vitality and overall health ( SF-36 dimensions ) . Iontophoresis , however , led to no significant improvements when added to the st and ard treatment . Conclusion : In patients with impingement syndrome , a combination of ultrasonophoresis and an exercise program are better than a combination of iontophoresis and the same exercise program or the exercise program alone", "OBJECTIVE Evidence for effective management of shoulder impingement is limited . The present study aim ed to quantify the clinical , neurophysiological , and biomechanical effects of a scapular motor control retraining for young individuals with shoulder impingement signs . METHOD Sixteen adults with shoulder impingement signs ( mean age 22 ± 1.6 years ) underwent the intervention and 16 healthy participants ( 24.8 ± 3.1years ) provided reference data . Shoulder function and pain were assessed using the Shoulder Pain and Disability Index ( SPADI ) and other question naires . Electromyography ( EMG ) and 3-dimensional motion analysis was used to record muscle activation and kinematic data during arm elevation to 90 ° and lowering in 3 planes . Patients were assessed pre and post a 10-week motor control based intervention , utilizing scapular orientation retraining . RESULTS Pre-intervention , patients reported pain and reduced function compared to the healthy participants ( SPADI in patients 20 ± 9.2 ; healthy 0 ± 0 ) . Post-intervention , the SPADI scores reduced significantly ( P ( ±4 ) . EMG showed delayed onset and early termination of serratus anterior and lower trapezius muscle activity pre-intervention , which improved significantly post-intervention ( P 4.6 - 7.4 ° less posterior tilt , which was significantly lower in 2 arm elevation planes ( P participants . Post-intervention , upward rotation and posterior tilt increased significantly ( P A 10-week motor control intervention for shoulder impingement increased function and reduced pain . Recovery mechanisms were indicated by changes in muscle recruitment and scapular kinematics . The efficacy of the intervention requires further examined in a r and omized control trial", "Objective To explore the effects of contralateral manual acupuncture ( MA ) on patients with chronic shoulder pain . Methods Eighty patients with chronic shoulder pain were r and omly allocated to receive contralateral MA ( n=38 ) for 4 weeks or to remain on a waiting list while receiving conventional orthopaedic therapy ( n=42 ) . Visual analogue scale ( VAS ) scores were taken as the primary outcome measure and used for a priori power calculation . Secondary outcome measures for the assessment of shoulder mobility and quality of life included the Jobe test , the Constant-Murley ( CM ) score , the Disabilities of the Arm , Shoulder and H and ( DASH ) score , and the 36 item Short Form Health Survey ( SF-36 ) . Results Intention-to-treat ( ITT ) analysis demonstrated significant pain relief with contralateral acupuncture , with mean differences in VAS scores compared to the waiting list group of −19.4 ( −28.0 to −10.8 ) at 2 weeks , −40.4 ( −49.0 to −31.8 ) at 4 weeks , −41.1 ( −49.7 to −32.5 ) at 8 weeks , and −40.9 ( −49.5 to −32.3 ) at 16 weeks . CM and DASH scores were also improved at all time points ( p were also improved by contralateral acupuncture at 8 weeks . No significant adverse effects were observed . Conclusions These results demonstrate beneficial effects of contralateral acupuncture in the treatment of chronic shoulder pain , both in terms of pain and function . Future research is required to compare directly the effects of local and contralateral acupuncture and to quantify the specific and non-specific effects . Trial Registration Number NCT01733914", "Purpose To investigate superior value of adding heavy load eccentric training to conservative treatment in patients with subacromial impingement . Methods Sixty-one patients with subacromial impingement were included and r and omly allocated to the traditional rotator cuff training ( TT ) group ( n = 30 , mean age = 39.4 ± 13.1 years ) or traditional rotator training combined with heavy load eccentric training ( TT + ET ) group ( n = 31 , mean age = 40.2 ± 12.9 years ) . Isometric strength was measured to abduction at 0 ° , 45 ° and 90 ° of scapular abduction and to internal and external rotation . The SPADI question naire was used to measure shoulder pain and function . Patients rated subjective perception of improvement . Outcome was assessed at baseline , at 6 and 12 weeks after start of the intervention . Both groups received 9 physiotherapy treatments over 12 weeks . At home , the TT group performed traditional rotator cuff strengthening exercises 1x/day . The TT + ET group performed the same exercises 1x/day and a heavy load eccentric exercise 2x/day . Results After treatment , isometric strength had significantly increased in all directions , and SPADI score had significantly decreased . The TT + ET group showed a 15 % higher gain in abduction strength at 90 ° of scapular abduction . Chi-square tests showed patients ’ self-rated perception of improvement was similar in both groups . Conclusion Adding heavy load eccentric training result ed in a higher gain in isometric strength at 90 ° of scapular abduction , but was not superior for decreasing pain and improving shoulder function . This study showed that the combination of a limited amount of physiotherapy sessions combined with a daily home exercise programme is highly effective in patients with impingement . Level of evidence II", "Background Evidence from a recent r and omized controlled trial indicated that supervised exercises ( SE ) were more effective than radial extracorporeal shock-wave therapy ( rESWT ) for the treatment of subacromial shoulder pain in the short to medium term . Little knowledge exists about the long-term results of rESWT for subacromial pain . Objective The aim of this study was to evaluate the results of rESWT and SE provided to patients with subacromial shoulder pain after 1 year . Design This was a single-blind r and omized controlled trial . Setting The study was conducted in the outpatient clinic of the Physical Medicine and Rehabilitation Department at Oslo University Hospital , Ullevaal , Norway . Patients One hundred four patients with subacromial shoulder pain lasting at least 3 months participated . Patients were r and omly assigned to either an rESWT group ( n=52 ) or an SE group ( n=52 ) . Intervention The rESWT intervention consisted of one session weekly for 4 to 6 weeks . The SE intervention consisted of two 45-minute sessions per week for up to 12 weeks . Measurements The primary outcome measure was the Shoulder Pain and Disability Index . Secondary outcome measures were questions regarding pain and function and work status . Results After 1 year , an intention-to-treat analysis showed no significant differences between the 2 groups for the primary outcome measure ( −7.6 points , 95 % confidence interval=−16.6 to 0.5 ) and pain , function , and medication use . Twenty-nine participants ( 60 % ) in the SE group versus 24 participants ( 52 % ) in the rESWT group were categorized as clinical ly improved . Thirty-eight participants in the SE group were at work compared with 30 participants in the rESWT group ( odds ratio=1.1 , 95 % confidence interval=1.0 to 1.2 ) . Fewer patients in the SE group had received additional treatments between 18 weeks and 1 year . Limitations The lack of a placebo control group , the lack of a cost-benefit analysis , and the small sample size were limitations of the study . Conclusion No significant difference was found between the SE and rESWT groups at the 1-year follow-up . More participants in the SE group had returned to work ", "Background Passive mobilization of shoulder region joints , often in conjunction with other treatment modalities , is used for the treatment of people with shoulder pain and minimal movement restriction . However , there is only limited evidence supporting the efficacy of this treatment modality . Objective The purpose of this study was to determine whether passive mobilization of shoulder region joints adds treatment benefit over exercise and advice alone for people with shoulder pain and minimal movement restriction . Design This was a r and omized controlled clinical trial with short- , medium- and longer-term follow-up . Setting The study was conducted in a metropolitan teaching hospital . Patients Ninety-eight patients with shoulder pain of local mechanical origin and minimal shoulder movement restriction were r and omly allocated to either a control group ( n=51 ) or an experimental group ( n=47 ) . Intervention Participants in both groups received advice and exercises design ed to restore neuromuscular control at the shoulder . In addition , participants in the experimental group received passive mobilization specifically applied to shoulder region joints . Measurements Outcome measurements of shoulder pain and functional impairment , self-rated change in symptoms , and painful shoulder range of motion were obtained at 1 , 3 , and 6 months after entry into the trial . All data were analyzed using the intention-to-treat principle by repeated- measures analyses of covariance . Results No statistically significant differences were detected in any of the outcome measurements between the control and experimental groups at short- , medium- , or longer-term follow-up . Limitations Therapists and participants were not blinded to the treatment allocation . Conclusion This r and omized controlled clinical trial does not provide evidence that the addition of passive mobilization , applied to shoulder region joints , to exercise and advice is more effective than exercise and advice alone in the treatment of people with shoulder pain and minimal movement restriction", "Abstract Purpose : Motor imagery ( MI ) has been used as a complementary therapeutic tool for motor recovery after central nervous system disease and peripheral injuries . However , it has never been used as a preventive tool . We investigated the use of MI in the rehabilitation of stage II shoulder impingement syndrome . For the first time , MI is used before surgery . Method : Sixteen participants were r and omly assigned to either a MI or control group . Shoulder functional assessment ( Constant score ) , range of motion and pain were measured before and after intervention . Results : Higher Constant score was observed in the MI than in the control group ( p = 0.04 ) . Participants in the MI group further displayed greater movement amplitude ( extension ( p flexion ( p = 0.025 ) ; lateral rotation ( p greater pain decrease ( p = 0.01 ) . Conclusion : MI intervention seems to alleviate pain and enhance mobility , this is probably due to changes in muscle control and consequently in joint amplitude . MI might contribute to postpone or even protect from passing to stage III that may require surgery . Implication s for Rehabilitation Adding motor imagery training to classical physical therapy in a stage II impingement syndrome : Helps in alleviating pain Enhances shoulder mobility Motor imagery is a valuable technique that can be used as a preventive tool before the stage III of the impingement syndrome" ]

[ "Background Web-based and mobile health interventions ( also called “ Internet interventions ” or \" eHealth/mHealth interventions \") are tools or treatments , typically behaviorally based , that are operationalized and transformed for delivery via the Internet or mobile platforms . These include electronic tools for patients , informal caregivers , healthy consumers , and health care providers . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the suboptimal reporting of r and omized controlled trials ( RCTs ) . While the CONSORT statement can be applied to provide broad guidance on how eHealth and mHealth trials should be reported , RCTs of web-based interventions pose very specific issues and challenges , in particular related to reporting sufficient details of the intervention to allow replication and theory-building . Objective To develop a checklist , dubbed CONSORT-EHEALTH ( Consoli date d St and ards of Reporting Trials of Electronic and Mobile HEalth Applications and onLine TeleHealth ) , as an extension of the CONSORT statement that provides guidance for authors of eHealth and mHealth interventions . Methods A literature review was conducted , followed by a survey among eHealth experts and a workshop . Results A checklist instrument was constructed as an extension of the CONSORT statement . The instrument has been adopted by the Journal of Medical Internet Research ( JMIR ) and authors of eHealth RCTs are required to su bmi t an electronic checklist explaining how they addressed each subitem . Conclusions CONSORT-EHEALTH has the potential to improve reporting and provides a basis for evaluating the validity and applicability of eHealth trials . Subitems describing how the intervention should be reported can also be used for non- RCT evaluation reports . As part of the development process , an evaluation component is essential ; therefore , feedback from authors will be solicited , and a before-after study will evaluate whether reporting has been improved", "BACKGROUND Technology-based interventions for Autism Spectrum Disorder ( ASD ) have proliferated , but few have been evaluated within the context of a r and omised controlled trial ( RCT ) . This RCT evaluated the efficacy of one technology-based early intervention programme ( Therapy Outcomes By You ; TOBY ) in young children with ASD . METHODS TOBY is an app-based learning curriculum design ed for children and parents as a complement to early behavioural intervention . Eighty children ( 16 female ) were recruited to this RCT within 12 months of receiving a diagnosis of ASD ( M age = 3.38 ; SD = 0.69 ) and r and omised to receive either treatment-as-usual ( community-based intervention , n = 39 ) or the TOBY therapy ( at least 20 min/day ) plus treatment-as-usual ( n = 41 ) for a period of 6 months . Outcomes were assessed at 3 and 6 months postbaseline . ( Australian New Zeal and Clinical Trials Registry : ACTRN12614000738628 ; www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=365463 ) . RESULTS Children in the TOBY intervention group averaged 19 min/day engaging with the app in the first 3 months , but only 2 min/day during the second 3 months . There was no group difference in scores on the primary outcome , the Autism Treatment Evaluation Checklist , at either the 3- or 6-month follow-up . However , significant improvements at the 6-month follow-up were observed in the TOBY intervention group relative to the treatment-as-usual group on three secondary outcomes : the Fine Motor and Visual Reception subscales of the Mullen Scale of Early Learning and the Total Words Understood scale of the MacArthur-Bates Communicative Development Index . Statistical trends towards improvement in the TOBY intervention group were observed on measures of adaptive function , although these decreased in magnitude from the 3- to 6-month follow-up . CONCLUSIONS This study provides evidence that technology-based interventions may provide a relatively low-cost addition to existing therapist-delivered interventions for children with ASD . However , sustained use of the app over the full 6-month period was a challenge for most families", "This study evaluated a technology-based early intervention for social communication skills in pre-schoolers in a r and omised controlled trial . Participants were 54 children aged under 6 years with a diagnosis of autism , assigned to either intervention or control conditions . The app engaged children , who played consistently , regardless of developmental level , and was rated highly by parents . There were no significant group differences in parent-report measures post-intervention , nor in a measure of parent – child play at follow-up . Therefore , this intervention did not have an observable impact on real-world social communication skills and caution is recommended about the potential usefulness of iPad ™ apps for amelioration of difficulties in interaction . However , positive attitudes among participants , lack of harms and the potential of apps to deliver therapeutic content at low economic cost suggest this approach is worth pursuing further , perhaps targeting other skill domains", "Abstract Background : Currently , there are over 400 smoking cessation smartphone apps available , downloaded an estimated 780,000 times per month . No prior studies have examined how individuals engage with specific features of cessation apps and whether use of these features is associated with quitting . Objectives : Using data from a pilot trial of a novel smoking cessation app , we examined : ( i ) the 10 most-used app features , and ( ii ) prospect i ve associations between feature usage and quitting . Methods : Participants ( n = 76 ) were from the experimental arm of a r and omized , controlled pilot trial of an app for smoking cessation called “ SmartQuit , ” which includes elements of both Acceptance and Commitment Therapy ( ACT ) and traditional cognitive behavioral therapy ( CBT ) . Utilization data were automatically tracked during the 8-week treatment phase . Thirty-day point prevalence smoking abstinence was assessed at 60-day follow-up . Results : The most-used features – quit plan , tracking , progress , and sharing – were mostly CBT . Only two of the 10 most-used features were prospect ively associated with quitting : viewing the quit plan ( p = 0.03 ) and tracking practice of letting urges pass ( p = 0.03 ) . Tracking ACT skill practice was used by fewer participants ( n = 43 ) but was associated with cessation ( p = 0.01 ) . Conclusions : In this exploratory analysis without control for multiple comparisons , viewing a quit plan ( CBT ) as well as tracking practice of letting urges pass ( ACT ) were both appealing to app users and associated with successful quitting . Aside from these features , there was little overlap between a feature ’s popularity and its prospect i ve association with quitting . Tests of causal associations between feature usage and smoking cessation are now needed", "Purpose This study examined the effects of incorporating a peer-mediated approach into a speech-generating device ( SGD ) intervention on communication of 45 nonverbal and minimally verbal preschoolers with autism spectrum disorder ( ASD ) and 95 peers without disabilities . The SGD was an iPad 2 ( Apple ) with voice output app . Method Effects were evaluated using a multivariate r and omized control trial design with repeated measures for 4 cohorts across baseline , intervention , generalization , and maintenance phases . Children were r and omly assigned to an experimental treatment that trained peers on use of the SGD or a business-as-usual comparison condition with untrained peers . Communication outcomes were measured for both children with ASD and peers . Results Children receiving the treatment demonstrated significant increases in rates of communication and more balanced responses and initiations ( a measure of reciprocity ) than children in the comparison group . They were able to generalize improvements and maintain communication gains . Treatment fidelity was high for school staff and peer implementation . Conclusions Results support positive effects on communication of teaching young children with ASD and peers without disabilities to use the same SGD system in typical preschool activities . SGD interventions that utilize peer-mediated approaches may improve core deficits in communication and reciprocity and allow for greater classroom social participation and interactions with peers", "This exploratory r and omised controlled trial tested the effectiveness of a tablet-based information communication technology early intervention application to augment existing therapy with the aim of improving visual motor , imitation , language and social skills in young children with ASD who reside in regional areas . Fifty-nine participants were recruited and r and omised to either a therapy-as-usual group or intervention group . With the exception of the expressive language subscale on the Mullen Scales of Early Learning , no significant between-group differences were recorded for visual motor , imitation , receptive language and social skills of participants between baseline and post-intervention . When all participants were pooled and measured over time , improvements were shown in receptive and pragmatic language and social skills ; these gains were maintained , thus suggesting skill acquisition", "A pilot community‐based r and omized controlled trial was conducted to compare the effects of the Picture Exchange Communication System ( PECS ) to a teaching sequence using a high‐tech Speech Generating Device ( SGD ) to teach social communication behaviors . The two approaches were compared to evaluate the effectiveness of the newer , more high‐tech intervention using technology to improve social and communicative behavior of children diagnosed with Autism Spectrum Disorder . A total of 35 school‐age children were r and omized to either a high‐tech ( SGD device ) or low‐tech ( PECS cards ) form of Augmentative and Alternative Communication ( AAC ) . Study participants received 4 months of communication training delivered in their classrooms , and the primary outcome measures of the trial were several functional communication skills emphasized in the PECS teaching sequence . Results indicated that both high‐tech and low‐tech AAC approaches result ed in significant improvements in communication , and that these improvements did not differ significantly between the two approaches . These findings support the use of high‐tech AAC , and highlight the need for evidence ‐based guidelines for its use as well as evaluation with individuals with a range impairments and disabilities . Autism Research 2018 , 11 : 1701–1711 . © 2018 International Society for Autism Research , Wiley Periodicals ,", "The current study evaluated the effectiveness of a mobile application , Camp Discovery , design ed to teach receptive language skills to children with autism spectrum disorder based on the principles of applied behavior analysis . Participants ( N = 28 ) were r and omly assigned to an immediate-treatment or a delayed-treatment control group . The treatment group made significant gains , p significant gains in the control group after using the application and maintenance of acquired skills in the treatment group after application usage was discontinued . Findings suggest that the application effectively teaches the targeted skills", "This r and omized controlled trial feasibility study tested the effectiveness of an iPad ® application ( app ) social script intervention for children with autism spectrum disorder ( ASD ) going to imaging and their parent ( n=32 parent/child dyads ) . Parents of the children exposed to the app ( n=16 ) had lower state anxiety compared to the parents whose children were not exposed to the app ( n=16 ) ( effect size 0.33 ) . Children exposed to the app had fewer externalized challenging behaviors than the control group ( effect size 0.56 ) . The results demonstrate feasibility and efficacy of the intervention . Further study of the iPad app is warranted" ]

[ "INTRODUCTION On average 40 % of all patients suffering from Parkinson s disease ( PD ) undergo bouts of depression . It is thought that this is due to a dysfunction in the orbitofrontal and dorsolateral circuits , together with hypometabolism in the orbital , cau date nucleus and frontal dorsolateral tract regions . AIMS The aim of this study is to compare the effectiveness of low doses of fluoxetin with that of low doses of amitriptyline in controlling depression in patients with PD . PATIENTS AND METHODS The study examined a total of 77 patients ( 34 females and 43 males ) , with an average age of 68.2 years , who had been suffering from PD ( according to the diagnostic criteria of Calne et al , in stage II of Hoehn and Yahr ) for an average of 6.9 years . They were divided r and omly into two groups which received fluoxetin ( 37 patients , dosage : 20 40 mg/day ) or amitriptyline ( 40 patients , dosage : between 25 and 75 mg/day ) . A basal evaluation and four others ( at 3 , 6 , 9 and 12 months of treatment ) were performed , including the STMS ( Short test of mental status ) , the Hamilton scale , and extent of functional disability using the UPDRS . A statistical analysis was performed by comparing the variance of the above mentioned parameters and the c2 test with Yates correction or the Fisher exact two tailed test , to evaluate the reasons for dropping out . In both cases a value of p 58 patients finished the study . Drop out because of side effects only took place in the group that received amitriptyline ( p fluoxetin at controlling the depression ( p amitriptyline is effective in controlling the depression presented by patients with PD . However , despite the low dosage , the side effects it caused forced 15 % of the patients ab and on the treatment", "In addition to treating the motor symptoms of Parkinson ’s disease , the dopamine agonist pramipexole has shown an antidepressant effect . The trials , however , included patients with motor complications , raising the question of whether the antidepressant benefit represented only a treatment – related motor improvement . To address this issue , we have conducted a 14–week r and omized trial comparing pramipexole with an established antidepressant in patients without motor complications . At seven Italian centers , 67 Parkinsonian out patients with major depression but no history of motor fluctuations and /or dyskinesia received open – label pramipexole ( at 1.5 to 4.5 mg/day ) or sertraline ( at 50 mg/day ) . In both groups , the Hamilton Depression Rating Scale ( HAM – D ) score decreased throughout 12 weeks of treatment , but in the pramipexole group the proportion of patients who recovered , as defined by a final HAM – D score ≤ 8,was significantly higher , at 60.6 % versus 27.3 % ( p = 0.006 ) . Patients ’ self – ratings improved in both groups . All adverse events were mild or moderate , but five patients ( 14.7 % ) withdrew from the sertraline group . Despite the absence of motor complications , the pramipexole recipients showed improvement on the Unified Parkinson ’s Disease Rating Scale ( UPDRS ) motor subscore . We conclude that dopamine agonists may be an alternative to antidepressants in Parkinson ’s disease", "Depression is one of the most common psychiatric disturbances in Parkinson 's disease ( PD ) . Recent review s have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD . We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor ( SSRI ) antidepressants differ in their short-term efficacy , because the time to onset of therapeutic benefit remains an important criterion in depression . The short-term efficacy ( after 14 and 30 days ) of two antidepressants ( desipramine , a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram , a SSRI ) was assessed in a double-blind , r and omized , placebo- controlled study of 48 nondemented PD patients suffering from major depression . After 14 days , desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale ( MADRS ) score , compared with citalopram and placebo . Both antidepressants produced significant improvements in the MADRS score after 30 days . Mild adverse events were twice as frequent in the desipramine group as in the other groups . A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI . However , desipramine 's lower tolerability may outweigh its slight short-term clinical advantage", "We assessed the effect of 3-month treatment of sertraline ( 50 mg ) or low-dose amitriptyline ( 25 mg ) on depression and quality of life in 31 patients with Parkinson 's disease in a prospect i ve single-blind r and omized study . Both drugs significantly reduced the Hamilton Depression Rating Scale ( HDRS-17 ) score . Completion rate was 75 % for sertraline ( 12 of 16 ) and 73 % for amitriptyline ( 11 of 15 ) . Responder rate ( HDRS-17 score reduction > /= 50 % ) was 83.3 % for sertraline and 72.7 % for amitriptyline . Sertraline but not amitriptyline treatment determined a significant benefit on quality of life ( PDQ-39 scale ) . We found no change in Unified Parkinson 's Disease Rating Scale scores . However , the improvement in specific PDQ-39 subscores ( mobility , activities of daily living , and stigma ) suggests that depression affects patient self-perception of motor function and further emphasizes the need for its treatment", "Objective : To study the efficacy of 15 Hz repetitive transcranial magnetic stimulation ( rTMS ) in treating depression in patients with Parkinson ’s disease . Methods : 42 patients were enrolled into two groups : group 1 , active rTMS ( 15 Hz rTMS for 10 days ) and placebo drug treatment ; group 2 , sham rTMS and fluoxetine 20 mg/day . A specially design ed sham coil was used for sham stimulation . The unified Parkinson ’s disease rating scale ( UPDRS ) , activities of daily living ( ADL ) , Hamilton rating scale for depression ( HRSD ) , Beck depression inventory ( BDI ) , and mini-mental state examination ( MMSE ) were assessed by a rater blinded to treatment arm . Results : HRSD and BDI were improved to the same extent in both groups after two weeks of treatment ( 38 % and 32 % for group 1 , 41 % and 33 % for group 2 , respectively ) . At week 8 there was a tendency for worse motor UPDRS scores in group 2 ( NS ) . ADL showed improvement at week 8 only in group 1 . MMSE improved in both groups after treatment , but faster in group 1 than in group 2 . There were fewer adverse effects in group 1 than in group 2 . Conclusions : rTMS has the same antidepressant efficacy as fluoxetine and may have the additional advantage of some motor improvement and earlier cognitive improvement , with fewer adverse effects", "Idiopathic Parkinson 's disease ( IPD ) is characterized by motor signs such as akinesia , rigidity , and often tremor at rest . In addition to these symptoms , depression is a common finding affecting 40 % of patients with IPD . This study evaluates the effect of the selective serotonin reuptake inhibitor , citalopram , on motor and nonmotor symptoms of depressed and nondepressed patients with IPD . Forty-six nondemented patients with IPD ( 24 men , 22 women ; mean age 64 ± 5.3 years ; mean ± SD disease duration , 6.4 ± 3.2 years ; mean ± SD Hoehn-Yahr stage , 2.8 ± 1.2 ) were included in the study . Patients were divided in two subgroups : depressed ( n = 18 ) and nondepressed ( n = 28 ) . Citalopram was added in an unblinded manner , starting with 10 mg/d , and , after a week , increased up to 20 mg/d in the depressed subgroup ( n = 18 ) and in half of the nondepressed subgroup ( n = 14 ) . Parkinsonian and depressive symptoms were evaluated before and after 1 and 4 months of treatment . Statistical evaluation was made by analysis of variance for repeated measures . Citalopram did not worsen motor performance in IPD , but improved bradykinesia and finger taps after 1 month and 4 months of treatment both in patients with and without depression ( p improvement in mood was also observed in 15 of 16 patients with depression . Although case reports indicate that citalopram can potentially worsen the motor symptoms in patients with PD , to date this effect has not been confirmed . Many of the symptoms , typically associated with depression , can be observed in nondepressed patients with IPD , because signs thought to represent depression can be produced by Parkinson 's disease . In this study , we observed that when combined with levodopa , citalopram induces an improvement of motor performance , in particular of subscores 23 and 31 of Unified Parkinson 's Disease Rating Scale both in depressed and in nondepressed patients with IPD", "Some of the selective serotonin reuptake inhibitors (SSRI)-induced motor side effects are mediated by stimulating 5-HT2 receptors in the basal ganglia , probably because serotonin inhibits the subsequent neuronal dopamine release . We hypothesized that nefazodone , a serotonin 2 antagonist/reuptake inhibitor ( SARI ) that selectively blocks 5-HT2 receptors , could disrupt the aforementioned inhibitory pathway . Therefore , increased dopamine levels in the postsynaptic milieu and an improvement in the motor symptoms in depressed patients with Parkinson disease ( PD ) should be observed . This study was design ed to determine whether nefazodone has a dual activity as an antidepressant and as an agent capable of reducing the extrapyramidal symptoms in depressed parkinsonian patients . Depressed patients with PD were r and omly assigned to 2 therapeutic groups : nefazodone or fluoxetine . Patients were evaluated by a psychiatrist and were blindly assessed by a neurologist with an array of scales . Patients on nefazodone ( n = 9 ) showed a significant improvement over time in the total Unified Parkinson Disease Rating Scale score ( UPDRS ) ( part II + part III ) ( P = 0.004 ) and in the UPDRS subscore part III ( P = 0.003 ) . None of these scores changed over time in the fluoxetine group ( n = 7 ) . Both , nefazodone and fluoxetine were equally effective as antidepressants : Beck Depression Inventory scores significantly improved ( P < 0.001 ) , with no significant differences between treatment groups ( P = 0.97 ) . If our results can be confirmed in a larger clinical trial , nefazodone ought to be considered over fluoxetine given its secondary beneficial effects regarding the reduction of extrapyramidal symptoms in depressed PD patients" ]

[ "Head impacts are common in contact sports , but only recently has there been a rising awareness of the effects of subconcussive impacts in adolescent athletes . A better underst and ing of how to attenuate head impacts is needed and therefore , this study investigated the relationship between neck strength , impact , and neurocognitive function in an acute bout of soccer heading in a sample of female high school varsity soccer players . Seventeen participants completed the ImPACT neurocognitive test and had their isometric neck strength tested ( flexion , extension , and bilateral flexion ) before heading drills . Each participant was outfitted with custom headgear with timing switches and a three-dimensional accelerometer affixed to the back of the head , which allowed for measurement of impact during heading . Participants performed a series of 15 directional headers , including 5 forward , 5 left and 5 right headers in a r and om order , then completed the ImPACT test again . Neurocognitive tests revealed no significant changes following heading . However , there were statistically significant , moderate , negative correlations ( r = -0.500:-0.757 , p neck strength and result ant header acceleration , indicating that those with weaker necks sustained greater impacts . This suggests neck strengthening may be an important component of any head injury prevention/reduction program", "Our purpose was to determine if an acute bout of heading soccer balls adversely affected postural control and self-reported symptoms of cerebral concussion . Thirty-one college-aged soccer players were r and omly placed into either a kicking group or a heading group . Subjects either kicked or headed 18 soccer balls over the course of 40 minutes . Subjects had their postural control assessed while st and ing on a force plate and completed a concussion symptoms checklist on three separate occasions : prior to , immediately following , and 24 hours after kicking or heading . There were no significant differences between the heading and kicking groups on the postural control measures prior to , immediately following , and 24 hours after kicking/heading . The heading group did , however , report significantly more concussion symptoms than the kicking group immediately after heading , but not 24 hours after heading . The number of previous concussions sustained by subjects did not influence the effects of heading . An acute bout of soccer heading appears to cause an increase in self-reported symptoms of cerebral concussion lasting less than 24 hours but no quantifiable deficits in postural control . Further research is needed to investigate the cumulative effects of soccer heading on postural control and other objective measures of brain function", "Abstract Objective : To examine the effect of soccer heading ball speed on S-100B serum concentration , concussion sideline assessment s and linear head impact acceleration . Methods : Sixteen division I soccer players participated in this pre-test post-test design study . Athletes performed five st and ing headers over a 10 minute period at 30 ( n = 5 ) , 40 ( n = 5 ) or 50 ( n = 6 ) miles per hour ( mph ) ( r and omized ) . S-100B serum concentration ( ng mL−1 ) and sideline concussion assessment s were measured prior to and post-heading . Peak result ant linear head acceleration ( gravitational units ; g ) was measured during soccer heading . Results : No statistically significant interaction effects were identified between ball velocity groups over time on S100B ( effect sizes ranged from 0.03–0.23 ) or concussion assessment s tests . There was a non-significant increase ( p = 0.06 ) in head impact acceleration from the 30 ( 30.6 ; SD = 6.2 g ) to 50 mph ( 50.7 ; SD = 7.7 g ) ball speed . Conclusions : In this controlled setting , an acute bout of soccer heading across various ball velocities did not affect S100B or concussion assessment test scores . These findings are preliminary , as the small sample size in each group may have played a role in the lack of significant findings", "Concussion is a known risk in youth soccer , but little is known about subconcussive head impacts . The authors provided a prospect i ve cohort study measuring frequency and magnitude of subconcussive head impacts using accelerometry in a middle school – age soccer tournament , and association between head impacts and changes in ( 1 ) symptoms , ( 2 ) cognitive testing , and ( 3 ) advanced neuroimaging . A total of 17 youth completed the study ( 41 % female , mean 12.6 years ) . There were 73 head impacts > 15 g measured ( 45 % headers ) and only 2 had a maximum peak linear acceleration > 50 g . No youth reported symptoms consistent with concussion . After correction for multiple comparisons and a sensitivity analysis excluding clear outliers , no significant associations were found between head impact exposure and neuropsychological testing or advanced neuroimaging . The authors conclude that head impacts were relatively uncommon and low in acceleration in youth playing a weekend soccer tournament . This study adds to the limited data regarding head impacts in youth soccer", "Primary objective : The purpose of this study was to investigate the relationship between soccer heading and computerized neurocognitive performance and symptoms in female and male youth soccer players . Research design : Cross-sectional and prospect i ve design . Methods and procedures : A total of 63 ( 27 females , 36 males ) youth soccer players aged 13–18 years ( M = 15.89 , SD = 1.17 ) participated in the study . Participants completed the Immediate Post-concussion Assessment and Cognitive Test ( ImPACT ) and symptom report . Main outcomes : Computerized neurocognitive performance ( e.g. , verbal and visual memory , motor processing , and reaction time ) and symptoms . Results : There were no differences in neurocognitive performance or symptoms among low- , moderate- , and high-exposure header groups . The current sample outperformed the 10th percentile norms for neurocognitive and symptom scores . Males headed the ball more frequently and reported lower verbal and visual memory and motor processing speed scores than females . Conclusion : The current findings did not support a relationship between soccer heading and computerized neurocognitive performance and symptoms . The research ers suggest that any purported effects of soccer heading in youth are subtle and may affect only a small number of athletes . The reported sex differences in heading exposure warrant further attention", "Objective The main objective of this study was to prospect ively examine the acute effects of heading in soccer on cognitive function . Design This was a prospect i ve cross-over study using a brief neuropsychological battery to assess cognitive function . The tests were performed before and after two separate practice sessions , with athletes serving as their own controls . Setting Male and female Division I college athletes . Participants Members of the men 's and women 's varsity collegiate Penn State University soccer teams . Forty-four males and 56 females entered and finished the study . All athletes had a normal physical examination . Interventions Before and after both practice sessions , all athletes had a brief battery of neuropsychological tests and a symptom checklist . Main Outcome Measures Neuropsychological tests symptom checklist compared at baseline with those after the practice sessions . Results There were no significant differences in pretest scores between groups and no difference on posttest scores between heading and nonheading groups . A significant difference was detected using MANOVA ( p = measures of attention and concentration , indicating a practice effect . A gender-specific effect in one test measuring attention and concentration was found . There was no difference in symptoms before and after heading as compared with exertional controls . Conclusions In this study , soccer players heading the ball does not appear to lead to acute changes in cognitive function as assessed by a brief neuropsychological battery . There are practice effects that occur with repetitive neuropsychological testing and gender differences with certain tests" ]

[ "Background — Prior primary prevention trials of statin therapy that used cholesterol criteria for enrollment have not reported significant decreases in stroke risk . We evaluated whether statin therapy might reduce stroke rates among individuals with low levels of cholesterol but elevated levels of high-sensitivity C-reactive protein . Methods and Results — In Justification for the Use of statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) , 17 802 apparently healthy men and women with low-density lipoprotein cholesterol levels were r and omly allocated to rosuvastatin 20 mg daily or placebo and then followed up for the occurrence of a first stroke . After a median follow-up of 1.9 years ( maximum , 5.0 years ) , rosuvastatin result ed in a 48 % reduction in the hazard of fatal and nonfatal stroke as compared with placebo ( incidence rate , 0.18 and 0.34 per 100 person-years of observation , respectively ; hazard ratio 0.52 ; 95 % confidence interval , 0.34 to 0.79 ; P=0.002 ) , a finding that was consistent across all examined subgroups . This finding was due to a 51 % reduction in the rate of ischemic stroke ( hazard ratio , 0.49 ; 95 % confidence interval , 0.30 to 0.81 ; P=0.004 ) , with no difference in the rates of hemorrhagic stroke between the active and placebo arms ( hazard ratio , 0.67 ; 95 % confidence interval , 0.24 to 1.88 ; P=0.44 ) . Conclusion — Rosuvastatin reduces by more than half the incidence of ischemic stroke among men and women with low levels of low-density lipoprotein cholesterol levels who are at risk because of elevated levels of high-sensitivity C-reactive protein . Clinical Trial Registration — clinical trial.gov . Unique identifier : NCT00239681", "Objectives : For large scale follow up studies with non-demented patients in which cognition is an endpoint , there is a need for short , inexpensive , sensitive , and reliable neuropsychological tests that are suitable for repeated measurements . The commonly used Mini-Mental-State-Examination fulfils only the first two requirements . Methods : In the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) , 5804 elderly subjects aged 70 to 82 years were examined using a learning test ( memory ) , a coding test ( general speed ) , and a short version of the Stroop test ( attention ) . Data presented here were collected at dual baseline , before r and omisation for active treatment . Results : The tests proved to be reliable ( with test/retest reliabilities ranging from acceptable ( r=0.63 ) to high ( r=0.88 ) and sensitive to detect small differences in subjects from different age categories . All tests showed significant practice effects : performance increased from the first measurement to the first follow up after two weeks . Conclusion : Normative data are provided that can be used for one time neuropsychological testing as well as for assessing individual and group change . Methods for analysing cognitive change are proposed", "Objective The CARDS trial , a multicentre , r and omized , controlled trial , found that atorvastatin 10 mg/day for patients with type 2 diabetes mellitus and normal low-density lipoprotein (LDL)-cholesterol significantly reduced cardiovascular ( CV ) events , including stroke . We estimated the cost effectiveness of atorvastatin as primary prevention against CV disease from the short-term and lifetime US payer perspectives . Research design and methods We constructed a decision analytic ( Markov ) model to evaluate long-term costs and outcomes for atorvastatin 10 mg/day versus no HMG-CoA reductase inhibitor ( statin ) therapy for patients with type 2 diabetes and no history of a CV event . CV event rates and survival were based on risk equations calibrated to CARDS and applied to a US type 2 diabetes population ; the atorvastatin effect on CV events was based on hazard ratios from CARDS ; direct medical care costs were based on US treatment patterns and published costs analyses of patients with diabetes . Costs were valued in $ US , year 2005 values ; costs and benefits were discounted at 3 % per annum . Results Within the time horizon of the trial ( 5 years ) , the cost effectiveness of atorvastatin was $ US137 276 per QALY . At 10 years , the incremental cost per QALY improved to $ US3640 per QALY . At 25 years , overall costs were lower and QALYs higher in the atorvastatin arm . Costs of managing CV events were lower after 5 years for patients treated with atorvastatin . Conclusions For patients with type 2 diabetes and one additional risk factor for CV disease , normal LDL-cholesterol and no history of a CV event , primary prevention with atorvastatin appears to be cost saving and improve outcomes over 25 years , although it is costly from a short-term US payer perspective . From both a medical and an economic viewpoint , primary prevention is desirable in this patient population", "Aims Patients with Type 2 diabetes have an elevated risk of stroke . The role of lipid levels and diabetes‐specific factors in risk prediction of stroke is unclear , and estimates of efficacy of lipid‐lowering therapy vary between trials . We examined predictors of stroke and the effect of atorvastatin on specific stroke subtypes in Type 2 diabetes in the Collaborative Atorvastatin Diabetes Study ( CARDS ) [ a trial of 2838 participants with mean low‐density lipoprotein cholesterol atorvastatin 10 mg daily or placebo ] ", "Lipid-lowering therapy in individuals with high risk of cardiovascular disease reduces the incidence of coronary heart disease . However , few studies have assessed the benefits of cholesterol lowering for primary prevention of coronary heart disease in hypertensive patients with mild dyslipidemia or without conventional dyslipidemia . The large , r and omized Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese Study showed a 33 % reduction in coronary heart disease incidence with pravastatin as the primary prevention in Japanese patients . We conducted an exploratory analysis of the effect of diet plus pravastatin therapy on the primary prevention of cardiovascular events ( coronary heart disease , coronary heart disease plus cerebral infa rct ion , and cardiovascular disease ) in the 3277 patients with hypertension during the 5-year follow-up . There were no significant differences in mean baseline total cholesterol , blood pressure levels , or variation in blood pressure during the 5-year period between the diet ( n=1664 ) and diet plus pravastatin ( n=1613 ) groups . In the diet plus pravastatin group , the relative risk of coronary heart disease plus cerebral infa rct ion was reduced by 35 % ( hazard ratio : 0.65 ; CI : 0.46 to 0.93 ; P=0.02 ) , cerebral infa rct ion by 46 % ( hazard ratio : 0.54 ; CI : 0.29 to 0.98 ; P=0.04 ) , and cardiovascular disease by 33 % ( hazard ratio : 0.67 ; CI : 0.49 to 0.91 ; P=0.01 ) . In patients without a history of cardiovascular disease who have hypertension and mildly elevated cholesterol , pravastatin was effective in reducing the incidence of cardiovascular disease , particularly cerebral infa rct ion . Hence , in patients with hypertension with mildly elevated cholesterol levels , treatment with a statin is advisable to reduce the burden of cardiovascular disease", "CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data", "Background Simvastatin reduces cardiovascular mortality and morbidity but , as with other HMG-CoA reductase inhibitors , can cause significant muscle toxicity and has been associated with elevations of liver transaminases . Methods Muscle and liver adverse effects of simvastatin 40 mg daily were evaluated in a r and omized placebo-controlled trial involving 20,536 UK patients with vascular disease or diabetes ( in which a substantial reduction of cardiovascular mortality and morbidity has previously been demonstrated ) . Results The excess incidence of myopathy in the simvastatin group was incidence of serious hepatobiliary disease . Conclusion Among the many different types of high-risk patient studied ( including women , older individuals and those with low cholesterol levels ) , there was a very low incidence ( myopathy during 5 years treatment with simvastatin 40 mg daily . The risk of hepatitis , if any , was undetectable even in this very large long-term trial . Routine monitoring of liver function tests during treatment with simvastatin 40 mg is not useful . Trial Registration IS RCT", "BACKGROUND Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events . Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol , we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment . METHODS We r and omly assigned 17,802 apparently healthy men and women with low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin , 20 mg daily , or placebo and followed them for the occurrence of the combined primary end point of myocardial infa rct ion , stroke , arterial revascularization , hospitalization for unstable angina , or death from cardiovascular causes . RESULTS The trial was stopped after a median follow-up of 1.9 years ( maximum , 5.0 ) . Rosuvastatin reduced LDL cholesterol levels by 50 % and high-sensitivity C-reactive protein levels by 37 % . The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio for rosuvastatin , 0.56 ; 95 % confidence interval [ CI ] , 0.46 to 0.69 ; P myocardial infa rct ion ( hazard ratio , 0.46 ; 95 % CI , 0.30 to 0.70 ; P=0.0002 ) , 0.18 and 0.34 for stroke ( hazard ratio , 0.52 ; 95 % CI , 0.34 to 0.79 ; P=0.002 ) , 0.41 and 0.77 for revascularization or unstable angina ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.70 ; P combined end point of myocardial infa rct ion , stroke , or death from cardiovascular causes ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.69 ; P death from any cause ( hazard ratio , 0.80 ; 95 % CI , 0.67 to 0.97 ; P=0.02 ) . Consistent effects were observed in all subgroups evaluated . The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes . CONCLUSIONS In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels , rosuvastatin significantly reduced the incidence of major cardiovascular events . ( Clinical Trials.gov number , NCT00239681 .", "BACKGROUND Chronic kidney disease ( CKD ) is associated with an increased risk of incident cardiovascular disease ( CVD ) ; however , the role of statins for the primary prevention of acute cardiovascular events in patients with CKD and the effect of statins on kidney function loss in persons without prevalent CVD have not been studied . STUDY DESIGN Post hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study . SETTING & PARTICIPANTS Multicenter , r and omized , double-blind , placebo-controlled trial of 5,608 men and 997 women without CVD r and omly assigned to treatment with lovastatin or placebo . INTERVENTION Placebo or lovastatin , 20 mg/d . OUTCOMES & MEASUREMENTS First major acute cardiovascular event in participants with mild CKD and kidney function loss in persons with or without CKD . Estimated glomerular filtration rate was calculated using the 4-variable Modification of Diet in Renal Disease Study equation . RESULTS At baseline , mean estimated glomerular filtration rate in participants with CKD ( n = 304 ) was 53.0 + /- 6.0 mL/min/1.73 m(2 ) . After an average follow-up of 5.3 + /- 0.8 years , the incidence of a fatal and nonfatal CVD event was lower in participants with CKD receiving lovastatin than in those receiving placebo ( adjusted relative risk [ RR ] , 0.31 ; 95 % CI , 0.13 - 0.72 ; P = 0.01 ) . Tests for interaction suggested that the benefit of lovastatin was independent of the presence of CKD . Lovastatin did not reduce the annualized mean decrease in estimated glomerular filtration rate ( -1.3 + /- 0.07 vs -1.4 + /- 0.07 mL/min/1.73 m(2)/y , respectively ; P = 0.1 ) or the frequency of a > or = 25 % decrease in kidney function ( adjusted RR , 1.10 ; 95 % CI , 0.96 - 1.28 ; P = 0.2 ) or incident CKD ( adjusted RR , 1.04 ; 95 % CI , 0.86 - 1.27 ; P = 0.6 ) . LIMITATIONS Unable to determine the cause and duration of kidney disease , and information regarding proteinuria was not available . CONCLUSIONS Lovastatin is effective for the primary prevention of CVD in patients with CKD , but is not effective in decreasing kidney function loss in persons with no CVD", "Conventional lipid-lowering agents displayed only limited efficacy in lowering total and LDL cholesterol and a high incidence of side effects . Pravastatin is a new potent cholesterol-lowering agent , which selectively inhibits hepatic HMG-CoA-reductase . In a double-blind , placebo-controlled Swiss multicenter study with determination of lipids and lipoprotein in a central laboratory , the efficacy and safety of 6 months ' therapy with pravastatin was evaluated in 50 patients with mild hypercholesterolemia and additional coronary risk factors . Compared to baseline and after 26 weeks ' therapy , pravastatin significantly reduced total cholesterol ( pravastatin vs placebo , -17 % vs + 7 % , p LDL cholesterol ( -26 vs + 2 % , p total/HDL cholesterol ratio ( = \" atherogenic index \" ) was comparable in the two groups at baseline ( 5.9 + /- 1.1 vs 6.3 + /- 0.9 ) , and was distinctly lowered by pravastatin but not placebo ( -20 vs 0 % , p serum total cholesterol after 13 weeks ' treatment with 20 mg pravastatin was still below target ( on average -9.1 % ) , doubling of the dose produced a further decrease of 4.3 % . Serum HDL cholesterol and serum triglyceride levels did not change significantly during pravastatin treatment as compared to baseline and placebo . Pravastatin was well tolerated during the 26 weeks without relevant subjective side-effects . There were 5 dropouts during the study , 2 patients in the pravastatin group and 3 in the placebo group . These findings document that pravastatin , administered in a single daily dose of 20 to 40 mg , effectively lowers serum cholesterol and total-/HDL-cholesterol improving action and is well tolerated", "In the multicenter , double-blind EXCEL ( Exp and ed Clinical Evaluation of Lovastatin ) study the efficacy of lovastatin in modifying plasma lipids and lipoproteins in 8,245 participants with moderate primary hypercholesterolemia was evaluated . Patients were r and omly assigned to 48 weeks of treatment with diet and placebo or diet and lovastatin 20 or 40 mg once a day , or 20 or 40 mg twice a day . At all of these dosages , lovastatin produced substantial dose-dependent reductions in low-density-lipoprotein (LDL)-cholesterol levels , averaging 24 % ( 20 mg/day ) to 40 % ( 80 mg/day ) . The magnitude of the effect of this lipoprotein was further reflected by the percentage of patients who achieved National Cholesterol Education Program ( NCEP ) goals . In the absence of coronary artery disease ( CAD ) or two other CAD risk factors , the LDL-cholesterol goal of 4.14 mmol/L ( 160 mg/dL ) was attained by 22 % of patients in the placebo group and between 81 % ( 20 mg/day ) and 96 % ( 80 mg/day ) of those treated with lovastatin . For those with CAD or at least two other CAD risk factors , the LDL-cholesterol goal of 3.36 mmol/L ( 130 mg/dL ) was attained by 4 % of placebo patients and between 38 % ( 20 mg/day ) and 83 % ( 80 mg/day ) of those treated with lovastatin . Lovastatin also increased high-density-lipoprotein cholesterol ( 7 - 10 % ) and decreased triglycerides ( 10 - 19 % ) in a dose-dependent manner . Thus , when used as an adjunct to a prudent diet , lovastatin produces favorable changes in the entire lipoprotein profile and is a highly effective agent for managing patients with primary hypercholesterolemia", "OBJECTIVE Coronary artery disease is the most important cause of mortality in patients with type 2 diabetes . We aim ed to determine the prevalence of silent myocardial ischemia ( SMI ) and the effect of statin therapy on SMI in type 2 diabetic patients without manifest cardiovascular disease . RESEARCH DESIGN AND METHODS A r and omized , placebo-controlled , double-blind trial was performed in 250 patients with type 2 diabetes without manifest cardiovascular disease . Patients were given either 0.4 mg cerivastatin or placebo daily . In August 2001 , when cerivastatin was withdrawn from the market , cerivastatin 0.4 mg was replaced by 20 mg simvastatin without deblinding the study . The primary end point was the change in ischemic episodes , duration , and burden as measured by 48-h ambulatory electrocardiography ( AECG ) over 2 years . RESULTS At baseline , 47 of 233 ( 20 % ) evaluable ambulatory electrocardiograms showed evidence of ischemia . After 2 years , there was a trend toward more ischemia in both treatment groups , without significant differences between the changes in ischemic parameters ( episodes P = 0.498 ; duration P = 0.697 ; burden P = 0.798 ) in the two treatment groups . Cardiovascular events occurred in 12 patients in the placebo group and in two patients in the statin group ( P = 0.006 ) . There was no relationship between these cardiovascular events and the presence of SMI at baseline . CONCLUSIONS SMI occurred in 20 % of type 2 diabetes patients without manifest cardiovascular disease . There was no effect from 2 years of statin therapy on SMI . In contrast , we observed a significantly lower cardiovascular event rate on statin therapy . AECG may not be a proper tool for risk stratification in patients with type 2 diabetes", "CONTEXT Individuals with diabetes are at increased risk for cardiovascular disease ( CVD ) , but more aggressive targets for risk factor control have not been tested . OBJECTIVE To compare progression of sub clinical atherosclerosis in adults with type 2 diabetes treated to reach aggressive targets of low-density lipoprotein cholesterol ( LDL-C ) of 70 mg/dL or lower and systolic blood pressure ( SBP ) of 115 mm Hg or lower vs st and ard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower . DESIGN , SETTING , AND PARTICIPANTS A r and omized , open-label , blinded-to-end point , 3-year trial from April 2003-July 2007 at 4 clinical centers in Oklahoma , Arizona , and South Dakota . Participants were 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events . INTERVENTIONS Participants were r and omized to aggressive ( n=252 ) vs st and ard ( n=247 ) treatment groups with stepped treatment algorithms defined for both . MAIN OUTCOME MEASURES Primary end point was progression of atherosclerosis measured by common carotid artery intimal medial thickness ( IMT ) . Secondary end points were other carotid and cardiac ultrasonographic measures and clinical events . RESULTS Mean target LDL-C and SBP levels for both groups were reached and maintained . Mean ( 95 % confidence interval ) levels for LDL-C in the last 12 months were 72 ( 69 - 75 ) and 104 ( 101 - 106 ) mg/dL and SBP levels were 117 ( 115 - 118 ) and 129 ( 128 - 130 ) mm Hg in the aggressive vs st and ard groups , respectively . Compared with baseline , IMT regressed in the aggressive group and progressed in the st and ard group ( -0.012 mm vs 0.038 mm ; P carotid arterial cross-sectional area also regressed ( -0.02 mm(2 ) vs 1.05 mm(2 ) ; P left ventricular mass index ( -2.4 g/m(2.7 ) vs -1.2 g/m(2.7 ) ; P = .03 ) in the aggressive group . Rates of adverse events ( 38.5 % and 26.7 % ; P = .005 ) and serious adverse events ( n = 4 vs 1 ; P = .18 ) related to blood pressure medications were higher in the aggressive group . Clinical CVD events ( 1.6/100 and 1.5/100 person-years ; P = .87 ) did not differ significantly between groups . CONCLUSIONS Reducing LDL-C and SBP to lower targets result ed in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes . Clinical events were lower than expected and did not differ significantly between groups . Further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates and costs and favorable risk-benefit outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00047424", "A large well conducted r and omised controlled trial from Shanghai shows conclusively that teaching women how to examine their breasts does not lead to a reduction in mortality due to breast cancer compared with no screening at all.1 The findings should bring to an end more than decade of controversy and confusion in the United Kingdom concerning the efficacy and effectiveness of self examination of the breast . In September 1991 , in his retirement speech , Chief Medical Officer Sir Donald Acheson announced that breast self examination was not effective and may give a false sense of security . His remarks outraged women 's health campaigners , fuelled by a media frenzy in favour of breast self examination that lasted several weeks . The introduction of a policy of breast awareness shortly afterwards only added to the confusion . Rather than ritually checking their breasts at a specific time each month according to a set technique , women were encouraged to take responsibility for their own health by taking convenient opportunities such as bathing or dressing to become familiar with their breasts at different times of the month and", "Background —We determined whether statin use ( versus nonuse ) is associated with superior lower-extremity functioning independently of cholesterol levels and other confounders in patients with and without peripheral arterial disease . Methods and Results — Participants included 392 men and women with an ankle brachial index ( ABI ) Functional outcomes included 6-minute walk distance and 4-meter walking velocity . A summary performance score combined performance in walking speed , st and ing balance , and time for 5 repeated chair rises into an ordinal score ranging from 0 to 12 ( 12=best ) . Adjusting for age , sex , ABI , comorbidities , education level , medical insurance status , cholesterol , and other confounders , participants taking statins had better 6-minute walk performance ( 1276 versus 1218 feet , P = 0.045 ) , faster walking velocity ( 0.93 versus 0.89 m/s , P = 0.006 ) , and a higher summary performance score ( 10.2 versus 9.4 , P taking statins . Positive associations were attenuated slightly after additional adjustment for C-reactive protein level but remained statistically significant for walking velocity and the summary performance score . We did not find significant associations between lower-extremity functioning and aspirin , ACE inhibitors , vasodilators , or & bgr;-blockers . Conclusions —Statin use is associated with superior leg functioning compared with no statin use , independent of cholesterol levels and other potential confounders . These data suggest that non – cholesterol-lowering properties of statins may favorably influence functioning in persons with and without peripheral arterial disease", "Atherosclerosis is a disease whose pathogenesis involves inflammatory and immunological mechanisms , including an autoimmune reaction against heat shock proteins ( Hsps ) . The purpose of this study was to analyze whether the antiatherogenic effect of statin therapy was not limited to its lipid lowering effect , but also included anti-inflammatory and immunomodulatory effects , paying special attention to the measurement of circulating concentrations of anti-Hsp70 and anti-Hsp60 antibodies previously related to vascular disease . Two-hundred and seventy-five subjects aged 40–60 years , r and omly selected in an epidemiological study on the incidence of vascular risk factors , were studied . Laboratory tests included a complete lipid profile after a 12-h fast and measurements of glucose , C-reactive-protein , anti-Hsp70 and anti-Hsp60 antibodies . Subjects with hypercholesterolemia had significantly higher concentrations of anti-Hsp70 antibodies as compared to subjects with normal cholesterol concentrations . Statin therapy was associated with 11.63 and 15.3 % reductions in total and LDL-cholesterol ( P = 0.005 and 0.017 , respectively ) as compared to untreated subjects , and with lower concentrations of circulating anti-Hsp70 ( P = 0.016 ) antibodies . No differences were found in C-reactive-protein values . Since statin therapy not only reduces lipid profile , but also anti-Hsp70 and anti-Hsp60 antibody concentrations , without changing C-reactive-protein values , it is suggested that such an effect could not be accounted for by the anti-inflammatory properties of statins , but by their direct immunomodulatory properties through their effects on lymphocyte function", "BACKGROUND HDL-cholesterol concentrations are inversely associated with occurrence of cardiovascular events . We addressed , using the JUPITER trial cohort , whether this association remains when LDL-cholesterol concentrations are reduced to the very low ranges with high-dose statin treatment . METHODS Participants in the r and omised placebo-controlled JUPITER trial were adults without diabetes or previous cardiovascular disease , and had baseline concentrations of LDL cholesterol of less than 3.37 mmol/L and high-sensitivity C-reactive protein of 2 mg/L or more . Participants were r and omly allocated by a computer-generated sequence to receive rosuvastatin 20 mg per day or placebo , with participants and adjudicators masked to treatment assignment . In the present analysis , we divided the participants into quartiles of HDL-cholesterol or apolipoprotein A1 and sought evidence of association between these quartiles and the JUPITER primary endpoint of first non-fatal myocardial infa rct ion or stroke , hospitalisation for unstable angina , arterial revascularisation , or cardiovascular death . This trial is registered with Clinical Trials.gov , number NCT00239681 . FINDINGS For 17,802 patients in the JUPITER trial , rosuvastatin 20 mg per day reduced the incidence of the primary endpoint by 44 % ( p placebo ( who had a median on-treatment LDL-cholesterol concentration of 2.80 mmol/L [ IQR 2.43 - 3.24 ] ) , HDL-cholesterol concentrations were inversely related to vascular risk both at baseline ( top quartile vs bottom quartile hazard ratio [ HR ] 0.54 , 95 % CI 0.35 - 0.83 , p=0.0039 ) and on-treatment ( 0.55 , 0.35 - 0.87 , p=0.0047 ) . By contrast , among the 8900 ( 50 % ) patients given rosuvastatin 20 mg ( who had a median on-treatment LDL-cholesterol concentration of 1.42 mmol/L [ IQR 1.14 - 1.86 ] ) , no significant relationships were noted between quartiles of HDL-cholesterol concentration and vascular risk either at baseline ( 1.12 , 0.62 - 2.03 , p=0.82 ) or on-treatment ( 1.03 , 0.57 - 1.87 , p=0.97 ) . Our analyses for apolipoprotein A1 showed an equivalent strong relation to frequency of primary outcomes in the placebo group but little association in the rosuvastatin group . INTERPRETATION Although measurement of HDL-cholesterol concentration is useful as part of initial cardiovascular risk assessment , HDL-cholesterol concentrations are not predictive of residual vascular risk among patients treated with potent statin therapy who attain very low concentrations of LDL cholesterol . FUNDING AstraZeneca", "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", "The PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) is a r and omized , double-blind , placebo-controlled trial design ed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women ( 70 to 82 years old ) with preexisting vascular disease or significant risk of developing this condition . Five thous and eight hundred four men and women in addition to receiving advice on diet and smoking , have been r and omized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers ( Cork , Irel and , Glasgow , Scotl and , and Leiden , The Netherl and s ) . Following an average 3.5-year intervention period , a primary assessment will be made of the influence of this therapy on major vascular events ( a combination of coronary heart disease , death , nonfatal myocardial infa rct ion , and fatal and nonfatal stroke ) . A number of additional analyses will also be conducted on the individual components of the primary end point , on men , on women , and on subjects with and without previous evidence of vascular disease . Finally , an assessment will be made of the effects of treatment on cognitive function , disability , hospitalization or institutionalization , vascular mortality , and all-cause mortality", "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 ", "OBJECTIVE —Rates of cardiovascular disease are highest in the elderly . Lipid-lowering statin therapy reduces the proportional risk as effectively in older patients as in younger individuals ; however , limited data are available for elderly patients with type 2 diabetes . We conducted a post hoc analysis to compare the efficacy and safety of atorvastatin among 1,129 patients aged 65–75 years at r and omization with 1,709 younger patients in the Collaborative Atorvastatin Diabetes Study ( CARDS ) . RESEARCH DESIGN AND METHODS —CARDS was a r and omized placebo-controlled trial of 10 mg/day atorvastatin for primary prevention of cardiovascular disease in patients aged 40–75 years with LDL cholesterol concentrations ≤4.14 mmol/l followed for a median of 3.9 years . The primary end point was time to first occurrence of acute coronary heart disease events , coronary revascularizations , or stroke . RESULTS —Atorvastatin treatment result ed in a 38 % reduction in relative risk ( [ 95 % CI −58 to −8 ] , P = 0.017 ) of first major cardiovascular events in older patients and a 37 % reduction ( [ −57 to −7 ] , P = 0.019 ) in younger patients . Corresponding absolute risk reductions were 3.9 and 2.7 % , respectively ( difference 1.2 % [ 95 % CI −2.8 to 5.3 ] , P = 0.546 ) ; numbers needed to treat for 4 years to avoid one event were 21 and 33 , respectively . All-cause mortality was reduced nonsignificantly by 22 % ( [ −49 to 18 ] , P = 0.245 ) and 37 % ( [ −64 to 9 ] , P = 0.98 ) , respectively . The overall safety profile of atorvastatin was similar between age-groups . CONCLUSIONS —Absolute and relative benefits of statin therapy in older patients with type 2 diabetes are substantial , and all patients warrant treatment unless specifically contraindicated", "The treatment of hypercholesterolemia may be associated with greater noncardiac mortality . This current pilot study sought to determine which behaviors , if any , are associated with decreases in cholesterol level . Twelve subjects received one of two cholesterol-reducing drugs or placebo . Cholesterol and behavioral ratings were measured at baseline , 4 , and 52 weeks with st and ardized scales . Cholesterol levels markedly declined with concomitant significant increases in impulsivity ratings at 4 weeks . At 52 weeks , the increase in impulsivity ratings was no longer apparent , but depression ratings showed a significant improvement . This pilot study , although limited in size , raises the possibility that cholesterol-lowering drugs are associated with mild , time-limited increases in impulsivity and with mild , time-delayed improvements in depression ratings", "Background — Recent clinical trials have suggested that intensive versus st and ard lipid-lowering therapy provides for additional benefit . Electron-beam computed tomography provides the opportunity to quantify the progression of coronary artery calcification ( CAC ) in serial measurements . Methods and Results — In a multicenter , r and omized , double-blind trial , 471 patients ( age 61±8 years ) who had no history of coronary artery disease and no evidence of high- grade coronary stenoses ( > 50 % diameter reduction ) were r and omized if they had ≥2 cardiovascular risk factors and moderate calcified coronary atherosclerosis as evidence d by a CAC score ≥30 . Patients were assigned to receive 80 mg or 10 mg of atorvastatin per day over 12 months . Progression of CAC volume scores could be analyzed in 366 patients . After pretreatment with 10 mg of atorvastatin for 4 weeks , 12 months of study medication reduced LDL cholesterol from 106±22 to 87±33 mg/dL in the group r and omized to receive 80 mg of atorvastatin ( P ) . The mean progression of CAC volume scores , corrected for the baseline CAC volume score , was 27 % ( 95 % CI 20.8 % to 33.1 % ) in the 80-mg atorvastatin group and 25 % ( 95 % CI 19.1 % to 30.8 % ) in the 10-mg atorvastatin group ( P=0.65 ) . CAC progression showed no relationship with on-treatment LDL cholesterol levels . Conclusions — We did not observe a relationship between on-treatment LDL cholesterol levels and the progression of calcified coronary atherosclerosis . Over a period of 12 months , intensive atorvastatin therapy was unable to attenuate CAC progression compared with st and ard atorvastatin therapy . The possibility remains that the time window was too short to demonstrate an effect", "BACKGROUND Elevated levels of C-reactive protein , even in the absence of hyperlipidemia , are associated with an increased risk of coronary events . Statin therapy reduces the level of C-reactive protein independently of its effect on lipid levels . We hypothesized that statins might prevent coronary events in persons with elevated C-reactive protein levels who did not have overt hyperlipidemia . METHODS The level of C-reactive protein was measured at base line and after one year in 5742 participants in a five-year r and omized trial of lovastatin for the primary prevention of acute coronary events . RESULTS The rates of coronary events increased significantly with increases in the base-line levels of C-reactive protein . Lovastatin therapy reduced the C-reactive protein level by 14.8 percent ( P lovastatin-induced changes in the lipid profile . As expected , lovastatin was effective in preventing coronary events in participants whose base-line ratio of total cholesterol to high-density lipoprotein ( HDL ) cholesterol was higher than the median ratio , regardless of the level of C-reactive protein ( number needed to treat for five years to prevent 1 event , 47 ; P=0.005 ) . However , lovastatin was also effective among those with a ratio of total to HDL cholesterol that was lower than the median and a C-reactive protein level higher than the median ( number needed to treat , 43 ; P=0.02 ) . In contrast , lovastatin was ineffective among participants with a ratio of total to HDL cholesterol and a C-reactive protein level that were both lower than the median ( number needed to treat , 983 ; P=0.80 ) . CONCLUSIONS Statin therapy may be effective in the primary prevention of coronary events among subjects with relatively low lipid levels but with elevated levels of C-reactive protein", "OBJECTIVE Cardiovascular disease ( CVD ) is the most important cause of mortality in patients with type 2 diabetes and is preceded by endothelial dysfunction . Flow-mediated dilation ( FMD ) is a noninvasive technique for measuring endothelial dysfunction . We aim ed to determine the effect of long-term statin therapy versus placebo on FMD in patients with type 2 diabetes without manifest CVD . RESEARCH DESIGN AND METHODS A r and omized , placebo-controlled , double-blind trial was performed with 250 type 2 diabetic patients . Patients were given 0.4 mg cerivastatin or placebo daily . In August 2001 , when cerivastatin was withdrawn from the market , the 0.4 mg cerivastatin was replaced by 20 mg simvastatin , without deblinding the study . The primary end point was the change in FMD , measured by B-mode ultrasound , after 2 years . RESULTS Determinants of baseline FMD were diabetes duration , common carotid intima-media thickness , and brachial artery diameter . FMD at baseline was 1.51 % in the placebo group and 1.66 % in the statin group and did not change significantly after 2 years . CONCLUSIONS The 2-year statin therapy had no effect on FMD in type 2 diabetes . Statin-induced improvement of cardiovascular risk in patients with type 2 diabetes may be mediated through mechanisms other than increased nitric oxide availability", "BACKGROUND A recent trial in Western countries has shown that rosuvastatin slows progression of carotid intima-media thickness ( IMT ) in patients with modest carotid IMT thickening and elevated levels of low-density lipoprotein cholesterol ( LDL-C ) . We conducted a prospect i ve , r and omized , open-label , blinded-endpoint trial to determine whether rosuvastatin is more effective than pravastatin in slowing progression of carotid IMT in Japanese patients . METHODS AND RESULTS Adult patients with hypercholesterolemia who had a maximum IMT ≥1.1 mm were r and omly assigned to receive rosuvastatin or pravastatin . The primary endpoint was the percent change in the mean-IMT , which was measured by a single observer who was blinded to the treatment assignments . The trial was stopped on April 2011 according to the recommendation by the data and safety monitoring committee . A total of 348 patients ( 173 rosuvastatin ; 175 pravastatin ) were enrolled and 314 ( 159 rosuvastatin ; 155 pravastatin ) were included in the primary analysis . Mean ( SD ) percentage changes in the mean-IMT at 12 months were 1.91 % ( 10.9 ) in the rosuvastatin group and 5.8 % ( 12.0 ) in the pravastatin group , with a difference of 3.89 % ( 11.5 ) between the groups ( P=0.004 ) . At 12 months , 85 patients ( 59.4 % ) in the rosuvastatin group achieved a LDL-C/high-density lipoprotein cholesterol ratio ≤1.5 compared with 24 patients ( 16.4 % ) in the pravastatin group ( P CONCLUSIONS Rosuvastatin significantly slowed progression of carotid IMT at 12 months compared with pravastatin ", "In the Justification for Use of statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) , r and om allocation of rosuvastatin compared to placebo among primary prevention patients with a low-density lipoprotein cholesterol level of or = 2 mg/L result ed in a highly significant 44 % reduction in major vascular events . However , the relation of baseline hs-CRP levels to risk within JUPITER has not previously been described and has been an area of controversy for study interpretation . As reported in the present study for the first time , despite enrolling patients with a constrained range of values , increasing baseline hs-CRP levels within JUPITER were nonetheless associated with increasing vascular risk in analyses treating hs-CRP as a continuous variable , as an ordinal variable , and as a threshold variable . As anticipated , the relative risk reduction associated with rosuvastatin was similar in magnitude across the tertile and threshold levels of entry hs-CRP . In conclusion , as the absolute risk increased with increasing hs-CRP , the absolute risk reduction associated with rosuvastatin within JUPITER was also greatest among those with the greatest entry hs-CRP levels", "Objective Older patients experience higher rates of cardiovascular disease than younger patients , but may be undertreated with statins due to doubts about efficacy and safety . The Lipid-Lowering Arm of the Anglo-Sc and inavian Cardiac Outcomes Trial allowed an evaluation of the efficacy and safety of atorvastatin among older ( ≥65 years ) and younger ( Methods A total of 10 305 patients with hypertension , at least three other cardiovascular risk factors , total cholesterol concentrations of 251 mg/dl or less , and no known coronary heart disease ( CHD ) were r and omized to receive atorvastatin 10 mg or placebo . The primary endpoint was a composite of nonfatal myocardial infa rct ion and fatal CHD . Results There were 4445 patients in the older group ( mean 71 years ) and 5860 patients ( mean 57 years ) in the younger group . Among those taking placebo , the older group experienced a higher rate of primary endpoints than the younger group ( 11.7 vs. 7.6 events per 1000 patient years , respectively ) . After a median follow-up of 3.3 years , the primary endpoint was reduced by a similar proportion in both older and younger patients ( 37 vs. 33 % , respectively ) . Although older patients reported more serious adverse events than younger patients , there were no significant differences between atorvastatin and placebo within each age group . Conclusion Atorvastatin reduced the risk of major cardiovascular events to a similar relative extent in both older and younger patients with treated hypertension . However , given that event rates were higher in older patients , the absolute benefits of atorvastatin were greater for older than younger patients", "Background Traditional methods for analyzing clinical and epidemiological cohort study data have been focused on the first occurrence of a health outcome . However , in many situations , recurrent event data are frequently observed . It is inefficient to use methods for the analysis of first events to analyse recurrent event data . Methods We applied several semi-parametric proportional hazards models to analyze the risk of recurrent myocardial infa rct ion ( MI ) events based on data from a very large r and omized placebo-controlled trial of cholesterol-lowering drug . The backward selection procedure was used to select the significant risk factors in a model . The best fitting model was selected using the log-likelihood ratio test , Akaike Information and Bayesian Information Criteria . Results A total of 8557 persons were included in the LIPID study . Risk factors such as age , smoking status , total cholesterol and high density lipoprotein cholesterol levels , qualifying event for the acute coronary syndrome , revascularization , history of stroke or diabetes , angina grade and treatment with pravastatin were significant for development of both first and subsequent MI events . No significant difference was found for the effects of these risk factors between the first and subsequent MI events . The significant risk factors selected in this study were the same as those selected by the parametric conditional frailty model . Estimates of the relative risks and 95 % confidence intervals were also similar between these two methods . Conclusions Our study shows the usefulness and convenience of the semi-parametric proportional hazards models for the analysis of recurrent event data , especially in estimation of regression coefficients and cumulative risks", "BACKGROUND The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome . No study , however , has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease ( CHD ) in hypertensive patients who are not conventionally deemed dyslipidaemic . METHODS Of 19342 hypertensive patients ( aged 40 - 79 years with at least three other cardiovascular risk factors ) r and omised to one of two antihypertensive regimens in the Anglo-Sc and inavian Cardiac Outcomes Trial , 10305 with non-fasting total cholesterol concentrations 6.5 mmol/L or less were r and omly assigned additional atorvastatin 10 mg or placebo . These patients formed the lipid-lowering arm of the study . We planned follow-up for an average of 5 years , the primary endpoint being non-fatal myocardial infa rct ion and fatal CHD . Data were analysed by intention to treat . FINDINGS Treatment was stopped after a median follow-up of 3.3 years . By that time , 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group ( hazard ratio 0.64 [ 95 % CI 0.50 - 0.83 ] , p=0.0005 ) . This benefit emerged in the first year of follow-up . There was no significant heterogeneity among prespecified subgroups . Fatal and non-fatal stroke ( 89 atorvastatin vs 121 placebo , 0.73 [ 0.56 - 0.96 ] , p=0.024 ) , total cardiovascular events ( 389 vs 486 , 0.79 [ 0.69 - 0.90 ] , p=0.0005 ) , and total coronary events ( 178 vs 247 , 0.71 [ 0.59 - 0.86 ] , p=0.0005 ) were also significantly lowered . There were 185 deaths in the atorvastatin group and 212 in the placebo group ( 0.87 [ 0.71 - 1.06 ] , p=0.16 ) . Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months , and by 1.1 mmol/L after 3 years of follow-up . INTERPRETATION The reductions in major cardiovascular events with atorvastatin are large , given the short follow-up time . These findings may have implication s for future lipid-lowering guidelines", "A double-blind , placebo-controlled , parallel-group study was performed to determine whether atorvastatin , a new HMG-CoA reductase inhibitor , could effectively and safely reduce plasma LDL-cholesterol concentrations in Japanese patients with type-2 diabetes without influencing glycemic control . The subjects were patients with hypercholesterolemia ( serum cholesterol concentration > or = 5.7 mmol/l ( 220 mg/dl ) ) and stable glycemic control . The fasting concentrations of hemoglobin A(1C ) ( HbA(1C ) ) , fructosamine , and 1,5-anhydroglucitol ( 1,5-AG ) were measured as indices of glycemic control . Plasma lipid concentrations and the safety of the drug were also examined . Forty eligible patients in two groups of 20 each were administered atorvastatin ( 10 mg/day ) or placebo . Neither atorvastatin nor placebo caused a significant change in HbA(1C ) , fructosamine , or 1,5-AG concentrations . Atorvastatin significantly reduced total cholesterol and LDL-cholesterol concentrations from baseline by 29.7 % ( p clinical adverse events and that of abnormal changes in laboratory test values did not differ between the two groups . In this trial , atorvastatin effectively and safely reduced LDL-cholesterol concentrations in diabetic patients with hypercholesterolemia without influencing glycemic control . These findings are clinical ly important because there are many diabetic patients with hypercholesterolemia and such patients have a high risk of developing arteriosclerotic disease", "CONTEXT Atherosclerosis is often advanced before symptoms appear and it is not clear whether treatment is beneficial in middle-aged individuals with a low Framingham risk score ( FRS ) and mild to moderate sub clinical atherosclerosis . OBJECTIVE To assess whether statin therapy could slow progression and /or cause regression of carotid intima-media thickness ( CIMT ) over 2 years . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled study ( Measuring Effects on Intima-Media Thickness : an Evaluation of Rosuvastatin [ METEOR ] ) of 984 individuals , with either age ( mean , 57 years ) as the only coronary heart disease risk factor or a 10-year FRS of less than 10 % , modest CIMT thickening ( 1.2- INTERVENTION Participants received either a 40-mg dose of rosuvastatin or placebo . MAIN OUTCOME MEASURES Rate of change in maximum CIMT ( assessed with B-mode ultrasound ) for 12 carotid sites ; changes in maximum CIMT of the common carotid artery , carotid bulb , and internal carotid artery sites and in mean CIMT of the common carotid artery sites . CIMT regression was assessed in the rosuvastatin group only . RESULTS Among participants in the rosuvastatin group , the mean ( SD ) baseline LDL cholesterol level of 155 ( 24.1 ) mg/dL declined to 78 ( 27.5 ) mg/dL , a mean reduction of 49 % ( P change in maximum CIMT for the 12 carotid sites was -0.0014 ( 95 % CI , -0.0041 to 0.0014 ) mm/y for the rosuvastatin group vs 0.0131 ( 95 % CI , 0.0087 - 0.0174 ) mm/y for the placebo group ( P change in maximum CIMT for the rosuvastatin group was -0.0038 ( 95 % CI , -0.0064 to -0.0013 ) mm/y for the common carotid artery sites ( P change in mean CIMT for the rosuvastatin group for the common carotid artery sites was 0.0004 ( 95 % CI , -0.0011 to 0.0019 ) mm/y ( P rosuvastatin was well tolerated with infrequent serious adverse cardiovascular events ( 6 participants [ 0.86 % ] had 8 events [ 1.1 % ] over 2 years ) . CONCLUSIONS In middle-aged adults with an FRS of less than 10 % and evidence of sub clinical atherosclerosis , rosuvastatin result ed in statistically significant reductions in the rate of progression of maximum CIMT over 2 years vs placebo . Rosuvastatin did not induce disease regression . Larger , longer-term trials are needed to determine the clinical implication s of these findings . TRIAL REGISTRATION clinical trials.gov Identifier :", "Background —Cholesterol modification reduces cardiovascular events in patients with atherosclerosis , including those with peripheral arterial disease . The purpose of this study was to determine whether cholesterol lowering with atorvastatin improves walking performance in patients with intermittent claudication . Methods and Results —This r and omized , double-blind , parallel- design study included 354 persons with claudication attributable to peripheral arterial disease . Patients were treated with placebo , atorvastatin ( 10 mg per day ) , or atorvastatin ( 80 mg per day ) for 12 months . The outcome measures included change in treadmill exercise time and patient-reported measures of physical activity and quality of life based on question naires . Maximal walking time after 12 months of treatment with atorvastatin did not change significantly . However , there was improvement in pain-free walking time after 12 months of treatment for the 80-mg ( P = 0.025 ) group compared with placebo . A physical activity question naire demonstrated improvement in ambulatory ability for the 10- and 80-mg groups ( P = 0.011 ) , whereas 2 quality of life instruments , the Walking Impairment Question naire and Short Form 36 Question naire , did not show significant change . Conclusions —Atorvastatin improves pain-free walking distance and community-based physical activity in patients with intermittent claudication . When treated with atorvastatin , patients with peripheral arterial disease may experience improvement in symptoms to complement the anticipated reduction in cardiovascular events reported in other studies of statins", "Left ventricular ( LV ) mass is a powerful predictor for future cardiovascular events . Epidemiologic studies have shown that hyperlipidemia is associated with higher LV mass . The effects of statin therapy for hyperlipidemia on LV mass have not been studied . To determine the effects of statin therapy on LV mass , we prospect ively studied 3 groups of age and body surface area-matched patients : group 1 ( n = 20 ) , patients with systemic hypertension and hyperlipidemia treated with pravastatin plus anti-hypertensive drugs ; group 2 ( n = 20 ) , patients with hypertension and hyperlipidemia treated with hypertensive agents and diet control alone ; and group 3 ( n = 20 ) , hypertensive patients with normolipidemia treated with antihypertensive agents . A group of controls without hypertension or hyperlipidemia was used for comparison . Echocardiograms were recorded at baseline and after 6-month therapy . All hypertensive groups showed significant decreases in LV mass index after treatment . Group 1 had the greatest decrease in LV mass and it was significantly higher than in groups 2 and 3 . Multivariate analysis revealed that regression of LV mass was significantly correlated only with the use of statins and sex ( p = 0.005 and 0.01 , respectively , R(2 ) = 0.47 ) . Linear regression analysis in group 1 showed a significant correlation between changes in arterial compliance and LV mass regression ( r = 0.57 , p = 0.01 ) . Thus , the addition of a statin may have an additional effect on reducing LV mass , independent of lipid-lowering effects", "CONTEXT In pre clinical models , inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase have been shown to positively affect bone remodeling balance . Observational studies and secondary analyses from lipid-lowering trials have yielded inconsistent results regarding the effect of these agents on bone mineral density and fracture risk . OBJECTIVE Our objective was to determine whether clinical ly significant skeletal benefits result from hydroxymethylglutaryl-coenzyme A reductase inhibition in postmenopausal women . DESIGN AND SETTING We conducted a prospect i ve , r and omized , double-blind , placebo-controlled , dose-ranging comparative clinical trial at 62 sites in the United States . PARTICIPANTS Participants included 626 postmenopausal women with low-density lipoprotein cholesterol levels of at least 130 mg/dl ( 3.4 mmol/liter ) and less than 190 mg/dl ( 4.9 mmol/liter ) , and lumbar ( L1-L4 ) spine bone mineral density T-score between 0.0 and -2.5 . INTERVENTION Once-daily placebo or 10 , 20 , 40 , or 80 mg atorvastatin was administered . MAIN OUTCOME MEASURES We assessed percent change from baseline in lumbar ( L1-L4 ) spine bone mineral density with each dose of atorvastatin compared with placebo . RESULTS At 52 wk , there was no significant difference between each atorvastatin and placebo group or change from baseline at any tested dose of atorvastatin or placebo in lumbar ( L1-L4 ) spine bone mineral density . Nor did atorvastatin produce a significant change in bone mineral density at any other site . Changes in biochemical markers of bone turnover did not differ significantly between each atorvastatin and placebo group . All doses of atorvastatin were generally well tolerated , with similar incidences of adverse events across all dose groups and placebo . CONCLUSIONS Clinical ly relevant doses of atorvastatin that lower lipid levels had no effect on bone mineral density or biochemical indices of bone metabolism in this study , suggesting that such oral agents are not useful in the prevention or treatment of osteoporosis", "OBJECTIVE The aim of this study was to assess obese patients with hypercholesterolemia whom were prescribed a st and ardized diet , comparing the action of orlistat , fluvastatin , orlistat with fluvastatin , and placebo on anthropometric measurements , blood pressure ( BP ) , and lipid profile . METHODS This was a 1-year , r and omized , double-blind , placebo-controlled trial . The patients were prescribed a controlled-energy diet and were r and omly allocated to receive placebo , orlistat 120 mg TID ( O group ) , fluvastatin 80 mg/d ( F group ) , or olistat 120 mg TID with fluvastatin 80 mg/d ( OF group ) . Clinical measurements ( body weight , body mass index [ BMI ] , waist circumference , and BP ) and lipid profile assessment ( total cholesterol [ TC ] , low-density lipoprotein cholesterol [ LDL-C ] , high-density lipoprotein cholesterol [ HDL-C ] , and triglycerides [ TGs ] ) were performed at baseline and after 6 months and 1 year of treatment . RESULTS The study included 99 obese patients with hypercholesterolemia ( 48 men and 51 women ; mean [ SD ] age , 51 [ 9 ] years ) . There were no significant differences between groups in baseline demographic , BP , or plasma lipid values . Three patients dropped out ( 2 women in the O group and 1 man in the OF group ) due to adverse events related to orlistat treatment , including gastrointestinal events ( oily spotting and fecal urgency ) . Ninety-six patients completed the study . There were significant differences from baseline ( mean [ SD ] ) in BMI , waist circumference reduction ( WCR ) , and body weight loss ( BWL ) at 6 months in the OF group ( 29.9 [ 1.1 ] kg/m(2 ) , 2.7 [ 0.8 ] cm , and 7.4 [ 0.9 ] kg , respectively ; all P BMI , WCR , and BWL at 1 year in the O group ( 29.0 [ 1.0 ] kg/m(2 ) , 3.0 [ 1.0 ] cm , and 8.6 [ 1.0 ] kg , respectively ; all P systolic and diastolic BP were observed at 1 year in the O and F groups ( all P TC and LDL-C in the F group ( both P TC , LDL-C , and TGs in the OF group ( P HDL-C in the OF group ( P TC in the O , F , and OF groups ( P LDL-C ( P TGs ( P HDL-C was significantly higher than baseline in the F and OF groups ( P < 0.02 and P < 0.01 , respectively ) . CONCLUSION Improvements in clinical and lipid-profile parameters were found at 1 year with all 3 treatments", "OBJECTIVE —Cardiovascular disease ( CVD ) risk is increased in type 2 diabetes . The purpose of this study was to assess the effect of 10 mg of atorvastatin versus placebo on CVD prevention in subjects with type 2 diabetes and LDL cholesterol levels below contemporary guideline targets . RESEARCH DESIGN AND METHODS —Subjects were r and omly assigned to receive 10 mg of atorvastatin or placebo in a 4-year , double-blind , parallel-group study . The composite primary end point comprised cardiovascular death , nonfatal myocardial infa rct ion , nonfatal stroke , recanalization , coronary artery bypass surgery , resuscitated cardiac arrest , and worsening or unstable angina requiring hospitalization . RESULTS —A total of 2,410 subjects with type 2 diabetes were r and omized . Mean LDL cholesterol reduction in the atorvastatin group over 4 years was 29 % versus placebo ( P atorvastatin versus placebo , composite primary end point rates were 13.7 and 15.0 % , respectively ( hazard ratio 0.90 [ 95 % CI 0.73–1.12 ] ) . In the subset of 1,905 subjects without prior myocardial infa rct ion or interventional procedure , 10.4 % of atorvastatin- and 10.8 % of placebo-treated subjects experienced a primary end point ( 0.97 [ 0.74–1.28 ] ) . In the 505 subjects with prior myocardial infa rct ion or interventional procedure , 26.2 % of atorvastatin- and 30.8 % of placebo-treated subjects experienced a primary end point ( 0.82 [ 0.59–1.15 ] ) . Relative risk reductions in fatal and nonfatal myocardial infa rct ion were 27 % overall ( P = 0.10 ) and 19 % ( P = 0.41 ) and 36 % ( P = 0.11 ) for subjects without and with prior myocardial infa rct ion or interventional procedure , respectively . CONCLUSIONS —Composite end point reductions were not statistically significant . This result may relate to the overall study design , the types of subjects recruited , the nature of the primary end point , and the protocol changes required because of changing treatment guidelines . For these reasons , the results of the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus ( ASPEN ) did not confirm the benefit of therapy but do not detract from the imperative that the majority of diabetic patients are at risk of coronary heart disease and deserve LDL cholesterol lowering to the currently recommended targets", "BACKGROUND HMG CoA reductase inhibitors ( or statins ) , a new class of lipid-lowering compounds , have raised expectations for more widespread use than that of the older lipid-lowering drugs . Not only are they more effective in lowering LDL cholesterol , but they are better tolerated as well . No data exist concerning the effect of statins on early carotid atherosclerosis and clinical events in men and women who have moderately elevated LDL cholesterol levels but are free of symptomatic cardiovascular disease . METHODS AND RESULTS Lovastatin ( 20 to 40 mg/d ) or its placebo was evaluated in a double-blind , r and omized clinical trial with factorial design along with warfarin ( 1 mg/d ) or its placebo . This report is limited to the lovastatin component of the trial . Daily aspirin ( 81 mg/d ) was recommended for everyone . Enrollment included 919 asymptomatic men and women , 40 to 79 years old , with early carotid atherosclerosis as defined by B-mode ultrasonography and LDL cholesterol between the 60th and 90th percentiles . The 3-year change in mean maximum intimal-medial thickness ( IMT ) in 12 walls of the carotid arteries was the primary outcome ; change in single maximum IMT and incidence of major cardiovascular events were secondary outcomes . LDL cholesterol fell 28 % , from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months ( P lovastatin groups and was largely unchanged in the lovastatin-placebo groups . Among participants not on warfarin , regression of the mean maximum IMT was seen after 12 months in the lovastatin group compared with the placebo group ; the 3-year difference was statistically significant ( P = .001 ) . A larger favorable effect of lovastatin was observed for the change in single maximum IMT but was not statistically significant ( P = .12 ) . Five lovastatin-treated participants suffered major cardiovascular events -- coronary heart disease mortality , nonfatal myocardial infa rct ion , or stroke -- versus 14 in the lovastatin-placebo groups ( P = .04 ) . One lovastatin-treated participant died , compared with eight on lovastatin-placebo ( P = .02 ) . CONCLUSIONS In men and women with moderately elevated LDL cholesterol , lovastatin reverses progression of IMT in the carotid arteries and appears to reduce the risk of major cardiovascular events and mortality . Results from ongoing large-scale clinical trials may further establish the clinical benefit of statins", "OBJECTIVES The study sought to determine the effects of lipid-lowering with pravastatin on the systemic fibrinolytic profile and on thrombus formation under dynamic flow conditions . BACKGROUND Lowering cholesterol ( C ) decreases clinical events in coronary artery disease ( CAD ) patients , but an analysis of the effects of lipid-lowering on the entire hemostatic and thrombotic profile has not been conducted . METHODS We prospect ively studied 93 stable patients with untreated low-density lipoprotein cholesterol ( LDL-C ) > 145 mg/dl . The CAD patients received pravastatin , and non-CAD patients were r and omized to pravastatin versus placebo ( double-blind ) . Thrombus formation upon an injured vascular surface was assessed in a sub study of 40 patients with a previously vali date d ex vivo perfusion chamber system . Systemic hemostatic markers and thrombus formation were evaluated at baseline , three and six months . RESULTS Placebo produced no changes in either the lipid profile , any of the hemostatic markers , or the ex vivo thrombus formation . Both pravastatin groups ( CAD and non-CAD ) showed decreased LDL-C by 30 % within 6 weeks ( 188 to 126 mg/dl , p plasminogen activator inhibitor-1 at 3- and 6-month follow-up compared to baseline ( 15 % to 18 % decrease at 3 months and 21 % to 23 % at 6 months ) . For the tissue plasminogen activator antigen , CAD and non-CAD groups showed significant decreases at 6 months compared to baseline ( 10 % and 13 % , respectively ) . No significant changes were observed with treatment in d-dimer , fibrinopeptide A , prothrombin fragment F1.2 , factor VIIa , von Willebr and factor , or C-reactive protein . Fibrinogen levels were significantly increased at 6 months compared to baseline , though still below the upper normal limit . In the perfusion chamber sub study , there was a decrease in thrombus area in non-CAD patients treated with pravastatin at both 3 and 6 months compared to baseline ( by 21 % and 34 % , respectively ) . The CAD patients showed decreases in thrombus formation by 13 % at 3 months , and by 16 % at 6 months . The change in LDL-C- correlated modestly with the change in thrombus formation ( r = 0.49 ; p Pravastatin therapy significantly decreased thrombus formation and improved the fibrinolytic profile in patients with and without CAD . These early effects may , in part , explain the benefit rendered in primary and secondary prevention of CAD", "OBJECTIVE --To examine the relation between serum cholesterol concentration and mortality ( from coronary heart disease and from other causes ) below the range of cholesterol values generally seen in Western population s. DESIGN -- Prospect i ve observational study based on 8 - 13 years of follow up of subjects in a population with low cholesterol concentrations . SETTING --Urban Shanghai , China . SUBJECTS--9021 Chinese men and women aged 35 - 64 at baseline . MAIN OUTCOME MEASURE -- Death from coronary heart disease and other causes . RESULTS --The average serum cholesterol concentration was 4.2 mmol/l at baseline examination , and only 43 ( 7 % ) of the deaths that occurred during 8 - 13 years of follow up were attributed to coronary heart disease . There was a strongly positive , and apparently independent , relation between serum cholesterol concentration and death from coronary heart disease ( z = 3.47 , p less than 0.001 ) , and within the range of usual serum cholesterol concentration studied ( 3.8 - 4.7 mmol/l ) there was no evidence of any threshold . After appropriate adjustment for the regression dilution bias , a 4 ( SD 1)% difference in usual cholesterol concentration was associated with a 21 ( SD 6)% ( 95 % confidence interval 9 % to 35 % ) difference in mortality from coronary heart disease . There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer . The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline . CONCLUSION --Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was , by Western st and ards , a \" low \" cholesterol concentration . There was no good evidence of an adverse effect of cholesterol on other causes of death", "The interlead variability of QT interval in the 12-lead electrocardiogram , QT dispersion ( QTd ) , has been shown to reflect dispersion of ventricular refractoriness and may provide a measure of arrhythmogenic potential in diabetic patients . QTd and heart rate corrected QTd ( QTcd ) were also proposed to be accurate predictors of cardiac death in patients with diabetes . In recent years , experimental and clinical evidence demonstrates that statins exert antiarrhythmic properties . Therefore , in the present study , we have examined whether simvastatin treatment has any effect on the QTd and QTcd in patients with diabetes mellitus . Sixty type 2 diabetic patients without known coronary artery disease and low-density lipoprotein cholesterol > 100mg/dl and 30 age and sex-matched non-diabetic controls were included in a prospect i ve study . Out of 60 diabetic patients , 30 were treated with simvastatin 40 mg/day for 1 year and the remaining 30 subjects were served as diabetic controls . No lipid lowering therapy was administered to the diabetic and the non-diabetic controls . QTd and QTcd of treated diabetics and the non-diabetic controls were measured at baseline , 6 , 12 weeks and at 1 year . QTd and QTcd of the diabetic controls were obtained at baseline , 6 and 12 weeks . Both QTd and QTcd were significantly greater in patients with the diabetes than in the non-diabetic controls at baseline ( 52+/-13 ms vs. 41+/-12 ms , p Simvastatin therapy significantly decreased both QTd and QTcd at the end of first year compared to baseline ( 51+/-15 ms vs. 33+/-11 ms , p QTd and QTcd in the non-diabetic ( p=0.29 and p=0.87 by ANOVA , respectively ) and in the diabetic controls ( p=0.72 and p=0.57 , by ANOVA , respectively ) . This study suggests for the first time that simvastatin treatment in diabetic patients with hyperlipidemia is associated with an improvement in the heterogeneity of cardiac repolarization . This may be one of the mechanisms for the reduction in clinical events reported in the survival studies with statins . Further prospect i ve r and omized studies are warranted to confirm our findings", "The r and omized , double-blind , placebo-controlled trial described in this report was undertaken to clarify the dose-response relation of lovastatin therapy to lipid-modifying efficacy ( lipid/lipoprotein modification ) and drug-related adverse events in a population with moderately elevated fasting plasma total cholesterol ( 240 to 300 mg/dl ) and low-density lipoprotein cholesterol ( greater than or equal to 160 mg/dl ) . Men or women ( postmenopausal or surgically sterile ) , aged 18 to 70 years , were entered into the trial with minimal exclusion criteria . After 4 to 6 weeks of an American Heart Association phase I diet or a more stringent diet , 8,245 patients from 362 sites were r and omized to 1 of 5 parallel diet and drug treatment groups : placebo ( n = 1,663 ) or lovastatin , 20 mg ( n = 1,642 ) and 40 mg ( n = 1,645 ) with the evening meal , and 20 mg ( n = 1,646 ) or 40 mg twice daily ( n = 1,649 ) . The regimen of diet and lovastatin ( or placebo ) was followed for 48 weeks . The 5 treatment groups were similar at baseline . The total cohort had the following characteristics : 59 % were men ( mean age 56 years ) ; 92 % were white ; 59 % had completed at least 1 year of education beyond high school ; 57 % had a history of cardiovascular and associated disease ; 40 % had a history of hypertension ; and 29 % had coronary artery disease . Health habits were similar among groups , with 18 % of patients reporting cigarette smoking , 14 % reporting that they consume greater than 1 alcoholic beverage daily and 67 % reporting no strenous exercise . Mean lipid/lipoprotein levels were also similar among groups , with the following average levels : total cholesterol ( 258 mg/dl ) , low-density lipoprotein cholesterol ( 180 mg/dl ) , high-density lipoprotein cholesterol ( 45 mg/dl ) and triglycerides ( median = 155 mg/dl ) . The large size of this trial , its placebo-controlled , double-blind design and the similarity of treatment groups at baseline should allow clear documentation of the long-term effects of lovastatin treatment and generalization of the results to a substantial portion of patients who may be c and i date s for lipid-modifying therapy", "Statins are widely prescribed for the primary and secondary prevention of coronary artery disease . They act by inhibiting the enzyme HMG CoA reductase , which controls synthesis of cholesterol in the liver . Most manufacturers of statins recommend that they are taken at night , on the basis of physiological studies which show that most cholesterol is synthesis ed when dietary intake is at its lowest.1 One small clinical trial found that taking smaller doses of simvastatin than are used in treatment , in the morning , was less efficient.2 However , a trial using atorvastatin found no significant difference in cholesterol concentrations between patients taking the statin in the morning and those taking it in the evening.3 Doubt has been cast on whether statins need to be taken at night,4 particularly as many patients also receive treatment with other cardioprotective drugs and compliance may be compromised by multiple", "Background PROSPER was design ed to investigate the benefits of treatment with pravastatin in elderly patients for whom a typical doctor might consider the prescription of statin therapy to be a realistic option . Methods The PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) is a r and omised , double blind , placebo-controlled trial to test the hypothesis that treatment with pravastatin ( 40 mg/day ) will reduce the risk of coronary heart disease death , non-fatal myocardial infa rct ion , and fatal or non-fatal stroke in elderly men and women with pre-existing vascular disease or with significant risk of developing this condition . Results In Scotl and , Irel and , and the Netherl and s , 23,770 individuals were screened , and 5,804 subjects ( 2,804 men and 3,000 women ) , aged 70 to 82 years ( average 75 years ) and with baseline cholesterol 4.0–9.0 mmol/l , were r and omised . R and omised subjects had similar distributions with respect to age , blood pressure , and body mass index when compared to the entire group of screenees , but had a higher prevalence of smoking , diabetes , hypertension , and a history of vascular disease . The average total cholesterol level at baseline was 5.4 mmol/l ( men ) and 6.0 mmol/l ( women ) . Conclusions Compared with previous prevention trials of cholesterol-lowering drugs , the PROSPER cohort is significantly older and for the first time includes a majority of women . The study , having achieved its initial goal of recruiting more than 5,500 elderly high-risk men and women , aims to complete all final subject follow-up visits in the first half of 2002 with the main results being available in the fourth quarter of 2002", "Abstract Objective To investigate risk factors , such as heavy alcohol consumption , that might explain any increased risk of haemorrhagic stroke associated with low blood cholesterol . Design Prospect i ve cohort study . Setting Korea . Participants 787 442 civil servants ( 661 700 men , 125 742 women ) aged 30 - 64 . Main outcome measures Cardiovascular risk factors were assessed at biennial health check . Data on morbidity and mortality were ascertained from 1990 to 2001 using hospital admissions and mortality surveillance systems . Results 6328 cases of ischaemic stroke ( 6021 men , 307 women ) , 3947 cases of haemorrhagic stroke ( 3748 men , 199 women ) , 3170 cases of undefined stroke ( 2902 men , 268 women ) , and 4417 cases of myocardial infa rct ion ( 4305 men , 112 women ) occurred . Ischaemic stroke and myocardial infa rct ion were strongly and positively associated with blood cholesterol ( hazard ratio per 1 mmol/l cholesterol 1.20 ( 95 % confidence 1.16 to 1.24 ) and 1.48 ( 1.43 to 1.53 ) , respectively ) . Haemorrhagic stroke showed an inverse association in fully adjusted models ( 0.91 , 0.87 to 0.95 ) . This inverse association was confined to participants with hypertension . When stratified by concentration of γ glutamyl transferase ( GGT ) , an indicator of alcohol consumption , the association was not seen in participants with low concentrations of GGT , and it was independent of hypertension in those with high concentrations of GGT ( > 80 U/l ) . Conclusion High alcohol consumption may underlie the association between low blood cholesterol and increased risk of haemorrhagic stroke ", "Simvastatin , a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor , has been administered to approximately 2,400 patients with primary hypercholesterolemia with a mean follow-up of 1 year in controlled clinical studies and their open extensions . Approximately 10 % of this population received simvastatin for a period of greater than or equal to 2 years . The population on whom this safety analysis is based had a mean age of 50 years ; 62 % were men and approximately 27 % had preexisting coronary artery disease . Simvastatin was titrated to the maximal daily dose of 40 mg each evening in 56 % of the study population ( last recorded dose ) . The most frequently reported drug-related clinical adverse experiences were constipation ( 2.5 % ) , abdominal pain ( 2.2 % ) , flatulence ( 2.0 % ) and headaches ( 1 % ) . Persistent elevations of serum transaminase levels greater than 3 times the upper limit of normal were observed in only 1 % of this cohort with only 0.1 % of the total population requiring discontinuation of therapy . There were no clinical ly apparent episodes of hepatitis . Discontinuation of therapy due to myopathy was extremely rare ( 0.08 % ) . Only minimal increases in the frequency of lens opacities ( 1 % ) were observed from baseline to the last lens examination during follow-up , consistent with the expected increase in lens opacity development due to normal aging . Patients who were greater than or equal to 65 years old had a clinical and laboratory safety profile comparable to the nonelderly population . ( ABSTRACT TRUNCATED AT 250 WORDS", "PURPOSE Animal research and cross-sectional studies suggest that serum lipid concentrations may influence cognitive function , mood , and behavior , but few clinical trials have studied these effects . SUBJECTS AND METHODS In this double-blind investigation , 209 generally healthy adults with a serum low-density-lipoprotein ( LDL ) cholesterol level of 160 mg/dL or higher were r and omly assigned to 6-month treatment with lovastatin ( 20 mg ) or placebo . Assessment s of neuropsychological performance , depression , hostility , and quality of life were conducted at baseline and at the end of the treatment period . Summary effect sizes were estimated as z scores on a st and ard deviation ( SD ) scale . RESULTS Placebo-treated subjects improved between baseline and posttreatment periods on neuropsychological tests in all five performance domains , consistent with the effects of practice on test performance ( all P lovastatin improved only on tests of memory recall ( P = 0.03 ) . Comparisons of the changes in performance between placebo- and lovastatin-treated subjects revealed small , but statistically significant , differences for tests of attention ( z score = 0.18 ; 95 % confidence interval ( CI ) , 0.06 to 0.31 ; P = 0.005 ) and psychomotor speed ( z score = 0.17 ; 95 % CI , 0.05 to 0.28 ; P = 0 . 004 ) that were consistent with greater improvement in the placebo group . Psychological well-being , as measured several ways , was not affected by lovastatin . CONCLUSION Treatment of hypercholesterolemia with lovastatin did not cause psychological distress or substantially alter cognitive function . Treatment did result in small performance decrements on neuropsychological tests of attention and psychomotor speed , the clinical importance of which is uncertain", "BACKGROUND Evidence -based treatment for hypercholesterolaemia in Japan has been hindered by the lack of direct evidence in this population . Our aim was to assess whether evidence for treatment with statins derived from western population s can be extrapolated to the Japanese population . METHODS In this prospect i ve , r and omised , open-labelled , blinded study , patients with hypercholesterolaemia ( total cholesterol 5.69 - 6.98 mmol/L ) and no history of coronary heart disease or stroke were r and omly assigned diet or diet plus 10 - 20 mg pravastatin daily . The primary endpoint was the first occurrence of coronary heart disease . Statistical analyses were done by intention to treat . This trial is registered at Clinical Trials.gov , number NCT00211705 . FINDINGS 3966 patients were r and omly assigned to the diet group and 3866 to the diet plus pravastatin group . Mean follow-up was 5.3 years . At the end of study , 471 and 522 patients had withdrawn , died , or been lost to follow-up in the diet and diet plus pravastatin groups , respectively . Mean total cholesterol was reduced by 2.1 % ( from 6.27 mmol/L to 6.13 mmol/L ) and 11.5 % ( from 6.27 mmol/L to 5.55 mmol/L ) and mean LDL cholesterol by 3.2 % ( from 4.05 mmol/L to 3.90 mmol/L ) and 18.0 % ( from 4.05 mmol/L to 3.31 mmol/L ) in the diet and the diet plus pravastatin groups , respectively . Coronary heart disease was significantly lower in the diet plus pravastatin group than in the diet alone group ( 66 events vs 101 events ; HR 0.67 , 95 % CI 0.49 - 0.91 ; p=0.01 ) . There was no difference in the incidence of malignant neoplasms or other serious adverse events between the two groups . INTERPRETATION Treatment with a low dose of pravastatin reduces the risk of coronary heart disease in Japan by much the same amount as higher doses have shown in Europe and the USA", "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", "AIMS To assess the effect of statins on a range of health outcomes . METHODS We undertook a population -based cohort study to assess the effect of statins on a range of health outcomes using a propensity score-based method to control for differences between people prescribed and not prescribed statins . We vali date d our design by comparing our results for vascular outcomes with the effects established in large r and omized trials . The study was based on the United Kingdom Health Improvement Network data base that includes the computerized medical records of over four and a half million patients . RESULTS People who initiated treatment with a statin ( n = 129,288 ) were compared with a matched sample of 600,241 people who did not initiate treatment , with a median follow-up period of 4.4 years . Statin use was not associated with an effect on a wide range of outcomes , including infections , fractures , venous thromboembolism , gastrointestinal haemorrhage , or on specific eye , neurological or autoimmune diseases . A protective effect against dementia was observed ( hazard ratio 0.80 , 99 % confidence interval 0.68 , 0.95 ) . There was no effect on the risk of cancer even after > or = 8 years of follow-up . The effect sizes for statins on vascular end-points and mortality were comparable to those observed in large r and omized trials , suggesting bias and confounding had been well controlled for . CONCLUSIONS We found little evidence to support wide-ranging effects of statins on health outcomes beyond their established beneficial effect on vascular disease", "Objective To quantify the unintended effects of statins according to type , dose , and duration of use . Design Prospect i ve open cohort study using routinely collected data . Setting 368 general practice s in Engl and and Wales supplying data to the Q Research data base . Participants 2 004 692 patients aged 30 - 84 years of whom 225 922 ( 10.7 % ) were new users of statins : 159 790 ( 70.7 % ) were prescribed simvastatin , 50 328 ( 22.3 % ) atorvastatin , 8103 ( 3.6 % ) pravastatin , 4497 ( 1.9 % ) rosuvastatin , and 3204 ( 1.4 % ) fluvastatin . Methods Cox proportional hazards models were used to estimate effects of statin type , dose , and duration of use . The number needed to treat ( NNT ) or number needed to harm ( NNH ) was calculated and numbers of additional or fewer cases estimated for 10 000 treated patients . Main outcome measure First recorded occurrence of cardiovascular disease , moderate or serious myopathic events , moderate or serious liver dysfunction , acute renal failure , venous thromboembolism , Parkinson ’s disease , dementia , rheumatoid arthritis , cataract , osteoporotic fracture , gastric cancer , oesophageal cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Results Individual statins were not significantly associated with risk of Parkinson ’s disease , rheumatoid arthritis , venous thromboembolism , dementia , osteoporotic fracture , gastric cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Statin use was associated with decreased risks of oesophageal cancer but increased risks of moderate or serious liver dysfunction , acute renal failure , moderate or serious myopathy , and cataract . Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin . A dose-response effect was apparent for acute renal failure and liver dysfunction . All increased risks persisted during treatment and were highest in the first year . After stopping treatment the risk of cataract returned to normal within a year in men and women . Risk of oesophageal cancer returned to normal within a year in women and within 1 - 3 years in men . Risk of acute renal failure returned to normal within 1 - 3 years in men and women , and liver dysfunction within 1 - 3 years in women and from three years in men . Based on the 20 % threshold for cardiovascular risk , for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 ( 95 % confidence interval 27 to 64 ) and for oesophageal cancer was 1266 ( 850 to 3460 ) and for men the respective values were 33 ( 24 to 57 ) and 1082 ( 711 to 2807 ) . In women the NNH for an additional case of acute renal failure over five years was 434 ( 284 to 783 ) , of moderate or severe myopathy was 259 ( 186 to 375 ) , of moderate or severe liver dysfunction was 136 ( 109 to 175 ) , and of cataract was 33 ( 28 to 38 ) . Overall , the NNHs and NNTs for men were similar to those for women , except for myopathy where the NNH was 91 ( 74 to 112 ) . Conclusions Cl aims of unintended benefits of statins , except for oesophageal cancer , remain unsubstantiated , although potential adverse effects at population level were confirmed and quantified . Further studies are needed to develop utilities to individualise the risks so that patients at highest risk of adverse events can be monitored closely", "OBJECTIVE Cardiovascular disease ( CVD ) is the most important cause of mortality in patients with type 2 diabetes . We aim ed to determine the effect of statin therapy versus placebo on the progression of carotid intima-media thickness ( IMT ) in type 2 diabetic patients without manifest CVD . RESEARCH DESIGN AND METHODS A r and omized , placebo-controlled , double-blind clinical trial was performed in 250 patients with type 2 diabetes . Patients were given either 0.4 mg cerivastatin or placebo daily . In August 2001 , when cerivastatin was withdrawn from the market , 0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the study . The primary end point was the change of mean common carotid IMT , as measured by B-mode ultrasound , over 2 years . RESULTS Common carotid IMT at baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and did not change significantly after 2 years . There was no significant difference in IMT change in any carotid segment between the groups . LDL cholesterol was reduced by 25 % in the statin group and increased by 8 % in the placebo group ( P Cardiovascular events occurred in 12 patients in the placebo group and two patients in the statin group ( P=0.006 ) . CONCLUSIONS There was no effect of 2 years ' statin therapy on carotid IMT in type 2 diabetic subjects . The natural history of IMT in our patients was milder than anticipated . In contrast , we observed a significantly lower cardiovascular event rate on statin therapy . Prognostic tools other than IMT should be explored in this patient group", "BACKGROUND Statins improve lipid profiles and reduce cardiovascular morbidity and mortality but there are few data on their relative effects in different ethnic groups . METHODS We used data from the r and omised , placebo-controlled Anglo-Sc and inavian Cardiac Outcomes Trial-Lipid Lowering Arm ( ASCOT-LLA ) to conduct a prespecified comparison of the lipid-lowering efficacy of statin therapy among hypertensive participants from different ethnic groups in the UK and Irel and . The effects of atorvastatin ( 10 mg daily ) and placebo on fasting plasma lipid profiles were compared in matched groups of Whites and Blacks ( of African-Caribbean or African origin ) and Whites and South Asians ( from the Indian subcontinent ) , adjusting for placebo effect . RESULTS In the active treatment group , 156 Blacks and 72 South Asians were compared with 419 and 198 Whites , respectively . In multivariable analyses adjusted for baseline lipid levels and other potential confounders , atorvastatin reduced total cholesterol , low-density lipoprotein (LDL)-cholesterol and triglycerides from baseline in all ethnic groups . There were no clinical ly or statistically significant differences in the effect between Whites and Blacks or between Whites and South Asians after adjusting for placebo effect ; similar proportions in each group achieved lipid targets . There was no significant effect of atorvastatin on high-density lipoprotein (HDL)-cholesterol in any group . CONCLUSIONS A st and ard dose of atorvastatin improved lipid profiles to a similar extent in Whites , Blacks and South Asians . Given the proven benefits of statins , these results suggest that , when used in st and ard doses , they are likely to be similarly effective for cardiovascular disease prevention in all ethnic groups", "Objective To investigate the possibility that statins reduce blood pressure as well as cholesterol concentrations through clinic and 24 hour ambulatory blood pressure monitoring . Design R and omised placebo controlled double blind trial . Setting 13 hospitals in Italy Participants 508 patients with mild hypertension and hypercholesterolaemia , aged 45 to 70 years . Intervention Participants were r and omised to antihypertensive treatment ( hydrochlorothiazide 25 mg once daily or fosinopril 20 mg once daily ) with or without the addition of a statin ( pravastatin 40 mg once daily ) . Main outcome measures Clinic and ambulatory blood pressure measured every year throughout an average 2.6 year treatment period . Results Both the group receiving antihypertensive treatment without pravastatin ( n=254 ) ( with little change in total cholesterol ) and the group receiving antihypertensive treatment with pravastatin ( n=253 ) ( with marked and sustained reduction in total cholesterol and low density lipoprotein cholesterol ) had a clear cut sustained reduction in clinic measured systolic and diastolic blood pressure as well as in 24 hour , and day and night , systolic and diastolic blood pressure . Pravastatin performed slightly worse than placebo , and between group differences did not exceed 1.9 ( 95 % confidence interval −0.6 to 4.3 , P=0.13 ) mm Hg throughout the treatment period . This was also the case when participants who remained on monotherapy with hydrochlorothiazide or fosinopril throughout the study were considered separately . Conclusions Administration of a statin in hypertensive patients in whom blood pressure is effectively reduced by concomitant antihypertensive treatment does not have an additional blood pressure lowering effect . Trial registration BRISQUI_*IV_2004_001 ( registered at Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali — National Monitoring Centre on Clinical Research with Medicines )", "Aims On the basis of the JUPITER trial , European health authorities recently approved the use of rosuvastatin to reduce first major cardiovascular events among ‘ high ' global risk primary prevention patients defined either by Framingham risk score > 20 % or European systematic coronary risk evaluation ( SCORE ) ≥5 % . However , as these are post hoc analyses , data describing these subgroups have not previously been available to the clinical community . Methods and results We r and omized 17 802 apparently healthy men aged ≥50 and women ≥60 with low-density lipoprotein cholesterol ( LDL-C ) to rosuvastatin 20 mg daily or placebo . Patients with high global cardiovascular risk at baseline were identified by 10-year Framingham risk score > 20 % or SCORE risk ≥5 % . During 1.8-year median follow-up ( maximum 5 years ) of patients with Framingham risk > 20 % , the rate of myocardial infa rct ion/stroke/cardiovascular death was 9.4 and 18.2 per 1000 person-years in rosuvastatin and placebo-allocated patients , respectively [ hazard ratio ( HR ) : 0.50 , 95 % confidence interval ( CI ) : 0.27–0.93 , P = 0.028 ] . Among patients with SCORE risk ≥5 % , the corresponding rates were 6.9 and 12.0 using a model extrapolating risk for age ≥65 years ( HR : 0.57 , 95 % CI : 0.43–0.78 , P = 0.0003 ) and rates were 5.9 and 12.7 when risk for age was capped at 65 years ( HR : 0.47 , 95 % CI : 0.32–0.68 , P elevated hs C-reactive protein who have high global cardiovascular risk ( 10-year Framingham risk score > 20 % or SCORE risk ≥5 % ) , but LDL-C levels not requiring pharmacologic treatment , rosuvastatin 20 mg significantly reduced major cardiovascular events . Clinical Trial.gov Identifier :", "Objectives . To investigate the independent and combined effects of lifestyle changes and statin treatment on soluble markers of atherosclerotic activity . Design . The study was a r and omised , 2 × 2 factorial 1 year intervention trial . Participants ( n=177 ) were sedentary , drug-treated , hypertensive men ( aged 40–74 years ) . They were r and omised to placebo , lifestyle intervention ( diet and physical activity ) , fluvastatin 40 mg , or the combination of lifestyle and fluvastatin . Results . Lifestyle intervention significantly reduced intercellular adhesion molecule-1 ( sICAM-1 ) compared to usual care ( p=0.003 ) . Thrombomodulin level remained higher among individuals receiving lifestyle intervention ( p=0.025 ) . sICAM-1 was less reduced among fluvastatin treated participants compared to the placebo treated ( p=0.029 ) . Changes of blood pressure , weight or waist circumference were not significantly different between treatment groups . Individuals who achieved improvement of classical risk factors also had a significant reduction of endothelial markers ( E-selectin , von Willebr and s factor , tissue plasminogen activator antigen ) . Conclusions . One year of lifestyle intervention reduced the level of sICAM-1 in sedentary , drug-treated hypertensives , in spite of no impact on traditional risk factors . Low dose fluvastatin had no beneficial effect on the measured markers", "The Justification for the Use of Statins in Primary Prevention : An Intervention Trial Evaluating Rosuvastatin ( JUPITER ) study was the first large-scale , prospect i ve study to examine the benefits of statin therapy in subjects with elevated levels of high-sensitivity C-reactive protein but with low-to-normal LDL-cholesterol levels , who were not qualified for lipid-lowering treatment according to the current guidelines for primary prevention . The JUPITER study aim ed to determine whether rosuvastatin 20 mg daily would reduce the rate of first major cardiovascular events , including cardiovascular death , nonfatal stroke , nonfatal myocardial infa rct ion , hospitalization for unstable angina or arterial revascularization . Rosuvastatin reduced LDL-cholesterol levels by 50 % and high-sensitivity C-reactive protein by 37 % . Compared with placebo , the combined primary end point was reduced in 44 % ( p total mortality in 20 % ( p = 0.02 ) . The trial confirmed the relationship between the rates of major cardiovascular events with both high-sensitivity C-reactive protein and LDL-cholesterol levels achieved after statin treatment . Interestingly , this was the first large , prospect i ve statin trial to show benefit in the reduction of venous thromboembolism", "CONTEXT Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease ( CHD ) , it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol ( LDL-C ) in patients without CHD extends to individuals with average serum cholesterol levels , women , and older persons . OBJECTIVE To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinical ly evident atherosclerotic cardiovascular disease with average total cholesterol ( TC ) and LDL-C levels and below-average high-density lipoprotein cholesterol ( HDL-C ) levels . DESIGN A r and omized , double-blind , placebo-controlled trial . SETTING Outpatient clinics in Texas . PARTICIPANTS A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C ( as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [ NHANES ] III ) . Mean ( SD ) TC level was 5.71 ( 0.54 ) mmol/L ( 221 [ 21 ] mg/dL ) ( 51 st percentile ) , mean ( SD ) LDL-C level was 3.89 ( 0.43 ) mmol/L ( 150 [ 17 ] mg/dL ) ( 60th percentile ) , mean ( SD ) HDL-C level was 0.94 ( 0.14 ) mmol/L ( 36 [ 5 ] mg/dL ) for men and 1.03 ( 0.14 ) mmol/L ( 40 [ 5 ] mg/dL ) for women ( 25th and 16th percentiles , respectively ) , and median ( SD ) triglyceride levels were 1.78 ( 0.86 ) mmol/L ( 158 [ 76 ] mg/dL ) ( 63rd percentile ) . INTERVENTION Lovastatin ( 20 - 40 mg daily ) or placebo in addition to a low-saturated fat , low-cholesterol diet . MAIN OUTCOME MEASURES First acute major coronary event defined as fatal or nonfatal myocardial infa rct ion , unstable angina , or sudden cardiac death . RESULTS After an average follow-up of 5.2 years , lovastatin reduced the incidence of first acute major coronary events ( 1 83 vs 116 first events ; relative risk [ RR ] , 0.63 ; 95 % confidence interval [ CI ] , 0.50 - 0.79 ; P myocardial infa rct ion ( 95 vs 57 myocardial infa rct ions ; RR , 0.60 ; 95 % CI , 0.43 - 0.83 ; P=.002 ) , unstable angina ( 87 vs 60 first unstable angina events ; RR , 0.68 ; 95 % CI , 0.49 - 0.95 ; P=.02 ) , coronary revascularization procedures ( 157 vs 106 procedures ; RR , 0.67 ; 95 % CI , 0.52 - 0.85 ; P=.001 ) , coronary events ( 215 vs 163 coronary events ; RR , 0.75 ; 95 % CI , 0.61 - 0.92 ; P = .006 ) , and cardiovascular events ( 255 vs 194 cardiovascular events ; RR , 0.75 ; 95 % CI , 0.62 - 0.91 ; P = .003 ) . Lovastatin ( 20 - 40 mg daily ) reduced LDL-C by 25 % to 2.96 mmol/L ( 115 mg/dL ) and increased HDL-C by 6 % to 1.02 mmol/L ( 39 mg/dL ) . There were no clinical ly relevant differences in safety parameters between treatment groups . CONCLUSIONS Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels . These findings support the inclusion of HDL-C in risk-factor assessment , confirm the benefit of LDL-C reduction to a target goal , and suggest the need for re assessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention", "OBJECTIVES The aim of this study was to evaluate the effect of statin treatment in primary prevention of cardiovascular events in different race/ethnic groups . BACKGROUND Clinical trial evidence about the efficacy of statins in the primary prevention of cardiovascular events among nonwhites is uncertain . METHODS JUPITER trial , a r and omized , double-blind , placebo-controlled evaluation of rosuvastatin 20 mg in the primary prevention of myocardial infa rct ion ( MI ) , stroke , arterial revascularization , hospitalization for unstable angina , and cardiovascular death included 12,683 whites and 5,117 nonwhites with low-density lipoprotein levels RESULTS R and om allocation to rosuvastatin result ed in a 45 % reduction in the primary end point among whites ( hazard ratio [ HR ] 0.55 , 95 % CI 0.43 - 0.69 ) and a 37 % reduction among nonwhites ( HR 0.63 , 95 % CI 0.41 - 0.99 ) . Blacks ( HR 0.65 , 95 % CI 0.35 - 1.22 ) and Hispanics ( HR 0.58 , 95 % CI 0.25 - 1.39 ) had similar risk reductions . Among nonwhites in the placebo group , the stroke rate exceeded the MI rate ( 0.44 vs 0.20 per 100 person-years ) ; an opposite pattern was observed among whites ( 0.31 vs 0.42 per 100 person-years ) . Nonwhites had higher death rates than whites ( 2.25 vs 0.93 per 100 person-years ) ; however , all-cause mortality was similar at 20 % with rosuvastatin treatment in both participant groups . CONCLUSIONS When used in primary prevention among individuals with low-density lipoprotein reduced first MI , stroke , arterial revascularization , hospitalization for unstable angina , and cardiovascular death among whites and nonwhites", "We undertook this prospect i ve double-blind , placebo-controlled study to evaluate the efficacy and safety of low-dose ( 15 mg ) pravastatin in elderly hypercholesterolemic hypertensive subjects with concurrent antihypertensive treatment and to determine whether fasting hyperinsulinemia could also be improved . At three hypertension and lipid clinics of two medical centers , 96 elderly ( 49 women , 47 men ) ambulatory subjects were r and omized to active treatment or placebo for 12 months after a 3-month single-blind lead-in period . Hypertensive subjects with plasma total cholesterol levels of at least 6.47 mmol/L ( 250 mg/dL ) and triglyceride levels less than 3.39 mmol/L ( 300 mg/dL ) were treated with 15 mg pravastatin for 12 months after receiving 3 months of the American Heart Association step I diet . Lipid , glucose , and fasting insulin levels were measured ; clinical laboratory tests included liver function and creatine kinase determinations . After 12 months of pravastatin therapy , plasma total cholesterol concentration decreased by 25.1 % ( from a mean of 7.29 to 5.47 mmol/L , P low-density lipoprotein cholesterol decreased by 30.2 % ( from 5.27 to 3.68 mmol/L , P triglycerides decreased by 10.7 % ( from 1.68 to 1.50 mmol/L , P High-density lipoprotein cholesterol increased by 9.2 % ( from 1.20 to 1.31 mmol/L , P Fasting insulin levels decreased from 89.0 to 61.5 pmol/L ( P Adverse events and clinical laboratory abnormalities were generally mild and transient in both placebo and pravastatin groups . Study drugs were withdrawn from one subject in each group with asymptomatic creatine kinase elevations . We conclude that low-dose pravastatin was effective and safe in the treatment of hypercholesterolemic hypertensive subjects on concurrent antihypertensive therapy . It also improved fasting hyperinsulinemia despite the use of beta-blockers and diuretics in these hypertensive subjects", "Objective : To assess the therapeutic value of treatment with an HMG-CoA reductase inhibitor in women with hypoestrogenic hyperlipidemia caused by menopause . Design : Fifty-six women with total cholesterol ( TC ) levels of 220 mg/dl or more who were within 7 years of menopause were r and omly assigned to receive an HMG-CoA reductase inhibitor ( pravastatin 10 mg/day ; treated group , 26 patients ) or no medical treatment ( nontreated group , 30 patients ) in this 6-month nonblinded prospect i ve trial . Results : In the treated group , the mean ( SD ) TC levels decreased significantly from 254.5 ± 22.3 mg/dl at baseline to 204.7 ± 22.2 mg/dl ( 19.6 % ) , and the mean low-density lipoprotein cholesterol ( LDL-C ) level decreased significantly from 146.7 ± 30.5 to 104.3 ± 22.5 mg/dl ( 28.9 % ) ; the mean arteriosclerotic index decreased significantly from 2.98 to 2.08 ( 30.2 % ) . There were no significant changes in either triglyceride levels or high-density lipoprotein cholesterol ( HDL-C ) levels . In the nontreated group , there were no significant changes in the TC , HDL-C , LDL-C , or triglyceride levels ; there was also no change in the arteriosclerotic index . After 6 months , the TC level , LDL-C level , and arteriosclerotic index were significantly lower in the treated group compared with the nontreated group ( p the HMG-CoA reductase inhibitor lowered TC and LDL-C levels and was useful in the treatment of hypoestrogenic hyperlipidemia for periods of at least 6 months", "BACKGROUND Statins are commonly prescribed for management of dyslipidaemia and cardiovascular disease . Increased fitness is also associated with low mortality and is recommended as an essential part of promoting health . However , little information exists about the combined effects of fitness and statin treatment on all-cause mortality . We assessed the combined effects of statin treatment and fitness on all-cause mortality risk . METHODS In this prospect i ve cohort study , we included dyslipidaemic veterans from Veterans Affairs Medical Centers in Palo Alto , CA , and Washington DC , USA , who had had an exercise tolerance test between 1986 , and 2011 . We assigned participants to one of four fitness categories based on peak metabolic equivalents ( MET ) achieved during exercise test and eight categories based on fitness status and statin treatment . The primary endpoint was all-cause mortality adjusted for age , body-mass index , ethnic origin , sex , history of cardiovascular disease , cardiovascular drugs , and cardiovascular risk factors . We assessed mortality from Veteran 's Affairs ' records on Dec 31 , 2011 . We compared groups with Cox proportional hazard model . FINDINGS We assessed 10,043 participants ( mean age 58·8 years , SD 10·9 years ) . During a median follow-up of 10·0 years ( IQR 6·0 - 14·2 ) , 2318 patients died , with an average yearly mortality rate of 22 deaths per 1000 person-years . Mortality risk was 18·5 % ( 935/5046 ) in people taking statins versus 27·7 % ( 1386/4997 ) in those not taking statins ( p took statins , mortality risk decreased as fitness increased ; for highly fit individuals ( > 9 MET ; n=694 ) , the hazard ratio ( HR ) was 0·30 ( 95 % CI 0·21 - 0·41 ; p with statins , the HR for least fit participants ( n=1024 ) was 1·35 ( 95 % CI 1·17 - 1·54 ; p INTERPRETATION Statin treatment and increased fitness are independently associated with low mortality among dyslipidaemic individuals . The combination of statin treatment and increased fitness result ed in substantially lower mortality risk than either alone , reinforcing the importance of physical activity for individuals with dyslipidaemia . FUNDING None", "Objectives : This study was conducted to evaluate the effect of simvastatin ( 40 mg/day ) as an adjuvant therapy to interferon beta ( IFNb 1a , 30 µg once weekly ) in relapsing — remitting multiple sclerosis patients , compared with placebo . Methods : We enrolled 85 patients with relapsing — remitting multiple sclerosis ( 71 % female ) who were already receiving IFNb 1a ( Avonex ) , with Exp and ed Disability Status Scale score of less than 5.0 . The patients were assigned ( in r and om and double-blinded fashion ) into the two groups of simvastatin and placebo . All patients continued to receive their current IFNb treatment . The outcome measures were total relapse rate , Exp and ed Disability Status Scale score , and the number of gadolinium-enhanced ( Gd+ ) and new T2 lesions in magnetic resonance imaging after a 1-year follow-up . We used Mann — Whitney and one-way multivariate analysis of variances to analyze the data . Results : Four patients in the placebo and two in the simvastatin group prematurely withdrew from the study due to experiencing two attacks . The total attack number in the simvastatin group was significantly lower than placebo group ( moderate effect size r = 0.29 ) ( p = 0.01 ) . The final Exp and ed Disability Status Scale scores were lower in the simvastatin group ( 1.01 ± 1.40 , mean ± SD ) than in the placebo group ( 1.73 ± 1.49 , mean ± SD ) , but this difference was not significant after controlling the baseline Exp and ed Disability Status Scale score ( p = 0.07 ) . In the simvastatin group , the mean ± SD of gadolinium-enhanced and new T2 lesions were 0.66 ± 1.18 and 3.39 ± 3.55 , respectively , ( compared with 0.74 ± 1.21 and 3.39 ± 3.55 in the placebo group ) . Although there was a decreasing trend in lesions on magnetic resonance imaging , this difference was not statistically significant ( p = 0.62 ) . The combination therapy was safe and well tolerated , and no serious adverse effect was noted . Conclusion : Our study supports the safety and efficacy of simvastatin as an add-on therapy to INFb 1a in patients with relapsing — remitting multiple sclerosis . TRIAL REGISTRATION : Clinical Trials.gov NCT00668343 . This interventional study provides Class I evidence stating that adding simvastatin 40 mg/day to IFNb 1a 30 µg a week in patients with relapsing — remitting multiple sclerosis may reduce the relapse rate ( moderate effect size r = 0.29 ) ( p = 0.01 ) compared with treatment with IFNb 1a alone", "OBJECTIVES Lipid-lowering drugs as 3-hydroxy-3-methyl glutaryl coenzyme A ( HMG-CoA ) reductase inhibitors and cholestyramine are effective in reducing cardiovascular morbidity both in primary and secondary prevention . Patient compliance is an important determinant of the outcome of therapy . This study was design ed to compare compliance with tolerance and lipid-lowering effectiveness of pravastatin and /or cholestyramine in primary care . DESIGN Nine hundred and eighty nine women and 1047 men were r and omized to treatment at 100 primary -care centres in Sweden . After dietary intervention , an eligible patient was r and omly assigned to one of four programs of daily treatment : group Q , 16 g cholestyramine , group QP , 8 g cholestyramine and 20 mg pravastatin , group P20 , 20 mg pravastatin or group P40 , 40 mg pravastatin . RESULTS In group Q , group QP , group P20 and group P40 the reductions in low density lipoprotein (LDL)-cholesterol were 26 % , 36 % , 27 % and 32 % . The dose actually taken was 91 - 95 % of the prescribed for the pravastatin treatment groups and 77 - 88 % for the cholestyramine groups . In the pravastatin and cholestyramine groups 76 - 78 % and 44 - 53 % , respectively , completed the trial . Only 8 - 27 % of the patients reached a serum cholesterol target level of 5.2 mmol L-1 . There was no difference in lipid-lowering effect between women and men . CONCLUSION Pravastatin alone is efficacious and compliance is high , independent of dose . Combined treatment with cholestyramine and pravastatin had a better cholesterol lowering effect ( although not statistically significant ) than 40 mg pravastatin . Despite this , only 8 - 27 % of the patients actually reached a serum cholesterol level of 5.2 mmol L-1 . No unexpected serious adverse events were detected in any of the treatment groups . As predicted , the gastrointestinal disturbances were more common on cholestyramine treatment . These two factors suggest that an increase in the dosage of the HMG-CoA reductase inhibitor may be appropriate . Results from other studies indicate that there also might be other positive effects of statin treatment beyond cholesterol lowering", "This study demonstrated that pravastatin 20 mg once daily significantly lowered total cholesterol ( by 19 % ) and LDL cholesterol by 25 %", "The Carotid Atherosclerosis Italian Ultrasound study ( CAIUS ) , a multicenter , double-blind clinical trial , performed in 305 asymptomatic , moderately hypercholesterolemic patients , clearly demonstrated beneficial effects of pravastatin on the carotid intima-media thickness ( IMT ) progression . The data base of the CAIUS study was examined in order to investigate the presence of a relationship , if any , between the activity of pravastatin on IMT progression rate and its hypocholesterolemic effect . Quantitative B-mode ultrasound imaging was used to quantify the individual mean maximum IMT progression rate in 3 years . In the overall group of patients ( placebo and pravastatin ) covariance analysis showed that while the variable ' treatment ' ( 0 = placebo , 1 = pravastatin ) was significantly related to the reduction of IMT progression ( F= 6.6 , P = 0.01 ) , the IMT progression did not correlate with the extent of LDL-C lowering ( F= 0.00 , P = 0.98 ) . To further investigate this issue . the pravastatin treated group was stratified into quartiles of LDL-C reduction . In contrast to what was observed in the placebo group , in which a positive mean IMT progression rate was observed , independent of the extent of LDL-C reduction , no IMT progressionwas observed in any subgroup treated with pravastatin . No significant difference was found among quartiles and no trend could be identified . In conclusion , the effect of pravastatin treatment on carotid IMT progression rate is beneficial ; however the CAIUS study demonstrated that lowering LDL-C by itself , does not explain the variability of beneficial changes in IMT", "The Justification for the Use of statins in Primary prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) is a r and omized , double-blind , placebo-controlled primary prevention trial of statin therapy among persons with average to low levels of low-density lipoprotein ( LDL ) cholesterol who are at increased cardiovascular risk due to elevated plasma concentrations of the inflammatory biomarker high-sensitivity C-reactive protein ( hs-CRP ) . A total of 17,802 persons with LDL cholesterol or=2 mg/L were recruited from 26 countries and r and omly allocated to 20 mg/day rosuvastatin or placebo . In contrast to previous studies of statin therapy in primary prevention , JUPITER is evaluating a group with modest plasma concentrations of LDL cholesterol ( median 108 mg/dl , interquartile range 94 to 119 ) . Further , the trial includes 6,801 women ( 38.2 % ) and 5,577 participants with metabolic syndrome ( 32.1 % ) . Thus , in addition to broadening our underst and ing of statin therapy and inflammation , the JUPITER trial will provide important and clinical ly relevant information on primary prevention among patients who do not currently qualify for lipid-lowering therapy . In conclusion , as 20 mg of rosuvastatin can reduce LDL cholesterol by up to 50 % , JUPITER will also provide crucial safety data for several thous and patients who should achieve LDL cholesterol levels mg/dl on a long-term basis", "Experimental evidence suggests that lipid lowering therapy could slow the progression of renal disease in humans . We have conducted a double-blind , placebo controlled trial of the HMG CoA reductase inhibitor simvastatin in patients with the nephrotic syndrome or significant proteinuria ( > 1 g/day ) and hypercholesterolemia ( > or = 6.5 mmol/liter ) . Patients were placed on a lipid lowering diet for at least 10 weeks before r and omization . After a four-week placebo run-in , 30 adults were r and omized to simvastatin or placebo therapy ( 10 mg/day , increasing to 20 to 40 mg/day as required ) for 24 weeks . There were seven dropouts , none of whom were \" definitely \" related to drug therapy . Total and LDL cholesterol levels fell by a mean of 33 and 31 % , respectively , in simvastatin treated patients , compared with only 5 and 1 % in patients on placebo ( P Apolipoprotein B100 levels fell by a mean of 31 % in the simvastatin group but rose 0.3 % in the placebo group ( P = 0.014 ) . There were no significant changes in HDL levels . There were no significant differences between the groups in their urine protein levels , their rise in plasma creatinine , or decline in plasma inulin clearance . Simvastatin is a safe , effective therapy for hypercholesterolemia in proteinuric states . A much larger trial is needed to show if potent lipid-lowering therapy slows progression of hypercholesterolemic proteinuric diseases", "BACKGROUND Total and lipoprotein cholesterol levels continue to be predictors of coronary heart disease risk in men and women over 65 years old . Cholesterol-lowering trials , however , while sometimes including such subjects , have not concentrated on this age group . The Cholesterol Reduction in Seniors Program was a five-center pilot study to assess feasibility of recruitment and efficacy of cholesterol lowering in this age group . METHODS The study was a r and omized , double-masked clinical trial with placebo , 20-mg lovastatin , and 40-mg lovastatin arms . Major efforts were made to recruit women and minorities . Participants were followed up for 1 year on a cholesterol-lowering diet plus placebo or study drug . End points were changes in blood lipid levels . Data on other blood chemistry values , as well as quality -of-life measures and coronary heart disease morbidity and mortality , were also collected . RESULTS Four hundred thirty-one subjects with low-density lipoprotein cholesterol levels greater than 4.1 and less than 5.7 mmol/L ( 159 and 221 mg/dL ) were r and omized , of whom 71 % were women and 21 % were African Americans ; the mean age was 71 years . In the 20- and 40-mg lovastatin groups , total cholesterol levels fell 17 % and 20 % ; low-density lipoprotein cholesterol levels fell 24 % and 28 % ; triglyceride levels fell 4.4 % and 9.9 % , respectively . High-density lipoprotein cholesterol levels rose 7.0 % and 9.0 % , respectively . No changes were observed in the placebo group . Gender , race , and age did not significantly affect responses . Coronary heart disease morbidity and mortality data were collected but not analyzed for this study . CONCLUSION Older subjects of both genders and a variety of racial and ethnic groups can be successfully recruited into a cholesterol-lowering trial . Lovastatin has effects similar to those reported in younger subjects in previous controlled trials . There is little advantage to the higher lovastatin daily dose . Side effects were remarkably low in all groups", "ABSTRACT Objective : Carotid intima-media thickness ( CIMT ) is an index for changes in atherosclerosis burden and changes in CIMT may relate to clinical events . We present baseline data from the METEOR study , a r and omized , placebo-controlled trial evaluating the efficacy of rosuvastatin 40 mg on changes in CIMT . We set out to compare differences in CIMT between several subgroups of individuals . Design and methods : A total of 984 individuals aged 45–70 years ( men ) or 55–70 ( women ) were r and omized . Participants were required to have : maximum CIMT ≥ 1.2– Demographic characteristics were compared in two groups : USA versus Europe , and individuals with maximum CIMT mean age was 57 years and mean low-density lipoprotein cholesterol was 152 mg/dL ( 3.9 mmol/L ) . Body mass index ( BMI ) , triglyceride and high-sensitivity C-reactive protein levels were all higher in US individuals , whereas smoking , hypertension and high-density lipoprotein cholesterol levels were higher in Europeans . Mean CIMT levels were the same in both population s , and the percentage of individuals with ≥ 2 CHD risk factors was similar . Increased baseline CIMT ( > 2 mm ) was related to increasing age , male gender , smoking , hypertension and lipid levels . Conclusions : In this global trial , differences in baseline characteristics between participants from the USA and Europe are apparent . However , a strong association between CIMT and several cardiovascular risk factors was observed across the two continents . Trial registration : Clinical Trials.gov identifier : NCT00225589", "BACKGROUND Percutaneous coronary revascularization is widely used in improving symptoms and exercise performance in patients with ischemic heart disease and stable angina pectoris . In this study , we compared percutaneous coronary revascularization with lipid-lowering treatment for reducing the incidence of ischemic events . METHODS We studied 341 patients with stable coronary artery disease , relatively normal left ventricular function , asymptomatic or mild-to-moderate angina , and a serum level of low-density lipoprotein ( LDL ) cholesterol of at least 115 mg per deciliter ( 3.0 mmol per liter ) who were referred for percutaneous revascularization . We r and omly assigned the patients either to receive medical treatment with atorvastatin , at 80 mg per day ( 164 patients ) , or to undergo the recommended percutaneous revascularization procedure ( angioplasty ) followed by usual care , which could include lipid-lowering treatment ( 177 patients ) . The follow-up period was 18 months . RESULTS Twenty-two ( 13 percent ) of the patients who received aggressive lipid-lowering treatment with atorvastatin ( result ing in a 46 percent reduction in the mean serum LDL cholesterol level , to 77 mg per deciliter [ 2.0 mmol per liter ] ) had ischemic events , as compared with 37 ( 21 percent ) of the patients who underwent angioplasty ( who had an 18 percent reduction in the mean serum LDL cholesterol level , to 119 mg per deciliter [ 3.0 mmol per liter ] ) . The incidence of ischemic events was thus 36 percent lower in the atorvastatin group over an 18-month period ( P=0.048 , which was not statistically significant after adjustment for interim analyses ) . This reduction in events was due to a smaller number of angioplasty procedures , coronary-artery bypass operations , and hospitalizations for worsening angina . As compared with the patients who were treated with angioplasty and usual care , the patients who received atorvastatin had a significantly longer time to the first ischemic event ( P=0.03 ) . CONCLUSIONS In low-risk patients with stable coronary artery disease , aggressive lipid-lowering therapy is at least as effective as angioplasty and usual care in reducing the incidence of ischemic events", "BACKGROUND The atherosclerotic progression-reducing effect of LDL cholesterol ( LDL-C ) lowering has been established in subjects with severe atherosclerotic disease but not in persons with elevated LDL cholesterols without severe atherosclerosis . KAPS ( Kuopio Atherosclerosis Prevention Study ) is the first population -based trial in the primary prevention of carotid and femoral atherosclerosis . METHODS AND RESULTS The eligibility requirements were serum LDL-C > or = 4.0 mmol/L and total cholesterol pravastatin ( 40 mg/d ) or placebo for 3 years . Less than 10 % of the subjects had prior myocardial infa rct ion . Thirty-nine men discontinued study medication ; however , efficacy data were available for 424 men . The primary outcome was the rate of carotid atherosclerotic progression , measured as the linear slope over annual ultrasound examinations in the average of the maximum carotid intima-media thickness ( IMT ) of the far wall of up to four arterial segments ( the right and left distal common carotid artery and the right and left carotid bulb ) . For the carotid arteries , at the overall mean baseline IMT of 1.66 mm , the rate of progression of carotid atherosclerosis was 45 % ( 95 % CI , 16 to 69 % ) less in the pravastatin ( 0.017 mm/y ) than the placebo ( 0.031 mm/y ) group ( P = .005 ) . In the common carotid artery there was a treatment effect of 66 % ( 95 % CI , 30 to 95 % ; pravastatin 0.010 mm/y ; placebo 0.029 mm/y ; P baseline IMT of 1.35 mm . A treatment effect of 30 % ( 95 % CI , -1 % to 54 % ) was found for the carotid bulb ( pravastatin , 0.028 ; placebo , 0.040 ; P = .056 ) at the overall mean baseline IMT of 2.0 mm . The treatment effect was larger in subjects with higher baseline IMT values , in smokers and in those with low plasma vitamin E levels . There was no significant treatment effect on atherosclerotic progression in the femoral arteries . CONCLUSIONS These data establish the antiatherogenic effect of LDL-C lowering by pravastatin in hypercholesterolemic men in a primary prevention setting and suggest a greater effect in smokers than in nonsmokers", "Among hypertensive patients , cardiovascular disease morbidity is common , even in those who are adequately treated . New pharmacological strategies to mitigate the burden of arterial hypertension are needed . This 12-month , r and omized , double-blind placebo-controlled study investigated the effect of statin ( fluvastatin ) treatment on ambulatory blood pressure ( ABP ) , exercise blood pressure ( EBP ) , myocardial structure , endothelial function and insulin resistance in 50 hypertensive patients . At baseline , the groups were comparable in terms of demographic characteristics , ABP , EBP , endothelial function and homeostasis model assessment of insulin resistance ( HOMA-IR ) . At the end of the study , there was no difference between groups in terms of resting systolic blood pressure . However , maximum systolic EBP was lower in the treatment group than in the placebo group ( 175±18 vs 192±23 mm Hg , P was left ventricular mass index ( LVMI ; 82±15 vs 100±23 , P ) , and HOMA-IR index was lower after fluvastatin treatment ( 2.77±1.46 vs 3.33±1.73 , P Changes in lipid profile were not correlated with blood pressure , endothelial function , LVMI or HOMA-IR data . In hypertensive patients , fluvastatin can improve maximum systolic EBP , myocardial remodelling and insulin resistance , independently of lipid profile variations and endothelial function", "BACKGROUND In several statin trials , vascular event rates for treatment groups begin to separate 1 year after commencement of treatment . For atherosclerosis progression , the temporal sequence of the effect has not been defined . We used data from the Measuring Effects on intima media Thickness : an Evaluation Of Rosuvastatin ( METEOR ) trial to determine the earliest time point at which significant differences in atherosclerosis progression rates could be detected after initiation of statin therapy . METHODS The METEOR trial was a double-blind , r and omized placebo-controlled trial that studied the effect of LDL-C lowering with 40 mg rosuvastatin on the rate of change of carotid intima media thickness ( CIMT ) measured by B-mode ultrasound amongst 984 low risk subjects . Ultrasound assessment s were made at baseline and every 6 months up to 2 years . RESULTS Rosuvastatin treatment was associated with a 49 % reduction in LDL-C-C , a 34 % reduction in total cholesterol , an 8.0 % increase in HDL-C and a 16 % reduction in triglycerides ( all P ) . The difference in rate of mean maximum CIMT progression between the rosuvastatin and placebo groups ( based on near and far wall measurements from both left and right common carotid and internal carotid segments and carotid bifurcation ) was not statistically significant after 6 months ( 0.0023 mm year(-1 ) and 0.0106 mm year(-1 ) , respectively P = 0.34 ) . After 12 months , CIMT progression rates were significantly different between the groups : 0.0032 mm year(-1 ) and 0.0133 mm year(-1 ) in the rosuvastatin-treated and placebo-treated groups , respectively ( P = 0.049 ) . This divergence grew with further follow-up : -0.0009 mm year(-1 ) and 0.0131 mm year(-1 ) after 18 months ( P mean common CIMT progression ( based on near and far wall measurements from both left and right common carotid segments ) . CONCLUSION Aggressive LDL-C lowering seems to exert its beneficial effect on atherosclerosis progression during the first 12 months of treatment . This parallels the timing of event reduction seen in clinical trials and suggests that the efficacy of lipid lowering treatment on CIMT progression can be evaluated in trials with a duration of 1 year , given sufficient sample size , high precision of measurements and a treatment effect comparable to that seen in METEOR", "OBJECTIVE To evaluate the effect of diet and drug intervention separately and combined in the treatment of primary hypercholesterolemia . DESIGN The study was conducted as a r and omized , placebo-controlled factorial trial , double-blinded for drug intervention . SETTING Subjects were recruited from a population -based cholesterol screening programme . SUBJECTS 215 middle-aged men with primary hypercholesterolemia , free from cardiovascular disease . INTERVENTIONS Subjects were r and omized to one of four intervention groups : ( 1 ) placebo and US National Cholesterol Education Program step 1 diet ; ( 2 ) placebo and step 2 diet ; ( 3 ) pravastatin 20 mg day-1 and step 1 diet ; or ( 4 ) pravastatin 20 mg day-1 and step 2 diet . The intervention period was 6 months . MAIN OUTCOME MEASUREMENTS Efficacy measurements included : serum total cholesterol , HDL cholesterol , triglycerides , apolipoproteins A1 and B. LDL cholesterol was calculated . For safety , values of ALAT , ASAT and CK were measured . RESULTS In the group receiving the step 1 diet only , lipid values were stable during the study period . In the placebo group on the step 2 diet , total cholesterol decreased by 6.3 % ( 0.47 mmol L-1 ( 95 % CI : 0.28 , 0.67 ) ) during 6 months . In the group receiving both pravastatin and the step 1 diet , there was a mean reduction in serum total cholesterol of 19.4 % ( 1.46 mmol L-1 ( 95 % CI : 1.20 , 1.72 ) ) . In the group treated with pravastatin and the step 2 diet , the 6 months of data show a reduction of 20.7 % ( 1.55 mmol L-1 ( 95 % CI : 1.30 , 1.80 ) ) . CONCLUSIONS If drug therapy with a HMG-CoA reductase inhibitor is considered necessary , a step 2 diet has no additional lipid-lowering effect compared with a step 1 diet in men with primary hypercholesterolaemia . However , favourable ' side-effects ' of a lipid-lowering diet , such as weight loss and lowering of blood pressure , may still warrant a low-fat diet in these cases", "OBJECTIVES We sought to analyze the disease-free intervals and calculate the freedom from atherosclerosis events in the Program on the Surgical Control of the Hyperlipidemias ( POSCH ) . BACKGROUND The POSCH study was a r and omized , secondary lipid/atherosclerosis intervention trial that provided strong evidence for reduction in atherosclerosis progression as demonstrated by clinical and arteriographic end points . The 417 control group patients received American Heart Association phase II diet instruction , and the 421 intervention group patients received identical dietary instruction and underwent a partial ileal bypass operation . METHODS Four outcome measures were determined : 1 ) overall mortality , 2 ) coronary heart disease mortality , 3 ) coronary heart disease mortality and confirmed nonfatal myocardial infa rct ion , and 4 ) coronary/cardiac interventions . RESULTS An overall mortality rate of 10 % occurred at 6.7 years in the control group and 9.4 years in the intervention group , for a gain in disease-free interval of 2.7 years in the intervention group ( p = 0.032 ) . A coronary heart disease mortality rate of 8 % occurred at 7.2 years in the control group and 11 years in the intervention group , for a gain of 3.8 years ( p = 0.046 ) . Twenty percent of patients demonstrated the combined end point of coronary heart disease mortality and confirmed nonfatal myocardial infa rct ion at 5.9 years in the control group and 11.4 years in the intervention group , for a gain of 5.5 years ( p coronary artery bypass graft surgery , percutaneous transluminal coronary angioplasty or heart transplantation at 5.4 years in the control group and 12.4 years in the intervention group , for a gain of 7 years ( p partial ileal bypass in the POSCH trial led to demonstrable increases in the disease-free intervals for overall mortality , coronary heart disease mortality , coronary heart disease mortality and confirmed nonfatal myocardial infa rct ion , and coronary intervention procedures . For the clinician and the patient , estimation of disease-free intervals may be more relevant than assessment of differences in incidence rates and risk ratios", "Statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals but their efficacy and safety in elderly people has not been confirmed . Several clinical trials including the Cholesterol and Recurrent Events ( CARE ) and Long-term Intervention with Pravastatin in Ischemic Disease ( LIPID ) , have sub-analysed their results for the ' elderly ' cohort , but the Prospect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) trial is the first trial to specifically evaluate the benefits of statin therapy on vascular risk in elderly men and women . The results have shown that pravastatin , given for 3 years , reduced the risk of coronary heart disease in elderly individuals . Within this same time frame , there was no significant benefit on the risk reduction of stroke but there was a trend to reduce the risk of transient ischemic attacks . It was discovered that those patients with the lowest baseline high-density lipoprotein cholesterol gained the most benefit from the intervention . Drug interactions between pravastatin and the concomitant medications seen in this elderly cohort , was not a significant clinical issue . Therefore , PROSPER extends to elderly individuals the treatment strategy currently used in middle-aged people", "The Program on the Surgical Control of the Hyperlipidemias ( POSCH ) provided the clearest and the most convincing evidence supporting the beneficial effects of cholesterol lowering in hypercholesterolemic survivors of a myocardial infa rct ion . In POSCH , 78 of the 838 patients ( 9.3 % ) were women , with 32 r and omized to the diet-control group and 46 to the diet plus partial ileal bypass surgery-intervention group . At 5 years , the mean per cent change from baseline was -23.9 % for total plasma cholesterol ( p low-density lipoprotein cholesterol ( p high-density lipoprotein cholesterol ( p = not significant ) . Because of the small number of women , no statistically significant changes in clinical event rates were observed between the control and the surgery groups . A comparison of 162 coronary arteriography film pairs in the POSCH women , between baseline and 3 , 5 , 7 , and 10 years , consistently showed less disease progression in the surgery group ( p = 0.013 for combined assessment s of the baseline to the longest follow-up film ) . Because the lipid and coronary arteriography findings in the POSCH women paralleled these findings in the total POSCH population and in the POSCH men , and because the arteriography changes in POSCH have previously been demonstrated to be statistically significant surrogate end points for certain clinical events and predictors of overall and atherosclerotic coronary heart disease mortality rates , we conclude that the lipid modification achieved in the POSCH women by partial ileal bypass reduced their atherosclerosis progression . The POSCH findings in women support the aggressive treatment of hyperlipidemia in the general management of atherosclerosis in women", "Abstract Objective : To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia . Design : Economic benefit analysis based on data from the West of Scotl and coronary prevention study . Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated . Scottish record linkage data provided disease specific survival . Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotl and coronary prevention study . Subjects : Men with hypercholesterolaemia similar to the subjects in the West of Scotl and coronary prevention study . Main outcome : Cost consequences , the number of transitions from health to cardiovascular disease prevented , the number needed to start treatment , and cost per life year gained . Results : If 10 000 of these men started taking pravastatin , 318 of them would not make the transition from health to cardiovascular disease ( number needed to treat , 31.4 ) , at a net discounted cost of £ 20 m over 5 years . These benefits imply an undiscounted gain of 2460 years of life , and thus £ 8121 per life year gained , or £ 20 375 per life year gained if benefits are discounted . Restriction to the 40 % of men at highest risk reduces the number needed to treat to 22.5 ( £ 5601 per life year gained ( undiscounted ) and £ 13 995 per life year gained ( discounted ) ) . Conclusions : In subjects without evidence of prior myocardial infa rct ion but who have hypercholesterolaemia , the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups . Key messages The West of Scotl and coronary prevention study showed that pravastatin can prevent cardiovascular disease in men with hypercholesterolaemia So far , reports have deemed this prevention unjustified due to adverse economic implication s This analysis , based on data from the West of Scotl and coronary prevention study and extensive data from the Scottish record linkage system , shows that using pravastatin in this way is worth considering because of its substantial clinical benefit at a reasonable cost Practitioners must now consider using pravastatin to prevent cardiovascular disease in men with hypercholesterolaemia Increased economic efficiency may be obtained by restricting prevention to patients with additional risk", "OBJECTIVES The Hypertension High Risk Management trial ( HYRIM ) investigated the effect of fluvastatin treatment and lifestyle intervention on development of carotid intima-media thickness ( IMT ) in drug-treated hypertensive patients . METHODS AND RESULTS HYRIM was a placebo-controlled , 2 x 2 factorial trial in which 568 drug-treated hypertensive men aged 40 - 74 years with total cholesterol 4.5 - 8.0 mmol/L , triglycerides to receive either fluvastatin , 40 mg daily , or placebo , and either intensive lifestyle intervention ( physical activity and diet ) or usual care ( treatment of hypertension and other disorders by own private physician ) . Carotid IMT was assessed by B-mode ultrasound vasculography and left ventricular ( LV ) mass was calculated from ultrasound recordings of the heart . Fluvastatin alone reduced the primary study endpoint of 4-year development of IMT in the common carotid artery ( CCA ) compared with placebo ( p=0.0297 ) . Carotid bulb IMT progression over 4 years was also significantly ( p=0.0214 ) reduced by fluvastatin compared with placebo . Fluvastatin significantly lowered LDL-C levels ( mean net difference through 4 years , 0.6 mmol/L ; p 2-year development of LV mass ( p=0.0144 ) compared with placebo . Lifestyle intervention had no significant effect on LDL-C , carotid IMT or LV mass , and did not increase the effects of fluvastatin . CONCLUSIONS In drug-treated hypertensive patients in a usual care setting , fluvastatin treatment reduces progression of carotid IMT and LV mass", "This multicenter , double‐blind , placebo‐controlled study was conducted to evaluate dose‐response effects and safety of once‐daily administration of pravastatin , a new inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A ( HMG‐CoA ) reductase . Pravastatin 5 , 10 , 20 , 40 mg or placebo was administered at bedtime to 150 patients with primary hypercholesterolemia inadequately controlled on a low‐fat , low‐cholesterol ( AHA Phase I ) diet . After 8 weeks of treatment , pravastatin produced dose‐dependent reductions in low‐density lipoprotein ( LDL ) cholesterol of 19.2 to 34.1 % ( p⩽.001 vs. baseline and placebo ) and reductions in total cholesterol of 14.3 to 25.1 % ( p⩽.01 to p⩽.001 vs. placebo and p⩽.001 vs. baseline ) . The relationship between the loge dose of pravastatin and decrease in LDL cholesterol was linear ( p ) . High‐density‐lipoprotein cholesterol increased up to 11.7 % and triglycerides decreased by as much as 23.9 % . Pravastatin was well tolerated ; no patient withdrew from the study as a consequence of treatment‐related adverse events . Despite its relatively short serum half‐life of approximately 2 h , once‐daily administration of pravastatin provides a safe and effective means of reducing elevated LDL and total cholesterol ", "BACKGROUND The majority of cardiovascular events and deaths attributable to both raised blood pressure and dyslipidaemia occur in subjects with relatively \" normal \" blood pressure and lipid levels respectively . The study was design ed to evaluate the potential benefits of cholesterol lowering in the primary prevention of coronary heart disease in hypertensive subjects with average and below average levels of serum cholesterol . MATERIAL AND METHODS Out of 19 342 hypertensive subjects ( aged 40 - 79 ) who were initially r and omized to one of two antihypertensive treatment strategies in the Anglo-Sc and inavian Cardiac Outcomes Trial ( ASCOT ) , 10 305 subjects with total cholesterol levels to either 10 mg atorvastatin or placebo . The primary endpoint was non-fatal myocardial infa rct ion or fatal coronary heart disease . RESULTS The lipid arm of the study was prematurely stopped after a median follow-up period of 3.3 years . One hundred events occurred in those r and omized to atorvastatin compared to 154 events in those receiving placebo , a 36 % relative risk reduction ( p = 0.0005 ) in the primary endpoint . Among secondary and tertiary endpoints , stroke was reduced with 27 % ( p = 0.02 ) . There was a non-significant 13 % reduction in total mortality . Non-cardiovascular mortality was similar in the two treatment limbs of the trial . After three years of follow-up , atorvastatin lowered total serum cholesterol by 1.1 mmol/L compared with placebo . INTERPRETATION Treatment with 10 mg atorvastatin o.d . in hypertensive patients at moderate risk gives a significant risk reduction of coronary heart disease , independent of baseline level of total cholesterol", "BACKGROUND Our purpose was to evaluate the efficacy and safety of atorvastatin , a potent cholesterol- and triglyceride-lowering agent , in peritoneal dialysis patients with dyslipidaemia . METHODS Peritoneal dialysis patients with hypercholesterolaemia were treated for 4 months with atorvastatin at a starting dose of 10 mg . The dose could be increased to 20 or 40 mg in order to achieve the following targets : plasma LDL-cholesterol of 130 mg/dl for primary prevention of coronary heart disease , plasma LDL cholesterol of 100 mg/dl for secondary prevention , and plasma triglycerides of 200 mg/dl . Plasma lipid profile and liver and muscle enzyme levels were assessed at baseline and then monthly during treatment . RESULTS Thirty-one patients with hypercholesterolaemia were included ( 16 males and 15 females ; mean age 57+/-16 years ; mean duration of peritoneal dialysis 27+/-17 months ) . Nineteen of the patients also had hypertriglyceridaemia and seven had diabetes . Twenty patients had no coronary history ( primary prevention ) , whereas nine had experienced a coronary event ( secondary prevention ) . In the primary and the secondary prevention patients , mean LDL-cholesterol levels ( mg/dl ) decreased significantly by 42 and 46 % from 204+/-23 to 119+/-27 ( P mean triglyceride levels ( mg/dl ) decreased by 37 and 26 % from 289+/-132 to 186+/-92 ( P LDL-cholesterol target . The triglyceride target was achieved by 15 of the 19 hypertriglyceridaemic patients . Two patients stopped treatment ( one because of gastrointestinal disturbances , the other because of an allergic skin reaction ) . After 4 months , there were no changes in enzyme levels . CONCLUSION Atorvastatin is an effective and safe lipid-lowering agent for peritoneal dialysis patients with mixed dyslipidaemia", "The MEGA Study was Japan 's first primary prevention trial of cardiovascular disease ( CVD ) by cholesterol lowering with low-dose pravastatin . Included were postmenopausal women aged total cholesterol ( TC ) level 220 - 270 mg/dL. In all , 8214 out patients were r and omly assigned to receive diet alone or diet plus pravastatin 10 - 20mg/day for an average follow-up of 5.3 years . The primary endpoint was a composite of fatal and nonfatal MI , angina , cardiac and sudden death , and coronary revascularization . TC was reduced by 11.5 % in the diet plus pravastatin group versus 2.1 % in the diet alone group . LDL-C was reduced by 18 % and 3.2 % in the two groups , respectively . TC was reduced to diet plus pravastatin group . There was a significant 33 % reduction of the primary endpoint in the diet plus pravastatin group compared with the diet alone group . Notable findings of the MEGA Study included the observation that despite pravastatin 's modest LDL-C reductions in this low-risk population , a 33 % reduction of CHD events was achieved . Even though 68 % of patients were women , who have been traditionally considered at less risk than men , significant CHD risk reduction was observed across all groups", "BACKGROUND AND METHODS The Program on the Surgical Control of the Hyperlipidemias ( POSCH ) , a r and omized clinical trial , was design ed to test whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality or mortality due to coronary heart disease . The study population consisted of 838 patients ( 417 in the control group and 421 in the surgery group ) , both men ( 90.7 percent ) and women , with an average age of 51 years , who had survived a first myocardial infa rct ion . The mean follow-up period was 9.7 years . RESULTS When compared with the control group at five years , the surgery group had a total plasma cholesterol level 23.3 percent lower ( 4.71 + /- 0.91 vs. 6.14 + /- 0.89 mmol per liter [ mean + /- SD ] ; P less than 0.0001 ) , a low-density lipoprotein cholesterol level 37.7 percent lower ( 2.68 + /- 0.78 vs. 4.30 + /- 0.89 mmol per liter ; P less than 0.0001 ) , and a high-density lipoprotein cholesterol level 4.3 percent higher ( 1.08 + /- 0.26 vs. 1.04 + /- 0.25 mmol per liter ; P = 0.02 ) . Overall mortality and mortality due to coronary heart disease were reduced , but not significantly so ( deaths overall [ control vs. surgery ] , 62 vs. 49 , P = 0.164 ; deaths due to coronary disease , 44 vs. 32 , P = 0.113 ) . The overall mortality in the surgery subgroup with an ejection fraction greater than or equal to 50 percent was 36 percent lower ( control vs. surgery , 39 vs. 24 ; P = 0.021 ) . The value for two end points combined -- death due to coronary heart disease and confirmed nonfatal myocardial infa rct ion -- was 35 percent lower in the surgery group ( 125 vs. 82 events ; P less than 0.001 ) . During follow-up , 137 control-group and 52 surgery-group patients underwent coronary-artery bypass grafting ( P less than 0.0001 ) . A comparison of base-line coronary arteriograms with those obtained at 3 , 5 , 7 , and 10 years consistently showed less disease progression in the surgery group ( P less than 0.001 ) . The most common side effect of partial ileal bypass was diarrhea ; others included occasional kidney stones , gallstones , and intestinal obstruction . CONCLUSIONS Partial ileal bypass produces sustained improvement in the blood lipid patterns of patients who have had a myocardial infa rct ion and reduces their subsequent morbidity due to coronary heart disease . The role of this procedure in the management of hypercholesterolemia remains to be determined . These results provide strong evidence supporting the beneficial effects of lipid modification in the reduction of atherosclerosis progression", "BACKGROUND R and omized trials have established statins as an agent for prevention of coronary heart disease ( CHD ) . The purpose of this study was to assess the hypothesis that st and ard-dose statin therapy has a beneficial effect in normocholesterolemic diabetic patients with CHD . METHODS AND RESULTS A prospect i ve , r and omized , open , blinded-endpoint trial was conducted from 2002 to 2004 at 55 hospitals in Japan to evaluate the effect of statins on subsequent cardiovascular events . A total number of 1,016 CHD patients ( 301 patients with type 2 diabetes mellitus [ DM ] and 715 non-DM patients ) with serum total cholesterol levels of 180 - 240 mg/dl were r and omly divided into non-statin and statin treatments . Clinical parameters were comparable between DM and non-DM groups . Serum low-density lipoprotein (LDL)-cholesterol levels were equally decreased after statin treatment in the 2 groups . Statin treatment improved prognosis in both the DM and non-DM groups ; however , the number needed to treat ( NNT ) and relative risk reduction ( RRR ) were remarkable especially in the DM group ( NNT=8 , RRR=67 % ) compared with the non-DM group ( NNT=30 , RRR=24 % ) . CONCLUSIONS St and ard-dose statin therapy provides incremental clinical benefits in DM patients with normal cholesterol levels compared with non-DM patients . The data suggest that DM patients may enjoy the pleiotropic effects of statins , independent of the LDL-cholesterol lowering effects of these agents", "Although there is little information from primary or secondary prevention trials on cholesterol-lowering medication in diabetic patients , the reduction of elevated cholesterol is widely recommended for this group . The American Diabetes Association ( ADA ) recommends drug therapy in diabetic patients if low density lipoprotein (LDL)-cholesterol remains at > 130 mg/dl , or > 100 mg/dl in patients with macroangiopathy , after dietary intervention . When cholesterollowering medication is indicated , the choice of the drug must take into account the other lipid abnormalities that are often present and the need to maintain optimal glycaemic control . In the present study we compared the efficacy and safety of the novel HMG-CoA reductase inhibitor atorvastatin at the dose of 10 mg/day with simvastatin , lovastatin and pravastatin at doses of 10 , 20 and 20 mg/day , respectively , and placebo , in type 2 diabetic patients with moderate elevation of LDL-cholesterol with or without elevation of triglycerides . All the quoted agents are enzyme inhibitors effective in lowering LDL-cholesterol in humans . The efficacy endpoints were the mean per cent changes in plasma LDL-cholesterol ( primary ) , total cholesterol , triglycerides , and high-density lipoprotein (HDL)-cholesterol concentrations from baseline to the end of treatment ( 24 weeks ) . Atorvastatin at a dose of 10 mg/day produced : ( 1 ) a significant reduction in LDL-cholesterol ( -37 % ) in comparison with equivalent doses of simvastatin ( -26 % ) , pravastatin ( -23 % ) , lovastatin ( -21 % ) , and placebo ( -1 % ) ; ( 2 ) HDL-cholesterol increases ( 7.4 % ) comparable to or greater than those obtained with simvastatin ( 7.1 % ) , pravastatin ( 3.2 % ) , lovastatin ( 7.21 % ) , and placebo ( -0.5 % ) ; ( 3 ) a significantly greater reduction in total cholesterol ( - 29 % ) than that obtained with simvastatin ( -21 % ) , pravastain ( -16 % ) , lovastatin ( -18 % ) , and placebo ( 1 % ) ; and ( 4 ) a significantly greater reduction in triglycerides than that obtained with all the other drugs and placebo . In all treatment groups no significant variation in fibrinogen concentration was observed . All reductase inhibitors studied had similar levels of tolerance . There were no incidents of persistent elevations of serum aminotransferases or myositis ", "Background Statins have anti-inflammatory actions which in theory are potentially beneficial in asthma . Small trials have failed to show a significant benefit , but a systematic study to evaluate the steroid-sparing effect of statin treatment has not been carried out . Methods A r and omised , placebo-controlled , crossover trial was conducted of simvastatin 40 mg at night with simultaneous stepwise reduction of fluticasone propionate dose until loss of control occurred , followed by an increase until regain of control ( ‘ minimum ’ dose required ) in 51 patients with asthma and sputum eosinophils ( steroid-free ) ≥2 % . Results 43 patients completed the study . There was no significant difference in ‘ minimum ’ inhaled corticosteroid ( ICS ) dose requirement between simvastatin and placebo : ( median ( IQR ) 50 μg daily ( 0–250 ) vs 100 μg daily ( 0–250 ) , p=0.931 ) . ‘ Minimum ’ dose distribution was similar ( p=0.269 ) . The fluticasone dose at which loss of control occurred did not differ significantly between simvastatin and placebo ( p=0.404 ) . In patients with loss of control in both treatment arms , fluticasone dose at loss of control was similar with simvastatin and placebo ( median ( IQR ) 50 μg daily ( 0–100 ) for both , p=0.620 ) . In those patients who reached 0 μg/day ( n=18 ) , Astma Control Question naire ( ACQ ) was lower ( p=0.037 ) , forced expiratory volume in 1 s ( FEV1 ) higher ( p ) and sputum eosinophils lower with simvastatin compared with placebo ( 9.5 % compared with 25.4 % , p=0.033 ) . Conclusions Simvastatin does not have clinical ly important steroid-sparing effects in patients with eosinophilic asthma . In the absence of steroid , simvastatin is associated with minor improvements in symptoms and lung function , and a reduction in sputum eosinophils . Clinical trial number ACTRN12606000531516", "BACKGROUND Controversy persists regarding the extent of shared pathways between arterial and venous thrombosis and whether treatments of known efficacy for one disease process have consistent benefits for the other . Observational studies have yielded variable estimates of the effect of statin therapy on the risk of venous thromboembolism , and evidence from r and omized trials is lacking . METHODS We r and omly assigned 17,802 apparently healthy men and women with both low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to receive rosuvastatin , 20 mg per day , or placebo . We followed participants for the first occurrence of pulmonary embolism or deep-vein thrombosis and performed analyses of the data on an intention-to-treat basis . RESULTS During a median follow-up period of 1.9 years ( maximum , 5.0 ) , symptomatic venous thromboembolism occurred in 94 participants : 34 in the rosuvastatin group and 60 in the placebo group . The rates of venous thromboembolism were 0.18 and 0.32 event per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio with rosuvastatin , 0.57 ; 95 % confidence interval [ CI ] , 0.37 to 0.86 ; P=0.007 ) ; the corresponding rates for unprovoked venous thromboembolism ( i.e. , occurring in the absence of a known malignant condition , trauma , hospitalization , or surgery ) were 0.10 and 0.17 ( hazard ratio , 0.61 ; 95 % CI , 0.35 to 1.09 ; P=0.09 ) and for provoked venous thromboembolism ( i.e. , occurring in patients with cancer or during or shortly after trauma , hospitalization , or surgery ) , 0.08 and 0.16 ( hazard ratio , 0.52 ; 95 % CI , 0.28 to 0.96 ; P=0.03 ) . The rates of pulmonary embolism were 0.09 in the rosuvastatin group and 0.12 in the placebo group ( hazard ratio , 0.77 ; 95 % CI , 0.41 to 1.45 ; P=0.42 ) , whereas the rates of deep-vein thrombosis only were 0.09 and 0.20 , respectively ( hazard ratio , 0.45 ; 95 % CI , 0.25 to 0.79 ; P=0.004 ) . Consistent effects were observed in all the subgroups examined . No significant differences were seen between treatment groups in the rates of bleeding episodes . CONCLUSIONS In this trial of apparently healthy persons , rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism . ( Clinical Trials.gov number , NCT00239681 .", "The West of Scotl and Coronary Prevention Study recently demonstrated the benefits of pravastatin therapy in the prevention of coronary heart disease events in middle-aged hypercholesterolemic men without prior myocardial infa rct ion . We present an analysis of the influence of baseline risk factors on coronary events and total mortality in the trial , and their interaction with therapy , using the Cox proportional hazards model . The multivariate predictors of fatal or nonfatal coronary events were treatment allocation ( pravastatin or placebo ) , current smoking , diabetes mellitus , nitrate consumption , minor electrocardiographic abnormalities , angina pectoris , family history of premature coronary death , widowhood , blood pressure , and total cholesterol/high density lipoprotein cholesterol ratio . Independent of other risk factors , pravastatin reduced the risk of definite coronary heart disease death or nonfatal myocardial infa rct ion by 32 % ( 95 % confidence interval 17 to 44 , p = 0.0001 ) , definite or suspected coronary heart disease death by 35 % ( 3 to 56 , p = 0.035 ) , cardiovascular death by 33 % ( 4 to 53 , p = 0.027 ) , coronary revascularization procedures by 38 % ( 11 to 56 , p = 0.009 ) , and all-cause mortality by 24 % ( 2 to 41 , p = 0.037 ) . The 5-year risk of fatal or nonfatal myocardial infa rct ion , calculated using the predictors identified in the Cox analysis , ranged from 9.6 % in the highest quartile . The proportional benefit achieved by pravastatin was independent of other risk factors ; hence , the absolute benefit of therapy was greatest in subjects with the highest baseline risk . Such subjects can be identified easily in the population and deserve high priority for treatment", "BACKGROUND Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease , but the role of lipid-lowering therapy with statins for the primary prevention of cardiovascular disease in diabetes is inadequately defined . We aim ed to assess the effectiveness of atorvastatin 10 mg daily for primary prevention of major cardiovascular events in patients with type 2 diabetes without high concentrations of LDL-cholesterol . METHODS 2838 patients aged 40 - 75 years in 132 centres in the UK and Irel and were r and omised to placebo ( n=1410 ) or atorvastatin 10 mg daily ( n=1428 ) . Study entrants had no documented previous history of cardiovascular disease , an LDL-cholesterol concentration of 4.14 mmol/L or lower , a fasting triglyceride amount of 6.78 mmol/L or less , and at least one of the following : retinopathy , albuminuria , current smoking , or hypertension . The primary endpoint was time to first occurrence of the following : acute coronary heart disease events , coronary revascularisation , or stroke . Analysis was by intention to treat . FINDINGS The trial was terminated 2 years earlier than expected because the prespecified early stopping rule for efficacy had been met . Median duration of follow-up was 3.9 years ( IQR 3.0 - 4.7 ) . 127 patients allocated placebo ( 2.46 per 100 person-years at risk ) and 83 allocated atorvastatin ( 1.54 per 100 person-years at risk ) had at least one major cardiovascular event ( rate reduction 37 % [ 95 % CI -52 to -17 ] , p=0.001 ) . Treatment would be expected to prevent at least 37 major vascular events per 1000 such people treated for 4 years . Assessed separately , acute coronary heart disease events were reduced by 36 % ( -55 to -9 ) , coronary revascularisations by 31 % ( -59 to 16 ) , and rate of stroke by 48 % ( -69 to -11 ) . Atorvastatin reduced the death rate by 27 % ( -48 to 1 , p=0.059 ) . No excess of adverse events was noted in the atorvastatin group . INTERPRETATION Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events , including stroke , in patients with type 2 diabetes without high LDL-cholesterol . No justification is available for having a particular threshold level of LDL-cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statins . The debate about whether all people with this disorder warrant statin treatment should now focus on whether any patients are at sufficiently low risk for this treatment to be withheld", "Laboratory investigations have demonstrated that blockade of HMG-CoA reductase in vitro reduces lymphocyte proliferation in response to mitogens as well as other facets of the immune system , such as natural killer cell cytotoxicity . However , in this r and omized and double-blind clinical investigation , treatment with 20-mg lovastatin for 6 months did not significantly alter several enumerative and functional characteristics of circulating immune cells", "BACKGROUND The West of Scotl and Coronary Prevention Study was a primary prevention trial that demonstrated the effectiveness of pravastatin ( 40 mg/d ) in reducing morbidity and mortality from coronary heart disease ( CHD ) in moderately hypercholesterolemic men . The present analysis examines the extent to which differences in LDL and other plasma lipids both at baseline and on treatment influenced CHD risk reduction . METHODS AND RESULTS Relationships between baseline lipid concentrations and incidence of all cardiovascular events and between on-treatment lipid concentrations and risk reduction in patients taking pravastatin were examined by use of Cox regression models and by division of the cohort into quintiles . Variation in plasma lipids at baseline did not influence the relative risk reduction generated by pravastatin therapy . Fall in LDL level in the pravastatin-treated group did not correlate with CHD risk reduction in multivariate regression . Furthermore , maximum benefit of an approximately 45 % risk reduction was observed in the middle quintile of LDL reduction ( mean 24 % fall ) ; further mean decrements in LDL ( up to 39 % ) were not associated with a greater decrease in CHD risk . Comparison of event rates between placebo- and pravastatin-treated subjects with the same LDL cholesterol level provided evidence for an apparent treatment effect that was independent of LDL . CONCLUSIONS We conclude that the treatment effect of 40 mg/d of pravastatin is proportionally the same regardless of baseline lipid phenotype . There is no CHD risk reduction unless LDL levels are reduced , but a fall in the range of 24 % is sufficient to produce the full benefit in patients taking this dose of pravastatin . LDL reduction alone does not appear to account entirely for the benefits of pravastatin therapy", "Background —Statins reduce the rates of heart attacks , strokes , and revascularization procedures ( ie , major vascular events ) in a wide range of circumstances . R and omized controlled trial data from 20 536 adults have been used to estimate the cost-effectiveness of prescribing statin therapy in the United States for people at different levels of vascular disease risk and to explore whether wider use of generic statins beyond the population s currently recommended for treatment in clinical guidelines is indicated . Methods and Results —R and omized controlled trial data , an internally vali date d vascular disease model , and US costs of statin therapy and other medical care were used to project lifetime risks of vascular events and evaluate the cost-effectiveness of 40 mg simvastatin daily . For an average of 5 years , allocation to simvastatin reduced the estimated US costs of hospitalizations for vascular events by ≈20 % ( 95 % CI , 15 to 24 ) in the different subcategories of participants studied . At a daily cost of $ 1 for 40 mg generic simvastatin , the estimated costs of preventing a vascular death within the 5-year study period ranged from a net saving of $ 1300 ( 95 % CI , $ 15 600 saving to $ 13 200 cost ) among participants with a 42 % 5-year major vascular event risk to a net cost of $ 216 500 ( $ 123 700 to $ 460 000 cost ) among those with a 12 % 5-year risk . The costs per life year gained with lifetime simvastatin treatment ranged from $ 2500 ( −$40 to $ 3820 ) in people aged 40 to 49 years with a 42 % 5-year major vascular event risk to $ 10 990 ( $ 9430 to $ 14 700 ) in people aged 70 years and older with a 12 % 5-year risk . Conclusions —Treatment with generic simvastatin appears to be cost-effective for a much wider population in the United States than that recommended by current guidelines", "BACKGROUND We examined whether atorvastatin affects diabetic kidney disease and whether the effect of atorvastatin on cardiovascular disease ( CVD ) varies by kidney status in patients with diabetes . STUDY DESIGN The Collaborative Atorvastatin Diabetes Study ( CARDS ) r and omized placebo-controlled trial . SETTING & PARTICIPANTS Patients with type 2 diabetes and no prior CVD ( n = 2,838 ) . INTERVENTION R and om allocation to atorvastatin , 10 mg/d , or placebo , with a median follow-up of 3.9 years . OUTCOMES Estimated glomerular filtration rate ( eGFR ) , albuminuria , CVD . MEASUREMENTS Baseline and follow-up GFRs were estimated by using the Modification of Diet in Renal Disease Study equation . Urinary albumin-creatinine ratio was measured on spot urine sample s. RESULTS At baseline , 34 % of patients had an eGFR of 30 to 60 mL/min/1.73 m(2 ) . Atorvastatin treatment was associated with a modest improvement in annual change in eGFR ( net , 0.18 mL/min/1.73 m(2)/y ; 95 % confidence interval [ CI ] , 0.04 to 0.32 ; P = 0.01 ) that was most apparent in those with albuminuria ( net improvement , 0.38 mL/min/1.73 m(2)/y ; P = 0.03 ) . At baseline , 21.5 % of patients had albuminuria and an additional 6.8 % developed albuminuria during follow-up . Atorvastatin did not influence the incidence of albuminuria ( hazard ratio , 1.49 ; 95 % CI , 0.73 to 3.04 ; P = 0.3 ) or regression to normoalbuminuria ( hazard ratio , 1.19 ; 95 % CI , 0.57 to 2.49 ; P = 0.6 ) . In 970 patients with a moderately decreased eGFR of 30 to 60 mL/min/1.73 m(2 ) , there was a 42 % reduction in major CVD events with treatment , including a 61 % reduction in stroke . This treatment effect was similar to the 37 % ( 95 % CI , 17 to 52 ; P CVD observed in the study overall ( P = 0.4 for the eGFR-treatment interaction ) . LIMITATIONS Low incidence rates of albuminuria and transition to more severe kidney status limit power to detect treatment effects . CONCLUSIONS A modest beneficial effect of atorvastatin on eGFR , particularly in those with albuminuria , was observed . Atorvastatin did not influence albuminuria incidence . Atorvastatin was effective at decreasing CVD in those with and without a moderately decreased eGFR and achieved a high absolute benefit", "The Chiba Lipid Intervention Program ( CLIP ) Study was design ed to clarify the prognosis of Japanese hypercholesterolemic patients taking pravastatin for 5 years . Hypercholesterolemic patients ( n = 2,529 ) with a total cholesterol level > or = 220 mg/dl and without histories of ischemic coronary heart disease and /or cerebral infa rct ion were administered pravastatin ( 10 - 20 mg/day ) . Among them , 2,131 took pravastatin fully ( Pravastatin-continued group ) , and 398 discontinued the treatment ( Discontinued group ) . The baseline total cholesterol level was 264.3 + /- 34.7 mg/dl ( mean + /- st and ard deviation ) . The mean reduction rates of total cholesterol and low-density lipoprotein ( LDL ) cholesterol were 18.0 % and 27.2 % , respectively . Mild and moderate adverse events occurred in 86 cases ( 3.6 % ) . Serious adverse events were not observed . Death rates of the pravastatin-continued group and of the discontinued group were 2.6 and 16.0/1,000 persons/year , respectively . Cardiac events ( fatal and nonfatal myocardial infa rct ion , cardiac death , angina pectoris ) in all , occurred in 35 patients ( incidence rate = 2.77/1,000 persons/year ) . In the pravastatin continued group , 9 causes of fatal and nonfatal myocardial infa rct ion occurred ( 0.84/1,000 persons/year ) , whereas in the discontinued group , 4 cases occurred ( 2.06/1,000 persons/ year ) . The risk ratio for cardiac events was correlated with the number of risks . In the low-risk group ( rates of LDL-cholesterol were less in the cardiac event group than the non-cardiac event group ( LDL-cholesterol ; 16 % vs 25 % , p = 0.04 ) . These results suggested the following ; 1 ) Pravastatin maintained a cholesterol lowering effect long-term without serious complications . 2 ) Pravastatin administration might reduce the mortality rate and myocardial infa rct ion . 3 ) The combination of multiple risks is a strong factor for a cardiac event in addition to hypercholesterolemia", "In the Exp and ed Clinical Evaluation of Lovastatin ( EXCEL ) Study , a multicenter , double-blind , diet- and placebo-controlled trial , we evaluated the efficacy and safety of lovastatin in 8245 patients with moderate hypercholesterolemia . Patients were r and omly assigned to receive placebo or lovastatin at a dosage of 20 mg once daily , 40 mg once daily , 20 mg twice daily , or 40 mg twice daily for 48 weeks . Lovastatin produced sustained , dose-related ( P less than .001 ) changes as follows ( for dosages of 20 to 80 mg/d ) : decreased low-density lipoprotein-cholesterol level ( 24 % to 40 % ) , increased high-density lipoprotein-cholesterol level ( 6.6 % to 9.5 % ) , decreased total cholesterol level ( 17 % to 29 % ) , and decreased triglyceride level ( 10 % to 19 % ) . The National Cholesterol Education Program 's low-density lipoprotein-cholesterol level goal of less than 4.14 mmol/L ( 160 mg/dL ) was achieved by 80 % to 96 % of patients , while the less than 3.36 mmol/L ( 130 mg/dL ) goal was achieved by 38 % to 83 % of patients . The difference between lovastatin and placebo in the incidence of clinical adverse experiences requiring discontinuation was small , ranging from 1.2 % at 20 mg twice daily to 1.9 % at 80 mg/d . Successive transaminase level elevations greater than three times the upper limit of normal were observed in 0.1 % of patients receiving placebo and 20 mg/d of lovastatin , increasing to 0.9 % in those receiving 40 mg/d and 1.5 % in those receiving 80 mg/d of lovastatin ( P less than .001 for trend ) . Myopathy , defined as muscle symptoms with a creatine kinase elevation greater than 10 times the upper limit of normal , was found in only one patient ( 0.1 % ) receiving 40 mg once daily and four patients ( 0.2 % ) receiving 80 mg/d of lovastatin . Thus , lovastatin , when added after an adequate trial of a prudent diet , is a highly effective and generally well-tolerated treatment for patients with moderate hypercholesterolemia", "Renal transplant recipients have a greatly increased risk of premature cardiovascular disease . The ALERT study was a multicenter , r and omized , double‐blind , placebo‐controlled trial of fluvastatin ( 40–80 mg/day ) in 2102 renal transplant recipients followed for 5–6 years . The main study used a composite cardiac end‐point including myocardial infa rct ion , cardiac death and cardiac interventions . Although reduced by fluvastatin , this primary end‐point failed to achieve statistical significance thus precluding analysis of predefined subgroups . Therefore , in the present survival analysis , we used an alternative primary end‐point of cardiac death or definite nonfatal myocardial infa rct ion ( as used in other cardiac outcome trials ) which was significantly reduced by Fluvastatin therapy and permits subgroup analysis . Fluvastatin reduced LDL‐cholesterol by 1 mmol/L compared with placebo , and the incidence of cardiac death or definite myocardial infa rct ion was reduced from 104 to 70 events ( RR 0.65 ; 95 % CI 0.48 , 0.88 ; p = 0.005 ) . Fluvastatin use was associated with reduction in cardiac death or nonfatal myocardial infa rct ion , which achieved statistical significance in many subgroups . The subgroups included patients at lower cardiovascular risk , who were younger , nondiabetic , nonsmokers and without pre‐existing CVD . These data support the early introduction of statins following renal transplantation", "Parkinson 's disease , a progressive neurodegenerative disorder , affects about 1 % of the population over the age of 50 . While it has no cure , it is the only neurodegenerative disorder with a range of medical and neurosurgical treatments that substantially reduce clinical symptoms.1 However , medical management of early Parkinson 's disease is controversial because of the potential risks and benefits to patients . Some clinicians prefer to use levodopa , a dopamine precursor , since it promptly relieves symptoms . Others prescribe dopamine agonists and withhold levodopa because of its long term complications , namely abnormal involuntary movements and potential neurotoxicity . Inevitably , managing the side effects of antiparkinsonian drugs becomes a therapeutic focus along with treating the primary motor abnormalities.1 Extended controlled clinical trials are the only means of obtaining evidence based guidance on the use of dopamine agonists or levodopa for the management of early Parkinson 's disease . The results of a recent multisite , five year , r and omised , double blind study comparing the incidence of dyskinesia with levodopa or ropinirole , a dopamine D2 receptor agonist,2 should sway practitioners towards initial treatment with agonists for early Parkinson 's disease . In contrast to the hypokinesis that characterises Parkinson 's disease , dyskinesias related to antiparkinsonian drugs involve hyperkinetic choreoathetoid , lurching , and jerky movements . These movements are thought", "OBJECTIVES To investigate the efficacy of 10 mg or 20 mg atorvastatin + long acting antihypertensive in carotid intima-medial thickness ( IMT ) . METHODS 151 patients of Han nationality in South China with mild hypertensive were r and omly divided into 3 groups : atorvastatin 10 mg group ( n = 50 ) receive 10 mg atorvastatin and amlodipine + benazepril ; atorvastatin 20 mg group ( n = 61 ) receive 20 mg atorvastatin and amlodipine + benazepril ; the control group ( n = 40 ) receive amlodipine + benazepril . The patients were detected IMT , vascular function , lipids and inflammatory factor in pretherapy and every 3 months . RESULTS atorvastatin 10 mg or 20 mg groups have significantly change contrast to control group : ( 1 ) IMT was decreased ( P Deltadia-P% and Deltadia-N% were increased ( P LDL-C level was decreased by 30 % in a atorvastatin 10 mg group and 40.48 % in 20 mg group respectively ( P Atorvastatin delays the development of atherosclerosis in hypertensive patients , improves endothelial function , and strengthens the effect of lipid-lowering", "Background : Reduction of serum cholesterol , most notably low-density lipoprotein choles terol is associated with reductions in cardiovascular morbidity and mortality . Statins have been shown to effectively reduce low-density lipoprotein cholesterol via inhibition of the hydroxymethyl-coenzyme A ( HMG-CoA ) reductase . Cerivastatin is the most potent HMG- CoA reductase inhibitor currently under study in the United States . Methods and Results : A parallel group , r and omized , placebo-controlled , double-blind , mul ticenter study was conducted to compare the efficacy and safety of three different dosing reg imens of 0.2 mg/day of cerivastatin , a new HMG-CoA reductase inhibitor , in patients with hypercholesterolemia . After a 10-week diet-placebo lead-in period , 319 patients with low- density lipoprotein cholesterol > 160 mg/dL were r and omized to 4 weeks of treatment with one of the following regimens : cerivastatin 0.1 mg twice daily , cerivastatin 0.2 mg once daily with the evening meal , cerivastatin 0.2 mg once daily at bedtime or placebo . All three active treatment groups produced statistically significant ( P total cholesterol ( 0.1 mg twice daily -18.9 % ; 0.2 mg once daily with the evening meal : -21.9 % ; 0.2 mg once daily at bedtime : -22.1 % ; placebo : 0.0 % ) , low-density lipoprotein cholesterol ( 0.1 mg twice daily : -25.7 % ; 0.2 mg once daily with the evening meal : -29.4 % ; 0.2 mg once daily at bedtime : -30.4 % ; placebo : 1.4 % ) and high-density lipoprotein cholesterol ( 0.1 mg twice daily : 5.3 % ; 0.2 mg once daily with the evening meal : 2.3 % ; 0.2 mg once daily at bedtime : 3.2 % ; placebo : -1.2 % ) . Triglycerides , compared to baseline and placebo , were also reduced by all active treatments ( 0.1 mg twice daily : -11.6 % [ P = .05 ] ; 0.2 mg once daily with the evening meal : -11.6 % [ P = .05 ] ; and 0.2 mg at bed time : -10.9 % [ P = .07 ] ) . The percentage change in total cholesterol and low-density lipopro tein cholesterol after 4 weeks of therapy for the once-daily cerivastatin groups was statisti cally significantly greater ( P cerivastatin twice daily regimen . A treatment response was seen by 1 week of therapy and was maximal by 3 weeks . The drug was well tolerated in all three dosing regimens and result ed in no significant increase in biochemical or clinical side effects compared to placebo . Conclusion : Cerivastatin is a novel , highly potent , well-tolerated HMG-CoA reductase inhibitor that produces low-density lipoprotein cholesterol reductions of approximately 30 % when administered at 0.2 mg once a day in the evenings", "The clinical efficacy and safety of pitavastatin ( NK-104 ) , a novel HMG-CoA reductase inhibitor , during long-term treatment , were examined in 25 patients ( male/female=11/14 , mean age=53+/-13 ( mean+/-SD ) years ) with heterozygous familial hypercholesterolemia ( FH ) . After a period on placebo of > 4 weeks , 2 mg/day of pitavastatin was administered for 8 weeks , and the dose was increased to 4 mg/day for up to 104 weeks . Total cholesterol ( TC ) decreased by 31 % from the initial value of 340+/-57 to 237+/-40 mg/dl ( P TC decreased even further to 212+/-35 mg/dl at week 12 ; it decreased by 37 % from the initial value ( P low-density lipoprotein (LDL)-cholesterol ( LDL-C ) decreased by 41 % at week 8 , and by 49 % at week 12 , from 267+/-61 mg/dl at baseline . These findings indicate a dose-dependent effect of the drug on TC and LDL-C concentrations . To examine whether the levels of circulating matrix metalloproteinases ( MMPs ) and their endogenous inhibitors ( tissue inhibitors of metalloproteinases : TIMPs ) are altered during lipid-lowering therapy , we also measured their plasma levels . The mean levels of MMP-2 and -3 were significantly increased . No significant alteration was found in MMP-9 , TIMP-1 and -2 levels . As for the safety of pitavastatin , adverse reactions were observed in one case ( 4 % ) of subjective and objective symptoms . The effects of pitavastatin on TC and LDL-C were stable during long treatment of patients with heterozygous FH", "Objectives : Non-HDL-cholesterol ( non-HDL-C ) and apolipoprotein ( apo ) B are proposed as treatment targets . The extent to which statin therapy affects relationships of LDL-C and non-HDL-C with apoB was examined in type 2 diabetes . Methods : Analyses were performed in 217 hypertriglyceridaemic type 2 diabetic patients ( Diabetes Atorvastatin Lipid Intervention ( DALI ) cohort ) . 61 patients r and omized to placebo , 70 to 10 mg atorvastatin daily and 65 – 80 mg atorvastin daily completed follow-up . Results : Baseline fasting LDL-C of 2.42 mmol/l and non-HDL-C of 3.69 mmol/l corresponded to the apoB guideline target of 0.90 g/l . During atorvastatin ( 10 and 80 mg daily ) , the LDL-C target was achieved most frequently , and lower LDL-C ( 2.38 and 2.29 mmol/l ) and non-HDL-C ( 3.24 and 3.19 mmol/l ) concentrations corresponded to this apoB goal . Decreases in LDL-C during atorvastatin treatment were negatively related ( p decreases in non-HDL-C were positively related to changes in triglycerides ( p in apoB ( p Decreases in LDL-C and non-HDL-C were positively associated with decreases in cholesteryl ester transfer protein mass ( p During atorvastatin lower LDL-C and non-HDL-C levels correspond to the apoB guideline target , which would favour its use as treatment target", "OBJECTIVES In addition to its LDL-C-lowering effects , statin treatment reduces the level of C-reactive protein ( CRP ) . Long-term data on this effect in low-risk population s are limited . Furthermore , whether the CRP reduction is a consequence of LDL-C lowering or occurs independently remains unclear . We studied these aspects in the Measuring Effects on intima media Thickness : an Evaluation Of Rosuvastatin ( METEOR ) study , a r and omized placebo-controlled trial amongst 984 low-risk subjects . METHODS METEOR is a r and omized placebo-controlled trial that evaluated the effect of 40 mg of rosuvastatin on 2-year change in carotid intima media thickness ( CIMT ) amongst 984 low-risk patients ( 10-year Framingham risk or = 1.2 and CRP levels were measured at baseline and after 2 years of treatment . RESULTS Median baseline CRP was 1.4 mg L(-1 ) . Rosuvastatin lowered CRP significantly compared with placebo : -36 % in the rosuvastatin group versus no change in the placebo group . There was no relation between change in CRP and change in LDL-C ( Spearman correlation : 0.08 ; SE : 0.04 ) . Stratified analyses showed that the CRP-lowering effect was present amongst all strata of baseline characteristics , including baseline lipids and CRP levels . However , the magnitude of CRP reduction was larger amongst women and participants older than 60 years . CONCLUSIONS Rosuvastatin ( 40 mg ) lowers CRP independently from its effects on LDL-C in low-risk subjects with normal baseline CRP levels and modest CIMT", "OBJECTIVE Assessment of the relationship between changes in sequential coronary arteriograms and subsequent clinical coronary events . DESIGN The Program on the Surgical Control of the Hyperlipidemias , a r and omized secondary atherosclerosis intervention trial , obtained coronary arteriograms at baseline , 3 , 5 , and 7 or 10 years of follow-up . Assessment s of changes between pairs of coronary arteriograms were made by two-member panels blinded to the patients ' assigned treatment and to the temporal sequence of the films . The relationship of changes between the baseline and the 3-year follow-up arteriograms and subsequent clinical coronary events was examined . SETTING Three university hospitals and one private primary care facility . PATIENTS A total of 838 patients , with 417 patients r and omized to the control group and 421 to the intervention group . Of all patients , 695 had baseline and 3-year arteriograms . INTERVENTION The control group received American Heart Association Phase II diet instruction and the intervention group received identical dietary instruction plus a partial ileal bypass operation . MAIN OUTCOME MEASURE The use of arteriographic changes as a predictor of subsequent clinical coronary events . RESULTS Changes between the baseline and the 3-year coronary arteriographic overall disease assessment were significantly associated with subsequent overall and atherosclerotic coronary heart disease mortality ( P less than .01 ) . For the combined end point of atherosclerotic coronary heart disease mortality or confirmed nonfatal myocardial infa rct ion , a significant relationship between the overall disease assessment and subsequent clinical events was found in the control group ( P less than .0001 ) and in the surgery group ( P = .04 ) . For this combined end point , however , the control and the surgery groups were different with respect to clinical coronary events after 3 years , stratified by the baseline to 3-year overall disease assessment ( P less than .001 , unadjusted ; P = .06 , adjusted for 3-year clinical covariates ) . CONCLUSIONS Coronary arteriographic changes can be used in atherosclerosis intervention trials as a limited surrogate end point for certain clinical coronary events . This relationship is statistically compelling for overall mortality and atherosclerotic coronary heart disease mortality . For an individual patient , changes in the severity of coronary atherosclerosis seen on sequential coronary arteriograms can serve as prognostic indicators for subsequent overall or atherosclerotic coronary heart disease mortality", "The objective of this study was to examine the effects of lovastatin on bone mineral density ( BMD ) of postmenopausal women with type 2 diabetes mellitus ( DM ) . The study was an open-label clinical trial conducted from March 2002 to November 2003 . Fifty-five postmenopausal women age 54–67 years with type 2 DM were allocated to lovastatin-treated and control ( without lovastatin ) groups based on low-density lipoprotein cholesterol ( LDL-C ) > 130 or ≤130 mg/dl . The first group received lovastatin ( 20 mg daily titrated every 3 months to keep LDL-C less than 130 mg/dl ) for a total of 18 months . The second group received their own diabetic regimen without statin . The BMD of the lumbar spine ( L1-L4 ) , femoral neck , Wards triangle , trochanter and total hip was measured by dual-energy X-ray absorptiometry at baseline and after 18 months . In the 28 women treated with lovastatin , the BMD increased in lumbar spine ( from 0.946 ( 0.122 ) to 0.978 ( 0.135 ) g/cm2 , p treated with statin , the changes in BMD at all bone sites were not statistically significant . BMD was higher in femoral neck ( 1.2 % vs. −2.7 % , p0.05 ) at the end of the study . Treatment with lovastatin may prevent bone loss in postmenopausal women with type 2 DM", "Objective To test the primary hypothesis that a newer antihypertensive treatment regimen ( calcium channel blocker ± an angiotensin converting enzyme inhibitor ) is more effective than an older regimen ( β-blocker ± a diuretic ) in the primary prevention of coronary heart disease ( CHD ) . To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol ⩽ 6.5 mmol/l . Design Prospect i ve , r and omized , open , blinded endpoint trial with a double-blinded 2 × 2 factorial component . Setting Patients were recruited mainly from general practice s. Patients Men and women aged 40–79 were eligible if their blood pressure was ⩾160 mmHg systolic or ⩾ 100 mmHg diastolic ( untreated ) or ⩾140 mmHg systolic or ⩾ 90 mmHg diastolic ( treated ) at r and omization . Interventions Patients received either amlodipine ( 5/10 mg ) ± perindopril ( 4/8 mg ) or atenolol ( 50/100 mg ) ± bendroflumethiazide ( 1.25/2.5 mg ) + K+ with further therapy as required to reach a blood pressure of ⩽140 mmHg systolic and 90 mmHg diastolic . Patients with a total cholesterol of ⩽ 6.5 mmol/l were further r and omized to receive either atorvastatin 10 mg or placebo daily . Main outcome measure Non-fatal myocardial infa rct ion ( MI ) and fatal coronary heart disease ( CHD ) . Results 19 342 men and women were initially r and omized , of these 10 297 were also r and omized into the lipid-lowering limb . All patients had three or more additional cardiovascular risk factors . Conclusions The study has 80 % power ( at the 5 % level ) to detect a relative difference of 20 % in CHD endpoints between the calcium channel blocker-based regimen and the β-blocker-based regimen . The lipid-lowering limb of the study has 90 % power at the 1 % level to detect a relative difference of 30 % in CHD endpoints between groups", "Abstract Objective : To evaluate the effects on mood of a substantial and prolonged reduction in total cholesterol concentration . Design : R and omised placebo controlled comparison of patients who had been allocated to receive simvastatin 20 mg or 40 mg daily versus those allocated matching placebo in a ratio of 2:1 . Follow up at an average of 152 weeks after r and omisation . Subjects : Men and women aged between 40 and 75 years at entry with blood total cholesterol of 3.5 mmol/l or greater , who were considered to be at higher than average risk of coronary heart disease based on medical history . Main outcome measures : The shortened profile of mood states question naire , reported use of psychotropic medication , and symptoms possibly related to mood . Results : Simvastatin reduced total cholesterol by 1.9 mmol/l ( 26.7 % ) at the time of follow up . Among all 621 patients r and omised to simvastatin ( 414 patients ) or placebo ( 207 patients ) there were no significant differences in the use of psychotropic medication or in reports of symptoms possibly related to mood . Of these patients , 491 ( 334 simvastatin , 157 placebo ) completed the mood question naire , and there were no significant differences between the treatment groups in total or subscale scores , even when patients with low baseline cholesterol concentrations or elderly subjects were considered separately . Conclusion : These results do not support the hypothesis that treatment to lower cholesterol concentration causes mood disturbance . Key messages A r and omised placebo controlled trial of simvas- tatin ( a drug that lowers cholesterol concentration substantially ) showed no associated mood distur- bance over a period of nearly three years in subjects with cardiovascular disease and no pre-existing psychiatric conditions No effects on mood were seen in individuals with low baseline cholesterol concentrations or in older individuals , and there were no differences in use of psychotropic drugs between the treatment groups These results give little support to the idea that reducing cholesterol concentration has adverse effects on", "INTRODUCTION The 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors , named statins , are well-established cholesterol-lowering drugs able to reduce cardiovascular risk in hypercholesterolemic patients . The possible effect of statin on bone tissue , so-called pleiotropic effects has received particular attention . Studies reported a positive effect of statin on bone tissue in both of animal and human study by enhancing the expression of the bone morphogenetic proteins ( BMPs ) , in particular of BMP2 , which in turn leads to osteoblast differentiation and bone formation including interfering with osteoclastic activity . In a systematic review , the lipophilic statin as simvastatin had positive effect to bone mineral density ( BMD ) better than the more hydrophilic statin such as atorvastatin and fluvastatin . This study was aim ed to compare efficacy of medical therapy between HMG-CoA reductase inhibitor and non-HMG-CoA reductase inhibitor group to changing of bone mineral density and bone markers in the patients with hyperlipidemia . MATERIAL S AND METHODS A prospect i ve r and omized control trial study enrolled the 212 hyperlipidemia with osteopenia patients to study in year 2006 - 2008 . All subjects were r and omized to 2 groups between statin and non-statin group ; the patients were screened by inclusion criteria and measured in bone mineral density ( BMD ) , bone marker and blood chemistry . All data were analyzed by difference of changing in bone marker and BMD between statin and non-statin groups using paired t test . RESULTS The present study showed 212 hyperlipidemia with osteopenia patients of which 106 patients in statin group had mean age ( 63.17+/-9.51 years ) and the same number of patients in non-statin group had mean age ( 60.96+/-8.9 years ) . All subjects were 63 patients in male and 149 patients in female . Difference of bone formation marker and BMD between after and before was significantly higher than in statin group and the difference of bone resorption marker was also significantly lower than in statin group . CONCLUSION The lipophilic statin as moderate to high dose of simvastatin had beneficial positive effect to increasing BMD and could be additive use for prevention of bone loss in hyperlipidemia patients", "PURPOSE The Carotid Atherosclerosis Italian Ultrasound Study ( CAIUS ) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness ( IMT ) in 305 asymptomatic patients from a Mediterranean country . PATIENTS AND METHODS Eligibility included hypercholesterolemia ( baseline means : low-density lipoprotein [ LDL ] = 4.68 mmol/L , high-density lipoprotein [ HDL ] = 1.37 mmol/L ) , and at least one 1.3 to pravastatin ( 40 mg/day , n = 151 ) or placebo ( n not equal to 154 ) . Ultrasound imaging was used to quantify IMT at baseline , and semiannually thereafter for up to 3 years . The mean of the 12 maximum IMTs ( MMaxIMT ) , was calculated for each patient visit , and used to determine each patient 's longitudinal progression slope . The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point . RESULTS Five serious cardiovascular events ( 1 fatal myocardial infa rct ion ) , and 7 drop-outs for cancer were registered . In the pravastatin group , LDL decreased -0.22 after 3 months versus -0.01 in the placebo group , and remained substantially unchanged afterward ( -0.23 versus + 0.01 at 36 months , respectively ) . Progression of the MMaxIMT was 0.009 + /- 0.0027 versus -0.0043 + /- 0.0028 mm/year ( mean + /- SE , P pravastatin groups , respectively . IMT progression slopes diverged after 6 months of treatment . CONCLUSIONS Pravastatin stops the progression of carotid IMT in asymptomatic , moderately hypercholesterolemic men and women . This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates , and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development", "BACKGROUND The JUPITER ( Justification for the Use of Statins in Prevention : An Intervention Trial Evaluating Rosuvastatin ) trial suggests that increased high-sensitivity C-reactive protein ( hsCRP ) concentrations may be useful in decisions about the initiation of statin therapy for primary prevention of vascular disease . Although studies of specific population s have suggested that hsCRP is a reliable longitudinal marker , it is unclear how strongly hsCRP tracks in individuals after a single increased concentration . METHODS We evaluated tracking of hsCRP in 8901 individuals r and omized to placebo in the JUPITER trial . These individuals had screening LDL cholesterol concentrations or = 2 mg/L , with subsequent hsCRP measurements made before r and omization ; at 13 weeks ; 1 , 2 , 3 , and 4 years later ; and at trial termination . Longitudinal trends and associations were evaluated nonparametrically with box plots and Spearman correlations . After data transformation to achieve normality , repeated- measures regression models estimated the intraclass correlation of hsCRP , with and without controlling for known demographic , lifestyle , and medical determinants of hsCRP concentration . For comparison , we evaluated tracking of systolic and diastolic blood pressure ; total , LDL , and HDL cholesterol ; and fasting triglycerides . RESULTS The median hsCRP concentration in these untreated individuals showed modest regression to the mean over time , declining from 3.8 mg/L at r and omization to 3.4 mg/L at 4 years . Tracking correlations for hsCRP over time were comparable to those for blood pressure and LDL cholesterol , but lower than those for HDL , fasting triglycerides , and total cholesterol . The intraclass correlation for repeated hsCRP measurements was 0.54 ( 95 % CI , 0.53 - 0.55 ) without covariate adjustment and 0.50 ( 95 % CI , 0.49 - 0.51 ) after adjustment for demographic , lifestyle , and comorbidity determinants . CONCLUSIONS Concentrations of hsCRP show strong tracking , even after selection of individuals with initially high values . Without statin therapy , increased concentrations of hsCRP generally remain high over time", "OBJECTIVE To determine the effect of lovastatin therapy on health-related quality of life in older persons . DESIGN A prospect i ve , r and omized , double blind clinical trial . SETTING Four university medical center research clinics . PARTICIPANTS There were 431 men and women , primarily 65 years of age or older , with low density lipoprotein levels greater than 159 mg/dL and less than 221 mg/dL. Exclusion criteria included a Mini-Mental state score less than 24 or presence of recent cardiovascular events or other serious chronic disease likely to shorten survival . INTERVENTION All participants were administered the National Cholesterol Education Program step one diet and were then r and omized to placebo , 20 mg lovastatin , or 40 mg lovastatin . MEASUREMENTS Areas of health-related quality of life assessed in the Cholesterol Reduction in Seniors Program ( CRISP ) included : ( 1 ) physical functioning , ( 2 ) sleep behavior , ( 3 ) social support , ( 4 ) depression , ( 5 ) cognitive function , and ( 6 ) health perception . Three global change questions asked the patients to judge change in general health since starting the study diet or the study medication and change in ability to function or care for self . Although some patients were followed for a total of 12 months , all participants were followed for 6 months , and 6-month data have been used for the primary analysis in this paper . RESULTS Patients treated with 20 mg of lovastatin had a 17 % and 24 % reduction in total cholesterol and LDL-cholesterol , respectively . Patients treated with the 40-mg lovastatin dose achieved reductions of 20 % for total cholesterol and 28 % for LDL-cholesterol . Complaints of possible adverse events were remarkably similar in the two active treatment groups and the placebo group . At 6 months of follow-up there were no statistically significant differences found in mean change scores from baseline between treatment groups on the health-related quality of life measures ( physical functioning , sleep , social support , depression , cognitive function scales , health perception ) or global questions . CONCLUSIONS This study demonstrates that lovastatin was extremely well tolerated in an older cohort , both with regard to symptoms and to health-related quality of life", "Table . SI Units and Drugs Many reports have shown the efficacy of the combination of bile-absorbing resin and 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor ( statin class ) therapies [ 1 - 4 ] . Primarily , this resin-statin treatment regimen has been targeted to patients with low-density lipoprotein ( LDL ) cholesterol levels greater than 6.47 mmol/L ( > 250 mg/dL ) , a population presumably enriched with familial hypercholesterolemic patients . Consequently , dosages have been large , with both the statin and resin agents administered at the upper ends of their respective dosing ranges . However , this group of markedly hypercholesterolemic patients does not represent the typical person identified through the adult National Cholesterol Education Program guidelines . For the considerably larger pool of persons with LDL cholesterol between 4.14 mmol/L and 6.21 mmol/L ( 160 mg/dL and 240 mg/dL ) , a safe , convenient , well-tolerated , and effective dosing method is essential . Low-dose combination therapy is thought to be beneficial because long-term compliance is enhanced and safety maximized while efficacy is preserved . It has been suggested that side effects with statin agents are dose-dependent , thereby implying a benefit with routine use of lower dosing . In contrast , side effects attributed to resin are equivalent at varying doses within the usual dosing range [ 5 , 6 ] . Thus , the benefit of lower resin dose would be confined to enhanced palatability and tolerability . The overall cholesterol lowering with such a low-dose combination , however , still remains unknown . Fluvastatin sodium ( Lescol , S and oz ; East Hanover , New Jersey ) , a new water-soluble cholesterol-lowering agent that acts through the inhibition of HMG-CoA reductase , is the first entirely synthetic HMG-CoA reductase inhibitor and differs structurally from the fungal derivatives of compactin [ 7 ] . Fluvastatin has a distinctive biopharmaceutical profile ; it has a high rate of absorption that is not influenced by food intake , possesses no circulating active metabolites , is 98 % protein-bound , does not cross the blood-brain barrier , has a systemic half-life of 30 minutes , and is 95 % excreted by the liver [ 8 ] . We evaluated the LDL cholesterol-lowering efficacy of various combinations of low-dose resin and statin treatments , using cholestyramine ( Questran Light ; Bristol ) and fluvastatin . The study population included mostly patients with hypercholesterolemia who would , according to the new National Cholesterol Education Program guidelines for adults ( LDL cholesterol > 4.91 mmol/L [ > 190 mg/dL ] or LDL cholesterol > 4.14 mmol/L [ > 160 mg/dL ] with two risk factors ) , be advised to receive medication . Methods The study protocol was design ed by mutual consent of the investigators and S and oz Research Institute , with all data collected by the investigators subject to review and analysis by S and oz Research Institute . The interpretation of the data in this article is based on the mutual consent of all su bmi tting authors . All patients were consecutively r and omized based on a diagnosis of hypercholesterolemia confirmed during drug washout with an LDL cholesterol level of at least 4.14 mmol/L ( 160 mg/dL ) , despite dietary intervention , and a plasma triglyceride level of no more than 3.39 mmol/L ( 300 mg/dL ) . Persons were excluded if they had a history of homozygous familial hypercholesterolemia , secondary hyperlipidemia , liver disease , renal disease , diabetes , myocardial infa rct ion or angioplasty within 6 months of study entry , or uncontrolled hypertension . The patients ' mean age was 54.1 years ; 54 % were male ; 95 % were white and 3 % were black . The treatment groups did not differ in baseline demographic characteristics . The study was approved by the institutional review boards for human research of all participating institutions . Informed consent was obtained from all patients . Treatment Plan This study consisted of a 6-week , single-blind , placebo washout period followed by a 24-week , double-blind treatment period divided into three phases ( Figure 1 ) . Patients were withdrawn from hypolipidemic therapy for at least 4 weeks ( 1 year for probucol ) before entry into the washout period . In addition , patients were instructed by a registered dietitian to follow a cholesterol-lowering diet ( American Heart Association or National Cholesterol Education Program step 1 ) for at least 8 weeks before entry into the washout period and throughout the study , and a Food Record Rating score of 15 or less was required for study entry [ 9 ] . Patients with aspartate aminotransferase or alanine aminotransferase values greater than 1.5 times the upper limit of laboratory normal during the washout period were excluded from the study . Figure 1 . Study design and numbers of patients initially assigned to each treatment group . At the end of the placebo washout period , patients who satisfied all entry criteria entered the 24-week , double-blind treatment period , which consisted of three 8-week phases . For the first 8 weeks ( phase 1 ) , patients were assigned r and omly into six groups receiving blinded study medication : two groups receiving placebo ; two receiving 10 mg of fluvastatin ; and two receiving 20 mg of fluvastatin . In phases 2 and 3 of the study , one placebo group , one 10-mg fluvastatin group , and one 20-mg fluvastatin group received open-label cholestyramine in addition to the blinded study drug , whereas the other three groups remained on fluvastatin or placebo monotherapy for the rest of the trial . In phase 2 , the dose of cholestyramine added to the regimen of patients in the three combination groups was 4 g twice daily . In phase 3 , the dose of cholestyramine was increased to 8 g twice a day for these patients . Blinded medication was taken once daily at bedtime , approximately 4 hours after the evening meal . Patients receiving open-label cholestyramine took their medication just before breakfast and dinner . Compliance with all treatment regimens was assessed by pill or packet count . Study Evaluations Patients were assessed every 2 weeks during the placebo washout period and every 4 weeks during the 24-week treatment period . Dietary compliance was determined by Food Record Rating scores derived from dietary records collected throughout the study [ 9 ] . Twelve-hour fasting blood sample s were obtained at each visit for lipid determinations , which were done by a central laboratory ( Medical Research Laboratories ; Cincinnati , Ohio ) . Low-density lipoprotein cholesterol was calculated according to the Friedewald formula [ 10 ] . Total cholesterol , high-density lipoprotein cholesterol , and plasma triglycerides were measured on a 737 Hitachi analyzer ( Boehringer Mannheim Diagnostics ; Indianapolis , Indiana ) with microenzymatic procedures [ 11 ] fully st and ardized , and part 3 was monitored through the National Heart , Lung , and Blood Institute and Centers for Disease Control and Prevention Lipid St and ardization Program [ 12 , 13 ] . Safety was evaluated at baseline and at intervals throughout the study . These evaluations included measurements of blood pressure and pulse ; physical , ophthalmologic , and electrocardiographic examinations ; and routine laboratory tests . Investigators were asked to assess , in a blinded fashion , each adverse event and laboratory abnormality for a potential relation to blinded study drug administration , based on their clinical experience and judgment . Statistical Analysis All statistical comparisons were made using two-tailed tests at the P total cholesterol , LDL cholesterol , high-density lipoprotein cholesterol , and triglycerides between the treatment groups . In each model , we did tests of significance of the percentage change from baseline within each group and of differences in mean percentage change between treatment groups . In determining safety , a newly occurring abnormality was defined as an abnormality reported during the active treatment period but not reported during the placebo washout period , and a worsening abnormality was an abnormality that worsened from the placebo washout period to the active treatment period . The number of patients with newly occurring or worsening abnormalities in each treatment group was determined , and the proportions were compared using the Fisher exact test . Results Of 460 patients from nine study centers screened , 224 met study criteria and were r and omized into the double-blind treatment period of this study ; 203 completed all phases of treatment . Fifteen ( 10 % ) of 150 fluvastatin-treated patients and 6 ( 8 % ) of 74 placebo- or cholestyramine-treated or both ( that is , non-fluvastatin-treated ) patients were dropped during the double-blind treatment period . Five fluvastatin-treated patients ( 1 receiving concomitant cholestyramine ) and 1 placebo-treated patient ( receiving concomitant cholestyramine ) dropped out because of adverse events . These events , each of which occurred in one patient , were angina , myalgia , stomatitis and glossitis , heartburn and indigestion , elevated transaminase levels , and alopecia . Of these , only the instance of stomatitis and glossitis was judged by the investigator to be definitely related to the drug . One patient", "Background Statins reduce cardiovascular events and progression of carotid intima-media thickness ( IMT ) . & bgr;-Blockers are also known to reduce cardiovascular events , but less is known about their effects on carotid IMT . Methods and Results We conducted a r and omized , double-blind , placebo-controlled , single-center trial to compare the effects of low-dose metoprolol CR/XL ( 25 mg once daily ) and fluvastatin ( 40 mg once daily ) on the progression of carotid IMT during 36 months of treatment in 793 subjects who had carotid plaque but no symptoms of carotid artery disease . Changes in mean IMT in the common carotid artery and maximal IMT in the bulb were the main outcome variables . Death and cardiovascular events were monitored . Progression of IMTmax in the carotid bulb at both 18 and 36 months was reduced by metoprolol CR/XL ( −0.058 mm/y ; 95 % CI , −0.094 to −0.023;P = 0.004 ; and −0.023 mm/y ; 95 % CI , −0.044 to −0.003;P = 0.014 , respectively ) . Incidence of cardiovascular events tended to be lower in metoprolol CR/XL – treated patients ( 5 versus 13 patients , P = 0.055 ) . Rate of IMTmean progression in the common carotid at 36 months was reduced by fluvastatin ( −0.009 mm/y ; 95 % CI , −0.015 to −0.003;P = 0.002 ) . Women in the fluvastatin group had increased frequency of transiently high liver enzymes . Conclusions This is the first r and omized trial to show that a & bgr;-blocker can reduce the rate of progression of carotid IMT in clinical ly healthy , symptom-free subjects with carotid plaque . This suggests that & bgr;-blockers may have a favorable effect on atherosclerosis development ", "OBJECTIVE The objectives of the Cost Effectiveness of Lipid Lowering ( CELL ) study were twofold : ( i ) to evaluate the effect on overall cardiovascular risk of two types of health care advice ( \" usual ' and \" intensive ' ) given in primary care , with or without pharmacological medication , with the target being to attain a moderate decrease in cholesterol ; ( ii ) to evaluate the ritual of daily medication on compliance with the health care advice . DESIGN A prospect i ve , double-blind , r and omized , controlled trial of 18 months ' duration . SETTING The study was carried out in 32 health centres ( out of a total of approximately 850 ) in Sweden . SUBJECTS In all , 681 subjects , aged 30 - 59 years , were r and omized . They had at least two cardiovascular risk factors in addition to moderate primary hyperlipidaemia ( total cholesterol of at least 6.50 mmol L-1 on three occasions measured by Reflotron triglycerides less than 4.0 mmol L-1 and an LDL : HDL cholesterol ratio of more than 4.0 ) . Most ( 87 % ) of the subjects were males ; 626 subjects ( 92 % ) completed the 18-month follow-up . INTERVENTION Half the subjects were r and omized to ' intensive advice ' given in group sessions led by doctors and nurses in primary care . The other half received ' usual advice ' . In each of the two advice groups , one-third received an active lipid-lowering drug ( pravastatin ) , one-third placebo , and one-third no drug at all . The tablets were titrated to achieve a 15 % reduction in cholesterol . MAIN OUTCOME MEASURES Changes in the overall Framingham risk score , and the development of adverse events in each group . RESULTS The change in Framingham risk score was significantly reduced only in subjects taking lipid-lowering medication ( together with intensive advice -0.13 ; 95 % CI-0.20 , -0.06 , and together with usual advice -0.16 ; 95 % CI -0.23 , -0.09 ) . The other subjects receiving intensive advice tended to fare better than those on usual advice . Lifestyle was not influenced significantly over the study period . The ritual of daily medication did not affect the outcome . CONCLUSION As expected , lipid-lowering medication reduced serum cholesterol as well as overall cardiovascular risk in subjects with several risk factors for cardiovascular disease . There was no additive effect of intensive advice to these subjects . However , there was a meagre but significant effect of intensive advice in subjects not receiving active lipid-lowering drugs . One explanation for this difference may be that those on active lipid-lowering medication who had substantial drops in cholesterol might have felt less inclined to change their lifestyle compared with those on other treatment regimens who had less successful drops in cholesterol . There was no benefit from the ritual of taking daily medication", "BACKGROUND There are few data on the role of lipid lowering in the primary prevention of coronary heart disease ( CHD ) in diabetic patients . This paper describes the design of a collaborative clinical trial between Diabetes UK , the NHS Research and Development Directorate and Pfizer UK , that addresses this question . METHODS The Collaborative AtoRvastatin Diabetes Study ( CARDS ) is a multicentre , r and omized , placebo-controlled , double-blind clinical trial of primary prevention of cardiovascular disease in patients with Type 2 diabetes . The primary objective is to investigate whether treatment with the hydroxymethylglutaryl coenzyme A reductase inhibitor , atorvastatin , reduces the incidence of major cardiovascular events . At entry patients have at least one other risk factor for CHD in addition to diabetes , namely current smoking , hypertension , retinopathy , or micro- or macroalbuminuria . At r and omization patients have been selected for a serum low-density lipoprotein ( LDL ) cholesterol concentration triglycerides The trial includes 2838 men and women aged 40 - 75 years . This report describes the design and administration of the study and review s the evidence to date of the effectiveness of lipid-lowering therapy in Type 2 diabetes . CONCLUSIONS The case for lipid-lowering therapy for the primary prevention of CHD in diabetes has not been demonstrated . CARDS will provide essential information on the extent of any benefits and adverse effects of lipid-lowering therapy in diabetic patients without prior CHD", "BACKGROUND Patients with coronary artery disease and abnormalities of serum lipids often have endothelial vasodilator dysfunction , which may contribute to ischemic cardiac events . Whether cholesterol-lowering or antioxidant therapy can restore endothelium-dependent coronary vasodilation is unknown . METHODS We r and omly assigned 49 patients ( mean serum cholesterol level , 209 + /- 33 mg per deciliter [ 5.40 + /- 0.85 mmol per liter ] ) to receive one of three treatments : an American Heart Association Step 1 diet ( the diet group , 11 patients ) ; lovastatin and cholestyramine ( the low-density lipoprotein [LDL]-lowering group , 21 patients ) ; or lovastatin and probucol ( the LDL-lowering-antioxidant group , 17 patients ) . Endothelium-dependent coronary-artery vasomotion in response to an intracoronary infusion of acetylcholine ( 10(-8 ) to 10(-6 ) M ) was assessed at base line and after one year of therapy . Vasoconstrictor responses to these doses of acetylcholine are considered to be abnormal . RESULTS Treatment result ed in significant reductions in LDL cholesterol levels of 41 + /- 22 percent in the LDL-lowering-antioxidant group and 38 + /- 20 percent in the LDL-lowering group ( P maximal changes in coronary-artery diameter with acetylcholine at base line and at follow-up were -19 and -2 percent , respectively , in the LDL-lowering-antioxidant group , -15 and -6 percent in the LDL-lowering group , and -14 and -19 percent in the diet group ( P vasoconstrictor response was seen in the LDL-lowering-antioxidant group . CONCLUSIONS The improvement in endothelium-dependent vasomotion with cholesterol-lowering and antioxidant therapy may have important implication s for the activity of myocardial ischemia and may explain in part the reduced incidence of adverse coronary events that is known to result from cholesterol-lowering therapy", "The objective of this multicenter , r and omized , open-label , parallel-group , 8-week study was to evaluate the comparative dose efficacy of the 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor atorvastatin 10 , 20 , 40 , and 80 mg compared with simvastatin 10 , 20 , and 40 mg , pravastatin 10 , 20 , and 40 mg , lovastatin 20 , 40 , and 80 mg , and fluvastatin 20 and 40 mg . Investigators enrolled 534 hypercholesterolemic patients ( low-density lipoprotein [ LDL ] cholesterol > or = 160 mg/dl [ 4.2 mmol/L ] and triglycerides The efficacy end points were mean percent change in plasma LDL cholesterol ( primary ) , total cholesterol , triglycerides , and high-density lipoprotein cholesterol concentrations from baseline to the end of treatment ( week 8) . Atorvastatin 10 , 20 , and 40 mg produced greater ( p LDL cholesterol , -38 % , -46 % , and -51 % , respectively , than the milligram equivalent doses of simvastatin , pravastatin , lovastatin , and fluvastatin . Atorvastatin 10 mg produced LDL cholesterol reductions comparable to or greater than ( p simvastatin 10 , 20 , and 40 mg , pravastatin 10 , 20 , and 40 mg , lovastatin 20 and 40 mg , and fluvastatin 20 and 40 mg . Atorvastatin 10 , 20 , and 40 mg produced greater ( p total cholesterol than the milligram equivalent doses of simvastatin , pravastatin , lovastatin , and fluvastatin . All reductase inhibitors studied had similar tolerability . There were no incidences of persistent elevations in serum transaminases or myositis", "BACKGROUND Statins lower high-sensitivity C-reactive protein ( hsCRP ) and cholesterol concentrations , and hypothesis generating analyses suggest that clinical outcomes improve in patients given statins who achieve hsCRP concentrations less than 2 mg/L in addition to LDL cholesterol less than 1.8 mmol/L ( However , the benefit of lowering both LDL cholesterol and hsCRP after the start of statin therapy is controversial . We prospect ively tested this hypothesis . METHODS In an analysis of 15 548 initially healthy men and women participating in the JUPITER trial ( 87 % of full cohort ) , we prospect ively assessed the effects of rosuvastatin 20 mg versus placebo on rates of non-fatal myocardial infa rct ion , non-fatal stroke , admission for unstable angina , arterial revascularisation , or cardiovascular death ( prespecified endpoints ) during a maximum follow-up of 5 years ( median 1.9 years ) , according to on-treatment concentrations of LDL cholesterol ( > /=1.8 mmol/L or /=2 mg/L or placebo , participants allocated to rosuvastatin who achieved LDL cholesterol less than 1.8 mmol/L had a 55 % reduction in vascular events ( event rate 1.11 vs 0.51 per 100 person-years ; hazard ratio [ HR ] 0.45 , 95 % CI 0.34 - 0.60 , p hsCRP less than 2 mg/L a 62 % reduction ( event rate 0.42 per 100 person-years ; HR 0.38 , 95 % CI 0.26 - 0.56 , p LDL cholesterol and hsCRP reductions were only weakly correlated in individual patients ( r values vascular events in participants allocated to rosuvastatin who achieved both LDL cholesterol less than 1.8 mmol/L and hsCRP less than 2 mg/L ( event rate 0.38 per 100 person-years ; adjusted HR 0.35 , 95 % CI 0.23 - 0.54 ) , versus a 33 % reduction in those who achieved one or neither target ( event rate 0.74 per 100 person-years ; HR 0.67 , 95 % CI 0.52 - 0.87 ) ( p across treatment groups LDL cholesterol less than 1.8 mmol/L and hsCRP less than 1 mg/L , we noted a 79 % reduction ( event rate 0.24 per 100 person-years ; HR 0.21 , 95 % CI 0.09 - 0.52 ) . Achieved hsCRP concentrations were predictive of event rates irrespective of the lipid endpoint used , including the apolipoprotein B to apolipoprotein AI ratio . INTERPRETATION For people choosing to start pharmacological prophylaxis , reduction in both LDL cholesterol and hsCRP are indicators of successful treatment with rosuvastatin", "Until recently , the role of statin therapy in diabetic patients without clinical signs or symptoms of coronary heart disease had been inadequately defined . The Collaborative Atorvastatin Diabetes Study ( CARDS ) is a prospect i ve , r and omized , placebo-controlled trial design ed to compare the effects of atorvastatin with placebo in preventing primary coronary events in diabetic patients . After a median of only 3.9 years ( the study was terminated approximately 2 years early due to the magnitude of benefit attributable to atorvastatin therapy ) , risk for major cardiovascular events was decreased by 37 % , acute coronary heart disease-related events were also reduced by 36 % , coronary revascularizations by 31 % , and stroke by 48 % . Benefit emerged within 1 year of initiating therapy", "OBJECTIVES This study investigated the effect of reducing serum lipids on carotid artery intima-media thickness ( IMT ) in asymptomatic patients with hypercholesterolemia from Fukuoka , Japan . BACKGROUND Carotid atherosclerosis is a strong , independent predictor of morbidity and mortality in patients with coronary heart disease ( CHD ) . METHODS A total of 246 asymptomatic hypercholesterolemic patients ( mean age 66 years ) were r and omized to receive either probucol ( 500 mg/day , n = 82 ) or pravastatin ( 10 mg/day , n = 83 ) or to enter a control group ( diet alone , n = 81 ) ; they were followed for two years . The change in IMT in the common carotid artery was the primary end point measure , and the incidence of major cardiovascular events was the secondary measure . RESULTS Over the two-year period , serum low-density lipoprotein ( LDL ) cholesterol was significantly reduced in the pravastatin group ( 36 % ) , the probucol group ( 29 % ) and the control group ( 12 % ) ( p probucol and pravastatin groups showed a significant reduction in IMT ( -13.9 % and -13.9 % and p IMT thickening ( 23.2 % ; p rate of IMT increase , independently of its reduction of LDL or high-density lipoprotein cholesterol . Moreover , there was a significantly lower incidence of cardiac events in the probucol group ( 2.4 % ) than in the control group ( 13.6 % ) ( p = 0.0136 ) . CONCLUSIONS Probucol reduced cholesterol levels and stabilized plaque , leading to a lower incidence of cardiac events in these hypercholesterolemic patients", "AIMS To assess the additional benefit gained from high compliance in the West of Scotl and Coronary Prevention Study and to examine cases where withdrawal from trial medication was due to an adverse event . METHODS The incidence of definite coronary heart disease or non-fatal myocardial infa rct ion , cardiovascular mortality , definite or suspect coronary heart disease death or non-fatal myocardial infa rct ion , the need for coronary revascularization procedures , all-cause mortality and incident cancers were measured in the entire cohort and compared with the high compliance group . The adverse events associated with withdrawal were coded by body system . RESULTS In subjects with compliance > or = 75 % , treatment with pravastatin result ed in a 38 % risk reduction for definite coronary heart disease death or non-fatal myocardial infa rct ion and for cardiovascular mortality , a 46 % reduction in risk or coronary revascularization and a 32 % risk reduction ( P = 0.015 ) for all-cause mortality . CONCLUSIONS The analysis of the effect of pravastatin in the subgroup of high compliers to r and omized medication demonstrated a substantial increase in the estimated risk reductions in comparison with that achieved in the intention-to-treat analysis . This result has significant implication s for the motivation of high compliance among patients and for the assessment of the cost-effectiveness of treatment", "Endothelial function is known to predict cardiovascular disease . The aim of the present study was to examine whether endothelial function in smokers with normal cholesterol levels could be normalized by treatment with 80 mg of atorvastatin in comparison with a control group . Healthy smokers ( n=20 ) and non-smokers ( n=20 ) were r and omized to receive 80 mg of atorvastatin or placebo in an open r and omized cross-over study , followed by measurement of endothelial functional [ FMD ( flow-mediated dilation ) ] . At baseline , smokers had a lower FMD compared with the non-smoking group ( 2.2+/-0.5 and 4.5+/-0.8 % respectively ; P FMD increased significantly ( P atorvastatin and returned to basal levels during placebo ( 2.3+/-0.6 % ) . In the non-smoking group , FMD was unaffected by both atorvastatin and placebo . The net change of total cholesterol or LDL ( low-density lipoprotein)-cholesterol was not associated with the net change in FMD when the study group was considered as a whole or the smoking group was considered separately . In conclusion , improved endothelial function was observed in a group of smokers when they were received 80 mg of atorvastatin , whereas atorvastatin had no effect on endothelial function in the non-smoking group . The improved FMD among smokers was independent of the decrease in LDL-cholesterol during atorvastatin treatment . The results show that poor endothelial function in smokers with normal lipid levels can be improved by a statin treatment", "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", "This double-blind study to evaluate long-term efficacy and safety of atorvastatin was performed in 31 community- and university-based research centers in the USA to directly compare a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor ( reductase inhibitor ) to an accepted drug of this class in patients with moderate hypercholesterolemia . Participants remained on a cholesterol-lowering diet throughout the study . One thous and forty-nine patients were r and omized to receive atorvastatin 10 mg , lovastatin 20 mg , or placebo . At 16 weeks the placebo group was r and omized to either atorvastatin or lovastatin treatment . At 22 weeks , patients who had not met low-density lipoprotein ( LDL ) cholesterol target levels doubled the dose of reductase inhibitor . Efficacy evaluation was mean percent change from baseline in LDL cholesterol , triglycerides , total cholesterol , high-density-lipoprotein cholesterol , and apolipoprotein B ( apoB ) . Safety profiles as determined by change from baseline in laboratory evaluations , ophthalmologic parameters , and reporting of adverse events were similar for the 2 reductase inhibitors . After 52 weeks , the atorvastatin group maintained a significantly greater reduction in LDL cholesterol ( -37 % vs -29 % ) , triglyceride ( -16 % vs -8 % ) , total cholesterol ( -27 % vs -21 % ) , and apoB ( -30 % vs -22 % ) ( p patients receiving atorvastatin achieved LDL cholesterol target levels than did lovastatin patients ( 78 % vs 63 % , respectively ) , particularly those with coronary heart disease ( 37 % vs 11 % , respectively ) . Atorvastatin is highly effective and well tolerated in patients with primary hypercholesterolemia with no increased risk of adverse events", "Lp(a ) level is relatively stable in each individual and is mainly under genetic control . Attempts made to lower Lp(a ) with pharmacological means gave conflicting results . In order to further evaluate the effect of hypocholesterolemic drugs on Lp(a ) level , 66 patients with primary hypercholesterolemia were selected . The vast majority of the patients had Lp(a ) concentration at the low end of the range of distribution , 7 had undetectable Lp(a ) levels and only 2 had Lp(a ) higher than 30 mg/dl . No relationship was found between Lp(a ) level and serum and lipoprotein lipids . In 12 patients serum cholesterol was well controlled by diet alone and the patients continued the diet for up to 8 months . The other patients were r and omly subdivided into 3 groups of therapy . The first group received slow release bezafibrate 400 mg once a day , the second one pravastatin 20 mg once a day and the third one simvastatin 10 - 40 mg once a day . Drug therapy lasted for 8 months . At the end of the period , 22 of 29 patients treated with the 2 HMG-CoA reductase inhibitors had Lp(a ) higher than baseline . The difference was statistically significant in both groups of patients . No significant change in Lp(a ) was observed in diet and in bezafibrate group . Serum and LDL cholesterol significantly decreased in all the 3 drug groups . The increase in Lp(a ) after the 2 HMG-CoA reductase was small enough to have negligible effects on cardiovascular risk , but raises the problem of the role of LDL receptor in the catabolism of Lp(a )", "The purpose of this double-blind , r and omized , placebo-controlled trial was to determine the long-term effects of pravastatin and fosinopril treatment on peripheral endothelial function in subjects with albuminuria . Subjects ( mean age 51 years , 63 % male ) were r and omized to pravastatin 40 mg or matching placebo and to fosinopril 20 mg or matching placebo . Using high resolution ultrasound , flow-mediated dilation ( FMD ) and nitroglycerin-induced dilation ( NID ) was assessed at baseline and after 4 years of treatment in a total of 276 subjects . At baseline , mean+/-st and ard error FMD was 4.73+/-0.49 % and NID was 10.86+/-0.67 % . Pravastatin significantly reduced total cholesterol and LDL cholesterol ( p pravastatin was associated with a non-significant improvement of 18.9 % in FMD ( + 0.80+/-0.95 , p=0.09 ) , without a significant change in NID . Interestingly , pravastatin significantly increased FMD by 34.9 % in men ( + 1.23 , p=0.04 ) , but only 1.1 % in women ( + 0.06 , p=0.95 ) . Fosinopril was not associated with a change in FMD or NID despite significantly decreasing urinary albumin excretion , systolic and diastolic blood pressure ( all p pravastatin treatment tended to increase FMD and this effect was predominantly present in men . Fosinopril treatment did not modify FMD during long-term follow-up", "Background and Purpose — The Plaque Hypertension Lipid-Lowering Italian Study ( PHYLLIS ) tested whether ( 1 ) the angiotensin-converting enzyme ( ACE ) inhibitor fosinopril ( 20 mg per day ) was more effective on carotid atherosclerosis progression than the diuretic hydrochlorothiazide ( 25 mg per day ) , ( 2 ) pravastatin ( 40 mg per day ) was more effective than placebo when added to either hydrochlorothiazide or fosinopril , and ( 3 ) there were additive effects of ACE inhibitor and lipid-lowering therapies . Methods — A total of 508 hypertensive , hypercholesterolemic patients with asymptomatic carotid atherosclerosis were r and omized to : ( A ) hydrochlorothiazide ; ( B ) fosinopril ; ( C ) hydrochlorothiazide plus pravastatin ; and ( D ) fosinopril plus pravastatin , and followed up blindly for 2.6 years . B-Mode carotid scans were performed yearly by certified sonographers in 13 hospitals and read central ly . Corrections for drift were calculated from readings repeated at study end . Primary outcome was change in mean maximum intima-media thickness of far and near walls of common carotids and bifurcations bilaterally ( CBMmax ) . Results — CBMmax significantly progressed ( 0.010±0.004 mm per year ; P=0.01 ) in group A ( hydrochlorothiazide alone ) but not in groups B , C , and D. CBMmax changes in groups B , C , and D were significantly different from changes in group A. Changes in group A were concentrated at the bifurcations . “ Clinic ” and “ ambulatory ” blood pressure reductions were not significantly different between groups , but total and low-density lipoprotein cholesterol decreased by ≈1 mmol/L in groups C and D. Conclusions — Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril . Progression could also be avoided by associating pravastatin with hydrochlorothiazide ", "High serum cholesterol levels are associated with death from coronary heart disease and statin therapy has been demonstrated to effectively lower low-density lipoprotein ( LDL ) cholesterol and reduce coronary events in broad sections of the population . Recently , the Justification for the Use of Statins in Primary Prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) r and omized 17 802 apparently healthy individuals , with levels of LDL cholesterol below current treatment thresholds but with elevated levels of high-sensitivity C-reactive protein , to rosuvastatin 20 mg daily , or placebo . At a median follow-up of almost 2 years , compared to placebo , rosuvastatin treatment was associated with a significant reduction in the incidence of major cardiovascular or cerebrovascular events , that is , almost twice the magnitude found in previous statin trials . Such a noteworthy finding is discussed herein", "The Exp and ed Clinical Evaluation of Lovastatin study , a r and omized , double-blind , placebo- and diet-controlled multicenter trial , evaluated the efficacy and tolerability of lovastatin over 48 weeks in 8,245 patients with moderately severe hypercholesterolemia . During year 1 of follow-up of the full cohort , lovastatin at 20 or 40 mg/day , or 20 or 40 mg twice daily , produced dose-dependent decreases in low-density lipoprotein ( LDL ) cholesterol ( 24 % to 40 % ) and triglyceride levels ( 10 % to 19 % ) , and increases in high-density lipoprotein ( HDL ) cholesterol ( 6.6 % to 9.5 % ) . In all , 977 patients continued their original blinded treatment for an additional year . In year 2 , the LDL cholesterol response to lovastatin was maintained , the triglyceride reductions were somewhat less , and the increases in HDL cholesterol were moderately greater than in year 1 . Successive transaminase elevations > 3 times the upper limit of normal were observed in only 1 patient in year 2 , yielding a cumulative 2-year incidence of from 0.1 % ( placebo or lovastatin 20 mg/day ) to 1.9 % ( lovastatin 80 mg/day ) . Myopathy occurred in only 1 patient during year 2 , and over the 2-year study was observed rarely and only at lovastatin dosages of 40 and 80 mg/day . This study indicates that lovastatin maintains its efficacy over long-term follow-up , particularly in effectively lowering LDL cholesterol , is generally well tolerated , and has a favorable safety profile", "Objective : To test whether the 3-hydroxy-3-methylglutaryl- coenzyme A reductase inhibitor atorvastatin can slow down the progression of presbycusis . Patients : Fifty patients 60- to 75-years-old with presbycusis and moderately elevated serum cholesterol . Intervention(s ) : In a double-blind design , patients were r and omly assigned to treatment with either atorvastatin ( 40 mg/d orally ) or placebo . Main Outcome Measure(s ) : Pure-tone audiometry and tinnitus evaluation at enrolment and after 7 and 13 months . Results : Development of hearing thresholds after 7 and 13 months showed no significant differences between the groups . Tinnitus score continuously improved in the atorvastatin group ( 34.8 at 7 and 27.6 at 13 mo ) , whereas it slightly deteriorated in the placebo group ( 24.8 at 7 and 26.8 at 13 mo ) . The effect on tinnitus was a tendency without statistic significance ( p = 0.0833 ) . Conclusion : Atorvastatin had no effect on the development of hearing thresholds , but result ed in a trend toward a relief of tinnitus", "Little information exists to quantify the functional status and economic consequences of lipid-lowering therapy in elderly patients . We describe the design of the cost-effectiveness component of the first large , r and omized , placebo-controlled trial of lipid-lowering therapy in subjects aged 70 years or older . The PROspect i ve Study of Pravastatin in the Elderly at Risk has r and omized 5804 men and women 70 - 82 years old , with existing vascular disease or related risk factors , to receive 40 mg/d of pravastatin or placebo . The cost-effectiveness study will be based on within-trial observations of differences between the two study arms in rates of myocardial infa rct ion , stroke and related vascular disease outcomes ( including vascular dementia ) . In addition to comparing within-trial clinical outcomes , we will model the projected changes in life expectancy and cardiovascular outcome rates that would be seen with lifelong use of the drug , based on the risk reduction rates seen in the trial as well as baseline observational data from the three countries where the trial is being conducted ( Scotl and , Irel and and the Netherl and s ) . A state transition ( Markov ) model will be constructed to estimate the likely states of health , functional status and health care re source utilization ( including lipid-lowering drug costs ) in a cohort of elderly patients with versus without pravastatin therapy over a series of 1-year cycles until death . In addition , a st and ard measure of utility ( the Health Utilities Index ) will be administered to all study subjects to permit calculation of quality -adjusted life-years gained with this regimen . This approach will make it possible to go beyond the calculation of a single endpoint for each subject , and to translate the trial findings into definitions of effectiveness and outcomes that will be relevant to the ongoing debate concerning how best to relate the benefits of such medications to their costs", "p w A s l fi r t t u w h In January 2003 , the Justification for the Use of statins in revention : an Intervention Trial Evaluating Rosuvastatin JUPITER ) investigators began to enroll 17,802 men and omen with no evidence of cardiovascular disease and ormal to low levels of low-density lipoprotein ( LDL ) choesterol into a controversial trial testing whether subjects ith enhanced inflammatory responses might benefit from ggressive statin therapy . At study entry , the mean LDL holesterol level for enrolled participants was just above 00 mg/dl , nearly half had Framingham scores of 10 % , nd none were considered c and i date s for statin therapy under ny current set of prevention guidelines . However , all trial articipants had levels of the inflammatory biomarker highensitivity C-reactive protein ( hsCRP ) 2 mg/L , putting them t substantial risk for future cardiovascular disease . As the JUPITER investigators have since reported in a eries of rigorously peer- review ed reports published in the ew Engl and Journal of Medicine , The Lancet , the nnals of Internal Medicine , Circulation , the Journal of he American College of Cardiology , and The American ournal of Cardiology , r and om allocation to rosuvastatin 0 mg compared to placebo within the trial population esulted in a 54 % reduction in myocardial infa rct ion ( p .0002 ) , a 51 % reduction in ischemic stroke ( p 0.004 ) , a 6 % reduction in need for bypass surgery or angioplasty p 0.0001 ) , a 43 % reduction in venous thromboembolism p 0.002 ) , and a 20 % reduction in all-cause mortality p 0.02 ) . For the JUPITER primary end point of", "OBJECTIVES We evaluated the efficacy of statin therapy in primary prevention among individuals with moderate chronic kidney disease ( CKD ) . BACKGROUND Whether patents with moderate CKD ( estimated glomerular filtration rate [ eGFR ] benefit from statin therapy is uncertain , particularly among those without hyperlipidemia or known cardiovascular disease . METHODS Within the JUPITER ( Justification for the Use of statins in Prevention-an Intervention Trial Evaluating Rosuvastatin ) primary prevention trial of rosuvastatin 20 mg compared with placebo among men and women free of cardiovascular disease who had low-density lipoprotein cholesterol ( LDL-C ) or=2 mg/l , we performed a secondary analysis comparing cardiovascular and mortality outcomes among those with moderate CKD at study entry ( n = 3,267 ) with those with baseline eGFR > or=60 ml/min/1.73 m(2 ) ( n = 14,528 ) . Median follow-up was 1.9 years ( maximum 5 years ) . RESULTS Compared with those with eGFR > or=60 ml/min/1.73 m(2 ) , JUPITER participants with moderate CKD had higher vascular event rates ( hazard ratio [ HR ] : 1.54 , 95 % confidence interval [ CI ] : 1.23 to 1.92 , p = 0.0002 ) . Among those with moderate CKD , rosuvastatin was associated with a 45 % reduction in risk of myocardial infa rct ion , stroke , hospital stay for unstable angina , arterial revascularization , or confirmed cardiovascular death ( HR : 0.55 , 95 % CI : 0.38 to 0.82 , p = 0.002 ) and a 44 % reduction in all-cause mortality ( HR : 0.56 , 95 % CI : 0.37 to 0.85 , p = 0.005 ) . Median LDL-C and hsCRP reductions as well as side effect profiles associated with rosuvastatin were similar among those with and without CKD . Median eGFR at 12 months was marginally improved among those allocated to rosuvastatin as compared with placebo . CONCLUSIONS Rosuvastatin reduces first cardiovascular events and all-cause mortality among men and women with LDL-C concomitant evidence of moderate CKD . ( JUPITER-Crestor 20 mg Versus Placebo in Prevention of Cardiovascular [ CV ] Events ; NCT00239681 )", "OBJECTIVES We sought to examine the incidence and clinical predictors of new-onset type 2 diabetes mellitus ( T2DM ) within 3 large r and omized trials with atorvastatin . BACKGROUND Statin therapy might modestly increase the risk of new-onset T2DM . METHODS We used a st and ard definition of diabetes and excluded patients with prevalent diabetes at baseline . We identified baseline predictors of new-onset T2DM and compared the event rates in patients with and without new-onset T2DM . RESULTS In the TNT ( Treating to New Targets ) trial , 351 of 3,798 patients r and omized to 80 mg of atorvastatin and 308 of 3,797 r and omized to 10 mg developed new-onset T2DM ( 9.24 % vs. 8.11 % , adjusted hazard ratio [ HR ] : 1.10 , 95 % confidence interval [ CI ] : 0.94 to 1.29 , p = 0.226 ) . In the IDEAL ( Incremental Decrease in End Points Through Aggressive Lipid Lowering ) trial , 239 of 3,737 patients r and omized to atorvastatin 80 mg/day and 208 of 3,724 patients r and omized to simvastatin 20 mg/day developed new-onset T2DM ( 6.40 % vs. 5.59 % , adjusted HR : 1.19 , 95 % CI : 0.98 to 1.43 , p = 0.072 ) . In the SPARCL ( Stroke Prevention by Aggressive Reduction in Cholesterol Levels ) trial , new-onset T2DM developed in 166 of 1,905 patients r and omized to atorvastatin 80 mg/day and in 115 of 1,898 patients in the placebo group ( 8.71 % vs. 6.06 % , adjusted HR : 1.37 , 95 % CI : 1.08 to 1.75 , p = 0.011 ) . In each of the 3 trials , baseline fasting blood glucose , body mass index , hypertension , and fasting triglycerides were independent predictors of new-onset T2DM . Across the 3 trials , major cardiovascular events occurred in 11.3 % of patients with and 10.8 % of patients without new-onset T2DM ( adjusted HR : 1.02 , 95 % CI : 0.77 to 1.35 , p = 0.69 ) . CONCLUSIONS High-dose atorvastatin treatment compared with placebo in the SPARCL trial is associated with a slightly increased risk of new-onset T2DM . Baseline fasting glucose level and features of the metabolic syndrome are predictive of new-onset T2DM across the 3 trials", "BACKGROUND R and omized data on statins for primary prevention in older persons are limited , and the relative hazard of cardiovascular disease associated with an elevated cholesterol level weakens with advancing age . OBJECTIVE To assess the efficacy and safety of rosuvastatin in persons 70 years or older . DESIGN Secondary analysis of JUPITER ( Justification for the Use of statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ) , a r and omized , double-blind , placebo-controlled trial . SETTING 1315 sites in 26 countries r and omly assigned participants in JUPITER . PARTICIPANTS Among the 17 802 participants r and omly assigned with low-density lipoprotein ( LDL ) cholesterol levels less than 3.37 mmol/L ( INTERVENTION Participants were r and omly assigned in a 1:1 ratio to receive 20 mg of rosuvastatin daily or placebo . MEASUREMENTS The primary end point was the occurrence of a first cardiovascular event ( myocardial infa rct ion , stroke , arterial revascularization , hospitalization for unstable angina , or death from cardiovascular causes ) . RESULTS The 32 % of trial participants 70 years or older accrued 49 % ( n = 194 ) of the 393 confirmed primary end points . The rates of the primary end point in this age group were 1.22 and 1.99 per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio , 0.61 [ 95 % CI , 0.46 to 0.82 ] ; P rates of all-cause mortality in this age group were 1.63 and 2.04 ( hazard ratio , 0.80 [ CI , 0.62 to 1.04 ] ; P = 0.090 ) . Although no significant heterogeneity was found in treatment effects by age , absolute reductions in event rates associated with rosuvastatin were greater in older persons . The relative rate of any serious adverse event among older persons in the rosuvastatin versus placebo group was 1.05 ( CI , 0.93 to 1.17 ) . LIMITATION Effect estimates from this exploratory analysis with age cut-point chosen after trial completion should be viewed in the context of the overall trial results . CONCLUSION In apparently healthy older persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels , rosuvastatin reduces the incidence of major cardiovascular events . PRIMARY FUNDING SOURCE AstraZeneca", "Background : The progression of cerebral atherosclerosis increases the risk of stroke and vascular events . Given the known benefits of statins in retarding coronary and carotid atherosclerosis progression , we studied the effects of statins on asymptomatic middle cerebral artery ( MCA ) stenosis progression . Methods : We conducted a r and omized , double-blind , placebo-controlled study to evaluate the effects of simvastatin on the progression of MCA stenosis among stroke-free individuals who had mild to moderately elevated LDL cholesterol ( 3.0–5.0 mmol/l ) . Two hundred and twenty-seven subjects were r and omized to either placebo ( n = 114 ) or simvastatin 20 mg daily ( n = 113 ) . The severity of MCA stenosis at baseline and at the end of the study was grade d by MRA into normal , minimal ( 90 % ) . The primary outcome was the change in grading of MCA stenosis over 2 years . Results : At the end of the study , the LDL cholesterol level decreased by 1.43 and 0.12 mmol/l for the active and placebo groups , respectively ( p proportion of patients having stable , progressive and regressive MCA stenosis between the placebo ( 72 , 22 and 6 % ) and active groups ( 78.6 , 15.5 and 5.8 % ) . The all-cause mortality was significantly lower in the active group ( n = 0 ) relative to the placebo group ( n = 7 , p = 0.014 ) . Any clinical events were also lower in the active group ( n = 5 ) than in the placebo group ( n = 13 , p = 0.052 ) . Conclusions : Simvastatin 20 mg daily had no apparent effect upon the evolution of asymptomatic MCA stenosis over 2 years", "Background — Aortic stenosis ( AS ) is an active process with similarities to atherosclerosis . The objective of this study was to assess the effect of cholesterol lowering with rosuvastatin on the progression of AS . Methods and Results — This was a r and omized , double-blind , placebo-controlled trial in asymptomatic patients with mild to moderate AS and no clinical indications for cholesterol lowering . The patients were r and omized to receive either placebo or rosuvastatin 40 mg daily . A total of 269 patients were r and omized : 134 patients to rosuvastatin 40 mg daily and 135 patients to placebo . Annual echocardiograms were performed to assess AS progression , which was the primary outcome ; the median follow-up was 3.5 years . The peak AS gradient increased in patients receiving rosuvastatin from a baseline of 40.8±11.1 to 57.8±22.7 mm Hg at the end of follow-up and in patients with placebo from 41.6±10.9 mm Hg at baseline to 54.8±19.8 mm Hg at the end of follow-up . The annualized increase in the peak AS gradient was 6.3±6.9 mm Hg in the rosuvastatin group and 6.1±8.2 mm Hg in the placebo group ( P=0.83 ) . Treatment with rosuvastatin was not associated with a reduction in AS progression in any of the predefined subgroups . Conclusion — Cholesterol lowering with rosuvastatin 40 mg did not reduce the progression of AS in patients with mild to moderate AS ; thus , statins should not be used for the sole purpose of reducing the progression of AS . Clinical Trial Registration Information— URL : http://www.controlled-trials.com/. Clinical trial registration number : IS RCT N 32424163" ]

[ "BACKGROUND Effects of diet on blood lipids are best known in white men , and effects of type of carbohydrate on triacylglycerol concentrations are not well defined . OBJECTIVE Our goal was to determine the effects of diet on plasma lipids , focusing on subgroups by sex , race , and baseline lipid concentrations . DESIGN This was a r and omized controlled outpatient feeding trial conducted in 4 field centers . The subjects were 436 participants of the Dietary Approaches to Stop Hypertension ( DASH ) Trial [ mean age : 44.6 y ; 60 % African American ; baseline total cholesterol : . The intervention consisted of 8 wk of a control diet , a diet increased in fruit and vegetables , or a diet increased in fruit , vegetables , and low-fat dairy products and reduced in saturated fat , total fat , and cholesterol ( DASH diet ) , during which time subjects remained weight stable . The main outcome measures were fasting total cholesterol , LDL cholesterol , HDL cholesterol , and triacylglycerol . RESULTS Relative to the control diet , the DASH diet result ed in lower total ( -0.35 mmol/L , or -13.7 mg/dL ) , LDL- ( -0.28 mmol/L , or -10.7 mg/dL ) , and HDL- ( -0.09 mmol/L , or -3.7 mg/dL ) cholesterol concentrations ( all P reductions in total and LDL cholesterol in men were greater than those in women by 0.27 mmol/L , or 10.3 mg/dL ( P = 0.052 ) , and by 0.29 mmol/L , or 11.2 mg/dL ( P Changes in lipids did not differ significantly by race or baseline lipid concentrations , except for HDL , which decreased more in participants with higher baseline HDL-cholesterol concentrations than in those with lower baseline HDL-cholesterol concentrations . The fruit and vegetable diet produced few significant lipid changes . CONCLUSIONS The DASH diet is likely to reduce coronary heart disease risk . The possible opposing effect on coronary heart disease risk of HDL reduction needs further study", "We served a low-fat ( 28 % of energy ) , high-fiber ( 3.3 g/MJ ) diet according to Nordic nutrition recommendations ( Rec diet ) , and a high-fat diet ( 39 % of energy ) corresponding to the average Danish diet ( Dane diet ) for periods of 2 wk in a r and omized crossover study of 21 healthy middle-aged individuals . The Rec diet result ed in lower serum concentrations of low-density-lipoprotein ( LDL ) cholesterol ( medians : 2.77 vs 3.04 mmol/L , P high-density-lipoprotein ( HDL ) cholesterol ( 1.08 vs 1.24 mmol/L , P higher fasting triglycerides ( 1.11 vs 0.86 mmol/L , P = 0.04 ) than did the Dane diet . Furthermore , the Rec diet lowered plasma factor VII coagulant activity ( FVIIc ) ( 88 % vs 96 % , P = 0.002 ) and raised plasma fibrinolytic activity . Our observations indicate that a low-fat , high-fiber diet may not only reduce the atherogenic but also the thrombogenic tendency of an individual compared with a diet corresponding to the average Danish diet", "BACKGROUND Reproduction has been identified as an important factor for long-term weight gain among women . A previous efficacy trial has successfully produced postpartum weight loss ; however , the effectiveness of this intervention needs to be established . OBJECTIVE This study was design ed to evaluate the short- and long-term effectiveness of a diet behavior modification treatment to produce weight loss in postpartum women within the primary health care setting in Sweden . DESIGN During 2011 - 2014 , 110 women with a self-reported body mass index ( BMI ; in kg/m(2 ) ) of ≥27 at 6 - 15 wk postpartum were r and omly assigned to the diet behavior modification group ( D group ) or the control group ( C group ) . Women r and omly assigned to the D group ( n = 54 ) received a structured 12-wk diet behavior modification treatment by a dietitian and were instructed to gradually implement a diet plan based on the Nordic Nutrition Recommendations and to self-weigh ≥3 times/wk . Women r and omly assigned to the C group ( n = 56 ) were given a brochure on healthy eating . The primary outcome was change in body weight after 12 wk and 1 y. The retention rate was 91 % and 85 % at 12 wk and 1 y , respectively . RESULTS At baseline , women had a median ( 1st , 3rd quartile ) BMI of 31.0 ( 28.8 , 33.6 ) , and 84 % were breastfeeding . After 12 wk , median weight change in the D group was -6.1 kg ( -8.4 , -3.2 kg ) compared with -1.6 kg ( -3.5 , -0.4 kg ) in the C group ( P reduced BMI , waist circumference , hip circumference , and body fat percentage more than did the C group at both 12 wk and 1 y ( all P A low-intensity diet treatment delivered by a dietitian within the primary health care setting can produce clinical ly relevant and sustainable weight loss in postpartum women with overweight and obesity . This trial was registered at clinical trials.gov as NCT01949558", "BACKGROUND The regional Mediterranean Diet has been associated with lower risk of disease . OBJECTIVE We tested the health effects of the New Nordic Diet ( NND ) , which is a gastronomically driven regional , organic , and environmentally friendly diet , in a carefully controlled but free-living setting . DESIGN A total of 181 central ly obese men and women , with a mean ( range ) age of 42 y ( 20 - 66 y ) , body mass index ( in kg/m(2 ) ) of 30.2 ( 22.6 - 47.3 ) , and waist circumference of 100 cm ( 80 - 138 cm ) were r and omly assigned to receive either the NND ( high in fruit , vegetables , whole grains , and fish ) or an average Danish diet ( ADD ) for 26 wk . Participants received cookbooks and all foods ad libitum and free of charge by using a shop model . The primary endpoint was the weight change analyzed by both completer and intention-to-treat analyses . RESULTS A total of 147 subjects [ 81 % ( NND 81 % ; ADD 82 % ) ] completed the intervention . A high dietary compliance was achieved , with significant differences in dietary intakes between groups . The mean ( ±SEM ) weight change was -4.7 ± 0.5 kg for the NND compared with -1.5 ± 0.5 kg for the ADD ( adjusted difference : -3.2 kg ; 95 % CI : -4.6 , -1.8 kg ; P greater reductions in systolic blood pressure ( adjusted difference : -5.1 mm Hg ; 95 % CI : -8.2 , -2.1 mm Hg ) and diastolic blood pressure ( adjusted difference : -3.2 mm Hg ; 95 % CI : -5.7 , -0.8 mm Hg ) than did the ADD . CONCLUSION An ad libitum NND produces weight loss and blood pressure reduction in central ly obese individuals . This trial was registered at www . clinical trials.gov as NCT01195610", "Children 's vitamin D intake and status can be optimised to meet recommendations . We investigated if nutritionally balanced school meals with weekly fish servings affected serum 25-hydroxyvitamin D ( 25(OH)D ) and markers related to bone in 8- to 11-year-old Danish children . We conducted an explorative secondary outcome analysis on data from 784 children from the OPUS School Meal Study , a cluster-r and omised cross-over trial where children received school meals for 3 months and habitual lunch for 3 months . At baseline , and at the end of each dietary period , 25(OH)D , parathyroid hormone ( PTH ) , osteocalcin ( OC ) , insulin-like growth factor-1 ( IGF-1 ) , bone mineral content ( BMC ) , bone area ( BA ) , bone mineral density ( BMD ) , dietary intake and physical activity were assessed . School meals increased vitamin D intake by 0·9 ( 95 % CI 0·7 , 1·1 ) μg/d . No consistent effects were found on 25(OH)D , BMC , BA , BMD , IGF-1 or OC . However , season-modified effects were observed with 25(OH)D , i.e. children completing the school meal period in January/February had higher 25(OH)D status ( 5·5 ( 95 % CI 1·8 , 9·2 ) nmol/l ; P = 0·004 ) than children completing the control period in these months . A similar tendency was indicated in November/December ( 4·1 ( 95 % CI –0·12 , 8·3 ) nmol/l ; P = 0·057 ) . However , the effect was opposite in March/April ( –4·0 ( 95 % CI –7·0 , –0·9 ) nmol/l ; P = 0·010 ) , and no difference was found in May/June ( P = 0·214 ) . Unexpectedly , the school meals slightly increased PTH ( 0·18 ( 95 % CI 0·07 , 0·29 ) pmol/l ) compared with habitual lunch . Small increases in dietary vitamin D might hold potential to mitigate the winter nadir in Danish children 's 25(OH)D status while higher increases appear necessary to affect status throughout the year . More trials on effects of vitamin D intake from natural foods are needed", "It is widely assumed that nutrition can improve school performance in children ; however , evidence remains limited and inconclusive . In the present study , we investigated whether serving healthy school meals influenced concentration and school performance of 8- to 11-year-old Danish children . The OPUS ( Optimal well-being , development and health for Danish children through a healthy New Nordic Diet ) School Meal Study was a cluster-r and omised , controlled , cross-over trial comparing a healthy school meal programme with the usual packed lunch from home ( control ) each for 3 months ( NCT 01457794 ) . The d2 test of attention , the Learning Rating Scale ( LRS ) and st and ard tests on reading and mathematics proficiency were administered at baseline and at the end of each study period . Intervention effects were evaluated using hierarchical mixed models . The school meal intervention did not influence concentration performance ( CP ; primary outcome , n 693 ) or processing speed ; however , the decrease in error percentage was 0·18 points smaller ( P increased reading speed ( 0·7 sentence , P=0·009 ) and the number of correct sentences ( 1·8 sentences , P The percentage of correct sentences also improved ( P the number correct improved relatively more than reading speed . There was no effect on overall math performance or outcomes from the LRS . In conclusion , school meals did not affect CP , but improved reading performance , which is a complex cognitive activity that involves inference , and increased errors related to impulsivity and inattention . These findings are worth examining in future trials", "The aim of the present study was to compare total food intake , total and relative edible plate waste and self-reported food likings between school lunch based on the new Nordic diet ( NND ) and packed lunch from home . In two 3-month periods in a cluster-r and omised controlled unblinded cross-over study 3rd- and 4th- grade children ( n 187 ) from two municipal schools received lunch meals based on NND principles and their usual packed lunch ( control ) . Food intake and plate waste ( n 1558 ) were calculated after weighing lunch plates before and after the meal for five consecutive days and self-reported likings ( n 905 ) assessed by a web-based question naire . Average food intake was 6 % higher for the NND period compared with the packed lunch period . The quantity of NND intake varied with the menu ( P self-reported likings . The edible plate waste was 88 ( sd 80 ) g for the NND period and 43 ( sd 60 ) g for the packed lunch period whereas the relative edible plate waste was no different between periods for meals having waste ( n 1050 ) . Edible plate waste differed between menus ( P period . Self-reported likings were negatively associated with percentage plate waste ( P reduction of plate waste , children 's likings and nutritious school meals are crucial from both a nutritional , economic and environmental point of view", "Objective : It has been suggested that overweight is negatively associated with cognitive functions . The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women . Methods : 20 overweight postmenopausal women were r and omized to either a modified paleolithic diet or a st and ard diet adhering to the Nordic Nutrition Recommendations for 6 months . We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions . Results : Episodic memory performance improved significantly ( p = 0.010 ) after the dietary interventions . Concomitantly , brain activity increased in the anterior part of the right hippocampus during memory encoding , without differences between diets . This was associated with decreased levels of plasma free fatty acids ( FFA ) . Brain activity increased in pre-frontal cortex and superior/middle temporal gyri . The magnitude of increase correlated with waist circumference reduction . During episodic retrieval , brain activity decreased in inferior and middle frontal gyri , and increased in middle/superior temporal gyri . Conclusions : Diet-induced weight loss , associated with decreased levels of plasma FFA , improves episodic memory linked to increased hippocampal activity", "The OPUS ( Optimal well-being , development and health for Danish children through a healthy New Nordic Diet ( NND ) ) School Meal Study investigated the effects on the intake of foods and nutrients of introducing school meals based on the principles of the NND covering lunch and all snacks during the school day in a cluster-r and omised cross-over design . For two 3-month periods , 834 Danish children aged 8 - 11 years from forty-six school classes at nine schools received NND school meals or their usual packed lunches brought from home ( control ) in r and om order . The whole diet of the children was recorded over seven consecutive days using a vali date d Web-based Dietary Assessment Software for Children . The NND result ed in higher intakes of potatoes ( 130 % , 95 % CI 2·07 , 2·58 ) , fish ( 48 % , 95 % CI 1·33 , 1·65 ) , cheese ( 25 % , 95 % CI 1·15 , 1·36 ) , vegetables ( 16 % , 95 % CI 1·10 , 1·21 ) , eggs ( 10 % , 95 % CI 1·01 , 1·19 ) and beverages ( 6 % , 95 % CI 1·02 , 1·09 ) , and lower intakes of bread ( 13 % , 95 % CI 0·84 , 0·89 ) and fats ( 6 % , 95 % CI 0·90 , 0·98 ) were found among the children during the NND period than in the control period ( all , P found in mean energy intake ( P= 0·4 ) , but on average children reported 0·9 % less energy intake from fat and 0·9 % higher energy intake from protein during the NND period than in the control period . For micronutrient intakes , the largest differences were found for vitamin D ( 42 % , 95 % CI 1·32 , 1·53 ) and iodine ( 11 % , 95 % CI 1·08 , 1·15 ) due to the higher fish intake . In conclusion , the present study showed that the overall dietary intake at the food and nutrient levels was improved among children aged 8 - 11 years when their habitual packed lunches were replaced by school meals following the principles of the NND", "Background : Type-2 diabetes ( T2D ) prevalence is rapidly increasing worldwide . Lifestyle factors , in particular obesity , diet , and physical activity play a significant role in the etiology of the disease . Of dietary patterns , particularly the Mediterranean diet has been studied , and generally a protective association has been identified . However , other regional diets are less explored . Objective : The aim of the present study was to investigate the association between adherence to a healthy Nordic food index and the risk of T2D . The index consists of six food items : fish , cabbage , rye bread , oatmeal , apples and pears , and root vegetables . Methods : Data was obtained from a prospect i ve cohort study of 57,053 Danish men and women aged 50–64 years , at baseline , of whom 7366 developed T2D ( median follow-up : 15.3 years ) . The Cox proportional hazards model was used to assess the association between the healthy Nordic food index and risk of T2D , adjusted for potential confounders . Results : Greater adherence to the healthy Nordic food index was significantly associated with lower risk of T2D after adjusting for potential confounders . An index score of 5−6 points ( high adherence ) was associated with a statistically significantly 25 % lower T2D risk in women ( HR : 0.75 , 95%CI : 0.61–0.92 ) and 38 % in men ( HR : 0.62 ; 95%CI : 0.53–0.71 ) compared to those with an index score of 0 points ( poor adherence ) . Conclusion : Adherence to a healthy Nordic food index was found to be inversely associated with risk of T2D , suggesting that regional diets other than the Mediterranean may also be recommended for prevention of T2D", "BACKGROUND In several intervention trials , a healthy Nordic diet showed beneficial effects on markers of cardiovascular disease . We investigated the association between a healthy Nordic diet and clinical diagnosis of cardiovascular disease . OBJECTIVE Our aim was first to examine the association between a healthy Nordic food index ( wholegrain bread , oatmeal , apples/pears , root vegetables , cabbages and fish ) and the incidence of overall cardiovascular disease ( ischaemic heart disease , stroke , arrhythmia , thrombosis and hypertensive disease ) , and secondly to test for possible effect modification by smoking , body mass index ( BMI ) , alcohol consumption and age . METHODS We conducted an analysis of data from the prospect i ve Swedish Women 's Lifestyle and Health cohort , including 43 310 women who completed a food frequency question naire in 1991 - 1992 , and followed up until 31 December 2012 through Swedish registries . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) were calculated using Cox proportional hazards models . RESULTS During follow-up , 8383 women developed cardiovascular disease . We found no association between the healthy Nordic food index and overall cardiovascular disease risk or any of the subgroups investigated . There was a statistically significant interaction with smoking status ( P = 0.02 ) , with a beneficial effect only amongst former smokers ( HR 0.96 , 95 % CI 0.94 - 0.99 per 1-point increment ) . CONCLUSION The present results do not support an association between a healthy Nordic food index and risk of cardiovascular disease in Swedish women . There was also no effect modification by alcohol intake , BMI or age . Our finding of an interaction with smoking status requires reproduction", "Background / Objectives : Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism . We aim ed to investigate the association between plasma alkylresorcinols ( AR ) , a biomarker of whole-grain rye and wheat intake , and glucose metabolism in individuals with metabolic syndrome (MetS).Subjects/ Methods : Participants were 30–65 years of age , with body mass index 27–40 kg/m2 and had MetS without diabetes . Individuals were recruited through six centers in the Nordic countries and r and omized to a healthy Nordic diet ( ND , n=96 ) , rich in whole-grain rye and wheat , or a control diet ( n=70 ) , for 18–24 weeks . In addition , associations between total plasma AR concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake , and glucose metabolism measures from oral glucose tolerance tests were investigated in pooled ( ND+control ) regression analyses at 18/24 weeks . Results : ND did not improve glucose metabolism compared with control diet , but the AR C17:0/C21:0 ratio was inversely associated with fasting insulin concentrations ( P=0.002 ) and positively associated with the insulin sensitivity indices Matsuda ISI ( P=0.026 ) and disposition index ( P=0.022 ) in pooled analyses at 18/24 weeks , even after adjustment for confounders . The AR C17:0/C21:0 ratio was not significantly associated with insulin secretion indices . Total plasma AR concentration was not related to fasting plasma glucose or fasting insulin at 18/24 weeks . Conclusions : The AR C17:0/C21:0 ratio , an indicator of relative whole-grain rye intake , is associated with increased insulin sensitivity in a population with", "We investigated the effect of olive oil , rapeseed oil , and sunflower oil on blood lipids and lipoproteins including number and lipid composition of lipoprotein subclasses . Eighteen young , healthy men participated in a double-blinded r and omized cross-over study ( 3-week intervention period ) with 50 g of oil per 10 MJ incorporated into a constant diet . Plasma cholesterol , triacylglycerol , apolipoprotein B , and very low density lipoprotein ( VLDL ) , intermediate density lipoprotein ( IDL ) , and low density lipoprotein ( LDL ) cholesterol concentrations were 10;-20 % higher after consumption of the olive oil diet compared with the rapeseed oil and sunflower oil diets [ analysis of variance ( ANOVA ) , P size of IDL , VLDL , and LDL subfractions did not differ between the diets , whereas a significantly higher number ( apolipoprotein B concentration ) and lipid content of the larger and medium-sized LDL subfractions were observed after the olive oil diet compared with the rapeseed oil and sunflower oil diets ( ANOVA , P Total HDL cholesterol concentration did not differ significantly , but HDL(2a ) cholesterol was higher after olive oil and rapeseed oil compared with sunflower oil ( ANOVA , P rapeseed oil and sunflower oil had more favorable effects on blood lipids and plasma apolipoproteins as well as on the number and lipid content of LDL subfractions compared with olive oil . Some of the differences may be attributed to differences in the squalene and phytosterol contents of the oils", "Background Increased circulating cathepsin S levels have been linked to increased risk of cardiometabolic diseases and cancer . However , whether cathepsin S is a modifiable risk factor is unclear . We aim ed to investigate the effects of a prudent diet on plasma cathepsin S levels in healthy individuals . Findings Explorative analyses of a r and omized study were performed in 88 normal to slightly overweight and hyperlipidemic men and women ( aged 25 to 65 ) that were r and omly assigned to ad libitum prudent diet , i.e. healthy Nordic diet ( ND ) or a control group ( habitual Western diet ) for 6 weeks . Whereas all foods in the ND were provided , the control group was advised to consume their habitual diet throughout the study . The ND was in line with dietary recommendations , e.g. low in saturated fats , sugars and salt , but high in plant-based foods rich in fibre and unsaturated fats . The ND significantly decreased cathepsin S levels ( from 20.1 ( + /-4.0 SD ) to 19.7 μg/L ( + /-4.3 SD ) ) compared with control group ( from 18.2 ( + /-2.9 SD ) to 19.1 μg/L ( + /-3.8 SD ) ) . This difference remained after adjusting for sex and change in insulin sensitivity ( P = 0.03 ) , and near significant after adjusting for baseline cathepsin S levels ( P = 0.06 ) , but not for change in weight or LDL-C. Changes in cathepsin S levels were directly correlated with change in LDL-C. Conclusions Compared with a habitual control diet , a provided ad libitum healthy Nordic diet decreased cathepsin S levels in healthy individuals , possibly mediated by weight loss or lowered LDL-C. These differences between groups in cathepsin S were however not robust and therefore need further investigation", "Fe and n-3 long-chain PUFA ( n-3 LCPUFA ) have both been associated with cognition , but evidence remains inconclusive in well-nourished school-aged children . In the Optimal Well-Being , Development and Health for Danish Children through a Healthy New Nordic Diet ( OPUS ) School Meal Study , the 3-month intervention increased reading performance , inattention , impulsivity and dietary intake of fish and Fe . This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and , if so , explored how these changes correlated with the changes in cognitive performance . The study was a cluster-r and omised cross-over trial comparing school meals with packed lunch ( control ) . At baseline and after each treatment , we measured serum ferritin , whole-blood n-3 LCPUFA and Hb , and performance in reading , mathematics and d2-test of attention . Data were analysed using mixed models ( n 726 ) and principal component analysis of test performances ( n 644 ) , which showed two main patterns : ' school performance ' and ' reading comprehension ' . The latter indicated that children with good reading comprehension were also more inattentive and impulsive ( i.e. higher d2-test error% ) . The intervention improved ' school performance ' ( P=0·015 ) , ' reading comprehension ' ( P=0·043 ) and EPA+DHA status 0·21 ( 95 % CI 0·15 , 0·27 ) w/w % ( P affect serum ferritin or Hb . At baseline , having small Fe stores was associated with poorer ' school performance ' in girls , but with better ' reading comprehension ' in both boys and girls . Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with ' school performance ' , suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect . These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study", "A New Nordic Diet ( NND ) was developed in the context of the Danish OPUS Study ( Optimal well-being , development and health for Danish children through a healthy New Nordic Diet ) . Health , gastronomic potential , sustainability and Nordic identity were crucial principles of the NND . The aim of the present study was to investigate the effects of serving NND school meals compared with the usual packed lunches on the dietary intake of NND signature foods . For two 3-month periods , 834 Danish children aged 8 - 11 years received NND school meals or their usual packed lunches brought from home ( control ) in r and om order . The entire diet was recorded over 7 consecutive days using a vali date d Web-based Dietary Assessment Software for Children . The NND result ed in higher intakes during the entire week ( % increase ) of root vegetables ( 116 ( 95 % CI 1·93 , 2·42 ) ) , cabbage ( 26 ( 95 % CI 1·08 , 1·47 ) ) , legumes ( 22 ( 95 % CI 1·06 , 1·40 ) ) , herbs ( 175 ( 95 % CI 2·36 , 3·20 ) ) , fresh berries ( 48 ( 95 % CI 1·13 , 1·94 ) ) , nuts and seeds ( 18 ( 95 % CI 1·02 , 1·38 ) ) , lean fish and fish products ( 47 ( 95 % CI 1·31 , 1·66 ) ) , fat fish and fish products ( 18 ( 95 % CI 1·02 , 1·37 ) ) and potatoes ( 129 ( 95 % CI 2·05 , 2·56 ) ) . Furthermore , there was a decrease in the number of children with zero intakes when their habitual packed lunches were replaced by NND school meals . In conclusion , this study showed that the children increased their intake of NND signature foods , and , furthermore , there was a decrease in the number of children with zero intakes of NND signature foods when their habitual packed lunches were replaced by school meals following the NND principles", "Several healthy dietary patterns have been linked to longevity . Recently , a Nordic dietary pattern was associated with a lower overall mortality . No study has , however , investigated this dietary pattern in relation to cause-specific mortality . The aim of the present study was to examine the association between adherence to a healthy Nordic food index ( consisting of wholegrain bread , oatmeal , apples/pears , root vegetables , cabbages and fish/shellfish ) and overall mortality , and death by cardiovascular disease , cancer , injuries/suicide and other causes . We conducted a prospect i ve analysis in the Swedish Women ’s Lifestyle and Health cohort , including 44,961 women , aged 29–49 years , who completed a food frequency question naire between 1991–1992 , and have been followed up for mortality ever since , through Swedish registries . The median follow-up time is 21.3 years , and mortality rate ratios ( MRR ) were calculated using Cox Proportional Hazards Models . Compared to women with the lowest index score ( 0–1 points ) , those with the highest score ( 4–6 points ) had an 18 % lower overall mortality ( MRR 0.82 ; 0.71–0.93 , p lower risk of all-cause mortality : 6 % ( 3–9 % ) , cancer mortality : 5 % ( 1–9 % ) and mortality from other causes : 16 % ( 8–22 % ) . When examining the diet components individually , only wholegrain bread and apples/pears were significantly inversely associated with all-cause mortality . We observed no effect-modification by smoking status , BMI or age at baseline . The present study encourages adherence to a healthy Nordic food index , and warrants further investigation of the strong association with non-cancer , non-cardiovascular and non-injury/suicide deaths", "Background The fatty acid ( FA ) composition of serum lipids is related to the quality of dietary fat intake . Objective To investigate the effects of a healthy Nordic diet ( ND ) on the FA composition of serum cholesterol esters ( CE-FA ) and assess the associations between changes in the serum CE-FA composition and blood lipoproteins during a controlled dietary intervention . Design The NORDIET trial was a 6-week r and omised , controlled , parallel-group dietary intervention study that included 86 adults ( 53±8 years ) with elevated low-density lipoprotein cholesterol ( LDL-C ) . Serum CE-FA composition was measured using gas chromatography . Diet history interviews were conducted , and daily intake was assessed using checklists . Results Food and nutrient intake data indicated that there was a reduction in the intake of fat from dairy and meat products and an increase in the consumption of fatty fish with the ND . The levels of saturated fatty acids in cholesterol esters ( CE-SFA ) 14:0 , 15:0 , and 18:0 , but not 16:0 , showed a significant decrease after intake of ND compared to the control diet ( p increase in serum 22:6n – 3 was observed compared with the control diet ( p changes in CE-SFA 14:0 , 15:0 , and 18:0 correlated positively with changes in LDL-C , HDL-C , LDL-C/HDL-C , ApoA1 , and ApoB ( p the changes in polyunsaturated fatty acids in cholesterol esters ( CE-PUFA ) 22:6n – 3 were negatively correlated with changes in the corresponding serum lipids . Conclusions The decreased intake of saturated fat and increased intake of n-3 PUFA in a healthy ND is partly reflected by changes in the serum CE-FA composition , which are associated with an improved serum lipoprotein pattern", "Bias in self-reported dietary intake is important when evaluating the effect of dietary interventions , particularly for intervention foods . However , few have investigated this in children , and none have investigated the reporting accuracy of fish intake in children using biomarkers . In a Danish school meal study , 8- to 11-year-old children ( n 834 ) were served the New Nordic Diet ( NND ) for lunch . The present study examined the accuracy of self-reported intake of signature foods ( berries , cabbage , root vegetables , legumes , herbs , potatoes , wild plants , mushrooms , nuts and fish ) characterising the NND . Children , assisted by parents , self-reported their diet in a Web-based Dietary Assessment Software for Children during the intervention and control ( packed lunch ) periods . The reported fish intake by children was compared with their ranking according to fasting whole-blood EPA and DHA concentration and weight percentage using the Spearman correlations and cross-classification . Direct observation of school lunch intake ( n 193 ) was used to score the accuracy of food-reporting as matches , intrusions , omissions and faults . The reporting of all lunch foods had higher percentage of matches compared with the reporting of signature foods in both periods , and the accuracy was higher during the control period compared with the intervention period . Both Spearman 's rank correlations and linear mixed models demonstrated positive associations between EPA+DHA and reported fish intake . The direct observations showed that both reported and real intake of signature foods did increase during the intervention period . In conclusion , the self-reported data represented a true increase in the intake of signature foods and can be used to examine dietary intervention effects", "Background : Recently , the Nordic diet has gained interest , and a healthy Nordic food index has been developed , which has been found inversely related to colorectal cancer among Danish women . This single finding , however , requires replication in other cohorts . Methods : We conducted a prospect i ve study in the Women 's Lifestyle and Health cohort , including 45,222 women , recruited in 1991–92 , and followed up ever since through Swedish registries . Participants were classified according to the Nordic food index ( consisting of whole grain bread , oatmeal , apples/pears , cabbages , root vegetables , and fish/shellfish ) , and the association between adherence and colorectal cancer was assessed using the Cox proportional hazards models . Results : In the fully adjusted models , we found no association , neither with the continuous index score [ incidence rate ratio ( IRR ) , 1.04 ; 95 % confidence interval ( CI ) , 0.95–1.12 , per 1-point increment ] nor in the categorical analyses ( IRR , 1.09 ; 95 % CI , 0.78–1.52 for highest vs. lowest adherers ) . Conclusion : The present study does , thus , not support a previous finding of an inverse association between a healthy Nordic food index and colorectal cancer . Impact : This article adds new evidence to the field of the Nordic diet in disease prevention . Cancer Epidemiol Biomarkers Prev ; 24(4 ) ; 755–7 . © 2015 AACR", "The healthy Nordic diet has been previously shown to have health beneficial effects among subjects at risk of CVD . However , the extent of food changes needed to achieve these effects is less explored . The aim of the present study was to investigate the effects of exchanging a few commercially available , regularly consumed key food items ( e.g. spread on bread , fat for cooking , cheese , bread and cereals ) with improved fat quality on total cholesterol , LDL-cholesterol and inflammatory markers in a double-blind r and omised , controlled trial . In total , 115 moderately hypercholesterolaemic , non-statin-treated adults ( 25 - 70 years ) were r and omly assigned to an experimental diet group ( Ex-diet group ) or control diet group ( C-diet group ) for 8 weeks with commercially available food items with different fatty acid composition ( replacing SFA with mostly n-6 PUFA ) . In the Ex-diet group , serum total cholesterol ( P and LDL-cholesterol ( P -11 % in total cholesterol and LDL-cholesterol , respectively . No difference in change in plasma levels of inflammatory markers ( high-sensitive C-reactive protein , IL-6 , soluble TNF receptor 1 and interferon-γ ) was observed between the groups . In conclusion , exchanging a few regularly consumed food items with improved fat quality reduces total cholesterol , with no negative effect on levels of inflammatory markers . This shows that an exchange of a few commercially available food items was easy and manageable and led to clinical ly relevant cholesterol reduction , potentially affecting future CVD risk", "Background / Objectives : Short-term studies have suggested beneficial effects of a Palaeolithic-type diet ( PD ) on body weight and metabolic balance . We now report the long-term effects of a PD on anthropometric measurements and metabolic balance in obese postmenopausal women , in comparison with a diet according to the Nordic Nutrition Recommendations (NNR).Subjects/ Methods : Seventy obese postmenopausal women ( mean age 60 years , body mass index 33 kg/m2 ) were assigned to an ad libitum PD or NNR diet in a 2-year r and omized controlled trial . The primary outcome was change in fat mass as measured by dual-energy X-ray absorptiometry . Results : Both groups significantly decreased total fat mass at 6 months ( −6.5 and −2.6 kg ) and 24 months ( −4.6 and −2.9 kg ) , with a more pronounced fat loss in the PD group at 6 months ( P ) . Waist circumference and sagittal diameter also decreased in both the groups , with a more pronounced decrease in the PD group at 6 months ( −11.1 vs−5.8 cm , P=0.001 and −3.7 vs−2.0 cm , P respectively ) . Triglyceride levels decreased significantly more at 6 and 24 months in the PD group than in the NNR group ( P P=0.004 ) . Nitrogen excretion did not differ between the groups . Conclusions : A PD has greater beneficial effects vs an NNR diet regarding fat mass , abdominal obesity and triglyceride levels in obese postmenopausal women ; effects not sustained for anthropometric measurements at 24 months . Adherence to protein intake was poor in the PD group . The long-term consequences of these changes remain to be studied", "We served a low-fat ( 28 % of energy ) high-fibre ( 3.3 g/MJ ) diet according to Nordic Nutrition Recommendations ( REC diet ) , and a high-fat diet ( 39 % of energy ) corresponding to the average Danish diet ( DANE diet ) to 21 healthy middle-aged individuals in a two times two weeks cross-over study . The REC diet result ed in lower serum concentrations of low density lipoprotein ( LDL ) cholesterol ( medians : 2.77 vs 3.04 mmol/l , p high-density lipoprotein ( HDL ) cholesterol ( 1.08 vs 1.24 mmol/l , p higher fasting triglycerides ( 1.11 vs 0.86 mmol/l , p = 0.04 ) than the DANE diet . Furthermore , the REC diet lowered plasma factor VII coagulant activity ( FVIIc ) ( 88 vs 96 % , p = 0.002 ) and raised plasma fibrinolytic activity . Our observations indicate that a low-fat high-fibre diet may not only reduce the atherogenic , but also the thrombogenic tendency of an individual compared with a diet corresponding to the average Danish diet", "Introduction : Danish children consume too much sugar and not enough whole grain , fish , fruit , and vegetables . The Nordic region is rich in such foods with a strong health-promoting potential . We lack r and omised controlled trials that investigate the developmental and health impact of serving school meals based on Nordic foods . Aim : This paper describes the rationale , design , study population , and potential implication s of the Optimal well-being , development and health for Danish children through a healthy New Nordic Diet ( OPUS ) School Meal Study . Methods : In a cluster-r and omised cross-over design , 1021 children from 3rd and 4th grade s ( 8–11 years old ) at nine Danish municipal schools were invited to participate . Classes were assigned to two 3-month periods with free school meals based on the New Nordic Diet ( NND ) or their usual packed lunch ( control ) . Dietary intake , nutrient status , physical activity , cardiorespiratory fitness , sleep , growth , body composition , early metabolic and cardiovascular risk markers , illness , absence from school , wellbeing , cognitive function , social and cultural features , food acceptance , waste , and cost were assessed . Results : In total , 834 children ( 82 % of those invited ) participated . Although their parents were slightly better educated than the background population , children from various socioeconomic background s were included . The proportion of overweight and obese children ( 14 % ) resembled that of earlier examinations of Danish school children . Drop out was 8.3 % . Conclusions : A high inclusion rate and low drop out rate was achieved . This study will be the first to determine whether school meals based on the NND improve children ’s diet , health , growth , cognitive performance , and early disease risk markers", "OBJECTIVE the aim of this study was to investigate the effects of a healthy Nordic diet ( ND ) on cardiovascular risk factors . DESIGN AND SUBJECTS in a r and omized controlled trial ( NORDIET ) conducted in Sweden , 88 mildly hypercholesterolaemic subjects were r and omly assigned to an ad libitum ND or control diet ( subjects ' usual Western diet ) for 6 weeks . Participants in the ND group were provided with all meals and foods . Primary outcome measurements were low-density lipoprotein ( LDL ) cholesterol , and secondary outcomes were blood pressure ( BP ) and insulin sensitivity ( fasting insulin and homeostatic model assessment -insulin resistance ) . The ND was rich in high-fibre plant foods , fruits , berries , vegetables , whole grains , rapeseed oil , nuts , fish and low-fat milk products , but low in salt , added sugars and saturated fats . RESULTS the ND contained 27 % , 52 % , 19 % and 2 % of energy from fat , carbohydrate , protein and alcohol , respectively . In total , 86 of 88 subjects r and omly assigned to diet completed the study . Compared with controls , there was a decrease in plasma cholesterol ( -16 % , P , LDL cholesterol ( -21 % , P , high-density lipoprotein ( HDL ) cholesterol ( -5 % , P , LDL/HDL ( -14 % , P and apolipoprotein (apo)B/apoA1 ( -1 % , P reduced insulin ( -9 % , P = 0.01 ) and systolic BP by -6.6 ± 13.2 mmHg ( -5 % , P body weight decreased after 6 weeks in the ND compared with the control group ( -4 % , P for blood lipids , but not for insulin sensitivity or BP . There were no significant differences in diastolic BP or triglyceride or glucose concentrations . CONCLUSIONS a healthy ND improves blood lipid profile and insulin sensitivity and lowers blood pressure at clinical ly relevant levels in hypercholesterolaemic subjects", "Biomarkers of dietary intake can be important tools in nutrition research . Our aim was to assess whether plasma alkylresorcinol ( AR ) and β-carotene concentrations could be used as dietary biomarkers for whole-grain , fruits and vegetables in a healthy Nordic diet ( ND ) . Participants ( n = 166 ) , 30 - 65 y with a body mass index of 27 - 40 kg/m(2 ) and two more features of metabolic syndrome ( International Diabetes Federation definition , slightly modified ) , were recruited through six centers in the Nordic countries and r and omly assigned to an ND or control diet for 18 or 24 wk , depending on study center . Plasma AR and β-carotene were analyzed and nutrient intake calculated from 4-d food records . Median fiber intake increased in the ND group from 2.5 g/MJ at baseline to 4.1 g/MJ ( P 24 ) , and median ( IQR ) fasting plasma total AR concentration increased from 73 ( 88 ) to 106 ( 108 ) nmol/L , or 45 % , from baseline to end point ( P 0.001 ) . The AR concentration was significantly higher in the ND group ( P at end point . β-Carotene intake tended to increase in the ND group ( P = 0.07 ) , but the plasma β-carotene concentration did not change significantly throughout the study and did not differ between the groups at follow-up . In conclusion , an ND result ed in higher dietary fiber intake and increased plasma total AR concentration compared with the control diet , showing that the total AR concentration might be a valid biomarker for an ND in which whole-grain wheat and rye are important components . No significant difference in plasma β-carotene concentrations was observed between the ND and control groups , suggesting that β-carotene may not be a sensitive enough biomarker of the ND" ]

[ "Thirty-nine U.S. Air Force enlisted men participated in a r and omized controlled study that evaluated an experimental program design ed to enhance fitness . Subjects were assigned to either a treatment ( access to the program ) or control ( no access to program ) group for 6 months . To improve treatment group fitness ( as measured by VO2 , subjects received individually tailored information ( based on a behavior change model ) via the Internet to encourage adoption of positive diet and exercise behaviors . Results showed no significant effect in improving fitness in treatment . However , significant effects were observed for secondary outcomes such as weight ( controls , + 1.0 kg vs. treatment , -2.2 kg , p body mass index ( + 0.3 kg/m2 vs. -0.7 kg/m2 , p percent body fat ( + 0.6 % vs. -1.5 % , p not effective in encouraging sufficient exercise intensity to impact fitness . However , the dietary tailored information appears to have encouraged the adoption of more positive nutritional practice s as demonstrated by the beneficial effects reflected in secondary outcomes", "Excess weight is associated with negative health outcomes . Meal replacements are effective in promoting favorable body composition changes in civilian population s ; however , their efficacy with military service members who have unique lifestyles is unknown . The objective of this r and omized controlled trial was to determine the efficacy of the Army 's education-based weight-management program , \" Weigh to Stay , \" with and without meal replacements for improving blood lipids , and to promote weight and body fat loss in overweight US Army soldiers . Soldiers ( n=113 ; 76 males/37 females ) attending Weigh to Stay at Fort Bragg , NC , in 2006/2007 were r and omized to Weigh to Stay only or a commercially available meal-replacement program ( two meal replacements per day ) in conjunction with Weigh to Stay , and followed until Army body fat st and ards were met or for 6 months if st and ards were not met . Study completers ( n=46 ) in both treatment groups lost weight ( Weigh to Stay : -2.7+/-4.3 kg ; meal replacers : -3.8+/-3.5 kg ) and fat mass ( Weigh to Stay , -2.7+/-3.2 kg ; meal replacers : -2.9+/-2.5 kg ) , and improved high-density lipoprotein cholesterol concentrations ( Weigh to Stay : 13+/-9 mg/dL [ 0.34+/-0.23 mmol/L ] ; meal replacers : 8+/-7 mg/dL [ 0.21+/-0.18 mmol/L ] ; P Attrition was lower ( P=0.009 ) and success in meeting body fat st and ards tended to be higher ( P=0.06 ) for the meal replacers vs Weigh to Stay participants . Intent-to-treat analysis demonstrated that meal replacers lost more weight ( 1.2+/-0.5 kg ) , percent body fat ( 1.0%+/-0.4 % ) , and fat mass ( 0.8+/-0.4 kg ) compared to Weigh to Stay volunteers ( P meal replacement use can be recommended as a potential adjunct strategy to Weigh to Stay", "A higher body mass index is associated with exercise-related injuries and increased risk for musculoskeletal and connective tissue disorders , which are relevant to military personnel . Studies show the efficacy of orlistat 60 mg for promoting weight and body fat loss in civilians ; however , its efficacy among predominantly young , male soldiers is unknown . This study 's objective was to examine the effect of a 6-month , st and ard education-based weight-management program with and without orlistat 60 mg on changes in weight and body fat in overweight soldiers . Data were collected for this r and omized , controlled trial from March 2008 to November 2010 at Fort Bragg , NC . Participants were enrolled in an education-based weight management program ( n=435 ; 75 % men ) and were r and omized to placebo or orlistat 60 mg , three capsules daily with meals . All participants were recommended to maintain a reduced-energy , low-fat diet . Among study completers ( 14 % retention rate ; placebo n=22 , orlistat n=35 ) members of both groups lost significant weight from baseline ( placebo -3.0±5.2 kg ; orlistat -3.2±4.7 kg ; P orlistat group lost fat mass ( -2.5±3.9 kg ; P lost lean mass ( -1.4±2.7 kg ; P the orlistat group lost more fat mass vs the placebo group ( -1.3±2.9 kg vs ? 0.6±1.8 kg , respectively ; P less lean mass ( -0.2±2.0 kg vs -0.8±1.8 kg , respectively ; P 60 mg may be an effective adjunct to an education-based weight management program in a mostly young , male soldier population", "The aim of the present investigation was to study the effect of a dietary intervention which combined nutrition information with increased availability of vegetables , fruits and wholegrain bread . The effect of the intervention was determined by changes in the intake of vegetables , fruits , wholegrain bread and estimated nutrients . Furthermore , the study investigated whether changes in relative contribution from different food sources of folate were related to changes in the concentration of plasma total homocysteine ( p-tHcy ) . The 5-month intervention study included 376 male recruits from the Norwegian National Guard , Vaernes ( intervention group ) and 105 male recruits from the Norwegian National Guard , Heggelia ( control group ) . The study result ed in an increase in the total consumption of vegetables , fruits , berries and juice ( P wholegrain bread ( P intake of dietary fibre ( P folate ( P relative contribution of folate intake from fruits , vegetables and wholegrain bread was higher in the intervention group compared with the control group ( P increased intake of folate from wholegrain bread was inversely associated with a reduced concentration of p-tHcy ( P = 0.017 ) . In summary , the dietary intervention result ed in an increased intake of vegetables , fruits and wholegrain bread and a subsequent increase in folate intake from these food components . Reduction in the concentration of p-tHcy was significantly related to an increased folate intake due to an increased consumption of wholegrain bread", "This study assessed the effects of eight weeks of military training on aerobic fitness indices , military skills and neuropsychological function . Thirty five ( n=35 ) male Irish Defence Forces personnel , divided into training ( n=20 ) and control ( n=15 ) subgroups , completed tests of military aptitude ( Kim ’s games , judging distance , fire order , map reading , weapon assembly ) and neuropsychological function ( Symbol digit modalities test ( SDMT ) , Trail making test , Stroop test and grooved pegboard test ) pre- and post-intervention . The repeated measures study design sought to account for any learning effect . Participants also completed a 10 km route march , a two mile run and three by 20 m shuttle run tests at both time points to quantify changes in fitness variables . The training sub-group significantly ( P improved mean 20 m shuttle-run distance and consequently estimated VO2 max pre- to post-intervention ( 49.8±1.0 vs. 52.4±0.9 mL.kg-1.min-1 ) . Two mile run time was not significantly improved . Mean % HRmax during the 10 km route march was significantly higher in both training ( P improved performance in 3/18 neuropsychological test components and 2/12 military skills test components . Training significantly improved ability to estimate both short ( error ; 36±6 vs. 12±1 % ) and intermediate ( error ; 72±12 vs. 11±3 % ) distances post-intervention . The training sub-group significantly ( P improved SDMT score and mean Trail 1 time pre- to post-intervention ( 58.0±2.8 vs. 69.5±3.4 ; 18.1±0.8 vs. 14.4±0.8s , respectively ) . In Part 3 of the Stroop test , time mediated a significant ( P conclusion , aerobic fitness and a minority of neuropsychological and military skills tests improved following 8 weeks of military training", "The more consistently someone records their food intake the more likely they are to lose weight . We hypothesized that subjects who kept track via their preferred method would demonstrate higher adherence and therefore improved outcomes compared to those who used a non-preferred method . Participants were r and omly assigned to use a paper , PDA , or Web-based diary and classified as \" Preferred \" if they used their preferred method and \" Non-Preferred \" if they did not . Days adherent to diary use were collected for 12 weeks . Weight , % body fat , waist circumference , and self-efficacy scores were measured at baseline , 6 and 12 weeks . Thirty nine participants completed the 12 week study . Fifty nine percent were male . The mean age was 35 and mean baseline BMI was 33 kg/m(2 ) ( + /-3.5 ) . Forty four % ( n=17 ) used their \" Preferred \" diary method and 56 % ( n=22 ) did not . Participants who used their preferred diary were more adherent to recording both food intake ( 64.2 % vs. 43.4 % , p=.015 ) and exercise ( 60.6 % vs. 31.2 % , p=.001 ) . Though no difference was seen between groups on weight management outcomes , these results suggest that diary preference affects adherence to diary use", "OBJECTIVE To analyse the 5-year sustainability of a worksite canteen intervention of serving more fruit and vegetables ( F&V ) . DESIGN Average F&V consumption per customer per meal per day was assessed in five worksite canteens by weighing F&V served and subtracting waste . Data were collected by the canteen staff during a 3-week continuous period and compared to data from the same five canteens measured at baseline , at end point and at 1-year follow-up . The intervention used a participatory and empowering approach , self-monitoring and networking among the canteen staff , management and a consultant . The method focused on providing ideas for increased F&V for lunch , making environmental changes in the canteens by giving access to tasteful and healthy food choices and reducing the availability of unhealthy options . SETTING Five Danish worksites serving from 50 to 500 meals a day : a military base , an electronic component distributor , a bank , a town hall and a waste-h and ling facility . SUBJECTS Worksite canteen managers , canteen staff . RESULTS Four of the five worksite canteens were able to either maintain the intervention or even increase the consumption of F&V. The average increase from baseline to 5-year follow-up was 95 g per customer per meal per day ( 18 , 144 , 66 , 105 and 141 g , respectively ) . On average , the five canteens at the long-term follow-up had an F&V consumption of 208 g/meal per customer . CONCLUSIONS The present study indicates that sustainability of F&V is possible in worksites where the participatory and empowering approach , self-monitoring , environmental change , dialogue with suppliers and networking among worksite canteens are applied", "OBJECTIVE The specific aim was to determine whether a multifaceted approach to weight loss and physical readiness could be implemented onboard a deployed combatant ship of the U.S. Navy . RESEARCH METHODS AND PROCEDURES Thirty-nine men ( 31+/-6 years old , mean+/-st and ard deviation ) assigned to the USS ENTERPRISE ( CVN 65 ) during a 6-month Mediterranean deployment who had failed their previous Physical Readiness Test due to excessive body weight ( 108+/-11 kg overweight ) were r and omly assigned to nutrition , cognitive-behavioral obesity treatment plus exercise or to the Navy 's usual treatment ( control ) , which is exercise alone . RESULTS Outcomes for the treatment group were significantly better than the controls , with 8.6+/-5.0 vs. 5.0+/-4.1 kg weight loss , 8 % vs. 5 % reduction in original body weight , and body fat loss of 7 % vs. 5 % . Triglycerides declined significantly greater in the treatment group than the controls ( 145 mg/dL to 109 mg/dL vs. 146 mg/dL to 145 mg/dL , p depression and eating behaviors significantly improved among treated men . Problematic environmental factors were the limited variety of heart healthy foods in the galley , short meal breaks , and long mess hall lines that led to eating snacks from vending machines and frequent port calls . DISCUSSION Although greater weight loss than would be expected of a Navy usual care group diluted the treatment effect , the treated men still fared significantly better . The physical readiness implication of this research has the potential to impact Navy health promotion programs and policy , the health and well-being of its personnel , and the Navy 's ability to meet mission requirements", "Objective : To examine whether obesity is associated with increased presenteeism ( health-related limitations at work ) . Methods : R and omly selected manufacturing employees ( n = 341 ) were assessed via height and weight measures , demographic survey , wage data , and the Work Limitations Question naire . The Work Limitations Question naire measures productivity on four dimensions . Analyses of variance and analyses of covariance were computed to identify productivity differences based on body mass index ( BMI ) . Results : Moderately or extremely obese workers ( BMI ≥35 ) experienced the greatest health-related work limitations , specifically regarding time needed to complete tasks and ability to perform physical job dem and s. These workers experienced a 4.2 % health-related loss in productivity , 1.18 % more than all other employees , which equates to an additional $ 506 annually in lost productivity per worker . Conclusions : The relationship between BMI and presenteeism is characterized by a threshold effect , where extremely or moderately obese workers are significantly less productive than mildly obese workers", "This study evaluated whether using a web-linked accelerometer , plus m and atory physical training , is associated with various weight- and fitness-related outcomes in overweight/obese active duty soldiers . Soldiers who failed the height/weight st and ards of the Army Physical Fitness Test ( APFT ) were r and omized to use a Polar FA20 accelerometer device ( polar accelerometer group [ PA ] , n = 15 ) or usual care ( UC , n = 13 ) for 6 months . Both groups received 1.5 hours of lifestyle instruction . We collected data at baseline , 2 , 4 , and 6 months , and evaluated group differences in temporal changes in study outcomes . At 6 months , 1/28 subjects ( UC ) passed the APFT height/weight st and ards . There were no group differences in changes in weight ( PA : -0.1 kg vs. UC : + 0.3 kg ; p = 0.9 ) , body fat ( PA : -0.9 % vs. UC : -1.1 % ; p = 0.9 ) , systolic blood pressure ( PA : + 1.3 mm Hg vs. UC : -2.1 mm Hg ; p = 0.2 ) , diastolic blood pressure ( PA : + 3.8 mm Hg vs. UC : -2.4 mm Hg ; p = 0.3 ) , or resting heart rate in beats per minute ( bpm ) ( PA : + 7.8 bpm vs. UC : + 0.1 bpm ; p = 0.2 ) . These results suggest that using an accelerometer with web-based feedback capabilities plus m and atory physical training does not assist in significant weight loss or ability to pass the APFT height/weight st and ards among overweight/obese soldiers", "PURPOSE The study investigated the efficacy and cost-effectiveness of a cognitive-behavioral weight management program , complemented by an interactive Web site and brief telephone/e-mail coaching . METHODS In 2006 - 2007 , 1755 overweight , non-active-duty TRICARE beneficiaries were r and omized to one of three conditions with increasing intervention intensity : written material s and basic Web access ( RCT 1 ) , plus an interactive Web site ( RCT 2 ) , plus brief telephone/e-mail coaching support ( RCT 3 ) . The study assessed changes in weight , blood pressure , and physical activity from baseline to 6 , 12 , and 15 - 18 months . ( Study retention was 31 % at 12 months . ) Average and incremental cost-effectiveness and cost-offset analyses were conducted . RESULTS Participants experienced significant weight loss ( -4.0 % , -4.0 % , and -5.3 % , respectively , in each RCT group after 12 months and -3.5 % , -3.8 % , and -5.1 % , respectively , after 15 to 18 months ) , increased physical activity , and decreased blood pressure . Cost-effectiveness ratios were $ 900 to $ 1100/ quality -adjusted life year ( QALY ) for RCT 1 and RCT 2 and $ 1900/QALY for RCT 3 . The cost recovery period to the government was 3 years for RCTs 1 and 2 and 6 years for RCT 3 . CONCLUSION A relatively inexpensive cognitive-behavioral weight management intervention improved patient outcomes . Extrapolation of savings for the entire TRICARE population would significantly reduce direct medical costs", "OBJECTIVE To determine whether adoption of dietary patterns consistent with the US Dietary Guidelines for Americans and the Food Guide Pyramid , combined with exercise training , result in significant reductions in cardiovascular risk compared with a regimen of exercise therapy alone . DESIGN A r and omized trial to compare the effects of exercise alone ( n = 17 ) with the effects of exercise and dietary intervention ( n = 15 ) . SETTING McClellan Air Force Base medical clinic ( Sacramento , Calif ) . SUBJECTS Thirty-two members of the Air Force ( 20 men and 12 women ) were recruited at the time they entered a 90-day fitness improvement program . Mean age was 32 years . INTERVENTION All subjects participated in a 90-day fitness program . Half of the group received individualized dietary counseling using the Food Guide Pyramid as a primary educational tool . MAIN OUTCOME MEASURES Changes in body mass index , plasma lipids and lipoprotein levels , aerobic capacity , and dietary intake were selected to evaluate the effectiveness of the intervention . STATISTICAL ANALYSES PERFORMED Outcome measures were evaluated by analysis of variance . A paired t test was performed to compare changes in food-group servings and food-group fat intake from baseline values for the exercise-plus-diet group . RESULTS Percentage of energy from fat decreased from 39 % to 23 % for the exercise-plus-diet group , and servings from each of the food groups changed to reflect current guidelines . This group also had significant reductions in body mass index , total cholesterol level , and low-density lipoprotein level : 2 % ( P = .0001 ) , 9 % ( P = .003 ) , and 13 % ( P = .005 ) , respectively . No change was observed for the exercise-only group . Additionally , a significant improvement in maximum oxygen consumption ( P = .01 ) of 38 % ( vs 14 % for the control group ) was achieved . CONCLUSIONS Dietary modification in accordance with the Food Guide Pyramid and the US Dietary Guidelines results in significant reductions in known cardiovascular risk factors and improves the response to exercise training", "To compare the effects of a pedometer-based behavioral intervention ( Fitness for Life [ FFL ] program ) and a traditional high-intensity fitness ( TRAD ) program on physical activity ( PA ) , Army Physical Fitness Test ( APFT ) , and coronary heart disease risk factors in Army National Guard members who failed the APFT 2-mile run . From a pool of 261 Army National Guard , a total of 156 were r and omized to TRAD or FFL for 24 weeks consisting of a 12-week progressive conditioning program followed by 12 weeks of maintenance . For both groups , the total APFT score and 2-mile run time/score improved from baseline to 12 weeks ( FFL : down 7.4 % , p = 0.03 ; TRAD : down 5 % , p = 0.08 ) but at 24 weeks they had regressed toward baseline . PA improved modestly and coronary risk profile changed minimally in both groups . A pedometer-based exercise intervention had results similar to a high-intensity program for improving PA , APFT , and 2-mile run times/score . Neither group sustained the improved run times over the 12 weeks of maintenance", "BACKGROUND Most weight-loss research targets obese individuals who desire large weight reductions . However , evaluation of weight-gain prevention in overweight individuals is also critical as most Americans become obese as a result of a gradual gain of 1 - 2 pounds per year over many years . METHOD This study evaluated the efficacy of an Internet-based program for weight-loss and weight-gain prevention with a two-group , prospect i ve , r and omized controlled trial . A military medical research center with a population of 17,000 active-duty military personnel supplied 446 overweight individuals ( 222 men ; 224 women ) with a mean age of 34 years and a mean BMI of 29 . Recruitment and study participation occurred 2003 - 2005 and data were analyzed in 2006 . Participants were r and omly assigned to receive the 6-month behavioral Internet treatment ( BIT , n=227 ) or usual care ( n=224 ) . Change in body weight , BMI , percent body fat , and waist circumference ; presented as group by time interactions , were measured . RESULTS After 6 months , completers who received BIT lost 1.3 kg while those assigned to usual care gained 0.6 kg ( F((df=366))=24.17 ; I BMI ( -0.5 vs + 0.2 kg/m(2 ) ; F((df=366))=24.58 ) ; percent body fat ( -0.4 vs + 0.6 % ; F((df=366))=10.45 ) ; and waist circumference ( -2.1 vs -0.4 cm ; F((df=366))=17.09 ) ; p Internet-based weight-management interventions result in small amounts of weight loss , prevent weight gain , and have potential for widespread dissemination as a population health approach . TRIAL REGISTRATION NCT00417599", "Elevated body weight among active duty Air Force ( ADAF ) members is a substantial and growing problem , and typically results from gaining small amounts of weight each year over many years . We design ed a strategy to prevent annual weight gain in ADAF members using self-directed behavior change booklets followed by weekly e-mails about diet and physical activity for a year . The intervention was universally offered to ADAF members meeting selection criteria at five U.S. Air Force bases ( n = 3,502 ) ; members at 60 other U.S. Air Force bases served as controls ( n = 65,089 ) . The intervention was completely effective at preventing weight gain in a subgroup of men ( those above the lowest three ranks , with baseline weight above maximum allowable ) and in women , while controls continued to gain weight . Since the intervention did not require personalized contact , this approach has promise for large-scale population -based efforts aim ed at preventing weight gain in working adults", "A weight-loss treatment program for active duty military personnel is discussed and evaluated . The Fat Loss and Exercise Program at U.S. Army Hospital , Bremerhaven , Germany , consisted of a 3-week inpatient treatment program and 6 months of weekly outpatient follow-up . The program combined a multidisciplinary team approach to the treatment of obesity -- psychology , internal medicine , nursing , nutrition care , and physical therapy . Patients showed a significant weight and body fat loss [ F(2,90 ) = 52.91 and 65.85 , p Changes in cholesterol levels by treatment phase are also discussed . Results demonstrate positive increases in high-density lipoprotein at each phase . These results support a comprehensive , multidisciplinary inpatient treatment of obesity within the military", "Objectives : The aim of the Obesity Intervention Program of the German Army was to enhance physical activity levels , to adjust diet behavior , and to reduce risk factors in out patients over a period of 24 months . Methods : The data of the participants in the outpatient intervention from 2003 till 2011 were analyzed . Results : In total , 665 participants took part . All examined parameters were improved by the intervention , already in the second follow-up , significant for all parameters . A total of 12.2 % of all patients reduced their body weight by 5 % , and 8.4 % by 10 % . Conclusions : A significant improvement in all examined parameters was found . With respect to the fact that the participants of this Obesity Intervention Program were only military servicemen and servicewomen , it should be tested if the program can be transferred on work health promotions outside the military", "OBJECTIVE To determine whether a behavioral Internet treatment ( BIT ) program for weight management is a viable , cost-effective option compared with usual care ( UC ) in a diverse sample of overweight ( average body mass index = 29 kg/m2 ) , healthy adults ( mean age = 34 years ) serving in the US Air Force . STUDY DESIGN Two-group parallel r and omized controlled trial . METHODS Participants were r and omly assigned into 2 groups : UC ( n = 215 ) and UC plus BIT ( n = 227 ) . Baseline and 6-month assessment s were included in the analyses . Primary outcome measures ( changes in body weight , percent body fat , and waist circumference ) and secondary outcome measures ( Weight Efficacy Lifestyle [ WEL ] question naire ) were included in an incremental cost-effectiveness analysis ( ICEA ) model . Costs were computed using the perspective of an agency wanting to replicate the intervention . Sensitivity analyses were performed to measure the robustness of models . RESULTS Overall cost for BIT intervention was $ 11,178.40 , or $ 49.24 per BIT participant . Total staff-time cost was $ 14.03 per BIT participant . Intervention cost was $ 25.92 per kilogram of weight loss and $ 28.96 per centimeter of waist-circumference loss . The cost was $ 37.88 for each additional point gained on the WEL subscale , where increasing scores indicate increased confidence in managing social pressures to eat . CONCLUSIONS The BIT program is a cost-effective choice for weight management . It may cost more initially , but it results in long-term cost savings . Such cost-effective , Internet-based behavioral interventions for weight management could provide a valuable tool for preventive care aim ed at improving individual and societal health", "Background and purpose : Female athletes struggle harder than male athletes to lose body fat and maintain a leaner physique . The purpose of this study was to determine the effects of an educational and cognitive behavioral therapy (CBT)‐based intervention on knowledge , body composition , anxiety , stress , and nutritional intake . Methods : A r and omized controlled trial was conducted with 153 female athletes from the U.S. Air Force Academy ( USAFA ) . Participants were assigned to one of three groups : ( a ) a combined energy balance and CBT‐based intervention ( E1 ) ; ( b ) a CBT‐based intervention alone ( E2 ) ; and ( c ) a control group ( C ) . Main outcomes included a DXA scan for body composition , a knowledge test , the GAD‐7 for anxiety , the brief inventory of perceived stress ( BIPS ) for stress , and a 24‐h food recall . Findings : Significant improvement on knowledge of energy balance occurred in all three groups E1 ( p reductions in percentage of body fat occurred in E1 ( p the percent of fat consumed by E1 ( p and saturated fat consumed by both E1 and E2 ( p increase in stress as measured by the BIPS ( p combined energy balance and CBT‐based intervention improves knowledge and body fat . Implication s : The importance to assess knowledge , anxiety , stress , nutrition intake , and percentage of body fat in female athletes and to deliver evidence ‐based interventions to improve their health outcomes" ]

[ "Aim The aim of the present study was to investigate the occurrence of postoperative delirium ( POD ) in elderly patients undergoing transurethral resection of prostate ( TURP ) and to identify those factors associated with delirium . Methods From July 2010 to February 2015 , 358 patients , aged ≥65 years and undergoing TURP were prospect ively enrolled . Personal , medical and cognitive data , laboratory assessment s , pain intensity , preoperative medications , and details of hemodynamic control were collected as predictors of delirium . POD was assessed using the Confusion Assessment Method . Results In the present study , POD occurred in 28 out of 358 cases ( 7.8 % ) after TURP , with duration of 1–4 days . The multivariate analysis showed that old age and visual analog scale pain scores were associated with POD . Marital status , body mass index , education , alcohol consumption , smoking history , preoperative psychotropic medication usage , activities of daily living scores , preoperative Mini-Mental Status Examination score , anesthesia type , American Society of Anesthesiologists classification , or hypotensive episodes during surgery did not significantly correlate with the occurrence of POD . Conclusion Old age and pain intensity after surgery were found as the risk factors for the development of delirium in elderly patients undergoing TURP . These findings might help develop preventive strategies to decrease POD through targeted evaluation", "OBJECTIVES To preoperatively determine c and i date s at definitive risk of postoperative delirium ( POD ) , we identified relevant factors in patients with arteriosclerosis obliterans who underwent bypass surgery . DESIGN A prospect i ve cohort study . PATIENTS AND METHODS 299 patients ( age ≥ 60 years ) who underwent bypasses in 1995 - 2006 were enrolled . Cognitive impairment was assessed by the Revised Hasegawa Dementia Scale , the Confusion Assessment Method was also used , and severity was grade d as Grade I-III ( mild to severe ) based on the Delirium Rating Scale . All patients were followed for 3 years . RESULTS POD occurred in 88 patients ( 29 % ) , with a median age of 75 ( 10 ) years ( IQR ) . Onset was 2 ( 1 ) days postoperatively , and a duration of 2 ( 2 ) days was observed . POD was hyperactive in 89 % and was Grade I , II , and III in 11 % , 68 % , and 21 % respectively . Multiple logistic regression analysis identified the following risk factors for POD : age ≥ 72 years ( end-stage renal failure ( 0.001 ) , multiple occlusive lesions ( cognitive impairment ( 0.003 ) , and critical limb ischaemia ( 0.034 ) . The 3-year survival rate was similar when comparing POD and non-POD patients ( 84 % vs. 88 % , NS ) . CONCLUSIONS This study identified 5 risk factors for POD in patients undergoing bypasses for limb ischaemia . Long-term outcomes were similar when comparing the patients who experienced POD with those who did not", "Multimodal exercise programs incorporating traditional progressive resistance training ( PRT ) , weight-bearing impact training and /or balance training are recommended to reduce risk factors for falls and fracture . However , muscle power , or the ability to produce force rapidly , has emerged as a more crucial variable to functional decline than muscle strength or mass . The aim of this 12-month community-based r and omized controlled trial , termed Osteo-cise : Strong Bones for Life , was to evaluate the effectiveness and feasibility of a multimodal exercise program incorporating high-velocity (HV)-PRT , combined with an osteoporosis education and behavioral change program , on bone mineral density ( BMD ) , body composition , muscle strength and functional muscle performance in older adults . Falls incidence was evaluated as a secondary outcome . A total of 162 older adults ( mean ± SD ; 67 ± 6 years ) with risk factors for falls and /or low BMD were r and omized to the Osteo-cise program ( n = 81 ) or a control group ( n = 81 ) . Exercise consisted of fitness center-based HV-PRT , weight-bearing impact and challenging balance/mobility activities performed three times weekly . After 12 months , the Osteo-cise program led to modest but significant net gains in femoral neck and lumbar spine BMD ( 1.0 % to 1.1 % , p 0.05 ) , muscle strength ( 10 % to 13 % , p ( Timed Stair Climb , 5 % , p ) and dynamic balance ( Four Square Step Test 6 % , p on total body lean mass or mobility ( timed-up- and -go ) , and no difference in falls rate ( incidence rate ratio [ IRR ] , 1.22 ; 95 % confidence interval [ CI ] , 0.72 - 2.04 ) . In conclusion , this study demonstrates that the Osteo-cise : Strong Bones for Life community-based , multimodal exercise program represents an effective approach to improve multiple musculoskeletal and functional performance measures in older adults with risk factors for falls and /or low BMD . Although this did not translate into a reduction in the rate of falls , further large-scale trials are needed to evaluate the efficacy of this multimodal approach on reducing falls and fracture", "Background and objectives : Postoperative confusion and delirium is a common complication in the elderly with a poorly understood pathophysiology . The aim of this study was to examine whether the type of anaesthesia ( general or regional ) plays a role in the development of cognitive impairment in elderly patients during the immediate postoperative period . Methods : Forty‐seven patients > 60 yr of age and undergoing major surgery were r and omly allocated to receive either regional or general anaesthesia . The mental status of the patients was assessed preoperatively and during the first three postoperative days with the Mini Mental State Examination . The incidence of delirium was also examined during the same period with the use of DSM III criteria . Results : Overall , during the first three postoperative days , the mean Mini Mental State Examination score decreased significantly ( P general anaesthesia ( P anaesthesia . Nine patients developed delirium but the type of anaesthesia did not affect its incidence . The only important factor for the development of delirium was pre‐existing cardiovascular disease irrespective of anaesthesia type ( P Elderly patients subjected to general anaesthesia displayed more frequent cognitive impairment during the immediate postoperative period in comparison to those who received a regional technique", "OBJECTIVE To determine the incidence , and severity of postoperative delirium ( POD ) in older patients undergoing elective orthopedic procedures and to identify potential preoperative risk factors . DESIGN A prospect ively studied cohort of elective orthopedic surgery patients . SETTING A University teaching hospital . PATIENTS Eighty patients who attended a preadmission clinic and , subsequently , underwent elective orthopedic surgery . All patients were aged 60 years or older , and all spoke English . MEASUREMENTS Patients underwent preoperative medical , cognitive , and activities of daily living assessment with st and ardized instruments and were followed postoperatively with daily visits , telephone interviews with attending nurses using a modified confusion assessment model ( CAM ) , and repeated cognitive testing . Suspected delirium was verified by direct physician assessment . RESULTS The elective group had 14 ( 17.5 % ) cases of POD , of which six ( 7.5 % ) were severe . These incidences are low compared with those of nonelective surgery groups reported elsewhere in the literature . Stepwise multiple logistic regression identified two POD risk factors : clock-drawing scores male gender ( OR = 5.6 , CI 1.9 to 33.8 ) . CONCLUSION A simple model using clock-drawing scores and male gender for preoperative identification of elective patients at greatest risk for POD appears sensitive , predictive , and practical for the preadmission clinic setting , but it should be vali date d in a prospect i ve trial", "OBJECTIVE To develop and vali date a new st and ardized confusion assessment method ( CAM ) that enables nonpsychiatric clinicians to detect delirium quickly in high-risk setting s. DESIGN Prospect i ve validation study . SETTING Conducted in general medicine wards and in an outpatient geriatric assessment center at Yale University ( site 1 ) and in general medicine wards at the University of Chicago ( site 2 ) . PATIENTS The study included 56 subjects , ranging in age from 65 to 98 years . At site 1 , 10 patients with and 20 without delirium participated ; at site 2 , 16 patients with and 10 without delirium participated . MEASUREMENTS AND MAIN RESULTS An expert panel developed the CAM through a consensus building process . The CAM instrument , which can be completed in less than 5 minutes , consists of nine operationalized criteria from the Diagnostic and Statistical Manual of Mental Disorders ( DSM-III-R ) . An a priori hypothesis was established for the diagnostic value of four criteria : acute onset and fluctuating course , inattention , disorganized thinking , and altered level of consciousness . The CAM algorithm for diagnosis of delirium required the presence of both the first and the second criteria and of either the third or the fourth criterion . At both sites , the diagnoses made by the CAM were concurrently vali date d against the diagnoses made by psychiatrists . At sites 1 and 2 values for sensitivity were 100 % and 94 % , respectively ; values for specificity were 95 % and 90 % ; values for positive predictive accuracy were 91 % and 94 % ; and values for negative predictive accuracy were 100 % and 90 % . The CAM algorithm had the highest predictive accuracy for all possible combinations of the nine features of delirium . The CAM was shown to have convergent agreement with four other mental status tests , including the Mini-Mental State Examination . The interobserver reliability of the CAM was high ( kappa = 0.81 - 1.0 ) . CONCLUSIONS The CAM is sensitive , specific , reliable , and easy to use for identification of delirium", "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", "OBJECTIVES Delirium is a common complication in elderly patients after cardiac surgery and is associated with adverse outcomes including prolonged hospital stay and increased mortality . Therefore , prevention or early detection of delirium is indicated . Our objective was to identify preoperative and operative characteristics that could predict delirium after cardiac surgery in elderly patients . METHODS We conducted a prospect i ve cohort study in which we analysed 201 patients of 70 years and older who underwent cardiac surgery , for developing a delirium . Patients were assessed daily using the Confusion Assessment Method -Intensive Care Unit . RESULTS Sixty-three patients ( 31 % ) developed a delirium after cardiac surgery . The Mini-Mental State Examination ( MMSE ) score prior to surgery was lower in the delirious patients when compared with the non-delirious patients ( 27 vs. 28 , P = 0.026 ) , creatinine level was higher ( 98 vs. 88 μmol/l , P = 0.003 ) and extracorporeal circulation ( ECC ) time was longer ( 145 vs. 113 min , P ) . Mortality during the first 30 days after surgery in patients with delirium was significantly higher than that in the non-delirious patients ( 14 vs. 0 % , P Low MMSE score and high creatinine level prior to surgery as well as increased ECC time are important independent predictors of delirium . In addition , delirium is an important predictor of 30-day mortality . Patients with a substantial risk for delirium should be c and i date s for interventions to reduce postoperative delirium and to potentially improve overall surgical outcomes", "BACKGROUND delirium is a clinical syndrome associated with multiple short and long-term complications and therefore prevention is an essential part of its management . This study was design ed to assess the efficacy of multicomponent intervention in delirium prevention . METHODS a total of 287 hospitalised patients at intermediate or high risk of developing delirium were r and omised to receive a non-pharmacological intervention delivered by family members ( 144 patients ) or st and ard management ( 143 patients ) . The primary efficacy outcome was the occurrence of delirium at any time during the course of hospitalisation . Three vali date d observers performed the event adjudication by using the confusion assessment method screening instrument . RESULTS there were no significant differences in the baseline characteristics between the two groups . The primary outcome occurred in 5.6 % of the patients in the intervention group and in 13.3 % of the patients in the control group ( relative risk : 0.41 ; confidence interval : 0.19 - 0.92 ; P = 0.027 ) . CONCLUSION the results of this study show that there is a benefit in the non-pharmacological prevention of delirium using family members , when compared with st and ard management of patients at risk of developing this condition", "Introduction Frail patients have decreased physiological reserves and consequently , they are unable to recover as quickly from surgery . Frailty , as an entity , is a risk factor of increased morbidity and mortality . It is also associated with a longer time to discharge . This trial is undertaken to determine if a novel prehabilitation protocol ( 10-day bundle of interventions —physiotherapy , nutritional supplementation and cognitive training ) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery , compared with st and ard care . Methods and analysis This is a prospect i ve , single-centre , r and omised controlled trial with two parallel arms . 62 patients who are frail and undergoing elective abdominal surgery will be recruited and r and omised to receive either a novel prehabilitation protocol or st and ard care . Participants will receive telephone reminders preoperatively to encourage protocol compliance . Data will be collected for up to 30 days postoperatively . The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission . Ethics and dissemination This study has been approved by the Singapore General Hospital Institutional Review Board ( CIRB Ref : 2016/2584 ) . The study is also listed on Clinical Trials.gov ( Trial number : NCT02921932 ) . All participants will sign an informed consent form before r and omisation and translators will be made available to non-English speaking patients . The results of this study will be published in peer- review ed journals as well as national and international conferences . The data collected will also be made available in a public data repository . Trial registration number NCT02921932 ( Clinical Trials.gov", "Introduction Smoking is highly addictive , and nicotine abstinence is associated with withdrawal syndrome in hospitalized patients . In this study , we aim ed to evaluate the impact of sudden nicotine abstinence on the development of agitation and delirium , and on morbidities and outcomes in critically ill patients who required respiratory support , either noninvasive ventilation or intubation , and mechanical ventilation . Methods We conducted a prospect i ve , observational study in two intensive care units ( ICUs ) . The 144 consecutive patients admitted to ICUs and requiring mechanical ventilation for > 48 hours were included . Smoking status was assessed at ICU admission by using the Fagerström Test of Nicotine Dependence ( FTND ) . Agitation , with the Sedation-Agitation Scale ( SAS ) , and delirium , with the Intensive Care Delirium Screening Checklist ( ICDSC ) , were tested twice daily during the ICU stay . Agitation and delirium were defined by SAS > 4 and ICDSC > 4 , respectively . Nosocomial complications and outcomes were evaluated . Results Smokers ( n = 44 ) were younger and more frequently male and were more likely to have a history of alcoholism and to have septic shock as the reason for ICU admission than were nonsmokers . The incidence of agitation , but not delirium , increased significantly in the smoker group ( 64 % versus 32 % ; P = 0.0005 ) . Nicotine abstinence was associated with higher incidences of self-removal of tubes and catheters , and with more interventions , including the need for supplemental sedatives , analgesics , neuroleptics , and physical restraints . Sedation-free days , ventilator-free days , length of stay , and mortality in ICUs did not differ between groups . Multivariate analysis identified active smoking ( OR , 3.13 ; 95 % CI , 1.45 - 6.74 ; P = 0.003 ) as an independent risk factor for agitation . Based on a subgroup of 56 patients , analysis of 28 pairs of patients ( smokers and nonsmokers in a 1:1 ratio ) matched for age , gender , and alcoholism status found similar results regarding the role of nicotine withdrawal in increasing the risk of agitation during an ICU stay . Conclusions Nicotine withdrawal was associated with agitation and higher morbidities in critically ill patients . These results suggest the need to look specifically at those patients with tobacco dependency by using the FTND in ICU setting s. Identifying patients at risk of behavioral disorders may lead to earlier interventions in routine clinical practice", "This systematic review examines the effectiveness of current exercise interventions for the management of frailty . Eight electronic data bases were search ed for r and omized controlled trials that identified their participants as “ frail ” either in the title , abstract , and /or text and included exercise as an independent component of the intervention . Three of the 47 included studies utilized a vali date d definition of frailty to categorize participants . Emerging evidence suggests that exercise has a positive impact on some physical determinants and on all functional ability outcomes reported in this systematic review . Exercise programs that optimize the health of frail older adults seem to be different from those recommended for healthy older adults . There was a paucity of evidence to characterize the most beneficial exercise program for this population . However , multicomponent training interventions , of long duration ( ≥5 months ) , performed three times per week , for 30–45 minutes per session , generally had superior outcomes than other exercise programs . In conclusion , structured exercise training seems to have a positive impact on frail older adults and may be used for the management of frailty", "BACKGROUND Since in hospitalized older patients delirium is associated with poor outcomes , we evaluated the effectiveness of a multicomponent strategy for the prevention of delirium . METHODS We studied 852 patients 70 years of age or older who had been admitted to the general-medicine service at a teaching hospital . Patients from one intervention unit and two usual-care units were enrolled by means of a prospect i ve matching strategy . The intervention consisted of st and ardized protocol s for the management of six risk factors for delirium : cognitive impairment , sleep deprivation , immobility , visual impairment , hearing impairment , and dehydration . Delirium , the primary outcome , was assessed daily until discharge . RESULTS Delirium developed in 9.9 percent of the intervention group as compared with 15.0 percent of the usual-care group , ( matched odds ratio , 0.60 ; 95 percent confidence interval , 0.39 to 0.92 ) . The total number of days with delirium ( 105 vs. 161 , P=0.02 ) and the total number of episodes ( 62 vs. 90 , P=0.03 ) were significantly lower in the intervention group . However , the severity of delirium and recurrence rates were not significantly different . The overall rate of adherence to the intervention was 87 percent , and the total number of targeted risk factors per patient was significantly reduced . Intervention was associated with significant improvement in the degree of cognitive impairment among patients with cognitive impairment at admission and a reduction in the rate of use of sleep medications among all patients . Among the other risk factors per patient there were trends toward improvement in immobility , visual impairment , and hearing impairment . CONCLUSIONS The risk-factor intervention strategy that we studied result ed in significant reductions in the number and duration of episodes of delirium in hospitalized older patients . The intervention had no significant effect on the severity of delirium or on recurrence rates ; this finding suggests that primary prevention of delirium is probably the most effective treatment strategy", "Primary arthroplasty may be denied to very elderly patients based upon the perceived outcome and risks associated with surgery . This prospect i ve study compared the outcome , complications , and mortality of total hip ( TKR ) and total knee replacement ( TKR ) in a prospect ively selected group of patients aged ≥ 80 years with that of a control group aged between 65 and 74 years . There were 171 and 495 THRs and 185 and 492 TKRs performed in the older and control groups , respectively . No significant difference was observed in the mean improvement of Oxford hip and knee scores between the groups at 12 months ( 0.98 , ( 95 % confidence interval ( CI ) -0.66 to 2.95 ) , p = 0.34 and 1.15 ( 95 % CI -0.65 to 2.94 ) , p = 0.16 , respectively ) . The control group had a significantly ( p = 0.02 and p = 0.04 , respectively ) greater improvement in the physical well being component of their SF-12 score , but the older group was more satisfied with their THR ( p = 0.047 ) . The older group had a longer hospital stay for both THR ( 5.9 versus 9.0 days , p p 0.0001 ) . The rates of post-operative complications and mortality were increased in the older group", "OBJECTIVE To examine the association between the outcomes of a pre-operative comprehensive geriatric assessment ( CGA ) and the risk of severe post-operative complications in elderly patients electively operated for colorectal cancer . METHODS One hundred seventy-eight consecutive patients ≥ 70 years electively operated for all stages of colorectal cancer were prospect ively examined . A pre-operative CGA was performed , and patients were categorized as fit , intermediate , or frail . The main outcome measure was severe complications within 30 days of surgery . RESULTS Twenty-one patients ( 12 % ) were categorized as fit , 81 ( 46 % ) as intermediate , and 76 ( 43 % ) as frail . Eighty-three patients experienced severe complications , including three deaths ; 7/21 ( 33 % ) of fit patients , 29/81 ( 36 % ) of intermediate patients and 47/76 ( 62 % ) of frail patients ( p=0.002 ) . Increasing age and ASA classification were not associated with complications in this series . CONCLUSION CGA can identify frail patients who have a significantly increased risk of severe complications after elective surgery for colorectal cancer", "BACKGROUND The prevalence of comorbidities and functional impairment among elderly patients may enhance the risk of operation-related complications , but the importance of these conditions in elderly patients undergoing thoracic surgery remains unclear . METHODS One hundred twenty patients > /= 60 years of age who underwent thoracic surgery were registered prospect ively and examined . A comprehensive geriatric assessment ( CGA ) that evaluated such diverse areas as functional status ( ie , performance status and activities of daily living [ ADLs ] using the Barthel index ) , comorbidity , nutrition ( ie , body mass index , arm-muscle circumference , albumin level , transferrin level , lymphocyte count , and cholinesterase level ) , and cognitive function ( ie , mini-mental state examination [ MMSE ] and negative emotions for operation ) was performed in the 2 weeks before patients underwent the operation . RESULTS The diseases of the 120 patients were as follows : lung cancer , 85 patients ; mediastinal tumor , 14 patients ; bullas , 12 patients ; and other diseases , 9 patients . Postoperative complications developed in 20 patients ( 16.7 % ) . The patients with dependence for performing the ADLs , and dementia were more likely to develop postoperative complications ( p = 0.041 , and p = 0.0065 , respectively ) . The patients who experienced longer operation times ( ie , > /= 300 min ; p = 0.018 ) were more likely to have complications . The incidence of prolonged air leak in the patients with malnutrition increased seven-fold ( p = 0.045 ) and that of postoperative infectious diseases in those patients with obesity increased 24-fold ( p = 0.0013 ) , while all patients who developed delirium had low scores in the MMSE preoperatively ( p = 0.0003 ) . Using multiple logistic regression , the best model was obtained with a combination of MMSE ( p = 0.031 ) and the Barthel index ( p = 0.04 ) . When the operation variables were added to this model , the operation time had the strongest effect ( p = 0.016 ) . CONCLUSIONS Dependence for the performance of ADLs and impaired cognitive conditions are important predictors of postoperative complications , especially when the operation time is long . CGA is necessary in addition to the conventional cardiopulmonary functional assessment in elderly patients", "Objective : The aim of this prospect i ve study was to determine incidence , duration , and risk factors for postoperative delirium ( PD ) in elderly patients undergoing major abdominal surgery . Summary Background Data : The incidence and risk factors of PD after major abdominal surgery in elderly patients are not well documented . Methods : From May 2006 to May 2008 , 118 patients aged 75 years or more without severe preoperative cognitive dysfunction ( mini mental state examination score > 10/30 ) and undergoing major elective abdominal surgery were included . The preoperative geriatric assessment battery consisted of 4 tests evaluating physical ( instrumental activities of daily living and timed get up and go test score ) and cognitive function ( mini mental state examination score ) , and detecting the presence of an underlying depression ( Short-GDS ) . After the operation , geriatric patients were assessed for PD by the Confusion Assessment Method . Univariate and multivariate analyses were used to determine risk factors for PD . Results : Overall , PD occurred in 28 patients ( 24 % ) . Multivariate analysis showed that an American Society of Anesthesiologists status of 3–4 ( P = 0.02 ) , impaired mobility ( timed get up and go test score > 20 seconds ) ( P = 0.009 ) and postoperative tramadol administration ( P = 0.0009 ) were risk factors for PD . The mortality rate was 14 % in 28 patients with PD and 3.3 % in 90 patients without PD ( P = 0.051 ) . The morbidity rate was 35.5 % in 28 patients with PD and 32 % in 90 patients without PD ( NS ) . The mean hospital stay was 19 ± 11 days for patients with PD and 14 ± 8 for patients without PD ( P = 0.01 ) . Fifteen of 24 ( 62.5 % ) surviving patients with PD and 28 of 87 ( 32 % ) surviving patients without PD were discharged to geriatric rehabilitation unit ( P = 0.007 ) . Conclusions : PD is a frequent and severe postoperative event in elderly patients after major abdominal surgery . A perioperative geriatric assessment should be recommended to patients with an American Society of Anesthesiologists status of 3–4 and preoperative impaired mobility to facilitate the management of PD . In these patients , the postoperative administration of tramadol should be avoided", "Background The aim of this study was to evaluate the long term effects after discharge of a hospital-based geriatric liaison intervention to prevent postoperative delirium in frail elderly cancer patients treated with an elective surgical procedure for a solid tumour . In addition , the effect of a postoperative delirium on long term outcomes was examined . Methods A three month follow-up was performed in participants of the Liaison Intervention in Frail Elderly study , a multicentre , prospect i ve , r and omized , controlled trial . Patients were r and omized to st and ard treatment or a geriatric liaison intervention . The intervention consisted of a preoperative geriatric consultation , an individual treatment plan targeted at risk factors for delirium and daily visits by a geriatric nurse during the hospital stay . The long term outcomes included : mortality , rehospitalisation , Activities of Daily Living ( ADL ) functioning , return to the independent pre-operative living situation , use of supportive care , cognitive functioning and health related quality of life . Results Data of 260 patients ( intervention n = 127 , Control n = 133 ) were analysed . There were no differences between the intervention group and usual-care group for any of the outcomes three months after discharge . The presence of postoperative delirium was associated with : an increased risk of decline in ADL functioning ( OR : 2.65 , 95 % CI : 1.02–6.88 ) , an increased use of supportive assistance ( OR : 2.45 , 95 % CI : 1.02–5.87 ) and a decreased chance to return to the independent preoperative living situation ( OR : 0.18 , 95 % CI : 0.07–0.49 ) . Conclusions A hospital-based geriatric liaison intervention for the prevention of postoperative delirium in frail elderly cancer patients undergoing elective surgery for a solid tumour did not improve outcomes 3 months after discharge from hospital . The negative effect of a postoperative delirium on late outcome was confirmed . Trial Registration Nederl and s Trial Register , Trial ID NTR 823", "Background : Postoperative delirium , a common complication in the elderly , can occur following any type of surgery and is associated with increased morbidity and mortality ; it may also be associated with subsequent cognitive problems . Effective therapy for postoperative delirium remains elusive because the causative factors of delirium are likely multiple and varied . Methods : Patients 65 yr or older undergoing elective knee arthroplasty were prospect ively evaluated for postoperative Diagnostic and Statistical Manual of Mental Disorders-IV delirium . Exclusion criteria included dementia , mini-mental state exam score less than 24 , delirium , clinical ly significant central nervous system/neurologic disorder , current alcoholism , or any serious psychiatric disorder . Delirium was assessed on postoperative days 2 and 3 using st and ardized scales . Patients ' preexisting medical conditions were obtained from medical charts . The occurrence of obstructive sleep apnea was confirmed by contacting patients to check their polysomnography records . Data were analyzed using Pearson chi-square or Wilcoxon rank sum tests and multiple logistic regressions adjusted for effects of covariates . Results : Of 106 enrolled patients , 27 ( 25 % ) developed postoperative delirium . Of the 15 patients with obstructive sleep apnea , eight ( 53 % ) experienced postoperative delirium , compared with 19 ( 20 % ) of the patients without obstructive sleep apnea ( P = 0.0123 , odds ratio : 4.3 ) . Obstructive sleep apnea was the only statistically significant predictor of postoperative delirium in multivariate analyses . Conclusions : This is the first prospect i ve study employing vali date d measures of delirium to identify an association between preexisting obstructive sleep apnea and postoperative delirium", "OBJECTIVES To investigate whether preoperative risk for delirium moderates the effect of postoperative pain and opioids on the development of postoperative delirium . DESIGN Prospect i ve cohort study . SETTING University medical center . PARTICIPANTS Patients 65 years of age or older scheduled for major noncardiac surgery . MEASUREMENTS A structured interview was conducted preoperatively and postoperatively to determine the presence of delirium , defined using the Confusion Assessment Method . We first developed a prediction model to determine which patients were at high versus low risk for the development of delirium based on preoperative patient data . We then computed a logistic regression model to determine whether preoperative risk for delirium moderates the effect of postoperative pain and opioids on incident delirium . RESULTS Of 581 patients , 40 % developed delirium on days 1 or 2 after surgery . Independent preoperative predictors of postoperative delirium included lower cognitive status , a history of central nervous system disease , high surgical risk , and major spine and joint arthroplasty surgery . Compared with the patients at low preoperative risk for developing delirium , the relative risk for postoperative delirium for those in the high preoperative risk group was 2.38 ( 95 % confidence interval : 1.67 - 3.40 ) . A significant three-way interaction indicates that preoperative risk for delirium significantly moderated the effect of postoperative pain and opioid use on the development of delirium . Among patients at high preoperative risk for development of delirium who also had high postoperative pain and received high opioid doses , the incidence of delirium was 72 % , compared with 20 % among patients with low preoperative risk , low postoperative pain , and those who received low opioid doses . CONCLUSIONS High levels of postoperative pain and using high opioid doses increased risk for postoperative delirium for all patients . The highest incidence of delirium was among patients who had high preoperative risk for delirium and also had high postoperative pain and used high opioid doses", "We investigated the relationship between postoperative confusion and duration of benzodiazepine exposure , preoperative anxiety , depressive state , and cognitive function in elderly patients regularly taking benzodiazepines . We studied 328 patients ranging in age from 65 to 80 yr who underwent orthopedic surgery . Information on benzodiazepine use was obtained by face-to-face interview and visual assessment of the patient ’s medicine chest . Postoperative confusion was assessed by using a confusion- assessment method . The patients were divided into two groups : those who regularly took benzodiazepines and those who did not . Fifty-seven ( 17 % ) of 328 patients were treated with benzodiazepines . There were no significant differences in preoperative Mini-Mental State ( MMS ) scores , anxiety scores , or depression scores between benzodiazepine users and nonusers . Postoperative confusion occurred in 15 ( 26 % ) of 57 benzodiazepine users and in 34 ( 13 % ) of 271 nonusers ( P score 23 on the MMS were 5 ( 9 % ) of 57 benzodiazepine users and 8 ( 3 % ) of 271 nonusers ( P Postoperative confusion occurred in 13 ( 35 % ) of 37 long-term benzodiazepine users ( daily use for > 1 yr ) and in 2 ( 10 % ) of 20 short-term users ( daily use for postoperative confusion was significantly more frequent in long-term than in short-term benzodiazepine users or nonusers of benzodiazepines . The patients who developed a score were 5 ( 14 % ) of 37 long-term benzodiazepine users and 0 ( 0 % ) of 20 short-term benzodiazepine users . In conclusion , the incidence of postoperative confusion was significantly more frequent in long-term benzodiazepine users", "BACKGROUND : Postoperative delirium ( POD ) is common in the elderly and associated with adverse outcomes . The cognitive and functional sequelae of POD in elective surgical patients are not known . We sought to determine whether ( 1 ) lower scores on sensitive neurocognitive tests are an independent risk factor for POD in elderly surgical patients , and ( 2 ) POD predicts cognitive and functional decline 3 months postoperatively . METHODS : We conducted a prospect i ve , cohort study on patients ≥65 years old undergoing total hip or knee arthroplasty . Participants underwent preoperative neurocognitive and functional testing . POD was diagnosed using the Confusion Assessment Method . Patients who developed POD and matched controls underwent repeat neurocognitive and functional testing 3 months after surgery . RESULTS : Four hundred eighteen patients met entry criteria , and 42 ( 10 % ) developed POD . There were no differences in baseline Mini-Mental State Examination scores , alcohol abuse , depression , and verbal intelligence between groups . Independent predictors of POD included age , history of psychiatric illness , decreased functional status , and decreased verbal memory . For all tests , changes from before to 3 months after surgery were similar between those patients with POD and matched controls . CONCLUSIONS : Subtly reduced preoperative neurocognitive and functional status predict POD . However , in the small group that developed POD , there was no evidence of cognitive and functional decline 3 months after surgery . POD is associated with decreased preoperative cognitive reserve but , in elderly elective surgical patients , may be without adverse cognitive or functional sequelae 3 months postoperatively", "OBJECTIVES Delirium is a common and critical clinical syndrome in older patients . We examined whether abnormalities in the brain that could be assessed by magnetic resonance imaging predisposed patients to develop delirium after coronary artery bypass graft surgery . We also analysed the association between delirium and cognitive dysfunction after coronary artery bypass graft surgery . METHODS Data were collected prospect ively on 153 patients aged 60 years or older who consecutively underwent elective isolated coronary artery bypass graft surgery . All patients were assessed for prior cerebral infa rct ions and craniocervical artery stenosis by magnetic resonance imaging ( MRI ) and angiography of their brains . Atherosclerosis of the ascending aorta was examined by epiaortic ultrasound at the time of surgery . Individual cognitive status was measured using four tests in all the patients before surgery and on the seventh postoperative day . A single psychiatrist diagnosed delirium using the Diagnostic and Statistical Manual of Mental Disorders 4th edition IV criteria . RESULTS Postoperative delirium occurred in 16 patients ( 10.5 % ) . Compared with patients who did not develop postoperative delirium , delirious patients had significantly higher rates of peripheral artery disease , preoperative decline in global cognitive function and pre-existing multiple cerebral infa rct ions on MRI . In addition , 9 ( 56 % ) of the delirious patients suffered postoperative cognitive dysfunction . Stepwise logistic regression analysis found significant independent predictors of postoperative delirium to be preoperative cerebral infa rcts on MRI ( odds ratio [ OR ] , 2.26 ; 95 % confidence interval [ CI ] 1.10 - 4.78 ) , preoperative decline in global cognitive function ( OR 4.54 ; 95 % CI 1.21 - 16.51 ) and atherosclerosis of the ascending aorta ( OR 2.44 ; 95 % CI 1.03 - 5.62 ) . CONCLUSIONS Our findings suggested that postoperative delirium was associated with pre-existing multiple cerebral infa rct ions on MRI , preoperative decline in global cognitive function and ascending aortic atherosclerosis in elderly patients undergoing coronary artery bypass graft surgery and increased risk of postoperative cognitive dysfunction", "Background : Although delirium is a common problem in elderly patients undergoing surgery , st and ard delirium care is not available in all wards . The object of this study was to determine the incidence , risk factors and outcomes of postoperative delirium among patients aged 65 and above undergoing elective abdominal surgery at a surgical ward with a high st and ard delirium care . Methods : Prospect i ve descriptive survey in 71 patients . The Delirium Observation Scale was used to screen for delirium . Patients were classified as having a delirium if they met the DSM IV- criteria . Delirious and nondelirious patients were compared and associated risk factors were calculated using logistic regression analyses . Results : Incidence of postoperative delirium was 24 % . Univariate analysis showed that age above 74 years , CST score , ASA score , length of ICU stay , length of hospital stay and number of complications were significant risk factors for delirium . Older age , however , was the only significant risk factor in multivariate analysis ( OR 1.16 ; 95 % CI 1.00–1.35 ; p = 0.05 ) . Lastly , mortality was significantly higher in the delirium group ( 29.4 vs. 3.7 % ; p = 0.001 ) . Conclusion : At a surgical ward with high st and ard delirium care , the incidence of delirium was 24 % and mortality was higher in delirious patients undergoing elective abdominal surgery", "Purpose : To compare the effectiveness of supervised Tai Chi exercises versus the conventional physical therapy exercises in a personalized rehabilitation program in terms of the incidence and severity of falls in a frail older population . Method : The participants were frail older adults living in the community , admitted to the day hospital program in Sherbrooke , Quebec , Canada ( n = 152 ) . They were r and omized to receive a 15-week intervention , either by supervised Tai Chi exercises ( n = 76 ) or conventional physical therapy ( n = 76 ) . Fall incidence and severity were assessed using both the calendar technique and phone interviews once a month during 12 months following the end of the intervention . Other variables were collected at baseline to compare the two groups : age , comorbidity , balance , sensory interaction on balance , and self-rated health . Results : Both interventions demonstrated a protective effect on falls but Tai Chi showed a greater one ( RR = 0.74 ; 95 % CI = 0.56–0.98 ) as compared to conventional physical therapy exercises . Conclusions : Supervised Tai Chi exercises as part of a rehabilitation program seem to be a more effective alternative to the conventional physical therapy exercises for this specific population . Implication s for Rehabilitation Seniors who have fallen have a 50 % chance of falling again during the following year , leading them to reduce their outings and thus decrease their social activities . Frail older people could benefit more from an individualized intervention than the regular group program generally used in a Tai Chi intervention . Tai Chi exercises seems to be a good alternative to regular physiotherapy exercises as a part of a multidisciplinary intervention in preventing a subsequent fall over a 12-month period", "RATIONALE Excess mortality and residual disability are common after hip fracture . HYPOTHESIS Twelve months of high-intensity weight-lifting exercise and targeted multidisciplinary interventions will result in lower mortality , nursing home admissions , and disability compared with usual care after hip fracture . DESIGN R and omized , controlled , parallel-group superiority study . SETTING Outpatient clinic PARTICIPANTS Patients ( n = 124 ) admitted to public hospital for surgical repair of hip fracture between 2003 and 2007 . INTERVENTION Twelve months of geriatrician-supervised high-intensity weight-lifting exercise and targeted treatment of balance , osteoporosis , nutrition , vitamin D/calcium , depression , cognition , vision , home safety , polypharmacy , hip protectors , self-efficacy , and social support . OUTCOMES Functional independence : mortality , nursing home admissions , basic and instrumental activities of daily living ( ADLs/IADLs ) , and assistive device utilization . RESULTS Risk of death was reduced by 81 % ( age-adjusted OR [ 95 % CI ] = 0.19 [ 0.04 - 0.91 ] ; P HIPFIT group ( n = 4 ) compared with usual care controls ( n = 8) . Nursing home admissions were reduced by 84 % ( age-adjusted OR [ 95 % CI ] = 0.16 [ 0.04 - 0.64 ] ; P Basic ADLs declined less ( P assistive device use was significantly lower at 12 months ( P = .02 ) in the intervention group compared with controls . The targeted improvements in upper body strength , nutrition , depressive symptoms , vision , balance , cognition , self-efficacy , and habitual activity level were all related to ADL improvements ( P basic ADLs , vision , and walking endurance were associated with reduced nursing home use ( P HIPFIT intervention reduced mortality , nursing home admissions , and ADL dependency compared with usual care", "OBJECTIVE The objective of this study was to determine the incidence of and specific preoperative and intraoperative risk factors for postoperative delirium ( POD ) in electively treated vascular surgery patients . METHODS Between March 2010 and November 2013 , all vascular surgery patients were included in a prospect i ve data base . Various preoperative , intraoperative , and postoperative risk factors were collected during hospitalization . The primary outcome variable was the incidence of POD . Secondary outcome variables were any surgical complication , hospital length of stay , and mortality . RESULTS In total , 566 patients were prospect ively evaluated ; 463 patients were 60 years or older at the time of surgery and formed our study cohort . The median age was 72 years ( interquartile range , 66 - 77 ) , and 76.9 % were male . Twenty-two patients ( 4.8 % ) developed POD . Factors that differed significantly by univariate analysis included current smoking ( P = .001 ) , increased comorbidity ( P = .001 ) , hypertension ( P = .003 ) , diabetes mellitus ( P = .001 ) , cognitive impairment ( P amputation surgery ( P elevated C-reactive protein level ( P blood loss ( P preoperative cognitive impairment ( odds ratio [ OR ] , 16.4 ; 95 % confidence interval [ CI ] , 4.7 - 57.0 ) , open aortic surgery or amputation surgery ( OR , 14.0 ; 95 % CI , 3.9 - 49.8 ) , current smoking ( OR , 10.5 ; 95 % CI , 2.8 - 40.2 ) , hypertension ( OR , 7.6 ; 95 % CI , 1.9 - 30.5 ) and age ≥80 years ( OR , 7.3 ; 95 % CI , 1.8 - 30.1 ) to be independent predictors of the occurrence of POD . The combination of these parameters allows us to predict delirium with a sensitivity of 86 % and a specificity of 92 % . The area under the curve of the corresponding receiver operating characteristics was 0.93 . Delirium was associated with longer hospital length of stay ( P more frequent and increased intensive care unit stays ( P = .008 and P = .003 , respectively ) , more surgical complications ( P more postdischarge institutionalization ( P , and higher 1-year mortality rates ( P = .0026 ) . CONCLUSIONS In vascular surgery patients , preoperative cognitive impairment and open aortic or amputation surgery were highly significant risk factors for the occurrence of POD . In addition , POD was significantly associated with a higher mortality and more institutionalization . Patients with these risk factors should be considered for high-st and ard delirium care to improve these outcomes", "IMPORTANCE The American Board of Internal Medicine Foundation Choosing Wisely Campaign recommends against the use of benzodiazepine drugs for adults 65 years and older . The effect of direct patient education to catalyze collaborative care for reducing inappropriate prescriptions remains unknown . OBJECTIVE To compare the effect of a direct-to-consumer educational intervention against usual care on benzodiazepine therapy discontinuation in community-dwelling older adults . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized trial ( EMPOWER [ Eliminating Medications Through Patient Ownership of End Results ] study [ 2010 - 2012 , 6-month follow-up ] ) . Community pharmacies were r and omly allocated to the intervention or control arm in nonstratified , blocked groups of 4 . Participants ( 303 long-term users of benzodiazepine medication aged 65 - 95 years , recruited from 30 community pharmacies ) were screened and enrolled prior to r and omization : 15 pharmacies r and omized to the educational intervention included 148 participants and 15 pharmacies r and omized to the \" wait list \" control included 155 participants . Participants , physicians , pharmacists , and evaluators were blinded to outcome assessment . INTERVENTIONS The active arm received a deprescribing patient empowerment intervention describing the risks of benzodiazepine use and a stepwise tapering protocol . The control arm received usual care . MAIN OUTCOMES AND MEASURES Benzodiazepine therapy discontinuation at 6 months after r and omization , ascertained by pharmacy medication renewal profiles . RESULTS A total of 261 participants ( 86 % ) completed the 6-month follow-up . Of the recipients in the intervention group , 62 % initiated conversation about benzodiazepine therapy cessation with a physician and /or pharmacist . At 6 months , 27 % of the intervention group had discontinued benzodiazepine use compared with 5 % of the control group ( risk difference , 23 % [ 95 % CI , 14%-32 % ] ; intracluster correlation , 0.008 ; number needed to treat , 4 ) . Dose reduction occurred in an additional 11 % ( 95 % CI , 6%-16 % ) . In multivariate subanalyses , age greater than 80 years , sex , duration of use , indication for use , dose , previous attempt to taper , and concomitant polypharmacy ( 10 drugs or more per day ) did not have a significant interaction effect with benzodiazepine therapy discontinuation . CONCLUSIONS AND RELEVANCE Direct-to-consumer education effectively elicits shared decision making around the overuse of medications that increase the risk of harm in older adults . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01148186", "BACKGROUND Postoperative delirium ( POD ) is a frequent postoperative disorder to the sick and elderly , and always has been associated with extended of day stay in hospital , and certainly more cost for the hospital as well . Additionally , delirium is associated with increased postoperative complications , longer length of stay , longer intensive care unit stay ( ICU ) , and much higher rates of discharge to a nursing home . As a result , delirium adds significant cost to hospitalization and subsequent medical care . The delirium causes an increased mortality and an increasing of mental status deterioration characterized by reduction of environmental recognition as well as the disorder of alertness . The purpose s of this study are : a ) the effectiveness of routine screening of postoperative Delirium in the elderly using Confusion Assessment Method ( CAM ) ) . In those cases psychiatrists are not necessary ; b ) underst and ing of risk factors and strategies for prevention and treatment ; c ) underst and ing of the impact of this psychotic disorders in postoperative morbidity and mortality ; d ) recognition of the economic impact of these disorders in the health service ; e ) describing of the etiology and incidence of Delirium post-operative . MATERIAL AND METHODS In this study are included 640 patients aged over 65 years who underwent an operation at the urologic clinic . This study is prospect i ve and casual . Are excluded from the study all patients with psychological problems in admission and that were treated for these pathologies before admission in Urology Clinic . RESULTS Are evaluated all the data taken from patients and from their examinations as : age , use of medications , symptoms and problems , biochemical and clinical balance , hemodynamic examination , and preoperative , intra operative and postoperative evaluations . Is observed that post operative Delirium occurred at 166 patients from 640 in total on the average of 26 % of patients . Incidence was increased with increasing of age from 19 % to 31 % . CONCLUSION Postoperative Delirium occurs as a result of the combination of several factors , not just those related to internal physiological age , but combining of these factors with the diseases which carries this age , with medications used for this age , with surgical stress , with biochemical imbalances , hemodynamic problems , and electrolytic disorders as well", "Importance Older patients undergoing abdominal surgery commonly experience preventable delirium , which extends their hospital length of stay ( LOS ) . Objective To examine whether a modified Hospital Elder Life Program ( mHELP ) reduces incident delirium and LOS in older patients undergoing abdominal surgery . Design , Setting , and Participants This cluster r and omized clinical trial of 577 eligible patients enrolled 377 older patients ( ≥65 years of age ) undergoing gastrectomy , pancreaticoduodenectomy , and colectomy at a 2000-bed urban medical center in Taipei , Taiwan , from August 1 , 2009 , through October 31 , 2012 . Consecutive older patients scheduled for elective abdominal surgery with expected LOS longer than 6 days were enrolled , with a recruitment rate of 65.3 % . Participants were cluster r and omized by room to receive the mHELP or usual care . Interventions The intervention ( implemented by an mHELP nurse ) consisted of 3 protocol s administered daily : orienting communication , oral and nutritional assistance , and early mobilization . Intervention group participants received all 3 mHELP protocol s postoperatively , in addition to usual care , as soon as they arrived in the inpatient ward and until hospital discharge . Adherence to protocol s was tracked daily . Main Outcomes and Measures Presence of delirium was assessed daily by 2 trained nurses who were masked to intervention status by using the Confusion Assessment Method . Data on LOS were abstract ed from the medical record . Results Of 577 eligible patients , 377 ( 65.3 % ) were enrolled and r and omly assigned to the mHELP ( n = 197 ; mean [ SD ] age , 74.3 [ 5.8 ] years ; 111 [ 56.4 % ] male ) or control ( n = 180 ; mean [ SD ] age , 74.8 [ 6.0 ] years ; 103 [ 57.2 % ] male ) group . Postoperative delirium occurred in 13 of 196 ( 6.6 % ) mHELP participants vs 27 of 179 ( 15.1 % ) control individuals , representing a relative risk of 0.44 in the mHELP group ( 95 % CI , 0.23–0.83 ; P = .008 ) . Intervention group participants received the mHELP for a median of 7 days ( interquartile range , 6–10 days ) and had a shorter median LOS ( 12.0 days ) than control participants ( 14.0 days ) ( P = .04 ) . Conclusions and Relevance For older patients undergoing abdominal surgery who received the mHELP , the odds of delirium were reduced by 56 % and LOS was reduced by 2 days . Our findings support using the mHELP to advance postoperative care for older patients undergoing major abdominal surgery . Trial Registration clinical trials.gov Identifier : NCT01045330", "OBJECTIVE To assess the frailty and the incidence of delirium in elderly patients undergoing elective and acute colorectal surgery in correlation with morbidity and mortality . METHODS Patients aged 65 years and older having elective and acute colorectal surgery , between April 2013 and December 2013 were included in a prospect i ve data base . Patients diagnosed with a colorectal carcinoma or diverticulitis who were operated on were included . Factors that characterize frailty of patients were noted . The incidence rates of delirium after elective and acute surgery were recorded . Delirium was diagnosed using the Delirium Observation Screening Scale ( DOSS ) . Preoperative evaluation , surgical outcome including morbidity , hospital stay and mortality were analyzed . RESULTS Patients ≥ 65 years were included , 83 ( 75 % ) received elective and 28 ( 25 % ) acute surgery . The overall incidence of delirium was 21 % , 18 % for elective and 29 % for patients having urgent surgery ( p = 0.24 ) . Patients with delirium were older than the non-delirious patients ( median 82 years vs. 74 years ; p higher incidence of adverse events . Hospital stay , mortality and discharge to a nursing home were significant higher in the delirious compared to the non-delirious group ( p = 0.01 ; 0.01 ; 0.02 respectively ) . CONCLUSION High incidence of delirium was found in both acute and elective colorectal surgery . Delirium was associated with adverse outcomes", "Objective : The aim was to evaluate symptoms of delirium from a psychogeriatric perspective occurring postoperative to coronary bypass surgery . Design : Patients , S 60 years , scheduled for coronary bypass surgery ( n = 52 ) were enrolled in a prospect i ve descriptive study . The patients were evaluated before and several times after surgery by the Organic Brain Syndrome scale , and delirium was diagnosed according to psychiatric codes . Results : Of the 52 patients , 23 % presented delirium . These patients were older than the control group , 73.5 - 4.2 and 69.3 - 5.9 years , respectively ( mean - SD , p Emotional delirium was seen in 83 % , hyperactive delirium in about 40 % , and 25 % were classified to have a psychotic delirium . A major finding was a 58 % frequency of hallucinations and illusions among patients with delirium , and a similar rate among those without delirium . Conclusion : Delirium is common after cardiac surgery in particular in older patients , but is often under-diagnosed . Hallucinations were common in both delirious and non-delirious patients", "OBJECTIVE To identify the risk factors for , and complications associated with , the development of delirium after radical cystectomy . MATERIAL S AND METHODS From July 2008 to December 2009 , 59 patients , aged ≥65 years and undergoing radical cystectomy , were prospect ively enrolled . The baseline cognitive status was assessed using the Mini-Mental Status Examination . Postoperative delirium was assessed using the Confusion Assessment Method . RESULTS A total of 49 patients completed the surgery and all assessment s. The incidence of postoperative delirium was 29 % , with duration of 1 - 5 days . On univariate analysis , older age and preoperative Mini-Mental Status Examination score were associated with postoperative delirium . On multivariate analysis , only age was associated with postoperative delirium ( odds ratio 1.52 , 95 % confidence interval 1.04 - 2.22 , P=.03 ) . The 2 groups did not differ in pathologic stage , length of surgery , intraoperative and postoperative narcotic usage , body mass index , age-adjusted Charlson comorbidity index , activities of daily living scores , smoking history , preoperative hematocrit , estimated blood loss , urinary tract infection , interval to a regular diet , or length of hospital stay . The patients who developed postoperative delirium were more likely to undergo readmission ( odds ratio 10.7 , 95 % confidence interval 2.2 - 51.8 , P=.01 ) and reoperation ( odds ratio 9.2 , 95 % confidence interval 1.5 - 55.3 , P=.03 ) but did not differ in the 90-day and 1-year mortality rates or incidence of postoperative complications . CONCLUSION In patients aged≥65 years , a lower preoperative Mini-Mental Status Examination score and older age were significantly associated with the development of postcystectomy delirium , as measured using the Confusion Assessment Method . The patients who developed delirium were more likely to undergo readmission and reoperation . Larger studies with multiple surgeons are needed to vali date these findings", "BACKGROUND Preoperative risk stratification is commonly performed by assessing end-organ function ( such as cardiac and pulmonary ) to define postoperative risk . Little is known about impaired preoperative cognition and outcomes . The purpose of this study was to evaluate the impact of baseline impaired cognition on postoperative outcomes in geriatric surgery patients . STUDY DESIGN Subjects 65 years and older undergoing a planned elective operation requiring postoperative ICU admission were recruited prospect ively . Preoperative baseline cognition was assessed using the vali date d Mini-Cog test . Impaired cognition was defined as a Mini-Cog score of ≤ 3 . Delirium was assessed using the Confusion Assessment Method -ICU by a trained research team . Adverse outcomes were defined using the Veterans Affairs Surgical Quality Improvement Program definitions . RESULTS One hundred and eighty-six subjects were included , with a mean age of 73 ± 6 years . Eighty-two subjects ( 44 % ) had baseline impaired cognition . The impaired cognition group had the following unadjusted outcomes : increased incidence of 1 or more postoperative complications ( 41 % vs 24 % ; p = 0.011 ) , higher incidence of delirium ( 78 % vs 37 % ; p , longer hospital stays ( 15 ± 14 vs 9 ± 9 days ; p = 0.001 ) , higher rate of discharge institutionalization ( 42 % vs 18 % ; p = 0.001 ) , and higher 6-month mortality ( 13 % vs 5 % ; p = 0.040 ) . Adjusting for potential confounders determined by univariate analysis , logistic regression found impaired cognition was still associated with the occurrence of 1 or more postoperative complications ( odds ratio = 2.401 ; 95 % CI , 1.185 - 4.865 ; p = 0.015 ) . Kaplan-Meier survival analysis revealed higher mortality in the impaired cognition group ( log-rank p = 0.008 ) . CONCLUSIONS Baseline cognitive impairment in older adults undergoing major elective operations is related to adverse postoperative outcomes including increased complications , length of stay , and long-term mortality . Improved underst and ing of baseline cognition and surgical outcomes can aid surgical decision making in older adults", "Background / Objective : The prevalence of postoperative delirium in elderly patients is > 30 % . The objective of this prospect i ve study was to determine the usefulness of the short form of the Informant Question naire on COgnitive Decline in the Elderly ( short IQCODE ) to predict the occurrence of postoperative delirium after elective hip and knee arthroplasty in the elderly . Methods : Consecutive patients , 60 years and older , who were admitted for elective hip or knee arthroplasty were included . The preoperative cognitive status was determined using the Mini-Mental State Examination ( MMSE ) and the short IQCODE . Postoperative delirium was diagnosed using the Confusion Assessment Method . Logistic regression was used to analyze the links between the preoperative test scores and the outcome of postoperative delirium . Results : One hundred and one patients completed the study ( mean age 73.6 ± 6.6 years ) . The mean ± SD MMSE score was 26 ± 3 , and the mean short IQCODE score was 50.7 ± 6.2 . Postoperative delirium developed in 15 patients ( 14.8 % ) . A short IQCODE score > 50 was significantly associated with postoperative delirium ( OR 12.7 , 95 % CI 1.4–115.5 ; p = 0.02 ) . Conclusions : The short IQCODE appears to be a useful tool to predict the risk of postoperative delirium in elderly patients undergoing elective surgery . Detecting this complication could be of great interest to improve the postoperative survey of elderly patients" ]

[ "Background Chronic low back pain remains a major health problem in Australia and around the world . Unfortunately the majority of treatments for this condition produce small effects because not all patients respond to each treatment . It appears that only 25–50 % of patients respond to exercise . The two most popular types of exercise for low back pain are grade d activity and motor control exercises . At present however , there are no guidelines to help clinicians select the best treatment for a patient . As a result , time and money are wasted on treatments which ultimately fail to help the patient . Methods This paper describes the protocol of a r and omised clinical trial comparing the effects of motor control exercises with a grade d activity program in the treatment of chronic non specific low back pain . Further analysis will identify clinical features that may predict a patient 's response to each treatment . One hundred and seventy two participants will be r and omly allocated to receive either a program of motor control exercises or grade d activity . Measures of outcome will be obtained at 2 , 6 and 12 months after r and omisation . The primary outcomes are : pain ( average pain intensity over the last week ) and function ( patient-specific functional scale ) at 2 and 6 months . Potential treatment effect modifiers will be measured at baseline . Discussion This trial will not only evaluate which exercise approach is more effective in general for patients will chronic low back pain , but will also determine which exercise approach is best for an individual patient . Trial registration", "Proper psychomotor performance is needed in work and in activities of daily living , but among subjects with low back pain this area has been studied Little . The present purpose was to evaluate the effect and permanence of a 3-mo . physical exercise program on the psychomotor performance of lower limbs in subjects with low back pain . The associations between psychomotor performance and intensity of low back pain and subjective disability were also evaluated . 90 subjects with nonspecific , subacute low back pain were assigned to one of the three groups : one given three months intensive training , one home exercise , or the control group . Four measurement sessions were made during the 1-yr . study . Psychomotor speed of lower limbs was analyzed with Choice Reaction Time , Movement Time , and Total Response Time . Flight Time of a vertical static jump was also measured . Muscle strength was assessed with conventional methods from trunk , lower limbs , and h and . Intensity of Current Back Pain was analyzed with the Borg scale . Subjective disability was evaluated with the Oswestry Index . Analysis showed that muscle strength and back pain intensity had associations with psychomotor performance but subjective disability or physical activity did not affect it noticeably . There were no changes in Choice Reaction Time , but Total Response Time and Movement Time decreased and Flight Time increased for all subjects . In the first postintervention measurement the home exercise group had significantly lower Movement Time than the intensively trained group . Back Pain Intensity decreased in both exercise groups for those subjects whose psychomotor performance values were below the mean value for the sample", "Background Activity advice and prescription are commonly used in the management of low back pain ( LBP ) . Although there is evidence for advising patients with LBP to remain active , facilitating both recovery and return to work , to date no research has assessed whether objective measurements of free living physical activity ( PA ) can predict outcome , recovery and course of LBP . Methods An observational longitudinal study will investigate PA levels in a cohort of community-dwelling working age adults with acute and sub-acute LBP . Each participant 's PA level , functional status , mood , fear avoidance behaviours , and levels of pain , psychological distress and occupational activity will be measured on three occasions during for 1 week periods at baseline , 3 months , and 1 year . Physical activity levels will be measured by self report , RT3 triaxial accelerometer , and activity recall question naires . The primary outcome measure of functional recovery will be the Rol and Morris Disability Question naire ( RMDQ ) . Free living PA levels and changes in functional status will be quantified in order to look at predictive relationships between levels and changes in free living PA and functional recovery in a LBP population . Discussion This research will investigate levels and changes in activity levels of an acute LBP cohort and the predictive relationship to LBP recovery . The results will assess whether occupational , psychological and behavioural factors affect the relationship between free living PA and LBP recovery . Results from this research will help to determine the strength of evidence supporting international guidelines that recommend restoration of normal activity in managing LBP.Trial registration [ Clinical Trial Registration Number , ACTRN12609000282280", "Background The treatment of non-specific chronic low back pain is often based on three different models regarding the development and maintenance of pain and especially functional limitations : the deconditioning model , the cognitive behavioral model and the biopsychosocial model . There is evidence that rehabilitation of patients with chronic low back pain is more effective than no treatment , but information is lacking about the differential effectiveness of different kinds of rehabilitation . A direct comparison of a physical , a cognitive-behavioral treatment and a combination of both has never been carried out so far . Methods The effectiveness of active physical , cognitive-behavioral and combined treatment for chronic non-specific low back pain compared with a waiting list control group was determined by performing a r and omized controlled trial in three rehabilitation centers . Two hundred and twenty three patients were r and omized , using concealed block r and omization to one of the following treatments , which they attended three times a week for 10 weeks : Active Physical Treatment ( APT ) , Cognitive-Behavioral Treatment ( CBT ) , Combined Treatment of APT and CBT ( CT ) , or Waiting List ( WL ) . The outcome variables were self-reported functional limitations , patient 's main complaints , pain , mood , self-rated treatment effectiveness , treatment satisfaction and physical performance including walking , st and ing up , reaching forward , stair climbing and lifting . Assessment s were carried out by blinded research assistants at baseline and immediately post-treatment . The data were analyzed using the intention-to-treat principle . Results For 212 patients , data were available for analysis . After treatment , significant reductions were observed in functional limitations , patient 's main complaints and pain intensity for all three active treatments compared to the WL . Also , the self-rated treatment effectiveness and satisfaction appeared to be higher in the three active treatments . Several physical performance tasks improved in APT and CT but not in CBT . No clinical ly relevant differences were found between the CT and APT , or between CT and CBT . Conclusion All three active treatments were effective in comparison to no treatment , but no clinical ly relevant differences between the combined and the single component treatments were found", "Abstract Chronic low back pain ( CLBP ) in older adults may be disabling and therapeutically challenging , largely because of the inefficacy and /or morbidity associated with traditional pain treatment . We conducted a r and omized controlled trial in 200 men and women ⩾ age 65 with CLBP to evaluate the efficacy of percutaneous electrical nerve stimulation ( PENS ) with and without general conditioning and aerobic exercise ( GCAE ) , for reducing pain and improving physical function . Participants were r and omized to receive ( 1 ) PENS , ( 2 ) control‐PENS ( brief electrical stimulation to control for treatment expectancy ) , ( 3 ) PENS + GCAE , or ( 4 ) control‐PENS + GCAE , twice a week for 6 weeks . All four groups experienced significantly reduced pain ( range −2.3 to −4.1 on the McGill Pain Question naire short form ) , improved self‐reported disability ( range −2.1 to −3.0 on Rol and scale ) and improved gait velocity ( 0.04–0.07 m/s ) , sustained at 6 months . The GCAE groups experienced significantly fewer fear avoidance beliefs immediately post‐intervention and at 6 months than non‐GCAE groups . There were no significant side effects . Since brief electrical stimulation ( i.e. , control‐PENS ) facilitated comparably reduced pain and improved function at 6 months as compared with PENS , the exact dose of electrical stimulation required for analgesia can not be determined . GCAE was more effective than PENS alone in reducing fear avoidance beliefs , but not in reducing pain or in improving physical function ", "Underst and ing the course of back pain is important for clinicians and research ers , but analyses of longitudinal data from multiple time points are lacking . A prospect i ve cohort study of consecutive back pain consulters from five general practice s in the United Kingdom was carried out between 2001 and 2003 to identify groups defined by their pain pathways . Patients were sent monthly question naires for a year . Longitudinal latent class analysis was performed by using pain intensity scores for 342 consulters . Analysis yielded four clusters representing different pathways of back pain . Cluster 1 ( \" persistent mild \" ; n = 122 ) patients had stable , low levels of pain . Patients in cluster 2 ( \" recovering \" ; n = 104 ) started with mild pain , progressing quickly to no pain . Cluster 3 ( \" severe chronic \" ; n = 71 ) patients had permanently high pain . For patients in cluster 4 ( \" fluctuating \" ; n = 45 ) , pain varied between mild and high levels . Distinctive patterns for each cluster were maintained throughout follow-up . Clusters showed statistically significant differences in disability , psychological status , and work absence ( p back pain patients . Identification of four distinct groups of patients improves underst and ing of the course of back pain and may provide a basis of classification for intervention", "Study Design . R and omized controlled trial . Objectives . To compare high- and low-intensity back schools with usual care in occupational health care . Summary of Background Data . The content and intensity of back schools vary widely and the method ologic quality of r and omized controlled trials is generally weak . Until now , no back school has proven to be superior for workers sick-listed because of subacute nonspecific low back pain . Methods . Workers ( n = 299 ) sick-listed for a period of 3 to 6 weeks because of nonspecific low back pain were recruited by the occupational physician and r and omly assigned to a high-intensity back school , a low-intensity back school , or care as usual . Outcome measures were days until return to work , total days of sick-leave , pain , functional status , kinesiophobia , and perceived recovery and were assessed at baseline and at 3 and 6 months of follow-up . Principal analyses were performed according to the intention-to-treat principle . Results . We r and omly allocated 299 workers . Workers in the low-intensity back school returned to work faster compared with usual care and the high-intensity back school , with hazard ratios of 1.4 ( P = 0.06 ) and 1.3 ( P = 0.09 ) , respectively . The comparison between high-intensity back school and usual care result ed in a hazard ratio of 1.0 ( P = 0.83 ) . The median number of sick-leave days was 68 , 75 , and 85 in the low-intensity back school , usual care , and high-intensity back school , respectively . Beneficial effects on functional status and kinesiophobia were found at 3 months in favor of the low-intensity back school . No substantial differences on pain and perceived recovery were found between groups . Conclusions . The low-intensity back school was most effective in reducing work absence , functional disability , and kinesiophobia , and more workers in this group scored a higher perceived recovery during the 6-month follow-up", "Study Design . A 5-year prospect i ve cohort study was conducted of men and women seeking care for a new period of low back pain ( LBP ) . Objectives . To study the natural course of pain and disability due to LBP during a 5-year follow-up period , and to investigate the possible influence of regular physical exercise on recovery . Summary of Background Data . LBP is major health problem , but its natural course is not very well studied . Several studies have investigated the role of physical exercise on LBP disorders , with inconsistent results . Methods . At baseline , a total of 790 subjects seeking care for LBP were interviewed about physical exercise during leisure time . Over 5 years , 3 follow-up assessment s were made by postal question naire . At all measuring points , pain intensity ratings and disability scores were compared between men and women , and among 3 exercise categories . Results . The pain intensity and disability scores were improved after 5 years for both men and women . The most prominent improvements occurred after 6 months , but less so thereafter . There were no significant differences between men and women with regard to individual changes at the 5-year follow-up concerning the pain intensity or disability scores . There were no significant differences , either for women or men , between low , median , or high intensity exercise groups regarding pain intensity or disability values for the individual change at the 5-year follow-up . Conclusions . Over a 5-year period , both men and women who had sought care for LBP reported a decrease in pain and disability ; however , only a few were fully restored . In this study , we found no effect of nonspecific physical exercise on recovery from LBP in men and women", "Context Low back pain causes frequent disability and lost productive time . Contribution This r and omized trial compared a behavioral-oriented grade d activity program with usual care in 134 Dutch airline company workers who had missed work because of persistent low back pain . Grade d activity consisted of biweekly 1-hour exercise sessions with physiotherapists who emphasized operant-conditioning principles . Over 6 months of follow-up , participants in the grade d activity program missed 58 days of work , while participants receiving usual care missed 87 days . Implication s A behavioral-oriented grade d activity program returned participants with low back pain to work more often than did usual care . The Editors Nonspecific low back pain is an uncomfortable medical condition that causes frequent disability and absence from work . Most episodes of low back pain resolve fairly quickly and cause only short periods of absence from work . However , some workers with low back pain miss work for several days to weeks and are at risk for more permanent disability ( 1 ) . To reduce the individual and socioeconomic burden related to this absenteeism , we need effective intervention strategies in occupational health care setting s that promote safe and rapid return to work . One promising and often-advocated intervention strategy for workers with prolonged nonspecific low back pain is active rehabilitation that is directed toward return to normal activity and work ( 2 ) . Examples are grade d activity interventions that include physical exercise , application of operant-conditioning behavioral principals , and promotion of improved functioning and safe return to work even if pain persists ( 3 - 6 ) . In a r and omized , controlled trial , Lindstrm and colleagues ( 3 , 4 ) found that a grade d activity intervention reduced absence from work more than did traditional care in Swedish workers employed in the automobile industry . We investigate , in a second r and omized , controlled trial , whether absence from work because of low back pain is reduced more with grade d activity intervention than with traditional care in an occupational health care setting in the Netherl and s. Methods Study Design and Sample The study was a single-blind , r and omized , controlled trial in an occupational health services center ( KLM Health , Safety and Environment ) at Schiphol Airport , Amsterdam , the Netherl and s. The center provides occupational health services for all employees of a major Dutch airline ( KLM Royal Dutch Airlines ) . The source sample ( n = 20 000 ) consisted of workers who were employed in the following organizational units of the airline : baggage and aircraft turnaround services , passenger services , engineering and maintenance , cargo , and cabin and cockpit . Workers who were listed as absent from work because of low back pain were invited for a consultation with the occupational physician . Those who were thought to be eligible for inclusion were referred to the research assistant , who judged whether they met the inclusion criteria : full or partial absence from work because of nonspecific low back pain and low back pain symptoms with a minimum duration of 4 weeks in succession . The exclusion criteria were low back pain with radiation below the knee with signs of nerve-root compression ( 7 ) ; cardiovascular contraindications for physical activity , as checked according to the Physical Activities Readiness Question naire ( 8 , 9 ) ; any conflict between worker and employer with legal involvement ; or pregnancy . Workers who met the inclusion criteria were informed of the purpose and procedures of the study and were enrolled after giving informed consent . The Medical Ethical Committee of the VU University Medical Center , Amsterdam , the Netherl and s , approved the study . Treatment Allocation The participants were assigned to grade d activity or usual care on the basis of block r and omization , after prestratification for the organizational unit in the workplace from which they were recruited ( the 5 organizational units listed earlier ) and for the severity of pain symptoms ( scored on a scale of 0 to 10 ; severity scores were points ) . This result ed in a total of 10 strata . R and omized , permuted blocks of 4 allocations were generated for each stratum through a computer-generated r and om-sequence table . Opaque , sequentially numbered , sealed envelopes were prepared for each stratum by a research er who was not involved in enrolling the participants or assigning them to their groups . The envelopes contained a sheet of paper that indicated 1 of the 2 interventions . Participants learned their group assignments after a research assistant completed the baseline measurements and delivered the sealed envelopes . Blinding The research assistants who collected the data were blinded to the treatment allocation . All participants were repeatedly asked not to reveal any information about their treatment allocation . The participants and treatment providers were not blinded to treatment allocation . Interventions In the Dutch occupational health care system , occupational physicians guide disabled workers who are absent from work through their disability period . These occupational physicians are employed by occupational health services that are paid for by the companies . The occupational physicians adhere to back pain management strategies that consist of advising workers on ergonomics , prevention , and return-to-work schedules and advising and communicating with other stakeholders ( such as health care providers and representatives of the workplace ) . Disabled workers who participated in the present study were assigned to either grade d activity or usual care within the context of the Dutch occupational health care setting . Grade d Activity The intervention group received the usual guidance from the occupational physician about work-related problems and barriers to return to work as well as the grade d activity intervention supervised by a physiotherapist . Three physiotherapists who worked in a private practice at Schiphol Airport provided the treatment according to the grade d activity protocol . Two of those physiotherapists were also trained as manual therapists , and 1 was also a human movement scientist . Before the study , the physiotherapists had been specifically trained to treat patients with low back pain according to behavioral principles . A research physiotherapist who was experienced in treating patients with chronic pain in rehabilitation centers instructed the physiotherapists in three 2-hour sessions and practice d patienttherapist interactions with them through role-play . Before the study , the physiotherapists treated several patients according to the grade d activity protocol to gain more experience . The physiotherapists made audiotapes of the intervention sessions before and during the study period . The contents of these audiotapes were assessed and discussed with the research physiotherapist in 3 additional meetings . Furthermore , the physiotherapists summarized the treatment after each session , and research ers used these summaries to review the sessions . The same physiotherapist treated participants each time , except for temporary st and -in sessions that were supervised by colleagues because of holidays or other reasons . Specific therapists were not systematic ally selected to treat specific participants ; selection was based on pragmatic reasons , such as the time available in the work schedules of the physiotherapists or the days of treatment preferred by the participants . Table 1 presents the concept and content of the grade d activity intervention . The intervention consisted of 1-hour exercise sessions that participants attended twice per week until they returned completely to regular work or until the maximum therapy duration of 3 months was reached . At the start of the intervention , the physiotherapist inquired about the participant 's medical history and completed a brief physical examination consisting of flexion , extension , and lateroflexion of the lumbar spine and a brief screening for nerve-root pain ( 10 ) . The purpose of the physical examination was to confirm the diagnosis of benign , nonspecific low back pain and to reduce participants ' fears about any presumed underlying disease . The participants were reassured that despite the annoying pain , nothing was seriously wrong with their backs . Subsequently , the physiotherapist and participant decided on a set of general exercises and individually tailored exercises . Both types of exercises had to be performed during each session . The general exercises were aerobic exercises , such as cycling or rowing , and strengthening exercises for large muscle groups , and most were carried out in a gym while using exercise equipment . The strengthening exercises were a floor abdominal sit-up exercise , a dynamic back extension exercise , a leg-press exercise , a latissimus pull-down exercise , and st and ing up from a low chair . Participants in the grade d activity group had to perform not only these general exercises but also individually tailored exercises , which imitated physical tasks at work or difficult and painful activities of daily living . For example , a participant who reported back problems while lifting and moving suitcases from a luggage wagon into an airplane might be given an exercise to practice lifting and moving a suitcase with a certain number of repetitions . During the first 3 sessions , the maximal performance ( for example , the maximum number of repetitions ) was assessed for each exercise separately , and the average score for each exercise over the 3 sessions was used as a baseline value for specifying a gradually progressive exercise scheme . Subsequently , the participant was asked to propose a date for full return to regular work , which would consequently be the end point of the physical exercise program . Before returning to full regular work , participants could return to work with modified hours and duties . Advised by the physiotherapist , the participant", "& NA ; Fear‐avoidance beliefs have been identified as an important psychosocial variable in patients with chronic disability doe to low back pain . The importance of fear‐avoidance beliefs for individuals with acute low back pain has not been explored . Seventy‐eight subjects with work‐related low back pain of less than 3 weeks ' duration were studied . Measurements of pain intensity , physical impairment , disability , nonorganic signs and symptoms , and depression were taken at the initial evaluation . Fear‐avoidance beliefs were measured with the work and physical activity subscales of the Fear‐avoidance Beliefs Question naire . Disability and work status were re‐assessed after 4 weeks of physical therapy . Patterns of correlation between fear‐avoidance beliefs and other concurrently‐measured variables were similar to those reported in patients with chronic low back pain . Fear‐avoidance beliefs did not explain a significant amount of the variability in initial disability levels after controlling for pain intensity and physical impairment . Fear‐avoidance beliefs about work were significant predictors of 4‐week disability and work status even after controlling for initial levels of pain intensity , physical impairment , and disability , and the type of therapy received . Fear‐avoidance beliefs are present in patients with acute low back pain , and may be an important factor in explaining the transition from acute to chronic conditions . Screening for fear‐avoidance beliefs may be useful for identifying patients at risk of prolonged disability and work absence", "& NA ; Using latent class analysis ( LCA ) , a previous study on patients attending primary care identified four courses of low back pain ( LBP ) over the subsequent 6 months . To date , no studies have used longitudinal pain recordings to examine the “ natural ” course of recurrent and chronic LBP in a population ‐based sample of individuals . This study examines the course of LBP in the general population and elaborates on the stability and criterion‐related validity of the clusters derived . A r and om sample of 400 individuals reporting LBP in a population ‐based study was asked to complete a comprehensive question naire at the start and end of the year 's survey , and 52 weekly pain diaries in between . The latter were analyzed using LCA . 305 individuals returned more than 50 % of the diaries . Four clusters were identified ( severe persistent , moderate persistent , mild persistent , and fluctuating ) . The clusters differed significantly with regards to pain and disability . Assessment of cluster stability showed that a considerable proportion of patients in the “ fluctuating ” group changed their classification over time . Three of the four clusters describing the typical course of pain matched the clusters described previously for patients in primary care . Due to the population ‐based design , this study achieves , for the first time , a close insight into the “ natural ” course of chronic and recurrent low back pain , including individuals that did not necessarily visit the general practitioner . The findings will help to underst and better the nature of this pain in the general population", "There has been a recent increase in research evaluating treatment-based subgroups of non-specific low back pain . The aim of these sub-classification schemes is to identify subgroups of patients who will respond preferentially to one treatment as opposed to another . Our article provides accessible guidance on to how to interpret this research and determine its implication s for clinical practice . We propose that studies evaluating treatment-based subgroups can be interpreted in the context of a three-stage process : ( 1 ) hypothesis generation-proposal of clinical features to define subgroups ; ( 2 ) hypothesis testing-a r and omised controlled trial ( RCT ) to test that subgroup membership modifies the effect of a treatment ; and ( 3 ) replication-another RCT to confirm the results of stage 2 and ensure that findings hold beyond the specific original conditions . At this point , the bulk of research evidence in defining subgroups of patients with low back pain is in the hypothesis generation stage ; no classification system is supported by sufficient evidence to recommend implementation into clinical practice", "BACKGROUND AND PURPOSE Improving functional performance in patients with chronic low back pain is of primary importance . The purpose of this study was to examine the effects of 2 proprioceptive neuromuscular facilitation ( PNF ) programs on trunk muscle endurance , flexibility , and functional performance in subjects with chronic low back pain ( CLBP ) . SUBJECTS Eighty-six women ( 40.2+/-11.9 [ mean+/-SD ] years of age ) who had complaints of CLBP were r and omly assigned to 3 groups : rhythmic stabilization training , combination of isotonic exercises , and control . METHODS Subjects trained with each program for 4 weeks with the aim of improving trunk stability and strength . Static and dynamic trunk muscle endurance and lumbar mobility were measured before , at the end of , and 4 and 8 weeks after training . Disability and back pain intensity also were measured with the Oswestry Index . RESULTS Multivariate analysis of variance indicated that both training groups demonstrated significant improvements in lumbar mobility ( 8.6%-24.1 % ) , static and dynamic muscle endurance ( 23.6%-81 % ) , and Oswestry Index ( 29.3%-31.8 % ) measurements . DISCUSSION AND CONCLUSION Static and dynamic PNF programs may be appropriate for improving short-term trunk muscle endurance and trunk mobility in people with CLBP", "BACKGROUND We evaluated the effect of a self-management program for low-income primary care patients with acute low back pain ( ALBP ) from inner-city neighborhood health centers . METHODS We conducted a r and omized controlled trial of a self-management program compared with usual care at university-affiliated neighborhood health centers and an emergency department of an inner-city public teaching hospital . We enrolled 211 patients who visited a physician for ALBP ( The self-management program consisted of 3 group sessions and telephone follow-up that focused on underst and ing back pain , increasing physical activity , and dealing with fears and frustrations . RESULTS At baseline , 4 months , and 12 months , blinded interviewers assessed back pain physical function ( Rol and Disability Question naire ) , health status ( Arthritis Impact Measurement Scales ) , self-efficacy , and time spent in physical activity . Compared with patients receiving usual care , intervention patients reported significantly better scores on the Rol and Disability Question naire ( P = .009 ) , mental functioning ( P = .009 ) , self-efficacy to manage ALBP ( P = .03 ) , time spent in physical activity ( P = .047 ) , and reduced fears of movement/reinjury ( P = .005 ) after 12 months . CONCLUSION A self-management program can improve and maintain functional status , mental functioning , and self-efficacy to manage future symptoms for 1 year among primary care patients with ALBP living in the urban , inner city", "OBJECTIVE To identify subgroups of workers absent from work due to low back pain who are more or less likely to return to work earlier as a result of a grade d activity intervention , and to investigate whether this intervention is effective in reducing pain-related fears and if so , whether these reductions in pain-related fears mediate return to work . METHODS A subgroup analysis was conducted on data from a previous r and omized controlled trial of 134 Dutch airline workers , which found that a behaviorally-oriented grade d activity intervention was more effective than usual care in stimulating return to work . The subgroup analyses added interaction terms to a Cox regression model that described the relationship between treatment allocation and return to work over 12 months of followup . Furthermore , we studied the effects of grade d activity on pain-related fears and added variables indicating a reduction in pain-related fears to the model in order to investigate their influence on return to work . RESULTS Statistically significant interactions were found for disability , fear-avoidance beliefs about physical activity , and fear-avoidance beliefs about work . No indication was found that the reduction in pain-related fears in the grade d activity group mediated more favorable return-to-work results in this group . CONCLUSION Workers who perceive their disability to be moderate and workers with moderate scores for fear-avoidance beliefs return to work more rapidly as a result of the grade d activity intervention than workers with higher scores . The return to work of workers receiving the grade d activity intervention is possibly independent from the reductions in pain-related fears caused by this intervention", "Objective : To examine the effectiveness of rhythmic stabilization exercises and transcutaneous electrical nerve stimulation ( TENS ) and their combination in treating women with chronic low back pain . Design : Sequentially allocated , single-blinded and controlled study , with a two-month follow-up . Setting : The data were collected in a patient rehabilitation setting . Subjects : A total of 92 women ( 34—46 years old ) with chronic low back pain were studied . Interventions : Sequential allocation was undertaken into four groups : ` rhythmic stabilization ' ( n=23 ) , ` rhythmic stabilization — TENS ' ( n=23 ) , TENS ( n=23 ) , and a placebo group ( n = 23 ) . Each programme lasted for four weeks . All outcome measures were assessed prior to , immediately after , four weeks and eight weeks post intervention . Main measures : Data were obtained on functional disability , pain intensity , trunk extension range of motion , dynamic endurance of trunk flexion and static endurance of trunk extension . Results : A total of 88 patients provided two-month follow-up data . The ` rhythmic stabilization ' and the ` rhythmic stabilization — TENS ' groups displayed statistically significant ( P functional disability and pain intensity ( ranging from 21.2 to 42.8 % ) , trunk extension range of motion ( ranging from 6.5 to 25.5 % ) , dynamic endurance of trunk flexion and static endurance of trunk extension ( ranging from 13.5 to 74.3 % ) compared with the remaining groups . Conclusions : The rhythmic stabilization programmes result ed in more gains in women with chronic low back pain regarding the present outcome variables compared with the other groups ; therefore , its application in female chronic low back pain patients aged 34—46 years is recommended" ]

[ "Background and Purpose — Cardioembolism in paroxysmal atrial fibrillation ( pxAF ) is a frequent cause of ischemic stroke . Sensitive detection of pxAF after stroke is crucial for adequate secondary stroke prevention ; the optimal diagnostic modality to detect pxAF on stroke units is unknown . We compared 24-hour Holter electrocardiography ( ECG ) with continuous stroke unit ECG monitoring ( CEM ) for pxAF detection . Methods — Patients with acute ischemic stroke or transient ischemic attack were prospect ively enrolled . After a 12-channel ECG on admission , all patients received 24-hour Holter ECG and CEM . Additionally , ECG monitoring data underwent automated analysis using dedicated software to identify pxAF . Patients with a history of atrial fibrillation or with atrial fibrillation on the admission ECG were excluded . Results — Four hundred ninety-six patients ( median age , 69 years ; 61.5 % male ) fulfilled all inclusion criteria ( ischemic stroke : 80.4 % ; transient ischemic attack : 19.6 % ) . Median stroke unit stay lasted 88.8 hours ( interquartile range , 65.0–122.0 ) . ECG data for automated CEM analysis were available for a median time of 64.0 hours ( 43.0–89.8 ) . Paroxysmal AF was documented in 41 of 496 patients ( 8.3 % ) . Of these , Holter detected pxAF in 34.1 % ; CEM in 65.9 % ; and automated CEM in 92.7 % . CEM and automated CEM detected significantly more patients with pxAF than Holter ( P detected more patients than CEM ( P Automated analysis of CEM improves pxAF detection in patients with stroke on stroke units compared with 24-hour Holter ECG . The comparative usefulness of prolonged or repetitive Holter ECG recordings requires further evaluation", "Aims Uncertainty exists over the importance of device-detected short- duration atrial arrhythmias . Continuous atrial diagnostics , through home monitoring ( HM ) technology ( BIOTRONIK , Berlin , Germany ) , provides a unique opportunity to assess frequency and quantity of atrial fibrillation ( AF ) episodes defined as atrial high-rate events ( AHRE ) . Methods and results Prospect i ve data from 560 heart failure ( HF ) patients ( age 67 ± 10 years , median ejection fraction 27 % ) patients with a cardiac resynchronization therapy ( CRT ) device capable of HM from two multi-centre studies were analysed . Atrial high-rate events burden was defined as the duration of mode switch in a 24-h period with atrial rates of > 180 beats for at least 1 % or total of 14 min per day . The primary endpoint was incidence of a thromboembolic ( TE ) event . Secondary endpoints were cardiovascular death , hospitalization because of AF , or worsening HF . Over a median 370-day follow-up AHRE occurred in 40 % of patients with 11 ( 2 % ) patients developing TE complications and mortality rate of 4.3 % ( 24 deaths , 16 with cardiovascular aetiology ) . Compared with patients without detected AHRE , patients with detected AHRE>3.8 h over a day were nine times more likely to develop TE complications ( P= 0.006 ) . The majority of patients ( 73 % ) did not show a temporal association with the detected atrial episode and their adverse event , with a mean interval of 46.7 ± 71.9 days ( range 0–194 ) before the TE complication . Conclusion In a high-risk cohort of HF patients , device-detected atrial arrhythmias are associated with an increased incidence of TE events . A cut-off point of 3.8 h over 24 h was associated with significant increase in the event rate . Routine assessment of AHRE should be considered with other data when assessing stroke risk and considering anti-coagulation initiation and should also prompt the optimization of cardioprotective HF therapy in CRT patients", "INTRODUCTION Despite extensive inpatient workup including telemetry monitoring , a significant proportion of stroke is classified as cryptogenic at hospital discharge . It is possible that a significant proportion of cryptogenic stroke is a result of intermittent atrial fibrillation ( AF ) . Thirty-day cardiac event monitors ( 30-DEM ) may increase the rate of AF detection compared with st and ard investigations that include a combination of electrocardiography , cardiac telemetry , and short-term Holter monitoring . METHODS Charts were review ed of patients who were admitted to a university stroke center or who were evaluated in the outpatient clinic during a 9-month period to determine whether the cause of stroke was cryptogenic . As a matter of protocol , such patients typically underwent 30-DEM and the results of such monitoring were documented along with the duration of inpatient cardiac monitoring if relevant . RESULTS In all , 218 patients with a diagnosis of ischemic stroke or transient ischemic attack were identified . Of the strokes , 36 ( 16.5 % ) were classified as cryptogenic . Twenty patients with cryptogenic stroke or transient ischemic attack were evaluated with 30-DEM . Four ( 20 % ) were found to have AF , and all 4 patients were treated with warfarin . CONCLUSION The 30-DEM changed the medical treatment of 20 % of patients with otherwise cryptogenic stroke because of the detection of intermittent AF despite no detection of AF on electrocardiography and inpatient telemetry monitoring in the majority of patients . Further prospect i ve studies of extended cardiac event monitors in the setting of cryptogenic stroke are warranted", "Background and Purpose — For patients having suffered ischemic stroke , the current diagnostic strategies often fail to detect atrial fibrillation as a potential cause of embolic events . The aim of the study was to identify paroxysmal atrial fibrillation in stroke patients . We hypothesized that patients with frequent atrial premature beats ( APBs ) recorded in 24-hour ECG will show more often atrial fibrillation when followed by repeated long-term ECG recordings than patients without or infrequent APBs . Methods — 127 patients with acute ischemic stroke and without known AF were enrolled in a prospect i ve study to detect paroxysmal AF . Patients were stratified according to the number of APBs recorded in a 24-hour ECG ( ≥70 APBs versus serial 7-day event-recorder monitoring at 0 , 3 , and 6 months . Results — Serial extended ECG monitoring identified AF in 26 % of patients with frequent APBs but only in 6.5 % when APBs were infrequent ( P=0.0021 ) . A multivariate analysis showed that the presence of frequent APBs in the initial 24-hour ECG was the only independent predictor of paroxysmal AF during follow-up ( odds ratio 6.6 , 95 % confidence intervals 1.6 to 28.2 , P=0.01 ) . Conclusions — In patients with acute ischemic stroke , frequent APBs ( ≥70/24 hours ) are a marker for individuals who are at greater risk to develop or have paroxysmal AF . For such patients , we propose a diagnostic workup with repeated prolonged ECG monitoring to diagnose paroxysmal AF", "Background and Purpose — Adequate diagnosis of atrial fibrillation ( AF ) , including paroxysmal AF , is an important part of stroke workup . Prolonged ECG monitoring may improve the detection of paroxysmal , previously undiagnosed AF ( unknown AF ) . Therefore , we evaluated systematic 72-hour Holter ECG monitoring to detect unknown AF for the workup of patients with stroke . Methods — Unselected survivors of a stroke or transient ischemic attack ( TIA ) without known AF were enrolled in a prospect i ve , multicenter cohort study of 72-hour Holter ECG monitoring in 9 German secondary and tertiary stroke centers between May 2010 and January 2011 . In addition to st and ardized workup of stroke pathogenesis according to the German Stroke Unit protocol , all patients underwent 72-hour Holter ECG monitoring directly after admission . All ECGs were central ly analyzed by 2 independent observers . We determined the proportion of unknown AF and compared the detection rates of 72- and 24-hour monitoring . Results — A total of 1135 patients were enrolled ( mean age , 67 years [ SD , 13.1 years ] , 45 % women , 29 % TIA ) . Unknown AF was detected in 49 out of 1135 patients ( 4.3 % , [ 95 % confidence interval , 3.4–5.2 % ] ) by 72-hour ECG monitoring . Unknown AF was diagnosed in 29 patients ( 2.6 % ) within the first 24 hours of ECG monitoring , and in 20 more patients only by 72 hours of ECG monitoring . The number needed to screen by 72-hour ECG was 55 patients ( 95 % confidence interval [ 35–123 ] ) for each additional AF diagnosis . Patients with unknown AF were significantly older and had more often a history of previous stroke . Patients with unknown AF were equally distributed within categories of pathogenesis according to Trial of Org 10172 in Acute Stroke Treatment ( TOAST ) classification . Conclusions — In unselected survivors of stroke or TIA , 72-hour ECG monitoring is feasible and improves the detection rate of silent paroxysmal AF", "Abstract Background and purpose Prolonged Holter monitoring of patients with cerebral ischemia increases the detection rate of paroxysmal atrial fibrillation ( PAF ) ; this leads to improved antithrombotic regimens aim ed at preventing recurrent ischemic strokes . The aim of this study was to compare a 7-day-Holter monitoring ( 7-d-Holter ) alone or in combination with prior selection via transthoracic echocardiography ( TTE ) to a st and ard 24-h-Holter using a cost-utility analysis . Methods Lifetime cost , quality -adjusted life years ( QALY ) , and incremental cost-effectiveness ratios ( ICER ) were estimated for a cohort of patients with acute cerebral ischemia and no contraindication to oral anticoagulation . A Markov model was developed to simulate the long-term course and progression of cerebral ischemia considering the different diagnostic algorithms ( 24-h-Holter , 7-d-Holter , 7-d-Holter after pre selection by TTE ) . Clinical data for these algorithms were derived from the prospect i ve observational Find-AF study ( IS RCT N 46104198 ) . Results Predicted lifelong discounted costs were 33,837 € for patients diagnosed by the 7-d-Holter and 33,852 € by the st and ard 24-h-Holter . Cumulated QALYs were 3.868 for the 7-d-Holter compared to 3.844 for the 24-h-Holter . The 7-d-Holter dominated the 24-h-Holter in the base-case scenario and remained cost-effective in extensive sensitivity analysis of key input parameter with a maximum of 8,354 € /QALY gained . Pre selecting patients for the 7-d-Holter had no positive effect on the cost-effectiveness . Conclusions A 7-d-Holter to detect PAF in patients with cerebral ischemia is cost-effective . It increases the detection which leads to improved antithrombotic regimens ; therefore , it avoids recurrent strokes , saves future costs , and decreases quality of life impairment . Pre selecting patients by TTE does not improve cost-effectiveness", "Background and Purpose Diagnosis of paroxysmal atrial fibrillation is difficult but highly relevant in patients presenting with cerebral ischemia yet free from atrial fibrillation on admission . Early initiation and prolongation of continuous Holter monitoring may improve diagnostic yield compared with the st and ard of care including a 24-hour Holter recording . Methods — In the observational Find-AF trial ( IS RCT N 46104198 ) , consecutive patients presenting with symptoms of cerebral ischemia were included . Patients free from atrial fibrillation at presentation received 7-day Holter monitoring . Results — Two hundred eighty-one patients were prospect ively included . Forty-four ( 15.7 % ) had atrial fibrillation documented by routine electrocardiogram on admission . All remaining patients received Holter monitors at a median of 5.5 hours after presentation . In those 224 patients who received Holter monitors but had no previously known paroxysmal atrial fibrillation , the detection rate with early and prolonged ( 7 days ) Holter monitoring ( 12.5 % ) was significantly higher than for any 24-hour ( mean of 7 intervals : 4.8 % , P=0.015 ) or any 48-hour monitoring interval ( mean of 6 intervals : 6.4 % , P=0.023 ) . Of those 28 patients with new atrial fibrillation on Holter monitoring , 15 ( 6.7 % ) had been discharged without therapeutic anticoagulation after routine clinical care ( ie , with data from 24-hour Holter monitoring only ) . Detection rates were 43.8 % or 6.3 % for short supraventricular runs of ≥10 beats or prolonged episodes ( respectively . Diagnostic yield appeared to be only slightly and not significantly increased during the first 3 days after the index event . Conclusions — Prolongation of Holter monitoring in patients with symptoms of cerebral ischemic events increases the rate of detection of paroxysmal atrial fibrillation up to Day 7 , leading to a relevant change in therapy in a substantial number of patients . Early initiation of monitoring does not appear to be crucial . Hence , prolonged Holter monitoring ( ≥7 days ) should be considered for all patients with unexplained cerebral ischemia", "BACKGROUND AND PURPOSE A significant proportion of cryptogenic ischaemic strokes are due to paroxysmal atrial fibrillation ( AF ) . As paroxysmal AF appears to inexorably progress to persistent or permanent AF , this study with long-term follow-up was design ed to establish the profile of patients who developed AF after hospital discharge . METHODS All patients with cryptogenic ischaemic stroke over a 1-year period were included ( n = 164 ) . Patients were prospect ively followed up at the outpatient clinic . Information on long-term outcome included the presence of newly diagnosed AF ( NDAF ) . A specific NDAF assessment was performed at least 2 years after the index stroke using a structured telephone interview . Baseline clinical , laboratory , and echocardiographic data of these patients were retrospectively recorded . Independent predictive factors were then used to produce a predictive grading score for NDAF , derived by logistic regression analysis . RESULTS With a median follow-up of 854 days , 22 cases of NDAF ( 13 % ) were observed . On multivariate analysis , factors associated with NDAF were age ≥72 years ( two points ) , history of coronary artery disease ( one point ) or stroke ( one point ) , and left atrial area ≥16 cm(2 ) ( two points ) ( total score ranging from 0 to 6 ) . Patients with a score ≤1 point did not have NDAF during follow-up . CONCLUSIONS In cryptogenic ischaemic stroke , the NDAF score can be used to target patients at high risk of developing AF after hospital discharge , as a score of 0 - 1 was highly predictive of the absence of NDAF during follow-up . These results need to be confirmed in prospect i ve studies", "BACKGROUND One quarter of strokes are of unknown cause , and sub clinical atrial fibrillation may be a common etiologic factor . Pacemakers can detect sub clinical episodes of rapid atrial rate , which correlate with electrocardiographically documented atrial fibrillation . We evaluated whether sub clinical episodes of rapid atrial rate detected by implanted devices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation . METHODS We enrolled 2580 patients , 65 years of age or older , with hypertension and no history of atrial fibrillation , in whom a pacemaker or defibrillator had recently been implanted . We monitored the patients for 3 months to detect sub clinical atrial tachyarrhythmias ( episodes of atrial rate > 190 beats per minute for more than 6 minutes ) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism . Patients with pacemakers were r and omly assigned to receive or not to receive continuous atrial overdrive pacing . RESULTS By 3 months , sub clinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients ( 10.1 % ) . Sub clinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation ( hazard ratio , 5.56 ; 95 % confidence interval [ CI ] , 3.78 to 8.17 ; P ischemic stroke or systemic embolism ( hazard ratio , 2.49 ; 95 % CI , 1.28 to 4.85 ; P=0.007 ) . Of 51 patients who had a primary outcome event , 11 had had sub clinical atrial tachyarrhythmias detected by 3 months , and none had had clinical atrial fibrillation by 3 months . The population attributable risk of stroke or systemic embolism associated with sub clinical atrial tachyarrhythmias was 13 % . Sub clinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke ( hazard ratio , 2.50 ; 95 % CI , 1.28 to 4.89 ; P=0.008 ) . Continuous atrial overdrive pacing did not prevent atrial fibrillation . CONCLUSIONS Sub clinical atrial tachyarrhythmias , without clinical atrial fibrillation , occurred frequently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism . ( Funded by St. Jude Medical ; ASSERT Clinical Trials.gov number , NCT00256152 . )", "BACKGROUND Atrial fibrillation ( AF ) , an important and treatable cause of ischaemic stroke , can occur as a sustained or a paroxysmal arrhythmia . Continuous cardiac rhythm monitoring ( Holter monitoring ) is often performed in stroke patients to identify paroxysmal AF , which is an indication for warfarin anti-coagulation in this patient population . AIM The aim of this study was to assess the clinical utility of Holter monitoring in detecting occult AF in patients with possible cardioembolic stroke . METHODS The medical records of ischaemic stroke patients consecutively hospitalized at a single academic centre during a one-year period were review ed . Data regarding patient demographics , stroke characteristics , electrocardiography and echocardiography results and duration and findings of Holter monitoring were abstract ed . The primary outcome was yield of newly diagnosed AF on Holter monitoring . RESULTS Of 465 consecutive patients admitted with a diagnosis of new ischaemic stroke , 210 underwent Holter monitoring . The mean duration of monitoring was 22.8 + /- 4.0 h. Previously undiscovered AF was -identified in five cases ( 2.4 % ) , all of which represented non-rheumatic AF . In three cases , the Holter test was negative despite AF documented on an admission electro-cardiogram . CONCLUSIONS Holter monitoring can identify occult paroxysmal AF , assisting targeted secondary prevention in patients with new ischaemic stroke . However , the st and ard 24-h duration of monitoring probably under-estimates the prevalence of paroxysmal AF in this population . Prospect i ve studies are indicated to evaluate the value of longer monitoring periods in stroke population", "Background and Purpose — Pathophysiological considerations and observational studies indicate that elevated body temperature , hypoxia , hypotension , and cardiac arrhythmias in the acute phase of ischemic stroke may aggravate brain damage and worsen outcome . Methods — Both units were organized with the same st and ard care and multidisciplinary approach to nursing and rehabilitation . A blinded observer assessed functional outcome at 3 months with the modified Rankin scale ( mRS ) and Barthel Index ( BI ) . End points were ( 1 ) poor outcome , defined as either mRS ≥4 or BI and ( 2 ) mortality . Results — Fifty-four patients meeting the inclusion criteria were r and omized . The groups were well matched for baseline characteristics , stroke subtype , stroke severity , vascular risk factors , and prognostic factors . Poor outcome was seen in 7 ( 25.9 % ) patients in the SCMU group and in 13 ( 48.1 % ) in the SU group ( P = 0.16 ) . Mortality was lower in the SCMU group than in the SU group ( 1 [ 3.7 % ] vs 7 [ 25.9 % ] ; odds ratio , 0.11 [ 95 % CI , 0.02 to 0.96 ] , P = 0.05 ) . Conclusions — This pilot study suggests that admission of acute stroke patients to an SCMU may reduce mortality and poor outcome . A larger trial is required to confirm these findings", "Diagnosis of paroxysmal atrial fibrillation ( AF ) in stroke patients is challenging , but highly clinical ly relevant . The percentage of stroke patients with permanent AF increases with age , but limited data are available for the age-dependent yield of paroxysmal AF by Holter monitoring . Patients with acute cerebral ischemia were included into the prospect i ve observational Find-AF study . Patients free from AF at presentation received 7 day Holter monitoring . We calculated the percentage of otherwise undetected paroxysmal AF and the number needed to screen for age groups under 60 years , and in 5 year clusters from the age of 60 up to 85 and older . 272 patients were included , 43 ( 15.8 % ) had AF at admission , 33 patients with paroxysmal AF were identified by 7 day Holter ( n = 29 ) or medical history ( n = 4).The yield of 7 day Holter ECG clearly increased with older age ( p = 0.004 ) : The number needed to screen ( NNS ) to find one patient with paroxysmal AF decreased with age : ≤60 years : 18 , 60–64 years : 20 , 65–69 years : 14 , 70–74 years : 9 , 75–79 years : 8 , 80–84 years : 4 , ≥85 years : 3 , respectively . In patients all AF cases were detected by Holter ECG . The percentage of paroxysmal AF in stroke patients increases with age . The 7 day Holter ECG is most efficient in elderly patients", "Background and Purpose — Patients with cryptogenic ischemic stroke may have undetected paroxysmal atrial fibrillation ( PAF ) . We established the Stroke and Monitoring for PAF in Real Time ( SMART ) Registry to determine the yield of 30-day outpatient PAF monitoring in cryptogenic ischemic stroke . Methods — The SMART Registry was a 3-year , prospect i ve multicenter registry of 239 patients with cryptogenic ischemic stroke undergoing 30-day outpatient autotriggered PAF detection in Kaiser Permanente Northern California . Results — In intention-to-monitor analysis , PAF was detected in 29 of 239 patients ( 12.1 % ; 95 % CI , 8.6%–16.9 % ) . After retrospective chart review was performed , a new diagnosis of PAF was confirmed in 26 of 236 patients ( 11.0 % ; 95 % CI , 7.6%–15.7 % ) . The majority of detected PAF events were asymptomatic ; only 6 of 98 recorded PAF events ( 6.1 % ) were patient-triggered or associated with symptoms . Conclusions — -Approximately 1 in every 9 patients with cryptogenic ischemic stroke was found to have new PAF within 30 days . Routine monitoring in this population should be strongly considered", "Purpose Ischemic stroke is a frequent pathology with high rate of recurrence and significant morbidity and mortality . There are several causes of stroke , affecting prognosis , outcomes , and management , but in many cases , the etiology remains undetermined . We hypothesized that atrial fibrillation was involved in this pathology but underdiagnosed by st and ard methods . The aim of the study was to determine the incidence of atrial fibrillation in cryptogenic ischemic stroke by using continuous monitoring of the heart rate over several months . The secondary objective was to test the value of atrial vulnerability assessment in predicting spontaneous atrial fibrillation . Methods and results We prospect ively enrolled 24 patients under 75 years of age , 15 men and 9 women of mean age 49 years , who within the last 4 months had experienced cryptogenic stroke diagnosed by clinical presentation and brain imaging and presumed to be of cardioembolic mechanism . All causes of stroke were excluded by normal 12-lead ECG , 24-h Holter monitoring , echocardiography , cervical Doppler , hematological , and inflammatory tests . All patients underwent electrophysiological study . Of the patients , 37.5 % had latent atrial vulnerability , and 33.3 % had inducible sustained arrhythmia . Patients were secondarily implanted with an implantable loop recorder to look for spontaneous atrial fibrillation over a mean follow-up interval of 14.5 months . No sustained arrhythmia was found . Only one patient had non-significant episodes of atrial fibrillation . Conclusion In this study , symptomatic atrial fibrillation or AF with fast ventricular rate has not been demonstrated by the implantable loop recorder in patients under 75 years with unexplained cerebral ischemia . The use of this device should not be generalized in the systematic evaluation of these patients . In addition , this study attests that the assessment of atrial vulnerability is poor at predicting spontaneous arrhythmia in such patients", "Background and Purpose — Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter ( AF ) . However , the condition remains underdiagnosed , because paroxysmal AF may be missed by diagnostic tests in the acute phase . In this study , the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data ( SEA-AF ) . Methods — Three hundred forty-six consecutive patients with acute ischemic stroke were prospect ively included and subjected to st and ard telemetric monitoring . In addition , telemetric data were separately analyzed following SEA-AF , consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration . Serial electrocardiograms were conducted in 24-hour intervals . Results — Median effective telemetry monitoring time was 75.5 hours ( interquartile range 64–86 hours ) . Overall , AF was diagnosed in 119 of 346 patients ( 34.4 % ) . The structured reading algorithm was the most sensitive method to detected AF . Conventional telemetry and serial electrocardiographic assessment s were less effective . However , only 35 % of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring . Conclusions — Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessment s and st and ard telemetry without structured reading . The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessment s. Clinical Trial Registration — URL : www . clinical trials.gov . Unique identifier : NCT01177748", "The purpose of this study was to compare the diagnostic sensitivity of 1-day Holter monitoring versus 7-day Holter monitoring ( 7DH ) to detect atrial and ventricular arrhythmias in a population of stable patients with chronic heart failure and left ventricular dysfunction . Sixty-three consecutive stable patients with chronic heart failure with left ventricular ejection fractions Blood sample s were obtained , the Minnesota Living With Heart Failure Question naire was administered , and echocardiography , 6-minute walk tests , and 7DH were performed at enrollment . The mean ejection fraction was 35.8 + /- 9.8 % , and the mean age was 55.5 + /- 13.9 years . Seven-day Holter monitoring did not significantly increase the detection of nonsustained atrial tachycardia or atrial fibrillation . In contrast , the incidence of nonsustained ventricular tachycardia increased in nonischemic patients from 35.1 % on day 1 to 54.1 % on day 7 ( p = 0.01 ) . In ischemic patients , the sensitivity increased from 11.5 % to 46.2 % ( p = 0.004 ) . Two patients without nonsustained ventricular tachycardia on day 1 had episodes of 13 and 16 beats on days 3 and 6 of monitoring . In patients with left ventricular ejection fractions > 35 % and N-terminal-pro-brain natriuretic peptide levels nonsustained ventricular tachycardia were detected on day 1 in nonischemic and ischemic patients , but 7DH detected 3 new patients in each group . In conclusion , 7DH clearly improves the detection and allows a better characterization of ventricular arrhythmic episodes but seems to be less useful for supraventricular events", "BACKGROUND Atrial fibrillation is a leading preventable cause of recurrent stroke for which early detection and treatment are critical . However , paroxysmal atrial fibrillation is often asymptomatic and likely to go undetected and untreated in the routine care of patients with ischemic stroke or transient ischemic attack ( TIA ) . METHODS We r and omly assigned 572 patients 55 years of age or older , without known atrial fibrillation , who had had a cryptogenic ischemic stroke or TIA within the previous 6 months ( cause undetermined after st and ard tests , including 24-hour electrocardiography [ ECG ] ) , to undergo additional noninvasive ambulatory ECG monitoring with either a 30-day event-triggered recorder ( intervention group ) or a conventional 24-hour monitor ( control group ) . The primary outcome was newly detected atrial fibrillation lasting 30 seconds or longer within 90 days after r and omization . Secondary outcomes included episodes of atrial fibrillation lasting 2.5 minutes or longer and anticoagulation status at 90 days . RESULTS Atrial fibrillation lasting 30 seconds or longer was detected in 45 of 280 patients ( 16.1 % ) in the intervention group , as compared with 9 of 277 ( 3.2 % ) in the control group ( absolute difference , 12.9 percentage points ; 95 % confidence interval [ CI ] , 8.0 to 17.6 ; P Atrial fibrillation lasting 2.5 minutes or longer was present in 28 of 284 patients ( 9.9 % ) in the intervention group , as compared with 7 of 277 ( 2.5 % ) in the control group ( absolute difference , 7.4 percentage points ; 95 % CI , 3.4 to 11.3 ; P oral anticoagulant therapy had been prescribed for more patients in the intervention group than in the control group ( 52 of 280 patients [ 18.6 % ] vs. 31 of 279 [ 11.1 % ] ; absolute difference , 7.5 percentage points ; 95 % CI , 1.6 to 13.3 ; P=0.01 ) . CONCLUSIONS Among patients with a recent cryptogenic stroke or TIA who were 55 years of age or older , paroxysmal atrial fibrillation was common . Noninvasive ambulatory ECG monitoring for a target of 30 days significantly improved the detection of atrial fibrillation by a factor of more than five and nearly doubled the rate of anticoagulant treatment , as compared with the st and ard practice of short- duration ECG monitoring . ( Funded by the Canadian Stroke Network and others ; EMBRACE Clinical Trials.gov number , NCT00846924 . )", "Background and Purpose — Atrial fibrillation ( AF ) elevates risk of recurrent stroke but is incompletely identified by st and ard investigation after stroke , though detection rates correlate with monitoring duration . We hypothesized that 7 days of noninvasive cardiac-event monitoring early after stroke would accelerate detection of AF and thus uptake of effective therapy . Methods — We performed a pragmatic r and omized trial with objective outcome assessment among patients presenting in sinus rhythm with no AF history , within 7 days of ischemic stroke symptom onset . Patients were r and omized to st and ard practice investigations ( SP ) to detect AF , or SP plus additional monitoring ( SP-AM ) . AM comprised 7 days of noninvasive cardiac-event monitoring reported by an accredited cardiac electrocardiology laboratory . Primary outcome was detection of AF at 14 days . Results — One-hundred patients were enrolled from 2 centers . Within 14 days of stroke , sustained paroxysms of AF were detected in 18 % of patients undergoing SP-AM versus 2 % undergoing SP ( P Paroxysms of any- duration were detected in 44 % of patients undergoing SP-AM versus 4 % undergoing SP ( P differences persisted at 90 days . Anticoagulant therapy was commenced within 14 days in 16 % of SP-AM patients versus none r and omized to SP ( P noninvasive cardiac-event monitoring after acute stroke enhances detection of paroxysmal AF and early anticoagulation . Extended monitoring should be offered to all eligible patients soon after acute stroke . Guidelines on investigation for AF in stroke patients could be strengthened . Clinical Trial Registration — URL : http://www.controlled-trials.com/is rct n/. Unique identifier : IS RCT N97412358", "Background —Current methods for detecting atrial fibrillation ( AF ) have limited diagnostic yield . Continuous monitoring with automatic arrhythmia detection and classification may improve detection of symptomatic and asymptomatic AF and subsequent patient treatment . The study purpose was to quantify the performance of the first implantable leadless cardiac monitor ( ICM ) with dedicated AF detection capabilities . Methods and Results — Patients ( n=247 ) with an implanted ICM ( Reveal XT , Medtronic Inc , Minneapolis , Minn ) who were likely to present with paroxysmal AF were selected . A special Holter device stored 46 hours of subcutaneously recorded ECG , ICM markers , and 2 surface ECG leads . The ICM automatic arrhythmia classification was compared with the core laboratory classification of the surface ECG . Of the 206 analyzable Holter recordings collected , 76 ( 37 % ) contained at least 1 episode of core laboratory classified AF . The sensitivity , specificity , positive predictive value , and negative predictive value for identifying patients with any AF were 96.1 % , 85.4 % , 79.3 % , and 97.4 % , respectively . The AF burden measured with the ICM was very well correlated with the reference value derived from the Holter ( Pearson coefficient=0.97 ) . The overall accuracy of the ICM for detecting AF was 98.5 % . Conclusions —In this ICM validation study , the dedicated AF detection algorithm reliably detected the presence or absence of AF and the AF burden was accurately quantified . The ICM is a promising new diagnostic and monitoring tool for the clinician to treat AF patients independently of symptoms . Long-term studies are needed to evaluate the clinical benefits of the technology . Clinical Trial Registration — clinical trials.gov Identifier NCT00680927", "An ECG recording time of 24 hours has a low yield to detect atrial arrhythmias in patients after an acute ischemic stroke . The present study investigated whether a recording time of 72 instead of 24 hours detects paroxysmal atrial fibrillation in more patients . The study prospect ively included 82 consecutive patients 2 - 3 weeks after an acute ischemic stroke . All patients had sinus rhythm in the resting ECGs and no history of atrial fibrillation or flutter . The frequency of atrial fibrillation was assessed after 24 , 48 , and 72 hours of ambulatory ECG monitoring . An ECG monitoring time of 72 hours documented paroxysmal atrial fibrillation in five ( 6 % ) patients . The episode of paroxysmal atrial fibrillation occurred in only one patient within 24 hours . The other patients had their first episode of atrial fibrillation between 24 and 48 hours ( n = 2 ) and between 48 and 72 hours ( n = 2 ) . These five patients were older ( age = 70 + /- 5 years ) , whereas the mean age of the remaining patients was 59 + /- 13 years . All five patients had cardiovascular disease in comparison to 36 of 77 patients and reported palpitations in comparison to 6 of 77 of the remaining patients . In conclusion , ambulatory ECG monitoring over 72 hours detected after the first recording day four of five patients in whom paroxysmal atrial fibrillation could be documented for the first time . The 72-hour recording time improved , compared to the 24-hour period , the detection of paroxysmal atrial fibrillation in patients after an ischemic stroke . It seems to be more efficient to perform prolonged ECG recording mainly in older patients with a cardiovascular disease and /or a history of palpitations", "BACKGROUND It is unclear if brief episodes of paroxysmal atrial fibrillation ( PAF ) detected by prolonged cardiac monitoring are an occult of cause of cryptogenic strokes ( CS ) . We compared the incidence of PAF in patients with CS and patients with stroke of known cause ( SKC ) using prolonged ambulatory cardiac monitoring . METHODS We prospect ively enrolled patients within 3 months of ischemic stroke to undergo noninvasive cardiac monitoring for 3 weeks . Primary end point was PAF detection independently confirmed by 2 blinded cardiologists . RESULTS The study consisted of 132 patients , 66 had CS and 66 had SKC . Episodes of PAF were detected in 16 of 64 ( 25 % ) patients with CS and 9 of 64 ( 14 % ) patients with SKC ( P=.12 ) . Duration and number of PAF episodes , PAF burden , and time of first PAF detection did not differ significantly between the 2 groups ( P>.05 for all ) . In patients younger than 65 years , PAF was more common in the CS group ( 22 % versus 3 % ; P=.07 ) , whereas in patients 65 years or older , the rates of detection were similar ( 27 % in CS versus 25 % in SKC ; P=.9 ) . Among patients younger than 65 years with embolic imaging pattern , PAF was only observed in the CS group ( 21 % versus 0 % ; P=.03 ) . CONCLUSIONS Very short episodes of PAF are common in patients with CS and with SKC , but their pathogenic significance is unclear . Predominance of PAF in younger patients with CS and embolic infa rct pattern suggests a causative role in these cases . More research is needed before prolonged cardiac rhythm monitoring can be recommended to guide anticoagulation in CS patients", "Background and Purpose — Observational studies indicate that outpatient cardiac monitoring detects previously undiagnosed atrial fibrillation ( AF ) in 5 % to 20 % of patients with recent stroke . However , it remains unknown whether the yield of monitoring exceeds that of routine clinical follow-up . Methods — In a pilot trial , we r and omly assigned 40 patients with cryptogenic ischemic stroke or high-risk transient ischemic attack to wear a Cardionet mobile cardiac outpatient telemetry monitor for 21 days or to receive routine follow-up alone . After thorough investigation , we excluded patients with documented AF or other apparent stroke pathogenesis . We contacted patients and their physicians at 3 months and at 1 year to ascertain any diagnoses of AF or recurrent stroke or transient ischemic attack . Results — The baseline characteristics of our cohort broadly matched those of previous observational studies of monitoring after stroke . In the monitoring group , patients wore monitors for 64 % of the assigned days , and 25 % of patients were not compliant at all with monitoring . No patient in either study arm received a diagnosis of AF . Cardiac monitoring revealed AF in zero patients ( 0 % ; 95 % confidence interval , 0%–17 % ) , brief episodes of atrial tachycardia in 2 patients ( 10 % ; 95 % confidence interval , 1%–32 % ) , and nonsustained ventricular tachycardia in 2 patients ( 10 % ; 95 % confidence interval , 1%–32 % ) . Conclusions — In the first reported r and omized trial of cardiac monitoring after cryptogenic stroke , the rate of AF detection was lower than expected , incidental arrhythmias were frequent , and compliance with monitoring was suboptimal . Our findings highlight the challenges of prospect ively identifying stroke patients at risk for harboring paroxysmal AF and ensuring adequate compliance with cardiac monitoring . Clinical Trial Registration — URL : http:// clinical trials.gov . Unique Identifier :", "BACKGROUND AND PURPOSE Detection of atrial fibrillation is of vital importance because oral anticoagulation decreases the risk of a stroke by 64 % . Current st and ards for stroke unit treatment require continuous electrocardiogram ( ECG ) monitoring for at least 24 h. Additionally , a 24-h HOLTER ECG ( HOLTER ) should be performed in selected patients . It remains unclear whether continuous monitoring at the bedside is equivalent to HOLTER for the detection of atrial fibrillation . Furthermore , we investigate how many additional patients with paroxysmal atrial fibrillation can be identified as a result of a longer duration of continuous monitoring . METHODS In this study , we prospect ively compared the detection rates of HOLTER and 24-h monitoring at the Stroke Unit at the University of Heidelberg over a period of 9 months . Continuous monitoring was analyzed by trained nurses , HOLTER by cardiologists . RESULTS We included 370 patients with ischemic stroke or transient ischemic attack ( TIA ) in our study . Of these , 192 patients underwent HOLTER . Previously unknown atrial fibrillation was detected in 44 patients , 13 patients had no atrial fibrillation in baseline ECG , but atrial fibrillation was detected by continuous monitoring . In two patients , the HOLTER showed atrial fibrillation ; both patients had also been detected by continuous monitoring . Median time to detection of the atrial fibrillation during continuous monitoring was 43 h after hospitalization . CONCLUSION In this study , use of HOLTER does not give any additional benefit in comparison with continuous monitoring with intermittent analysis by trained staff alone . The median detection time of 43 h emphasizes the importance of longer continuous monitoring", "BACKGROUND Several studies have suggested that after ischemic stroke , continuous electrocardiographic ( ECG ) monitoring ( CEM ) increases the atrial fibrillation ( AF ) detection rate . However , optimal CEM terms of use are not clear . The aim of our study was to evaluate the usefulness of CEM in detecting AF and define optimal terms of the use of CEM . METHODS We prospect ively enrolled consecutive patients with acute ischemic stroke who were admitted to the stroke unit without AF on baseline ECG . We compared 2 strategies of AF detection : the first using CEM and the second with routine clinical practice ( 24-hour Holter ECG and additional ECGs ) . Adjusted odds ratios for the association between AF diagnosis and the use of CEM stratified by monitoring duration were calculated using multivariate logistic regression analysis . RESULTS Of the 1166 patients included , 220 ( 18.87 % ) had AF on baseline ECG and were excluded . Of the 946 remaining patients , 592 underwent CEM . The prevalence of AF using CEM was 12.50 % compared 2.26 % using the routine strategy . After adjustment ( demographic data , vascular risk factors , and National Institutes of Health Stroke Scale scores ) , using CEM increased 5.29 fold the odds of finding AF ( 95 % confidence interval [ CI ] 2.43 - 11.55 ) compared to the routine strategy . The adjusted odds ratio ( 9.82 ; 95 % CI 3.01 - 32.07 ) was maximum for the first day of monitoring and decreased later . Beyond 5 days , CEM usefulness was not significantly higher than the routine strategy . CONCLUSIONS We suggest that in order to enhance the detection rate of AF , CEM could be generalized in the stroke unit . It must be started early in patients with acute stroke and prolonged over a minimum of 4 days", "UNLABELLED Detection of paroxysmal atrial fibrillation ( PAF ) in patients with recent ischemic stroke or TIA suggests a cardioembolic etiology and leads to initiation of oral anticoagulation in suitable c and i date s. We assessed the diagnostic and therapeutic impact of adding ambulatory electrocardiography ( 24 hr ECG ) to a st and ardised ischemic stroke workup . METHODS We measured the frequency of detection of PAF in consecutive stroke patients who underwent 24 hr ECG that was not diagnosed clinical ly or on a st and ard 12-lead ECG . RESULTS One hundred forty five ischemic stroke patients were included . 24 hr ECG was obtained in 136 patients ( 93.8 % ) . Clinical ly unsuspected PAF was detected on 24 hr ECG in 7 patients ( 5.1 % ) . The secondary prevention measure changed from antiplatelet agents to oral anticoagulation in 6 of 7 patients . CONCLUSION Our findings suggest that ambulatory electrocardiography is a valuable diagnostic tool in the workup of stroke patients . Further prospect i ve studies are needed to identify , subtypes of patients in whom the yield of ambulatory electrocardiography is higher", "Atrial fibrillation ( AF ) is intermittent in 30 % of patients with cardioembolic stroke and , therefore , might not be seen in a single st and ard ECG recording . The aim of this study was to evaluate if prolonged ECG monitoring ( 96 h ) finds episodes of intermittent AF beyond the 24 h ECG monitoring in patients with cryptogenic stroke or transient ischemic attack ( TIA ) . We prospect ively evaluated consecutive patients affected by cryptogenic stroke or TIA who had sinus rhythm on a 12-lead ECG on admission , and during ECG monitoring performed in the acute phase ( for at least 24 h ) . Patients had continuous 96 h Holter ECG monitoring within 30 days from stroke onset . 114 patients were included in the study ( mean age 63.1 ± 15.1 , 59 males ) . AF was found in 29 patients ( 24.3 % ) . In 20 patients , AF was found in the first 24 h of recording , and in nine patients after 24 h. In addition , several other dysrhythmias such as supraventricular ectopic activity ( 33 ) , ventricular tachycardia ( 10 ) , sinus pause ( 4 ) and sinus-atrial block ( 1 ) were found . In patients with cryptogenic stroke or TIA , 96 h ECG monitoring detected a high rate of AF . One-third of AF was seen beyond 24 h of ECG monitoring", "BACKGROUND Studies about continuous electrocardiographic ( ECG ) monitoring in detection of paroxysmal atrial fibrillation ( PAF ) in Asian patients with acute ischemic stroke are very limited . We looked for the prevalence and associated factors of atrial fibrillation ( AF ) and PAF in Thai patients with acute ischemic stroke . METHODS In all , 204 patients with acute ischemic stroke were prospect ively included . Snapshot 12-lead ECG and continuous ECG monitoring for at least the first 24 hours were performed . Multivariate analyses were performed to find out the associated factors of AF and PAF . RESULTS AF was diagnosed in 31 patients ( 15 % ) and PAF in 15 patients ( 7 % ) . Twelve and 3 patients with PAF were diagnosed by continuous ECG monitoring and snapshot 12-lead ECG , respectively . Mean duration of continuous ECG monitoring and mean time to detect PAF were 55 and 23 hours , respectively . Multivariate analysis revealed that age of 70 years or older ( odds ratio [ OR ] 3.52 , 95 % confidence interval [ CI ] 1.68 - 7.35 , P = .001 ) and heart diseases ( OR 4.26 , 95 % CI 1.14 - 15.95 , P = .031 ) were associated with AF and PAF . CONCLUSIONS AF/PAF was one of the common causes of ischemic stroke in Thai patients . Most PAF was detected by continuous ECG monitoring . Snapshot 12-lead ECG and continuous ECG monitoring should be recommended in all patients with acute ischemic stroke", "BACKGROUND Patients with atrial fibrillation ( AF ) are at increased risk for ischemic stroke . In patients who have suffered a stroke , screening for AF is routinely performed only for a short period after the stroke as part of the evaluation for possible causes . If AF is detected after an ischemic stroke , oral anticoagulation therapy is recommended for secondary stroke prevention . In 25 % to 30 % of stroke patients , the stroke mechanism can not be determined ( cryptogenic stroke ) . The incidence of paroxysmal AF undetected by short-term monitoring in patients with cryptogenic stroke is unknown , but has important therapeutic implication s on patient care . The optimum monitoring duration and method of AF detection after stroke are unknown . The purpose of this study is to evaluate the incidence of AF and time to AF detection in patients with cryptogenic stroke using an insertable cardiac monitor . STUDY DESIGN The CRYSTAL AF trial is a r and omized prospect i ve study to evaluate a novel approach to long-term monitoring for AF detection in patients with cryptogenic stroke . Four hundred fifty cryptogenic stroke patients ( by definition , without a history of AF ) will be enrolled at approximately 50 sites in Europe , Canada , and the United States . Patients will be r and omized in a 1:1 fashion to st and ard arrhythmia monitoring ( control arm ) or implantation of the subcutaneous cardiac monitor ( Reveal XT ; Medtronic , Inc , Minneapolis , MN ) ( continuous monitoring arm ) . OUTCOMES The primary end point is time to detection of AF within 6 months after stroke . The clinical follow-up period will be at least 12 months . Study completion is expected at the end of 2012", "Atrial fibrillation and atrial flutter are common cardiac arrhythmias associated with an increased risk of stroke in patients with additional risk factors . Anticoagulation ameliorates stroke risk , but because these arrhythmias may occur intermittently without symptoms , initiation of prophylactic therapy is often delayed until electrocardiographic documentation is obtained . The IMPACT study is a multicenter , r and omized trial of remote surveillance technology in patients with implanted dual-chamber cardiac resynchronization therapy defibrillator ( CRT-D ) devices design ed to test the hypothesis that initiation and withdrawal of oral anticoagulant therapy guided by continuous ambulatory monitoring of the atrial electrogram improve clinical outcomes by reducing the combined rate of stroke , systemic embolism , and major bleeding compared with conventional clinical management . For those in the intervention group , early detection of atrial high-rate episodes ( AHRE ) generates an automatic alert to initiate anticoagulation based on patient-specific stroke risk stratification . Subsequently , freedom from AHRE for predefined periods prompts withdrawal of anticoagulation to avoid bleeding . Patients in the control arm are managed conventionally , the anticoagulation decision prompted by incidental detection of atrial fibrillation or atrial flutter during routine clinical follow-up . The results will help define the clinical utility of wireless remote cardiac rhythm surveillance and help establish the critical threshold of AHRE burden warranting anticoagulant therapy in patients at risk of stroke . In this report , we describe the study design and baseline demographic and clinical features of the initial cohort ( 227 patients )", "Background : Atrial fibrillation ( AF ) is a frequent cause of stroke , but detecting paroxysmal AF ( pAF ) poses a challenge . We investigated whether continuous bedside ECG monitoring in a stroke unit detects pAF more sensitively than 24-hour Holter ECG , and tested whether examining RR interval dynamics on short-term ECG recordings using an automated screening algorithm ( ASA ) for pAF detection is a useful tool to predict the risk of pAF outside periods of manifest AF . Methods : Patients > 60 years with acute ischemic stroke or transient ischemic attacks ( TIA ) were prospect ively enrolled unless initial ECG revealed AF or they had a history of paroxysmal or persistent AF . ASA was performed on 1- to 2-hour ECG recordings in the emergency room and patients were classified into 5 risk categories for pAF . All patients underwent continuous bedside ECG monitoring for > 48 h. Additionally , 24-hour Holter ECG was performed . Results : 136 patients were enrolled ( median age : 72 years , male : 58.8 % ) . In 29 ( 21.3 % ) , pAF was newly diagnosed by continuous bedside ECG monitoring . pAF increased with age ( p = 0.031 ) . Median time to first pAF detection on continuous bedside ECG monitoring was 36 h. In 16 patients , pAF was detected by continuous bedside ECG monitoring prior to the performance of 24-hour Holter ECG . Thirteen of the remaining patients were pAF positive on continuous bedside ECG monitoring , but 24-hour Holter detected only 3 patients . Accordingly , the sensitivity of 24-hour Holter was 0.23 . Sensitivity of higher-risk categories of ASA compared to continuous bedside ECG monitoring was 0.72 , and specificity 0.63 . Conclusion : Continuous bedside ECG monitoring is more sensitive than 24-hour Holter ECG for pAF detection in acute stroke/TIA patients . Screening patients for pAF outside AF episodes using ASA requires further development", "This pilot study in a prospect i ve cohort of 20 cryptogenic stroke patients showed that a significant proportion has paroxysmal atrial fibrillation undetected by 24-h Holter monitoring . However , longer monitoring with 28-day Holter was poorly tolerated and still insufficiently sensitive for paroxysmal atrial fibrillation detection . Further studies are urgently needed to eluci date the optimal timing , method and duration of cardiac rhythm monitoring following ischaemic stroke", "Atrial fibrillation ( AF ) and paroxysmal AF ( PAF ) are common causes of stroke which may not be detected by a single electrocardiogram ( EKG ) . We conducted a prospect i ve study to determine if 48 hours of telemetry monitoring increased the rate of detection of AF in patients with acute stroke and thus identified patients requiring anticoagulation . One hundred and fifty consecutive patients with acute ischemic stroke were placed on telemetry monitoring for 48 hours . Thirty-five patients had AF related strokes . There were 12 patients with AF related stroke who did not have a previous history of AF and were found to have AF following the stroke . Six of these 12 patients were found to have AF on their admission EKG . The remaining six patients had normal admission EKGs and were diagnosed with AF only during telemetry monitoring for 48 hrs . Patients with AF were older , had larger strokes , which were more likely to be non-lacunar , than patients without AF . Our study suggests that AF is sometimes undiagnosed until a stroke occurs . Improved methods of detection of AF are needed in high-risk patients for primary stroke prevention . Patients older than 65 years of age with non-lacunar strokes should have 48 hours of telemetry monitoring to detect previously undiagnosed AF", "BACKGROUND Current guidelines recommend at least 24 hours of electrocardiographic ( ECG ) monitoring after an ischemic stroke to rule out atrial fibrillation . However , the most effective duration and type of monitoring have not been established , and the cause of ischemic stroke remains uncertain despite a complete diagnostic evaluation in 20 to 40 % of cases ( cryptogenic stroke ) . Detection of atrial fibrillation after cryptogenic stroke has therapeutic implication s. METHODS We conducted a r and omized , controlled study of 441 patients to assess whether long-term monitoring with an insertable cardiac monitor ( ICM ) is more effective than conventional follow-up ( control ) for detecting atrial fibrillation in patients with cryptogenic stroke . Patients 40 years of age or older with no evidence of atrial fibrillation during at least 24 hours of ECG monitoring underwent r and omization within 90 days after the index event . The primary end point was the time to first detection of atrial fibrillation ( lasting > 30 seconds ) within 6 months . Among the secondary end points was the time to first detection of atrial fibrillation within 12 months . Data were analyzed according to the intention-to-treat principle . RESULTS By 6 months , atrial fibrillation had been detected in 8.9 % of patients in the ICM group ( 19 patients ) versus 1.4 % of patients in the control group ( 3 patients ) ( hazard ratio , 6.4 ; 95 % confidence interval [ CI ] , 1.9 to 21.7 ; P atrial fibrillation had been detected in 12.4 % of patients in the ICM group ( 29 patients ) versus 2.0 % of patients in the control group ( 4 patients ) ( hazard ratio , 7.3 ; 95 % CI , 2.6 to 20.8 ; P ECG monitoring with an ICM was superior to conventional follow-up for detecting atrial fibrillation after cryptogenic stroke . ( Funded by Medtronic ; CRYSTAL AF Clinical Trials.gov number , NCT00924638 . )", "Background : Paroxysmal atrial fibrillation ( PAF ) may remain underdiagnosed after stroke , as suggested by long- duration EKG monitoring . Here we report the sensitivity of transtelephonic EKG monitoring ( TTM ) for detection of PAF in patients following a recent stroke or TIA and a negative 24-hour Holter . Methods : We analyzed data from 98 consecutive patients with TTM and noncardioembolic TOAST stroke ( n = 78 ) or TIA ( n = 20 ) . Most were cryptogenic events ( 82 % ) . Patients started TTM 0.8 months ( interquartile range 0.4–2.5 ) after the indexed event and r and omly recorded about 1 EKG per day for 1 month . Univariate and multivariate analyses were run to identify PAF predictors . Results : Seventeen PAF episodes were detected in 9.2 % ( 9/98 ) of the patients . The estimated duration of PAF episodes ranged from 4 to 72 hours . Two predictors were identified : premature atrial ectopic beats ( more than 100 ) in 24-hour routine Holter ( odds ratio [ OR ] = 11.0 ; 95 % confidence interval [ CI ] 1.9–62 ; p = 0.007 ) and nonlacunar anterior circulation DWI hypersignals ( OR = 9.9 ; 95 % CI 1.1–90.6 ; p = 0.04 ) . The PAF detection rate varied from 42.6 % for patients meeting both criteria to 0 % for patients with neither of them . Conclusions : Transtelephonic EKG monitoring increases detection rate of paroxysmal atrial fibrillation in stroke and TIA patients whose 24-hour Holter result was negative , especially if they had frequent premature atrial ectopic beats , recent anterior circulation infa rct on MRI , or both" ]

[ "Propensity score based methods are used increasingly to evaluate the effectiveness of treatments when evidence from r and omised trials is not available . However , users need to be aware of their strengths and", "Vaccination of one person may prevent the infection of another either because the vaccine prevents the first from being infected and from infecting the second , or because , even if the first person is infected , the vaccine may render the infection less infectious . We might refer to the first of these mechanisms as a contagion effect and the second as an infectiousness effect . In the simple setting of a r and omized vaccine trial with households of size two , we use counterfactual theory under interference to provide formal definitions of a contagion effect and an unconditional infectiousness effect . Using ideas analogous to mediation analysis , we show that the indirect effect ( the effect of one person 's vaccine on another 's outcome ) can be decomposed into a contagion effect and an unconditional infectiousness effect on the risk difference , risk ratio , odds ratio , and vaccine efficacy scales . We provide identification assumptions for such contagion and unconditional infectiousness effects and describe a simple statistical technique to estimate these effects when they are identified . We also give a sensitivity analysis technique to assess how inferences would change under violations of the identification assumptions . The concepts and results of this paper are illustrated with hypothetical vaccine trial data", "Introduction Enteric infections are common during the first years of life in low-income countries and contribute to growth faltering with long-term impairment of health and development . Water quality , sanitation , h and washing and nutritional interventions can independently reduce enteric infections and growth faltering . There is little evidence that directly compares the effects of these individual and combined interventions on diarrhoea and growth when delivered to infants and young children . The objective of the WASH Benefits study is to help fill this knowledge gap . Methods and analysis WASH Benefits includes two cluster-r and omised trials to assess improvements in water quality , sanitation , h and washing and child nutrition — alone and in combination — to rural households with pregnant women in Kenya and Bangladesh . Geographically matched clusters ( groups of household compounds in Bangladesh and villages in Kenya ) will be r and omised to one of six intervention arms or control . Intervention arms include water quality , sanitation , h and washing , nutrition , combined water+sanitation+h and washing ( WSH ) and WSH+nutrition . The studies will enrol newborn children ( N=5760 in Bangladesh and N=8000 in Kenya ) and measure outcomes at 12 and 24 months after intervention delivery . Primary outcomes include child length-for-age Z-scores and caregiver-reported diarrhoea . Secondary outcomes include stunting prevalence , markers of environmental enteropathy and child development scores ( verbal , motor and personal/social ) . We will estimate unadjusted and adjusted intention-to-treat effects using semiparametric estimators and permutation tests . Ethics and dissemination Study protocol s have been review ed and approved by human subjects review boards at the University of California , Berkeley , Stanford University , the International Centre for Diarrheal Disease Research , Bangladesh , the Kenya Medical Research Institute , and Innovations for Poverty Action . Independent data safety monitoring boards in each country oversee the trials . This study is funded by a grant from the Bill & Melinda Gates Foundation to the University of California , Berkeley . Registration Trial registration identifiers ( http://www . clinical trials.gov ) : NCT01590095 ( Bangladesh ) , NCT01704105 ( Kenya )", "BACKGROUND We evaluated the herd protection conferred by an oral cholera vaccine using 2 approaches : cluster design and geographic information system ( GIS ) design . METHODS Residents living in 3933 dwellings ( clusters ) in Kolkata , India , were cluster-r and omized to receive either cholera vaccine or oral placebo . Nonpregnant residents aged≥1 year were invited to participate in the trial . Only the first episode of cholera detected for a subject between 14 and 1095 days after a second dose was considered . In the cluster design , indirect protection was assessed by comparing the incidence of cholera among non participants in vaccine clusters vs those in placebo clusters . In the GIS analysis , herd protection was assessed by evaluating association between vaccine coverage among the population residing within 250 m of the household and the occurrence of cholera in that population . RESULTS Among 107 347 eligible residents , 66 990 received 2 doses of either cholera vaccine or placebo . In the cluster design , the 3-year data showed significant total protection ( 66 % protection , 95 % confidence interval [ CI ] , 50%-78 % , P indirect protection . With the GIS approach , the risk of cholera among placebo recipients was inversely related to neighborhood-level vaccine coverage , and the trend was highly significant ( P CONCLUSIONS Indirect protection was evident in analyses using the GIS approach but not the cluster design approach , likely owing to considerable transmission of cholera between clusters , which would vitiate herd protection in the cluster analyses . CLINICAL TRIALS REGISTRATION NCT00289224", "BACKGROUND Information and behaviour can spread through interpersonal ties . By targeting influential individuals , health interventions that harness the distributive properties of social networks could be made more effective and efficient than those that do not . Our aim was to assess which targeting methods produce the greatest cascades or spillover effects and hence maximise population -level behaviour change . METHODS In this cluster r and omised trial , participants were recruited from villages of the Department of Lempira , Honduras . We blocked villages on the basis of network size , socioeconomic status , and baseline rates of water purification , for delivery of two public health interventions : chlorine for water purification and multivitamins for micronutrient deficiencies . We then r and omised villages , separately for each intervention , to one of three targeting methods , introducing the interventions to 5 % sample s composed of either : r and omly selected villagers ( n=9 villages for each intervention ) ; villagers with the most social ties ( n=9 ) ; or nominated friends of r and om villagers ( n=9 ; the last strategy exploiting the so-called friendship paradox of social networks ) . Participants and data collectors were not aware of the targeting methods . Primary endpoints were the proportions of available products redeemed by the entire population under each targeting method . This trial is registered with Clinical Trials.gov , number NCT01672580 . FINDINGS Between Aug 4 , and Aug 14 , 2012 , 32 villages in rural Honduras ( 25 - 541 participants each ; total study population of 5773 ) received public health interventions . For each intervention , nine villages ( each with 1 - 20 initial target individuals ) were r and omised , using a blocked design , to each of the three targeting methods . In nomination-targeted villages , 951 ( 74·3 % ) of 1280 available multivitamin tickets were redeemed compared with 940 ( 66·2 % ) of 1420 in r and omly targeted villages and 744 ( 61·0 % ) of 1220 in indegree-targeted villages . All pairwise differences in redemption rates were significant ( p increased adoption of the nutritional intervention by 12·2 % compared with r and om targeting ( 95 % CI 6·9 - 17·9 ) . Targeting the most highly connected individuals , by contrast , produced no greater adoption of either intervention , compared with r and om targeting . INTERPRETATION Introduction of a health intervention to the nominated friends of r and om individuals can enhance that intervention 's diffusion by exploiting intrinsic properties of human social networks . This method has the additional advantage of scalability because it can be implemented without mapping the network . Deployment of certain types of health interventions via network targeting , without increasing the number of individuals targeted or the re sources used , could enhance the adoption and efficiency of those interventions , thereby improving population health . FUNDING National Institutes of Health , The Bill & Melinda Gates Foundation , Star Family Foundation , and the Canadian Institutes of Health Research", "Spatial analyses of the effect of insecticide (permethrin)-treated bed nets ( ITNs ) on nearby households both with and without ITNs was performed in the context of a large-scale , group-r and omized , controlled mortality trial in Asembo , western Kenya . Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality , moderate anemia , high-density parasitemia , and hemoglobin levels . This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs . This implies that in areas with intense malaria transmission with high ITN coverage , the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not , as commonly supposed , by simple imposition of a physical barrier protecting individuals from biting . The strength of the community effect depended upon the proportion of nearby compounds with treated nets . To maximize their public health impact , high coverage with treated nets is essential", "We consider the problem of separating the direct effects of an exposure from effects relayed through an intermediate variable ( indirect effects ) . We show that adjustment for the intermediate variable , which is the most common method of estimating direct effects , can be biased . We also show that , even in a r and omized crossover trial of exposure , direct and indirect effects can not be separated without special assumptions ; in other words , direct and indirect effects are not separately identifiable when only exposure is r and omized . If the exposure and intermediate never interact to cause disease and if intermediate effects can be controlled , that is , blocked by a suitable intervention , then a trial r and omizing both exposure and the intervention can separate direct from indirect effects . Nonetheless , the estimation must be carried out using the G-computation algorithm . Conventional adjustment methods remain biased . When exposure and the intermediate interact to cause disease , direct and indirect effects will not be separable even in a trial in which both the exposure and the intervention blocking intermediate effects are r and omly assigned . Nonetheless , in such a trial , one can still estimate the fraction of exposure-induced disease that could be prevented by control of the intermediate . Even in the absence of an intervention blocking the intermediate effect , the fraction of exposure-induced disease that could be prevented by control of the intermediate can be estimated with the G-computation algorithm if data are obtained on additional confounding variables . ( Epidemiology 1992;3:143–155", "Key information about human observational studies should be publicly available before the study is initiated . The vast majority of health-related observational studies are not prospect ively registered and the advantages of registration have not been fully appreciated . Nonetheless , international st and ards require approval of study protocol s by an independent ethics committee before the study can begin . We suggest that there is an ethical and scientific imperative to publicly preregister key information from newly approved protocol s , which should be required by funders . Ultimately , more complete information may be publicly available by disclosing protocol s , analysis plans , data sets , and raw data", "Latrine use has been promoted as a component of an integrated strategy for trachoma control . As part of a r and omized trial in Ethiopia , 12 communities received a mass azithromycin distribution followed by a latrine promotion intervention . A r and om sample of children ages 0 - 9 years in each community was monitored longitudinally for ocular chlamydia . After latrine construction ended , those communities with a higher proportion of households using latrines were more likely to experience a reduction in the prevalence of ocular chlamydia . Specifically , for each 10 % increase in latrine use , there was a 2.0 % decrease ( 95 % confidence interval = 0.2 - 3.9 % decrease ) in the community prevalence of ocular chlamydia over the subsequent year ( P = 0.04 )", "BACKGROUND Zanzibar , in east Africa , has been severely and repeatedly affected by cholera since 1978 . We assessed the effectiveness of oral cholera vaccination in high-risk population s in the archipelago to estimate the indirect ( herd ) protection conferred by the vaccine and direct vaccine effectiveness . METHODS We offered two doses of a killed whole-cell B-subunit cholera vaccine to individuals aged 2 years and older in six rural and urban sites . To estimate vaccine direct protection , we compared the incidence of cholera between recipients and non-recipients using generalised estimating equations with the log link function while controlling for potential confounding variables . To estimate indirect effects , we used a geographic information systems approach and assessed the association between neighbourhood-level vaccine coverage and the risk for cholera in the non-vaccinated residents of that neighbourhood , after controlling for potential confounding variables . This study is registered with Clinical Trials.gov , number NCT00709410 . FINDINGS Of 48,178 individuals eligible to receive the vaccine , 23,921 ( 50 % ) received two doses . Between February , 2009 , and May , 2010 , there was an outbreak of cholera , enabling us to assess vaccine effectiveness . The vaccine conferred 79 % ( 95 % CI 47 - 92 ) direct protection against cholera in participants who received two doses . Indirect ( herd ) protection was shown by a decrease in the risk for cholera of non-vaccinated residents within a household 's neighbourhood as the vaccine coverage in that neighbourhood increased . INTERPRETATION Our findings suggest that the oral cholera vaccine offers both direct and indirect ( herd ) protection in a sub-Saharan African setting . Mass oral cholera immunisation campaigns have the potential to provide not only protection for vaccinated individuals but also for the unvaccinated members of the community and should be strongly considered for wider use . Because this is an internationally-licensed vaccine , we could not undertake a r and omised placebo-controlled trial , but the absence of vaccine effectiveness against non-cholera diarrhoea indicates that the noted protection against cholera could not be explained by bias . FUNDING Bill & Melinda Gates Foundation , Swedish International Development Cooperation Agency , and the South Korean Government", "A fundamental assumption usually made in causal inference is that of no interference between individuals ( or units ) ; that is , the potential outcomes of one individual are assumed to be unaffected by the treatment assignment of other individuals . However , in many setting s , this assumption obviously does not hold . For example , in the dependent happenings of infectious diseases , whether one person becomes infected depends on who else in the population is vaccinated . In this article , we consider a population of groups of individuals where interference is possible between individuals within the same group . We propose estim and s for direct , indirect , total , and overall causal effects of treatment strategies in this setting . Relations among the estim and s are established ; for example , the total causal effect is shown to equal the sum of direct and indirect causal effects . Using an experimental design with a two-stage r and omization procedure ( first at the group level , then at the individual level within groups ) , unbiased estimators of the proposed estim and s are presented . Variances of the estimators are also developed . The methodology is illustrated in two different setting s where interference is likely : assessing causal effects of housing vouchers and of vaccines", "In r and omized trials , the treatment assignment mechanism is independent of the outcome of interest and other covariates thought to be relevant in determining this outcome . It also allows , on average , for a balanced distribution of these covariates in the vaccine and placebo groups . R and omization , however , does not guarantee that the estimated effect is an unbiased estimate of the biological effect of interest . We show how exposure to infection can be a confounder even in r and omized vaccine field trials . Based on a simple model of the biological efficacy of interest , we extend the arguments on comparability and collapsibility to examine the limits of r and omization to control for unmeasured covariates . Estimates from r and omized , placebo-controlled Phase III vaccine field trials that differ in baseline transmission are not comparable unless explicit control for baseline transmission is taken into account", "Significance Although pneumococcal conjugate vaccines ( PCVs ) are widely available in industrialized nations , the cost of these vaccines and the strategy of universal vaccination of infants , as endorsed by the World Health Organization , are daunting obstacles to the adoption of these vaccines in developing countries . Using spatial epidemiological methods to examine the spatial variation in vaccine efficacy ( VE ) in an 11-valent PCV trial in Bohol , Philippines , we suggest an alternative strategy to universal vaccination . Our main finding suggests that areas with poor access to healthcare have the highest VE . An alternative vaccination strategy could target vaccination to areas where children are most likely to benefit , rather than focus on nationwide immunization . Pneumococcal conjugate vaccines ( PCVs ) have demonstrated efficacy against childhood pneumococcal disease in several regions globally . We demonstrate how spatial epidemiological analysis of a PCV trial can assist in developing vaccination strategies that target specific geographic sub population s at greater risk for pneumococcal pneumonia . We conducted a secondary analysis of a r and omized , placebo-controlled , double-blind vaccine trial that examined the efficacy of an 11-valent PCV among children less than 2 y of age in Bohol , Philippines . Trial data were linked to the residential location of each participant using a geographic information system . We use spatial interpolation methods to create smoothed surface maps of vaccination rates and local-level vaccine efficacy across the study area . We then measure the relationship between distance to the main study hospital and local-level vaccine efficacy , controlling for ecological factors , using spatial autoregressive models with spatial autoregressive disturbances . We find a significant amount of spatial variation in vaccination rates across the study area . For the primary study endpoint vaccine efficacy increased with distance from the main study hospital from −14 % for children living less than 1.5 km from Bohol Regional Hospital ( BRH ) to 55 % for children living greater than 8.5 km from BRH . Spatial regression models indicated that after adjustment for ecological factors , distance to the main study hospital was positively related to vaccine efficacy , increasing at a rate of 4.5 % per kilometer distance . Because areas with poor access to care have significantly higher VE , targeted vaccination of children in these areas might allow for a more effective implementation of global programs", "Interference occurs when the treatment of one person affects the outcome of another . For example , in infectious diseases , whether one individual is vaccinated may affect whether another individual becomes infected or develops disease . Quantifying such indirect ( or spillover ) effects of vaccination could have important public health or policy implication s. In this article we use recently developed inverse-probability weighted ( IPW ) estimators of treatment effects in the presence of interference to analyze an individually-r and omized , placebo-controlled trial of cholera vaccination that targeted 121,982 individuals in Matlab , Bangladesh . Because these IPW estimators have not been employed previously , a simulation study was also conducted to assess the empirical behavior of the estimators in setting s similar to the cholera vaccine trial . Simulation study results demonstrate the IPW estimators can yield unbiased estimates of the direct , indirect , total , and overall effects of vaccination when there is interference provided the untestable no unmeasured confounders assumption holds and the group-level propensity score model is correctly specified . Application of the IPW estimators to the cholera vaccine trial indicates the presence of interference . For example , the IPW estimates suggest on average 5.29 fewer cases of cholera per 1000 person-years ( 95 % confidence interval 2.61 , 7.96 ) will occur among unvaccinated individuals within neighborhoods with 60 % vaccine coverage compared to neighborhoods with 32 % coverage . Our analysis also demonstrates how not accounting for interference can render misleading conclusions about the public health utility of vaccination", "Abstract We propose the minicommunity design to estimate indirect effects of vaccination . Establishing indirect effects of vaccination in unvaccinated sub population s could have important implication s for global vaccine policies . In the minicommunity design , the household or other small transmission unit serves as the cluster in which to estimate indirect effects of vaccination , similar to studies in larger communities to estimate indirect , total , and overall effects . Examples from the literature include studies in small transmission units to estimate indirect effects of pertussis , pneumococcal , influenza , and cholera vaccines . We characterize the minicommunity design by several method ologic considerations , including the assignment mechanism , ascertainment , the role of transmission outside the transmission unit , and the relation of the size of the transmission unit to number of people vaccinated . The minicommunity study for indirect effects is contrasted with studies to estimate vaccine effects on infectiousness and protective effects under conditions of household exposure within small transmission units . The minicommunity design can be easily implemented in individually r and omized studies by enrolling and following-up members of households of the r and omized individuals . The methodology for the minicommunity design for estimating indirect effects of vaccination deserves much future research", "BACKGROUND Trachoma-control programmes distribute oral azithromycin to treat the ocular strains of chlamydia that cause the disease and to control infection . Theoretically , elimination of infection is feasible if untreated individuals receive an indirect protective effect from living in repeatedly treated communities , which is similar to herd protection in vaccine programmes . We assessed indirect protection against trachoma with mass azithromycin distributions . METHODS In a cluster r and omised trial , 24 subkebeles ( government-defined units ) in Amhara , Ethiopia , were r and omised , with use of a simple r and om sample , to distribution four times per year of single-dose oral azithromycin to children aged 1 - 10 years ( 12 subkebeles , 4764 children ) , or to delayed treatment until after the study ( control ; 12 subkebeles , 6014 children ) . We compared the prevalence of ocular chlamydial infection in untreated individuals 11 years and older between baseline and 12 months in the treated subkebeles , and at 12 months between the treated and control subkebeles . Health-care and laboratory personnel were blinded to study group . Analysis was intention to treat . The study is registered with clinical trials.gov , number NCT00322972 . FINDINGS At 12 months , 637 children aged 1 - 10 years and 561 adults and children aged 11 years and older were analysed in the children-treated group , and 618 and 550 , respectively , in the control group . The mean prevalence of infection in children decreased from 48.4 % ( 95 % CI 42.9 - 53.9 ) to 3.6 % ( 0.8 - 6.4 ) after four mass treatments . At 12 months , the mean prevalence of infection in the untreated age group ( > /=11 years ) was 47 % ( 95 % CI 33 - 57 ) less than baseline ( p=0.002 ) , and 35 % ( 95 % CI 1 - 57 ) less than that in untreated communities ( p=0.04 ) . INTERPRETATION Frequent treatment of children , who are a core group for transmission of trachoma , could eventually eliminate infection from the entire community . Herd protection is offered by repeated mass antibiotic treatments , providing a strategy for elimination of a bacterial disease when an effective vaccine is unavailable . FUNDING National Institutes of Health", " The design and analysis of cluster r and omized trials has been a recurrent theme in Statistics in Medicine since the early volumes . In celebration of 25 years of Statistics in Medicine , this paper review s recent developments , particularly those that featured in the journal . Issues in design such as sample size calculations , matched paired design s , cohort versus cross-sectional design s , and practical design problems are covered . Developments in analysis include modification of robust methods to cope with small numbers of clusters , generalized estimation equations , population averaged and cluster specific models . Finally , issues on presenting data , some other clustering issues and the general problem of evaluating complex interventions are briefly mentioned", "Social scientists should adopt higher transparency st and ards to improve the quality and credibility of research . There is growing appreciation for the advantages of experimentation in the social sciences . Policy-relevant cl aims that in the past were backed by theoretical arguments and inconclusive correlations are now being investigated using more credible methods . Changes have been particularly pronounced in development economics , where hundreds of r and omized trials have been carried out over the last decade . When experimentation is difficult or impossible , research ers are using quasi-experimental design s. Governments and advocacy groups display a growing appetite for evidence -based policy-making . In 2005 , Mexico established an independent government agency to rigorously evaluate social programs , and in 2012 , the U.S. Office of Management and Budget advised federal agencies to present evidence from r and omized program evaluations in budget requests ( 1 , 2 )" ]

[ "OBJECTIVE To evaluate the potential body weight-lowering effects of dietary supplementation with eicosapentaenoic acid ( EPA ) and α-lipoic acid separately or combined in healthy overweight/obese women following a hypocaloric diet . METHODS This is a short-term double-blind placebo-controlled study with parallel design that lasted 10 weeks . Of the r and omized participants , 97 women received the allocated treatment [ Control , EPA ( 1.3 g/d ) , α-lipoic acid ( 0.3 g/d ) , and EPA+α-lipoic acid ( 1.3 g/d+0.3 g/d ) ] , and 77 volunteers completed the study . All groups followed an energy-restricted diet of 30 % less than total energy expenditure . Body weight , anthropometric measurements , body composition , resting energy expenditure , blood pressure , serum glucose , and insulin and lipid profile , as well as leptin and ghrelin levels , were assessed at baseline and after nutritional intervention . RESULTS Body weight loss was significantly higher ( P with α-lipoic acid . EPA supplementation significantly attenuated ( P in leptin levels that occurs during weight loss . Body weight loss improved lipid and glucose metabolism parameters but without significant differences between groups . CONCLUSIONS The intervention suggests that α-lipoic acid supplementation alone or in combination with EPA may help to promote body weight loss in healthy overweight/obese women following energy-restricted diets", "AIM To determine an influence of alpha-lipoic acid to reduction of body weight and regulation of total cholesterol concentration , triglycerides and glucose serum levels in obese patients with diabetes mellitus type 2 . METHODS A prospect i ve study includes two groups of obese patients with diabetes mellitus and signs of peripheral polyneuropathia : examined group ( 30 patients ; 15 females and 15 males ) , and control group ( 30 patients ; 12 females and 18 males ) . All were treated with metformin ( 850 - 1700 mg/day ) . Examined patients were additionally treated with alpha-lipoic acid 600 mg/day during 20 weeks . Body mass index and concentrations of total cholesterol , triglycerides and glucose in serum were compared before and after the treatment . RESULTS The group treated with 600 mg alpha-lipoic acid lost significantly more weight , and had lower triglyceride level than the control group . There were no significant differences in total cholesterol and glucose serum levels between the groups . CONCLUSION Alpha-lipoic acid of 600 mg/day treatment have influenced weight and triglycerides loss in obese patients with diabetes mellitus type 2 . It should be considered as an important additive therapy in obese patients with diabetes mellitus type 2", "Several studies showed that impairment of endothelium-dependent arterial dilation ( EDAD ) exists in subjects with impaired fasting glucose ( IFG ) . The crucial mechanism of this endothelial dysfunction remains unclear . We hypothesized that oxidative stress may be partially responsible for the impairment in EDAD in subjects with IFG . Thus , the present study was design ed to assess whether the antioxidant α-lipoic acid can improve endothelial dysfunction in subjects with IFG . Sixty subjects with newly diagnosed IFG and 32 healthy individuals with normal glucose tolerance were enrolled . Subjects were r and omized into 2 groups : untreated experimental group ( n = 30 ) and α-lipoic acid treatment group ( n = 30 , α-lipoic acid 600 mg via intravenous infusion once a day for 3 weeks ) . We measured EDAD at baseline and after 3 weeks of intervention . At baseline , EDADs in α-lipoic acid and untreated experimental groups were 4.03 % and 4.14 % , respectively , which were significantly lower than that in controls ( 5.72 % ) ( P increase in EDAD ( reaching 5.10 % ; ΔEDAD , 26.5 % ) ( P decrease in plasma thiobarbituric acid reactive substances ( TBARS ) ( 29.1 % ) ( P α-lipoic acid . Endothelium-dependent arterial dilation and TBARS remained unchanged before and after intervention in the untreated experimental group . The absolute changes in EDAD showed a significant negative correlation with the changes in TBARS ( r = -0.444 , P = .014 ) . Our data showed that IFG subjects have impaired endothelial function and that antioxidant α-lipoic acid can improve endothelial function through a decrease of oxygen-derived free radicals ", "PURPOSE alpha-lipoic acid is an essential cofactor for mitochondrial respiratory enzymes that improves mitochondrial function . We previously reported that alpha-lipoic acid markedly reduced body weight gain in rodents . The purpose of this study was to determine whether alpha-lipoic acid reduces body weight in obese human subjects . METHODS in this r and omized , double-blind , placebo-controlled , 20-week trial , 360 obese individuals ( body mass index [ BMI ] ≥ 30 kg/m(2 ) or BMI 27 - 30 kg/m(2 ) plus hypertension , diabetes mellitus , or hypercholesterolemia ) were r and omized to alpha-lipoic acid 1200 or 1800 mg/d or placebo . The primary end point was body weight change from baseline to end point . RESULTS the 1800 mg alpha-lipoic acid group lost significantly more weight than the placebo group ( 2.1 % ; 95 % confidence interval , 1.4 - 2.8 ; P ) . Urticaria and itching sensation were the most common adverse events in the alpha-lipoic acid groups , but these were generally mild and transient . CONCLUSION alpha-lipoic acid 1800 mg/d led to a modest weight loss in obese subjects . Alpha-lipoic acid may be considered as adjunctive therapy for obesity", "The objective of the present study was to determine the effects of a long-term moderate-fat diet ( 30 % energy from fat ) v. a low-fat one ( 20 % energy from fat ) on metabolic risks . The study was a r and omised , prospect i ve 14-month trial on overweight and obese patients ( eighty-nine overweight and obese men and women ) . The intervention was a moderate-fat diet ( 30 % energy ) or a low-fat diet ( 20 % energy ) . The main outcome measurements were change in body weight , waist circumference , LDL-cholesterol , HDL-cholesterol , total cholesterol , TAG , and systolic and diastolic blood pressure . Forty-five subjects on the moderate-fat diet and forty-four subjects on the low-fat one were studied . Characteristics of all r and omised participants were similar in both groups . After 7 months , the moderate- and low-fat diets had similar effects on cardiovascular risks . The moderate-fat diet was more successful after 14 months in reducing weight ( -5.0 ( SD 2.5 ) kg in the moderate-fat group v. -1.2 ( SD 1.1 ) kg in the low-fat one ; P waist circumference ( -5.5 ( SD 2.4 ) cm in the moderate-fat group v. - 2.3 ( SD 1.3 ) cm in the low-fat one ; P cardiovascular risk factors as well ( LDL , TAG , total cholesterol and systolic blood pressure ) . In conclusion , a moderate-fat energy-restricted diet in the long term might have more beneficial effects on weight maintenance and cardiovascular risk factors compared with a low-fat diet . Better dietary adherence with the moderate-fat diet may be the reason for its successful effects", "OBJECTIVE We examined the effects of alpha-lipoic acid ( ALA ) supplementation on inflammation , oxidative stress , and serum lipid profile levels in hemodialysis ( HD ) patients . DESIGN This was a double-blinded , r and omized , placebo-controlled clinical trial . SETTING The present study involved HD centers in Tabriz , Iran . PATIENTS Participants included 63 patients with end-stage renal disease ( 43 men and 20 women ; age range : 22 - 79 years ) undergoing maintenance HD . INTERVENTION HD patients were r and omly assigned into the supplemented group ( n = 31 ) , receiving a daily dose of ALA ( 600 mg ) , or a control group ( n = 32 ) , receiving placebo for 8 weeks . MAIN OUTCOME MEASURES High sensitivity C-reactive protein ( hsCRP ) , malondialdehyde , total antioxidant status , total cholesterol , triglyceride , high-density lipoprotein cholesterol ( HDL-C ) , and low-density lipoprotein cholesterol ( LDL-C ) were measured at baseline and after 8 weeks of supplementation . RESULTS At the end of intervention , 11 patients were excluded from the study . HsCRP levels decreased by 18.7 % in the supplemented group after 8 weeks of supplementation , and the reduction was significant in comparison with the placebo group ( P mean malondialdehyde and total antioxidant status levels did not change significantly in the 2 groups during the study . The mean high-density lipoprotein cholesterol concentrations increased significantly in the supplemented group at the end of the study ( P lipid profile parameters within each group during the study . CONCLUSION ALA supplementation significantly reduced hsCRP levels , which is a risk factor for cardiovascular disease in HD patients", "Background : Soy milk replacement in the diet might have beneficial effects on waist circumference and cardiovascular risk factors for overweight and obese subjects . Therefore , we are going to determine the effects of soy milk replacements on the waist circumference and cardiovascular risk factors among overweight and obese female adults . Methods : In this crossover r and omized clinical trail , 24 over weight and obese female adults were on a diet with soy milk or the diet with cow 's milk for four weeks . In the diet with soy milk only one glass of soy milk ( 240 cc ) was replaced instead of one glass of cow 's milk ( 240 cc ) . Measurements were done according to the st and ard protocol . Results : Waist circumference reduced significantly following soy milk period ( mean percent change in soy milk period for waist circumference : -3.79 ± 0.51 vs. -1.78 ± 0.55 % ; P = 0.02 in the cow 's milk period ) . Blood pressure , weight , liver enzymes and glycemic control indices did not changed significantly after soy milk period compared to the cow 's milk period . Conclusion : Among over weight and obese patients , soy milk can play an important role in reducing waist circumference . However , soy milk replacement had no significant effects on weight , glycemic control indices , liver enzymes , fibrinogen and blood pressure in a short term trial", "Study design : A r and omized , double-blind , placebo-controlled clinical trial . Objective : To assess the effect of alpha-lipoic acid ( ALA ) supplementation on IL-6 , hs-CRP , FBS , anthropometric indices , food intake and blood pressure in male patients with chronic spinal cord injury ( SCI ) . Setting : Imam Khomeini Hospital , Tehran University of Medical Sciences , Tehran , Iran . Methods : Fifty-eight men with chronic SCI participated in the study . Participants were divided in two groups : one group received 600 mg of supplemental ALA ( n=28 ) and the other group received placebo ( n=30 ) for 12 weeks . At the beginning and end of the study , biochemical parameters , anthropometric indices , blood pressure and dietary intakes were measured . Dietary intake was measured using N4 software , and statistical analyses were carried out using SPSS16 . Results : No significant reduction was found in IL-6 ( P=0.97 ) and hs-CRP levels ( P=0.23 ) . There was significant reduction in fasting blood sugar ( P=0.001 ) , body weight ( P=0.001 ) , BMI ( P=0.001 ) , waist circumference ( P=0.001 ) and blood pressure ( P=0.001 ) . Dietary intake was significantly reduced , including fat ( P=0.001 ) , carbohydrate ( P=0.001 ) , protein ( P=0.002 ) and energy intakes ( P=0.001 ) . Conclusion : Lipoic acid supplementation had no significant effect on the measured inflammatory markers but it reduces fasting blood sugar , anthropometric parameters , food intake and blood pressure in men with chronic SCI", "& agr;-Lipoic acid ( ALA ) has been reported to be effective in reducing body weight in rodents and obese patients . Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics . The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics . In a 12-week , double-blind r and omized placebo-controlled study , 22 overweight and clinical ly stable patients with schizophrenia were r and omly assigned to receive ALA or placebo . ALA was administered at 600–1800 mg , as tolerated . Weight , BMI , abdomen fat area measured by computed tomography , and metabolic values were determined . Adverse effects were also assessed to examine safety . Overall , 15 patients completed 12 weeks of treatment . There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group . There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects . ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen . Moreover , ALA was well tolerated throughout this study . ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics", "OBJECTIVE To examine the effects of alpha-lipoic acid ( ALA ) treatment over a period of 2 months on fasting blood glucose ( FBG ) , insulin resistance ( IR ) , and glutathione peroxidase ( GH-Px ) activity in type 2 diabetes ( T2DM ) patients . METHODS This study took place in Motahari Clinic , Shiraz , Iran , which is affiliated to Shiraz University of Medical Sciences from May to October 2006 . Type 2 DM patients ( n=57 ) were divided into 2 groups to receive either ALA ( 300 mg daily ) or placebo by systematic r and omization , and were followed-up for 8 weeks . After an overnight fasting and 2 hours after breakfast , patients ' blood sample s were drawn and tested for FBG , 2 hours PPG , serum insulin level , and GH-Px activity . RESULTS The result of the study showed a significant decrease in FBG and PPG levels , IR-Homeostasis Model Assessment ( IR-HOMA index ) and GH-Px level in the ALA group . The comparison of differences between FBG and IR at the beginning and at the end of study in the ALA treated group and the placebo group were also significant . CONCLUSION This study supports the use of ALA as an antioxidant in the care of diabetic patients" ]

[ "Background Neurocognitive testing has been endorsed as a “ cornerstone ’ of concussion management by recent Vienna and Prague meetings of the Concussion in Sport Group . Neurocognitive testing is important given the potential unreliability of athlete self-report after injury . Relying only on athletes'ormalities after injury . Study Design Case control study ; Level of evidence , 3 . Methods High school and college athletes with a diagnosed concussion were tested 2 days after injury . Postinjury neurocognitive performance ( Immediate Postconcussion Assessment and Cognitive Testing ) and symptom ( postconcussion symptom ) scores were compared with preinjury ( baseline ) scores and with those of an agex and education-matched noninjured athlete control group . “ Abnormal ” test performance was determined statistically with Reliable Change Index scores . Results Sixty-four percent of concussed athletes reported a significant increase in symptoms , as judged by postconcussion symptom scores , compared with preinjury baseline at 2 days after injury . Eighty-three percent of the concussed sample demonstrated significantly poorer neurocognitive test results relative to their own baseline performance . The addition of neurocognitive testing result ed in a net increase in sensitivity of 19 % . Ninety-three percent of the sample had either abnormal neurocognitive test results or a significant increase in symptoms , relative to their own baseline ; 30 % of a control group demonstrated either abnormalities in neurocognitive testing or elevated symptoms , as judged by postconcussion symptom scores . For the concussed group , use of symptom and neurocognitive test results result ed in an increased yield of 29 % overreliance on symptoms alone . In contrast , 0 % of the control group had both symptoms and abnormal neurocognitive testing . Conclusion Reliance on patients ’ self-reported symptoms after concussion is likely to result in underdiagnosis of concussion and may result in premature return to play . Neurocognitive testing increases diagnostic accuracy when used in conjunction with self-reported symptoms", "Objective Compare the visuomotor response times of children after a mild traumatic brain injury ( mTBI ) with those of noninjured children matched for age , sex , and premorbid level of physical activity . Design Prospect i ve cohort study . Setting Pediatric trauma center . Participants Thirty-eight children aged 7 to 16 years in each group . Children with mTBI had a mean Glasgow Coma Scale score of 14.8 and were considered normal on a neurological assessment carried out at the time of hospital discharge . Noninjured children were friends of those with mTBI . Intervention Assessment s of response time were conducted at 1 , 4 , and 12 weeks after mTBI and at corresponding time intervals for the control children . Main Outcome Measures The response speed subtest of the Bruininks-Oseretsky Test of Motor Proficiency ( BOTMP ) ; reaction and movement time for upper and lower extremities , for simple , choice , and reversed choice response time paradigms . Results Over the assessment period , children with mTBI performed worse than the control group only on the response speed subtest of the BOTMP . The mTBI children however tended to have slower movement times 1 week postinjury for the reversed choice response time paradigm for the lower extremities . Conclusions Some children with mTBI may have some problems in response time persisting until 12 weeks postinjury . Further research is required to better identify and underst and the severity of these problems and determine their impact , if any , on participation in physical activities", "Objective : To assess patterns of regional brain activation in response to varying working memory loads shortly after mild traumatic brain injury ( MTBI ) . Background : Many individuals complain of memory difficulty shortly after MTBI . Memory performance in these individuals can be normal despite these complaints . Methods : Brain activation patterns in response to a working memory task ( auditory n-back ) were assessed with functional MRI in 12 MTBI patients within 1 month of their injury and in 11 healthy control subjects . Results : Brain activation patterns differed between MTBI patients and control subjects in response to increasing working memory processing loads . Maximum intensity projections of statistical parametric maps in control subjects showed bifrontal and biparietal activation in response to a low processing load , with little additional increase in activation associated with the high load task . MTBI patients showed some activation during the low processing load task but significantly increased activation during the high load condition , particularly in the right parietal and right dorsolateral frontal regions . Task performance did not differ significantly between groups . Conclusion : MTBI patients differed from control subjects in activation pattern of working memory circuitry in response to different processing loads , despite similar task performance . This suggests that injury-related changes in ability to activate or to modulate working memory processing re sources may underlie some of the memory complaints after MTBI", "OBJECT The aim of this study was to develop a decision rule for physicians in developing countries to identify patients with minor head injury who will benefit from emergency brain CT scanning . METHODS Three hundred eighteen patients with a history of blunt head trauma and a Glasgow Coma Scale ( GCS ) score > or= 13 who had presented within 12 hours of trauma underwent nonenhanced brain CT and were included in this prospect i ve study . Computed tomography findings that necessitated neurosurgical care ( either observation or intervention ) were considered as positive findings . Logistic regression was used to develop the decision rule . RESULTS Computed tomography scans were always normal in patients obvious head wound , a raccoon sign , vomiting , memory deficit , or a decrease in their GCS score . Patients with 1 major criterion ( GCS score 65 years , or vomiting ) or 2 minor criteria ( wound at the scalp or GCS score abnormal CT scan in 13 % of the cases . CONCLUSIONS The decision rule developed by the authors appears to be 100 % sensitive and 46 % specific for positive findings on brain CT and will , in developing countries , help clarify the decision to obtain scans", "OBJECTIVE : The purpose of this study was to compare concussion rates and recovery times for athletes wearing newer helmet technology compared to traditional helmet design . METHODS : This was a three-year , prospect i ve , naturalistic , cohort study . Participants were 2,141 high school athletes from Western Pennsylvania . Approximately half of the sample wore the Revolution helmet manufactured by Riddell , Inc. ( n = 1,173 ) and the remainder of the sample used st and ard helmets ( n = 968 ) . Athletes underwent computerized neurocognitive testing through the use of ImPACT at the beginning of the study . Following a concussion , players were reevaluated at various time intervals until recovery was complete . RESULTS : In the total sample , the concussion rate in athletes wearing the Revolution was 5.3 % and in athletes wearing st and ard helmets was 7.6 % [ & khgr;2 ( 1 , 2 , 141 ) = 4.96 , P relative risk estimate was 0.69 ( 95 % confidence interval = 0.499– 0.958 ) . Wearing the Revolution helmet was associated with approximately a 31 % decreased relative risk and 2.3 % decreased absolute risk for sustaining a concussion in this cohort study . The athletes wearing the Revolution did not differ from athletes wearing st and ard helmets on the mechanism of injury ( e.g. , head-to-head strike ) , on-field concussion markers ( e.g. , amnesia or loss of consciousness ) , or on-field presentation of symptoms ( e.g. , headaches , dizziness , or balance problems ) . CONCLUSION : Recent sophisticated laboratory research has better eluci date d injury biomechanics associated with concussion in professional football players . This data has led to changes in helmet design and new helmet technology , which appears to have beneficial effects in reducing the incidence of cerebral concussion in high school football players", "OBJECTIVE To investigate whether postconcussion syndrome ( PCS ) represents long-term sequelae associated with mild traumatic brain injury ( mTBI ) . METHODS Prospect i ve consecutive admissions to a Level 1 trauma hospital were assessed a mean 4.9 days and again 106.2 days post-injury . The final sample comprised 62 mTBI and 58 nonbrain injured trauma controls ( TC ) . Change or lack of change in individual PCS-like symptoms and PCS was examined . Multilevel logistic regression was used to analyze whether mTBI predicts 3-month PCS ( Time 2 ; T2 ) ; whether predictors of PCS ( within 14 days of injury , Time 1 ; T1 ) predict 3-month PCS , and how change in these predictors from T1 to T2 were associated with change in PCS status . Variables included demographic , injury-related , financial incentives , neuropsychological , and psychiatric disorder . RESULTS MTBI did not predict PCS . PCS was comparable ( T1 : mTBI : 40.3 % , TC : 50.0 % ; T2 : mTBI : 46.8 % , TC : 48.3 % ) . At T2 , 38.6 % were new cases of PCS ; between 30.8 % and 86.2 % reported either a new or more frequent symptom . A pre-injury depressive or anxiety disorder ( OR = 2.99 , 95 % CI [ 1.38 , 6.45 ] ) , and acute posttraumatic stress ( OR = 1.05 , 95 % CI [ 1.00 , 1.00 ] ) were early markers of PCS , regardless of mTBI . An interaction between time and posttraumatic stress disorder ( PTSD ) suggested the relationship between the severity of PTSD symptoms and PCS strengthened over time ( OR = 2.66 , 95 % CI [ 1.08 , 6.55 ] ) . Pain was related to PCS . Females were more likely than males to have PCS . CONCLUSION The data suggest the phenomenon of PCS in trauma patients does not show an association with mTBI", "OBJECTIVE Our purpose was to determine whether sex differences exist with respect to post-concussion symptoms and neurocognitive function in concussed collegiate athletes . METHODS A prospect i ve dependent- sample cohort design was used to compare baseline and post-concussion neuropsychological test scores and endorsed symptoms as functions of serial post-concussion assessment with respect to time and sex . The Immediate Post-concussion Assessment and Cognitive Testing ( ImPACT ) battery was administered to a multicenter analysis group of 79 concussed athletes . This computerized neuropsychological test was given to the athletes during the preseason and , on average , 2 and 8 days postinjury . RESULTS Multivariate analyses revealed no significant between-group differences on baseline test performance with respect to sex on any of the ImPACT composite scores or on the total symptom score . Multivariate analyses of post-concussion data revealed a significant main effect of time on ImPACT scores , but no main effect of sex was identified , and no time-by-sex interaction existed . Post hoc analysis revealed that concussed female athletes performed significantly worse than concussed male athletes on visual memory tasks ( P = 0.001 ) , and analysis of endorsed post-concussion symptoms revealed that concussed men were significantly more likely than concussed women to report post-concussion symptoms of vomiting ( P = 0.001 ) and sadness ( P = 0.017 ) . Athletes ' scores were examined individually using the reliable-change methodology . At 2 days post-injury , 58 % of concussed athletes had one or more reliable incidents of performance decline or increases in symptom reporting . At 8 days post-concussion , 30 % of concussed athletes were still showing one or more reliable change from preseason values . CONCLUSIONS College athletes exhibit differences on visual memory composite scores and symptoms post-concussion as a function of sex . These data support the importance of evaluating neuropsychological status and post-concussion symptoms in concussed athletes . In addition , these data illustrate the importance of analyzing an individual athlete 's recovery pattern , because individual differences in recovery trajectories may be overshadowed by global norm-group comparisons", "Objective : Examine frequency , character and course of symptoms until 3 months after MTBI and the relation between symptoms and disability . Methods : Prospect i ve cohort study of 122 consecutive patients with MTBI . Symptom assessment after 1 , 7 and 14 days and 3 months post-injury by use of Rivermead Post-concussional Question naire . Disability assessment by use of Rivermead Head Injury Follow-up Question naire . Results : Patients reporting one or more symptoms declined from 86 % on day 1 to 49 % 3 months post-injury , when 25 % also reported change in one or more domains of everyday activities . Poor memory , sleep disturbance and fatigue were most commonly reported . Symptom and disability scores were correlated ( τ = 0.60 ; p with disability at 3 months . Patients with early high symptom load are at risk for developing persisting complaints", "The purpose of the current study was to explore potential differences in pre- and post-concussion performance on a computerized neurocognitive concussion test between African American and White high-school and collegiate student-athletes . A prospect i ve case-control design was used to compare baseline and 2- and 7-day post-concussion computerized neurocognitive performance and symptoms between 48 White and 48 African American athletes matched for age , gender , and concussion history . The Immediate Post-Concussion Assessment Cognitive Test ( ImPACT ) version 2.0 ( NeuroHealth System , LLC , Pittsburgh , PA , USA ) computer software program was used to assess neurocognitive function ( i.e. , verbal and visual memory , motor processing speed , and reaction time ) and concussion symptoms . Regardless of race/ethnicity , there were significant decrements in computerized neurocognitive performance and increased symptoms following a concussion for the entire sample . African Americans and Whites did not differ significantly on baseline or post-concussion verbal memory , visual memory , reaction time , and total reported symptoms . However , African American participants were 2.4 × more likely to have at least one clinical ly significant cognitive decline on ImPACT at 7 days post-concussion and scored lower at 7 days post-concussion compared with baseline on processing speed than White participants . The authors concluded that the baseline ImPACT test was culturally equivalent and construct valid for use with these two racial/ethnic groups . However , in contrast , the findings support deleterious performance for the African American athletes compared with the White athletes on the ImPACT post-concussion evaluation that is of critical clinical relevance and warrants further research", "OBJECTIVE The relationship between athlete reports of symptoms , neurophysiological activation , and neuropsychological functioning is investigated in a sample of high school athletes . METHODS All athletes were evaluated using functional magnetic resonance imaging ( fMRI ) , a computer-based battery of neurocognitive tests , and a subjective symptom scale . Athletes were evaluated within approximately 1 week of injury and again after clinical recovery using all assessment modalities . RESULTS This study found that abnormal fMRI results during the first week of recovery predicted clinical recovery . As a group , athletes who demonstrated hyperactivation on fMRI scans at the time of their first fMRI scan demonstrated a more prolonged clinical recovery than athletes who did not demonstrate hyperactivation at the time of their first fMRI scan . CONCLUSION These results demonstrate the relationship between neurophysiological , neuropsychological , and subjective symptom data in a relatively large sample composed primarily of concussed high school athletes . fMRI represents an important evolving technology for the underst and ing of brain recovery after concussion and may help shape return-to-play guidelines in the future", "BACKGROUND : This study compared early serum levels of ubiquitin C-terminal hydrolase ( UCH-L1 ) from patients with mild and moderate traumatic brain injury ( TBI ) with uninjured and injured controls and examined their association with traumatic intracranial lesions on computed tomography ( CT ) scan ( CT positive ) and the need for neurosurgical intervention ( NSI ) . METHODS : This prospect i ve cohort study enrolled adult patients presenting to three tertiary care Level I trauma centers after blunt head trauma with loss of consciousness , amnesia , or disorientation and a Glasgow Coma Scale ( GCS ) score 9 to 15 . Control groups included normal uninjured controls and nonhead injured trauma controls presenting to the emergency department with orthopedic injuries or motor vehicle crash without TBI . Blood sample s were obtained in all trauma patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for UCH-L1 ( ng/mL ± st and ard error of the mean ) . RESULTS : There were 295 patients enrolled , 96 TBI patients ( 86 with GCS score 13–15 and 10 with GCS score 9–12 ) , and 199 controls ( 176 uninjured , 16 motor vehicle crash controls , and 7 orthopedic controls ) . The AUC for distinguishing TBI from uninjured controls was 0.87 ( 95 % confidence interval [ CI ] , 0.82–0.92 ) and for distinguishing those TBIs with GCS score 15 from controls was AUC 0.87 ( 95 % CI , 0.81–0.93 ) . Mean UCH-L1 levels in patients with CT negative versus CT positive were 0.620 ( ±0.254 ) and 1.618 ( ±0.474 ) , respectively ( p the GCS score , CT lesions , and NSI . Further study is required to vali date these findings before clinical application . LEVEL OF EVIDENCE : II , prognostic study", "Previous studies have presented conflicting results regarding the predictive value of various clinical symptoms and signs for performing computed tomography ( CT ) scan in minor head injury . Moreover , despite the presence in the literature of several similar publications regarding whether or not CT should be employed at the time of presentation of minor head injured patients , data regarding delayed CT are limited . The objective of this study was to determine whether high-risk criteria represent a significant indication for initial CT scan in patients with minor head trauma , and whether or not analysis using delayed CT scan is necessary in patients with high-risk criteria before being discharged . Patients presenting to the Emergency Department with minor head trauma between September 1 , 2003 and September 1 , 2004 were evaluated prospect ively . After being divided into two main groups , low- and high-risk , four separate sub-groups based on age were established . Initial spiral CT examination was done within 3 h of trauma on all patients in addition to a delayed control CT scan in those with high-risk criteria between 16 and 24 h after trauma . The difference between the high- and low-risk groups in terms of abnormal CT findings was statistically significant ( p Glasgow Coma Scale ( GCS ) score of 13 or 14 and those with a GCS score of 15 ( p relationship between vomiting and abnormal CT scan was significant ( odds ratio 4.61 , 95 % confidence interval 2.20 - 9.64 , p = 0.0001 ) , and the relationship between abnormal CT scan and suspected skull fracture was also significant ( odds ratio 3.46 , 95 % confidence interval 1.52 - 7.91 , p = 0.0032 ) . No significant correlations between other high-risk criteria and abnormal CT scan were determined . The difference between initial and delayed CT scans in patients with high-risk criteria was not significant ( p = 0.161 ) . Low-risk patients with a GCS score of 15 may be discharged without initial CT scan being performed . Initial CT scan absolutely must be performed , however , on patients with GCS CT scans in patients with high-risk criteria is not significant , it is our opinion that it is still prudent for delayed CT scan to be performed , particularly on patients whose GCS score does not rise to 15 , or decreases", "Background Recent concussion management guidelines have suggested that athletes with mild ( grade 1 ) concussions may be returned to play if asymptomatic for 15 minutes . The purpose of this study was to assess the utility of a current concussion management guideline in classifying and managing mild concussion . Hypothesis High school athletes diagnosed with a grade 1 concussion will demonstrate measurable decline in neuropsychological functioning that persists during the 1st week of recovery . Study Design Prospect i ve study design ed to evaluate neuropsychological functioning both prior to and following concussion . Methods Forty-three high school athletes completed neuropsychological test performance and symptom ratings prior to the season and at two times during the 1st week following mild concussion . Results Thirty-six hours after injury , mildly concussed high school athletes demonstrated a decline in memory ( P self-reported symptoms ( P Athletes with grade 1 concussion demonstrated memory deficits and symptoms that persisted beyond the context in which they were injured . These data suggest that current grade 1 return-to-play recommendations that allow for immediate return to play may be too liberal . Clinical Relevance A reconsideration of current concussion grading systems appears to be warranted", "Context Available prediction rules to guide selective use of computed tomography in patients with minor head injuries were developed for use in patients with a history of loss of consciousness . Contribution This prospect i ve study included 3181 adults with minor head injury with or without loss of consciousness . A prediction rule based on risk factors ( such as age ; Glasgow Coma Scale score ; skull fracture ; and posttraumatic vomiting , amnesia , or seizure ) successfully identified patients who had intracranial computed tomography findings ( sensitivity , approximately 95 % ) or neurosurgical intervention ( sensitivity , 100 % ) . Caution External validation in different population s is needed before widespread application of the rule . The Editors Minor head injury is one of the most common injuries seen in western emergency departments , with an estimated incidence of 100 to 300 per 100000 people ( 1 ) . Patients with minor head injury include those with blunt injury to the head who have a normal or minimally altered level of consciousness on presentation in the emergency department , that is , a Glasgow Coma Scale ( GCS ) score of 13 to 15 , and a maximum loss of consciousness of 15 minutes , posttraumatic amnesia for 60 minutes , or both ( 2 ) . Intracranial complications after minor head injury are infrequent but commonly require in-hospital observation and occasionally require neurosurgical intervention ( 3 , 4 ) . The imaging procedure of choice for reliable , rapid diagnosis of intracranial complications is computed tomography ( CT ) ( 5 , 6 ) . Because most patients with minor head injury do not show traumatic abnormalities on CT , it seems inefficient to scan all patients with minor head injury to exclude intracranial complications . Of the published prediction rules for the selective use of CT in patients with minor head injury , the New Orleans Criteria ( NOC ) and the Canadian CT Head Rule ( CCHR ) have been externally vali date d ( 79 ) . Research ers in internal and external validation studies have shown that both rules identify 100 % of patients requiring neurosurgical intervention and most patients with traumatic intracranial findings on CT ( 3 , 1012 ) . The external validation studies , however , yielded lower specificities than the development studies ( 10 , 12 ) . The originally reported specificities were probably too optimistic because of their partial derivation from data sets that were also used for the model development ( 13 ) . Also , in both studies research ers included only a subset of patients with minor head injury . Most notably , research ers developed the NOC and the CCHR for patients with minor head injury who have a history of loss of consciousness or amnesia , which many of these patients presenting to emergency departments do not have . Generalizability of the NOC and the CCHR is therefore limited . We aim ed to develop a widely applicable and easy-to-implement prediction rule for the selective use of CT in all patients with minor head injury with or without a history of loss of consciousness . To avoid optimism for the model 's performance , we used penalty factors and internal validation by using bootstrapping procedures to attain more realistic predictions of the model 's performance in an external patient population ( 13 ) . Methods Patients We prospect ively collected data on consecutive patients in 4 university hospitals in the Netherl and s that were participating in the CT in Head Injury Patients ( CHIP ) study ( Figure 1 ) ( 14 ) . Inclusion criteria included initial presentation within 24 hours of blunt injury to the head , a minimum age of 16 years , and a Glasgow Coma Scale ( GCS ) score of 13 to 14 or a GCS score of 15 , with at least 1 of the following risk factors : history of loss of consciousness , short-term memory deficit , amnesia for the traumatic event , posttraumatic seizure , vomiting , severe headache , clinical evidence of intoxication with alcohol or drugs , use of anticoagulants or history of coagulopathy , external evidence of injury above the clavicles , and neurologic deficit . Exclusion criteria were transfer from another hospital , contraindications for CT , or concurrent injuries precluding a head CT at presentation . Figure 1 . Study flow diagram . The number of patients presenting with head injury is an estimate based on the proportion of patients included out of the total number of trauma patients seen by a neurologist or neurologist-in-training in the emergency department of the participating center that included most patients . CT = computed tomography . A neurologist or a neurologist-in-training under telephone supervision of a neurologist examined patients , after which a head CT was performed as soon as possible , in accordance with the current Dutch guidelines ( 15 ) . We performed head CT according to a routine trauma protocol , with a maximum slice thickness of 5 mm infratentorially and 8 mm supratentorially , without intravenous contrast administration . A neuroradiologist or a trauma radiologist ( 9 in total , not blinded to the patients ' history and clinical findings ) interpreted scans in brain and bone window setting s. The institutional review board waived patient informed consent after review of our study protocol because current Dutch guidelines and European Federation of Neurological Societies ' guidelines recommend routine head CT for patients meeting our inclusion criteria ( 15 , 16 ) . Definitions We considered a patient to have a history of loss of consciousness when a witness or the patient reported it . We defined short-term memory deficit as persistent antero grade amnesia . We deemed amnesia present for the traumatic event if the patient could not recall the entire traumatic event . We defined posttraumatic seizure as a seizure witnessed or suspected after the injury and vomiting as an episode of emesis after the traumatic event . We classified headache as being either diffuse or localized . We evaluated the presence and severity of intoxication clinical ly by evidence of slurred speech , alcoholic fetor , or nystagmus ; we did not perform routine blood toxicology tests . Anticoagulant treatment included only coumarin derivatives . We scored the use of platelet aggregation inhibitors ( for example , aspirin and clopidrogel ) , but we did not consider it to be a risk factor . We assessed noniatrogenic coagulopathy , which we considered a risk factor , by patient history , but we did not perform routine blood coagulation tests . We defined external evidence of injury as clinical ly significant discontinuity of the skin or extensive bruising . We classified injury suspect of a fracture as clinical signs of fracture , whereas we classified other injuries , such as contusions , lacerations , or abrasions , as contusion . We defined focal neurologic deficit as any abnormality on routine clinical neurologic examination that indicated a focal cerebral lesion . Data Collection We collected data on patient and trauma characteristics , symptoms , and risk factors ; physical and neurologic examination ; CT findings ; and neurosurgical intervention . Examining physicians entered data on patient history and examination into a data base ( OpenSDE , Erasmus MCUniversity Medical Center Rotterdam , Rotterdam , the Netherl and s ) before the patient underwent CT . If this interfered with their clinical workflow , they entered the data after the CT ( 17 ) . The reading radiologist added the CT findings . We collected data on neurosurgical intervention , additional CT scans performed , and the clinical outcomes of patients by search ing the hospital 's patient information system . Outcome Measures Our primary outcome measure for this analysis was any intracranial traumatic finding on CT , which included all neurocranial traumatic findings except for isolated linear skull fractures . A secondary outcome measure was neurosurgical intervention contingent to initial CT . We defined neurosurgical intervention as any neurosurgical procedure ( craniotomy , intracranial pressure monitoring , elevation of skull fracture , or ventricular drainage ) within 30 days of the traumatic event . Risk Factors We selected all of the risk factors from the NOC and the CCHR ( 7 , 9 ) : age , headache , vomiting , intoxication , persistent antero grade amnesia , retro grade amnesia more than 30 minutes , injury above the clavicles ( including clinical signs of skull or basal skull fracture ) , GCS score less than 15 at 2 hours postinjury , and dangerous trauma mechanism ( pedestrian vs. vehicle , fall from height , and ejected from motor vehicle ) . We tested other risk factors from clinical guidelines for the use of CT in minor head injury ( 15 , 16 , 1821 ) for additional effects . We combined the variables cyclist versus vehicle and pedestrian versus vehicle into 1 variable ( pedestrian or cyclist vs. vehicle ) for statistical analysis because they are similar trauma mechanisms . Statistical Analysis We based sample size on an estimated 25 variables for multivariable logistic regression analysis . For reliable analysis , we required at least 10 events of the primary outcome measure per variable , that is , 250 events for 25 variables ( 22 ) . Given an incidence of traumatic findings on CT of 8 % to 10 % , we needed to include 3125 patients . We assumed that missing data were missing at r and om , and we imputed them on the basis of the available data means to avoid bias ( 2327 ) . The proportion of imputed data was 3.8 % , which included items documented as unknown and items that were not documented . Of all cases , 1956 ( 62 % ) were complete . Loss of consciousness and posttraumatic amnesia had the highest proportion of missing or unknown data ( 18 % and 10 % , respectively ) . We imputed both as present on the basis of the available variable means and as consistent with clinical practice . We used the entire data set , after missing value imputation , for all analyses . We evaluated the study sample for demographic characteristics , mechanism of injury , traumatic findings , neurosurgical intervention , GCS scores , and the presence of risk factors . We tested associations of each risk factor with the primary", "STUDY OBJECTIVE This study examines whether serum levels of glial fibrillary acidic protein breakdown products ( GFAP-BDP ) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography ( CT ) scan ( positive CT result ) and with having a neurosurgical intervention . METHODS This prospect i ve cohort study enrolled adult patients presenting to 3 Level I trauma centers after blunt head trauma with loss of consciousness , amnesia , or disorientation and a Glasgow Coma Scale ( GCS ) score of 9 to 15 . Control groups included normal uninjured controls and trauma controls presenting to the emergency department with orthopedic injuries or a motor vehicle crash without traumatic brain injury . Blood sample s were obtained in all patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for GFAP-BDP ( nanograms/milliliter ) . RESULTS Of the 307 patients enrolled , 108 were patients with traumatic brain injury ( 97 with GCS score 13 to 15 and 11 with GCS score 9 to 12 ) and 199 were controls ( 176 normal controls and 16 motor vehicle crash controls and 7 orthopedic controls ) . Receiver operating characteristic curves demonstrated that early GFAP-BDP levels were able to distinguish patients with traumatic brain injury from uninjured controls with an area under the curve of 0.90 ( 95 % confidence interval [ CI ] 0.86 to 0.94 ) and differentiated traumatic brain injury with a GCS score of 15 with an area under the curve of 0.88 ( 95 % CI 0.82 to 0.93 ) . Thirty-two patients with traumatic brain injury ( 30 % ) had lesions on CT . The area under these curves for discriminating patients with CT lesions versus those without CT lesions was 0.79 ( 95 % CI 0.69 to 0.89 ) . Moreover , the receiver operating characteristic curve for distinguishing neurosurgical intervention from no neurosurgical intervention yielded an area under the curve of 0.87 ( 95 % CI 0.77 to 0.96 ) . CONCLUSION GFAP-BDP is detectable in serum within an hour of injury and is associated with measures of injury severity , including the GCS score , CT lesions , and neurosurgical intervention . Further study is required to vali date these findings before clinical application", "BACKGROUND The brain acoustic monitor ( BAM ) , an indicator of cerebral autoregulation , has previously shown high sensitivity but low specificity for computed tomographic ( CT ) abnormality in patients following the clinical diagnosis of traumatic brain injury . We assessed the utility of the BAM in diagnosing mild TBI ( mTBI ) in patients with and without normal findings of CT scan , a population for which there are a few objective markers of disease . METHODS We prospect ively studied 369 patients with mechanism of injury consistent with TBI . The diagnosis was evaluated by five methods : ( a ) study enrollment ( i.e. , mechanism of injury ) , ( b ) signs of head trauma , ( c ) expert physician assessment , ( d ) presence of initial symptoms ( loss of consciousness [ LOC ] ; amnesia ) , and ( e ) BAM . All patients had a head CT scan . We compared the BAM screen results with the diagnosis of mTBI and BAM data from 50 normal volunteers and 49 trauma control patients not thought to have TBI . RESULTS None of the diagnostic methods correlated well with the others . Correlation between the methods ranged from 21 % to 71 % . BAM discriminated between patients with mTBI versus without TBI ( p findings of CT scans . A history of LOC and physical signs of head injury were associated with a new abnormality on head CT ( p sensitivity of BAM abnormality for head CT abnormality was 100 % , with a specificity of 30.14 % . CONCLUSION There is no gold st and ard for the diagnosis of mTBI . BAM screening is a useful diagnostic adjunct in patients with mTBI and may facilitate decision making . An abnormal BAM reading adds significance to LOC as a predictor of a new abnormality on head CT . In our study , opting not to CT scan patients with a normal BAM signal would have missed no new CT findings and no patients who required medical intervention for TBI , at a cost savings of $ 202,950", "Abstract Objective : To extend previous research design s and examine cognitive performance up to 30 days postconcussion . Method : A prospect i ve cohort design was used to examine 2000 athletes from 8 mid-Michigan area high schools to compare baseline neurocognitive performance with postconcussion neurocognitive performance . All concussed athletes were readministered the Immediate Post Assessment and Cognitive Test ( ImPACT ) at 2 , 7 , 14 , 21 , and 30 days postconcussion . Results : A total of 72 high school athletes ( aged 15.8 ± 1.34 years ) sustained a concussion . A significant with in-subjects effect for reaction time ( F = 10.01 ; P = 0.000 ) , verbal memory ( F = 3.05 ; P = 0.012 ) , motor processing speed ( F = 18.51 ; P = 0.000 ) , and total symptoms following an injury ( F = 16.45 ; P = 0.000 ) was found . Concussed athletes demonstrated a significant decrease in reaction time up to 14 days postconcussion ( P = 0.001 ) compared with baseline reaction time . Reaction time returned to baseline levels at 21 days postinjury ( P = 0.25 ) . At 7 days postinjury , impairments in verbal memory ( P = 0.003 ) and motor processing speed ( P = 0.000 ) were documented and returned to baseline levels by 14 days postinjury . Concussed athletes self-reported significantly more symptoms at 2 days postconcussion ( P = 0.000 ) and exhibited a resolution of symptoms by 7 days postinjury ( P = 0.06 ) . Conclusion : High school athletes could take up to 21 days to return to baseline levels for reaction time . These data support current recommendations for the conservative management of concussion in the high school athlete", "The level of parent-child agreement on post-concussive symptoms ( PCS ) was examined in children following mild traumatic brain injuries ( TBI ) . As part of a larger longitudinal study , 186 children with mild TBI and 99 with orthopedic injuries ( OI ) , from 8 to 15 years of age , were recruited prospect ively . Parents and children completed the PCS Interview ( PCS-I ) and the Health and Behavior Inventory ( HBI ) at 2 weeks , 1 month , 3 months , and 12 months postinjury . Item-level correlations between child and parent ratings on both measures of PCS were significant but modest in both groups . Parent-child correlations for composite scales on the HBI and the total score on the PCS-I were significant in both groups , but somewhat higher in the OI group than in the mild TBI group . Mean symptom ratings tended to be significantly higher for children as compared to parents , especially for somatic symptoms . Parents and children display modest agreement when reporting PCS ; their ratings correlate significantly , but children report higher mean levels of symptoms than parents", "Using a prospect i ve , cohort design , we investigated whether children with mild traumatic brain injury ( TBI ) differed from individually matched controls on measures of intellectual , neuropsychological , academic , and \" real world \" functioning . Subjects included children between the ages of 6 and 15 years who sustained mild , moderate , and severe closed head injuries and were consecutively identified on presentation to the emergency departments of two regional , university medical centers . One hundred twenty-nine children were eligible for enrollment . Seventeen refused enrollment . Fifty-nine of the 112 enrolled children were classified as mildly injured . Six of these children dropped out , leaving 53 mildly injured cases for analysis . Individually matched controls from the classroom of the injured cases were identified based on age , gender , and premorbid academic achievement and behavior . Assessment measures included st and ardized intellectual , neuropsychological , and academic measures . Also , parent and teacher question naires , measuring social , educational , domestic , and community living skills were used . Among 51 outcome variables only five were significantly associated with injury at initial or 1-year testing after adjusting for multiple comparisons . However , these five associations were either very weak or implausible . Results from this study suggest that mild TBI produces virtually no clinical ly significant long-term deficits in intellectual , neuropsychological , academic , or \" real world \" functioning", "OBJECTIVE To determine if clinical variables or neurobehavioural test ( NBT ) scores obtained in the ED within 24 hours of minor head injury ( MHI ) predict the development of postconcussive syndrome ( PCS ) . METHODS Prospect i ve , observational study of 71 MHI patients and 60 orthopaedic controls . MHI defined as loss of consciousness if done ) . All patients received a seven part NBT battery in the ED . Telephone follow-up was done at 1 , 3 and 6 months to determine if patients met the DSM IV definition of PCS . ANALYSIS Stepwise , multivariate , logistic regression . RESULTS Predictors of PCS at 1 month were female gender ( OR = 7.8 ; 95 % CI = 41.6 , 1.98 ) , presence of both retro grade and antero grade amnesia ( OR = 0.055 ; CI = 0.002 , 0.47 ) , Digit Span Forward Scores ( OR = 0.748 ; CI = 0.52 , 1.03 ) and Hopkins Verbal Learning A scores ( OR = 0.786 ; CI = 0.65 , 0.91 ) ; at 3 months , presence of both retro grade and antero grade amnesia ( OR = 0.13 ; CI = 0.0 , 0.93 ) , Digit Span Forward Scores ( OR = 0.744 ; CI = 0.58 , 0.94 ) . No variables fit the model at 6 months . 92 % of males scoring > 25 on Hopkins Verbal Learning A did not have PCS at 1 month , and 89 % of females scoring Digit Span Forward did have PCS at 1 month . CONCLUSIONS Gender and two NBTs can help predict PCS after MHI", "OBJECTIVE To prospect ively measure the immediate neurocognitive effects and early course of recovery from concussion and to examine the effects of loss of consciousness ( LOC ) and posttraumatic amnesia ( PTA ) on the severity of neurocognitive impairment immediately after concussion . METHODS A sports-related concussion research model was used to allow prospect i ve immediate evaluation of concussion . A total of 2385 high school and college football players were studied . Ninety-one players ( 3.8 % ) sustained concussions during the study . A brief neurocognitive and neurological screening measure , the St and ardized Assessment of Concussion , was used to assess cognitive functioning before the football season , immediately after injury , and 15 minutes , 48 hours , and 90 days after injury . RESULTS St and ardized Assessment of Concussion scores immediately after concussion were significantly lower than the preseason baseline score and the noninjured population baseline mean , even for injured subjects without LOC or PTA . Subjects with LOC were most severely impaired immediately after injury , whereas those without LOC or PTA were least impaired . Significant impairment was also detected 15 minutes after injury , but all three groups returned to baseline levels of cognitive functioning within 48 hours . CONCLUSION These findings are the first to demonstrate not only that a gradient of increasing concussion severity is represented by PTA and LOC but also that measurable neurocognitive abnormalities are evident immediately after injury without PTA or LOC", "CONTEXT Lack of empirical data on recovery time following sport-related concussion hampers clinical decision making about return to play after injury . OBJECTIVE To prospect ively measure immediate effects and natural recovery course relating to symptoms , cognitive functioning , and postural stability following sport-related concussion . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1631 football players from 15 US colleges . All players underwent preseason baseline testing on concussion assessment measures in 1999 , 2000 , and 2001 . Ninety-four players with concussion ( based on American Academy of Neurology criteria ) and 56 noninjured controls underwent assessment of symptoms , cognitive functioning , and postural stability immediately , 3 hours , and 1 , 2 , 3 , 5 , 7 , and 90 days after injury . MAIN OUTCOME MEASURES Scores on the Grade d Symptom Checklist ( GSC ) , St and ardized Assessment of Concussion ( SAC ) , Balance Error Scoring System ( BESS ) , and a neuropsychological test battery . RESULTS No player with concussion was excluded from participation ; 79 players with concussion ( 84 % ) completed the protocol through day 90 . Players with concussion exhibited more severe symptoms ( mean GSC score 20.93 [ 95 % confidence interval [ CI ] , 15.65 - 26.21 ] points higher than that of controls ) , cognitive impairment ( mean SAC score 2.94 [ 95 % CI , 1.50 - 4.38 ] points lower than that of controls ) , and balance problems ( mean BESS score 5.81 [ 95 % CI , -0.67 to 12.30 ] points higher than that of controls ) immediately after concussion . On average , symptoms gradually resolved by day 7 ( GSC mean difference , 0.33 ; 95 % CI , -1.41 to 2.06 ) , cognitive functioning improved to baseline levels within 5 to 7 days ( day 7 SAC mean difference , -0.03 ; 95 % CI , -1.33 to 1.26 ) , and balance deficits dissipated within 3 to 5 days after injury ( day 5 BESS mean difference , -0.31 ; 95 % CI , -3.02 to 2.40 ) . Mild impairments in cognitive processing and verbal memory evident on neuropsychological testing 2 days after concussion resolved by day 7 . There were no significant differences in symptoms or functional impairments in the concussion and control groups 90 days after concussion . CONCLUSIONS Collegiate football players may require several days for recovery of symptoms , cognitive dysfunction , and postural instability after concussion . Further research is required to determine factors that predict variability in recovery time after concussion . St and ardized measurement of postconcussive symptoms , cognitive functioning , and postural stability may enhance clinical management of athletes recovering from concussion", "OBJECT During recent years , several biomarkers have been introduced for use in the diagnosis of traumatic brain injury ( TBI ) . The primary objective of this investigation was to determine if S100B ( or S100 calcium-binding protein B ) and neuron-specific enolase ( NSE ) serum concentrations can effectively be used to discriminate between symptomatic and asymptomatic children with minor head trauma . METHODS The authors conducted a prospect i ve clinical study that involved patients age 6 months to 15 years who had sustained minor head trauma . Children with concomitant extracranial injuries were excluded . Blood sample s were obtained within 6 hours of injury to measure S100B and NSE levels in serum . The authors defined 2 diagnostic groups : a mild TBI group ( patients with Glasgow Coma Scale [ GCS ] scores of 13 - 15 ) in whom there were clinical signs of concussion ( short loss of consciousness , amnesia , nausea , vomiting , somnolence , headache , dizziness , or impaired vision ) and a head contusion group ( patients with a GCS score of 15 ) in whom symptoms were absent . Both S100B and NSE concentrations were compared between the 2 groups . Secondary end points were defined as follows : correlation of S100B/NSE and a ) the presence of scalp lacerations , b ) GCS score , c ) age , and d ) correlation between S100B and NSE . RESULTS One hundred forty-eight patients were enrolled ( 53 in the contusion group , 95 in the mild TBI group ) . After adjusting for differences in age and time of injury to blood sample withdrawal , there was no significant difference in S100B or NSE between patients in the 2 groups . Scalp lacerations and GCS score had no affect on posttraumatic S100B or NSE concentrations . The correlation between S100B and NSE was significant . Both markers showed a significant negative correlation with age . CONCLUSIONS The authors demonstrated that S100B and NSE do not discriminate between symptomatic and asymptomatic children with minor head injury . There seem to be limitations in marker sensitivity when investigating pediatric patients with mild TBI", "Objective : This study sought to examine the effects of mild traumatic brain injury ( TBI ) on executive functions in school-aged children . Participants and method : The prospect i ve , longitudinal study involved 8–15 year old children , 186 with mild TBI and 99 with mild orthopaedic injuries ( OI ) . They were administered the Stockings of Cambridge and Spatial Working Memory sub-tests from the Cambridge Neuropsychological Testing Automated Battery ( CANTAB ) ∼10 days , 3 months and 12 months post-injury . Parents completed the Behavior Rating Inventory of Executive Functions ( BRIEF ) on each occasion , with ratings at the initial assessment intended to assess pre-morbid functioning retrospectively . Results : On the CANTAB , the groups did not differ on the Stockings of Cambridge and the mild TBI group unexpectedly performed better than the OI group on Spatial Working Memory . On the BRIEF , children with mild TBI showed a marginally significant trend toward more problems than the OI group on the Metacognition Index composite . The only BRIEF sub-scale on which they demonstrated significantly more problems was Organization of Material s. The presence of intracranial abnormalities on MRI was associated with more problems on the BRIEF Organization of Material s sub-scale at 3 months , but other findings were not consistent with hypothesized effects of TBI severity . The CANTAB sub-tests were significant predictors of later ratings on the BRIEF , but accounted for modest variance . Discussion : Children with mild TBI show limited evidence of deficits in executive functions , either cognitively or behaviourally , irrespective of injury characteristics . Cognitive tests of executive functions are modest predictors of ratings of executive functions in everyday life , for children both with and without mild TBI", "Traumatic brain injury ( TBI ) may have a profound impact on a child 's ongoing development . Various risk factors have been found to predict outcome , but considerable variability remains unexplained . This study used a prospect i ve , longitudinal design to examine recovery of memory function following TBI within the pre school period . Ninety-six children with TBI were divided according to injury severity ( mild , moderate , severe ) , and compared to age and SES matched healthy controls ( n = 35 ) . Children were evaluated acutely and at 6,12 and 18 months post-injury using intellectual and memory measures . Results showed a relationship between greater injury severity and poorer intellectual ability . This dose-response relationship was not clearly evident for memory function within the acute phase of recovery , but developed over time , with greater memory impairments evident for children with more severe TBI by 12 months post-injury . Children with mild TBI exhibited few memory problems . Findings are discussed in the context of theories of plasticity and recovery of function", "The purpose of this study was to investigate the sensitivity of orientation and recent memory questions in the diagnosis of concussion . In a prospect i ve study over 7 consecutive years ( 1985 - 1991 ) , all players at a professional Australian Rules Football club who sustained a concussive injury ( n = 28 ) were administered a set of questions evaluating orientation and recent memory . Concussion was diagnosed independently on the basis of loss or disturbance of consciousness and clinical symptoms . A control group of age-matched nonconcussed players was administered the same set of questions . The results showed that items evaluating recently acquired information were more sensitive in the assessment of concussion than st and ard orientation items . The relative sensitivity of orientation questions must be considered when they are used in the clinical diagnosis of concussion in sport", "PURPOSE The purpose of this analysis was to determine which of the initial symptoms after mild traumatic brain injury ( MTBI ) can best predict the development of persistent postconcussive syndrome ( PCS ) . METHODS One hundred eighty MTBI patients admitted to a level I trauma center were enrolled in a prospect i ve study and 110 followed for 3 months . MTBI was defined as a Glasgow Coma Score of 13 to 15 with a transient loss of consciousness or report of being dazed or confused . PCS was defined as the persistence of four or more symptoms long term . Patients were screened at admission and at 3 days to 10 days and 3 months . Symptom checklists were administered to ascertain the presence of symptoms ( cognitive , emotional , and physical ) after concussion . For a subset of patients that were physically able , balance tests were also conducted . Stepwise logistic regression was used to identify which symptoms best predicted PCS . RESULTS The mean age of the subjects was 35 years , and 65 % were men . Physical symptoms were the most prevalent in the 3 days to 10 days postinjury with most declining thereafter to baseline levels . Emotional and cognitive symptoms were less prevalent but more likely to remain elevated at 3 months ; 41.8 % of subjects reported PCS at 3 months . The strongest individual symptoms that predicted long-term PCS included anxiety , noise sensitivity ( NS ) , and trouble thinking ; reported by 49 % , 27 % , and 31 % of the subjects at 3 days to 10 days , respectively . In multivariate regressions including age , gender , and early symptoms , only anxiety , NS and gender remained significant in the prediction of PCS . Interactions revealed that the effect of anxiety was seen primarily among women . NS had an odds ratio of 3.1 for PCS at 3 months . CONCLUSIONS After MTBI , anxiety among women and NS are important predictors of PCS . Other physical symptoms , while more prevalent are poor predictors of PCS", "Objective To examine the utility of neuropsychological tests in assessing college athletes prior to and following a sports-related mild Traumatic Brain Injury ( mTBI ) . Design A prospect i ve study of college athletes who sustained mTBI while engaged in sport . Preinjury baseline neuropsychological test data were obtained for athletes at risk for mTBI . Following an mTBI , the athlete and his or her matched noninjured control were evaluated at 2 hours , 48 hours , 1 week , and 1 month postinjury . Setting Male and female athletes from a Division I college . Participants Male and female athletes from the football , men 's ice hockey , men 's and women 's soccer , and men 's and women 's basketball teams at Penn State University . A total of 29 injured and 20 noninjured athletes participated in the study . Interventions Neuropsychological test batteries were administered at baseline and serially following mTBI . Main Outcome Measures Post-Concussion Symptom Checklist , Hopkins Verbal Learning Test , Symbol Digit Modalities Test , Stroop Color-Word Test , Trail Making Test , VIGIL/W , List Learning , Digit Span , Penn State Cancellation Test , and Controlled Oral Word Association . Results Neuropsychological test data yielded significant differences between injured athletes and controls at 2 hours and 48 hours following cerebral concussion ; injured athletes performing significantly worse than controls . Injured athletes reported a significantly greater number of postconcussion symptoms 2 hours following injury but not at the 48-hour assessment . No multivariate group differences were found at 1 week , but univariate analyses suggested significant differences on a few measures . At 1 month postinjury , a statistically significant difference was found on one measure with injured athletes marginally outperforming controls . Conclusions Neuropsychological tests are useful in the detection of cognitive impairment following mTBI . The test data appear to be more effective than subjective report of symptoms in differentiating between injured and noninjured athletes at 48 hours postinjury . Although significant individual variability existed , most injured athletes recovered within 1 week of injury . A battery of tests , rather than any single test , is necessary to capture the variability that exists among injured athletes", "Primary objective : To investigate the occurrence of post-concussive symptoms ( PCS ) and symptoms of post-traumatic stress disorder ( PTSD ) in children following mild traumatic brain injuries ( TBI ) . Research design : Longitudinal study comparing the outcomes of mild TBI and orthopaedic injuries ( OI ) in children aged 8–15 . Methods and procedures : One hundred and eighty-six children with mild TBI and 99 with OI were recruited prospect ively . Parents rated children 's PCS and symptoms of PTSD at 2 weeks , 3 months and 12 months post-injury . One hundred and sixty-seven with mild TBI and 84 with OI completed all assessment s. Main outcomes and results : Controlling for symptoms of PTSD , the mild TBI group demonstrated more PCS than the OI group , although the magnitude of group differences diminished with time . Controlling for PCS , the OI group displayed more symptoms of PTSD than the mild TBI group at baseline , but not thereafter . Symptoms of PTSD and PCS were correlated significantly , but more highly in the OI group than the mild TBI group . Conclusions : Although PCS and symptoms of PTSD are correlated , children with mild TBI are more distinguishable from children with OI based on PCS than on symptoms of PTSD . The latter symptoms , moreover , do not account for increased PCS following mild TBI in children", "Primary objective : To examine the frequency of acute mild traumatic brain injury ( mTBI ) symptoms in children using a concussion symptom inventory and to identify which symptoms are most useful in identifying mTBI . It was hypothesized that symptoms associated with mTBI are more common in children with head injury than orthopaedic injury and certain symptoms are more useful than others in identifying mTBI . Research design : Prospect i ve case-control study conducted in a paediatric trauma centre emergency department . Methods and procedures : Children of 6–18 years old with head injury or a minor extremity injury were enrolled . Symptoms were assessed using a grade d symptom checklist . Symptom frequency was compared using a chi-square test . The association between individual symptoms with AMS was evaluated with logistic regression analysis . Main outcomes and results : Children with head injury displayed more frequent symptoms than controls . Head-injured cases with altered mental status ( AMS ) demonstrated the most frequent and severe symptoms ( median symptom scores : control = 1 , cases without AMS = 5 , cases with AMS = 10 ; p . Headache , nausea , dizziness , blurred/double vision and not feeling ‘ sharp ’ were associated with AMS . Conclusions : Symptoms associated with mTBI are more frequent in children with head injury . AMS magnifies this effect . A symptom inventory is integral to the evaluation of mTBI in children ; a smaller set of dichotomized symptoms may be as useful as and more easily administered than lengthier symptom scales" ]

[ "Background The role of postoperative radiotherapy in breast-conserving therapy is undisputed . However , optimal timing of adjuvant radiotherapy is an issue of ongoing debate . This retrospective clinical cohort study was performed to investigate the impact of a delay in surgery – radiotherapy intervals on local control and overall survival . Patients and methods Data from an unselected cohort of 1393 patients treated at a single institution over a 17-year period ( 1990–2006 ) were analyzed . Patients were assigned to two groups ( CT+/CT− ) according to chemotherapy status . A delay in the initiation of radiotherapy was defined as > 7 weeks ( CT− group ) and > 24 weeks ( CT+ group ) . Results The 10-year regional recurrence-free survival for the CT− and CT+ groups were 95.6 and 86.0 % , respectively . A significant increase in the median surgery – radiotherapy interval was observed over time ( CT− patients : median of 5 weeks in 1990–1992 to a median of 6 weeks in 2005–2006 ; CT+ patients : median of 5 weeks in 1990–1992 to a median of 21 weeks in 2005–2006 ) . There was no association between a delay in radiotherapy and an increased local recurrence rate ( CT− group : p = 0.990 for intervals 0–6 weeks vs. ≥ 7 weeks ; CT+ group : p = 0.644 for intervals 0–15 weeks vs. ≥ 24 weeks ) or decreased overall survival ( CT− group : p = 0.386 for intervals 0–6 weeks vs. ≥ 7 weeks ; CT+ group : p = 0.305 for intervals 0–15 weeks vs. ≥ 24 weeks ) . Conclusion In the present cohort , a delay of radiotherapy was not associated with decreased local control or overall survival in the two groups ( CT−/CT+ ) . However , in the absence of r and omized evidence , delays in the initiation of radiotherapy should be avoided . ZusammenfassungHintergrundDie zentrale Rolle der postoperativen Strahlentherapie i m Rahmen der brusterhaltenden Therapie ist mittlerweile unbestritten . Allerdings ist der optimale Zeitpunkt für den Beginn der adjuvanten Strahlentherapie weiterhin ungewiss . In dieser retrospektiven Kohortenstudie wurde die mögliche Auswirkung einer verzögerten Einleitung der postoperativen Strahlentherapie auf die lokale Kontrolle , sowie auf das Gesamtüberleben untersucht . Patienten und Method eInsgesamt wurden Date n von 1393 Patienten über einen 17-Jahres-Zeitraum ( 1990–2006 ) analysiert . In Abhängigkeit vom Chemotherapiestatus wurden getrennte Analysen durchgeführt ( CT+/CT− ) . Eine verzögerte Einleitung der Strahlentherapie wurde als ein Intervall von > 7 Wochen ( CT− ) , bzw . > 24 Wochen ( CT+ ) definiert . ErgebnisseDas lokale rezidivfreie Überleben für die CT− und CT+ Gruppe lag nach 10 Jahren bei 95,6 % bzw . 86,0 % . Über den gesamten Zeitraum konnte ein signifikanter Anstieg des medianen Intervalls zwischen Operation und Strahlentherapie festgestellt werden ( CT− : von median 5 Wochen von 1990–1992 auf median 6 Wochen von 2005–2006 ; CT+ : von median 5 Wochen von 1990–1992 auf median 21 Wochen von 2005–2006 ) . Eine Korrelation zwischen verzögertem Beginn der Strahlentherapie und einer erhöhten lokalen Rezidivrate ( CT− : p = 0,990 für Intervalle 0–6 Wochen vs. ≥ 7 Wochen ; CT+ : p = 0,644 für Intervalle 0–15 Wochen vs. ≥ 24 Wochen ) oder einem verringerten Gesamtüberleben ( CT− : p = 0,386 für Intervalle 0–6 Wochen vs. ≥ 7 Wochen ; CT+ : p = 0,305 für Intervalle 0–15 Wochen vs. ≥ 24 Wochen ) wurde nicht gefunden . SchlussfolgerungIn der vorliegenden Kohorte f and sich kein Hinweis auf eine erhöhte Lokalrezidivrate oder ein verringertes Gesamtüberleben bei verzögertem Beginn der Strahlentherapie . Dennoch sollte bei fehlender r and omisierter Evidenz eine Verzögerung bei der Initiierung der Strahlentherapie aufgrund radiobiologischer Erwägungen grundsätzlich vermieden werden", "BACKGROUND Studies with pertuzumab , a novel anti-HER2 antibody , show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy . We investigated the combination of pertuzumab or trastuzumab , or both , with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting . METHODS In this multicentre , open-label , phase 2 study , treatment-naive women with HER2-positive breast cancer were r and omly assigned ( 1:1:1:1 ) central ly and stratified by operable , locally advanced , and inflammatory breast cancer , and by hormone receptor expression to receive four neoadjuvant cycles of : trastuzumab ( 8 mg/kg loading dose , followed by 6 mg/kg every 3 weeks ) plus docetaxel ( 75 mg/m(2 ) , escalating , if tolerated , to 100 mg/m(2 ) every 3 weeks ; group A ) or pertuzumab ( loading dose 840 mg , followed by 420 mg every 3 weeks ) and trastuzumab plus docetaxel ( group B ) or pertuzumab and trastuzumab ( group C ) or pertuzumab plus docetaxel ( group D ) . The primary endpoint , examined in the intention-to-treat population , was pathological complete response in the breast . Neither patients nor investigators were masked to treatment . This study is registered with Clinical Trials.gov , number NCT00545688 . FINDINGS Of 417 eligible patients , 107 were r and omly assigned to group A , 107 to group B , 107 to group C , and 96 to group D. Patients given pertuzumab and trastuzumab plus docetaxel ( group B ) had a significantly improved pathological complete response rate ( 49 of 107 patients ; 45·8 % [ 95 % CI 36·1 - 55·7 ] ) compared with those given trastuzumab plus docetaxel ( group A ; 31 of 107 ; 29·0 % [ 20·6 - 38·5 ] ; p=0·0141 ) . 23 of 96 ( 24·0 % [ 15·8 - 33·7 ] ) women given pertuzumab plus docetaxel ( group D ) had a pathological complete response , as did 18 of 107 ( 16·8 % [ 10·3 - 25·3 ] ) given pertuzumab and trastuzumab ( group C ) . The most common adverse events of grade 3 or higher were neutropenia ( 61 of 107 women in group A , 48 of 107 in group B , one of 108 in group C , and 52 of 94 in group D ) , febrile neutropenia ( eight , nine , none , and seven , respectively ) , and leucopenia ( 13 , five , none , and seven , respectively ) . The number of serious adverse events was similar in groups A , B , and D ( 15 - 20 serious adverse events per group in 10 - 17 % of patients ) but lower in group C ( four serious adverse events in 4 % of patients ) . INTERPRETATION Patients given pertuzumab and trastuzumab plus docetaxel ( group B ) had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel , without substantial differences in tolerability . Pertuzumab and trastuzumab without chemotherapy eradicated tumours in a proportion of women and showed a favourable safety profile . These findings justify further exploration in adjuvant trials and support the neoadjuvant approach for accelerating drug assessment in early breast cancer . FUNDING F Hoffmann-La Roche", "PURPOSE To evaluate the efficacy of radiation in patients treated with neoadjuvant chemotherapy and mastectomy . PATIENTS AND METHODS We retrospectively analyzed the outcomes of 542 patients treated on six consecutive institutional prospect i ve trials with neoadjuvant chemotherapy , mastectomy , and radiation . These data were compared to those of 134 patients who received similar treatment in these same trials but without radiation . RESULTS Irradiated patients had a lower rate of local-regional recurrence ( LRR ) ( 10-year rates : 11 % v 22 % , P = .0001 ) . Radiation reduced LRR for patients with clinical T3 or T4 tumors , stage > or = IIB disease ( AJCC 1988 ) , pathological tumor size > 2 cm , or four or more positive nodes ( P rate of LRR , which was significantly reduced with radiation ( 10-year rates : 33 % v 3 % , P = .006 ) . Radiation improved cause-specific survival ( CSS ) in the following subsets : stage > or = IIIB disease , clinical T4 tumors , and four or more positive nodes ( P LRR and CSS , the hazard ratios for lack of radiation were 4.7 ( 95 % CI , 2.7 to 8.1 ; P neoadjuvant chemotherapy and mastectomy , comprehensive radiation was found to benefit both local control and survival for patients presenting with clinical T3 tumors or stage III-IV ( ipsilateral supraclavicular nodal ) disease and for patients with four or more positive nodes . Radiation should be considered for these patients regardless of their response to initial chemotherapy", "PURPOSE To report the clinical and dose-volume histogram results of the first 47 patients accrued to a protocol of accelerated partial breast irradiation . Patients were treated in the prone position with three-dimensional conformal radiotherapy after breast-conserving surgery . METHODS AND MATERIAL S Postmenopausal women with Stage T1N0 breast cancer were eligible only after they had first refused to undergo 6 weeks of st and ard radiotherapy . Planning CT in the prone position was performed on a dedicated table . The postoperative cavity was defined as the clinical target volume , with a 1.5-cm margin added to determine the planning target volume . A total dose of 30 Gy at 6 Gy/fraction was delivered in five fractions within 10 days . RESULTS The median age of the patients was 67.5 years ( range , 51 - 88 years ) . The median tumor diameter was 9 mm ( range , 1.3 - 19 mm ) . In all patients , the prescribed dose encompassed the planning target volume . The mean volume of the ipsilateral breast receiving 100 % of the prescription dose was 26 % ( range , 10 - 45 % ) , and the mean volume contained within the 50 % isodose surface was 47 % ( range , 23 - 75 % ) . The lung and heart were spared by treating in the prone position . Acute toxicity was modest , limited mainly to Grade 1 - 2 erythema . With a median follow-up of 18 months , only Grade 1 late toxicity occurred , and no patient developed local recurrence . CONCLUSION These data suggest that this approach is well tolerated , with only mild acute side effects and sparing of the heart and lung", "BACKGROUND 5-year results of the UK St and ardisation of Breast Radiotherapy ( START ) trials suggested that lower total doses of radiotherapy delivered in fewer , larger doses ( fractions ) are at least as safe and effective as the historical st and ard regimen ( 50 Gy in 25 fractions ) for women after primary surgery for early breast cancer . In this prespecified analysis , we report the 10-year follow-up of the START trials testing 13 fraction and 15 fraction regimens . METHODS From 1999 to 2002 , women with completely excised invasive breast cancer ( pT1 - 3a , pN0 - 1 , M0 ) were enrolled from 35 UK radiotherapy centres . Patients were r and omly assigned to a treatment regimen after primary surgery followed by chemotherapy and endocrine treatment ( where prescribed ) . R and omisation was computer-generated and stratified by centre , type of primary surgery ( breast-conservation surgery or mastectomy ) , and tumour bed boost radiotherapy . In START-A , a regimen of 50 Gy in 25 fractions over 5 weeks was compared with 41·6 Gy or 39 Gy in 13 fractions over 5 weeks . In START-B , a regimen of 50 Gy in 25 fractions over 5 weeks was compared with 40 Gy in 15 fractions over 3 weeks . Eligibility criteria included age older than 18 years and no immediate surgical reconstruction . Primary endpoints were local-regional tumour relapse and late normal tissue effects . Analysis was by intention to treat . Follow-up data are still being collected . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N59368779 . FINDINGS START-A enrolled 2236 women . Median follow-up was 9·3 years ( IQR 8·0 - 10·0 ) , after which 139 local-regional relapses had occurred . 10-year rates of local-regional relapse did not differ significantly between the 41·6 Gy and 50 Gy regimen groups ( 6·3 % , 95 % CI 4·7 - 8·5 vs 7·4 % , 5·5 - 10·0 ; hazard ratio [ HR ] 0·91 , 95 % CI 0·59 - 1·38 ; p=0·65 ) or the 39 Gy ( 8·8 % , 95 % CI 6·7 - 11·4 ) and 50 Gy regimen groups ( HR 1·18 , 95 % CI 0·79 - 1·76 ; p=0·41 ) . In START-A , moderate or marked breast in duration , telangiectasia , and breast oedema were significantly less common normal tissue effects in the 39 Gy group than in the 50 Gy group . Normal tissue effects did not differ significantly between 41·6 Gy and 50 Gy groups . START-B enrolled 2215 women . Median follow-up was 9·9 years ( IQR 7·5 - 10·1 ) , after which 95 local-regional relapses had occurred . The proportion of patients with local-regional relapse at 10 years did not differ significantly between the 40 Gy group ( 4·3 % , 95 % CI 3·2 - 5·9 ) and the 50 Gy group ( 5·5 % , 95 % CI 4·2 - 7·2 ; HR 0·77 , 95 % CI 0·51 - 1·16 ; p=0·21 ) . In START-B , breast shrinkage , telangiectasia , and breast oedema were significantly less common normal tissue effects in the 40 Gy group than in the 50 Gy group . INTERPRETATION Long-term follow-up confirms that appropriately dosed hypofractionated radiotherapy is safe and effective for patients with early breast cancer . The results support the continued use of 40 Gy in 15 fractions , which has already been adopted by most UK centres as the st and ard of care for women requiring adjuvant radiotherapy for invasive early breast cancer . FUNDING Cancer Research UK , UK Medical Research Council , UK Department of Health", "In a prospect i ve r and omized study , the efficacy of two combined modality approaches ( chemotherapy plus radiotherapy or chemotherapy plus mastectomy ) was tested in a total of 132 women with locally advanced breast cancer . Chemotherapy consisted of Adriamycin plus vincristine ( AV ) administered for three cycles before either local-regional modality and subsequently for seven additional cycles . Although a higher proportion of women achieved complete remission after mastectomy ( 100 % ) compared to women given radiotherapy ( 60 % ) , the total response rate at the end of combined modality was identical ( 75 % ) . There was no significant difference between the two treatment groups in terms of patterns of treatment failure , median duration of response , and total survival . Treatment was not influenced by menopausal or estrogen receptor status . Two patients of the surgical group showed Adriamycin-induced cardiomyopathy after cumulative doses less than 500 mg/m2 . The results of present study failed to indicate that surgery per se improved the overall results including local control , over radiotherapy in a combined modality setting", "We have previously demonstrated high pathologic response rates after neoadjuvant concurrent chemoradiation in patients with locally advanced breast cancer ( LABC ) . We now report disease-free survival ( DFS ) and overall survival ( OS ) in the context of pathologic response . 105 LABC patients ( White 46 % , Non-White 54 % ) were treated with paclitaxel ( 30 mg/m2 intravenously twice a week ) for 10–12 weeks . Daily radiotherapy was delivered to breast , axillary , and supraclavicular lymph nodes during weeks 2–7 of paclitaxel treatment , at 1.8 Gy per fraction to a total dose of 45 Gy with a tumor boost of 14 Gy at 2 Gy/fraction . Pathological complete response ( pCR ) was defined as the absence of invasive cancer in breast and lymph nodes and pathological partial response ( pPR ) as the persistence of Pathologic response ( pCR and pPR ) after neoadjuvant chemoradiation was achieved in 36/105 patients ( 34 % ) and was associated with significantly better DFS and OS . Pathological responders had a lower risk of recurrence or death ( HR = 0.35 , P = 0.01 ) and a longer OS ( HR = 4.27 , P = 0.01 ) compared with non-responders . Median DFS and OS were 57 and 84 months for non-responders , respectively , and have not yet been reached for responders . Importantly , pathologic response was achieved in 54 % of patients with HR negative tumors ( 26/48 ) . In conclusion , pathologic response to concurrent paclitaxel-radiation translated into superior DFS and OS . Half of the patients with HR negative tumors achieved a pathologic response ", "PURPOSE To assess the long-term contribution of adjuvant chemotherapy ( CT ) and hormonal therapy ( HT ) in patients with locally advanced breast cancer , and to evaluate the impact of time of analysis on the results during accrual and up to 8 years after closure of a r and omized phase III trial . MATERIAL S AND METHODS In a trial using a factorial design , 410 patients were r and omized between radiotherapy ( RT ) alone , RT plus CT , RT plus HT , and RT plus HT plus CT . RESULTS CT and HT each produced a significant prolongation of the time to locoregional tumor recurrence and to distant progression of disease , with the combined treatments providing the greatest therapeutic effect . At the time of trial closure , a significant improvement of survival was observed in patients who received CT ( P = .004 ) ; however , with a longer follow-up duration , this effect disappeared ( P > .05 ) . HT did not initially appear to improve survival ( P = .16 ) ; however , in the latest analysis with a long-term follow-up duration , a significant improvement of survival was seen ( P = .02 ) . A consistent 25 % reduction in the death hazards ratio has been seen at all evaluations since trial closure in patients who received HT . The best survival results were observed in patients who received RT , HT , and CT ( P = .02 ) , with a reduction of 35 % in the death hazards ratio . CONCLUSION An improvement in survival attributable to HT has been shown in patients with locally advanced breast cancer . The greatest therapeutic effect was seen in the treatment group that received both CT and HT . The improvement obtained with HT became apparent only after long-term follow-up evaluation", "PURPOSE To examine the importance of estrogen receptor ( ER ) , progesterone receptor ( PgR ) , human epidermal growth factor receptor 2 ( HER-2 ) , and constructed subtypes in a large study r and omly assigning patients to receive or not receive postmastectomy radiotherapy ( PMRT ) . PATIENTS AND METHODS The present analysis included 1,000 of the 3,083 high-risk breast cancer patients r and omly assigned to PMRT in the Danish Breast Cancer Cooperative Group ( DBCG ) protocol 82 trials b and c. Tissue microarray sections were stained for ER , PgR , and HER-2 . Median follow-up time for patients alive was 17 years . End points were locoregional recurrence as isolated first event , distant metastases , and overall survival . For statistical analyses four subgroups were constructed from hormonal receptors ( Rec ) . Rec+ was defined as ER+ and /or PgR+ . Rec-as both ER- and PgR- . The four subgroups were Rec+/HER-2- , Rec+/HER-2 + , Rec-/HER-2-(triple negative ) , and Rec-/HER-2 + . RESULTS A significantly improved overall survival after PMRT was seen only among patients characterized by good prognostic markers such as hormonal receptor-positive and HER-2- patients ( including the two Rec+ subtypes ) . No significant overall survival improvement after PMRT was found among patients with an a priori poor prognosis , the hormonal receptor-negative and HER-2 + patients , and in particular the Rec-/HER-2 + subtype . Furthermore , comparing hazard ratios and 95 % CIs , significantly smaller improvements in locoregional recurrence control after PMRT were found for ER- and PgR-tumors compared with the ER+ and PgR+ tumors ( P = .003 and .04 , respectively ) , and for the triple-negative ( P = .02 ) , and the Rec-/HER-2 + subtypes ( P = .003 ) compared with the Rec+/HER-2-subtype . CONCLUSION Hormonal receptor status , HER-2 , and the constructed subtypes may be predictive of locoregional recurrence and survival after postmastectomy radiotherapy", "Background and Purpose : The aim of the present paper is to up date the practical guidelines for radiotherapy of breast cancer published in 2006 by the breast cancer expert panel of the German Society for Radiooncology ( DEGRO ) . These recommendations were complementing the S3 guidelines of the German Cancer Society ( DKG ) elaborated in 2004 . The present DEGRO recommendations are based on a revision of the DKG guidelines provided by an interdisciplinary panel and published in February 2008 . Methods : The DEGRO expert panel ( authors of the present manuscript ) performed a comprehensive survey of the literature . Data from lately published meta-analyses , recent r and omized trials and guidelines of international breast cancer societies , yielding new aspects compared to 2006 , provided the basis for defining recommendations referring to the criteria of evidence -based medicine . In addition to the more general statements of the DKG , this paper emphasizes specific radiooncologic issues relating to radiotherapy after mastectomy ( PMRT ) , locally advanced disease , irradiation of the lymphatic pathways , and sequencing of local and systemic treatment . Technique , targeting , and dose are described in detail . Results : PMRT significantly reduces local recurrence rates in patients with T3/T4 tumors and /or positive axillary lymph nodes ( 12.9 % with and 40.6 % without PMRT in patients with four or more positive nodes ) . The more local control is improved , the more substantially it translates into increased survival . In node-positive women the absolute reduction in 15-year breast cancer mortality is 5.4 % . Data referring to the benefit of lymphatic irradiation are conflicting . However , radiotherapy of the supraclavicular area is recommended when four or more nodes are positive and otherwise considered individually . Evidence concerning timing and sequencing of local and systemic treatment is sparse ; therefore , treatment decisions should depend on the dominating risk of recurrence . Conclusion : There is common consensus that PMRT is m and atory for patients with T3/T4 tumors and /or four or more positive axillary nodes and should be considered for patients with one to three involved nodes . Irradiation of the lymphatic pathways and the optimal time point for onset of radiotherapy are still under debate . Hintergrund und Ziel : Ziel der Arbeit ist eine Aktualisierung der 2006 publizierten Leitlinie der „ Expertengruppe Mammakarzinom “ der Deutschen Gesellschaft für Radioonkologie ( DEGRO ) . Diese war seinerzeit in Ergänzung zur interdisziplinären S3-Leitlinie der Deutschen Krebsgesellschaft ( DKG ) von 2004 verfasst worden . Zwischenzeitlich erfolgten eine Überarbeitung und Aktualisierung der S3-Leitlinie der DKG , die i m Februar 2008 publiziert wurde . Method ik : Die Expertengruppe ( identisch mit den Autoren dieses Manuskripts ) führte eine umfassende Literaturrecherche durch . Aktuelle Metaanalysen und r and omisierte Studien , die neue Aspekte gegenüber 2006 ergaben , sowie Empfehlungen internationaler Fachgesellschaften wurden in die Bewertung von Therapieindikationen einbezogen . Diese orientieren sich an den Kriterien evidenzbasierter Medizin . In Ergänzung zu den eher allgemeinen Statements der DKG 2008 werden spezielle radiotherapeutische Fragestellungen beh and elt , die eine Strahlentherapie nach Mastektomie ( PMRT ) und/oder bei fortgeschrittenen Tumoren , die Bestrahlung der Lymphabflusswege und die Sequenz von Radio- und Systemtherapie betreffen . Zielvolumendefinition und Dosierung werden i m Detail beschrieben . Ergebnisse : Die PMRT senkt die Lokalrezidivrate bei Patientinnen mit hohem Rückfallrisiko ( T3/T4-Tumoren und/oder befallene axilläre Lymphknoten ; 12,9 % mit und 40,6 % ohne PMRT ) . Je ausgeprägter die durch die Radiotherapie bewirkte lokale Tumorkontrolle ist , desto stärker wirkt sich dies auf die Überlebenswahrscheinlichkeit aus . Bei lymphonodal positiven Patientinnen ergab sich eine absolute Verminderung der tumorspezifischen Sterblichkeit um 5,4 % nach 15 Jahren . Hinsichtlich des Nutzens einer Strahlentherapie der Lymphabflusswege ist die Date nlage widersprüchlich . Eine Bestrahlung der Supraklavikularregion ist jedoch bei vier oder mehr befallenen axillären Lymphknoten stets indiziert und sollte bei ein bis drei positiven Lymphknoten erwogen werden . Bezüglich der Sequenz von Radio- und Systemtherapie gibt es keine richtungweisenden Evidenzen zugunsten einer Therapiemodalität . Postoperativ sollte die Sequenz vom dominierenden Risiko abhängig gemacht werden . Schlussfolgerung : Nach Mastektomie ist die PMRT bei T3/T4-Tumoren , Resttumor und/oder axillären Lymphknotenmetastasen obligat . Die Bestrahlung der regionalen Lymphabflusswege und die Sequenz von Radio- und Systemtherapie bleiben bei unzureichender Date nlage Gegenst and interdisziplinärer Diskussionen", "PURPOSE This was a retrospective observational study to elicit the outcome of the therapeutic strategy of concurrent neoadjuvant chemoradiotherapy protocol for locally advanced breast cancer . METHODS AND MATERIAL S A large series of 1,117 consecutive cases of locally advanced breast cancer treated at the Cancer Institute ( WIA ) , in Chennai , South India , between 1990 and 1999 and followed through 2004 formed the basis for this study . Disease-free survival was the main outcome , and nodal and tumor downstaging were the intermediate outcome measures studied . RESULTS Primary tumor downstaging was observed in 45 % and nodal downstaging in 57.5 % . The disease-free survival rate of nodal downstaged patients at 5 , 10 , and 15 years was 75 % , 65 % , and 58 % , respectively . The corresponding rates for pre- and postoperative node-negative patients were 70 % , 60 % , and 59 % . The best survival was seen among those who were tumor and node negative postoperatively . Nodal downstaging halved the risk of disease recurrence and death compared with node positivity , irrespective of tumor sterility . CONCLUSIONS A r and omized trial using cyclophosphamide , methotrexate , and 5-fluorouracil vs. an anthracycline-based regimen in the setting of concurrent chemoradiotherapy appears indicated . Additional preoperative chemotherapy to maximize nodal and tumor downstaging should be investigated . A change in postoperative chemotherapy according to nodal status could also be explored", "One hundred thirteen evaluable patients with previously untreated stage III breast carcinoma were treated with three monthly cycles of cyclophosphamide ( CYC ) , doxorubicin ( DOX ) , 5-fluorouracil ( 5-FU ) , vincristine ( VCR ) , and prednisone ( PRED ) ( CAFVP ) . Subsequently , 91 ( 81 % ) were deemed operable . Patients were then r and omized to receive surgery or radiotherapy ( RT ) to determine which of these modalities afforded better local tumor control . All patients also received 2 additional years of CAFVP in a further attempt to eradicate local disease and systemic micrometastases . Forty-one of the r and omized patients have relapsed . Approximately half of the initial relapses in each arm were local . The overall duration of disease control was similar following either modality , with a median of 29.2 months for surgery patients and 24.4 months for RT patients . Similarly , there was no major difference in survival related to r and omized treatment with an overall median of 39 months ( median follow-up 37 months ) . Pre- or perimenopausal status and inflammatory disease were associated with shorter disease control and survival . Treatment was generally well tolerated and toxicity was acceptable . This study demonstrates that prolonged control of stage III breast carcinoma can be achieved with combined modality therapy in which cytotoxic chemotherapy precedes and follows treatment directly primarily at the breast tumor , using either surgery or RT . Nevertheless , new regimens must be design ed if significant advances that may lead to the cure of this disease are to be achieved", "Abstract During the past decade planning of adjuvant radiotherapy ( RT ) of early breast cancer has changed from two-dimensional ( 2D ) to 3D conformal techniques . In the planning computerised tomography ( CT ) scan both the targets for RT and the organs at risk ( OARs ) are visualised , enabling an increased focus on target dose coverage and homogeneity with only minimal dose to the OARs . To ensure uniform RT in the national prospect i ve trials of the Danish Breast Cancer Cooperative Group ( DBCG ) , a national consensus for the delineation of clinical target volumes ( CTVs ) and OARs was required . Material and methods . A CT scan of a breast cancer patient after surgical breast conservation and axillary lymph node ( LN ) dissection was used for delineation . During multiple dummy-runs seven experienced radiation oncologists contoured all CTVs and OARs of interest in adjuvant breast RT . Two meetings were held in the DBCG Radiotherapy Committee to discuss the contouring and to approve a final consensus . The Dice similarity coefficient ( DSC ) was used to evaluate the delineation agreement before and after the consensus . Results . The consensus delineations of CTVs and OARs are available online and a table is presented with a contouring description of the individual volumes . The consensus provides recommendations for target delineation in a st and ard patient both in case of breast conservation or mastectomy . Before the consensus , the average value of the DSC was modest for most volumes , but high for the breast CTV and the heart . After the consensus , the DSC increased for all volumes . Conclusion . The DBCG has provided the first national guidelines and a contouring atlas of CTVs and OARs definition for RT of early breast cancer . The DSC is a useful tool in quantifying the effect of the introduction of guidelines indicating improved inter-delineator agreement . This consensus will be used by the DBCG in our prospect i ve trials", "Background Currently , therapy for breast cancer patients with stage IV disease and an intact primary tumor is metastasis directed ; the primary tumor is treated only when it causes symptoms . A recent review suggested that surgery may improve long-term survival in such patients . We evaluated the effect of surgery in such patients on long-term survival and disease progression . Methods We review ed the records of all breast cancer patients treated at our institution between 1997 and 2002 who presented with stage IV disease and an intact primary tumor . Information collected included demographics , tumor characteristics , site(s ) of metastases , type/ date of operation , use of radiotherapy , chemotherapy and hormonal therapy , disease progression ( time to progression and location of progression ) in the first year after diagnosis , and last follow-up . Overall and metastatic progression-free survival were compared between surgery and nonsurgery patients . Results Of 224 patients identified , 82 ( 37 % ) underwent surgical extirpation of the primary tumor ( segmental mastectomy in 39 [ 48 % ] and mastectomy in 43 [ 52 % ] ) , and 142 ( 63 % ) were treated without surgery . The median follow-up time was 32.1 months . After adjustment for other covariates , surgery was associated with a trend toward improvement in overall survival ( P = .12 ; relative risk , .50 ; 95 % confidence interval , .21–1.19 ) and a significant improvement in metastatic progression-free survival ( P = .0007 ; relative risk , .54 ; 95 % confidence interval , .38–.77 ) . Conclusions Removal of the intact primary tumor for breast cancer patients with synchronous stage IV disease is associated with improvement in metastatic progression-free survival . Prospect i ve studies are needed to vali date these findings", "Aim The purpose of this work is to up date the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology ( DEGRO ) . Methods A comprehensive survey of the literature concerning regional nodal irradiation ( RNI ) was performed using the following search terms : “ breast cancer ” , “ radiotherapy ” , “ regional node irradiation ” . Recent r and omized trials were analyzed for outcome as well as for differences in target definition . Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas . Moreover , data from recently published meta-analyses and guidelines of international breast cancer societies , yielding new aspects compared to 2008 , provided the basis for defining recommendations according to the criteria of evidence -based medicine . In addition to the more general statements of the German interdisciplinary S3 guidelines up date d in 2012 , this paper addresses indications , targeting , and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer . Results International guidelines reveal substantial differences regarding indications for RNI . Patients with 1–3 positive nodes seem to profit from RNI compared to whole breast ( WBI ) or chest wall irradiation alone , both with regard to locoregional control and disease-free survival . Irradiation of the regional lymphatics including axillary , supraclavicular , and internal mammary nodes provided a small but significant survival benefit in recent r and omized trials and one meta- analysis . Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection ( ALND ) , while reducing the rate of lymph edema . Data concerning the impact of 1–2 macroscopically affected sentinel node ( SN ) or microscopic metastases on prognosis are conflicting . Conclusion Recent data suggest that the current restrictive use of RNI should be scrutinized because the risk – benefit relationship appears to shift towards an improvement of outcome .ZusammenfassungZielAktualisierung der DEGRO-Leitlinie von 2008 zur adjuvanten Strahlentherapie des regionalen Lymphabflusses bei Mammakarzinom und Ergänzung der allgemeinen Empfehlungen der interdisziplinären S3-Leitlinie der Deutschen Krebsgesellschaft von 2012 durch spezifisch radioonkologische Leitlinien zur Indikation , Zielvolumendefinition und Technik der postoperativen Radiotherapie . Method enDie DEGRO-Expertengruppe Mammakarzinom führte eine systematische Literaturrecherche nach r and omisierten Studien , Metaanalysen sowie internationalen Leitlinien durch , die nach 2008 publiziert wurden und sich an den Kriterien evidenzbasierter Medizin orientierten . Suchbegriffe waren „ breast cancer “ , „ radiotherapy “ und „ regional node irradiation “ . Die Studien wurden sowohl auf ihre Ergebnisse als auch hinsichtlich der Unterschiede in den Zielvolumina analysiert und auf 3-D-Planungsschnittbilder mit CT-konturierten Lymphabflussgebieten projiziert . ErgebnisseDie Indikation zur regionalen Lymphabflussbestrahlung ( RNI ) wird in internationalen Leitlinien unterschiedlich gestellt . Bei Patientinnen mit 1–3 befallenen axillären Lymphknoten wurden nach RNI i m Vergleich zur alleinigen Bestrahlung der Brust oder Brustw and Verbesserungen der lokoregionalen Kontrolle und des Überlebens beobachtet . Mehrere r and omisierte Studien und eine Metaanalyse zeigten nach RNI ( mit unterschiedlichen Zielvolumina ) eine zwar geringe , jedoch signifikante Verbesserung des Überlebens . Bei positivem Sentinel-Lymphknoten ( SN ) ist die Lymphabflussbestrahlung einer axillären Lymphonodektomie ( ALND ) gleichwertig in der lokalen Tumorkontrolle , geht aber mit einer deutlich geringeren Lymphödemrate einher . Zur Frage , ob ein solch limitierter Lymphknotenbefall und selbst eine Mikrometastasierung langfristig einen Einfluss auf die Prognose haben , ist die Date nlage widersprüchlich . SchlussfolgerungDie restriktive Indikationsstellung zur Lymphabflussbestrahlung muss angesichts neuer Date n aus r and omisierten Studien kritisch überdacht werden", "PURPOSE To determine whether breast conservation and prolonged neoadjuvant chemotherapy have efficacy in locally advanced breast cancer ( LABC ) , as measured by survival and rate of breast conservation . MATERIAL S AND METHODS Eighty-nine patients with stage III disease were enrolled at the University of Michigan ( UM ) onto a prospect i ve nonr and omized trial . Patients received nine 21-day cycles of neoadjuvant chemohormonal therapy that consisted of doxorubicin 30 mg/m2 and cyclophosphamide 750 mg/m2 intravenously on day 1 , conjugated estrogens 0.625 mg orally twice daily on days 6 to 8 , methotrexate 40 mg/m2 and fluorouracil 500 mg/m2 intravenously on day 8 , and tamoxifen 10 mg orally twice daily on days 9 to 14 . Patients with a negative biopsy received radiation only , while those with residual disease underwent mastectomy and postoperative radiotherapy . Eight more cycles of chemohormonal therapy were administered after local-regional therapy . RESULTS The clinical response rate to neoadjuvant therapy was 97 % , 28 % of patients had a complete pathologic response evaluated at biopsy . Five-year overall and disease-free survival probabilities were 54 % and 44 % , respectively . The median disease-free survival time was 2.4 years . The 5-year actuarial rates of local-regional control with local failure as only first failure were 82 % and 78 % following radiotherapy , and mastectomy and radiotherapy , respectively ( P = .99 ) . CONCLUSION Prolonged neoadjuvant chemohormonal therapy and biopsy-driven local therapy have efficacy in LABC , with 28 % of patients being c and i date s for breast conservation and a 5-year overall survival rate of 54 %", "223 inflammatory breast cancer patients were diagnosed at the Institut Curie between 1977 and 1987 . Patients received chemotherapy and radiation treatment according to three consecutive r and omised trials . Five- and 10- year survival rates were 41 and 32 % , respectively . Disease-free interval rates were 25.5 % at 5 years and 19 % at 10 years . Parameters significantly linked with a pejorative prognosis in a multivariate analysis were : diffuse erythema , lymph node involvement , chest wall adherence , and age above 50 years . When therapeutic response parameters were included in the multivariate analysis , the five most important prognostic factors in order of significance were complete tumour regression after completion of induction treatment ( at 8 months ) , complete regression of inflammatory symptoms after 3 months of neoadjuvant chemotherapy , limited erythema at presentation and , less significantly , complete regression of inflammatory symptoms at 8 months and tumour regression at 3 months . In conclusion , patients who achieved a rapid and complete remission had a better prognosis than patients who had an incomplete response to chemotherapy . High-dose chemotherapy and reversal or prevention of drug resistance will be evaluated in future trials . Detailed information on the biology of this disease should allow the design of new strategies aim ing to improve patient management", "The objective of this study was to compare the antitumor activity of single-agent paclitaxel ( Taxol ; Bristol-Myers Squibb Company , Princeton , NJ ) with that of the 5-fluorouracil/doxorubicin/cyclophosphamide ( FAC ) combination by evaluating the extent of residual disease in the breast and regional lymph nodes of patients with breast cancer following four cycles of induction chemotherapy . Patients with histologically confirmed invasive but noninflammatory carcinoma of the breast stages T2 - 3 , N0 - 1 , M0 were eligible to enter the study . Patients were treated with four cycles of either FAC or single-agent paclitaxel before local therapy . Following local therapy , treatment of the two arms was identical . Of 104 operable breast cancer patients who were treated with either regimen , 78 were evaluable for response to preoperative chemotherapy and had undergone local therapy . Age , TNM classification , and estrogen receptor status of the patients were similar in the two groups . Following induction chemotherapy , the extent of disease in the breast and the distribution and number of positive nodes were similar between the two treatment arms . Disease progressed in two patients in the FAC arm and in none in the paclitaxel arm during the induction phase of therapy . A higher fraction of patients had neutropenic fever during the paclitaxel treatment . Initial data from this ongoing r and omized study show that paclitaxel alone has comparable anticancer activity with FAC in patients with early breast cancer . The degree of cytoreduction was similar with both induction therapies", "PURPOSE This retrospective analysis aim ed to identify whether breast cancer patients receiving radiotherapy alone following a complete clinical remission ( cCR ) to neoadjuvant chemotherapy had a worse outcome than those treated with surgery . PATIENTS AND METHODS One hundred thirty-six patients who had achieved a cCR to neoadjuvant chemotherapy for early breast cancer were identified from a prospect ively maintained data base of 453 patients . Of these , 67 patients had undergone surgery as their primary locoregional therapy , and 69 patients had radiotherapy alone . Outcome was assessed in relation to local recurrence-free survival , disease-free survival , and overall survival . RESULTS Median follow-up was 63 months in the surgery group and 87 months in the no surgery group . Prognostic characteristics were well balanced between the two groups . For surgery and no surgery , respectively , there were no significant differences in disease-free survival or overall survival ( 5-year , 74 % v 76 % ; 10-year , 60 % v 70 % , P = .9 ) between the two groups . There was a nonsignificant trend toward increased locoregional-only recurrence for the no surgery group ( 21 % v 10 % at 5 years ; P = .09 ) , but no long-term failures of local control . Patients in the no surgery group who also achieved an ultrasound complete remission had a 5-year local recurrence rate of only 8 % . CONCLUSION In patients achieving a cCR to neoadjuvant chemotherapy , radiotherapy alone achieve survival rates as good as with surgery , but with higher local recurrence rates . Ultrasound may identify a low recurrence rate subgroup for assessing no surgery in a prospect i ve trial", "PURPOSE We investigated the pattern of rash , diarrhea , and hepatic adverse events ( AEs ) secondary to lapatinib and their association with age and pathologic complete response ( pCR ) in the Neoadjuvant Lapatinib and /or Trastuzumab Treatment Optimisation ( NeoALLTO ) phase III trial . PATIENTS AND METHODS Patients with HER2-positive early breast cancer were r and omly assigned to receive lapatinib ( Arm A ) , trastuzumab ( Arm B ) , or their combination ( Arm C ) for 6 weeks followed by the addition of paclitaxel for 12 weeks before surgery . We investigated the frequency and time to developing each AE according to age ( ≤ 50 v > 50 years ) and their association with pCR in a logistic regression model adjusted for age , hormone receptors , tumor size , nodal status , planned breast surgery , completion of lapatinib administration , and treatment arm . RESULTS Only patients r and omly assigned to arms A and C were eligible ( n = 306 ) . Younger patients ( ≤ 50 years ) experienced significantly more rash compared with older patients ( 74.4 % v 47.9 % ; P were observed in 78.8 % and 41.2 % of patients , respectively , with no differences in rate or severity or time of onset according to age . Early rash ( ie , before starting paclitaxel ) was independently associated with a higher chance of pCR , mainly in patients older than 50 years ( odds ratio [ OR ] = 3.76 ; 95 % CI , 1.69 to 8.34 ) but not in those ≤ 50 years ( OR = 0.92 ; 95 % CI , 0.45 to 1.88 ; P for interaction = .01 ) . No significant association was observed between pCR and diarrhea or hepatic AEs . CONCLUSION Our results indicate that the frequency and clinical relevance of lapatinib-related rash is largely dependent on patient age" ]

[ "The aim of the present study was to compare intraindividually a type III fissure-sealant , glass ionomer cement with a resin-based sealant . One hundred and forty-eight first permanent molars were sealed in forty-seven children . After three years 20.8 percent of the resin and 34.7 percent of the glass ionomer cement sealants were partially lost , and 0 percent and 37.5 percent , respectively , were totally lost . One tooth ( 1.4 percent ) in the glass ionomer cement group and three teeth ( 4.2 percent ) in the resin group developed caries", "The aim of the present trial was to ( 1 ) compare the caries-preventive effect of glass ionomer sealants , placed according to the atraumatic restorative treatment ( ART ) procedure , with composite resin sealants over time and ( 2 ) investigate the caries-preventive effect after complete disappearance of sealant material . Forty-six boys and 57 girls , mean age 7.8 years , were r and omly divided into two treatment groups in a parallel-group study design . A light-polymerized composite resin sealant material and a high-viscosity glass ionomer were each placed in 180 fully erupted first molars in their respective treatment groups . Evaluation took place annually for 5 years by calibrated examiners . After 5 years , 86 % composite resin and 88 % glass ionomer sealants did not survive . Three categories of re-exposure periods for caries development in pits and fissures after complete loss of sealants were distinguished : 0–1 , 1–2 and 2–3 years . In the 2- to 3-year group , 13 and 3 % of pits and fissures previously sealed with composite resin and glass ionomer , respectively , were diagnosed as having developed a dentine lesion . The relative risks ( 95 % CI ) of dentine lesion development in surfaces sealed with glass ionomer compared to those sealed with composite resin after 3 , 4 and 5 years were 0.22 ( 0.06–0.82 ) , 0.32 ( 0.14–0.73 ) and 0.28 ( 0.13–0.61 ) , respectively . The relative risks of dentine lesion development in pits and fissures previously sealed with glass ionomer compared with composite resin over re-exposure periods of 1–2 and 2–3 years were 0.26 ( 0.14–0.48 ) and 0.25 ( 0.09–0.68 ) , respectively . We conclude that the caries-preventive effect of high-viscosity glass ionomer sealants , placed using the ART procedure , was between 3.1 and 4.5 times higher than that of composite resin sealants after 3–5 years . Furthermore , high-viscosity ( ART ) glass ionomer sealants appear to have a four times higher chance of preventing caries development in re-exposed pits and fissures of occlusal surfaces in first molars than light-cured composite resin sealant material over a 1- to 3-year period . A well- design ed clinical trial using different types of oral health personnel should be implemented to confirm these initial results", "OBJECTIVE To compare the retention and the caries preventive effect of a glass-ionomer developed for fissure sealing ( Fuji III ) and a chemically polymerized resin-based fissure sealant ( Delton ) . DESIGN A split mouth r and omized design using contralateral teeth . SETTING WHO Regional Demonstration , Training and Research Center for Oral Health , Damascus , Syrian Arab Republic . SAMPLE AND METHODS 179 children , 7 years old at the start of the study , were recruited from schools close to the Center . Only children with at least one pair of permanent first molars that were caries free or only had incipient lesions were included in the study . Follow-up examinations for sealant retention were done after 6 months , 1 year , 2 years and 3 years . The number of children available for reexamination was 129 ( after 6 months ) ; 121 ( after 1 year ) ; 115 ( after 2 years ) and 116 ( after 3 years ) . Four dental hygienists were trained in the sealant procedures and did approximately one fourth of the sealants each . RESULTS After 3 years the glass-ionomer sealant was completely lost in almost 90 % of the teeth compared to less than 10 % of the resin sealed teeth . After 3 years the relative risk of a tooth sealed with glass-ionomer over that of a tooth sealed with resin was 3.38 ( 95 % CL : 1.98 ; 5.79 ) . This finding was consistent over type of tooth . CONCLUSIONS The glass-ionomer sealant tested in the present study had poorer retention and less caries protective effect than the resin-based sealant used", "OBJECTIVE In this in vitro study we evaluated the enamel mineral loss effect of fluoride-containing and non-fluoride-containing material s at different distances from the sealant margin , and verified the fluoride-releasing capability of these material s. MATERIAL AND METHODS Extracted molars were r and omly assigned into nine groups ( n = 12 ) : Concise ( C ) , FluroShield ( F ) , Helioseal Clear Chroma ( H ) , Vitremer ( V ) , Fuji II-LC ( FII ) , Ketac Molar ( KM ) , Fuji IX ( FIX ) , Single Bond ( SB ) , and Clearfil Protect Bond ( CF ) . All groups were subjected to thermo and pH cycling . Enamel mineral loss was evaluated by cross-section micro-hardness analysis at distances : -100 microm , 0 microm , 100 microm , 200 microm . The mineral loss data were analyzed using a multi-factor ANOVA with split-plot design , and fluoride-released data were su bmi tted to ANOVA and Tukey tests . RESULTS FIX demonstrated a lower mineral loss than C , F , and H , but did not differ from the SB , CF , V , FII , and KM groups , which also demonstrated no difference among them . C , F , H , and V presented the highest mineral loss , with no difference among them . V did not differ from the other groups ( p > 0.05 ) . Regarding the different distances from the sealant margin , -100 microm presented the lowest mineral loss . FIX showed the highest fluoride release on the 7th and 14th days of evaluation , while CF showed high fluoride release only on the 7th day . CONCLUSION Resin sealant did not prevent enamel mineral loss , contrary to glass-ionomer cement , which showed the highest capacity for fluoride release . It is not exclusively the presence of fluoride in a material 's composition that indicates its capability to interfere with the development of enamel caries-like lesions", "Abstract Fissure sealing using partially filled resins is an established caries preventive practice . Glass ionomer cement ( GIC ) sealants may offer additional advantages due to their ability to bond chemically to enamel and release fluoride . The aim of this study was to compare the caries preventive effect and retention of a GIC and a resin-based sealant . Ketac-fil ® was tested against a chemically cured resin-based material ( Delton ® ) using a split mouth design . Perth ( Western Australia ) schoolchildren ( n= 465 ) , mean age 7 yr±0.72 ( S.D. ) , received sealants on the occlusal surfaces of sound homologous permanent first molar pairs . Test ( GIC ) and control ( resin ) sealants were systematic ally allocated to left and right sides based on the child 's month of birth , and were placed by dental therapists . After 3.64±0.11 yr , 415 children were examined by different clinicians , and the clinical status of the teeth and the extent of sealant retention recorded . Sealants were deemed retained when at least 2/3 of the fissure pattern was still sealed . In 252 tooth pairs , neither sealant was retained to this extent . In 71 pairs , the GIC was not retained and the resin sealant retained . In 40 pairs the reverse occurred ( McNemar 's test , χ2= 8.66 , P ( additional lesions prevented by the test agent per 100 treatments ) was 6.1%(95 % CI 3.3 % , 8.9 % ) . Effectiveness of the GIC was 80.6 % ( 95 % CI 59.6 % , 90.7 % ) . The relative risk of caries in test teeth was 0.19 ( 95 % CI 0.09 , 0.40 ) . The study suggests that complete retention of GIC sealant is not necessary for caries prevention in newly erupted permanent first molars", "OBJECTIVES The objectives of the study were to investigate the clinical use of two fluoride-releasing fissure sealants and to study fluoride release under laboratory conditions . METHODS In the clinical part of the study the two material s , FluroShield and Baseline , were applied to matched contralateral caries-free first permanent molars in 86 children aged 7 - 8 years . In the laboratory study fluoride release from each material was measured using a model cavity system . RESULTS After 3 years FluroShield was intact on 70 % of teeth . Retention was significantly better on lower molars than upper molars . Baseline was lost from all except two teeth within 6 months . After 3 years , caries had affected four teeth sealed with FluroShield and 24 teeth sealed with Baseline ; this difference was highly significant . The laboratory study showed that FluroShield released twice as much fluoride over 9 days than did Baseline . Long term studies using FluroShield showed a small steady fluoride release over 6 months . CONCLUSIONS The conclusion of the study was that FluroShield was a much more effective fissure sealant than Baseline . The clinical performance of FluroShield was comparable to that of other inert composite resin sealants and superior to that of fluoride-releasing sealants used previously", "The aim of this community-oriented study was to evaluate different methods to prevent fissure caries . The following products and measures were tested : 1 ) glass ionomer cement ( GIC ) applied by dentist ; 2 ) same material applied by short term ( 3 days ) trained personnel ( teachers ) ; 3 ) application of a 0.5 % HF solution three times ; 4 ) an established autopolymerized resin based sealant ( Delton ) . The study was performed in Bangkok , Thail and , a city in a developing country experiencing increasing caries prevalence . Children with at least three sound permanent molars from two age groups , 7 - 8 and 12 - 13-yr-olds respectively were chosen from very low to medium socioeconomic level families . 1264 children were systematic ally assigned to experiment or control groups based on school and DMFT . For the younger age group , the 2 yr mean DFS occlusal increment in the Control group was 0.66 surfaces . Significantly lower increments were observed in the GIC experimental group : 0.17 surfaces applied by the teachers and 0.32 applied by dentist , corresponding to 74 % and 52 % reductions , respectively . The mean increment in the HF group was 0.44 surfaces , a 33 % reduction in relation to the Control group . For the 12 - 13-yr-olds , the mean occlusal surface DF increment was 0.70 surfaces in the Control group . Almost no occlusal increment was found in the Delton group , 0.05 DFS , a 93 % reduction . In the GIC Dentist group , the DFS increment was 0.48 and in the Teacher group 0.56 , corresponding to 31 % and 20 % reduction , respectively . A slight and nonsignificant increase of caries in relation to the Control group was observed in the HF group . ( ABSTRACT TRUNCATED AT 250 WORDS", "PURPOSE To evaluate the retention and caries-preventive effectiveness of two ionomeric material s ( conventional and resin-modified ) , used as fissure sealants . MATERIAL S AND METHODS 100 children ( 6 - 8 years old ) with a total of 400 permanent first molars received 200 conventional glass-ionomer ( Ketac Bond ) and 200 resin-modified glass-ionomer ( Vitremer ) sealants . Additionally , 108 children constituted the control group ( 432 teeth ) . Two dentists assisted by dental hygienists performed the sealant application . Clinical evaluations were carried out 6 , 12 , 24 , and 36 months after the sealant application by two other dentists , not carrying out clinical procedures , previously calibrated ( Kappa > 0.75 ) . RESULTS Total retention rates of 26 % , 12 % , 3 % , and 4 % for Ketac Bond and 61 % , 31 % , 14 % , and 13 % for Vitremer , being 6 , 12 , 24 , and 36 months after clinical evaluation , respectively . The differences between the two material s were statistically significant . The experimental groups showed a caries incidence of 93 % , 78 % , 49 % , and 56 % lower than the control group ( P retention rates of ionomeric material s were low . Nevertheless , these material s showed a cariostatic effect , supported by statistically lower caries incidence in experimental groups compared to control group . Presence of active incipient caries was statistically associated with caries incidence in the first molars after 36 months , in relation to either experimental or control group", "The aim of this study was to compare the retention and caries preventive efficacy of glass ionomer ( Fuji III ; GIC ) and light-cured resin-based ( Delton ; LCR ) fissure sealants . One hundred and sixty-six 5 - 14-year-old schoolchildren received sealants on their newly erupted first or second molars ; a split mouth design was used . Previously reported 2-year results showed low retention rates for GIC sealants , but no difference in the caries increment between the groups . The same persons were invited to a dental check-up 6.1 to 7.8 ( mean 7.1 ) years after the application of sealants ; 111 persons ( 66.8 % of the original group ) participated in the study . The retention of sealants , and the caries status of occlusal surfaces and adjacent proximal surfaces was recorded . On the sealed occlusal surfaces , 10 % of GIC and 45 % of LCR sealants were totally and 9 % of GIC and 20 % of LCR sealants partially present . Twenty-three ( 23.5 % ) of the occlusal surfaces sealed with GIC and 16 ( 16.5 % ) of those sealed with LCR were carious or filled . Compared to LCR sealants , the effectiveness of GIC sealants was -44 % ( 95 % CI -71 % , -16 % ) and net gain -7 % ( 95 % CI -18 % , 4 % ) . The relative risk of caries occurring was 1.44 ( 95 % CI 0.96 , 2.14 )", "The 4-year results of a fissure sealant trial are reported . Glass polyalkenoate and bis GMA sealant were applied to 590 first permanent molar teeth using a half mouth study design in a group of 228 6 - 8-year-old children . Similar cariostasis was observed for the two material s at the end of 4 years despite marked differences in retention . Polyalkenoate cements probably should be regarded as ' fluoride depot ' material s rather than fissure sealants when used in this" ]

[ "The majority of adults in the UK and US are overweight or obese due to multiple factors including excess energy intake . Training people to inhibit simple motor responses ( key presses ) to high-energy density food pictures reduces intake in laboratory studies . We examined whether online response inhibition training reduced real-world food consumption and weight in a community sample of adults who were predominantly overweight or obese ( N = 83 ) . Participants were allocated in a r and omised , double-blind design to receive four 10-min sessions of either active or control go/no-go training in which either high-energy density snack foods ( active ) or non-food stimuli ( control ) were associated with no-go signals . Participants ' weight , energy intake ( calculated from 24-h food diaries ) , daily snacking frequency and subjective food evaluations were measured for one week pre- and post-intervention . Participants also provided self-reported weight and monthly snacking frequency at pre-intervention screening , and one month and six months after completing the study . Participants in the active relative to control condition showed significant weight loss , reductions in daily energy intake and a reduction in rated liking of high-energy density ( no-go ) foods from the pre-to post-intervention week . There were no changes in self-reported daily snacking frequency . At longer-term follow-up , the active group showed significant reductions in self-reported weight at six months , whilst both groups reported significantly less snacking at one- and six-months . Excellent rates of adherence ( 97 % ) and positive feedback about the training suggest that this intervention is acceptable and has the potential to improve public health by reducing energy intake and overweight", "The present study investigated the effects of hunger and visuo-spatial interference on imagery-induced food cravings . Forty-two women were r and omly assigned to a hungry ( no food for prior 4h ) or not hungry condition . Participants were asked to form and maintain images of desired foods while looking at a blank computer screen ( control condition ) or performing a task design ed to load the visuo-spatial sketchpad of working memory ( dynamic visual noise ) . They then rated the vividness of their images and their craving intensity . Although hungry participants reported stronger food cravings , dynamic visual noise made images less vivid and cravings less intense , irrespective of participant hunger status . Thus concurrent visuo-spatial processing may offer a useful technique for treating problematic food cravings that are predominantly psychological in origin , as well as those that are hunger-driven", "Existing strategies for coping with food cravings are of unknown efficacy and rely on principles that have been shown to have paradoxical effects . The present study evaluated novel , acceptance-based strategies for coping with craving by r and omly assigning 48 overweight women to either an experimental psychological acceptance-oriented intervention or a st and ard cognitive re appraisal /distraction intervention . Participants were required to carry a box of sweets on their person for 72 h while abstaining from any consumption of sweets . Results suggested that the acceptance-based coping strategies result ed in lower cravings and reduced consumption , particularly for those who demonstrate greater susceptibility to the presence of food and report a tendency to engage in emotional eating", "The present study utilized an analog paradigm to investigate the effectiveness of two strategies for coping with food cravings , which was theorized to be critical to the maintenance of weight loss . Ninety-eight undergraduate students were given transparent boxes of chocolate Hershey 's Kisses and instructed to keep the chocolates with them , but not to eat them , for 48 h. Before receiving the Kisses , participants were r and omized to receive either ( a ) no intervention , ( b ) instruction in control-based coping strategies such as distraction and cognitive restructuring , or ( c ) instruction in acceptance-based strategies such as experiential acceptance and defusion techniques . Measures included the Power of Food Scale ( PFS ; a measure of psychological sensitivity to the food environment ) , self-report ratings of chocolate cravings and surreptitiously recorded chocolate consumption . Results suggested that the effect of the intervention depended on baseline PFS levels , such that acceptance-based strategies were associated with better outcomes ( cravings , consumption ) among those reporting the highest susceptibility to the presence of food , but greater cravings among those who scored lowest on the PFS . It was observed that craving self-report measures predicted chocolate consumption , and baseline PFS levels predicted both cravings and consumption . Results are discussed in terms of the implication s for weight loss maintenance strategies", "Objective To determine whether acceptance-based behavioral treatment ( ABT ) would result in greater weight loss than st and ard behavioral treatment ( SBT ) , and whether treatment effects were moderated by interventionist expertise or participants ’ susceptibility to eating cues . Recent research suggests that poor long-term weight control outcomes are due to lapses in adherence to weight control behaviors , and that adherence might be improved by enhancing SBT with acceptance-based behavioral strategies . Design and Methods Overweight participants ( n = 128 ) were r and omly assigned to 40 weeks of SBT or ABT . Results Both groups produced significant weight loss and , when administered by experts , weight loss was significantly higher in ABT than SBT at post-treatment ( 13.17 % v. 7.54 % ) and 6-month follow-up ( 10.98 % v. 4.83 % ) . Moreover , 64 % of those receiving ABT from experts ( v. 46 % for SBT ) maintained at least a 10 % weight loss by follow-up . Moderation analyses revealed a powerful advantage , at follow-up , of ABT over SBT in those potentially more susceptible to eating cues . For participants with greater baseline depression symptomology , weight loss at follow-up was 11.18 % in ABT vs. 4.63 % in SBT ; other comparisons were 10.51 % vs. 6.00 % ( emotional eating ) , 8.29 % v. 6.35 % ( disinhibition ) and 9.70 % v. 4.46 % ( responsivity to food cues ) . Mediation analyses produced partial support for theorized food-related psychological acceptance as a mechanism of action . Conclusions Results offer strong support for the incorporation of acceptance-based skills into behavioral weight loss treatments , particularly among those with greater levels of depression , responsivity to the food environment , disinhibition and emotional eating , and especially when interventions are provided by weight control experts . Trial Registration clinical trials.gov identifier :", "The study aim ed to investigate the effects of an acute exercise bout on urges to eat chocolate , affect , and psychological and physiological responses to stress and a chocolate cue . Following 3 days of chocolate abstinence , 25 regular chocolate eaters , took part , on separate days , in two r and omly ordered conditions , in a within-subject design : a 15-min brisk semi-self-paced brisk walk or a passive control . Following each , participants completed two tasks : the Stroop colour-word interference task , and unwrapping and h and ling a chocolate bar . Chocolate urges [ State Food Cravings Question naire ( FCQ-S ) ; Rodríguez , S. , Fernández , M. C. , Cepeda-Benito , A. , & Vila , J. ( 2005 ) . Subjective and physiological reactivity to chocolate images in high and low chocolate cravers . Biological Psychology , 70 , 9 - 18 ] , affective activation [ Felt Arousal Scale ; Svebak , S. , & Murgatroyd , S. ( 1985 ) . Metamotivational dominance : a multi method validation of reversal theory constructs . Journal of Perception and Social Psychology , 48 , 107 - 116 ] , affective pleasure/valence [ Feelings Scale ; Hardy , C. J. , & Rejeski , W. J. ( 1989 ) . Not what , but how one feels : the measurement of affect during exercise . Journal of Sport and Exercise Psychology , 11 , 304 - 317 ] , and systolic/diastolic blood pressure ( SBP/DBP ) were assessed throughout . Exercise reduced chocolate urges and there was a trend towards attenuated urges in response to the chocolate cue . Exercise also attenuated SBP/DBP increases in response to the stressor and chocolate cue . The effects on urges varied across the dimensions of the", "Humans have the ability to engage in prospect i ve imagery to anticipate the future consequences of present behaviors ( Suddendorf & Busby , 2005 ) , but we often let our desire for immediate gratification lead us to devalue larger future consequences in favor of smaller immediate rewards . Discounting large future rewards in favor of smaller immediate rewards is known as delay discounting and increases with greater temporal distance between the rewards ( Bickel & Marsch , 2001 ) . One approach to reducing delay discounting is episodic future thinking ( Atance & O'Neill , 2001 ) . Episodic future thinking engages the episodic memory in prospect ively experiencing future events ( Atance & O'Neill , 2001 ; Schacter , Addis , & Buckner , 2007 ) and activates brain regions involved in prospect i ve thinking ( Benoit , Gilbert , & Burgess , 2011 ; Schacter et al. , 2007 ) . Episodic future thinking during intertemporal decision making reduces delay discounting , with the vividness of prospect i ve imagery predicting the degree of the reduction ( Peters & Buchel , 2010 ) . The inability to delay gratification is related to obesity ( Davis , Patte , Curtis , & Reid , 2010 ; Francis & Susman , 2009 ; Weller , Cook , Avsar , & Cox , 2008 ) . Delay discounting predicts intake of energy-dense convenience foods in obese women ( Appelhans et al. , 2012 ) , and poor impulse control predicts a lack of success in weight loss ( Best et al. , 2012 ) . To determine episodic future thinking 's effect on impulsive behavior , we assessed whether episodic future thinking , compared with engagement in a control imagery task , reduced impulsivity and energy intake in overweight and obese individuals", "Obese individuals tend to behave more impulsively than healthy weight individuals across a variety of measures , but it is unclear whether this pattern can be altered . The present study examined the effects of a mindful eating behavioral strategy on impulsive and risky choice patterns for hypothetical food and money . In Experiment 1 , 304 participants completed computerized delay and probability discounting tasks for food-related and monetary outcomes . High percent body fat ( PBF ) predicted more impulsive choice for food , but not small-value money , replicating previous work . In Experiment 2 , 102 r and omly selected participants from Experiment 1 were assigned to participate in a 50-min workshop on mindful eating or to watch an educational video . They then completed the discounting tasks again . Participants who completed the mindful eating session showed more self-controlled and less risk-averse discounting patterns for food compared to baseline ; those in the control condition discounted similarly to baseline rates . There were no changes in discounting for money for either group , suggesting stimulus specificity for food for the mindful eating condition", "The present study compared the relative effectiveness of simple , commercially available food and non-food olfactory tasks on chocolate craving reduction . Chocolate cravings were induced by a series of coloured photographs and 67 undergraduate women were asked to smell one of three odours ( green apple , jasmine , or water ) . The non-food odorant ( jasmine ) significantly reduced chocolate cravings relative to both the food and control odorants . Thus simple non-food odorants offer potential scope as a technique for curbing unwanted food cravings", "Few factors have been identified that bolster self-control processes and prevent overeating in restrained eaters ; however , research on counteractive-control theory suggests that exposure to food cues may represent such a protective factor . To further investigate the effects of food-cue exposure , restrained and unrestrained eaters were r and omly assigned to either a food-cue or no-cue condition , and their intake was measured . The results indicated that food-cue-exposed restrained eaters ate less than did non-exposed restrained eaters . The possible role of incidental food-cue exposure as a means for inhibiting intake in restrained eaters is explored", "The classic answer to what makes a decision good concerns outcomes . A good decision has high outcome benefits ( it is worthwhile ) and low outcome costs ( it is worth it ) . I propose that , independent of outcomes or value from worth , people experience a regulatory fit when they use goal pursuit means that fit their regulatory orientation , and this regulatory fit increases the value of what they are doing . The following postulates of this value from fit proposal are examined : ( a ) People will be more inclined toward goal means that have higher regulatory fit , ( b ) people 's motivation during goal pursuit will be stronger when regulatory fit is higher , ( c ) people 's ( prospect i ve ) feelings about a choice they might make will be more positive for a desirable choice and more negative for an undesirable choice when regulatory fit is higher , ( d ) people 's ( retrospective ) evaluations of past decisions or goal pursuits will be more positive when regulatory fit was higher , and ( e ) people will assign higher value to an object that was chosen with higher regulatory fit . Studies testing each of these postulates support the value-from-fit proposal . How value from fit can enhance or diminish the value of goal pursuits and the quality of life itself is discussed", "We explored the effect of controlled and autonomous learning choices on the consumption of a high-energy snack food , and also examined whether snack consumption during a controlled choice learning activity could ' up-regulate ' subsequent performance on a self-regulation task . Participants were r and omly assigned to a controlled choice learning condition in which food was provided , a controlled choice learning condition in which food was not provided , or an autonomous choice learning condition in which food was provided . Results indicated that the autonomous choice group consumed significantly less snack food than the controlled-choice- and -food group . Participants in the autonomous choice condition also performed better on the subsequent self-regulation task than the controlled-choice- and -food group , even after controlling for the amount of food consumed . Furthermore , within the controlled-choice- and -food condition , there was no association between food consumption and subsequent self-regulation task performance . Discussion focuses on the potential impact of a controlled learning climate on snack food consumption and on the degradation of self-regulation capacities", "Poor self-regulation of high energy snacking has been linked to weight gain . Physical activity can acutely reduce chocolate consumption and cravings but the effects on attentional bias ( AB ) are unknown . The study aim ed to test the effects of exercise among normal and overweight/obese individuals during temporary and longer abstinence . Participants were 20 normal and 21 overweight regular female chocolate eaters ( after 24 h abstinence ) , and 17 females ( after ≥1 week abstinence during Lent ) . They were r and omly assigned to engage in 15 min brisk walking or rest , on separate days . AB was assessed using an adapted dot probe task pre and post-treatment at each session , with chocolate/neutral paired images presented for 200 ms ( initial AB ; IAB ) or 1000 ms ( maintained AB ; MAB ) . Chocolate craving was assessed pre , during , immediately after , and 5 min and 10 min after treatment , using a 0 - 100 visual analogue score . Three-way mixed ANOVAs revealed that there was no significant interaction effect between group ( i.e. , BMI status , or abstinence status ) and condition × time for craving and AB to chocolate cues . Fully repeated 2-way ANOVAS revealed a significant condition × time interaction for IAB ( F(1,57)=6.39 ) and chocolate craving ( F(2.34,133.19)=14.44 ) . After exercise IAB ( t(57)=2.78 , p condition . Craving was significantly lower than the rest condition at all assessment s post-baseline . A short bout of physical activity reduces cravings and AB to chocolate cues , relative to control , irrespective of BMI or abstinence period", "Workplace snacking can contribute to obesity . Exercise reduces chocolate cravings but effects on chocolate consumption are unknown . This study investigated the effect of brief exercise on ad libitum consumption during breaks in a computerised task . Seventy-eight regular chocolate eaters , age : 24.90±8.15 years , BMI : 23.56±3.78 kg/m(2 ) abstained for 2 days . They were r and omly assigned to one of four conditions , in a 2 × 2 factorial design , involving either a 15 min brisk walk or quiet rest , and then computerised Stroop tasks with low or high dem and ing conditions , in three 180 s blocks with a 90 s interval . Throughout , a pre-weighed bowl of chocolates was available for ad libitum eating . A two-way ANOVA revealed no interaction effect of exercise and stress on total chocolate consumption , or main effect of stress , but a main effect of exercise [ F(1 , 74)=7.12 , p was less ( t(73.5)=2.69 , 95 % CI for difference 3.4 - 22.9 , ES=0.61 ) for the exercise ( 15.6 g ) than control ( 28.8 g ) group . Exercise also increased affective activation , but there was no mediating effect of change in affect on chocolate consumption . A brief walk may help to reduce ad libitum snacking in regular chocolate eaters" ]

[ "Background / Objectives : Restrictive Anorexia nervosa ( ANR ) is an eating disorder ( ED ) characterized by a low bone mineral content ( BMC ) and by an alteration in body composition ( reduction and abnormal distribution of fat mass — FM and lean mass — LM ) . The aim of our study was to address whether bone and body composition changes could be influenced by hormonal status and sport in female adolescents with restrictive anorexia nervosa-ANR.Subjects/ Methods : Prospect i ve study on 79 adolescents with ANR su bmi tted to Dual Energy X-Ray Absorptiometry — DXA at baseline-T0 and after 12 months-T12 . Among the 46/79—58.2 % patients that completed the study , we evaluated total and regional FM and LM% , as well as lumbar bone mineral density ( BMD ) and Z-score , linking them to clinical variables : menarche/amenorrhea/hormonal therapy and physical activity . Results : At T0 : body mass index ( BMI ) = 16.4±1.4 kg/m2 with low levels of FM% ( 21.7±5.7 ) low BMC in 12/46—26.0 % ( mean Z-score : −1.21±1.27 , with higher values related to physical activity — P=0.001 ) . At T12 : a significant increase in BMI —P=0.001 , with LM reduction and FM increase ( more evident in the trunk — P in FM distribution , more evident in trunk region ( potential and adjunctive risk factor for the relapse of the psychiatric condition ) . The complexity of these clinical findings suggested DXA , a low-dose and low-cost technique , in long-term monitoring of ANR patients", "BACKGROUND Anorexia nervosa is a disease of severe acquired undernutrition with a high and increasing prevalence among young women in the United States . OBJECTIVE The objective was to investigate the effects of spontaneous outpatient weight recovery and estrogen administration on fat distribution in patients with anorexia nervosa . DESIGN Twenty-seven amenorrheic women aged 26.6 + /- 1.2 y with anorexia nervosa were identified through an outpatient study of bone loss and were r and omly assigned to receive or not receive estrogen without any dietary intervention other than calcium and multivitamin supplements . Body composition was measured at baseline and at 6 and 9 mo and was compared with cross-sectional values obtained in 20 healthy , eumenorrheic , age-matched ( 25.4 + /- 0.5 y ) control subjects . RESULTS Twenty of the 27 patients with anorexia aged 27.0 + /- 1.3 y spontaneously gained weight ( 4.1 + /- 0.9 kg ) ; body mass index ( in kg/m(2 ) ) increased from 16.1 + /- 0.3 to 17.5 + /- 0.4 . Fat mass and lean mass accounted for 68 % and 32 % of the gain in total body mass , respectively . With spontaneous weight gain , there was a significant increase in the percentage of trunk fat from 32.4 + /- 1.3 % at baseline to 36.5 + /- 1.0 % at 9 mo ( P = 0.03 ) , which correlated with urinary free cortisol ( r = 0.66 , P = 0.003 ) . Estrogen treatment was not protective against the gain in trunk fat with spontaneous weight gain . CONCLUSIONS In women with anorexia nervosa , spontaneous weight gain is associated with a significant increase in trunk adiposity , and estrogen administration may not protect against the accumulation of central fat with weight gain", "BACKGROUND Recent clinical guidelines on the health risks of obesity use body mass index ( BMI ; calculated as weight in kilograms divided by the square of height in meters ) and waist circumference , but the waist-hip ratio may provide independent information . METHODS To assess the joint and relative associations of BMI , waist circumference , and waist-hip ratio with multiple disease end points , we conducted a prospect i ve cohort study of 31,702 Iowa women , aged 55 to 69 years and free of cancer , heart disease , and diabetes , assembled by r and om sampling and mail survey in 1986 . Study end points were total and cause-specific mortality and incidence of site-specific cancers and self-reported diabetes , hypertension , and hip fracture over 11 to 12 years . RESULTS The waist-hip ratio was the best anthropometric predictor of total mortality , with the multivariable-adjusted relative risk for quintile 5 vs 1 of 1.2 ( 95 % confidence interval , 1.1 - 1.4 ) , compared with 0.91 ( 95 % confidence interval , 0.8 - 1.0 ) for BMI and 1.1 ( 95 % confidence interval , 1.0 - 1 . 3 ) for waist circumference . The waist-hip ratio was also associated positively with mortality from coronary heart disease , other cardiovascular diseases , cancer , and other causes . The waist-hip ratio was associated less consistently than BMI or waist circumference with cancer incidence . All anthropometric indexes were associated with incidence of diabetes and hypertension . For example , women simultaneously in the highest quintiles of BMI and waist-hip ratio had a relative risk of diabetes of 29 ( 95 % confidence interval , 18 - 46 ) vs. women in the lowest combined quintiles . CONCLUSION The waist-hip ratio offers additional prognostic information beyond BMI and waist circumference", "BACKGROUND Although the effect of immediate weight restoration on body composition and body fat distribution has previously been studied in anorexia nervosa ( AN ) , its influence in women with AN on eating disorder psychopathology and psychological distress has not previously been investigated to our knowledge . OBJECTIVES We assessed body composition and fat mass distribution before and after body weight restoration and investigated any relation between changes in body fat patterns of patients with AN treated in a specialist inpatient unit and their eating disorder and psychological distress features . DESIGN Body composition was measured by using dual-energy X-ray absorptiometry in 50 female , adult patients with AN before and after complete weight restoration [ body mass index ( BMI ; in kg/m² ) ≥18.5 ] and 100 healthy control subjects matched by age and posttreatment BMI of study group participants . Eating disorder psychopathology and psychological distress were assessed in the AN group before and after weight restoration by using the Eating Disorder Examination interview and the Global Severity Index of the Brief Symptom Inventory ( BSI-GSI ) , respectively . RESULTS After the achievement of complete weight restoration , patients with AN had higher trunk ( P and roid ( P and gynoid ( P fat masses and lower arm ( P and leg ( P = 0.001 ) fat masses with respect to control subjects . No relation was shown between body-composition variables and eating disorder psychopathology in the AN group , and the only significant predictor of change in BSI-GSI was the baseline BSI-GSI score . CONCLUSION The normalization of body weight in patients with AN is associated with a preferential distribution of body fat in central regions , which does not , however , seem to influence either eating disorder psychopathology or psychological distress scores", "OBJECTIVE We aim ed to replicate and extend our previous findings of an association between percent body fat in recently weight-restored patients with Anorexia Nervosa ( AN ) and clinical outcome in the year following treatment . METHOD Twenty-two hospitalized , weight-restored women with AN underwent whole body MRI to determine percent adipose tissue . Following hospital discharge , patients were contacted regularly , and at the end of the year , clinical outcome was determined using modified Morgan-Russell ( MR ) criteria : full , good , fair or poor . Identical to our previous study , outcome was dichotomized into \" full , good or fair \" and \" poor \" groups . RESULTS Data from 21 subjects were available for analysis . Percent body fat was significantly lower in the poor outcome group ( 22 % ± 5 % ) compared to the \" full , good or fair \" outcome group ( 27 % ± 4%)(p 26 subjects on whom we had previously reported . Univariate analysis of variance ( ANOVA ) demonstrated a significant difference in percent adipose tissue across the four MR outcome groups ( F = 3.416 , df = 3 , p<0.03 ) . DISCUSSION Lower percent adipose tissue after short-term weight normalization is associated with poor clinical outcome in the year following inpatient treatment . These findings may be important in the assessment of risk for relapse in patients with AN", "OBJECTIVE The goal of this study was to investigate the relationship of body composition and neuroendocrine levels with clinical outcome in women with anorexia nervosa in a relapse-prevention trial . METHOD Body composition and fasting cortisol and leptin levels were assessed before r and om assignment in 32 weight-recovered subjects with anorexia nervosa from the New York site of the Fluoxetine to Prevent Relapse in Women With Anorexia Nervosa trial . Clinical outcome at the end of study participation was defined using modified Morgan-Russell criteria ( full , good , fair , poor ) , then dichotomized into treatment \" success \" or \" failure . \" RESULTS In a binary logistic regression model examining the effect of percent body fat , body mass index , anorexia nervosa subtype , waist-to-hip ratio , and serum cortisol and leptin levels on treatment outcome , only percent body fat was significantly associated with outcome . CONCLUSIONS In recently weight-restored women with anorexia nervosa , lower percent body fat was associated with poor long-term outcome" ]

[ "BACKGROUND Low birth weight infants have been noted to have low zinc concentrations in cord blood , and zinc deficiency in childhood is associated with reduced immunocompetence and increased infectious disease morbidity . This study investigates whether zinc supplementation of infants born full term and small for gestational age affects mortality . METHODS A r and omized , double-blind , controlled trial with 2-by-2 factorial design enrolled 1154 full-term small for gestational age infants to receive in syrup 1 of the following : riboflavin ; riboflavin and zinc ( 5 mg as sulfate ) ; riboflavin , calcium , phosphorus , folate , and iron ; or riboflavin , zinc , calcium , phosphorus , folate , and iron . A fixed dosage of 5 mL per child was given daily from 30 to 284 days of age . Household visits were made 6 days per week to provide the syrup and conduct surveillance for illness and death . When a child 's death was reported , parental reports and medical records were used to ascertain the cause . The effects of zinc and of the combination of iron , folate , calcium , and phosphorus were analyzed by intent to treat . The mortality analysis was performed using a survival analytic approach that models time until death as the dependent variable ; all models had 2 terms as independent variables : 1 for the zinc effect and 1 for the vitamin and mineral ( calcium and phosphorus , folate and iron ) effect . RESULTS Zinc supplementation was associated with significantly lower mortality , with a rate ratio of 0.32 ( 95 % confidence interval : 0.12 - 0.89 ) . Calcium , phosphorus , folate , and iron supplementation was not associated with a mortality reduction , although a statistically nonsignificant trend toward reduction was observed with a rate ratio of 0.88 ( 95 % confidence interval : 0.36 - 2.15 ) . CONCLUSIONS Zinc supplementation in small for gestational age infants can result in a substantial reduction in infectious disease mortality", "Objective : To test whether zinc supplementation reduces the deficits in mental development and behaviour that are found in term infants of low birth weight in the study population . Design : A prospect i ve double-blind , part-r and omised efficacy trial . Setting : A low-income population in Pernambuco , northeast Brazil , where the economy is largely dependent on sugar-cane production , and where over 90 % of deliveries occur in health facilities . Subjects : During a 20-month period , all singleton , term infants weighing 1500–2499 g born to families of low income ( birth ( n=205 ) . At 6 and 12-months , the numbers tested were 163 and 138 respectively . Intervention : Infants born from January 1993–January 1994 were r and omly assigned to receive daily , except Sundays , a placebo ( n=66 ) or 1 mg zinc ( n=68 ) . Those born February – August 1994 were given 5 mg zinc ( n=71 ) . Supplementation was for eight weeks , starting at birth . Field workers visited each infant at home to administer the supplement . Results : At 6 and 12-months , mental and psychomotor development was assessed with the Bayley Scales of Infant Development and no significant differences in the scores of the three groups were found . At 12-months , behaviour was also assessed on 5 ratings . Ratings were highest in infants given 5 mg zinc ( P=0.042 ) . Conclusions : Zinc supplementation ( 5 mg/d ) for eight weeks may reverse some of the poor behaviours , particularly responsiveness , exhibited by low birth weight infants . No amelioration of their mental and psychomotor deficits was found . Sponsorship : The Wellcome Trust , United Kingdom , provided financial support ( Grant no. 036605/Z/92 ) . Dr Lira was supported by CAPES ( Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ) , Brazil", "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", "BACKGROUND Undernourished children have poor levels of development that benefit from stimulation . Zinc deficiency is prevalent in undernourished children and may contribute to their poor development . OBJECTIVE We assessed the effects of zinc supplementation and psychosocial stimulation given together or separately on the psychomotor development of undernourished children . DESIGN This was a r and omized controlled trial with 4 groups : stimulation alone , zinc supplementation alone , both interventions , and control ( routine care only ) . Subjects were 114 children aged 9 - 30 mo and below -1.5 z scores of the National Center for Health Statistics weight-for-age references who were recruited from 18 health clinics . Clinics were r and omly assigned to receive stimulation or not ; individual children were r and omly assigned to receive zinc or placebo . The stimulation program comprised weekly home visits during which play was demonstrated and maternal-child interactions were encouraged . The supplementation was 10 mg Zn as sulfate daily or placebo . Development ( assessed by use of the Griffiths Mental Development Scales ) , length , and weight were measured at baseline and 6 mo later . Weekly morbidity histories were taken . RESULTS Significant interactions were found between zinc supplementation and stimulation . Zinc benefited the developmental quotient only in children who received stimulation , and benefits from zinc to h and and eye coordination were greater in stimulated children . Zinc supplementation alone improved h and and eye coordination , and stimulation alone benefited the developmental quotient , hearing and speech , and performance . Zinc supplementation also reduced diarrheal morbidity but did not significantly improve growth . CONCLUSION Zinc supplementation benefits development in undernourished children , and the benefits are enhanced if stimulation is also provided", "BACKGROUND Iron and zinc deficiency are prevalent during infancy in low-income countries . OBJECTIVES The objectives were to examine whether a weekly supplement of iron , zinc , iron+zinc , or a micronutrient mix ( MM ) of 16 vitamins and minerals would alter infant development and behavior . DESIGN The participants were 221 infants from rural Bangladesh at risk of micronutrient deficiencies . Development and behavior were evaluated at 6 and 12 mo of age by using the Bayley Scales of Infant Development II and the Home Observation Measurement of Environment ( HOME ) scale . In this double-blind trial , the infants were r and omly assigned to 1 of 5 treatment conditions : iron ( 20 mg ) , zinc ( 20 mg ) , iron+zinc , MM ( 16 vitamins and minerals , including iron and zinc ) , or riboflavin weekly from 6 to 12 mo . Multivariate analyses were conducted to examine the change in development and behavior for each supplementation group , with control for maternal education , HOME score , months breastfed , anemia , growth at 6 mo , and change in growth from 6 to 12 mo . RESULTS Iron and zinc administered together and with other micronutrients had a beneficial effect on infant motor development . Iron and zinc administered individually and in combination had a beneficial effect on orientation-engagement . Two-thirds of the infants were mildly anemic , no treatment effects on hemoglobin concentration were observed , and hemoglobin was not associated with measures of development or behavior . CONCLUSION The beneficial effects of weekly iron and zinc supplementation on motor development and orientation-engagement suggest that infants benefit from these minerals when administered together", "Zinc deficiency has been associated with growth deficits , reduced dietary intake and appetite , and has been hypothesized to result in reduced activity . This r and omized , double-blind , placebo-controlled study examined whether 10 mg of oral zinc as zinc sulfate , given daily for up to 7 mo , affected activity patterns of 85 Guatemalan infants recruited at 6 - 9 mo of age . Infant activity was assessed by time sampling-observation method at 10-min intervals during a 12-h data collection period , at base line , 3 and 7 mo follow-up . Motor development and the percentage of time infants were observed in various positions ( being carried , lying down , sitting , crawling , st and ing or walking ) and engaged in various activities ( eating , sleeping , resting , crying/whining or playing ) were compared by treatment group . No differences in motor development were observed by treatment group . However , at follow-up 2 ( after 7 mo of supplementation ) , zinc-supplemented infants were significantly more frequently observed sitting up compared with lying down , and were playing during 4.18 + /- 1.95 % ( P crying or whining ( P activity patterns associated with zinc supplementation in this setting", "BACKGROUND It has been documented that growth patterns differ between breastfed and formula-fed infants . Some investigators have suggested that these differences may be related to differences in zinc nutriture . OBJECTIVE The objective of this study was to examine the effect of zinc supplementation on growth , morbidity , and motor development in healthy , term , breastfed infants . DESIGN We conducted a r and omized double-blind intervention comparing zinc supplementation ( 5 mg/d as zinc sulfate ) with placebo in breastfed infants aged 4 - 10 mo . Growth and indexes of body composition and gross motor development were measured monthly from 3 to 10 mo . Morbidity data were collected weekly . RESULTS Eighty-five infants were enrolled , and 70 completed the study . The baseline characteristics , attained weight or length at 10 mo , growth velocity , gross motor development , and morbidity did not differ significantly between groups , even after control for potentially confounding variables . CONCLUSIONS The dietary zinc intake of these breastfed infants appeared to be adequate , given that zinc supplementation did not affect growth , development , or risk of infection ( although sample size for detection of differences in development or infection was limited ) . Previously described differences in growth between breastfed and formula-fed infants in such population s do not appear to be due to differences in zinc nutriture", "Changes in growth , body composition , and zinc indexes were evaluated after 25 wk in a double-blind zinc-supplementation study of 162 periurban Guatemalan children aged 81.5 + /- 7.0 mo ( mean + /- SD ) . Children receiving the zinc supplement ( 10 mg Zn/d as amino acid chelate ) for 90.1 + /- 9.2 d had higher mean fasting plasma zinc ( 16.2 + /- 2.9 vs 14.9 + /- 2.1 mumol/L , P median triceps skinfold Z score ( 0.50 vs 0.38 , P median midarm circumference ( MAC ) Z score ( -0.03 vs -0.20 , P hair zinc classified as 1.68 mumol/g was the only laboratory variable that explained some of the variance in final Z scores of midarm-muscle area ( P MAC ( P zinc supplement with changes in indexes of body composition rather than growth", "Iron and zinc deficiencies have been associated with delayed motor development in nutritionally at-risk children , albeit inconsistently . In this community-based , r and omized double-blind trial , iron+folic acid ( FeFA ) ( 12.5 mg Fe + 50 mug folic acid ) , zinc ( Zn ) ( 10 mg ) , and iron+folic acid+zinc ( FeFA+Zn ) supplements or a placebo were given daily for 1 y to nutritionally at-risk children in Pemba , Zanzibar . The effects of these treatments on attaining unassisted walking were evaluated using survival analysis for 354 children aged 5 - 11 mo at the start of supplementation . Treatment effects on changes in hemoglobin ( Hb ) and zinc protoporphyrin ( ZPP ) and height-for-age ( HAZ ) and weight-for-age ( WAZ ) Z scores were evaluated using linear regression . Attained motor milestone was recorded every 2 wk for 1 y. Hb , ZPP , HAZ , and WAZ were measured at baseline and after 6 mo of treatment . FeFA with or without Zn reduced the time it took for children to walk assisted . Children who received any iron walked unassisted sooner than those who received no iron [ median difference approximately 15 d , P = 0.035 , risk ratio ( RR ) = 1.28 , 95 % CI = 1.02 , 1.61 ] and this effect was stronger in those who had iron deficiency anemia ( IDA ) at baseline ( median difference was approximately 30 d ; P = 0.002 ; RR = 1.68 ; 95 % CI = 1.21 , 2.32 ) . FeFA alone and Zn alone improved Hb and ZPP compared with placebo . There were no significant treatment effects on changes in HAZ or WAZ . The effects of treatment on time to walking may have been mediated by improvements in iron status or hemoglobin , but were not mediated through improvements in growth", "Iron deficiency is prevalent in children and infants worldwide . Zinc deficiency may be prevalent , but data are lacking . Both iron and zinc deficiency negatively affect growth and psychomotor development . Combined iron and zinc supplementation might be beneficial , but the potential interactions need to be verified . In a r and omized , placebo-controlled trial using 2 x 2 factorial design , 609 Thai infants aged 4 - 6 mo were supplemented daily with 10 mg of iron and /or 10 mg of zinc for 6 mo to investigate effects and interactions on micronutrient status and growth . Iron supplementation alone increased hemoglobin and ferritin concentrations more than iron and zinc combined . Anemia prevalence was significantly lower in infants receiving only iron than in infants receiving iron and zinc combined . Baseline iron deficiency was very low , and iron deficiency anemia was almost nil . After supplementation , prevalence of iron deficiency and iron deficiency anemia were significantly higher in infants receiving placebo and zinc than in those receiving iron or iron and zinc . Serum zinc was higher in infants receiving zinc ( 16.7 + /- 5.2 micromol/L ) , iron and zinc ( 12.1 + /- 3.8 micromol/L ) or iron alone ( 11.5 + /- 2.5 micromol/L ) than in the placebo group ( 9.8 + /- 1.9 micromol/L ) . Iron and zinc interacted to affect iron and zinc status , but not hemoglobin . Iron supplementation had a small but significant effect on ponderal growth , whereas zinc supplementation did not . To conclude , in Thai infants , iron supplementation improved hemoglobin , iron status , and ponderal growth , whereas zinc supplementation improved zinc status . Overall , for infants , combined iron and zinc supplementation is preferable to iron or zinc supplementation alone", "BACKGROUND Deficiencies of iron and zinc are associated with delayed development , growth faltering , and increased infectious-disease morbidity during infancy and childhood . Combined iron and zinc supplementation may therefore be a logical preventive strategy . OBJECTIVE The objective of the study was to compare the effects of combined iron and zinc supplementation in infancy with the effects of iron and zinc as single micronutrients on growth , psychomotor development , and incidence of infectious disease . DESIGN Indonesian infants ( n = 680 ) were r and omly assigned to daily supplementation with 10 mg Fe ( Fe group ) , 10 mg Zn ( Zn group ) , 10 mg Fe and 10 mg Zn ( Fe+Zn group ) , or placebo from 6 to 12 mo of age . Anthropometric indexes , developmental indexes ( Bayley Scales of Infant Development ; BSID ) , and morbidity were recorded . RESULTS At 12 mo , two-factor analysis of variance showed a significant interaction between iron and zinc for weight-for-age z score , knee-heel length , and BSID psychomotor development . Weight-for-age z score was higher in the Zn group than in the placebo and Fe+Zn groups , knee-heel length was higher in the Zn and Fe groups than in the placebo group , and the BSID psychomotor development index was higher in the Fe group than in the placebo group . No significant effect on morbidity was found . CONCLUSIONS Single supplementation with zinc significantly improved growth , and single supplementation with iron significantly improved growth and psychomotor development , but combined supplementation with iron and zinc had no significant effect on growth or development . Combined , simultaneous supplementation with iron and zinc to infants can not be routinely recommended at the iron-to-zinc ratio used in this study", "BACKGROUND Zinc deficiency is thought to be common in young children in developing countries and some data suggest that it may detrimentally affect children 's development . OBJECTIVE Our goal was to assess the effect of zinc supplementation on the developmental levels and behavior of Bangladeshi infants . DESIGN This was a r and omized , double-blind , controlled trial conducted in Dhaka , Bangladesh . Three hundred one infants aged 1 mo were r and omly assigned to receive either 5 mg elemental Zn or placebo daily for 5 mo , and subsequent growth and morbidity were observed . For the present study , developmental levels were assessed in a sub sample of 212 infants at 7 and 13 mo of age with use of the Bayley Scales of Infant Development , and the infants ' behavior during the tests was observed . The children 's social background s , weights , and lengths were also recorded . RESULTS The children 's nutritional status was generally poor . The zinc-treated group had slightly lower scores on the mental development index of the Bayley Scales than did the placebo group ( beta = 3.7 , SE = 1.3 , P mental development index scores of the zinc-treated group were slightly but significantly lower than those of the placebo group . This finding may have been due to micronutrient imbalance . Caution should be exercised when supplementing undernourished infants with a single micronutrient", "BACKGROUND Rates of mental illness in children are increasing throughout the world . Observational studies of depression , anxiety , and attention-deficit hyperactivity disorder suggest that zinc is an alternative treatment . OBJECTIVE We examined the effect of zinc supplementation on the mental health of school-age children in Guatemala . DESIGN From January to October 2006 , we conducted a 6-mo r and omized , double-blind , controlled trial comparing zinc supplementation ( 10 mg ZnO/d for 5 d/wk ) with a placebo ( 10 mg glucose ) in 674 Guatemalan children in grade s 1 - 4 . Outcome measures included internalizing ( ie , depression and anxiety ) and externalizing ( ie , hyperactivity and conduct disorder ) problem behaviors , positive behaviors ( ie , socialization and leadership ) , and serum zinc concentrations . RESULTS Zinc and placebo groups did not differ significantly in any behavioral measures at baseline or at follow-up . At baseline , 21.4 % of children had serum zinc concentrations zinc concentrations were higher in the zinc group . Increases in serum zinc concentrations were inversely associated with decreases in depressive symptoms ( estimate : -0.01 points per μg Zn/dL ; P = 0.01 ) , anxiety ( estimate : -0.012 points per μg Zn/dL ; P = 0.02 ) , internalizing symptoms ( estimate : -0.021 points per μg Zn/dL ; P = 0.02 ) , and social skills ( estimate : -0.019 points per μg Zn/dL ; P = 0.01 ) in adjusted models that were controlled for child age , sex , socioeconomic status , household , and treatment group . CONCLUSIONS Six months of zinc supplementation did not induce differences in mental health outcomes between zinc and placebo groups . However , increases in serum zinc concentrations were associated with decreases in internalizing symptoms ( ie , depression and anxiety ) in a community-based sample of children at risk of zinc deficiency . This trial was registered at clinical trials.gov as NCT00283660", "Objective : To test the efficacy of zinc supplementation through diet or ayurvedic zinc tablet on cognitive function and taste acuity in adolescent girls . Methods : Using zinc-rich food items , snacks were prepared by adopting food-processing methods that enhance zinc bioavailability . Ayurvedic zinc tablet ( jasad bhasma ) was chosen as a natural elemental zinc supplement . Efficacy of snacks and the tablet was assessed in 180 schoolgirls ( 12.5 ± 0.85 years ) from Pune City , India , who were r and omly allocated to any of the 3 groups : ( 1 ) ayurvedic zinc tablet — J , ( 2 ) zinc-rich snacks — D , or ( 3 ) Control — C. Supplementation was given on every school day ( 6 days/wk ) for 10 weeks . All measurements were recorded at baseline and at the end of the study period . Food intake was recorded by 24-hour diet recall on 3 r and om days . Hemoglobin , serum ferritin , and plasma zinc were estimated on a fasting blood sample . Cognitive assessment was done on each participant using tests for simple reaction time ( SRT ) , recognition reaction time ( RRT ) , visual memory , and Raven 's Progressive Matrices ( RPM ) . Taste acuity was determined by recognition thresholds for salt ( RTS ) over a range of 10 different salt concentrations . Results : A higher increase in plasma zinc ( 61.3 % ) was observed in the J group than in the D group ( 9.9 % ) ( p ) , whereas plasma zinc declined in the control group ( −2.2 % ) over baseline ( p > 0.1 ) . Hemoglobin showed no change in all 3 groups ( p > 0.1 ) . Percent increment in scores for memory and RPM was significantly more in the D and J groups ( 24.5%–29.6 % ) than in the C group ( 6.5 % ) ( p 0.05 ) . Mean SRT and RRT were reduced more in the D and J groups ( 5%–16 % ) than in the C group ( 1.6 % ) ( p significant fall in median RTS from 5 to 2.5 mmol/L was noted after both diet and zinc supplementation ( p performance and the recognition threshold for salt of adolescent girls", "The knowledge that zinc is essential for growth and neuropsychologic performance and a report of zinc-responsive stunting in Chinese children prompted this project . This article summarizes findings from a 10-wk , double-blind , controlled trial of zinc repletion in 740 urban , 6 - 9-y-old first grade rs from low-income families in Chongqing , Qingdao , and Shanghai , People 's Republic of China . Treatments were 20 mg Zn alone ( Z ) , 20 mg Zn with micronutrients ( ZM ) , and micronutrients alone ( M ) . The M mixture was based on National Research Council guidelines . Nutrients that might interfere with zinc retention were excluded or given in lower amounts . Main outcomes were changes in neuropsychologic performance and knee height . Hemoglobin , serum ferritin , plasma and hair zinc , and whole blood and hair lead were also measured . Anemia was not common , and serum ferritin concentrations were usually within the range of normal . Mean baseline plasma zinc concentrations were marginal in children from Chongqing and Qingdao and normal in children from Shanghai . After treatment with ZM or M plasma zinc increased . Hair zinc tended to decrease after all treatments . Mean baseline whole blood lead concentrations were slightly below the limit considered excessive for children by the US Centers for Disease Control and Prevention . Neuropsychologic performance and growth were most improved after treatment with ZM . These findings were consistent with the presence of zinc and other micronutrient deficiencies", "Although the trace element boron has yet to be recognized as an essential nutrient for humans , recent data from animal and human studies suggest that boron may be important for mineral metabolism and membrane function . To investigate further the functional role of boron , brain electrophysiology and cognitive performance were assessed in response to dietary manipulation of boron ( approximately 0.25 versus approximately 3.25 mg boron/2000 kcal/day ) in three studies with healthy older men and women . Within-subject design s were used to assess functional responses in all studies . Spectral analysis of electroencephalographic data showed effects of dietary boron in two of the three studies . When the low boron intake was compared to the high intake , there was a significant ( p proportion of low-frequency activity , and a decrease in the proportion of higher-frequency activity , an effect often observed in response to general malnutrition and heavy metal toxicity . Performance ( e.g. , response time ) on various cognitive and psychomotor tasks also showed an effect of dietary boron . When contrasted with the high boron intake , low dietary boron result ed in significantly poorer performance ( p manual dexterity ( studies II and III ) ; eye-h and coordination ( study II ) ; attention ( all studies ) ; perception ( study III ) ; encoding and short-term memory ( all studies ) ; and long-term memory ( study I ) . Collectively , the data from these three studies indicate that boron may play a role in human brain function and cognitive performance , and provide additional evidence that boron is an essential nutrient for humans", "OBJECTIVE To evaluate the effect of zinc supplementation on growth and development during infancy . DESIGN We r and omized 150 term neonates of low socioeconomic status to receive supplemental zinc 5 mg/d ( SG ) or a lactose placebo ( PG ) ; 112 completed a 1-year follow-up . All were breast-fed and given cow milk formula after weaning ; solid foods and iron were added at 5 months . Anthropometry measured monthly , psychomotor development ( PDI ) , mental development ( MDI ) , and behavior including motor quality factor were assessed by Bayley Scales at 6 and 12 months . The groups were comparable in maternal characteristics , birth weight , home environment , and mother-infant interaction . RESULTS No effects of zinc on weight , length , and weight for length at 12 months were found controlling for sex and breast-feeding . The mean PDI ( SG : 84.5 + /- 11.5 vs PG : 87.6 + /- 9.9 ) and MDI ( 90.9 + /- 10.5 vs 88.9 + /- 9.1 ) were similar ; however , 46 of 52 infants in the PG scored MDI vs 42 of 57 in the SG ( P low in motor quality factor at 6 months compared with the PG , 8 of 52 ( P = .02 ) . The mean at 12 months for the SG was 31.9 + /- 2.8 and for the PG 30.8 + /- 2.9 ( P mental development and motor quality behavior of healthy term infants", "A community-based , cluster-r and omized , placebo-controlled trial of daily zinc and /or iron+folic acid supplementation was conducted in rural southern Nepal to examine motor milestone attainment among 3264 children 1 - 36 mo of age between 2001 and 2006 . Treatment groups included placebo , zinc ( 10 mg ) , iron+folic acid ( 12.5 mg iron + 50 microg folic acid ) , and zinc+iron+folic acid ( 10 mg zinc + 12.5 mg iron + 50 microg folic acid ) . Infants received half of these doses . The iron arms were stopped November 2003 by recommendation of the Data Safety and Monitoring Board ; zinc and placebo continued until January 2006 . A total of 2457 children had not walked at the time of entry into the trial and 1775 were followed through 36 mo . Mean age at first walking unassisted did not differ among groups and was 444 + /- 81 d ( mean + /- SD ) in the placebo group , 444 + /- 81 d in the zinc group , 464 + /- 85 d in the iron+folic acid group , and 446 + /- 87 d in the iron+folic acid+zinc group . Results were similar after adjustment for age at enrollment , asset ownership , maternal literacy , and prior child deaths in the household and in children who consumed at least 60 tablets . Compared with placebo , iron+folic acid was associated with an adjusted mean delay of 28.0 d ( 95 % CI : 11.3 , 44.7 ) in time to walking among infants and the delay was more pronounced with mid-upper arm circumference ( MUAC ) iron+folic acid supplementation of infants beyond improved hematologic status deserve further consideration", "Inadequate zinc intake may lead to poor growth and developmental outcome in very-low-birth-weight ( VLBW ; were r and omly allocated to two groups . SUPP infants received a regular term formula plus zinc supplements ( 4.4 mg/L ; final content , 11 mg/L ) ; PLAC infants received the same formula plus placebo ( final content , 6.7 mg/L ) . Infants started their formula at 1,853 + /- 109 g and consumed the formula for 6 months . All subjects were evaluated at 3 , 6 , 9 , and 12 + /- 0.75 months corrected-for-gestational-age . At each evaluation , weight , length , and head circumference were measured , a Griffiths developmental assessment was performed , and a blood sample was taken . Higher plasma zinc levels ( p linear growth velocity was found in the SUPP group over the study period for the whole group as well as for girls alone . Maximum motor development scores were higher ( p = 0.018 ) in the SUPP ( 98 + /- 10 ) than the PLAC ( 90 + /- 8) group , indicating that increased zinc intake in early infancy may be beneficial to VLBW infants", "OBJECTIVE . Lead exposure in children has been associated with both global and specific cognitive deficits . Although chelation therapy is advised for children with blood lead concentrations of > 44 μg/dL , treatment options for children with lower blood lead values are limited . Because lead absorption is related to children 's nutritional status , micronutrient supplements may be 1 strategy for combating low-level , chronic lead exposure . This study was design ed to test the efficacy of iron and zinc supplementation for lowering blood lead concentrations and improving cognitive performance in schoolchildren who live in a lead-contaminated city . METHODS . This r and omized , double-blind , placebo-controlled field trial was conducted in public elementary schools in Torreón , an industrialized city in northern Mexico . A metal foundry , located close to the city center and within 3.5 km of 9 schools , was the main source of lead exposure . A total of 602 children who were aged 6 to 8 years and regularly attending first grade in the study schools were enrolled . Children were given 30 mg of iron , 30 mg of zinc , both , or a placebo daily for 6 months . A total of 527 completed the treatment , and 515 were available for long-term follow-up , after another 6 months without supplementation . Eleven cognitive tests of memory , attention , visual-spatial abilities , and learning were administered at baseline and each follow-up . RESULTS . There were no consistent or lasting differences in cognitive performance among treatment groups . CONCLUSIONS . Daily supplementation with iron and /or zinc may be of limited usefulness for improving cognition in lead-exposed schoolchildren . However , these treatments may be effective in setting s with higher prevalence of nutritional deficiencies or in younger children", "OBJECTIVE To determine the efficacy of iron and zinc supplementation on behavior ratings of lead-exposed children . STUDY DESIGN In this double-blind , r and omized trial , 602 first- grade children received 30 mg ferrous fumarate , 30 mg zinc oxide , both , or placebo daily for 6 months . Lead , iron , and zinc status were determined at baseline and follow-up . Parents and teachers provided ratings of child behavior using the Conners Rating Scales . RESULTS The baseline mean ( SD ) blood lead concentration was 11.5 ( 6.1 ) mug/dL , with 51 % of children > or = 10 microg/dL. The prevalence of attention deficit hyperactivity disorder , estimated by combined parent and teacher ratings , was 6 % . At follow-up , parent ratings of oppositional , hyperactive , cognitive problems , and attention deficit hyperactivity disorder decreased by 1.5 , 1.2 , 2.5 , and 3.4 points , respectively ( P Teacher ratings of hyperactivity increased by 1.1 points ( P = .008 ) , and the mean cognitive problem score declined by 0.7 points ( P = .038 ) . There were no treatment effects on mean change in scores , but children receiving any zinc had a higher likelihood of no longer receiving clinical ly-significant teacher ratings of oppositional behaviors . CONCLUSIONS This regimen of supplementation did not result in consistent improvements in ratings of behavior in lead-exposed children over 6 months", "OBJECTIVES To investigate whether supplementation of zinc in preschool children is associated with improvement in observed activity levels . METHODS On 2 consecutive days , we performed 5-hour observations with momentary time sampling ( instant activity every 10 minutes ) in children selected from an ongoing double-blind , r and omized trial of zinc supplementation . The study was conducted in Kalkaji , a low-socioeconomic urban population of New Delhi with high diarrheal incidence and rates of malnutrition . A total of 93 children ( 48 zinc and 45 control ) 12 to 23 months of age from an ongoing community-based , r and omized , controlled trial received supplements for at least 1 month before study ; 71 % had received supplementation for more than 120 days . Zinc gluconate ( 10 mg of elemental zinc ) was given daily , with both zinc and control groups receiving vitamins A , B1 , B2 , B6 , D3 , and E and niacinamide in addition . RESULTS Outcomes were percentages of time spent in each of five activity levels and two groups representing high and low movement and overall rating by two activity scores . Children in the zinc group spent 72 % more time performing activities in the high-movement group . Among the zinc-supplemented children , the activity rating by the children 's activity rating score was 12 % higher and by the energy expenditure score was 8.3 % higher than in the control group . CONCLUSIONS In conclusion , zinc supplementation , given along with selected vitamins , was associated with significantly greater activity levels in children . The relationship between the activity increase and locomotor development needs to be investigated , as do the long-term implication s of zinc supplementation in terms of developmental status and school performance", "OBJECTIVE Zinc is essential for growth and cognition of experimental animals . Past research found zinc repletion improved growth of stunted Chinese children . Therefore we measured effects of zinc repletion on growth and neuropsychological functions of children . DESIGN Double-blind r and omized controlled treatment trial . SETTING Elementary schools in low income districts of Chongqing , Qingdao and Shanghai . SUBJECTS Three hundred-seventy-two 6 to 9 year old first grade rs . INTERVENTIONS Treatments were 20 mg zinc , 20 mg zinc with micronutrients , or micronutrients alone . The micronutrient mixture was based on guidelines of the US NAS/NRC . Treatments were assigned to classrooms of 40 or more children each , and administered by teachers 6 days per week for 10 weeks . MEASURES OF OUTCOME Changes in knee height and neuropsychological functions . RESULTS Zinc alone had the least effect on growth while zinc with micronutrients had the largest effect ; micronutrients alone had an intermediate effect . Zinc-containing treatments improved neuropsychological functions , but micronutrients alone had little effect . CONCLUSIONS The findings confirm the essentiality of zinc for growth of children , and show , for the first time , the essentiality of zinc for neuropsychological functions of children . In addition , the need for repletion of other potentially limiting nutrients in studies examining the effects of specific nutrients on growth and neuropsychological functions was confirmed", "OBJECTIVE To evaluate the effect of zinc supplementation on mental and psychomotor scores in children aged 12 to 18 months . STUDY DESIGN In this double-blind , r and omized , placebo-controlled trial , children aged 6 to 30 months received daily elemental zinc ( 10 mg for infants and 20 mg for others ) or placebo for 4 months . Bayley Scales of Infant Development II were used for development assessment in the 12- to 18-month subgroup at enrollment and the end of the study . RESULTS At the end of the study , the adjusted mean mental ( P = .36 ) and psychomotor ( P = .28 ) index scores were similar in the intervention and control groups . In a multivariate model , the baseline mental development index score was positively associated with the mother 's schooling , the child 's height for age , packed cell volumes , hospital birth , and attendance at a day care center , and was negatively associated with the child 's age . Breastfeeding , the child 's weight for height , and packed cell volumes were positively associated with the baseline psychomotor index score . CONCLUSION Zinc supplementation did not affect the mental or psychomotor development index scores in a setting in which zinc deficiency is common", "OBJECTIVE Infants who are born small for gestational age ( SGA ) are at risk for developmental delays , which may be related to deficiencies in zinc , an essential trace metal , or to deficiencies in their ability to elicit caregiver responsiveness ( functional isolation hypothesis ) . The objective of this study was to evaluate at 6 and 10 months of age the impact of a 9-month supplementation trial of 5 mg of zinc on the development and behavior of infants who were born SGA and to evaluate infants ' ability to elicit responsive caregiver behavior . METHODS A r and omized , controlled trial of zinc supplementation was conducted among 200 infants in a low-income , urban community in Delhi , India . Infants were recruited when they were full term ( > 36 weeks ) and SGA ( birth weight were r and omized to receive daily supplements of a micronutrient mix ( folate , iron , calcium , phosphorus , and riboflavin ) with or without 5 mg of zinc sulfate . The supplement was administered by field workers daily from 30 days to 9 months of age . At 6 and 10 months , infant development and behavior were measured in a clinical setting using the Bayley Scales of Infant Development II . Caregiver responsiveness , observed on an Indian version of the Home Observation for Measurement of the Environment scale , was measured during a home visit at 10 months . During both the clinic and home visits , caregivers reported on their infant 's temperament . RESULTS There were no direct effects of zinc supplementation on the infants ' development or behavior at either 6 or 10 months . In a subgroup analysis among the zinc-supplemented infants , lower birth weight infants were perceived to be more temperamentally difficult than higher weight infants ; in the control group , birth weight was not associated with temperament . Heavier birth weight infants had better scores on all measures of development and behavior at 6 months and on changes in mental and motor development from 6 to 10 months , compared with lighter birth weight infants . Boys had better weight gain and higher scores on mental development and emotional regulation than girls . Infants who were from families of higher socioeconomic status ( indexed by parental education , house size , and home ownership ) had higher scores on mental development and orientation/engagement ( exploratory behavior ) than infants who were from families of lower socioeconomic status . In keeping with the functional isolation hypothesis , caregiver responsiveness was associated with infant irritability , controlling for socioeconomic status , gender , birth weight , and weight gain . Responsive mothers were more likely to perceive their infants to be temperamentally easy than less responsive mothers . CONCLUSION Possible explanations for the lack of effects of zinc supplementation on infant development and behavior include 1 ) subtle effects of zinc supplementation that may not have been detected by the Bayley Scales , 2 ) interference with other nutritional deficiencies , or 3 ) no impact of zinc deficiency on infants ' development and behavior . The link between birth weight and irritability among infants in the zinc supplementation group suggests that the response to zinc supplementation may differ by birth weight , with irritability occurring among the most vulnerable infants . Longer term follow-up studies among zinc-supplemented infants are needed to examine whether early supplementation leads to developmental or behavioral changes that have an impact on school-age performance . The relationship between infant irritability and low maternal responsiveness lends support to the functional isolation hypothesis and the importance of asking caregivers about infant temperament", "OBJECTIVE Our objective was to examine whether improvement in maternal zinc status during pregnancy is positively associated with fetal neurobehavioral development in a Peruvian population . STUDY DESIGN We electronically monitored , at 32 and 36 weeks ' gestation , 55 fetuses whose mothers were r and omly assigned to receive , during pregnancy , a daily supplement containing 60 mg iron and 250 microg folate , with or without 15 mg zinc . Fetal heart rate and movement patterns were quantified in 55 and 34 fetuses , respectively , as indexes of neurobehavioral development . RESULTS Fetuses of mothers who received zinc supplementation showed fewer episodes of minimal fetal heart rate variability , increased fetal heart rate range , an increased number of accelerations , an increased number of movement bouts , an increased amount of time spent moving , and an increased number of large movements . Differences by supplementation type increased with gestational age and were statistically significant at 36 weeks ' gestation ( P < .05 ) . CONCLUSION Improving maternal zinc status through prenatal supplementation may improve fetal neurobehavioral development", "The relation of zinc ( Zn ) nutriture to brain development and function has been eluci date d. The purpose of this study is to examine whether Zn supplementation improves mood states in young women . The study used a double-blind , r and omized and placebo-controlled procedure . The major outcomes were psychological measures , somatic symptoms and serum Zn . Thirty women were placed r and omly and in equal numbers into two groups , and they ingested one capsule containing multivitamins ( MVs ) or MV and 7 mg Zn daily for 10 weeks . Women who took MV and Zn showed a significant reduction in anger – hostility score ( P=0.009 ) and depression – dejection score ( P=0.011 ) in the Profile of Moods State ( POMS ) and a significant increase in serum Zn concentration ( P=0.008 ) , whereas women who took only MV did not . Our results suggest that Zn supplementation may be effective in reducing anger and depression", "BACKGROUND Iron and zinc are important micronutrients for child growth and development . One would expect that iron and zinc supplementation in infancy would affect long-term cognitive development and school achievement , but this has not been evaluated . OBJECTIVE We investigated the effect of iron or zinc supplementation or both during infancy on cognitive performance 8 y later . DESIGN A follow-up study was performed in 560 children aged 9 y or 92 % of those who had participated in a r and omized controlled trial involving 4 groups who received daily iron , zinc , iron plus zinc , or a placebo at 4 - 6 mo of age for 6 mo . Cognitive performance was assessed by using the Wechsler Intelligence Scale for Children-Third Edition ( Thai version ) , the Raven 's Colored Progressive Matrices ( CPM ) , and school performance tests . General linear mixed models were used to assess long-term effects . RESULTS No significant differences in any of the outcomes at 9 y of age were observed at follow-up between the 4 groups . Mean intelligence quotients ranged across groups from 92.9 to 93.7 for full scale , 93.9 - 95.4 for verbal , and 93.1 - 94.0 for performance . The Raven 's CPM score ranged from 21.4 to 22.4 . CONCLUSION Supplementation with iron or zinc or both during infancy does not lead to long-term cognitive improvement in 9-y-old children . This trial was registered at clinical trials.gov as NCT00824304", "Adolescents with anorexia nervosa were evaluated for clinical and biochemical evidence of zinc deficiency . To assess whether these patients would benefit from zinc supplementation , a double-blind , r and omized , controlled trial was conducted . The mean zinc intake of the anorexic group calculated on the basis of three-day dietary records was 7.7 + /- 5.2 mg/day , which is significantly below the recommended daily allowance of 15 mg for adolescents ( p less than 0.001 ) . The mean urinary zinc excretion in the anorexic group was 257.1 + /- 212.7 micrograms/24 hours compared to 749.9 + /- 897.8 micrograms/24 hours in the control group ( p less than 0.005 ) . This result suggests that the zinc status of anorexia nervosa patients may be compromised due to an inadequate zinc intake . Zinc supplementation ( 50 mg elemental zinc/day ) was followed by a decrease in the level of depression and anxiety as assessed by the Zung Depression Scale ( p less than 0.05 ) and the State-Trait Anxiety Inventory ( p less than 0.05 ) , respectively . Our data suggest that individuals with anorexia nervosa may be at risk for zinc deficiency and may respond favorably after zinc supplementation", "A double-blind , pair-matched 12-mo study examined the effects of a zinc supplement ( 10 mg Zn/d as ZnSO4 ) on linear growth , taste acuity , attention span , biochemical indices , and energy intakes of 60 boys ( aged 5 - 7 y ) with height less than or equal to 15th and midparent height greater than 25th percentiles . Boys with initial hair Zn less than 1.68 mumol/g ( n = 16 ) had a lower mean ( + /- SD ) weight-for-age Z score ( -0.44 + /- 0.59 vs -0.08 + /- 0.84 ) , and a higher median recognition threshold for salt ( 15 vs 7.5 mmol ; p = 0.02 ) than those with hair Zn greater than 1.68 mumol/g . Only boys with hair Zn less than 1.68 mumol/g responded to the Zn supplement with a higher mean change in height-for-age Z score ( p less than 0.05 ) ; taste acuity , energy intakes , and attention span were unaffected . A growth-limiting Zn deficiency syndrome exists in boys with low height percentiles , hair Zn levels less than 1.68 mumol/g , and impaired taste acuity", "Background : There is some evidence that sleep patterns may be affected by iron deficiency anemia but the role of iron in sleep has not been tested in a r and omized iron supplementation trial . Objective : We investigated the effect of iron supplementation on maternal reports of sleep in infants in 2 r and omized , placebo-controlled trials from Pemba Isl and , Zanzibar , and Nepal . Design : In both studies , which had parallel design s and were carried out in years 2002 to 2003 , infants received iron – folic acid with or without zinc daily for 12 months , and assessment s of development were made every 3 months for the duration of the study . Eight hundred seventy-seven Pemban ( 12.5 ± 4.0 months old ) and 567 Nepali ( 10.8 ± 4.0 months ) infants participated . Maternal reports of sleep patterns ( napping frequency and duration , nighttime sleep duration , frequency of night waking ) were collected . Results : Mean Hb concentration was 9.2 ± 1.1 for Pemban and 10.1 ± 1.2 g/dL for Nepali infants . Approximately , one-third of the children were stunted . Supplemental iron was consistently associated with longer night and total sleep duration . The effects of zinc supplementation also included longer sleep duration . Conclusions : Micronutrient supplementation in infants at high risk for iron deficiency and iron deficiency anemia was related to increased night sleep duration and less night waking " ]

[ "Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading , despite our best efforts to improve the design and analysis of studies . Mendelian r and omization-the r and om assortment of genes from parents to offspring that occurs during gamete formation and conception-provides one method for assessing the causal nature of some environmental exposures . The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies . Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian r and omization and are described . The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study , that polymorphisms may have several phenotypic effects associated with disease , the lack of suitable polymorphisms for study ing modifiable exposures of interest , and canalization-the buffering of the effects of genetic variation during development . Nevertheless , Mendelian r and omization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to underst and ing and preventing the adverse effects on human health of modifiable exposures", "Background — Whether physical activity reduces the impact of obesity on the risk of acute coronary events is much debated . However , little is known about the role of other potentially modifiable lifestyle factors in combination with obesity . Methods and Results — We followed up 54 783 women and men from the prospect i ve Danish Diet , Cancer and Health study who were 50 to 64 years at baseline ( 1993 to 1997 ) and free of coronary artery disease and cancer . During a median of 7.7 years , 1127 incident cases of acute coronary syndrome ( ACS ) occurred . After multivariable adjustments , each unit of body mass index was associated with a 5 % and 7 % higher risk of ACS among women and men , respectively ( both P risk of ACS among the physically active and inactive , in nonsmokers and smokers , and among those who adhered more or less to a heart-healthy dietary pattern . Obese individuals who were active 1 to 3.5 h/wk had a lower risk than sedentary , obese individuals . In addition , obese nonsmokers had a lower risk than obese smokers . Adherence to a healthy diet was associated with a lower risk of ACS ; however , the relative risk was not different among obese individuals with the most healthy diet versus obese individuals with a less healthy diet . Conclusions — Obesity confers an elevated risk of ACS in both healthy and less healthy subgroups of lifestyle behaviors . Adherence to healthy lifestyle behaviors was associated with a lower risk even among obese individuals", "Editors ' Notes Context Whether there is added benefit from performing the same amount of exercise at a higher intensity is unclear . Contribution In this 24-week study , participants r and omly assigned to complete the same total amount of exercise at higher or lower intensities had similar reductions in waist circumference and weight . High-intensity exercise alone improved 2-hour glucose tolerance and led to the greatest increase in cardiorespiratory fitness . Caution The importance of improved 2-hour glucose tolerance in participants without diabetes is unclear . Implication For the same amount of exercise , higher-intensity exercise may not result in greater reduction in waist circumference or weight but may provide benefits in glucose tolerance and cardiorespiratory fitness . The high prevalence of obesity and associated type 2 diabetes mellitus among adults presents a major public health challenge ( 1 ) . Physical inactivity is a significant determinant of obesity , and most adults in the United States are inactive ( 2 ) . Although progress has been made to eluci date the effects of exercise as a strategy for reducing obesity and related glucose tolerance , the specific exercise exposures required to achieve optimal benefit continue to be the source of considerable uncertainty and debate . Implicit within current guidelines for physical activity and health is the observation that 75 minutes of weekly high-intensity exercise is equivalent to 150 minutes of weekly lower-intensity exercise ( 3 , 4 ) . Therefore , guidelines suggest that there are no added health benefits of high-intensity exercise other than the shorter time frame needed to expend the appropriate amount of energy . Thus , the benefits of engaging in high-intensity exercise are attributed to the greater amount of energy expenditure per unit of time and do not relate to intensity per se ( 3 ) . The scientific committee report from which current guidelines were developed recognized that many unanswered issues exist in response to the question of how much of what type of activity is appropriate for a given health outcome , and acknowledged that future investigations need to evaluate the effects of exercise intensity at fixed amounts of energy expenditure . We therefore performed a r and omized clinical trial to investigate the separate effects of habitual exercise differing in amount and intensity on abdominal obesity and glucose tolerance . We studied abdominally obese adults because they are at substantially increased risk for morbidity ( 5 ) and mortality ( 6 ) and because it is estimated that 60 % of men and 45 % of women between the ages of 35 and 65 years in the United States are abdominally obese ( 7 ) . Methods Setting and Participants Details of the trial design and methods are published ( 8) . We conducted a 24-week , single-center , parallel-group , r and omized , controlled trial between 2009 to 2013 . Potential participants were excluded if they reported a history of heart disease , stroke , or any condition that would prevent them from engaging in exercise ; were already engaging in 2 or more planned exercise sessions per week ; or were diabetic . All participants provided informed consent before participation . The study was approved by the Queen 's University Health Sciences Research Ethics Board , Kingston , Ontario , Canada . Interventions Participants were r and omly assigned to 1 of the following groups : control ( no exercise ) or 5 sessions per week of low-amount , low-intensity exercise ( LALI ) ( 180 and 300 kcal/session for women and men , respectively , at 50 % of maximum oxygen consumption [ V̇o 2peak ] ) ; high-amount , low-intensity exercise ( HALI ) ( 360 and 600 kcal/session for women and men , respectively , at 50 % of V̇o 2peak ) ; or high-amount , high-intensity exercise ( HAHI ) ( 360 and 600 kcal/session for women and men , respectively , at 75 % of V̇o 2peak ) . Exercise Interventions All participants performed walk/jog exercise consistent with consensus recommendations on a treadmill for the time required to achieve the desired amount of exercise ( energy expenditure in kilocalories per session , relative to V̇o 2peak ) 5 times per week for 24 weeks . Using the heart rate and V̇o 2 data obtained from the baseline exercise test , we assigned the target heart rate associated with a V̇o 2peak of approximately 50 % ( LALI and HALI ) and approximately 75 % ( HAHI ) for each participant . At these exercise intensities , the energy expenditure targets ( exercise amount ) for women and men , respectively , were 180 and 300 kcal for the LALI group and 360 and 600 kcal for the HALI and HAHI groups . Follow-up exercise tests to measure V̇o 2peak were performed at weeks 4 , 8 , and 16 to verify the relationship between heart rate and V̇o 2 . Continual adjustment of the heart rateV̇o 2 relationship accounted for improvement in cardiorespiratory fitness ( CRF ) , which alters the time required to achieve the prescribed exercise amount ( for example , energy expenditure ) . Heart rate was monitored continuously for all exercise participants at every session to ensure adherence to the prescribed exercise intensity . All exercise sessions were supervised , and all exercise participants were asked not to engage in any structured exercise outside of the supervised sessions . Nonexercise Control Group Participants in the control group were asked to maintain their level of physical activity throughout the trial and received diet composition advice similar to that received in the exercise groups . Daily Physical Activity Unsupervised physical activity was monitored using ActiGraph GT3X accelerometers for 1-week periods at baseline and at 8 , 16 , and 25 weeks . Participants were required to wear the accelerometer for at least 4 days each period . Established accelerometer cut points were used to estimate physical activity and sedentary time ( 9 ) . Dietary Regimen During a 1-week baseline period , participants were instructed to maintain baseline body weight by monitoring their calorie intake and recording their daily consumption of self-selected foods . During the intervention , participants were instructed to maintain the calorie intake targets measured during baseline . All participants were prescribed a balanced diet and were asked to su bmi t daily dietary intake records during the intervention . Two weeks of records for all groups were analyzed using a computerized program to assess the accuracy of self-reported records . Outcomes and Follow-up Primary outcome variables were waist circumference ( WC ) , which was measured at the superior edge of the iliac crest ( 10 ) at baseline and at 8 ( exercise groups only ) , 16 , and 24 weeks , and 2-hour glucose level , which was measured in response to a 2-hour , 75-g oral glucose tolerance test between 36 and 48 hours after the last exercise session at baseline and at 16 and 24 weeks ( 8) . Secondary outcomes included CRF ( V̇o 2peak ) assessed by using st and ard open-circuit spirometry techniques with a mass flow sensor ( SensorMedics ) during a grade d exercise test in which participants walked on a treadmill at a self-selected speed at 0 elevation for 3 minutes , after which the incline was increased every 2 minutes until the participant stopped voluntarily . Levels of glucose , triglycerides , high- and low-density lipoprotein cholesterol , and insulin and blood pressure were measured using established procedures ( 8) . The Matsuda index ( an indication of insulin sensitivity ) was calculated as follows : ( 10000/[{fasting glucose levelfasting insulin level}{mean glucose levelmean insulin level during the oral glucose tolerance test}]1/2 ) ( 11 ) . There were separate assessment and intervention personnel , and all assessment personnel were blinded to participant r and omization assignment . Sample Size and Power Sample size was determined for WC and 2-hour glucose level on the basis of reduction after treatment . Previous trials suggested that exercise-induced weight loss of approximately 6 % was associated with WC reductions of 6.9 cm ( SD , 2.6 ) in men ( 12 ) and 6.5 cm ( SD , 2.6 ) in women ( 13 ) . For 2-hour glucose level , mean reductions of 0.70 mmol/L ( SD , 1.9 ) ( 12.6 mg/dL [ SD , 34.2 ] ) and 0.94 mmol/L ( SD , 0.7 ) ( 16.9 mg/dL [ SD , 12.6 ] ) were seen in men and women , respectively ( 12 , 13 ) . The sample size calculation incorporated the larger SDs for WC and 2-hour glucose level . The sample -size formula ( equation 13 of Overall and Doyle [ 14 ] ) relevant to the repeated- measures analysis of variance design was applied . The formula is based on a simple 2-group comparison of the pretreatment and posttreatment outcome changes , and it accounts for the correlation between the pretreatment and posttreatment outcome variables . With a correlation of 0.7 between pretreatment and posttreatment glucose tolerance and WC , and allowance for a dropout rate of 30 % , a sample of 40 men or women with 28 completers in each treatment group gives more than 85 % power to detect a mean difference of 2 cm in WC and a mean difference of 1.9 mmol/L ( 34.2 mg/dL ) in glucose tolerance between any 2 treatment groups . R and omization Participants were r and omly assigned to the 4 groups using the method of permuted blocks , with r and om block sizes of 4 , 8 , or 12 within strata . R and omization was stratified by sex and age , with a fifth stratum for the few couples participating to ensure that they were r and omly assigned to the same treatment . The computer-generated r and omization list was maintained by an independent statistician otherwise uninvolved in the study and was concealed from study personnel until the time of r and omization . After baseline data collection , the study coordinator contacted the statistician by e-mail to obtain treatment assignment . Statistical Analysis Analyses were done on an intention-to-treat basis ( 15 ) . All r and omly assigned participants were included in the analyses . Differences in continuous and categorical variables between dropouts and participants who completed the study were examined by using a 2-tailed t test and a chi-square test , respectively . For WC , 2-hour glucose level ,", "CONTEXT Deciphering the early processes occurring in adipose tissue during weight gain is a major issue for underst and ing the development of fat mass and obesity . Experimental overfeeding in humans is a unique situation to tackle these events . OBJECTIVE Our aim was to identify the pathways involved in sc adipose tissue remodeling during the initial phase of weight gain . RESEARCH DESIGN AND METHODS Forty-four healthy men were involved in an overfeeding protocol with a lipid-enriched diet ( + 760 kcal/d ) for 2 months . Subcutaneous abdominal adipose tissue biopsies were taken for histology , transcriptomics , and Western blotting in the basal state , after 14 d , and at the end of the protocol . RESULTS Overfeeding significantly increased body weight ( + 2.5 kg ) and fat mass . Reorganization of gene expression patterns occurred in adipose tissue with an up-regulation of numerous genes involved in lipid metabolism and storage , followed by clusters of genes related to angiogenesis and extracellular matrix remodeling . Histological examination showed increased microvascular density and connective tissue deposition after 56 d of overfeeding , with no changes in the number of macrophages or inflammatory cells . Inhibition of the canonical Wnt/β-catenin signaling pathway and induction of the renin-angiotensin system might be implicated in the remodeling of sc adipose tissue . CONCLUSIONS We characterize the coordinated and time-dependent processes that occur in human adipose tissue during the early phase of weight gain in healthy subjects and identify pathways representing potential targets in pathologies of adipose development , including obesity", "BACKGROUND Physical activity and body mass index ( calculated as weight in kilograms divided by height in meters squared ) independently alter the risk of coronary heart disease ( CHD ) ; however , their combined effect on CHD is not established . Our objective was to study the combined association of physical activity and body mass index on CHD . METHODS Prospect i ve cohort study of 38,987 women free of cardiovascular disease , cancer , and diabetes at baseline in the Women 's Health Study , with 10.9 mean years of follow-up . Weight , height , and recreational activities were reported on entry . Body mass index was categorized as normal weight ( overweight ( 25 to obese ( > or = 30 ) . Active was defined as 1000 kilocalories or more expended on recreational activities weekly . Six joint body weight-physical activity categories were defined . The main outcome measure was the occurrence of incident CHD during follow-up , defined as a cardiovascular event including nonfatal myocardial infa rct ion , coronary artery bypass graft , percutaneous transluminal coronary angioplasty , or CHD death . RESULTS A total of 948 cases of incident CHD occurred during follow-up . Higher body mass index and physical inactivity were individual predictors of CHD . In joint analyses , compared with active normal-weight individuals , the multivariate-adjusted hazard ratios ( 95 % confidence intervals ) were 1.54 ( 1.14 - 2.08 ) for overweight-active ; 1.87 ( 1.29 - 2.71 ) for obese-active ; 1.08 ( 0.84 - 1.39 ) for normal weight-inactive ; 1.88 ( 1.46 - 2.42 ) for overweight-inactive ; and 2.53 ( 1.94 - 3.30 ) for obese-inactive . Increasing levels of walking also result ed in significant reductions in CHD risk for overweight and obese individuals . CONCLUSIONS The risk of CHD associated with elevated body mass index is considerably reduced by increased physical activity levels . However , the risk is not completely eliminated , reinforcing the importance of being lean and physically active", "Here , Timpson and colleagues performed a Mendelian R and omization analysis to determine whether childhood adiposity causally influences levels of physical activity . The results suggest that increased adiposity causes a reduction in physical activity in children ; however , this study does not exclude lower physical activity also leading to increasing adiposity . Please see later in the article for the Editors '", "In 1997 , the World Health Organization published a l and mark document recognizing obesity as a worldwide disease that poses a serious threat to public health ( 1 ) . Persons who are overweight or obese have substantially increased risk for morbidity from numerous chronic disorders , such as diabetes ( 2 , 3 ) , hypertension ( 4 , 5 ) , and cardiovascular disease ( 6 , 7 ) . Obesity-related health risk is greater when excess fat is deposited in the abdomen region because this phenotype is a stronger predictor of cardiovascular disease and type 2 diabetes mellitus than general obesity is ( 8 - 11 ) . This may be partially explained by excess accumulation of visceral fat , an independent correlate of insulin resistance ( 9 - 11 ) and dyslipidemia ( 8 , 9 ) . These observations highlight the need to identify appropriate treatment strategies to prevent and reduce obesity and suggest that the effectiveness of these treatments would be enhanced if abdominal obesity , particularly visceral fat , was substantially reduced . Diet restriction remains the most common method of obesity reduction ( 12 ) . Despite the observation that low levels of physical activity are a major cause of obesity ( 13 ) , increased physical activity alone is not thought to be a useful strategy for obesity reduction . Some reports have suggested that physical activity in obese adults results in only modest weight loss ( approximately 1 to 2 kg ) independent of the effects of diet restriction ( 14 ) . However , these conclusions are drawn from studies in which individual energy intake and expenditure were not rigorously controlled or accurately measured ( 15 - 17 ) . Moreover , in most studies , the negative energy balance induced by exercise was modest enough that substantial weight loss was not expected ( 15 - 17 ) . Currently , no compelling evidence supports the observation that exercise alone is not a useful method for reducing total or abdominal obesity . It is well known that a single exercise session is associated with a significant improvement in insulin-stimulated glucose uptake ( 18 , 19 ) . It is also clear that weight loss is associated with an improvement in insulin action ( 20 - 24 ) . It is unclear , however , whether regular exercise improves glucose metabolism after the short-term effects of exercise and changes in body fat distribution are considered . Segal and colleagues ( 25 ) controlled for the confounding effect of the last exercise session and body composition changes and found that exercise had no independent effect on insulin sensitivity ( 25 ) . Given the established importance of insulin resistance as an antecedent to both cardiovascular disease and type 2 diabetes mellitus ( 26 ) , it is important to clarify whether exercise improves insulin action independent of fat loss . We performed a r and omized , controlled trial to determine the independent effect of diet-induced or exercise-induced weight loss on obesity and insulin resistance in moderately obese men . We also evaluated whether exercise without weight loss was associated with reductions in abdominal obesity and insulin resistance . Methods Participants Participants were recruited from Kingston , Ontario , Canada , a typical suburban region , through the general media . We selected men with a body mass index greater than 27 kg/m2 and a waist circumference greater than 100 cm whose weight had been stable ( 2 kg ) for 6 months before study entry . Participants were nonsmokers who consumed an average of fewer than two alcoholic beverages per day , had a sedentary lifestyle , and took no medications known to affect the principal outcome measures . All participants had a preparticipation medical examination that included screening for normal glucose tolerance and plasma lipid profile . A computer program was used to r and omly assign eligible men to one of the following four groups : control , diet-induced weight loss , exercise-induced weight loss , and exercise without weight loss ( Figure 1 ) . Of the 101 participants who were r and omly assigned to groups , 34 chose not to participate because they were dissatisfied with their assigned group , 5 were diabetic or dyslipidemic , and 3 were relocated because of job transfers . Those who chose not to participate and those who completed the trial were similar with regard to anthropometric variables . In addition , those who completed the trial were similar to those who did not in each group ( P > 0.10 ) . Baseline characteristics among groups were similar for all participants ( Table 1 ) . All participants gave fully informed written consent . The study was conducted in accordance with the ethical guidelines of Queen 's University . The participants did not receive monetary compensation . Figure 1 . Flow of participants through the study . Table 1 . Selected Anthropometric , Magnetic Resonance Imaging , and Metabolic Variables before Treatment and 3 Months after Treatment Diet and Exercise Regimen During the baseline period , daily energy requirements for all participants were determined by estimating resting energy expenditure and multiplying the obtained value by a factor of 1.5 ( 27 ) . All participants followed a weight maintenance diet ( 55 % to 60 % carbohydrate , 15 % to 20 % protein , and 20 % to 25 % fat ) for a 4- to 5-week baseline period . During this period , body weight was monitored to determine the accuracy of the prescribed energy requirement , which was adjusted accordingly to maintain body weight . Controls were asked to maintain body weight throughout the 12-week treatment period . Participants in the diet-induced weight loss group were asked to reduce the isocaloric diet by 700 kcal/d during the treatment period to achieve a weekly weight loss of approximately 0.6 kg . To lose the same amount of weight , participants in the exercise-induced weight loss group were asked to maintain the isocaloric diet for the duration of the treatment period and to perform exercise that expended 700 kcal/d . Participants assigned to exercise without weight loss were asked to maintain body weight . Therefore , they consumed enough calories to compensate for the energy expended during the daily exercise sessions ( approximately 700 kcal ) . At the end of the treatment period , isocaloric requirements were determined and prescribed for a 2-week weight stabilization period . All participants were free-living and consumed self-selected foods . No vitamins or other nutritional supplements were prescribed . Each person participated in a series of weekly 1-hour seminars in which a dietitian taught proper food selection and preparation . Participants were told that the composition of the maintenance and energy-reduced diets should be approximately 55 % to 60 % carbohydrate , 15 % to 20 % protein , and 20 % to 25 % fat . Participants kept and analyzed daily , detailed food records for the duration of the study period ( approximately 20 weeks ) ; the study dietitian also review ed these records . For the 2-week period during which doubly labeled water measurements were acquired ( weeks 6 and 7 ) , the diet records were analyzed by using a computerized program ( Food Processor , Esha Research , Salem , Oregon ) . Participants in both exercise groups performed daily exercise ( brisk walking or light jogging ) on a motorized treadmill for the duration of the 12-week trial . The length of each exercise session was determined by the time required to expend 700 kcal . Participants were asked to exercise at an intensity not greater than 70 % of their peak oxygen uptake ( Vo 2 ) ( approximately 80 % of maximal heart rate ) . Energy expenditure was determined by using the heart rate and oxygen consumption data that were obtained from the pretreatment grade d exercise test and were adjusted according to the results of two subsequent tests performed at weeks 4 and 8 . During each session , heart rate was monitored every 5 minutes by using an automated heart rate monitor ( Polar Oy , Kempele , Finl and ) . All exercise sessions were by appointment and were supervised . Peak Vo 2 was determined by using a grade d treadmill test and st and ard open-circuit spirometry techniques ( SensorMedics , Yorba Linda , California ) . Energy Expenditure Total energy expenditure for 14 days was measured by using a two-point doubly labeled water method ( 28 ) . Deuterium enrichment was analyzed by using a 903 deuterium dual-inlet isotope ratio mass spectrometer ( VG Isogas , Cheshire , United Kingdom ) . Oxygen-18 was determined by using a SIRA 12 isotope ratio mass spectrometer ( VG Isogas ) . Total energy expenditure was calculated by using the DeWeir formula ( 29 ) . After an overnight stay in the hospital , resting metabolic rate was measured at 7:00 a.m. by using indirect calorimetry with a modified mask system ( Teem 100 , Aerosport , Inc. , Ann Arbor , Michigan ) . Values were obtained for 30 minutes , and the last 25 minutes were used to determine resting metabolic rate . Resting systolic and diastolic blood pressure were measured when the participant was supine . Magnetic Resonance Imaging and Anthropometric Measurements Whole-body data from magnetic resonance imaging ( approximately 45 equidistant images ) were obtained with a General Electric 1.5-Tesla magnet ( Milwaukee , Wisconsin ) by using an established protocol described in detail elsewhere ( 30 ) . Once acquired , the data were transferred to a st and -alone work station ( Silicon Graphics , Mountain View , California ) for analysis with specially design ed computer software ( Tomovision , Inc. , Montreal , Canada ) , the procedures for which are described elsewhere ( 31 ) . For adipose tissue ( fat ) and skeletal muscle , volume units ( L ) were converted to mass units ( kg ) by multiplying the volumes by the assumed constant density for fat ( 0.92 kg/L ) and fat-free skeletal muscle ( 1.04 kg/L ) ( 32 ) . All anthropometric circumference measurements were obtained by using st and ard procedures described elsewhere ( 30 ) . Insulin Sensitivity and Glucose Tolerance Participants consumed a weight-maintenance diet consisting of at least 200 g of carbohydrate for a minimum of 4 days and were asked to avoid strenuous physical activity for 3 days before insulin", "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 )", "OBJECTIVE —The purpose of this study was to examine the associations of cardiorespiratory fitness ( hereafter fitness ) and various obesity measures with risks of incident impaired fasting glucose ( IFG ) and type 2 diabetes . RESEARCH DESIGN AND METHODS —This was a prospect i ve cohort study of 14,006 men ( 7,795 for the analyses of IFG ) , who did not have an abnormal electrocardiogram or a history of heart attack , stroke , cancer , or diabetes . RESULTS —Of the men , 3,612 ( 39,610 person-years ) and 477 ( 101,419 person-years ) developed IFG and type 2 diabetes , respectively . Compared with the least fit 20 % in multivariate analyses , IFG and type 2 diabetes risks in the most fit 20 % were 14 and 52 % lower , respectively ( both P Men with BMI ≥30.0 kg/m2 , waist girth > 102.0 cm , or percent body fat ≥25 had 2.7- , 1.9- , and 1.3-fold higher risks for type 2 diabetes , respectively , compared with those for nonobese men ( all P higher risk for type 2 diabetes compared with normal-weight fit ( most fit 80 % ) men . We observed similar trends for the joint associations of BMI and fitness with IFG and those of waist girth or percent body fat and fitness with both IFG and type 2 diabetes . CONCLUSIONS —Low fitness and obesity increased the risks of IFG and type 2 diabetes by approximately similar magnitudes . When considered simultaneously , fitness attenuated but did not eliminate the increased risks of IFG and type 2 diabetes associated with obesity , and the highest risk was found in obese and unfit men", "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", "CONTEXT Low levels of cardiorespiratory fitness are associated with high risk of mortality , and improvements in fitness are associated with reduced mortality risk . However , a poor underst and ing of the physical activity-fitness dose response relation remains . OBJECTIVE To examine the effect of 50 % , 100 % , and 150 % of the NIH Consensus Development Panel recommended physical activity dose on fitness in women . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of 464 sedentary , postmenopausal overweight or obese women whose body mass index ranged from 25.0 to 43.0 and whose systolic blood pressure ranged from 120.0 to 159.9 mm Hg . Enrollment took place between April 2001 and June 2005 in the Dallas , Tex , area . INTERVENTION Participants were r and omly assigned to 1 of 4 groups : 102 to the nonexercise control group and 155 to the 4-kcal/kg , 104 to the 8-kcal/kg , and 103 to the 12-kcal/kg per week energy-expenditure groups for the 6-month intervention period . Target training intensity was the heart rate associated with 50 % of each woman 's peak Vo2 . MAIN OUTCOME MEASURE The primary outcome was aerobic fitness assessed on a cycle ergometer and quantified as peak absolute oxygen consumption ( Vo2abs , L/min ) . RESULTS The mean ( SD ) baseline Vo2abs values were 1.30 ( 0.25 ) L/min . The mean ( SD ) minutes of exercising per week were 72.2 ( 12.3 ) for the 4-kcal/kg , 135.8 ( 19.5 ) for the 8-kcal/kg , and 191.7 ( 33.7 ) for the 12-kcal/kg per week exercise groups . After adjustment for age , race/ethnicity , weight , and peak heart rate , the exercise groups increased their Vo2abs compared with the control group by 4.2 % in the 4-kcal/kg , 6.0 % in the 8-kcal/kg , and 8.2 % in the 12-kcal/kg per week groups ( P age , body mass index , weight , baseline Vo2abs , race/ethnicity , or baseline hormone therapy use . There were no significant changes in systolic or diastolic blood pressure values from baseline to 6 months in any of the exercise groups vs the control group . CONCLUSION In this study , previously sedentary , overweight or obese postmenopausal women experienced a grade d dose-response change in fitness across levels of exercise training . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00011193", "BACKGROUND A high body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) is associated with increased mortality from cardiovascular disease and certain cancers , but the precise relationship between BMI and all-cause mortality remains uncertain . METHODS We used Cox regression to estimate hazard ratios and 95 % confidence intervals for an association between BMI and all-cause mortality , adjusting for age , study , physical activity , alcohol consumption , education , and marital status in pooled data from 19 prospect i ve studies encompassing 1.46 million white adults , 19 to 84 years of age ( median , 58 ) . RESULTS The median baseline BMI was 26.2 . During a median follow-up period of 10 years ( range , 5 to 28 ) , 160,087 deaths were identified . Among healthy participants who never smoked , there was a J-shaped relationship between BMI and all-cause mortality . With a BMI of 22.5 to 24.9 as the reference category , hazard ratios among women were 1.47 ( 95 percent confidence interval [ CI ] , 1.33 to 1.62 ) for a BMI of 15.0 to 18.4 ; 1.14 ( 95 % CI , 1.07 to 1.22 ) for a BMI of 18.5 to 19.9 ; 1.00 ( 95 % CI , 0.96 to 1.04 ) for a BMI of 20.0 to 22.4 ; 1.13 ( 95 % CI , 1.09 to 1.17 ) for a BMI of 25.0 to 29.9 ; 1.44 ( 95 % CI , 1.38 to 1.50 ) for a BMI of 30.0 to 34.9 ; 1.88 ( 95 % CI , 1.77 to 2.00 ) for a BMI of 35.0 to 39.9 ; and 2.51 ( 95 % CI , 2.30 to 2.73 ) for a BMI of 40.0 to 49.9 . In general , the hazard ratios for the men were similar . Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up . CONCLUSIONS In white adults , overweight and obesity ( and possibly underweight ) are associated with increased all-cause mortality . All-cause mortality is generally lowest with a BMI of 20.0 to 24.9" ]